Socioeconomic disadvantage and psychological deficits: Pathways from early cumulative risk to late-adolescent criminal conviction.

PubMed

Savolainen, Jukka; Eisman, Andria; Mason, W Alex; Schwartz, Joseph A; Miettunen, Jouko; Järvelin, Marjo-Riitta

2018-06-01

Early exposure to multiple risk factors has been shown to predict criminal offending, but the mechanisms responsible for this association are poorly understood. Integrating social-environmental and dispositional theories of crime this research investigated the capacity of family socioeconomic disadvantage and individual psychological deficits to mediate the association between childhood cumulative risk and late adolescent criminal convictions. Male participants in the 1986 Northern Finland Birth Cohort Study (n = 3414) were followed from the prenatal period through age 19-20. The data were analyzed by estimating a structural equation model of the hypothesized pathways. The results found support for both processes of influence, and the model sustained a statistically significant direct effect of cumulative risk on crime. Socioeconomic disadvantage and psychological deficits contribute to criminal offending independently and with roughly equal magnitude. The results point to the utility of both environmental and psychological interventions to prevent criminality among children at risk. Copyright © 2018. Published by Elsevier Ltd.

Cumulative Risk and Adolescent's Internalizing and Externalizing Problems: The Mediating Roles of Maternal Responsiveness and Self-Regulation

ERIC Educational Resources Information Center

Doan, Stacey N.; Fuller-Rowell, Thomas E.; Evans, Gary W.

2012-01-01

The purpose of the present study was to examine longitudinal associations among maternal responsiveness, self-regulation, and behavioral adjustment in adolescents. The authors used structural equation modeling to test a model that demonstrates that the effects of early cumulative risk on behavioral problems is mediated by maternal responsiveness…

Toward a cumulative ecological risk model for the etiology of child maltreatment

PubMed Central

MacKenzie, Michael J.; Kotch, Jonathan B.; Lee, Li-Ching

2011-01-01

The purpose of the current study was to further the integration of cumulative risk models with empirical research on the etiology of child maltreatment. Despite the well-established literature supporting the importance of the accumulation of ecological risk, this perspective has had difficulty infiltrating empirical maltreatment research and its tendency to focus on more limited risk factors. Utilizing a sample of 842 mother-infant dyads, we compared the capacity of individual risk factors and a cumulative index to predict maltreatment reports in a prospective longitudinal investigation over the first sixteen years of life. The total load of risk in early infancy was found to be related to maternal cognitions surrounding her new role, measures of social support and well-being, and indicators of child cognitive functioning. After controlling for total level of cumulative risk, most single factors failed to predict later maltreatment reports and no single variable provided odd-ratios as powerful as the predictive power of a cumulative index. Continuing the shift away from simplistic causal models toward an appreciation for the cumulative nature of risk would be an important step forward in the way we conceptualize intervention and support programs, concentrating them squarely on alleviating the substantial risk facing so many of society’s families. PMID:24817777

Cumulative Risk Disparities in Children's Neurocognitive Functioning: A Developmental Cascade Model

ERIC Educational Resources Information Center

Wade, Mark; Browne, Dillon T.; Plamondon, Andre; Daniel, Ella; Jenkins, Jennifer M.

2016-01-01

The current longitudinal study examined the role of cumulative social risk on children's theory of mind (ToM) and executive functioning (EF) across early development. Further, we also tested a cascade model of development in which children's social cognition at 18 months was hypothesized to predict ToM and EF at age 4.5 through intermediary…

Cumulative Risk for Early Sexual Initiation among American Indian Youth: A Discrete-Time Survival Analysis

ERIC Educational Resources Information Center

Mitchell, Christina M.; Whitesell, Nancy Rumbaugh; Spicer, Paul; Beals, Janette; Kaufman, Carol E.

2007-01-01

Approximately 3 million teens are diagnosed with a sexually transmitted disease (STD) annually; STDs rates for American Indian young adults are among the highest of any racial/ethnic group. An important risk factor for STDs is early initiation of sex. In this study, we examined risk for early initiation with 474 American Indian youth ages 14-18,…

Early introduction and cumulative consumption of sugar-sweetened beverages during the pre-school period and risk of obesity at 8-14 years of age.

PubMed

Cantoral, A; Téllez-Rojo, M M; Ettinger, A S; Hu, H; Hernández-Ávila, M; Peterson, K

2016-02-01

Consumption of sugar-sweetened beverages (SSB) has been associated with risk of obesity, but little evidence exists to evaluate if age of introduction and cumulative SSB consumption increases risk in children. The objective of the study was to estimate the relationship between age of introduction and cumulative SSB consumption with risk of obesity in 227 Mexican children. SSB intake was measured every 6 months; age of introduction and cumulative consumption during the pre-school period were calculated. Height, weight, waist circumference, SSB intake and other relevant variables were measured at age 8-14 years and obesity defined using standard criteria. All participants were introduced to SSB before age 24 months and most (73%) before 12 months. Early SSB introduction (≤12 months) was not significantly associated with increased odds of obesity (odds ratio [OR] = 2.00, 95% confidence interval [CI]: 0.87, 4.59). However, children in the highest tertile of cumulative SSB consumption, compared with the lowest, had almost three times the odds of general (OR = 2.99, 95% CI: 1.27, 7.00) and abdominal (OR = 2.70, 95% CI: 1.03, 7.03) obesity at age 8-14 years. High SSB consumption increased the likelihood of obesity in 8-14-year-old children. Our results suggest that SSB intake should be delayed and excessive SSB consumption in pre-school period should be avoided. © 2015 World Obesity.

Childhood Poverty, Cumulative Risk Exposure, and Mental Health in Emerging Adults

PubMed Central

Evans, Gary W.; Cassells, Rochelle C.

2014-01-01

One out of four American children are born into poverty, but little is known about the long-term, mental health implications of early deprivation. The more time in poverty from birth-age-9, the worse mental health as emerging adults (n = 196, M = 17.30 years, 53% male). These results maintain independently of concurrent, adult income levels for self-reported externalizing symptoms and a standard learned helplessness behavioral protocol, but internalizing symptoms were unaffected by childhood poverty. We then demonstrate that part of the reason why early poverty exposure is harmful to mental health among emerging adults is because of elevated cumulative risk exposure assessed at age 13. The significant, prospective, longitudinal relations between early childhood poverty and externalizing symptoms plus learned helplessness behavior are mediated, in part, by exposure to a confluence of psychosocial (violence, family turmoil, child separation from family) and physical (noise, crowding, substandard housing) risk factors during adolescence. PMID:26609499

Genetic moderation of multiple pathways linking early cumulative socioeconomic adversity and young adults' cardiometabolic disease risk.

PubMed

Wickrama, Kandauda A S; Lee, Tae Kyoung; O'Neal, Catherine Walker

2018-02-01

Recent research suggests that psychosocial resources and life stressors are mediating pathways explaining socioeconomic variation in young adults' health risks. However, less research has examined both these pathways simultaneously and their genetic moderation. A nationally representative sample of 11,030 respondents with prospective data collected over 13 years from the National Study of Adolescent to Adult Health was examined. First, the association between early cumulative socioeconomic adversity and young adults' (ages 25-34) cardiometabolic disease risk, as measured by 10 biomarkers, through psychosocial resources (educational attainment) and life stressors (accelerated transition to adulthood) was examined. Second, moderation of these pathways by the serotonin transporter linked polymorphic region gene (5-HTTLPR) was examined. There was evidence for the association between early socioeconomic adversity and young adults' cardiometabolic disease risk directly and indirectly through educational attainment and accelerated transitions. These direct and mediating pathways were amplified by the 5-HTTLPR polymorphism. These findings elucidate how early adversity can have an enduring influence on young adults' cardiometabolic disease risk directly and indirectly through psychosocial resources and life stressors and their genetic moderation. This information suggests that effective intervention and prevention programs should focus on early adversity, youth educational attainment, and their transition to young adulthood.

Childhood Psychosocial Cumulative Risks and Carotid Intima-Media Thickness in Adulthood: The Cardiovascular Risk in Young Finns Study

PubMed Central

Hakulinen, Christian; Pulkki-Råback, Laura; Elovainio, Marko; Kubzansky, Laura D.; Jokela, Markus; Hintsanen, Mirka; Juonala, Markus; Kivimäki, Mika; Josefsson, Kim; Hutri-Kähönen, Nina; Kähönen, Mika; Viikari, Jorma; Keltikangas-Järvinen, Liisa; Raitakari, Olli T

2015-01-01

Objective Adverse experiences in childhood may influence cardiovascular risk in adulthood. We examined the prospective associations between types of psychosocial adversity as well as having multiple adversities (e.g., cumulative risk) with carotid intima-media thickness (IMT) and its progression among young adults. Higher cumulative risk score in childhood was expected to be associated with higher IMT and its progression. Methods Participants were 2265 men and women (age range: 24-39 years in 2001) from the on-going Cardiovascular Risk in Young Finns study whose carotid IMT were measured in 2001 and 2007. A cumulative psychosocial risk score, assessed at the study baseline in 1980, was derived from four separate aspects of the childhood environment that may impose risk (childhood stressful life-events, parental health behavior family, socioeconomic status, and childhood emotional environment). Results The cumulative risk score was associated with higher IMT in 2007 (b=.004; se=.001; p<.001) and increased IMT progression from 2001 to 2007 (b=.003; se=.001; p=.001). The associations were robust to adjustment for conventional cardiovascular risk factors in childhood and adulthood, including adulthood health behavior, adulthood socioeconomic status and depressive symptoms. Among the individual childhood psychosocial risk categories, having more stressful life-events was associated with higher IMT in 2001 (b=.007; se=.003; p=.016) and poorer parental health behavior predicted higher IMT in 2007 (b=.004; se=.002; p=.031) after adjustment for age, sex and childhood cardiovascular risk factors. Conclusions Early life psychosocial environment influences cardiovascular risk later in life and considering cumulative childhood risk factors may be more informative than individual factors in predicting progression of preclinical atherosclerosis in adulthood. PMID:26809108

Childhood Psychosocial Cumulative Risks and Carotid Intima-Media Thickness in Adulthood: The Cardiovascular Risk in Young Finns Study.

PubMed

Hakulinen, Christian; Pulkki-Råback, Laura; Elovainio, Marko; Kubzansky, Laura D; Jokela, Markus; Hintsanen, Mirka; Juonala, Markus; Kivimäki, Mika; Josefsson, Kim; Hutri-Kähönen, Nina; Kähönen, Mika; Viikari, Jorma; Keltikangas-Järvinen, Liisa; Raitakari, Olli T

2016-01-01

Adverse experiences in childhood may influence cardiovascular risk in adulthood. We examined the prospective associations between types of psychosocial adversity and having multiple adversities (e.g., cumulative risk) with carotid intima-media thickness (IMT) and its progression among young adults. Higher cumulative risk score in childhood was expected to be associated with higher IMT and its progression. Participants were 2265 men and women (age range, 24-39 years in 2001) from the ongoing Cardiovascular Risk in Young Finns study whose carotid IMTs were measured in 2001 and 2007. A cumulative psychosocial risk score, assessed at the study baseline in 1980, was derived from four separate aspects of the childhood environment that may impose risk (childhood stressful life events, parental health behavior family, socioeconomic status, and childhood emotional environment). The cumulative risk score was associated with higher IMT in 2007 (b = 0.004, standard error [SE] = 0.001, p < .001) and increased IMT progression from 2001 to 2007 (b = 0.003, SE = 0.001, p = .001). The associations were robust to adjustment for conventional cardiovascular risk factors in childhood and adulthood, including adulthood health behavior, adulthood socioeconomic status, and depressive symptoms. Among the individual childhood psychosocial risk categories, having more stressful life events was associated with higher IMT in 2001 (b = 0.007, SE = 0.003, p = .016) and poorer parental health behavior predicted higher IMT in 2007 (b = 0.004, SE = 0.002, p = .031) after adjustment for age, sex, and childhood cardiovascular risk factors. Early life psychosocial environment influences cardiovascular risk later in life, and considering cumulative childhood risk factors may be more informative than individual factors in predicting progression of preclinical atherosclerosis in adulthood.

Weighted comparison of two cumulative incidence functions with R-CIFsmry package.

PubMed

Li, Jianing; Le-Rademacher, Jennifer; Zhang, Mei-Jie

2014-10-01

In this paper we propose a class of flexible weight functions for use in comparison of two cumulative incidence functions. The proposed weights allow the users to focus their comparison on an early or a late time period post treatment or to treat all time points with equal emphasis. These weight functions can be used to compare two cumulative incidence functions via their risk difference, their relative risk, or their odds ratio. The proposed method has been implemented in the R-CIFsmry package which is readily available for download and is easy to use as illustrated in the example. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Cumulative Social Risk and Obesity in Early Childhood

PubMed Central

Duarte, Cristiane S.; Chambers, Earle C.; Boynton-Jarrett, Renée

2012-01-01

OBJECTIVES: The goal of this study was to examine the relationship between cumulative social adversity and childhood obesity among preschool-aged children (N = 1605) in the Fragile Families and Child Wellbeing Study. METHODS: Maternal reports of intimate partner violence, food insecurity, housing insecurity, maternal depressive symptoms, maternal substance use, and father’s incarceration were obtained when the child was 1 and 3 years of age. Two cumulative social risk scores were created by summing the 6 factors assessed at ages 1 and 3 years. Child height and weight were measured at 5 years of age. Logistic regression models stratified according to gender were used to estimate the association between cumulative social risk and obesity, adjusting for sociodemographic factors. RESULTS: Seventeen percent of children were obese at age 5 years, and 57% had at least 1 social risk factor. Adjusting for sociodemographic factors, girls experiencing high cumulative social risk (≥2 factors) at age 1 year only (odds ratio [OR]: 2.1 [95% confidence interval [CI]: 1.1–4.1]) or at 3 years only (OR: 2.2 [95% CI: 1.2–4.2]) were at increased odds of being obese compared with girls with no risk factors at either time point. Those experiencing high cumulative risk at age 1 and 3 years were not at statistically significant odds of being obese (OR: 1.9 [95% CI: 0.9–4.0]). No significant associations were noted among boys. CONCLUSIONS: There seems to be gender differences in the effects of cumulative social risk factors on the prevalence of obesity at 5 years of age. Understanding the social context of families could make for more effective preventive efforts to combat childhood obesity. PMID:22508921

Early life socioeconomic position and immune response to persistent infections among elderly Latinos.

PubMed

Meier, Helen C S; Haan, Mary N; Mendes de Leon, Carlos F; Simanek, Amanda M; Dowd, Jennifer B; Aiello, Allison E

2016-10-01

Persistent infections, such as cytomegalovirus (CMV), herpes simplex virus-1 (HSV-1), Helicobacter pylori (H. pylori), and Toxoplasma gondii (T. gondii), are common in the U.S. but their prevalence varies by socioeconomic status. It is unclear if early or later life socioeconomic position (SEP) is a more salient driver of disparities in immune control of these infections. Using data from the Sacramento Area Latino Study on Aging, we examined whether early or later life SEP was the strongest predictor of immune control later in life by contrasting two life course models, the critical period model and the chain of risk model. Early life SEP was measured as a latent variable, derived from parental education and occupation, and food availability. Indicators for SEP in later life included education level and occupation. Individuals were categorized by immune response to each pathogen (seronegative, low, medium and high) with increasing immune response representing poorer immune control. Cumulative immune response was estimated using a latent profile analysis with higher total immune response representing poorer immune control. Structural equation models were used to examine direct, indirect and total effects of early life SEP on each infection and cumulative immune response, controlling for age and gender. The direct effect of early life SEP on immune response was not statistically significant for the infections or cumulative immune response. Higher early life SEP was associated with lower immune response for T. gondii, H. pylori and cumulative immune response through pathways mediated by later life SEP. For CMV, higher early life SEP was both directly associated and partially mediated by later life SEP. No association was found between SEP and HSV-1. Findings from this study support a chain of risk model, whereby early life SEP acts through later life SEP to affect immune response to persistent infections in older age. Copyright © 2016 Elsevier Ltd. All rights reserved.

Infant Parasympathetic and Sympathetic Activity during Baseline, Stress and Recovery: Interactions with Prenatal Adversity Predict Physical Aggression in Toddlerhood.

PubMed

Suurland, J; van der Heijden, K B; Huijbregts, S C J; van Goozen, S H M; Swaab, H

2018-05-01

Exposure to prenatal adversity is associated with aggression later in life. Individual differences in autonomic nervous system (ANS) functioning, specifically nonreciprocal activation of the parasympathetic (PNS) and sympathetic (SNS) nervous systems, increase susceptibility to aggression, especially in the context of adversity. Previous work examining interactions between early adversity and ANS functioning in infancy is scarce and has not examined interaction between PNS and SNS. This study examined whether the PNS and SNS moderate the relation between cumulative prenatal risk and early physical aggression in 124 children (57% male). Cumulative risk (e.g., maternal psychiatric disorder, substance (ab)use, and social adversity) was assessed during pregnancy. Parasympathetic respiratory sinus arrhythmia (RSA) and sympathetic pre-ejection period (PEP) at baseline, in response to and during recovery from emotional challenge were measured at 6 months. Physical aggression and non-physical aggression/oppositional behavior were measured at 30 months. The results showed that cumulative prenatal risk predicted elevated physical aggression and non-physical aggression/oppositional behavior in toddlerhood; however, the effects on physical aggression were moderated by PNS and SNS functioning. Specifically, the effects of cumulative risk on physical aggression were particularly evident in children characterized by low baseline PNS activity and/or by nonreciprocal activity of the PNS and SNS, characterized by decreased activity (i.e., coinhibition) or increased activity (i.e., coactivation) of both systems at baseline and/or in response to emotional challenge. These findings extend our understanding of the interaction between perinatal risk and infant ANS functioning on developmental outcome.

Medical history of discordant twins and environmental etiologies of autism.

PubMed

Willfors, C; Carlsson, T; Anderlid, B-M; Nordgren, A; Kostrzewa, E; Berggren, S; Ronald, A; Kuja-Halkola, R; Tammimies, K; Bölte, S

2017-01-31

The environmental contributions to autism spectrum disorder (ASD) and their informative content for diagnosing the condition are still largely unknown. The objective of this study was to investigate associations between early medical events and ASD, as well as autistic traits, in twins, to test the hypothesis of a cumulative environmental effect on ASD risk. A total of 80 monozygotic (MZ) twin pairs (including a rare sample of 13 twin pairs discordant for clinical ASD) and 46 dizygotic (DZ) twin pairs with varying autistic traits, were examined for intra-pair differences in early medical events (for example, obstetric and neonatal factors, first year infections). First, differences in early medical events were investigated using multisource medical records in pairs qualitatively discordant for ASD. The significant intra-pair differences identified were then tested in relation to autistic traits in the remaining sample of 100 pairs, applying generalized estimating equations analyses. Significant association of the intra-pair differences in the MZ pairs were found for the cumulative load of early medical events and clinical ASD (Z=-2.85, P=0.004) and autistic traits (β=78.18, P=0.002), as well as infant dysregulation (feeding, sleeping abnormalities, excessive crying and worriedness), when controlling for intelligence quotient and attention deficit hyperactivity disorder comorbidity. The cumulative load of early medical events in general, and infant dysregulation in particular, may index children at risk of ASD owing to non-shared environmental contributions. In clinical practice, these findings may facilitate screening and early detection of ASD.

Individual differences in the activity of the hypothalamic pituitary adrenal axis: Relations to age and cumulative risk in early childhood.

PubMed

Holochwost, Steven J; Gariépy, Jean-Louis; Mills-Koonce, W Roger; Propper, Cathi B; Kolacz, Jacek; Granger, Douglas A

2017-07-01

This study examined individual differences in the function of the hypothalamic-pituitary-adrenal (HPA) axis with regard to age and cumulative risk during challenging laboratory tasks administered at 6, 12, 24, and 36 months. Saliva samples were collected from a majority-minority sample of N=185 children (57% African American, 50% female) prior to and following these tasks and later assayed for cortisol. Cumulative distal risk was indexed via a composite of maternal marital status, maternal education, income-to-needs ratio, the number of children in the household, and maternal age at childbirth. Probing of hierarchical models in which cortisol levels and age were nested within child revealed significant differences in cortisol as a function of both age and cumulative risk, such that children exposed to high levels of risk exhibited higher levels of cortisol both within and across age. These results highlight the sensitivity of the HPA axis to environmental context at the level of the individual, even as that sensitivity is manifest against the background of species-typical biological development. Copyright © 2017 Elsevier Ltd. All rights reserved.

Early risk factors for suicide in an epidemiological first episode psychosis cohort.

PubMed

Dutta, Rina; Murray, Robin M; Allardyce, Judith; Jones, Peter B; Boydell, Jane

2011-03-01

Much remains unknown about whether there are early risk factors for suicide in psychosis. The aim of the study was to determine whether there are any identifiable early symptom clusters, aetiological factors or illness course markers for suicide in first episode psychosis. A total of 2132 patients with first episode psychosis presenting to secondary care services in London (1965-2004; n=1474), Nottingham (1997-1999; n=195) and Dumfries and Galloway (1979-1998; n=463) were traced after up to 40 years (mean 13 years) following first presentation. Risk factors were identified from the Operational Checklist for Psychotic Disorders rated for the first year following presentation. Overall, there were 51 suicides and 373 deaths from other causes. Male gender (RR 2.84, 95% CI 1.20-6.69, p=0.02) and a cumulative threshold effect of symptoms early in the illness (RR 6.81, 95% CI 2.33-19.85, p<0.001) were associated with a higher propensity for later completed suicide. There was also a suggestion that early manic symptoms might increase the risk of later suicide irrespective of initial diagnosis. Suicide risk was associated with a cumulative threshold effect of symptoms and manic symptoms. As suicide is a relatively rare event in psychotic disorders, general population-based prevention strategies may have more impact in this vulnerable group as well as the wider population. Copyright © 2010 Elsevier B.V. All rights reserved.

Ketorolac use may increase risk of postoperative pancreatic fistula after pancreaticoduodenectomy.

PubMed

Kowalsky, Stacy J; Zenati, Mazen S; Steve, Jennifer; Lee, Kenneth K; Hogg, Melissa E; Zeh, Herbert J; Zureikat, Amer H

2018-01-01

Ketorolac (Toradol), a commonly used nonselective nonsteroidal anti-inflammatory drug (NSAID) in the postoperative period, has been associated with increased risk of anastomotic leak after colon resection. The effect of postoperative NSAID and ketorolac use on postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD) is unknown. Retrospective review of consecutive PDs at a high-volume pancreas center from 2012 to 2015. POPF was identified and graded using International Study Group on Pancreatic Fistula criteria. Demographics, operative variables and 30-d postoperative NSAID use, dosage, and timing (early = postoperative day [POD] 0-5, late > POD 5) were collected. Univariate and multivariate logistic regressions were used to identify predictors of POPF. Four hundred twenty-three PDs were analyzed (mean age 66 y, 47% female), and 60% received NSAIDs postoperatively. Ketorolac (median POD 0-5 cumulative dose = 90 mg, interquartile range 60-165) was used in 35.7% (n = 151). POPF occurred in 90 patients (21.3%). Early (POD 0-5) ketorolac use was associated with increased POPF, especially grade A (odds ratio [OR] 2.16, P = 0.036). Each 25 mg incremental increase in ketorolac use was associated with a 10% increase in the incidence of POPF (OR 1.10, P = 0.021), whereas a cumulative dose of >150 mg was associated with a 44% increased risk of POPF (OR 1.44, 95% confidence interval 1.03-2.01, P = 0.035). A multivariate regression model identified estimated blood loss, soft gland, pancreatic duct diameter, body mass index, and cumulative ketorolac dose >150 mg as independent predictors of POPF (P < 0.0001, pseudo R 2  = 0.149). Increasing doses of ketorolac in the early postoperative period are associated with increased risk of POPF, whereas a cumulative dose of >150 mg is an independent predictor of POPF after PD. Copyright © 2017 Elsevier Inc. All rights reserved.

Long-term follow up of gallbladder polyps.

PubMed

Park, Jeong Youp; Hong, Sung Pil; Kim, Yoon Jae; Kim, Hong Jeoung; Kim, Hee Man; Cho, Jae Hee; Park, Seung Woo; Song, Si Young; Chung, Jae Bock; Bang, Seungmin

2009-02-01

The management of gallbladder polyps (GBP) is directly linked to the early diagnosis of gallbladder cancer (GBC). This study aimed to evaluate the malignant risk of GBP. In total, 1558 patients diagnosed with GBP were followed. Neoplastic polyps were defined as GBC and its premalignant lesions. The risk for malignancy was estimated with the cumulative detection rate of neoplastic polyps. Thirty-three cases (2.1%) were diagnosed with neoplastic polyps. The cumulative detection rates of neoplastic polyps were 1.7% at 1 year, 2.8% at 5 years, and 4% at 8 years after diagnosis. The size of GBP and the presence of gallstones were risk factors for neoplastic polyps. Polyps > or = 10 mm had a 24.2 times greater risk of malignancy than polyps < 10 mm. However, 15 of 33 neoplastic polyps (45.5%) were < 10 mm at the time of diagnosis of GBP. During follow up in 36 (3.5%) of 1027 cases, an increase in size was detected; of these, nine (25%) had neoplastic polyps. Even small polyps have a risk of malignancy, and careful long-term follow up of GBP will help detect and treat early GBC.

Use of cumulative mortality data in patients with acute myocardial infarction for early detection of variation in clinical practice: observational study.

PubMed

Lawrance, R A; Dorsch, M F; Sapsford, R J; Mackintosh, A F; Greenwood, D C; Jackson, B M; Morrell, C; Robinson, M B; Hall, A S

2001-08-11

Use of cumulative mortality adjusted for case mix in patients with acute myocardial infarction for early detection of variation in clinical practice. Observational study. 20 hospitals across the former Yorkshire region. All 2153 consecutive patients with confirmed acute myocardial infarction identified during three months. Variable life-adjusted displays showing cumulative differences between observed and expected mortality of patients; expected mortality calculated from risk model based on admission characteristics of age, heart rate, and systolic blood pressure. The performance of two individual hospitals over three months was examined as an example. One, the smallest district hospital in the region, had a series of 30 consecutive patients but had five more deaths than predicted. The variable life-adjusted display showed minimal variation from that predicted for the first 15 patients followed by a run of unexpectedly high mortality. The second example was the main tertiary referral centre for the region, which admitted 188 consecutive patients. The display showed a period of apparently poor performance followed by substantial improvement, where the plot rose steadily from a cumulative net lives saved of -4 to 7. These variations in patient outcome are unlikely to have been revealed during conventional audit practice. Variable life-adjusted display has been integrated into surgical care as a graphical display of risk-adjusted survival for individual surgeons or centres. In combination with a simple risk model, it may have a role in monitoring performance and outcome in patients with acute myocardial infarction.

Turbulent times: effects of turbulence and violence exposure in adolescence on high school completion, health risk behavior, and mental health in young adulthood.

PubMed

Boynton-Jarrett, Renée; Hair, Elizabeth; Zuckerman, Barry

2013-10-01

Turbulent social environments are associated with health and developmental risk, yet mechanisms have been understudied. Guided by a life course framework and stress theory, this study examined the association between turbulent life transitions (including frequent residential mobility, school transitions, family structure disruptions, and homelessness) and exposure to violence during adolescence and high school completion, mental health, and health risk behaviors in young adulthood. Participants (n = 4834) from the U.S. National Longitudinal Survey of Youth, 1997 cohort were followed prospectively from age 12-14 years for 10 years. We used structural equation models to investigate pathways between turbulence and cumulative exposure to violence (CEV), and high school completion, mental health, and health risk behaviors, while accounting for early life socio-demographics, family processes, and individual characteristics. Results indicated that turbulence index was associated with cumulative exposure to violence in adolescence. Both turbulence index and cumulative exposure to violence were positively associated with higher health risk behavior, poorer mental health, and inversely associated with high school completion. These findings highlight the importance of considering the cumulative impact of turbulent and adverse social environments when developing interventions to optimize health and developmental trajectory for adolescents transitioning into adulthood. Copyright © 2012 Elsevier Ltd. All rights reserved.

Cumulative Effects of Prenatal Substance Exposure and Early Adversity on Foster Children's HPA-Axis Reactivity during a Psychosocial Stressor

ERIC Educational Resources Information Center

Fisher, Philip A.; Kim, Hyoun K.; Bruce, Jacqueline; Pears, Katherine C.

2012-01-01

Dysregulated hypothalamic-pituitary-adrenocortical (HPA) axis stress response has been reported among individuals with prenatal substance exposure and those with early adversity exposure. However, few researchers have examined the combined effects of these risk factors. Patterns of HPA reactivity among maltreated foster children with and without…

When there Seem to be No Predetermining Factors: Early Child and Proximal Family Risk Predicting Externalizing Behavior in Young Children Incurring No Distal Family Risk

ERIC Educational Resources Information Center

Roskam, I.; Meunier, J.-C.; Stievenart, M.; Noel, M.-P.

2013-01-01

The main objective of the current study was to examine the impact of two child risk factors, i.e. personality and inhibition, and two proximal family risk factors, i.e. parenting and attachment, and the impact of their cumulative effect on later externalizing behavior among young children incurring no distal family risk. Data were collected in a…

Cumulative Environmental Risk in Substance Abusing Women: Early Intervention, Parenting Stress, Child Abuse Potential and Child Development.

ERIC Educational Resources Information Center

Kelley, Susan J.

2003-01-01

A study of 161 substance-abusing mothers assessed 10 maternal risk factors: maternal depression; domestic violence; nondomestic violence; family size; incarceration; no significant other at home; negative life events; psychiatric problems; homelessness; and drug use severity. Parenting stress and child abuse potential was higher for women with…

Effects of early exposure and lifetime exposure to intimate partner violence (IPV) on child adjustment.

PubMed

Graham-Bermann, Sandra A; Perkins, Suzanne

2010-01-01

Children exposed to overwhelming and potentially traumatic events early in their lives are considered at-risk for problems in adjustment. Yet it is not known whether it is the age of first exposure (AFE) to violence or the amount of violence that the child witnessed in their lifetime that has the greatest impact on adjustment. For a sample of 190 children ages 6 to 12 exposed to intimate partner violence, their mothers reported that the average length of their abusive relationship was 10 years. The majority of children were first exposed to family violence as infants (64%), with only 12% first exposed when school-aged. Both the AFE and an estimate of the cumulative amount of violence were significantly and negatively related to children's behavioral problems. However, in regression analyses controlling for child sex, ethnicity, age, and family environment variables, cumulative violence exposure accounted for greater variance in adjustment than did AFE. Furthermore, cumulative violence exposure mediated the relationship between AFE and externalizing behavior problems, indicating that the cumulative exposure to IPV outweighed the AFE in its effect on child adjustment.

Splenectomy and the incidence of venous thromboembolism and sepsis in patients with immune thrombocytopenia

PubMed Central

Boyle, Soames; White, Richard H.; Brunson, Ann

2013-01-01

Patients with immune thrombocytopenia (ITP) who relapse after an initial trial of corticosteroid treatment present a therapeutic challenge. Current guidelines recommend consideration of splenectomy, despite the known risks associated with surgery and the postsplenectomy state. To better define these risks, we identified a cohort of 9976 patients with ITP, 1762 of whom underwent splenectomy. The cumulative incidence of abdominal venous thromboembolism (AbVTE) was 1.6% compared with 1% in patients who did not undergo splenectomy; venous thromboembolism (VTE) (deep venous thrombosis and pulmonary embolus) after splenectomy was 4.3% compared with 1.7% in patients who did not undergo splenectomy. There was increased risk of AbVTE early (<90 days; hazard ratio [HR] 5.4 [confidence interval (CI), 2.3-12.5]), but not late (≥90 days; HR 1.5 [CI, 0.9-2.6]) after splenectomy. There was increased risk of VTE both early (HR 5.2 [CI, 3.2-8.5]) and late (HR 2.7 [CI, 1.9-3.8]) after splenectomy. The cumulative incidence of sepsis was 11.1% among the ITP patients who underwent splenectomy and 10.1% among the patients who did not. Splenectomy was associated with a higher adjusted risk of sepsis, both early (HR 3.3 [CI, 2.4-4.6]) and late (HR 1.6 or 3.1, depending on comorbidities). We conclude that ITP patients post splenectomy are at increased risk for AbVTE, VTE, and sepsis. PMID:23637127

Risk of Fatal Cerebrovascular Accidents after External Beam Radiation Therapy for Early Stage Glottic Larynx Cancer

PubMed Central

Swisher-McClure, Samuel; Mitra, Nandita; Lin, Alexander; Ahn, Peter; Wan, Fei; O’Malley, Bert; Weinstein, Gregory S.; Bekelman, Justin E.

2013-01-01

Background This study compared the risk of fatal cerebrovascular accidents (CVA) in patients with early stage glottic larynx cancer receiving surgery or external beam radiation therapy (EBRT). Methods and Materials Using a competing risks survival analysis, we compared the risk of death due to CVA among patients with early stage glottic larynx cancer receiving surgery or EBRT in the SEER database. Results The cumulative incidence of fatal CVA at 15 years was higher in patients receiving EBRT (2.8 %; 95% CI 2.3%–3.4%) compared to surgery (1.5 %; 95% CI 0.8 %–2.3%, p= 0.024). In multivariable competing risks regression models, EBRT remained associated with an increased risk of fatal CVA compared to surgery (adjusted HR 1.75; 95% CI 1.04–2.96, p= 0.037). Conclusion Treatment of early stage glottic larynx cancer with EBRT was associated with a small increase in the risk of late fatal CVA events relative to surgery. PMID:23595858

Prognostic discrimination for early chronic phase chronic myeloid leukemia in imatinib era: comparison of Sokal, Euro, and EUTOS scores in Korean population.

PubMed

Yahng, Seung-Ah; Jang, Eun-Jung; Choi, Soo-Young; Lee, Sung-Eun; Kim, Soo-Hyun; Kim, Dong-Wook

2014-08-01

Beyond the conventional Sokal and Euro scores, a new prognostic risk classification, based on the European Treatment Outcome Study (EUTOS), has been developed to predict the outcome of treatment with tyrosine kinase inhibitors (TKI) in chronic myeloid leukemia (CML). In the present study, each risk score was validated by various endpoints in 206 Korean patients with early chronic-phase CML treated with up-front standard dose imatinib. In our analysis, all three scores were found to be valid. The 5-year event-free survival (EFS) was significantly discriminated using Sokal (P = 0.002), Euro (P = 0.003), and EUTOS (P = 0.029), with the worst probability by Euro high-risk (62 vs. 49 vs. 67 %) and better EFS in Sokal low-risk (89 vs. 86 vs. 82 %). Combining all scores identified 6 % of all patients having homogeneous high-risk with distinctively worse outcomes (5-year EFS of 41 %, cumulative complete cytogenetic response rate of 56 %, and cumulative major molecular response rate of 27 %), whereas the group of discordance in risk scores (60 %) had similar results to those of intermediate-risk groups of Sokal and Euro scores. Combining all risk scores for baseline risk assessment may be useful in clinical practice for identifying groups of patients who may benefit from treatment initiation with a more potent TKI among the currently available first-line TKIs.

Attachment and attention: protection in relation to gender and cumulative social-contextual adversity.

PubMed

Fearon, R M Pasco; Belsky, Jay

2004-01-01

Data from 918 children from the National Institute of Child Health and Human Development (NICHD) Study of Early Child Care were examined to test the interrelation of attachment and attentional performance and 2 known risks for poor attentional performance: male gender and social-contextual adversity. Attachment was measured using the Strange Situation at 15 months, attentional performance by a Continuous Performance Test (CPT) and maternal questionnaires at 54 months, and social-contextual adversity by a variety of measures from birth to 54 months. Findings indicated (a) that children with secure attachment were less susceptible to the effects of cumulative risk and gender on CPT attentional performance than their insecure counterparts and that (b) no such differential risk susceptibility was evident for maternal reports of attention-related behavior problems.

Early physiological markers of cardiovascular risk in community based adolescents with a depressive disorder.

PubMed

Waloszek, Joanna M; Byrne, Michelle L; Woods, Michael J; Nicholas, Christian L; Bei, Bei; Murray, Greg; Raniti, Monika; Allen, Nicholas B; Trinder, John

2015-04-01

Depression is recognised as an independent cardiovascular risk factor in adults. Identifying this relationship early on in life is potentially important for the prevention of cardiovascular disease (CVD). This study investigated whether clinical depression is associated with multiple physiological markers of CVD risk in adolescents from the general community. Participants aged 12-18 years were recruited from the general community and screened for depressive symptoms. Individuals with high and low depressive symptoms were administered a diagnostic interview. Fifty participants, 25 with a current depressive episode and 25 matched healthy controls, subsequently completed cardiovascular assessments. Variables assessed were automatic brachial and continuous beat-to-beat finger arterial blood pressure, heart rate, vascular functioning by pulse amplitude tonometry following reactive hyperaemia and pulse transit time (PTT) at rest. Blood samples were collected to measure cholesterol, glucose and glycohaemoglobin levels and an index of cumulative risk of traditional cardiovascular risk factors was calculated. Depressed adolescents had a significantly lower reactive hyperaemia index and shorter PTT, suggesting deterioration in vascular integrity and structure. Higher fasting glucose and triglyceride levels were also observed in the depressed group, who also had higher cumulative risk scores indicative of increased engagement in unhealthy behaviours and higher probability of advanced atherosclerotic lesions. The sample size and number of males who completed all cardiovascular measures was small. Clinically depressed adolescents had poorer vascular functioning and increased CVD risk compared to controls, highlighting the need for early identification and intervention for the prevention of CVD in depressed youth. Copyright © 2015 Elsevier B.V. All rights reserved.

Beyond Cumulative Risk: A Dimensional Approach to Childhood Adversity.

PubMed

McLaughlin, Katie A; Sheridan, Margaret A

2016-08-01

Children who have experienced environmental adversity-such as abuse, neglect, or poverty-are more likely to develop physical and mental health problems, perform poorly at school, and have difficulties in social relationships than children who have not encountered adversity. What is less clear is how and why adverse early experiences exert such a profound influence on children's development. Identifying developmental processes that are disrupted by adverse early environments is the key to developing better intervention strategies for children who have experienced adversity. Yet, much existing research relies on a cumulative risk approach that is unlikely to reveal these mechanisms. This approach tallies the number of distinct adversities experienced to create a risk score. This risk score fails to distinguish between distinct types of environmental experience, implicitly assuming that very different experiences influence development through the same underlying mechanisms. We advance an alternative model. This novel approach conceptualizes adversity along distinct dimensions, emphasizes the central role of learning mechanisms, and distinguishes between different forms of adversity that might influence learning in distinct ways. A key advantage of this approach is that learning mechanisms provide clear targets for interventions aimed at preventing negative developmental outcomes in children who have experienced adversity.

Effect of liver cirrhosis on metastasis in colorectal cancer patients: a nationwide population-based cohort study.

PubMed

Chiou, Wen-Yen; Chang, Chun-Ming; Tseng, Kuo-Chih; Hung, Shih-Kai; Lin, Hon-Yi; Chen, Yi-Chun; Su, Yu-Chieh; Tseng, Chih-Wei; Tsai, Shiang-Jiun; Lee, Moon-Sing; Li, Chung-Yi

2015-02-01

The aim of this study is to evaluate the liver metastasis risk among colorectal cancer patients with liver cirrhosis. This was a nationwide population-based cohort study of 2973 newly diagnosed colorectal cancer patients with liver cirrhosis and 11 892 age-sex matched controls enrolled in Taiwan between 2000 and 2010. The cumulative risk by Kaplan-Meier method, hazard ratio by the multivariate Cox proportional model and the incidence density were evaluated. The median time interval from the colorectal cancer diagnosis to the liver metastasis event was 7.42 months for liver cirrhosis group and 7.67 months for non-liver cirrhosis group. The incidence density of liver metastasis was higher in the liver cirrhosis group (61.92/1000 person-years) than in the non-liver cirrhosis group (47.48/1000 person-years), with a significantly adjusted hazard ratio of 1.15 (95% CI = 1.04-1.28, P = 0.007). The 10-year cumulative risk of liver metastasis for the liver cirrhosis and the non-liver cirrhosis group was 27.1 and 23.6%, respectively (P = 0.006). For early cancer stage with locoregional disease patients receiving surgery alone without adjuvant anti-cancer treatments, patients with liver cirrhosis (10-year cumulative risk 23.9 vs. 15.7%, P < 0.001) or cirrhotic symptoms (10-year cumulative risk 25.6 vs. 16.6%, P = 0.009) both still had higher liver metastasis risk compared with their counterparts. For etiologies of liver cirrhosis, the 10-year cumulative risk for hepatitis B virus and hepatitis C virus, hepatitis B virus, hepatitis C virus, other causes and non-liver cirrhosis were 29.5, 28.9, 27.5, 26.7 and 23.4%, respectively, (P = 0.03). Our study found that liver metastasis risk was underestimated and even higher in colorectal cancer patients with liver cirrhosis. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Cumulative risk on the oxytocin receptor gene (OXTR) underpins empathic communication difficulties at the first stages of romantic love

PubMed Central

Schneiderman, Inna; Kanat-Maymon, Yaniv; Ebstein, Richard P.

2014-01-01

Empathic communication between couples plays an important role in relationship quality and individual well-being and research has pointed to the role of oxytocin in providing the neurobiological substrate for pair-bonding and empathy. Here, we examined links between genetic variability on the oxytocin receptor gene (OXTR) and empathic behaviour at the initiation of romantic love. Allelic variations on five OXTR single nucleotide polymorphisms (SNPs) previously associated with susceptibility to disorders of social functioning were genotyped in 120 new lovers: OXTRrs13316193, rs2254298, rs1042778, rs2268494 and rs2268490. Cumulative genetic risk was computed by summing risk alleles on each SNP. Couples were observed in support-giving interaction and behaviour was coded for empathic communication, including affective congruence, maintaining focus on partner, acknowledging partner's distress, reciprocal exchange and non-verbal empathy. Hierarchical linear modelling indicated that individuals with high OXTR risk exhibited difficulties in empathic communication. OXTR risk predicted empathic difficulties above and beyond the couple level, relationship duration, and anxiety and depressive symptoms. Findings underscore the involvement of oxytocin in empathic behaviour during the early stages of social affiliation, and suggest the utility of cumulative risk and plasticity indices on the OXTR as potential biomarkers for research on disorders of social dysfunction and the neurobiology of empathy. PMID:23974948

Psychobiological Influences on Maternal Sensitivity in the Context of Adversity

PubMed Central

Finegood, Eric D.; Blair, Clancy; Granger, Douglas A.; Hibel, Leah C.; Mills-Koonce, Roger

2016-01-01

This study evaluated prospective longitudinal relations among an index of poverty-related cumulative risk, maternal salivary cortisol, child negative affect, and maternal sensitivity across the first two postpartum years. Participants included 1,180 biological mothers residing in rural and predominantly low-income communities in the US. Multilevel growth curve analyses indicated that an index of cumulative risk was positively associated with maternal cortisol across the postpartum (study visits occurring at approximately 7, 15, and 24 months postpartum) over and above effects for African American ethnicity, time of day of saliva collection, age, parity status, having given birth to another child, contraceptive use, tobacco smoking, body mass index, and breastfeeding. Consistent with a psychobiological theory of mothering, maternal salivary cortisol was negatively associated with maternal sensitivity observed during parent-child interactions across the first two postpartum years over and above effects for poverty-related cumulative risk, child negative affect, as well as a large number of covariates associated with cortisol and maternal sensitivity. Child negative affect expressed during parent-child interactions was negatively associated with observed maternal sensitivity at late (24 months) but not early time points of observation (7 months) and cumulative risk was negatively associated with maternal sensitivity across the postpartum and this effect strengthened over time. Results advance our understanding of the dynamic, transactional, and psychobiological influences on parental caregiving behaviors across the first two postpartum years. PMID:27337514

Syndromic surveillance system based on near real-time cattle mortality monitoring.

PubMed

Torres, G; Ciaravino, V; Ascaso, S; Flores, V; Romero, L; Simón, F

2015-05-01

Early detection of an infectious disease incursion will minimize the impact of outbreaks in livestock. Syndromic surveillance based on the analysis of readily available data can enhance traditional surveillance systems and allow veterinary authorities to react in a timely manner. This study was based on monitoring the number of cattle carcasses sent for rendering in the veterinary unit of Talavera de la Reina (Spain). The aim was to develop a system to detect deviations from expected values which would signal unexpected health events. Historical weekly collected dead cattle (WCDC) time series stabilized by the Box-Cox transformation and adjusted by the minimum least squares method were used to build the univariate cycling regression model based on a Fourier transformation. Three different models, according to type of production system, were built to estimate the baseline expected number of WCDC. Two types of risk signals were generated: point risk signals when the observed value was greater than the upper 95% confidence interval of the expected baseline, and cumulative risk signals, generated by a modified cumulative sum algorithm, when the cumulative sums of reported deaths were above the cumulative sum of expected deaths. Data from 2011 were used to prospectively validate the model generating seven risk signals. None of them were correlated to infectious disease events but some coincided, in time, with very high climatic temperatures recorded in the region. The harvest effect was also observed during the first week of the study year. Establishing appropriate risk signal thresholds is a limiting factor of predictive models; it needs to be adjusted based on experience gained during the use of the models. To increase the sensitivity and specificity of the predictions epidemiological interpretation of non-specific risk signals should be complemented by other sources of information. The methodology developed in this study can enhance other existing early detection surveillance systems. Syndromic surveillance based on mortality monitoring can reduce the detection time for certain disease outbreaks associated with mild mortality only detected at regional level. The methodology can be adapted to monitor other parameters routinely collected at farm level which can be influenced by communicable diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

Likelihood of early detection of breast cancer in relation to false-positive risk in life-time mammographic screening: population-based cohort study.

PubMed

Otten, J D M; Fracheboud, J; den Heeten, G J; Otto, S J; Holland, R; de Koning, H J; Broeders, M J M; Verbeek, A L M

2013-10-01

Women require balanced, high-quality information when making an informed decision on screening benefits and harms before attending biennial mammographic screening. The cumulative risk of a false-positive recall and/or (small) screen-detected or interval cancer over 13 consecutive screening examinations for women aged 50 from the start of screening were estimated using data from the Nijmegen programme, the Netherlands. Women who underwent 13 successive screens in the period 1975-1976 had a 5.3% cumulative chance of a screen-detected cancer, with a 4.2% risk of at least one false-positive recall. The risk of being diagnosed with interval cancer was 3.7%. Two decades later, these estimates were 6.9%, 7.3% and 2.9%, respectively. The chance of detection of a small, favourable invasive breast cancer, anticipating a normal life-expectancy, rose from 2.3% to 3.7%. Extrapolation to digital screening mammography indicates that the proportion of false-positive results will rise to 16%. Dutch women about to participate in the screening programme can be reassured that the chance of false-positive recall in the Netherlands is relatively low. A new screening policy and improved mammography have increased the detection of an early screening carcinoma and lowering the risk of interval carcinoma.

Language delay in severely neglected children: a cumulative or specific effect of risk factors?

PubMed

Sylvestre, Audette; Mérette, Chantal

2010-06-01

This research sought to determine if the language delay (LD) of severely neglected children under 3 years old was better explained by a cumulative risk model or by the specificity of risk factors. The objective was also to identify the risk factors with the strongest impact on LD among various biological, psychological, and environmental factors. Sixty-eight severely neglected children and their mothers participated in this cross-sectional study. Children were between 2 and 36 months of age. Data included information about the child's language development and biological, psychological, and environmental risk factors. Prevalence of LD is significantly higher in this subgroup of children than in the population as a whole. Although we observed that the risk of LD significantly increased with an increase in the cumulative count of the presence of the child's biological-psychological risk factors, the one-by-one analysis of the individual factors revealed that the cumulative effect mainly reflected the specific impact of the child's cognitive development. When we considered also the environmental risk factors, multivariate logistic regression established that cognitive development, the mother's own physical and emotional abuse experience as a child, and the mother's low acceptability level towards her child are linked to LD in severely neglected children. Language development is the result of a complex interaction between risk factors. LD in severely neglected children is better explained by the specificity of risk factors than by the cumulative risk model. Most prevention and early intervention programs promote and target an increase in the quantity and quality of language stimulation offered to the child. Our results suggest that particular attention should be given to other environmental factors, specifically the mother's psychological availability and her sensitivity towards the child. It is essential to suggest interventions targeting various ecological dimensions of neglectful mothers to help break the intergenerational neglect transmission cycle. It is also important to develop government policies and ensure that efforts among the various response networks are concerted since in-depth changes to neglect situations can only come about when all interested parties become involved. Copyright 2010 Elsevier Ltd. All rights reserved.

Affiliation buffers stress: cumulative genetic risk in oxytocin-vasopressin genes combines with early caregiving to predict PTSD in war-exposed young children.

PubMed

Feldman, R; Vengrober, A; Ebstein, R P

2014-03-11

Research indicates that risk for post-traumatic stress disorder (PTSD) is shaped by the interaction between genetic vulnerability and early caregiving experiences; yet, caregiving has typically been assessed by adult retrospective accounts. Here, we employed a prospective longitudinal design with real-time observations of early caregiving combined with assessment of genetic liability along the axis of vasopressin-oxytocin (OT) gene pathways to test G × E contributions to PTSD. Participants were 232 young Israeli children (1.5-5 years) and their parents, including 148 living in zones of continuous war and 84 controls. A cumulative genetic risk factor was computed for each family member by summing five risk alleles across three genes (OXTR, CD38 and AVPR1a) previously associated with psychopathology, sociality and caregiving. Child PTSD was diagnosed and mother-child interactions were observed in multiple contexts. In middle childhood (7-8 years), child psychopathology was re-evaluated. War exposure increased propensity to develop Axis-I disorder by threefold: 60% of exposed children displayed a psychiatric disorder by middle childhood and 62% of those showed several comorbid disorders. On the other hand, maternal sensitive support reduced risk for psychopathology. G × E effect was found for child genetic risk: in the context of war exposure, greater genetic risk on the vasopressin-OT pathway increased propensity for psychopathology. Among exposed children, chronicity of PTSD from early to middle childhood was related to higher child, maternal and paternal genetic risk, low maternal support and greater initial avoidance symptoms. Child avoidance was predicted by low maternal support and reduced mother-child reciprocity. These findings underscore the saliency of both genetic and behavioral facets of the human affiliation system in shaping vulnerability to PTSD as well as providing an underlying mechanism of post-traumatic resilience.

Affiliation buffers stress: cumulative genetic risk in oxytocin–vasopressin genes combines with early caregiving to predict PTSD in war-exposed young children

PubMed Central

Feldman, R; Vengrober, A; Ebstein, R P

2014-01-01

Research indicates that risk for post-traumatic stress disorder (PTSD) is shaped by the interaction between genetic vulnerability and early caregiving experiences; yet, caregiving has typically been assessed by adult retrospective accounts. Here, we employed a prospective longitudinal design with real-time observations of early caregiving combined with assessment of genetic liability along the axis of vasopressin–oxytocin (OT) gene pathways to test G × E contributions to PTSD. Participants were 232 young Israeli children (1.5–5 years) and their parents, including 148 living in zones of continuous war and 84 controls. A cumulative genetic risk factor was computed for each family member by summing five risk alleles across three genes (OXTR, CD38 and AVPR1a) previously associated with psychopathology, sociality and caregiving. Child PTSD was diagnosed and mother–child interactions were observed in multiple contexts. In middle childhood (7–8 years), child psychopathology was re-evaluated. War exposure increased propensity to develop Axis-I disorder by threefold: 60% of exposed children displayed a psychiatric disorder by middle childhood and 62% of those showed several comorbid disorders. On the other hand, maternal sensitive support reduced risk for psychopathology. G × E effect was found for child genetic risk: in the context of war exposure, greater genetic risk on the vasopressin–OT pathway increased propensity for psychopathology. Among exposed children, chronicity of PTSD from early to middle childhood was related to higher child, maternal and paternal genetic risk, low maternal support and greater initial avoidance symptoms. Child avoidance was predicted by low maternal support and reduced mother–child reciprocity. These findings underscore the saliency of both genetic and behavioral facets of the human affiliation system in shaping vulnerability to PTSD as well as providing an underlying mechanism of post-traumatic resilience. PMID:24618689

Life Course Associations between Victimization and Aggression: Distinct and Cumulative Contributions

PubMed Central

Logan-Greene, Patricia; Nurius, Paula S.; Hooven, Carole; Thompson, Elaine Adams

2014-01-01

The connections between early maltreatment and later aggression are well established in the literature, however gaps remain in our understanding of developmental processes. This study investigates the cascading lifecourse linkages between victimization experiences from childhood through early adulthood andlater aggressive behavior. The diverse, at-risk sample is of particular importance to child and adolescent specialists, as it represents highly vulnerable youth accessible through conventional school settings. In addition to direct pathways from proximal life periods, path analysis revealed significant indirect mediated pathways through which earlier life victimizationcontributes to aggressive behaviors in later life periods as well as revictimization. Multivariateregressions support theorized cumulative effects of multi-form victimization as well as distinct contributions of victimization domains (emotional, witnessing, physical, property, and sexual) in explaining aggressive behavior.Consistent with theorizing about the developmental impact of early maltreatment, results bolster the importance of interrupting pathways from victimization to revictimization and later aggression. Findings are evaluated in light of implications for early identification and prevention programming. PMID:26190899

Life Course Associations between Victimization and Aggression: Distinctive and Cumulative Contributions

PubMed Central

Logan-Greene, Patricia; Nurius, Paula S.; Hooven, Carole; Thompson, Elaine Adams

2014-01-01

The connections between early maltreatment and later aggression are well established in the literature, however gaps remain in our understanding of developmental processes. This study investigates the cascading life course linkages between victimization experiences from childhood through early adulthood and later aggressive behavior. The diverse, at-risk sample is of particular importance to child and adolescent specialists, as it represents highly vulnerable youth accessible through conventional school settings. In addition to direct pathways from proximal life periods, path analysis revealed significant indirect mediated pathways through which earlier life victimization contributes to aggressive behaviors in later life periods as well as revictimization. Multivariate regressions support theorized cumulative effects of multi-form victimization as well as distinct contributions of victimization domains (emotional, witnessing, physical, property, and sexual) in explaining aggressive behavior. Consistent with theorizing about the developmental impact of early maltreatment, results bolster the importance of interrupting pathways from victimization to revictimization and later aggression. Findings are evaluated in light of implications for early identification and prevention programming. PMID:26190900

Risk of fatal cerebrovascular accidents after external beam radiation therapy for early-stage glottic laryngeal cancer.

PubMed

Swisher-McClure, Samuel; Mitra, Nandita; Lin, Alexander; Ahn, Peter; Wan, Fei; O'Malley, Bert; Weinstein, Gregory S; Bekelman, Justin E

2014-05-01

This study compared the risk of fatal cerebrovascular accidents (CVAs) in patients with early-stage glottic laryngeal cancer receiving surgery or external beam radiation therapy (EBRT). Using a competing risks survival analysis, we compared the risk of death because of CVA among patients with early-stage glottic laryngeal cancer receiving surgery or EBRT in the Surveillance, Epidemiology, and End Results (SEER) database. The cumulative incidence of fatal CVA at 15 years was higher in patients receiving EBRT (2.8%; 95% confidence interval [CI], 2.3% to 3.4%) compared to surgery (1.5%; 95% CI, 0.8% to 2.3%; p = .024). In multivariable competing risks regression models, EBRT remained associated with an increased risk of fatal CVA compared to surgery (adjusted hazard ratio [HR], 1.75; 95% CI, 1.04-2.96; p = .037). Treatment for early-stage glottic laryngeal cancer with EBRT was associated with a small increase in the risk of late fatal CVA events relative to surgery. Copyright © 2013 Wiley Periodicals, Inc.

The Role of Sleep in Childhood Psychiatric Disorders

PubMed Central

Alfano, Candice A.; Gamble, Amanda L.

2009-01-01

Although sleep problems often comprise core features of psychiatric disorders, inadequate attention has been paid to the complex, reciprocal relationships involved in the early regulation of sleep, emotion, and behavior. In this paper, we review the pediatric literature examining sleep in children with primary psychiatric disorders as well as evidence for the role of early sleep problems as a risk factor for the development of psychopathology. Based on these cumulative data, possible mechanisms and implications of early sleep disruption are considered. Finally, assessment recommendations for mental health clinicians working with children and adolescents are provided toward reducing the risk of and improving treatments for sleep disorders and psychopathology in children and adolescents. PMID:19960111

Risk of marrow neoplasms after adjuvant breast cancer therapy: the national comprehensive cancer network experience.

PubMed

Wolff, Antonio C; Blackford, Amanda L; Visvanathan, Kala; Rugo, Hope S; Moy, Beverly; Goldstein, Lori J; Stockerl-Goldstein, Keith; Neumayer, Leigh; Langbaum, Terry S; Theriault, Richard L; Hughes, Melissa E; Weeks, Jane C; Karp, Judith E

2015-02-01

Outcomes for early-stage breast cancer have improved. First-generation adjuvant chemotherapy trials reported a 0.27% 8-year cumulative incidence of myelodysplastic syndrome/acute myelogenous leukemia. Incomplete ascertainment and follow-up may have underestimated subsequent risk of treatment-associated marrow neoplasm (MN). We examined the MN frequency in 20,063 patients with stage I to III breast cancer treated at US academic centers between 1998 and 2007. Time-to-event analyses were censored at first date of new cancer event, last contact date, or death and considered competing risks. Cumulative incidence, hazard ratios (HRs), and comparisons with Surveillance, Epidemiology, and End Results estimates were obtained. Marrow cytogenetics data were reviewed. Fifty patients developed MN (myeloid, n = 42; lymphoid, n = 8) after breast cancer (median follow-up, 5.1 years). Patients who developed MN had similar breast cancer stage distribution, race, and chemotherapy exposure but were older compared with patients who did not develop MN (median age, 59.1 v 53.9 years, respectively; P = .03). Two thirds of patients had complex MN cytogenetics. Risk of MN was significantly increased after surgery plus chemotherapy (HR, 6.8; 95% CI, 1.3 to 36.1) or after all modalities (surgery, chemotherapy, and radiation; HR, 7.6; 95% CI, 1.6 to 35.8), compared with no treatment with chemotherapy. MN rates per 1,000 person-years were 0.16 (surgery), 0.43 (plus radiation), 0.46 (plus chemotherapy), and 0.54 (all three modalities). Cumulative incidence of MN doubled between years 5 and 10 (0.24% to 0.48%); 9% of patients were alive at 10 years. In this large early-stage breast cancer cohort, MN risk after radiation and/or adjuvant chemotherapy was low but higher than previously described. Risk continued to increase beyond 5 years. Individual risk of MN must be balanced against the absolute survival benefit of adjuvant chemotherapy. © 2014 by American Society of Clinical Oncology.

Cumulative environmental risk in substance abusing women: early intervention, parenting stress, child abuse potential and child development☆

PubMed Central

Schuler, Maureen E.; Black, Maureen M.; Kettinger, Laurie; Harrington, Donna

2011-01-01

Objective To assess the relationship between cumulative environmental risks and early intervention, parenting attitudes, potential for child abuse and child development in substance abusing mothers. Method We studied 161 substance-abusing women, from a randomized longitudinal study of a home based early intervention, who had custody of their children through 18 months. The intervention group received weekly home visits in the first 6 months and biweekly visits from 6 to 18 months. Parenting stress and child abuse potential were assessed at 6 and 18 months postpartum. Children’s mental and motor development (Bayley MDI and PDI) and language development (REEL) were assessed at 6, 12, and 18 months postpartum. Ten maternal risk factors were assessed: maternal depression, domestic violence, nondomestic violence, family size, incarceration, no significant other in home, negative life events, psychiatric problems, homelessness, and severity of drug use. Level of risk was recoded into four categories (2 or less, 3, 4, and 5 or more), which had adequate cell sizes for repeated measures analysis. Data analysis Repeated measures analyses were run to examine how level of risk and group (intervention or control) were related to parenting stress, child abuse potential, and children’s mental, motor and language development over time. Results Parenting stress and child abuse potential were higher for women with five risks or more compared with women who had four or fewer risks; children’s mental, motor, and language development were not related to level of risk. Children in the intervention group had significantly higher scores on the PDI at 6 and 18 months (107.4 vs. 103.6 and 101.1 vs. 97.2) and had marginally better scores on the MDI at 6 and 12 months (107.7 vs. 104.2 and 103.6 vs. 100.1), compared to the control group. Conclusion Compared to drug-abusing women with fewer than five risks, women with five or more risks found parenting more stressful and indicated greater inclination towards abusive and neglectful behavior, placing their infants at increased risk for poor parenting, abuse and neglect. Early home-based intervention in high-risk families may be beneficial to infant development. PMID:14550327

Investigating the Influences of Language Delay and/or Familial Risk for Dyslexia on Brain Structure in 5-Year-Olds

PubMed Central

Raschle, Nora Maria; Becker, Bryce Larkin Chessell; Smith, Sara; Fehlbaum, Lynn Valérie; Wang, Yingying; Gaab, Nadine

2017-01-01

Abstract Early language delay has often been associated with atypical language/literacy development. Neuroimaging studies further indicate functional disruptions during language and print processing in school-age children with a retrospective report of early language delay. Behavioral data of 114 5-year-olds with a retrospective report of early language delay in infancy (N = 34) and those without (N = 80) and with a familial risk for dyslexia and those without are presented. Behaviorally, children with a retrospective report of early language delay exhibited reduced performance in language/reading-related measures. A voxel-based morphometry analysis in a subset (N = 46) demonstrated an association between reduced gray matter volume and early language delay in left-hemispheric middle temporal, occipital, and frontal regions. Alterations in middle temporal cortex in children with a retrospective report of early language delay were observed regardless of familial risk for dyslexia. Additionally, while children with isolated familial risk for dyslexia showed gray matter reductions in temporoparietal and occipitotemporal regions, these effects were most profound in children with both risk factors. An interaction effect of early language delay and familial risk was revealed in temporoparietal, occipital, and frontal cortex. Our findings support a cumulative effect of early behavioral and genetic risk factors on brain development and may ultimately inform diagnosis/treatment. PMID:26585334

Psychobiological influences on maternal sensitivity in the context of adversity.

PubMed

Finegood, Eric D; Blair, Clancy; Granger, Douglas A; Hibel, Leah C; Mills-Koonce, Roger

2016-07-01

This study evaluated prospective longitudinal relations among an index of poverty-related cumulative risk, maternal salivary cortisol, child negative affect, and maternal sensitivity across the first 2 postpartum years. Participants included 1,180 biological mothers residing in rural and predominantly low-income communities in the United States. Multilevel growth curve analyses indicated that an index of cumulative risk was positively associated with maternal cortisol across the postpartum (study visits occurring at approximately 7, 15, and 24 months postpartum) over and above effects for African American ethnicity, time of day of saliva collection, age, parity status, having given birth to another child, contraceptive use, tobacco smoking, body mass index, and breastfeeding. Consistent with a psychobiological theory of mothering, maternal salivary cortisol was negatively associated with maternal sensitivity observed during parent-child interactions across the first 2 postpartum years over and above effects for poverty-related cumulative risk, child negative affect, as well as a large number of covariates associated with cortisol and maternal sensitivity. Child negative affect expressed during parent-child interactions was negatively associated with observed maternal sensitivity at late (24 months) but not early time points of observation (7 months) and cumulative risk was negatively associated with maternal sensitivity across the postpartum and this effect strengthened over time. Results advance our understanding of the dynamic, transactional, and psychobiological influences on parental caregiving behaviors across the first 2 postpartum years. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Using exposomics to assess cumulative risks and promote health.

PubMed

Smith, Martyn T; de la Rosa, Rosemarie; Daniels, Sarah I

2015-12-01

Under the exposome paradigm all nongenetic factors contributing to disease are considered to be 'environmental' including chemicals, drugs, infectious agents, and psychosocial stress. We can consider these collectively as environmental stressors. Exposomics is the comprehensive analysis of exposure to all environmental stressors and should yield a more thorough understanding of chronic disease development. We can operationalize exposomics by studying all the small molecules in the body and their influence on biological pathways that lead to impaired health. Here, we describe methods by which this may be achieved and discuss the application of exposomics to cumulative risk assessment in vulnerable populations. Since the goal of cumulative risk assessment is to analyze, characterize, and quantify the combined risks to health from exposures to multiple agents or stressors, it seems that exposomics is perfectly poised to advance this important area of environmental health science. We should therefore support development of tools for exposomic analysis and begin to engage impacted communities in participatory exposome research. A first step may be to apply exposomics to vulnerable populations already studied by more conventional cumulative risk approaches. We further propose that recent migrants, low socioeconomic groups with high environmental chemical exposures, and pregnant women should be high priority populations for study by exposomics. Moreover, exposomics allows us to study interactions between chronic stress and environmental chemicals that disrupt stress response pathways (i.e., 'stressogens'). Exploring the impact of early life exposures and maternal stress may be an interesting and accessible topic for investigation by exposomics using biobanked samples. © 2015 Wiley Periodicals, Inc.

Cumulative risk on the oxytocin receptor gene (OXTR) underpins empathic communication difficulties at the first stages of romantic love.

PubMed

Schneiderman, Inna; Kanat-Maymon, Yaniv; Ebstein, Richard P; Feldman, Ruth

2014-10-01

Empathic communication between couples plays an important role in relationship quality and individual well-being and research has pointed to the role of oxytocin in providing the neurobiological substrate for pair-bonding and empathy. Here, we examined links between genetic variability on the oxytocin receptor gene (OXTR) and empathic behaviour at the initiation of romantic love. Allelic variations on five OXTR single nucleotide polymorphisms (SNPs) previously associated with susceptibility to disorders of social functioning were genotyped in 120 new lovers: OXTRrs13316193, rs2254298, rs1042778, rs2268494 and rs2268490. Cumulative genetic risk was computed by summing risk alleles on each SNP. Couples were observed in support-giving interaction and behaviour was coded for empathic communication, including affective congruence, maintaining focus on partner, acknowledging partner's distress, reciprocal exchange and non-verbal empathy. Hierarchical linear modelling indicated that individuals with high OXTR risk exhibited difficulties in empathic communication. OXTR risk predicted empathic difficulties above and beyond the couple level, relationship duration, and anxiety and depressive symptoms. Findings underscore the involvement of oxytocin in empathic behaviour during the early stages of social affiliation, and suggest the utility of cumulative risk and plasticity indices on the OXTR as potential biomarkers for research on disorders of social dysfunction and the neurobiology of empathy. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Cumulative contextual risk at birth in relation to adolescent substance use, conduct problems, and risky sex: General and specific predictive associations in a Finnish birth cohort.

PubMed

Mason, W Alex; January, Stacy-Ann A; Chmelka, Mary B; Parra, Gilbert R; Savolainen, Jukka; Miettunen, Jouko; Järvelin, Marjo-Riitta; Taanila, Anja; Moilanen, Irma

2016-07-01

Research indicates that risk factors cluster in the most vulnerable youth, increasing their susceptibility for adverse developmental outcomes. However, most studies of cumulative risk are cross-sectional or short-term longitudinal, and have been based on data from the United States or the United Kingdom. Using data from the Northern Finland Birth Cohort 1986 Study (NFBC1986), we examined cumulative contextual risk (CCR) at birth as a predictor of adolescent substance use and co-occurring conduct problems and risky sex to determine the degree to which CCR predicts specific outcomes over-and-above its effect on general problem behavior, while testing for moderation of associations by gender. Analyses of survey data from 6963 participants of the NFBC1986 followed from the prenatal/birth period into adolescence were conducted using structural equation modeling. CCR had long-term positive associations with first-order substance use, conduct problems, and risky sex factors, and, in a separate analysis, with a second-order general problem behavior factor. Further analyses showed that there was a positive specific effect of CCR on risky sex, over-and-above general problem behavior, for girls only. This study, conducted within the Finnish context, showed that CCR at birth had long-term general and specific predictive associations with substance use and co-occurring problem behaviors in adolescence; effects on risky sex were stronger for girls. Results are consistent with the hypothesis that early exposure to CCR can have lasting adverse consequences, suggesting the need for early identification and intervention efforts for vulnerable children. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prevalence and risk factors of adhesive capsulitis of the shoulder after breast cancer treatment.

PubMed

Yang, Seoyon; Park, Dae Hwan; Ahn, Sei Hyun; Kim, Jisun; Lee, Jong Won; Han, Jun Young; Kim, Dong Kyu; Jeon, Jae Yong; Choi, Kyoung Hyo; Kim, Won

2017-04-01

The present study investigated the prevalence and risk factors of adhesive capsulitis of the shoulder in breast cancer patients between 13 and 18 months after surgery. This study included 271 women who underwent surgery for breast cancer with a postoperative period of 13-18 months. Current adhesive capsulitis was defined as restriction of external rotation and one or more additional directional restrictions with history of shoulder pain. Cumulative adhesive capsulitis was defined as current adhesive capsulitis or a previous history of adhesive capsulitis after breast cancer surgery. Multivariate logistic regression analysis was performed to examine associations between current or cumulative adhesive capsulitis and potential risk factors. Among the 271 study patients, 28 (10.3%) and 21 (7.7%) had cumulative or current adhesive capsulitis, respectively. The incidences of cumulative and current adhesive capsulitis were higher in those aged 50-59 years (odds ratio [OR], 9.912; 95% confidence interval [CI], 1.790-54.880; and OR, 12.395; 95% CI, 1.187-129.444, respectively) and those who underwent mastectomy (OR, 6.805; 95% CI, 1.800-25.733; and OR, 9.645; 95% CI, 2.075-44.829, respectively) or mastectomy with reconstruction (OR, 13.122; 95% CI, 2.488-69.218; and OR, 20.075; 95% CI, 2.873-140.261, respectively). Adhesive capsulitis of the shoulder is a common problem after breast cancer treatment. An age of 50-59 years and mastectomy are major risk factors for adhesive capsulitis, and breast reconstruction additionally increases the risk. Patients with these risk factors require greater attention for early diagnosis and proper treatment.

Association between adjuvant chemotherapy and risk of acute kidney injury in elderly women diagnosed with early-stage breast cancer.

PubMed

Li, Shuling; Liu, Jiannong; Virnig, Beth A; Collins, Allan J

2017-02-01

We studied elderly Medicare enrollees newly diagnosed with early-stage breast cancer to examine the association between adjuvant chemotherapy and acute kidney injury (AKI). Using the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we conducted a retrospective cohort study including women diagnosed with stages I-III breast cancer at ages 66-89 years between 1992 and 2007. We performed one-to-one matching on time-dependent propensity score on the day of adjuvant chemotherapy initiation within 6 months after the first cancer-directed surgery based on the estimated probability of chemotherapy initiation at each day for each patient, using a Cox proportional hazards model. We estimated the cumulative incidence of AKI using Kaplan-Meier methods. We used Cox proportional hazards models to evaluate the association between chemotherapy and the risk of AKI, and compared the risk among major chemotherapy types. The study included 28,048 women. The 6-month cumulative incidence of AKI was 0.80% for chemotherapy-treated patients, compared with 0.30% for untreated patients (P < 0.001). Adjuvant chemotherapy was associated with a nearly threefold increased risk of AKI [hazard ratio (HR) 2.73; 95% CI 1.8-4.1]. Compared with anthracycline-based chemotherapy, the HRs (95% CIs) were 1.66 (0.94-2.91), 0.88 (0.53-1.47), and 1.15 (0.57-2.32) for taxane-based, CMF, and other chemotherapy, respectively. Our findings showed that adjuvant chemotherapy was associated with increased risk of AKI in elderly women diagnosed with early-stage breast cancer. The risk seemed to vary by regimen type, but the differences were not statistically significant.

An instrument for broadened risk assessment in antenatal health care including non-medical issues

PubMed Central

Vos, Amber A.; van Veen, Mieke J.; Birnie, Erwin; Denktaş, Semiha; Steegers, Eric A.P.; Bonsel, Gouke J.

2015-01-01

Introduction Growing evidence on the risk contributing role of non-medical factors on pregnancy outcomes urged for a new approach in early antenatal risk selection. The evidence invites to more integration, in particular between the clinical working area and the public health domain. We developed a non-invasive, standardized instrument for comprehensive antenatal risk assessment. The current study presents the application-oriented development of a risk screening instrument for early antenatal detection of risk factors and tailored prevention in an integrated care setting. Methods A review of published instruments complemented with evidence from cohort studies. Selection and standardization of risk factors associated with small for gestational age, preterm birth, congenital anomalies and perinatal mortality. Risk factors were weighted to obtain a cumulative risk score. Responses were then connected to corresponding care pathways. A cumulative risk threshold was defined, which can be adapted to the population and the availability of preventive facilities. A score above the threshold implies multidisciplinary consultation between caregivers. Results The resulting digital score card consisted of 70 items, subdivided into four non-medical and two medical domains. Weighing of risk factors was based on existing evidence. Pilot-evidence from a cohort of 218 pregnancies in a multi-practice urban setting showed a cut-off of 16 points would imply 20% of all pregnant women to be assessed in a multidisciplinary setting. A total of 28 care pathways were defined. Conclusion The resulting score card is a universal risk screening instrument which incorporates recent evidence on non-medical risk factors for adverse pregnancy outcomes and enables systematic risk management in an integrated antenatal health care setting. PMID:25780351

Multiple imputation for estimating the risk of developing dementia and its impact on survival.

PubMed

Yu, Binbing; Saczynski, Jane S; Launer, Lenore

2010-10-01

Dementia, Alzheimer's disease in particular, is one of the major causes of disability and decreased quality of life among the elderly and a leading obstacle to successful aging. Given the profound impact on public health, much research has focused on the age-specific risk of developing dementia and the impact on survival. Early work has discussed various methods of estimating age-specific incidence of dementia, among which the illness-death model is popular for modeling disease progression. In this article we use multiple imputation to fit multi-state models for survival data with interval censoring and left truncation. This approach allows semi-Markov models in which survival after dementia depends on onset age. Such models can be used to estimate the cumulative risk of developing dementia in the presence of the competing risk of dementia-free death. Simulations are carried out to examine the performance of the proposed method. Data from the Honolulu Asia Aging Study are analyzed to estimate the age-specific and cumulative risks of dementia and to examine the effect of major risk factors on dementia onset and death.

Role of HIV Infection Duration and CD4 Cell Level at Initiation of Combination Anti-Retroviral Therapy on Risk of Failure

PubMed Central

Lodi, Sara; Phillips, Andrew; Fidler, Sarah; Hawkins, David; Gilson, Richard; McLean, Ken; Fisher, Martin; Post, Frank; Johnson, Anne M.; Walker-Nthenda, Louise; Dunn, David; Porter, Kholoud

2013-01-01

Background The development of HIV drug resistance and subsequent virological failure are often cited as potential disadvantages of early cART initiation. However, their long-term probability is not known, and neither is the role of duration of infection at the time of initiation. Methods Patients enrolled in the UK Register of HIV seroconverters were followed-up from cART initiation to last HIV-RNA measurement. Through survival analysis we examined predictors of virologic failure (2HIV-RNA ≥400 c/l while on cART) including CD4 count and HIV duration at initiation. We also estimated the cumulative probabilities of failure and drug resistance (from the available HIV nucleotide sequences) for early initiators (cART within 12 months of seroconversion). Results Of 1075 starting cART at a median (IQR) CD4 count 272 (190,370) cells/mm3 and HIV duration 3 (1,6) years, virological failure occurred in 163 (15%). Higher CD4 count at initiation, but not HIV infection duration at cART initiation, was independently associated with lower risk of failure (p=0.033 and 0.592 respectively). Among 230 patients initiating cART early, 97 (42%) discontinued it after a median of 7 months; cumulative probabilities of resistance and failure by 8 years were 7% (95% CI 4,11) and 19% (13,25), respectively. Conclusion Although the rate of discontinuation of early cART in our cohort was high, the long-term rate of virological failure was low. Our data do not support early cART initiation being associated with increased risk of failure and drug resistance. PMID:24086588

Salivary cortisol reactivity in preschoolers is associated with hair cortisol and behavioral problems.

PubMed

Kao, Katie; Doan, Stacey N; St John, Ashley M; Meyer, Jerrold S; Tarullo, Amanda R

2018-01-01

The interplay between children's cortisol reactivity to challenge and cumulative cortisol exposure is not well understood. Examining the role of cortisol reactivity in early childhood may elucidate biological mechanisms that contribute to children's chronic physiological stress and behavioral dysregulation. In a sample of 65 preschool-aged children, we examined the relation between children's salivary cortisol reactivity to challenging tasks and their hair cortisol concentration (HCC). While both are biomarkers of the hypothalamic-pituitary-adrenal (HPA) axis, salivary cortisol reactivity reflects an acute cortisol response to a stressor and HCC reflects cumulative cortisol exposure. In addition, we examined the relations of these stress biomarkers with internalizing and externalizing problems. Salivary cortisol reactivity was associated with higher HCC and with increased externalizing behaviors. Child HCC also was positively correlated with parent HCC. Results highlight the contributions of salivary cortisol reactivity to children's cumulative cortisol exposure, which may add to their biological risk for health problems later. The observed association between externalizing problems and salivary cortisol reactivity indicates concordances between dysregulated behavioral reactions and dysregulated cortisol responses to challenges. The finding that salivary cortisol reactivity to challenge in early childhood plays a role in children's cumulative cortisol exposure and behavioral development suggests pathways through which cortisol reactivity may influence long-term physical and mental health.

Markers of inflammation, oxidative stress, and endothelial dysfunction and the 20-year cumulative incidence of early age-related macular degeneration: the Beaver Dam Eye Study.

PubMed

Klein, Ronald; Myers, Chelsea E; Cruickshanks, Karen J; Gangnon, Ronald E; Danforth, Lorraine G; Sivakumaran, Theru A; Iyengar, Sudha K; Tsai, Michael Y; Klein, Barbara E K

2014-04-01

IMPORTANCE Modifying levels of factors associated with age-related macular degeneration (AMD) may decrease the risk for visual impairment in older persons. OBJECTIVE To examine the relationships of markers of inflammation, oxidative stress, and endothelial dysfunction to the 20-year cumulative incidence of early AMD. DESIGN, SETTING, AND PARTICIPANTS This longitudinal population-based cohort study involved a random sample of 975 persons in the Beaver Dam Eye Study without signs of AMD who participated in the baseline examination in 1988-1990 and up to 4 follow-up examinations in 1993-1995, 1998-2000, 2003-2005, and 2008-2010. EXPOSURES Serum markers of inflammation (high-sensitivity C-reactive protein, tumor necrosis factor-α receptor 2, interleukin-6, and white blood cell count), oxidative stress (8-isoprostane and total carbonyl content), and endothelial dysfunction (soluble vascular cell adhesion molecule-1 and soluble intercellular adhesion molecule-1) were measured. Interactions with complement factor H (rs1061170), age-related maculopathy susceptibility 2 (rs10490924), complement component 3 (rs2230199), and complement component 2/complement factor B (rs4151667) were examined using multiplicative models. Age-related macular degeneration was assessed from fundus photographs. MAIN OUTCOMES AND MEASURES Early AMD defined by the presence of any size drusen and the presence of pigmentary abnormalities or by the presence of large-sized drusen (≥125-μm diameter) in the absence of late AMD. RESULTS The 20-year cumulative incidence of early AMD was 23.0%. Adjusting for age, sex, and other risk factors, high-sensitivity C-reactive protein (odds ratio comparing fourth with first quartile, 2.18; P = .005), tumor necrosis factor-α receptor 2 (odds ratio, 1.78; P = .04), and interleukin-6 (odds ratio, 1.78; P = .03) were associated with the incidence of early AMD. Increased incidence of early AMD was associated with soluble vascular cell adhesion molecule-1 (odds ratio per SD on the logarithmic scale, 1.21; P = .04). CONCLUSIONS AND RELEVANCE We found modest evidence of relationships of serum high-sensitivity C-reactive protein, tumor necrosis factor-α receptor 2, interleukin-6, and soluble vascular cell adhesion molecule-1 to the 20-year cumulative incidence of early AMD independent of age, smoking status, and other factors. It is not known whether these associations represent a cause and effect relationship or whether other unknown confounders accounted for the findings. Even if inflammatory processes are a cause of early AMD, it is not known whether interventions that reduce systemic inflammatory processes will reduce the incidence of early AMD.

75 FR 69662 - Workshop: Cumulative Mixtures Risk of Six Selected Phthalates in Support of Summary Information...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-15

...: Cumulative Mixtures Risk of Six Selected Phthalates in Support of Summary Information on the Integrated Risk... Workshop on the Cumulative Mixtures Risk of Six Selected Phthalates; Request for Public Comments. SUMMARY...) Review the recommendations for evaluation of the cumulative mixtures risk of phthalates as set forth in...

76 FR 82296 - Pyrethrins/Pyrethroid Cumulative Risk Assessment; Extension of Comment Period

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-30

... Cumulative Risk Assessment; Extension of Comment Period AGENCY: Environmental Protection Agency (EPA). ACTION..., 2011, concerning the availability of EPA's cumulative risk assessment for the naturally occurring... cumulative risk assessment for the pyrethroids. Based on this assessment, the EPA concluded that the...

Beyond Cumulative Risk: Distinguishing Harshness and Unpredictability as Determinants of Parenting and Early Life History Strategy

ERIC Educational Resources Information Center

Belsky, Jay; Schlomer, Gabriel L.; Ellis, Bruce J.

2012-01-01

Drawing on life history theory, Ellis and associates' (2009) recent across- and within-species analysis of ecological effects on reproductive development highlighted two fundamental dimensions of environmental variation and influence: harshness and unpredictability. To evaluate the unique contributions of these factors, the authors of present…

Exploring Cumulative Risk and Family Literacy Practices in Low-Income Latino Families

ERIC Educational Resources Information Center

Marcella, Jennifer; Howes, Carollee; Fuligni, Allison Sidle

2014-01-01

Research Findings: The home literacy environment and other early learning settings such as preschool play a role in children's language and literacy outcomes, yet research suggests that Latino, Spanish-speaking families are less likely than other families to participate in family literacy activities. This study explored the relations among…

Exploring School- and Home-Related Protective Factors for Economically Disadvantaged Middle School Students

ERIC Educational Resources Information Center

Okilwa, Nathern S. A.

2016-01-01

This study explored the experiences of middle school students, particularly focusing on the academic achievement of economically disadvantaged students. For low SES middle school students, the known cumulative effects of poverty coupled with school transition and early adolescence development heighten the potential risks for school failure. By…

Mismatch or cumulative stress: the pathway to depression is conditional on attention style.

PubMed

Nederhof, Esther; Ormel, Johan; Oldehinkel, Albertine J

2014-03-01

In the study reported here, the main question we investigated was whether attention style could be a conditional adaptation. We organized participants of the TRacking Adolescents' Individual Lives Survey (TRAILS; N = 2,230) into shifters, sustainers, and two comparison groups, depending on their performance on a shifting- and a sustained-attention task at age 11 years. Compared with sustainers, shifters reported more pre- and perinatal risk factors and more childhood stress, and they adopted a faster life-history strategy. These differences were not found between the comparison groups, who performed well or poorly on both tasks, which suggests that specialization for either sustained or shifting attention is the key to conditional adaptation. In a subsample (n = 860), we found that stress did not increase depression risk in shifters, whereas a mismatch between early and recent stress predicted depression in sustainers. Cumulative stress predicted depression in the comparison group. These results suggest that shifters retain high levels of plasticity throughout life, whereas sustainers' adapted their phenotype early in life to the expected mature environment.

Early outcome of patients undergoing transcatheter aortic valve implantation (TAVI): The Auckland City Hospital experience 2011-2015.

PubMed

Wu, Sylvia S Y; Wang, Tom Kai Ming; Nand, Parma; Ramanathan, Tharumenthiran; Webster, Mark; Stewart, Jim

2016-01-08

Transcatheter aortic valve implantation (TAVI) is an alternative to surgical aortic valve replacement (AVR) in high-risk patients. We report the initial TAVI experience at Auckland City Hospital. The records of patients undergoing TAVI between 2011 and 2015 at Auckland City Hospital were reviewed. We report the procedural success and outcome, including major adverse events (death, stroke, myocardial infarction, bleeding, vascular complications and rehospitalisations), degree of aortic regurgitation and symptom status up to 1-year follow-up. Mean age was 80.7 years and mean Euroscore II and Society of Thoracic Surgeons' scores were 8.2% and 6.3% respectively; 50% had undergone previous cardiac surgery. Successful deployment of the valve was achieved in all patients. The cumulative mortality rates at 30 days, 6 months and 1 year were 2.4%, 6.1% and 12.2% and cumulative stroke rates 1.2%, 3% and 8.2% respectively. Severe aortic regurgitation occurred in 2.3% TAVI is available in the New Zealand public hospital system for patients who are high-risk candidates for AVR. Early results are excellent and indicate that the technology is being used appropriately, according to current access criteria. If the early cost effectiveness data are confirmed, the indications for TAVI may widen.

Measuring women's cumulative neighborhood deprivation exposure using longitudinally linked vital records: a method for life course MCH research.

PubMed

Kramer, Michael R; Dunlop, Anne L; Hogue, Carol J R

2014-02-01

A life course conceptual framework for MCH research demands new tools for understanding population health and measuring exposures. We propose a method for measuring population-based socio-environmental trajectories for women of reproductive age. We merged maternal longitudinally-linked births to Georgia-resident women from 1994 to 2007 with census economic and social measures using residential geocodes to create woman-centered socio-environmental trajectories. We calculated a woman's neighborhood deprivation index (NDI) at the time of each of her births and, from these, we calculated a cumulative NDI. We fit Loess curves to describe average life course NDI trajectories and binomial regression models to test specific life course theory hypotheses relating cumulative NDI to risk for preterm birth. Of the 1,815,944 total live births, we linked 1,000,437 live births to 413,048 unique women with two or more births. Record linkage had high specificity but relatively low sensitivity which appears non-differential with respect to maternal characteristics. Georgia women on average experienced upward mobility across the life course, although differences by race, early life neighborhood quality, and age at first birth produced differences in cumulative NDI. Adjusted binomial models found evidence for modification of the effect of history of prior preterm birth and advancing age on risk for preterm birth by cumulative NDI. The creation of trajectories from geocoded maternal longitudinally-linked vital records is one method to carry out life course MCH research. We discuss approaches for investigating the impact of truncation of the life course, selection bias from migration, and misclassification of cumulative exposure.

Early life adversity and adult biological risk profiles.

PubMed

Friedman, Esther M; Karlamangla, Arun S; Gruenewald, Tara L; Koretz, Brandon; Seeman, Teresa E

2015-01-01

To determine whether there is a relationship between early life adversity (ELA) and biological parameters known to predict health risks and to examine the extent to which circumstances in midlife mediate this relationship. We analyzed data on 1180 respondents from the biomarker subsample of the second wave of the National Survey of Midlife Development in the United States. ELA assessments were based on childhood socioeconomic disadvantage (i.e., on welfare, perceived low income, and less educated parents) and other stressors (e.g., parental death, parental divorce, and parental physical abuse). The outcome variable was cumulative allostatic load (AL), a marker of biological risk. We also incorporate information on adult circumstances, including than following: education, social relationships, and health behaviors. Childhood socioeconomic adversity and physical abuse were associated with increased AL (B = 0.094, standard error = 0.041, and B = 0.263, standard error = 0.091 respectively), with nonsignificant associations for parental divorce and death with AL. Adult education mediated the relationship between socioeconomic ELA and cumulative AL to the point of nonsignificance, with this factor alone explaining nearly 40% of the relationship. The association between childhood physical abuse and AL remained even after adjusting for adult educational attainments, social relationships, and health behaviors. These associations were most pronounced for secondary stress systems, including inflammation, cardiovascular function, and lipid metabolism. The physiological consequences of early life socioeconomic adversity are attenuated by achieving high levels of schooling later on. The adverse consequences of childhood physical abuse, on the other hand, persist in multivariable-adjusted analysis.

Featured Article: Community Crime Exposure and Risk for Obesity in Preschool Children: Moderation by the Hypothalamic-Pituitary-Adrenal-Axis Response.

PubMed

Gartstein, Maria A; Seamon, Erich; Thompson, Stephanie F; Lengua, Liliana J

2018-05-01

Identification of early risk factors related to obesity is critical to preventative public health efforts. In this study, we investigated links between the Hypothalamic-Pituitary-Adrenal (HPA)-axis activity (diurnal cortisol pattern), geospatially operationalized exposure to neighborhood crime, and body mass index (BMI) for a sample of 5-year-old children. Greater community crime exposure and lower HPA-axis activity were hypothesized to contribute to higher BMI, with child HPA-axis moderating the association between crime exposure and BMI. Families residing within the boundaries of the City of Seattle (N = 114) provided information concerning demographic/psychosocial risk factors, used to calculate a Cumulative Risk Index, indicating the number of contextual adversities present. Child BMI and diurnal cortisol pattern (derived from assays of saliva samples) were examined, along with neighborhood crime indices computed with publically available information, based on participants' locations. Hierarchical multiple regression analyses, adjusted for covariates (cumulative risk, age, and sex), indicated that crime proximity made a unique contribution to child BMI, in the direction signaling an increase in the risk for obesity. Consistent with our hypothesis, a significant interaction was observed, indicative of moderation by diurnal cortisol pattern. Follow-up simple slope analyses demonstrated that crime exposure was significantly related to higher BMI for children with low-flat (blunted) diurnal cortisol patterns, where community crime and BMI were not significantly associated at higher levels of cortisol. Community crime exposure contributes to higher BMI as early as the preschool period, and blunted diurnal cortisol patterns may place children experiencing neighborhood adversity at greater risk for obesity.

Attachment and Attention: Protection in Relation to Gender and Cumulative Social-Contextual Adversity

ERIC Educational Resources Information Center

Pasco Fearon, R. M.; Belsky, Jay

2004-01-01

Data from 918 children from the National Institute of Child Health and Human Development (NICHD) Study of Early Child Care were examined to test the interrelation of attachment and attentional performance and 2 known risks for poor attentional performance: male gender and social-contextual adversity. Attachment was measured using the Strange…

Association Between Physical Therapy and Risk of Coronary Artery Disease and Dyslipidemia Among Osteoarthritis Patients: A Nationwide Database Study.

PubMed

Yeh, Huan-Jui; Chou, Yiing-Jenq; Yang, Nan-Ping; Cheng, Chi-Chia; Huang, Nicole

2016-01-01

To provide empirical evidence on the effect of early physical therapy (PT) within the first year of osteoarthritis (OA) diagnosis on reduction in OA-related comorbidities in patients with OA. Retrospective cohort study. The study was conducted using a nationally representative sample of 1 million National Health Insurance enrollees. Newly diagnosed patients with OA (N=13,545). One-to-one propensity score matching was used to match patients who received PT within the first year of OA diagnosis (PT group; n=3403) with an equal number of patients with OA who did not receive PT (non-PT group). Not applicable. The 4-year cumulative risk of comorbidities including coronary artery disease (CAD), diabetes mellitus, dyslipidemia, osteoporosis, gastrointestinal tract ulcer, and renal failure was estimated. A Cox proportional hazards regression analysis was performed to identify the dose-response relation between the PT dosage and the risk of OA-related comorbidities. A total of 3403 patients (25.1%) received PT within the first year of OA diagnosis. The PT group had a significantly lower 4-year cumulative risk of dyslipidemia (P=.05) and a potentially lower 4-year cumulative risk of CAD (P=.09). After adjusting for other potential confounders, the Cox proportional hazards regression analysis showed that patients with OA who received a high PT dosage had a low risk of CAD and dyslipidemia. Patients with OA who received PT had a lower risk of OA-related comorbidities such as dyslipidemia or CAD. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Failure-to-thrive, maltreatment and the behavior and development of 6-year-old children from low-income, urban families: a cumulative risk model.

PubMed

Kerr, M A; Black, M M; Krishnakumar, A

2000-05-01

A cumulative risk model was used to examine the relationship among failure-to-thrive (FTT), maltreatment, and four aspects of children's development: cognitive performance (standardized testing), adaptive functioning at school, and classroom behavior (teacher report), and behavior at home (maternal report). The sample included 193 6-year-old children and their families, recruited from pediatric clinics serving inner-city, low-income, primarily African-American families, who were part of a longitudinal investigation of child development and maltreatment. Four risk groups were formed based on their growth and maltreatment history: neither FTT nor Maltreatment, FTT Only, Maltreatment Only, and both FTT and Maltreatment. FTT was defined as a deceleration in weight gain (weight-for-age below the 5th percentile) prior to 25 months of age among children born at term with birth weight appropriate for gestational age. Maltreatment was defined as having at least one report to CPS for neglect, physical abuse and/or sexual abuse. Risk status was negatively associated with each of the four developmental outcomes. Children with a history of both FTT and maltreatment had more behavior problems and worse cognitive performance and school functioning than children with neither risk factor. Children with only one risk factor (either FTT or maltreatment) achieved intermediate scores. Findings support a cumulative risk model as being more detrimental to children's development than the presence of a single risk factor alone, consistent with theories linking the accumulation of environmental risks to negative consequences. These results underscore the importance of interventions to prevent both FTT and maltreatment during children's early years.

Sociodemographic risk, parenting, and inhibitory control in early childhood: the role of respiratory sinus arrhythmia.

PubMed

Holochwost, Steven J; Volpe, Vanessa V; Gueron-Sela, Noa; Propper, Cathi B; Mills-Koonce, W Roger

2018-03-13

Deficits of inhibitory control in early childhood are linked to externalizing behaviors and attention problems. While environmental factors and physiological processes are associated with its etiology, few studies have examined how these factors jointly predict inhibitory control. This study examined whether respiratory sinus arrhythmia (RSA) functioned as a mediator or moderator of both cumulative sociodemographic risk and parenting behaviors on inhibitory control during early childhood. The sample included 206 children and their biological mothers. At 24, 30, and 36 months of child age dyads participated in a series of laboratory visits in which sociodemographic, parenting, and baseline RSA (RSAB) data were collected. Inhibitory control was assessed at 36 months using a gift-wrap delay task. A series of structural equation models yielded no evidence that RSAB mediated the relations of risk or parenting and inhibitory control. RSAB moderated the effects of risk, such that high-risk children with low RSAB performed more poorly on tasks of inhibitory control, while high-risk children with high RSAB did not. These results suggest that higher levels of RSAB may mitigate the influence of environmental risk on the development of inhibitory control early childhood. © 2018 Association for Child and Adolescent Mental Health.

Stressful life experiences in adolescence and cardiometabolic risk factors in young adulthood.

PubMed

Wickrama, Kandauda A S; Lee, Tae-Kyoung; O'Neal, Catherine Walker

2015-04-01

An increasing number of studies have provided evidence for the persistent influence of childhood/adolescent socioeconomic adversities on subsequent health outcomes. However, less is known about the distinct and additive influences of these early socioeconomic adversities and adolescents' own stressful life experiences on health outcomes in young adulthood. We used data from 11,030 adolescents who participated in the National Longitudinal Study of Adolescent Health at Waves 1, 3, and 4 and provided biomarker data at Wave 4. Three early socioeconomic adversities (community socioeconomic adversity, family economic hardship, and low parental education) were evaluated. Adolescents' stressful transition to young adulthood was captured by six specific precocious life events as follows: early sex, early marriage or cohabitation, early leaving home, early pregnancy, early employment, and truncated education. A summary measure of cardiovascular and metabolic disease risk was assessed using nine biomarkers. Univariate, bivariate, and multivariate regression analyses were employed. Early socioeconomic adversities and stressful life transition events were uniquely associated with elevated levels of cardiometabolic (CM) biomarkers and cumulative CM disease risk. For all of the biomarkers, young adults in high-adversity/stress groups were more likely to be in the high CM disease risk groups (>75th percentile) than in the low-adversity/stress groups. These findings provide support for the influence of multiple early socioeconomic adversities and adolescents' stressful life transitions on their CM disease risk as young adults. Increased efforts to prevent and mitigate these experiences may improve disease risks across a number of biomarkers. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Cumulative Risk Exposure and Mental Health Symptoms among Maltreated Youths Placed in Out-of-Home Care

PubMed Central

Raviv, Tali; Taussig, Heather N.; Culhane, Sara E.; Garrido, Edward F.

2010-01-01

Maltreated children placed in out-of-home care are at high risk for exhibiting symptoms of psychopathology by virtue of their exposure to numerous risk factors. Research examining cumulative risk has consistently found that the accumulation of risk factors increases the likelihood of mental health problems. The goal of the current study was to elucidate the relation between cumulative risk and mental health symptomatology within a sample of 252 maltreated youths (aged 9–11) placed in out-of-home care. Results confirmed the high-risk nature of this sample and identified seven salient risk variables. The cumulative risk index comprised of these seven indicators was a strong predictor of mental health symptoms, differentiating between children who scored in the clinical range with regard to mental health symptoms and those who did not. Finally, the data supported a linear model in which each incremental increase in cumulative risk was accompanied by an increase in mental health problems. This is the first known study to examine cumulative risk within a sample of youths in out-of-home care. PMID:20932576

Higher Fluid Balance Increases the Risk of Death From Sepsis: Results From a Large International Audit.

PubMed

Sakr, Yasser; Rubatto Birri, Paolo Nahuel; Kotfis, Katarzyna; Nanchal, Rahul; Shah, Bhagyesh; Kluge, Stefan; Schroeder, Mary E; Marshall, John C; Vincent, Jean-Louis

2017-03-01

Excessive fluid therapy in patients with sepsis may be associated with risks that outweigh any benefit. We investigated the possible influence of early fluid balance on outcome in a large international database of ICU patients with sepsis. Observational cohort study. Seven hundred and thirty ICUs in 84 countries. All adult patients admitted between May 8 and May 18, 2012, except admissions for routine postoperative surveillance. For this analysis, we included only the 1,808 patients with an admission diagnosis of sepsis. Patients were stratified according to quartiles of cumulative fluid balance 24 hours and 3 days after ICU admission. ICU and hospital mortality rates were 27.6% and 37.3%, respectively. The cumulative fluid balance increased from 1,217 mL (-90 to 2,783 mL) in the first 24 hours after ICU admission to 1,794 mL (-951 to 5,108 mL) on day 3 and decreased thereafter. The cumulative fluid intake was similar in survivors and nonsurvivors, but fluid balance was less positive in survivors because of higher fluid output in these patients. Fluid balances became negative after the third ICU day in survivors but remained positive in nonsurvivors. After adjustment for possible confounders in multivariable analysis, the 24-hour cumulative fluid balance was not associated with an increased hazard of 28-day in-hospital death. However, there was a stepwise increase in the hazard of death with higher quartiles of 3-day cumulative fluid balance in the whole population and after stratification according to the presence of septic shock. In this large cohort of patients with sepsis, higher cumulative fluid balance at day 3 but not in the first 24 hours after ICU admission was independently associated with an increase in the hazard of death.

Adverse Childhood Experiences and Alcohol Consumption in Midlife and Early Old-Age

PubMed Central

Leung, Jessica Pui Kei; Britton, Annie; Bell, Steven

2016-01-01

Aims To examine the individual and cumulative effects of adverse childhood experiences (ACEs) on alcohol consumption in midlife and early old-age, and the role of ACEs in 10-year drinking trajectories across midlife. Methods Data were from the Whitehall II study, a longitudinal British civil service-based cohort study (N = 7870, 69.5% male). Multinomial logistic regression was used to examine the individual and cumulative effects of ACEs on weekly alcohol consumption. Mixed-effect multilevel modelling was used to explore the relationship between ACEs and change in alcohol consumption longitudinally. Results Participants who were exposed to parental arguments/fights in childhood were 1.24 (95% CI 1.06, 1.45) times more likely to drink at hazardous levels in midlife (mean age 56 years) after controlling for covariates and other ACEs. For each additional exposure to an ACE, the risk of hazardous drinking versus moderate drinking was increased by 1.12 (95% CI 1.03, 1.21) after adjusting for sex, age, adult socio-economic status, ethnicity and marital status. No associations between ACEs and increased risk of hazardous drinking in early old-age (mean age 66 years) were found. In longitudinal analyses, ACEs did not significantly influence 10-year drinking trajectories across midlife. Conclusion The effect of exposure to parental arguments on hazardous drinking persists into midlife. PMID:26553290

Cumulative Risk Assessment: An Overview of Methodological Approaches for Evaluating Combined Health Effects from Exposure to Multiple Environmental Stressors

PubMed Central

Sexton, Ken

2012-01-01

Systematic evaluation of cumulative health risks from the combined effects of multiple environmental stressors is becoming a vital component of risk-based decisions aimed at protecting human populations and communities. This article briefly examines the historical development of cumulative risk assessment as an analytical tool, and discusses current approaches for evaluating cumulative health effects from exposure to both chemical mixtures and combinations of chemical and nonchemical stressors. A comparison of stressor-based and effects-based assessment methods is presented, and the potential value of focusing on viable risk management options to limit the scope of cumulative evaluations is discussed. The ultimate goal of cumulative risk assessment is to provide answers to decision-relevant questions based on organized scientific analysis; even if the answers, at least for the time being, are inexact and uncertain. PMID:22470298

Mixture models for undiagnosed prevalent disease and interval-censored incident disease: applications to a cohort assembled from electronic health records.

PubMed

Cheung, Li C; Pan, Qing; Hyun, Noorie; Schiffman, Mark; Fetterman, Barbara; Castle, Philip E; Lorey, Thomas; Katki, Hormuzd A

2017-09-30

For cost-effectiveness and efficiency, many large-scale general-purpose cohort studies are being assembled within large health-care providers who use electronic health records. Two key features of such data are that incident disease is interval-censored between irregular visits and there can be pre-existing (prevalent) disease. Because prevalent disease is not always immediately diagnosed, some disease diagnosed at later visits are actually undiagnosed prevalent disease. We consider prevalent disease as a point mass at time zero for clinical applications where there is no interest in time of prevalent disease onset. We demonstrate that the naive Kaplan-Meier cumulative risk estimator underestimates risks at early time points and overestimates later risks. We propose a general family of mixture models for undiagnosed prevalent disease and interval-censored incident disease that we call prevalence-incidence models. Parameters for parametric prevalence-incidence models, such as the logistic regression and Weibull survival (logistic-Weibull) model, are estimated by direct likelihood maximization or by EM algorithm. Non-parametric methods are proposed to calculate cumulative risks for cases without covariates. We compare naive Kaplan-Meier, logistic-Weibull, and non-parametric estimates of cumulative risk in the cervical cancer screening program at Kaiser Permanente Northern California. Kaplan-Meier provided poor estimates while the logistic-Weibull model was a close fit to the non-parametric. Our findings support our use of logistic-Weibull models to develop the risk estimates that underlie current US risk-based cervical cancer screening guidelines. Published 2017. This article has been contributed to by US Government employees and their work is in the public domain in the USA. Published 2017. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

The social course of drug injection and sexual activity among YMSM and other high-risk youth: an agenda for future research.

PubMed

Clatts, Michael C; Goldsamt, Lloyd; Neaigus, Alan; Welle, Dorinda L

2003-12-01

The cumulative epidemiologic literature indicates that many injecting drug users (IDUs) initiate injection as a mode of drug administration during late adolescence or early adulthood. Recent studies have shown that IDUs are often exposed to viral infections relatively early in the course of injection, highlighting the importance of understanding this initiation process for both epidemiology and prevention. Epidemiologic evidence similarly suggests that at least some youth populations, most notably young men who have sex with men (YMSM), are at substantial risk for exposure to HIV and other sexually transmitted diseases (STDs) from early sexual activity. Despite the importance of this issue for both epidemiology and prevention, however, surprisingly little information is available on the social course of injection initiation, including the individual, social, or ecological factors that might mitigate or exacerbate transmission risks within the critical phase of early injection drug use. Similarly, we know little about the ways that YMSM and other high-risk youth understand risk, the kinds of exchanges and relationships in which they participate in the context of initiating sexual activity, or how drug use is operant in these exchanges and early sexual experiences. In this article, we explore key dimensions of the early initiation of injection and sexual risk, and discuss how a social network approach might be instrumental in understanding the social course of drug injection and sexual activities among youth and young adult populations.

When More Is Not Better: The Role of Cumulative Risk in Child Behavior Outcomes

ERIC Educational Resources Information Center

Appleyard, Karen; Egeland, Byron; van Dulmen, Manfred H. M.; Sroufe, L. Alan

2005-01-01

Background: Cumulative risk research has established the deleterious effects of co-occurring risk factors on child behavior outcomes. However, extant literature has not addressed potential differential effects of cumulative risk at different points in development and has left open questions about whether a threshold model or a linear risk model…

Latent Classes and Cumulative Impacts of Adverse Childhood Experiences.

PubMed

Barboza, Gia Elise

2018-05-01

Studies of adverse childhood experiences (ACEs) have gauged severity using a cumulative risk (CR) index. Few studies have focused on the nature of the context of adversity and their association with psychosocial outcomes. The objective of this study was to examine the patterning of ACEs and to explore the resultant patterns' association with HIV risk-taking, problem drinking, and depressive symptoms in adulthood. Latent class analysis (LCA) was used to identify homogeneous, mutually exclusive "classes" of 11 of the most commonly used ACEs. The LCA resulted in four high-risk profiles and one low-risk profile, which were labeled: (1) highly abusive and dysfunctional (3.3%; n = 1,983), (2) emotionally abusive alcoholic with parental conflict (6%, n = 3,303), (3) sexual abuse only (4.3%, n = 2,260), (4) emotionally abusive and alcoholic (30.3%, n = 17,460), and (5) normative, low risk (56.3%, n = 32,950). Compared to the low-risk class, each high-risk profile was differentially associated with adult psychosocial outcomes even when the conditional CR within that class was similar. The results further our understanding about the pattern of ACEs and the unique pathways to poor health. Implications for child welfare systems when dealing with individuals who have experienced multiple forms of early childhood maltreatment and/or household dysfunction are discussed.

Having older siblings is associated with gut microbiota development during early childhood.

PubMed

Laursen, Martin Frederik; Zachariassen, Gitte; Bahl, Martin Iain; Bergström, Anders; Høst, Arne; Michaelsen, Kim F; Licht, Tine Rask

2015-08-01

Evidence suggests that early life infections, presence of older siblings and furred pets in the household affect the risk of developing allergic diseases through altered microbial exposure. Recently, low gut microbial diversity during infancy has also been linked with later development of allergies. We investigated whether presence of older siblings, furred pets and early life infections affected gut microbial communities at 9 and 18 months of age and whether these differences were associated with the cumulative prevalence of atopic symptoms of eczema and asthmatic bronchitis at 3 years of age. Bacterial compositions and diversity indices were determined in fecal samples collected from 114 infants in the SKOT I cohort at age 9 and 18 months by 16S rRNA gene sequencing. These were compared to the presence of older siblings, furred pets and early life infections and the cumulative prevalence of diagnosed asthmatic bronchitis and self-reported eczema at 3 years of age. The number of older siblings correlated positively with bacterial diversity (p = 0.030), diversity of the phyla Firmicutes (p = 0.013) and Bacteroidetes (p = 0.004) and bacterial richness (p = 0.006) at 18 months. Further, having older siblings was associated with increased relative abundance of several bacterial taxa at both 9 and 18 months of age. Compared to the effect of having siblings, presence of household furred pets and early life infections had less pronounced effects on the gut microbiota. Gut microbiota characteristics were not significantly associated with cumulative occurrence of eczema and asthmatic bronchitis during the first 3 years of life. Presence of older siblings is associated with increased gut microbial diversity and richness during early childhood, which could contribute to the substantiation of the hygiene hypothesis. However, no associations were found between gut microbiota and atopic symptoms of eczema and asthmatic bronchitis during early childhood and thus further studies are required to elucidate whether sibling-associated gut microbial changes influence development of allergies later in childhood.

Adolescent Risk Factors for Child Maltreatment

PubMed Central

Matsuda, Mauri; Greenman, Sarah J.; Augustyn, Megan Bears; Henry, Kimberly L.; Smith, Carolyn A.; Ireland, Timothy O.

2014-01-01

We investigate adolescent risk factors, measured at both early and late adolescence, for involvement in child maltreatment during adulthood. Comprehensive assessments of risk factors for maltreatment that use representative samples with longitudinal data are scarce and can inform multilevel prevention. We use data from the Rochester Youth Development Study, a longitudinal study begun in 1988 with a sample of 1,000 seventh and eighth graders. Participants have been interviewed 14 times and, at the last assessment (age 31), 80% were retained. Risk factors represent 10 developmental domains: area characteristics, family background/structure, parent stressors, exposure to family violence, parent-child relationships, education, peer relationships, adolescent stressors, antisocial behaviors, and precocious transitions to adulthood. Maltreatment is measured by substantiated reports from Child Protective Services records. Many individual risk factors (20 at early adolescence and 14 at later adolescence) are significantly, albeit moderately, predictive of maltreatment. Several developmental domains stand out, including family background/structure, education, antisocial behaviors, and precocious transitions. In addition, there is a pronounced impact of cumulative risk on the likelihood of maltreatment. For example, only 3% of the youth with no risk domains in their background at early adolescence were involved in later maltreatment, but for those with risk in 9 developmental domains the rate was 45%. Prevention programs targeting youth at high risk for engaging in maltreatment should begin during early adolescence when risk factors are already at play. These programs need to be comprehensive, capable of addressing the multiple and interwoven nature of risk that is associated with maltreatment. PMID:24075569

Risk factors for early adolescent drug use in four ethnic and racial groups.

PubMed

Vega, W A; Zimmerman, R S; Warheit, G J; Apospori, E; Gil, A G

1993-02-01

It is widely believed that risk factors identified in previous epidemiologic studies accurately predict adolescent drug use. Comparative studies are needed to determine how risk factors vary in prevalence, distribution, sensitivity, and pattern across the major US ethnic/racial groups. Baseline questionnaire data from a 3-year epidemiologic study of early adolescent development and drug use were used to conduct bivariate and multivariate risk factor analyses. Respondents (n = 6760) were sixth- and seventh-grade Cuban, other Hispanic, Black, and White non-Hispanic boys in the 48 middle schools of the greater Miami (Dade County) area. Findings indicate 5% lifetime illicit drug use, 4% lifetime inhalant use, 37% lifetime alcohol use, and 21% lifetime tobacco use, with important intergroup differences. Monotonic relationships were found between 10 risk factors and alcohol and illicit drug use. Individual risk factors were distributed disproportionately, and sensitivity and patterning of risk factors varied widely by ethnic/racial subsample. While the cumulative prevalence of risk factors bears a monotonic relationship to drug use, ethnic/racial differences in risk factor profiles, especially for Blacks, suggest differential predictive value based on cultural differences.

Childhood Disadvantage and Health Problems in Middle and Later Life: Early Imprints on Physical Health?

PubMed Central

Ferraro, Kenneth F.; Schafer, Markus H.; Wilkinson, Lindsay R.

2016-01-01

Drawing from cumulative inequality theory, we examine the relationship between childhood disadvantage and health problems in adulthood. Using two waves of data from Midlife Development in the United States, we investigate whether childhood disadvantage is associated with adult disadvantage, including fewer social resources, and the effect of lifelong disadvantage on health problems measured at the baseline survey and a 10-year follow-up. Findings reveal that childhood socioeconomic disadvantage and frequent abuse by parents are generally associated with fewer adult social resources and more lifestyle risks. Health problems, in turn, are affected by childhood disadvantage and by lifestyle risks, especially smoking and obesity. Not only was early disadvantage related to health problems at the baseline survey, but childhood socioeconomic disadvantage and frequent abuse also were related to the development of new health problems at the follow-up survey. These findings reveal the imprint of early disadvantage on health decades later and suggest greater attention to resources, even during midlife, can interrupt the chain of risks. PMID:27445413

Childhood Disadvantage and Health Problems in Middle and Later Life: Early Imprints on Physical Health?

PubMed

Ferraro, Kenneth F; Schafer, Markus H; Wilkinson, Lindsay R

2016-02-01

Drawing from cumulative inequality theory, we examine the relationship between childhood disadvantage and health problems in adulthood. Using two waves of data from Midlife Development in the United States, we investigate whether childhood disadvantage is associated with adult disadvantage, including fewer social resources, and the effect of lifelong disadvantage on health problems measured at the baseline survey and a 10-year follow-up. Findings reveal that childhood socioeconomic disadvantage and frequent abuse by parents are generally associated with fewer adult social resources and more lifestyle risks. Health problems, in turn, are affected by childhood disadvantage and by lifestyle risks, especially smoking and obesity. Not only was early disadvantage related to health problems at the baseline survey, but childhood socioeconomic disadvantage and frequent abuse also were related to the development of new health problems at the follow-up survey. These findings reveal the imprint of early disadvantage on health decades later and suggest greater attention to resources, even during midlife, can interrupt the chain of risks.

Risk factors for child maltreatment in an Australian population-based birth cohort.

PubMed

Doidge, James C; Higgins, Daryl J; Delfabbro, Paul; Segal, Leonie

2017-02-01

Child maltreatment and other adverse childhood experiences adversely influence population health and socioeconomic outcomes. Knowledge of the risk factors for child maltreatment can be used to identify children at risk and may represent opportunities for prevention. We examined a range of possible child, parent and family risk factors for child maltreatment in a prospective 27-year population-based birth cohort of 2443 Australians. Physical abuse, sexual abuse, emotional abuse, neglect and witnessing of domestic violence were recorded retrospectively in early adulthood. Potential risk factors were collected prospectively during childhood or reported retrospectively. Associations were estimated using bivariate and multivariate logistic regressions and combined into cumulative risk scores. Higher levels of economic disadvantage, poor parental mental health and substance use, and social instability were strongly associated with increased risk of child maltreatment. Indicators of child health displayed mixed associations and infant temperament was uncorrelated to maltreatment. Some differences were observed across types of maltreatment but risk profiles were generally similar. In multivariate analyses, nine independent risk factors were identified, including some that are potentially modifiable: economic disadvantage and parental substance use problems. Risk of maltreatment increased exponentially with the number of risk factors experienced, with prevalence of maltreatment in the highest risk groups exceeding 80%. A cumulative risk score based on the independent risk factors allowed identification of individuals at very high risk of maltreatment, while a score that incorporated all significant risk and protective factors provided better identification of low-risk individuals. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cumulative Incidence of Cancer Among Persons With HIV in North America: A Cohort Study.

PubMed

Silverberg, Michael J; Lau, Bryan; Achenbach, Chad J; Jing, Yuezhou; Althoff, Keri N; D'Souza, Gypsyamber; Engels, Eric A; Hessol, Nancy A; Brooks, John T; Burchell, Ann N; Gill, M John; Goedert, James J; Hogg, Robert; Horberg, Michael A; Kirk, Gregory D; Kitahata, Mari M; Korthuis, Philip T; Mathews, William C; Mayor, Angel; Modur, Sharada P; Napravnik, Sonia; Novak, Richard M; Patel, Pragna; Rachlis, Anita R; Sterling, Timothy R; Willig, James H; Justice, Amy C; Moore, Richard D; Dubrow, Robert

2015-10-06

Cancer is increasingly common among persons with HIV. To examine calendar trends in cumulative cancer incidence and hazard rate by HIV status. Cohort study. North American AIDS Cohort Collaboration on Research and Design during 1996 to 2009. 86 620 persons with HIV and 196 987 uninfected adults. Cancer type-specific cumulative incidence by age 75 years and calendar trends in cumulative incidence and hazard rates, each by HIV status. Cumulative incidences of cancer by age 75 years for persons with and without HIV, respectively, were as follows: Kaposi sarcoma, 4.4% and 0.01%; non-Hodgkin lymphoma, 4.5% and 0.7%; lung cancer, 3.4% and 2.8%; anal cancer, 1.5% and 0.05%; colorectal cancer, 1.0% and 1.5%; liver cancer, 1.1% and 0.4%; Hodgkin lymphoma, 0.9% and 0.09%; melanoma, 0.5% and 0.6%; and oral cavity/pharyngeal cancer, 0.8% and 0.8%. Among persons with HIV, calendar trends in cumulative incidence and hazard rate decreased for Kaposi sarcoma and non-Hodgkin lymphoma. For anal, colorectal, and liver cancer, increasing cumulative incidence, but not hazard rate trends, were due to the decreasing mortality rate trend (-9% per year), allowing greater opportunity to be diagnosed. Despite decreasing hazard rate trends for lung cancer, Hodgkin lymphoma, and melanoma, cumulative incidence trends were not seen because of the compensating effect of the declining mortality rate. Secular trends in screening, smoking, and viral co-infections were not evaluated. Cumulative cancer incidence by age 75 years, approximating lifetime risk in persons with HIV, may have clinical utility in this population. The high cumulative incidences by age 75 years for Kaposi sarcoma, non-Hodgkin lymphoma, and lung cancer support early and sustained antiretroviral therapy and smoking cessation.

Adverse adolescent relationship histories and young adult health: Cumulative effects of loneliness, low parental support, relationship instability, intimate partner violence and loss

PubMed Central

Adam, Emma K.; Chyu, Laura; Hoyt, Lindsay; Doane, Leah D.; Boisjoly, Johanne; Duncan, Greg; Chase-Lansdale, Lindsay; McDade, Thomas W.

2011-01-01

Purpose To examine the associations between adverse interpersonal relationship histories experienced during adolescence and health in young adulthood in a large, nationally representative sample. Methods Using data from Waves I, II and III of the National Longitudinal Study of Adolescent Health, multiple adverse relationship experiences are examined, including high loneliness, low perceived parental support, frequent transitions in romantic relationships (relationship instability), exposure to intimate partner violence, and loss by death of important relationship figures. These histories are assessed, both individually and in a relationship risk index, as predictors of self-reported general health and depressive symptoms at Wave III (ages 18 to 27), controlling for baseline (Wave I) health and for demographic and health behavior covariates. Results Net of baseline health and covariates, each type of relationship risk (experienced between Wave I and Wave III) was related to either depression or general health at Wave III, with the strongest effects seen for exposure to intimate partner violence. In addition, a cumulative relationship risk index examining the extent to which youth experienced high levels of multiple relationship risk factors revealed that each additional adverse relationship experience increased the odds of reporting poor mental and general health at Wave III, with increases occurring in an additive manner. Conclusions Multiple types of adverse relationship experiences predicted increases in poor general health and depressive symptoms from adolescence to early adulthood. Consistent with a cumulative risk hypothesis, the more types of adverse relationship experiences a youth experienced, the worse their young adult health outcomes. PMID:21856520

Early Course of Inflammatory Bowel Disease in a Population-Based Inception Cohort Study From 8 Countries in Asia and Australia.

PubMed

Ng, Siew C; Zeng, Zhirong; Niewiadomski, Ola; Tang, Whitney; Bell, Sally; Kamm, Michael A; Hu, Pinjin; de Silva, H Janaka; Niriella, Madunil A; Udara, W S A A Yasith; Ong, David; Ling, Khoon Lin; Ooi, Choon Jin; Hilmi, Ida; Lee Goh, Khean; Ouyang, Qin; Wang, Yu Fang; Wu, Kaichun; Wang, Xin; Pisespongsa, Pises; Manatsathit, Sathaporn; Aniwan, Satimai; Limsrivilai, Julajak; Gunawan, Jeffri; Simadibrata, Marcellus; Abdullah, Murdani; Tsang, Steve W C; Lo, Fu Hang; Hui, Aric J; Chow, Chung Mo; Yu, Hon Ho; Li, Mo Fong; Ng, Ka Kei; Ching, Jessica Y L; Chan, Victor; Wu, Justin C Y; Chan, Francis K L; Chen, Minhu; Sung, Joseph J Y

2016-01-01

The incidence of inflammatory bowel disease (IBD) is increasing in Asia, but little is known about disease progression in this region. The Asia-Pacific Crohn's and Colitis Epidemiology Study was initiated in 2011, enrolling subjects from 8 countries in Asia (China, Hong Kong, Indonesia, Sri Lanka, Macau, Malaysia, Singapore, and Thailand) and Australia. We present data from this ongoing study. We collected data on 413 patients diagnosed with IBD (222 with ulcerative colitis [UC], 181 with Crohn's disease [CD], 10 with IBD unclassified; median age, 37 y) from 2011 through 2013. We analyzed the disease course and severity and mortality. Risks for medical and surgical therapies were assessed using Kaplan-Meier analysis. The cumulative probability that CD would change from inflammatory to stricturing or penetrating disease was 19.6%. The cumulative probabilities for use of immunosuppressants or anti-tumor necrosis factor agents were 58.9% and 12.0% for patients with CD, and 12.7% and 0.9% for patients with UC, respectively. Perianal CD was associated with an increased risk of anti-tumor necrosis factor therapy within 1 year of its diagnosis (hazard ratio, 2.97; 95% confidence interval, 1.09-8.09). The cumulative probabilities for surgery 1 year after diagnosis were 9.1% for patients with CD and 0.9% for patients with UC. Patients with CD and penetrating disease had a 7-fold increase for risk of surgery, compared with patients with inflammatory disease (hazard ratio, 7.67; 95% confidence interval, 3.93-14.96). The overall mortality for patients with IBD was 0.7%. In a prospective population-based study, we found that the early course of disease in patients with IBD in Asia was comparable with that of the West. Patients with CD frequently progress to complicated disease and have accelerated use of immunosuppressants. Few patients with early stage UC undergo surgery in Asia. Increasing our understanding of IBD progression in different populations can help optimize therapy and improve outcomes. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Adjuvant Hypofractionated Versus Conventional Whole Breast Radiation Therapy for Early-Stage Breast Cancer: Long-Term Hospital-Related Morbidity From Cardiac Causes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chan, Elisa K.; Woods, Ryan; McBride, Mary L.

Purpose: The risk of cardiac injury with hypofractionated whole-breast/chest wall radiation therapy (HF-WBI) compared with conventional whole-breast/chest wall radiation therapy (CF-WBI) in women with left-sided breast cancer remains a concern. The purpose of this study was to determine if there is an increase in hospital-related morbidity from cardiac causes with HF-WBI relative to CF-WBI. Methods and Materials: Between 1990 and 1998, 5334 women ≤80 years of age with early-stage breast cancer were treated with postoperative radiation therapy to the breast or chest wall alone. A population-based database recorded baseline patient, tumor, and treatment factors. Hospital administrative records identified baseline cardiacmore » risk factors and other comorbidities. Factors between radiation therapy groups were balanced using a propensity-score model. The first event of a hospital admission for cardiac causes after radiation therapy was determined from hospitalization records. Ten- and 15-year cumulative hospital-related cardiac morbidity after radiation therapy was estimated for left- and right-sided cases using a competing risk approach. Results: The median follow-up was 13.2 years. For left-sided cases, 485 women were treated with CF-WBI, and 2221 women were treated with HF-WBI. Mastectomy was more common in the HF-WBI group, whereas boost was more common in the CF-WBI group. The CF-WBI group had a higher prevalence of diabetes. The 15-year cumulative hospital-related morbidity from cardiac causes (95% confidence interval) was not different between the 2 radiation therapy regimens after propensity-score adjustment: 21% (19-22) with HF-WBI and 21% (17-25) with CF-WBI (P=.93). For right-sided cases, the 15-year cumulative hospital-related morbidity from cardiac causes was also similar between the radiation therapy groups (P=.76). Conclusions: There is no difference in morbidity leading to hospitalization from cardiac causes among women with left-sided early-stage breast cancer treated with HF-WBI or CF-WBI at 15-year follow-up.« less

Histologic Subtype in Core Lung Biopsies of Early-Stage Lung Adenocarcinoma is a Prognostic Factor for Treatment Response and Failure Patterns After Stereotactic Body Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leeman, Jonathan E.; Rimner, Andreas; Montecalvo, Joseph

Purpose: Stereotactic body radiation therapy (SBRT) has emerged as an effective treatment for early-stage lung cancer. The histologic subtype of surgically resected lung adenocarcinoma is recognized as a prognostic factor, with the presence of solid or micropapillary patterns predicting poor outcomes. We describe the outcomes after SBRT for early-stage lung adenocarcinoma stratified by histologic subtype. Methods and Materials: We identified 119 consecutive patients (124 lesions) with stage I to IIA lung adenocarcinoma who had undergone definitive SBRT at our institution from August 2008 to August 2015 and had undergone core biopsy. Histologic subtyping was performed according to the 2015 Worldmore » Health Organization classification. Of the 124 tumors, 37 (30%) were a high-risk subtype, defined as containing a component of solid and/or micropapillary pattern. The cumulative incidences of local, nodal, regional, and distant failure were compared between the high-risk and non–high-risk adenocarcinoma subtypes using Gray's test, and multivariable-adjusted hazard ratios (HRs) were estimated from propensity score–weighted Cox regression models. Results: The median follow-up for the entire cohort was 17 months and for surviving patients was 21 months. The 1-year cumulative incidence of and adjusted HR for local, nodal, regional, and distant failure in high-risk versus non–high-risk lesions was 7.3% versus 2.7% (HR 16.8; 95% confidence interval [CI] 3.5-81.4), 14.8% versus 2.6% (HR 3.8; 95% CI 0.95-15.0), 4.0% versus 1.2% (HR 20.9; 95% CI 2.3-192.3), and 22.7% versus 3.6% (HR 6.9; 95% CI 2.2-21.1), respectively. No significant difference was seen with regard to overall survival. Conclusions: The outcomes after SBRT for early-stage adenocarcinoma of the lung correlate highly with histologic subtype, with micropapillary and solid tumors portending significantly higher rates of locoregional and metastatic progression. In this context, the histologic subtype determined from core biopsies is a prognostic factor and could have important implications for patient selection, adjuvant treatment, biopsy methods, and clinical trial design.« less

Histologic Subtype in Core Lung Biopsies of Early-Stage Lung Adenocarcinoma is a Prognostic Factor for Treatment Response and Failure Patterns After Stereotactic Body Radiation Therapy.

PubMed

Leeman, Jonathan E; Rimner, Andreas; Montecalvo, Joseph; Hsu, Meier; Zhang, Zhigang; von Reibnitz, Donata; Panchoo, Kelly; Yorke, Ellen; Adusumilli, Prasad S; Travis, William; Wu, Abraham J

2017-01-01

Stereotactic body radiation therapy (SBRT) has emerged as an effective treatment for early-stage lung cancer. The histologic subtype of surgically resected lung adenocarcinoma is recognized as a prognostic factor, with the presence of solid or micropapillary patterns predicting poor outcomes. We describe the outcomes after SBRT for early-stage lung adenocarcinoma stratified by histologic subtype. We identified 119 consecutive patients (124 lesions) with stage I to IIA lung adenocarcinoma who had undergone definitive SBRT at our institution from August 2008 to August 2015 and had undergone core biopsy. Histologic subtyping was performed according to the 2015 World Health Organization classification. Of the 124 tumors, 37 (30%) were a high-risk subtype, defined as containing a component of solid and/or micropapillary pattern. The cumulative incidences of local, nodal, regional, and distant failure were compared between the high-risk and non-high-risk adenocarcinoma subtypes using Gray's test, and multivariable-adjusted hazard ratios (HRs) were estimated from propensity score-weighted Cox regression models. The median follow-up for the entire cohort was 17 months and for surviving patients was 21 months. The 1-year cumulative incidence of and adjusted HR for local, nodal, regional, and distant failure in high-risk versus non-high-risk lesions was 7.3% versus 2.7% (HR 16.8; 95% confidence interval [CI] 3.5-81.4), 14.8% versus 2.6% (HR 3.8; 95% CI 0.95-15.0), 4.0% versus 1.2% (HR 20.9; 95% CI 2.3-192.3), and 22.7% versus 3.6% (HR 6.9; 95% CI 2.2-21.1), respectively. No significant difference was seen with regard to overall survival. The outcomes after SBRT for early-stage adenocarcinoma of the lung correlate highly with histologic subtype, with micropapillary and solid tumors portending significantly higher rates of locoregional and metastatic progression. In this context, the histologic subtype determined from core biopsies is a prognostic factor and could have important implications for patient selection, adjuvant treatment, biopsy methods, and clinical trial design. Copyright © 2016 Elsevier Inc. All rights reserved.

A Review of Non-Chemical Stressors and Their Importance in Cumulative Risk Assessment

EPA Science Inventory

Cumulative exposure/risk assessments need to include non-chemical stressors as well as human activities and chemical data. Multiple stressor research can offer information on the interactions between chemical and non-chemical stressors needed for cumulative risk assessment resea...

Life course pathways of adverse childhood experiences toward adult psychological well-being: A stress process analysis.

PubMed

Nurius, Paula S; Green, Sara; Logan-Greene, Patricia; Borja, Sharon

2015-07-01

Growing evidence suggests that toxic stressors early in life not only convey developmental impacts but also augment risk of proliferating chains of additional stressors that can overwhelm individual coping and undermine recovery and health. Examining trauma within a life course stress process perspective, we posit that early childhood adversity carries a unique capacity to impair adult psychological well-being both independent of and cumulative with other contributors, including social disadvantage and stressful adult experiences. This study uses data from a representative population-based health survey (N=13,593) to provide one of the first multivariate assessments of unique, cumulative, and moderated effects of adverse childhood experiences (ACEs) toward explaining 3 related yet distinct measures of adult mental health: perceived well-being, psychological distress, and impaired daily activities. Results demonstrate support for each set of hypothesized associations, including exacerbation and amelioration of ACEs effects by adult stress and resilience resources, respectively. Implications for services and future research are discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Life Course Pathways of Adverse Childhood Experiences Toward Adult Psychological Well-Being: A Stress Process Analysis

PubMed Central

Nurius, Paula S.; Green, Sara; Logan-Greene, Patricia; Borja, Sharon

2015-01-01

Growing evidence suggests that toxic stressors early in life not only convey developmental impacts but also augment risk of proliferating chains of additional stressors that can overwhelm individual coping and undermine recovery and health. Examining trauma within a life course stress process perspective, we posit that early childhood adversity carries a unique capacity to impair adult psychological well-being both independent of and cumulative with other contributors, including social disadvantage and stressful adult experiences. This study uses data from a representative population-based health survey (N = 13,593) to provide one of the first multivariate assessments of unique, cumulative, and moderated effects of adverse childhood experiences (ACEs) toward explaining 3 related yet distinct measures of adult mental health: perceived well-being, psychological distress, and impaired daily activities. Results demonstrate support for each set of hypothesized associations, including exacerbation and amelioration of ACEs effects by adult stress and resilience resources, respectively. Implications for services and future research are discussed. PMID:25846195

Appraisal and coping as mediators of the effects of cumulative risk on preadolescent adjustment

PubMed Central

Thompson, Stephanie F.; Lengua, Liliana J.; Garcia, Connie Meza

2016-01-01

This study examined the concurrent and longitudinal relations among cumulative risk, appraisal, coping, and adjustment. Longitudinal path models were tested in a community sample of 316 children in preadolescence to examine hypotheses that threat appraisal and avoidant coping mediate the effects of cumulative risk on child adjustment, whereas positive appraisal and active coping were hypothesized to predict better adjustment independently. Children and their mothers were assessed during in-home interviews at three time points at one-year intervals. Children reported on appraisal and coping strategies. Mothers and children reported on child adjustment problems and positive adjustment. Rank-order changes in appraisal and coping predicted rank-order changes in adjustment. Cumulative risk was concurrently related to higher threat appraisal and avoidant coping at each time point. Threat appraisal and avoidant coping mediated the relations of cumulative risk to rank-order changes in adjustment. There is specificity in the relations of cumulative risk to threat appraisal and avoidant coping, whereas positive appraisal and active coping are independent of risk and operate as individual resource factors. PMID:27110087

Risk factors for early cytologic abnormalities after loop electrosurgical excision procedure.

PubMed

Dietrich, Charles S; Yancey, Michael K; Miyazawa, Kunio; Williams, David L; Farley, John

2002-02-01

To evaluate risk factors for early cytologic abnormalities and recurrent cervical dysplasia after loop electrosurgical excision procedure (LEEP). A retrospective analysis was performed of all pathology records for LEEPs performed at our institution from January 1996 through July 1998. Follow-up cytology from 2 through 12 months after LEEP was reviewed. Patients with abnormal cytology were referred for further colposcopic evaluation. Statistical analysis using chi2 test for trend, proportional hazards model test, Fisher exact tests, and life table analysis were performed to identify risk factors for early cytologic abnormalities after LEEP and to determine relative risk of recurrent dysplasia. A total of 298 women underwent LEEP during the study period, and 29% of these had cytologic abnormalities after LEEP. Grade of dysplasia, ectocervical marginal status, endocervical marginal status, and glandular involvement with dysplasia were not found to be independent risk factors for early cytologic abnormalities. However, when risk factors were analyzed cumulatively, the abnormal cytology rate increased from 24% with no risk factors to 67% with three risk factors present (P =.037). Of patients with abnormal cytology after LEEP, 40% developed subsequent dysplasia, and the mean time to diagnosis was approximately 6 months. The relative risk of subsequent dysplasia ranged from a 20% increase to twice the risk if post-LEEP cytology was low-grade squamous intraepithelial lesion or high-grade squamous intraepithelial lesion, respectively. Based on these results, consideration should be given for early colposcopic examination of patients who have evidence of marginal involvement or endocervical glandular involvement with dysplasia. These patients are at increased risk for abnormal cytology and recurrent dysplasia. This initial visit should occur at 6 months, as the mean time to recurrence of dysplasia was 6.5 months.

Direct comparison of risk-adjusted and non-risk-adjusted CUSUM analyses of coronary artery bypass surgery outcomes.

PubMed

Novick, Richard J; Fox, Stephanie A; Stitt, Larry W; Forbes, Thomas L; Steiner, Stefan

2006-08-01

We previously applied non-risk-adjusted cumulative sum methods to analyze coronary bypass outcomes. The objective of this study was to assess the incremental advantage of risk-adjusted cumulative sum methods in this setting. Prospective data were collected in 793 consecutive patients who underwent coronary bypass grafting performed by a single surgeon during a period of 5 years. The composite occurrence of an "adverse outcome" included mortality or any of 10 major complications. An institutional logistic regression model for adverse outcome was developed by using 2608 contemporaneous patients undergoing coronary bypass. The predicted risk of adverse outcome in each of the surgeon's 793 patients was then calculated. A risk-adjusted cumulative sum curve was then generated after specifying control limits and odds ratio. This risk-adjusted curve was compared with the non-risk-adjusted cumulative sum curve, and the clinical significance of this difference was assessed. The surgeon's adverse outcome rate was 96 of 793 (12.1%) versus 270 of 1815 (14.9%) for all the other institution's surgeons combined (P = .06). The non-risk-adjusted curve reached below the lower control limit, signifying excellent outcomes between cases 164 and 313, 323 and 407, and 667 and 793, but transgressed the upper limit between cases 461 and 478. The risk-adjusted cumulative sum curve never transgressed the upper control limit, signifying that cases preceding and including 461 to 478 were at an increased predicted risk. Furthermore, if the risk-adjusted cumulative sum curve was reset to zero whenever a control limit was reached, it still signaled a decrease in adverse outcome at 166, 653, and 782 cases. Risk-adjusted cumulative sum techniques provide incremental advantages over non-risk-adjusted methods by not signaling a decrement in performance when preoperative patient risk is high.

Cumulative Incidence of Cancer among HIV-infected Individuals in North America

PubMed Central

Silverberg, Michael J.; Lau, Bryan; Achenbach, Chad J.; Jing, Yuezhou; Althoff, Keri N.; D’Souza, Gypsyamber; Engels, Eric A.; Hessol, Nancy; Brooks, John T.; Burchell, Ann N.; Gill, M. John; Goedert, James J.; Hogg, Robert; Horberg, Michael A.; Kirk, Gregory D.; Kitahata, Mari M.; Korthuis, Phillip T.; Mathews, William C.; Mayor, Angel; Modur, Sharada P.; Napravnik, Sonia; Novak, Richard M.; Patel, Pragna; Rachlis, Anita R.; Sterling, Timothy R.; Willig, James H.; Justice, Amy C.; Moore, Richard D.; Dubrow, Robert

2016-01-01

Background Cancer is increasingly common among HIV patients given improved survival. Objective To examine calendar trends in cumulative cancer incidence and hazard rate by HIV status. Design Cohort study Setting North American AIDS Cohort Collaboration on Research and Design during 1996–2009 Patients 86,620 HIV-infected and 196,987 uninfected adults Measurements We estimated cancer-type-specific cumulative incidence by age 75 years by HIV status and calendar era, and examined calendar trends in cumulative incidence and hazard rates. Results Cumulative incidences (%) of cancer by age 75 (HIV+/HIV−) were: Kaposi sarcoma (KS), 4.4/0.01; non-Hodgkin’s lymphoma (NHL), 4.5/0.7; lung, 3.4/2.8; anal, 1.5/0.1; colorectal, 1.0/1.5; liver, 1.1/0.4; Hodgkin lymphoma (HL), 0.9/0.1; melanoma, 0.5/0.6; and oral cavity/pharyngeal, 0.8/0.8. Among HIV-infected subjects, we observed decreasing calendar trends in cumulative incidence and hazard rate for KS and NHL. For anal, colorectal and liver cancers, increasing cumulative incidence, but not hazard rate trends, were due to the decreasing mortality rate trend (−9% per year), allowing greater opportunity to be diagnosed with these cancer types. Despite decreasing hazard rate trends for lung, HL, and melanoma, we did not observe cumulative incidence trends due to the compensating effect of the declining mortality rate on cumulative incidence. Limitations Secular trends in screening, smoking, and viral co-infections were not evaluated. Conclusions Our analytic approach helped disentangle the effects of improved survival and changing cancer-specific hazard rates on cumulative incidence trends among HIV patients. Cumulative cancer incidence by age 75, approximating lifetime risk in HIV patients, may have clinical utility in this population. The high cumulative incidences by age 75 for KS, NHL, and lung cancer supports early and sustained ART and smoking cessation. Primary Funding Source National Institutes of Health PMID:26436616

A Multimethodological Analysis of Cumulative Risk and Allostatic Load among Rural Children.

ERIC Educational Resources Information Center

Evans, Gary W.

2003-01-01

This study modeled physical and psychosocial aspects of home environment and personal characteristics in a cumulative risk heuristic. Found that elevated cumulative risk was associated with heightened cardiovascular and neuroendocrine parameters, increased deposition of body fat, and higher summary index of total allostatic load. Replicated…

Development of inhibitory control among prenatally cocaine exposed and non-cocaine exposed youths from late childhood to early adolescence: The effects of gender and risk and subsequent aggressive behavior.

PubMed

Bridgett, David J; Mayes, Linda C

2011-01-01

The goal of the present investigation was to characterize the development of inhibitory control, an aspect of executive functions, in a sample of prenatally cocaine exposed (CE; n=165) children compared to an at risk, but prenatally cocaine unexposed (NCE; n=119) sample across time (i.e. 7.5 to 11.5 years of age). Gender and cumulative risk, a combination of postnatal medical (i.e. low birth weight and APGAR scores) and demographic risk, indexed by maternal educational attainment, were examined as predictors of change in inhibitory control across time and aggression was modeled as an outcome when children reached 14 years of age. Multiple group latent growth models indicated that CE children made more errors at 7.5 years of age during a standard Stroop interference task, however, over time CE children had greater age-related improvements, narrowing the initial gap, with NCE children in the ability to inhibit errors. Gender effects at 7.5 years within the NCE group were identified with NCE boys making initially more errors than NCE girls; both NCE and CE girls improved faster across development compared to NCE and CE boys, respectively. Greater cumulative risk was associated with more errors at 7.5 years in the CE and NCE groups. No differences were observed between CE and NCE children on time to complete the Stroop task at 7.5 years. However, NCE children had greater age-related improvements in their time to complete the Stroop interference task relative to their CE counterparts. NCE girls improved the fastest over time relative to NCE boys; a similar trend emerged (p<0.10) with CE girls improving faster over time than CE boys. Although all participants improved across development, higher cumulative risk in both groups was associated with slower age-related improvements (i.e. higher slopes) in the time to complete the Stroop task across development. After accounting for gender and cumulative risk, findings in both groups indicated that those who made more errors at 7.5 years of age and/or who had slower age-related changes (i.e. higher slopes) of time to complete the Stroop task across development were more aggressive as rated by caregivers at 14 years of age. Although qualified by gender and cumulative risk, these findings are consistent with reduced cognitive processing efficiency and executive function difficulties in CE children relative to NCE children. Findings suggest that executive function difficulties in CE children may be subtle as development continues to unfold over time. Furthermore, these findings indicate that development of inhibitory control may be an important mechanism linking prenatal cocaine exposure, gender, and cumulative risk to later adverse outcomes. Copyright © 2010 Elsevier Inc. All rights reserved.

Cumulative poor psychosocial and behavioral health among low-income women at 6 weeks postpartum.

PubMed

Walker, Lorraine O; Sterling, Bobbie Sue; Guy, Sarah; Mahometa, Michael J

2013-01-01

During the postpartum period, women may experience unfavorable psychosocial and behavioral health in multiple domains with adverse effects on parenting and maternal and infant health. Yet, little is known about the accumulation of poor health across the domains of depressive symptoms; body image; diet and physical activity; substance use including smoking and alcohol; and general self-care at 6 weeks postpartum, the usual end of maternity care. The aims of this study were to evaluate relationships among the domains comprising psychosocial and behavioral health and to examine the distribution and risk factors associated with cumulative poor psychosocial and behavioral health at 6 weeks postpartum. This study was a secondary analysis of cumulative poor health assessed by self-report scales for depressive symptoms, body image dissatisfaction, diet and exercise, substance use, and general self-care among 419 low-income White, African American, and Hispanic women at 6 weeks postpartum. Multivariable Poisson and logistic regression were used in key analyses. The correlation among psychosocial and behavioral domains had a range of r = .50-.00. In this sample of women, 45% had two or more domains in which they had poor health. The model testing risk factors for cumulative poor health was significant (likelihood ratio chi-square = 39.26, df = 11, p < 0.05), with two significant factors: not exclusively breastfeeding (odds ratio [OR] = 1.459, 95% confidence interval [CI] [1.119, 1.901]) and Hispanic ethnicity (OR = 0.707, 95% CI [0.582, 0.858], psuedo-R = .029). Within individual domains, significant risk factors (body mass index, not exclusively breastfeeding, ethnicity, education level, and parity) varied by domain. Many low-income women postpartum have poor psychosocial and behavioral health in multiple domains, which constitute areas for health promotion and early disease prevention.

Longitudinal Pathways from Cumulative Contextual Risk at Birth to School Functioning in Adolescence: Analysis of Mediation Effects and Gender Moderation.

PubMed

January, Stacy-Ann A; Mason, W Alex; Savolainen, Jukka; Solomon, Starr; Chmelka, Mary B; Miettunen, Jouko; Veijola, Juha; Moilanen, Irma; Taanila, Anja; Järvelin, Marjo-Riitta

2017-01-01

Children and adolescents exposed to multiple contextual risks are more likely to have academic difficulties and externalizing behavior problems than those who experience fewer risks. This study used data from the Northern Finland Birth Cohort 1986 (a population-based study; N = 6961; 51 % female) to investigate (a) the impact of cumulative contextual risk at birth on adolescents' academic performance and misbehavior in school, (b) learning difficulties and/or externalizing behavior problems in childhood as intervening mechanisms in the association of cumulative contextual risk with functioning in adolescence, and (c) potential gender differences in the predictive associations of cumulative contextual risk at birth with functioning in childhood or adolescence. The results of the structural equation modeling analysis suggested that exposure to cumulative contextual risk at birth had negative associations with functioning 16 years later, and academic difficulties and externalizing behavior problems in childhood mediated some of the predictive relations. Gender, however, did not moderate any of the associations. Therefore, the findings of this study have implications for the prevention of learning and conduct problems in youth and future research on the impact of cumulative risk exposure.

Longitudinal Pathways from Cumulative Contextual Risk at Birth to School Functioning in Adolescence: Analysis of Mediation Effects and Gender Moderation

PubMed Central

January, Stacy-Ann A.; Mason, W. Alex; Savolainen, Jukka; Solomon, Starr; Chmelka, Mary B.; Miettunen, Jouko; Veijola, Juha; Moilanen, Irma; Taanila, Anja; Järvelin, Marjo-Riitta

2016-01-01

Children and adolescents exposed to multiple contextual risks are more likely to have academic difficulties and externalizing behavior problems than those who experience fewer risks. This study used data from the Northern Finland Birth Cohort 1986 (a population-based study; N = 6,961; 51% female) to investigate (a) the impact of cumulative contextual risk at birth on adolescents’ academic performance and misbehavior in school, (b) learning difficulties and/or externalizing behavior problems in childhood as intervening mechanisms in the association of cumulative contextual risk with functioning in adolescence, and (c) potential gender differences in the predictive associations of cumulative contextual risk at birth with functioning in childhood or adolescence. The results of the structural equation modeling analysis suggested that exposure to cumulative contextual risk at birth had negative associations with functioning 16 years later, and academic difficulties and externalizing behavior problems in childhood mediated some of the predictive relations. Gender, however, did not moderate any of the associations. Therefore, the findings of this study have implications for the prevention of learning and conduct problems in youth and future research on the impact of cumulative risk exposure. PMID:27665276

Family cumulative risk and at-risk kindergarteners' social competence: the mediating role of parent representations of the attachment relationship.

PubMed

Sparks, Lauren A; Trentacosta, Christopher J; Owusu, Erika; McLear, Caitlin; Smith-Darden, Joanne

2018-08-01

Secure attachment relationships have been linked to social competence in at-risk children. In the current study, we examined the role of parent secure base scripts in predicting at-risk kindergarteners' social competence. Parent representations of secure attachment were hypothesized to mediate the relationship between lower family cumulative risk and children's social competence. Participants included 106 kindergarteners and their primary caregivers recruited from three urban charter schools serving low-income families as a part of a longitudinal study. Lower levels of cumulative risk predicted greater secure attachment representations in parents, and scores on the secure base script assessment predicted children's social competence. An indirect relationship between lower cumulative risk and kindergarteners' social competence via parent secure base script scores was also supported. Parent script-based representations of the attachment relationship appear to be an important link between lower levels of cumulative risk and low-income kindergarteners' social competence. Implications of these findings for future interventions are discussed.

Effects of cumulative stress and impulsivity on smoking status.

PubMed

Ansell, Emily B; Gu, Peihua; Tuit, Keri; Sinha, Rajita

2012-03-01

The stress-vulnerability model of addiction predicts that environmental factors, such as cumulative stress, will result in individual adaptations that decrease self-control, increase impulsivity, and increase risk for addiction. Impulsivity and cumulative stress are risk factors for tobacco smoking that are rarely examined simultaneously in research. We examined the indirect and direct effects of cumulative adversity in a community sample consisting of 291 men and women who participated in an assessment of cumulative stress, self-reported impulsivity, and smoking history. Data were analyzed using bootstrapping techniques to estimate indirect effects of stress on smoking via impulsivity. Cumulative adversity is associated with smoking status via direct effects and indirect effects through impulsivity scores. Additional models examining specific types of stress indicate contributions of traumatic stress and recent life events as well as chronic relationship stressors. Overall, cumulative stress is associated with increased risk of smoking via increased impulsivity and via pathways independent of impulsivity. These findings support the stress-vulnerability model and highlight the utility of mediation models in assessing how, and for whom, cumulative stress increases risk of current cigarette smoking. Increasing self-control is a target for interventions with individuals who have experienced cumulative adversity. Copyright © 2012 John Wiley & Sons, Ltd.

Effects of cumulative stress and impulsivity on smoking status

PubMed Central

Ansell, Emily B.; Gu, Peihua; Tuit, Keri; Sinha, Rajita

2013-01-01

Objective The stress-vulnerability model of addiction predicts that environmental factors, such as cumulative stress, will result in individual adaptations that decrease self-control, increase impulsivity, and increase risk for addiction. Impulsivity and cumulative stress are risk factors for tobacco smoking that are rarely examined simultaneously in research. Methods We examined the indirect and direct effects of cumulative adversity in a community sample consisting of 291 men and women who participated in an assessment of cumulative stress, self-reported impulsivity, and smoking history. Data were analyzed using bootstrapping techniques to estimate indirect effects of stress on smoking via impulsivity. Results Cumulative adversity is associated with smoking status via direct effects and indirect effects through impulsivity scores. Additional models examining specific types of stress indicate contributions of traumatic stress and recent life events as well as chronic relationship stressors. Conclusions Overall, cumulative stress is associated with increased risk of smoking via increased impulsivity and via pathways independent of impulsivity. These findings support the stress-vulnerability model and highlight the utility of mediation models in assessing how, and for whom, cumulative stress increases risk of current cigarette smoking. Increasing self-control is a target for interventions with individuals who have experienced cumulative adversity. PMID:22389084

Adverse childhood experiences and sexual victimization in adulthood.

PubMed

Ports, Katie A; Ford, Derek C; Merrick, Melissa T

2016-01-01

Understanding the link between adverse childhood experiences (ACEs) and sexual victimization (SV) in adulthood may provide important information about the level of risk for adult SV and sexual re-victimization among childhood sexual abuse (CSA) survivors. In the present paper, we explore the relationship between ACEs, including CSA, and SV in adulthood. Data from the CDC-Kaiser ACE Study were used to examine the effect of experiences of early adversity on adult SV. Adult HMO members (n=7,272) undergoing a routine health exam provided detailed information about ACEs that occurred at age 18 or younger and their experiences of SV in adulthood. Analyses revealed that as ACE score increased, so did risk of experiencing SV in adulthood. Each of the ACE variables was significantly associated with adult SV, with CSA being the strongest predictor of adult SV. In addition, for those who reported CSA, there was a cumulative increase in adult SV risk with each additional ACE experienced. As such, early adversity is a risk factor for adult SV. In particular, CSA is a significant risk factor for sexual re-victimization in adulthood, and additional early adversities experienced by CSA survivors may heighten adult SV risk above and beyond the risk associated with CSA alone. Given the interconnectedness among various experiences of early adversity, adult SV prevention actions must consider how other violence-related and non-violence-related traumatic experiences may exacerbate the risk conferred by CSA on subsequent victimization. Published by Elsevier Ltd.

An analysis of cumulative risks based on biomonitoring data for six phthalates using the Maximum Cumulative Ratio

EPA Science Inventory

The Maximum Cumulative Ratio (MCR) quantifies the degree to which a single chemical drives the cumulative risk of an individual exposed to multiple chemicals. Phthalates are a class of chemicals with ubiquitous exposures in the general population that have the potential to cause ...

Cumulative positive fluid balance is a risk factor for acute kidney injury and requirement for renal replacement therapy after liver transplantation.

PubMed

Codes, Liana; de Souza, Ygor Gomes; D'Oliveira, Ricardo Azevedo Cruz; Bastos, Jorge Luiz Andrade; Bittencourt, Paulo Lisboa

2018-04-24

To analyze whether fluid overload is an independent risk factor of adverse outcomes after liver transplantation (LT). One hundred and twenty-one patients submitted to LT were retrospectively evaluated. Data regarding perioperative and postoperative variables previously associated with adverse outcomes after LT were reviewed. Cumulative fluid balance (FB) in the first 12 h and 4 d after surgery were compared with major adverse outcomes after LT. Most of the patients were submitted to a liberal approach of fluid administration with a mean cumulative FB over 5 L and 10 L, respectively, in the first 12 h and 4 d after LT. Cumulative FB in 4 d was independently associated with occurrence of both AKI and requirement for renal replacement therapy (RRT) (OR = 2.3; 95%CI: 1.37-3.86, P = 0.02 and OR = 2.89; 95%CI: 1.52-5.49, P = 0.001 respectively). Other variables on multivariate analysis associated with AKI and RRT were, respectively, male sex and Acute Physiology and Chronic Health Disease Classification System (APACHE II) levels and sepsis or septic shock. Mortality was shown to be independently related to AST and APACHE II levels (OR = 2.35; 95%CI: 1.1-5.05, P = 0.02 and 2.63; 95%CI: 1.0-6.87, P = 0.04 respectively), probably reflecting the degree of graft dysfunction and severity of early postoperative course of LT. No effect of FB on mortality after LT was disclosed. Cumulative positive FB over 4 d after LT is independently associated with the development of AKI and the requirement of RRT. Survival was not independently related to FB, but to surrogate markers of graft dysfunction and severity of postoperative course of LT.

The Role of Child Temperament on Head Start Preschoolers' Social Competence in the Context of Cumulative Risk

ERIC Educational Resources Information Center

Corapci, Feyza

2008-01-01

This study examined the main and interactive effects of cumulative risk and child temperament on teacher ratings of social competence and observer ratings of peer play in a sample of Head Start preschoolers. A cumulative risk index (CRI) was computed by summing the total number of risk factors for each family. There was a difference in the…

Novel Risk Stratification Score for Predicting Early Distant Brain Failure and Salvage Whole Brain Radiotherapy after Stereotactic Radiosurgery for Brain Metastases

PubMed Central

Press, Robert H.; Prabhu, Roshan S.; Nickleach, Dana C.; Liu, Yuan; Shu, Hui-Kuo G.; Kandula, Shravan; Patel, Kirtesh R.; Curran, Walter J.; Crocker, Ian

2015-01-01

Background The purpose of this study was to evaluate predictors of early distant brain failure (DBF) and salvage whole brain radiotherapy (WBRT) after treatment with stereotactic radiosurgery (SRS) for brain metastases and create a clinically relevant risk score in order to stratify patients’ risk of these events. Methods We reviewed records of 270 patients with brain metastases treated with SRS between 2003-2012. Pre-treatment patient and tumor characteristics were analyzed by univariate and multivariable analyses. Cumulative incidence (CI) of first DBF and salvage WBRT were calculated. Significant factors were used to create a score for stratifying early (6-month) DBF risk. Results No prior WBRT, total lesion volume <1.3 cm3, primary breast cancer or malignant melanoma histology, and multiple metastases (≥2) were found to be significant predictors for early DBF. Each factor was ascribed one point due to similar hazard ratios. Scores of 0-1, 2, and 3-4 were considered low, intermediate, and high risk, respectively. This correlated with 6-month CI of DBF of 16.6%, 28.8%, and 54.4%, respectively (p<0.001). For patients without prior WBRT, the 6-month CI of salvage WBRT by 6-months was 2%, 17.7%, and 25.7%, respectively (p<0.001). Conclusion Early DBF after SRS requiring salvage WBRT remains a significant clinical problem. Patient stratification for early DBF can better inform the decision for initial treatment strategy for brain metastases. The provided risk score may help predict for early DBF and subsequent salvage WBRT if initial SRS is used. External validation is needed prior to clinical implementation. PMID:26242475

Drug safety evaluation of sorafenib for treatment of solid tumors: consequences for the risk assessment and management of cancer patients.

PubMed

Huillard, Olivier; Boissier, Emilie; Blanchet, Benoit; Thomas-Schoemann, Audrey; Cessot, Anatole; Boudou-Rouquette, Pascaline; Durand, Jean-Philippe; Coriat, Romain; Giroux, Julie; Alexandre, Jerome; Vidal, Michel; Goldwasser, Francois

2014-05-01

Sorafenib is a multi-tyrosine kinase inhibitor (TKI). Considerable clinical experience has been accumulated since its first Phase III clinical trial in metastatic renal cancer patients in 2007. The management of its early acute toxicity in fit patients is well known. The management of prolonged treatment becomes the new challenge. Using sorafenib as a key word for PubMed search, we review preclinical and clinical data and discuss the pharmacokinetics and pharmacodynamics of sorafenib, its acute and cumulative toxicities and their consequences for patient management. The systematic multi-disciplinary risk assessment of cancer patients prior to TKI initiation reduces the risks of acute and late toxicity, especially drug-drug interactions and arterial risks. Sarcopenia is now identified as a major risk of severe toxicity. The very diverse clinical pictures of cumulative toxicity must be known. The monitoring of sorafenib systemic exposure is helpful especially in elderly patients. Moreover, at disease progression, it allows distinguishing between underexposure to sorafenib and truly acquired resistance to the drug. The optimal use of sorafenib should allow improving the reported results of flat-dose. Finally, most of this knowledge could be used for the development and optimal use of the other TKIs.

Eye lens radiation exposure to interventional cardiologists: a retrospective assessment of cumulative doses.

PubMed

Jacob, Sophie; Donadille, Laurent; Maccia, Carlo; Bar, Olivier; Boveda, Serge; Laurier, Dominique; Bernier, Marie-Odile

2013-03-01

Radiation dose to the eye lens is a crucial issue for interventional cardiologists (ICs) who are exposed during the procedures they perform. This paper presents a retrospective assessment of the cumulative eye lens doses of ICs enrolled in the O'CLOC study for Occupational Cataracts and Lens Opacities in interventional Cardiology. Information on the workload in the catheterisation laboratory, radiation protection equipment, eye lens dose per procedure and dose reduction factors associated with eye-protective equipment were considered. For the 129 ICs at an average age of 51 who had worked for an average period of 22 years, the estimated cumulative eye lens dose ranged from 25 mSv to more than 1600 mSv; the mean ± SD was 423 ± 359 mSv. After several years of practice, without eye protection, ICs may exceed the new ICRP lifetime eye dose threshold of 500 mSv and be at high risk of developing early radiation-induced cataracts. Radiation protection equipment can reduce these doses and should be used routinely.

Temporal analysis of the October 1989 proton flare using computerized anatomical models

NASA Technical Reports Server (NTRS)

Simonsen, L. C.; Cucinotta, F. A.; Atwell, W.; Nealy, J. E.

1993-01-01

The GOES-7 time history data of hourly averaged integral proton fluxes at various particle kinetic energies are analyzed for the solar proton event that occurred between October 19 and 29, 1989. By analyzing the time history data, the dose rates which may vary over many orders of magnitude in the early phases of the flare can be estimated as well as the cumulative dose as a function of time. Basic transport calculations are coupled with detailed body organ thickness distributions from computerized anatomical models to estimate dose rates and cumulative doses to 20 critical body organs. For a 5-cm-thick water shield, cumulative skin, eye, and blood-forming-organ dose equivalents of 1.27, 1.23, and 0.41 Sv, respectively, are estimated. These results are approximately 40-50 percent less than the widely used 0- and 5-cm slab dose estimates. The risk of cancer incidence and mortality are also estimated for astronauts protected by various water shield thicknesses.

An Analysis of Cumulative Risks Indicated by Biomonitoring Data of Six Phthalates Using the Maximum Cumulative Ratio

EPA Science Inventory

The Maximum Cumulative Ratio (MCR) quantifies the degree to which a single component of a chemical mixture drives the cumulative risk of a receptor.1 This study used the MCR, the Hazard Index (HI) and Hazard Quotient (HQ) to evaluate co-exposures to six phthalates using biomonito...

Interaction between prenatal risk and infant parasympathetic and sympathetic stress reactivity predicts early aggression.

PubMed

Suurland, J; van der Heijden, K B; Huijbregts, S C J; van Goozen, S H M; Swaab, H

2017-09-01

Nonreciprocal action of the parasympathetic (PNS) and sympathetic (SNS) nervous systems, increases susceptibility to emotional and behavioral problems in children exposed to adversity. Little is known about the PNS and SNS in interaction with early adversity during infancy. Yet this is when the physiological systems involved in emotion regulation are emerging and presumably most responsive to environmental influences. We examined whether parasympathetic respiratory sinus arrhythmia (RSA) and sympathetic pre-ejection period (PEP) response and recovery at six months, moderate the association between cumulative prenatal risk and physical aggression at 20 months (N=113). Prenatal risk predicted physical aggression, but only in infants exhibiting coactivation of PNS and SNS (i.e., increase in RSA and decrease in PEP) in response to stress. These findings indicate that coactivation of the PNS and SNS in combination with prenatal risk is a biological marker for the development of aggression. Copyright © 2017 Elsevier B.V. All rights reserved.

The Family Life Project: an epidemiological and developmental study of young children living in poor rural communities.

PubMed

Vernon-Feagans, Lynne; Cox, Martha

2013-10-01

About 20% of children in the United States have been reported to live in rural communities, with child poverty rates higher and geographic isolation from resources greater than in urban communities. There have been surprisingly few studies of children living in rural communities, especially poor rural communities. The Family Life Project helped fill this gap by using an epidemiological design to recruit and study a representative sample of every baby born to a mother who resided in one of six poor rural counties over a 1-year period, oversampling for poverty and African American. 1,292 children were followed from birth to 36 months of age. This monograph described these children and used a cumulative risk model to examine the relation between social risk and children's executive functioning, language development, and behavioral competence at 36 months. Using both the Family Process Model of development and the Family Investment Model of development, observed parenting was examined over time in relation to child functioning at 36 months. Different aspects of observed parenting were examined as mediators/moderators of risk in predicting child outcomes. Results suggested that cumulative risk was important in predicting all three major domains of child outcomes and that positive and negative parenting and maternal language complexity were mediators of these relations. Maternal positive parenting was found to be a buffer for the most risky families in predicting behavioral competence. In a final model using both family process and investment measures, there was evidence of mediation but with little evidence of the specificity of parenting for particular outcomes. Discussion focused on the importance of cumulative risk and parenting in understanding child competence in rural poverty and the implications for possible intervention strategies that might be effective in maximizing the early development of these children.

Laboratory database population surveillance to improve detection of progressive chronic kidney disease.

PubMed

Kennedy, David M; Chatha, Kamaljit; Rayner, Hugh C

2013-09-01

Some patients with chronic kidney disease are still referred late for specialist care despite the evidence that earlier detection and intervention can halt or delay progression to end-stage kidney disease (ESKD). To develop a population surveillance system using existing laboratory data to enable early detection of patients at high risk of ESKD by reviewing cumulative graphs of estimated glomerular filtration rate (eGFR). A database was developed, updated daily with data from the laboratory computer. Cumulative eGFR graphs containing up to five years of data are reviewed by clinical scientists for all primary care patients or out-patients with a low eGFR for their age. For those with a declining trend, a report containing the eGFR graph is sent to the requesting doctor. A retrospective audit was performed using historical data to assess the predictive value of the graphs. In nine months, we reported 370,000 eGFR results, reviewing 12,000 eGFR graphs. On average 60 graphs per week were flagged as 'high' or 'intermediate' risk. Patients with graphs flagged as high risk had a significantly higher mortality after 3.5 years and a significantly greater chance of requiring renal replacement therapy after 4.5 years of follow-up. Five patients (7%) with graphs flagged as high risk had a sustained >25% fall in eGFR without evidence of secondary care referral. Feedback about the service from requesting clinicians was 73% positive. We have developed a system for laboratory staff to review cumulative eGFR graphs for a large population and identify patients at highest risk of developing ESKD. Further research is needed to measure the impact of this service on patient outcomes. © 2013 European Dialysis and Transplant Nurses Association/European Renal Care Association.

Early Probiotic Supplementation for Eczema and Asthma Prevention: A Randomized Controlled Trial.

PubMed

Cabana, Michael D; McKean, Michelle; Caughey, Aaron B; Fong, Lawrence; Lynch, Susan; Wong, Angela; Leong, Russell; Boushey, Homer A; Hilton, Joan F

2017-09-01

To determine if probiotic administration during the first 6 months of life decreases childhood asthma and eczema. We conducted a randomized, double-blind controlled trial of Lactobacillus rhamnosus GG (LGG) supplementation on the cumulative incidence of eczema (primary end point) and asthma and rhinitis (secondary end points) in high-risk infants. For the first 6 months of life, intervention infants ( n = 92) received a daily dose of 10 billion colony-forming units of LGG and 225 mg of inulin (Amerifit Brands, Cromwell, CT), and control infants ( n = 92) received 325 mg of inulin alone. We used survival analysis methods to estimate disease incidences in the presence or absence of LGG and to estimate the efficacy of LGG in delaying or preventing these diseases. Infants were accrued over a 6-year period (median follow-up: 4.6 years; 95% retention rate at 2 years). At 2 years of age, the estimated cumulative incidence of eczema was 30.9% (95% confidence interval [CI], 21.4%-40.4%) in the control arm and 28.7% (95% CI, 19.4%-38.0%) in the LGG arm, for a hazard ratio of 0.95 (95% CI, 0.59-1.53) (log-rank P = .83). At 5 years of age, the cumulative incidence of asthma was 17.4% (95% CI, 7.6%-27.1%) in the control arm and 9.7% (95% CI, 2.7%-16.6%) in the LGG arm, for a hazard ratio of 0.88 (95% CI, 0.41-1.87) (log-rank P = .25). For high-risk infants, early LGG supplementation for the first 6 months of life does not appear to prevent the development of eczema or asthma at 2 years of age. Copyright © 2017 by the American Academy of Pediatrics.

Cumulative radiation exposure and associated cancer risk estimates for scoliosis patients: Impact of repetitive full spine radiography.

PubMed

Law, Martin; Ma, Wang-Kei; Lau, Damian; Chan, Eva; Yip, Lawrance; Lam, Wendy

2016-03-01

To quantitatively evaluate the cumulative effective dose and associated cancer risk for scoliotic patients undergoing repetitive full spine radiography during their diagnosis and follow up periods. Organ absorbed doses of full spine exposed scoliotic patients at different age were computer simulated with the use of PCXMC software. Gender specific effective dose was then calculated with the ICRP-103 approach. Values of lifetime attributable cancer risk for patients exposed at different age were calculated for both patient genders and for Asian and Western population. Mathematical fitting for effective dose and for lifetime attributable cancer risk, as function of exposed age, was analytically obtained to quantitatively estimate patient cumulated effective dose and cancer risk. The cumulative effective dose of full spine radiography with posteroanterior and lateral projection for patients exposed annually at age between 5 and 30 years using digital radiography system was calculated as 15mSv. The corresponding cumulative lifetime attributable cancer risk for Asian and Western population was calculated as 0.08-0.17%. Female scoliotic patients would be at a statistically significant higher cumulated cancer risk than male patients under the same full spine radiography protocol. We demonstrate the use of computer simulation and analytic formula to quantitatively obtain the cumulated effective dose and cancer risk at any age of exposure, both of which are valuable information to medical personnel and patients' parents concern about radiation safety in repetitive full spine radiography. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Emotion dysregulation mediates the relationship between lifetime cumulative adversity and depressive symptomatology.

PubMed

Abravanel, Benjamin T; Sinha, Rajita

2015-02-01

Repeated exposure to stressful events across the lifespan, referred to as cumulative adversity, is a potent risk factor for depression. Research indicates that cumulative adversity detrimentally affects emotion regulation processes, which may represent a pathway linking cumulative adversity to vulnerability to depression. However, empirical evidence that emotion dysregulation mediates the relationship between cumulative adversity and depression is limited, particularly in adult populations. We examined the direct and indirect effects of cumulative adversity on depressive symptomatology in a large community sample of adults (n = 745) who were further characterized by risk status: never-depressed (n = 638) and "at-risk" remitted mood-disordered (n = 107). All participants completed the Cumulative Adversity Inventory (CAI), the Difficulties in Emotion Regulation Scale (DERS), and the Center for Epidemiologic Studies Depression Scale (CES-D). Bootstrapped confidence intervals were computed to estimate the indirect effect of emotion dysregulation on the relationship between cumulative adversity and depressive symptomatology and to test whether this indirect effect was moderated by risk status. Emotion dysregulation partially and significantly mediated the relationship between cumulative adversity and depressive symptomatology independent of risk status. Overall, cumulative adversity and emotion dysregulation accounted for 50% of the variance in depressive symptomatology. These findings support the hypothesis that disruption of adaptive emotion regulation processes associated with repeated exposure to stressful life events represents an intrapersonal mechanism linking the experience of adverse events to depression. Our results support the utility of interventions that simultaneously emphasize stress reduction and emotion regulation to treat and prevent depressive vulnerability and pathology. Copyright © 2014 Elsevier Ltd. All rights reserved.

Infant Medical Trauma in the Neonatal Intensive Care Unit (IMTN): A Proposed Concept for Science and Practice.

PubMed

DʼAgata, Amy L; Young, Erin E; Cong, Xiaomei; Grasso, Damion J; McGrath, Jacqueline M

2016-08-01

Trauma is an innately subjective experience ensuing from a deeply distressing event. Research has demonstrated that while the environment of the neonatal intensive care unit (NICU) is capable of providing extraordinary lifesaving measures following birth, the experience may be disruptive to several key aspects of early development, placing infants at risk for adverse behavioral, cognitive, and emotional outcomes. This article provides rationale for the concept of Infant Medical Trauma in the NICU (IMTN) as a means of describing this unique stress experience. A triad of cumulative early life NICU experiences (stress, parental separation, and pain) is proposed to influence an infant's swinging neurodevelopmental pendulum amid the potential outcomes of risk and resilience. Creating language that describes the infant experience brings meaning and calls caregivers and parents to action to consider strategies that may improve long-term health. Actively seeking opportunities to decrease the allostatic load of at-risk infants may support an infant's pendulum to swing toward a path of resilience, thereby moderating his or her early life adverse experience.

The use of satellite data to measure ultraviolet-B penetrance and its potential association with age of multiple sclerosis onset.

PubMed

Amram, Ofer; Schuurman, Nadine; Randall, Ellen; Zhu, Feng; Saeedi, Jameelah; Rieckmann, Peter; Yee, Irene; Tremlett, Helen

2018-04-01

Studies have indicated an association between low Ultraviolet B (UVB) exposure and an increased risk of developing multiple sclerosis (MS). Few studies, however, have explored whether UVB exposure is associated with the age at MS symptom onset. We investigated the potential association between cumulative early life ambient UVB exposure and age at MS onset, using satellite data to measure ambient UVB exposure. Adult onset MS patients were selected from the University of British Columbia's MS genetic database (1980-2005). Patients' places of residence from birth to age 18 years were geocoded (latitude and longitude) and assigned UVB values using NASA's Total Ozone Mapping Spectrometer (TOMS) dataset. Linear regression was used to explore the relationship between cumulative UVB exposure (measured for age periods 0-6, 7-12, 13-18, 0-12, and 0-18) and age at MS onset. 3226 patients were included in the analysis. Of these, 74% were female, with an overall mean symptom onset age of 33.3 years. At onset, a total of 2944 (91%) had a relapsing-remitting disease course, 254 (8%) had primary progressive and the disease course for 28 (1%) was unknown. No significant associations between cumulative early life ambient UVB exposure and age at MS onset were observed. Patient sex, MS phenotype, and immigration to Canada after age 18 were significantly associated with age of onset (p < 0.01). Early life ambient UVB, as measured by satellite imagery, was not significantly associated with the age at MS onset. Copyright © 2018 Elsevier B.V. All rights reserved.

Cortisol Function Among Early School-aged Homeless Children

PubMed Central

Cutuli, J. J.; Wiik, Kristen L.; Herbers, Janette E.; Gunnar, Megan R.; Masten, Ann S.

2009-01-01

SUMMARY Homelessness represents a context of extreme poverty and risk for child development. This study compared the relative influence of two classes of risk in the context of homelessness. Levels of socioeconomic resource-related risk and negative lifetime events were examined with respect to morning cortisol levels and cortisol response to a set of cognitive tasks. Participants were 66 children between the ages of 4 and 7 years staying in an emergency shelter for families. Adversities largely reflecting family level negative life events predicted higher levels of morning cortisol and differences in initial level and change over the course of the session of cognitive tasks. In contrast, a socioeconomic cumulative risk score was not associated with morning or session-related differences in cortisol. PMID:20022181

Individual differences in early adolescents' latent trait cortisol (LTC): Relation to early adversity.

PubMed

Stroud, Catherine B; Chen, Frances R; Doane, Leah D; Granger, Douglas A

2016-09-01

Substantial evidence suggests that youth who experience early adversity exhibit alterations in hypothalamic pituitary adrenal (HPA) axis functioning, thereby increasing risk for negative health outcomes. However, few studies have explored whether early adversity alters enduring trait indicators of HPA axis activity. Using objective contextual stress interviews with adolescents and their mothers to assess early adversity, we examined the cumulative impact of nine types of early adversity on early adolescents girls' latent trait cortisol (LTC). Adolescents (n = 122; M age = 12.39 years) provided salivary cortisol samples three times a day (waking, 30 min post-waking, and bedtime) over 3 days. Latent state-trait modeling indicated that the waking and 30 min post-waking samples contributed to a LTC factor. Moreover, greater early adversity was associated with a lower LTC level. Implications of LTC for future research examining the impact of early adversity on HPA axis functioning are discussed. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 58:700-713, 2016. © 2016 Wiley Periodicals, Inc.

Cumulative environmental risk and youth maladjustment: the role of youth attributes.

PubMed

Gerard, Jean M; Buehler, Cheryl

2004-01-01

Using data from 5,070 youth ages 11 to 18 years old who participated in the National Longitudinal Study of Adolescent Health, concurrent and longitudinal associations among cumulative risk, protective factors, and youth maladjustment were examined. Cumulative risk was associated with concurrent conduct problems and depressed mood. For conduct problems, a compensatory effect was found for scholastic achievement and problem-solving ability. For depressed mood, a compensatory effect was found for scholastic achievement. A protective-reactive effect of self-esteem was found for both forms of maladjustment. Youth gender, grade, and ethnicity moderated these associations. Cumulative risk predicted change over time in depressed mood. Scholastic achievement and self-esteem compensated for this risk. Findings indicate that youth attributes offer limited protection when adolescents experience risk factors across life domains.

Classical cardiovascular disease risk factors associate with vascular function and morphology in rheumatoid arthritis: a six-year prospective study

PubMed Central

2013-01-01

Introduction Patients with rheumatoid arthritis (RA) are at an increased risk for cardiovascular disease (CVD). An early manifestation of CVD is endothelial dysfunction which can lead to functional and morphological vascular abnormalities. Classical CVD risk factors and inflammation are both implicated in causing endothelial dysfunction in RA. The objective of the present study was to examine the effect of baseline inflammation, cumulative inflammation, and classical CVD risk factors on the vasculature following a six-year follow-up period. Methods A total of 201 RA patients (155 females, median age (25th to 75th percentile): 61 years (53 to 67)) were examined at baseline (2006) for presence of classical CVD risk factors and determination of inflammation using C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). At follow-up (2012) patients underwent assessments of microvascular and macrovascular endothelium-dependent and endothelium-independent function, along with assessment of carotid atherosclerosis. The CRP and ESR were recorded from the baseline study visit to the follow-up visit for each patient to calculate cumulative inflammatory burden. Results Classical CVD risk factors, but not RA disease-related inflammation, predicted microvascular endothelium-dependent and endothelium-independent function, macrovascular endothelium-independent function and carotid atherosclerosis. These findings were similar in a sub-group of patients free from CVD, and not receiving non-steroidal anti-inflammatory drugs, cyclooxygenase 2 inhibitors or biologics. Cumulative inflammation was not associated with microvascular and macrovascular endothelial function, but a weak association was apparent between area under the curve for CRP and carotid atherosclerosis. Conclusions Classical CVD risk factors may be better long-term predictors of vascular function and morphology than systemic disease-related inflammation in patients with RA. Further studies are needed to confirm if assessments of vascular function and morphology are predictive of long-term CV outcomes in RA. PMID:24289091

A Missing Link in the Evolution of the Cumulative Recorder

ERIC Educational Resources Information Center

Asano, Toshio; Lattal, Kennon A.

2012-01-01

A recently recovered cumulative recorder provides a missing link in the evolution of the cumulative recorder from a modified kymograph to a reliably operating, scientifically and commercially successful instrument. The recorder, the only physical evidence of such an early precommercial cumulative recorder yet found, was sent to Keio University in…

Black-White Disparity in Young Adults' Disease Risk: An Investigation of Variation in the Vulnerability of Black Young Adults to Early and Later Adversity.

PubMed

Wickrama, Kandauda A S; Bae, Dayoung; O'Neal, Catherine Walker

2016-08-01

Socioeconomic adversity in early years and young adulthood are risk factors for poor health in young adulthood. Population differences in exposure to stressful socioeconomic conditions partly explain the higher prevalence of disease among black young adults. Another plausible mechanism is that blacks are differentially vulnerable to socioeconomic adversity (differential vulnerability hypothesis), which has not been adequately investigated in previous research. The present study investigated variation in the vulnerability of black young adults leading to cardiometabolic (CM) disease risk. We used a nationally representative sample of 8,824 adolescents who participated in the Add Health study. Early and later adversity was measured using a cumulative index of social and material adversity in adolescence and young adulthood. CM disease risk was assessed using nine biomarkers. Path analysis within a structural equation modeling framework was used. The findings indicated that both early and later socioeconomic adversity act as stressors with independent additive influences on young adults' CM disease risk, consistent with the differential exposure hypothesis. Moreover, the results showed that black youth are less vulnerable to early socioeconomic adversity than whites, but they are more vulnerable to later adversity. The findings provide support for the unique and additive influences of early and later socioeconomic adversity on CM disease risk contributing to the black-white health disparity in young adulthood. The results also suggest that vulnerability to adversity varies depending on the life stage, which highlights the need for life-stage specific interventions to mitigate the existing black-white disparity in young adults' physical health. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

U.S. EPA Authority to Use Cumulative Risk Assessments in Environmental Decision-Making

PubMed Central

Alves, Sarah; Tilghman, Joan; Rosenbaum, Arlene; Payne-Sturges, Devon C.

2012-01-01

Conventionally, in its decision-making, the U.S. EPA has evaluated the effects and risks associated with a single pollutant in a single exposure medium. In reality, people are exposed to mixtures of pollutants or to the same pollutant through a variety of media, including the air, water, and food. It is now more recognized than before that environmental exposure to pollutants occurs via multiple exposure routes and pathways, including inhalation, ingestion, and dermal absorption. Moreover, chemical, biologic, radiologic, physical, and psychologic stressors are all acknowledged as affecting human health. Although many EPA offices attempt to consider cumulative risk assessment and cumulative effects in various ways, there is no Agency-wide policy for considering these risks and the effects of exposure to these risks when making environmental decisions. This article examines how U.S. courts might assess EPA’s general authority and discretion to use cumulative risk assessment as the basis for developing data in support of environmental decision-making, and how courts might assess the validity of a cumulative risk assessment methodology itself. PMID:22829786

Cumulative hip contact stress predicts osteoarthritis in DDH.

PubMed

Mavcic, Blaz; Iglic, Ales; Kralj-Iglic, Veronika; Brand, Richard A; Vengust, Rok

2008-04-01

Hip stresses are generally believed to influence whether a hip develops osteoarthritis (OA); similarly, various osteotomies have been proposed to reduce contact stresses and the risk of OA. We asked whether elevated hip contact stress predicted osteoarthritis in initially asymptomatic human hips. We identified 58 nonoperatively treated nonsubluxated hips with developmental dysplasia (DDH) without symptoms at skeletal maturity; the control group included 48 adult hips without hip disease. The minimum followup was 20 years (mean, 29 years; range, 20-41 years). Peak contact stress was computed with the HIPSTRESS method using anteroposterior pelvic radiographs at skeletal maturity. The cumulative contact stress was determined by multiplying the peak contact stress by age at followup. We compared WOMAC scores and radiographic indices of OA. Dysplastic hips had higher mean peak contact and higher mean cumulative contact stress than normal hips. Mean WOMAC scores and percentage of asymptomatic hips in the study group (mean age 51 years) were similar to those in the control group (mean age 68 years). After adjusting for gender and age, the cumulative contact stress, Wiberg center-edge angle, body mass index, but not the peak contact stress, independently predicted the final WOMAC score in dysplastic hips but not in normal hips. Cumulative contact stress predicted early hip OA better than the Wiberg center-edge angle. Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Modeling the Interplay of Multilevel Risk Factors for Future Academic and Behavior Problems: A Person-Centered Approach

PubMed Central

Lanza, Stephanie T.; Rhoades, Brittany L.; Nix, Robert L.; Greenberg, Mark T.

2010-01-01

This study identified profiles of 13 risk factors across child, family, school, and neighborhood domains in a diverse sample of children in kindergarten from 4 US locations (n = 750; 45% minority). It then examined the relation of those early risk profiles to externalizing problems, school failure, and low academic achievement in Grade 5. A person-centered approach, latent class analysis, revealed four unique risk profiles, which varied considerably across urban African American, urban white, and rural white children. Profiles characterized by several risks that cut across multiple domains conferred the highest risk for negative outcomes. Compared to a variable-centered approach, such as a cumulative risk index, these findings provide a more nuanced understanding of the early precursors to negative outcomes. For example, results suggested that urban children in single-parent homes that have few other risk factors (i.e., show at least average parenting warmth and consistency and report relatively low stress and high social support) are at quite low risk for externalizing problems, but at relatively high risk for poor grades and low academic achievement. These findings provide important information for refining and targeting preventive interventions to groups of children who share particular constellations of risk factors. PMID:20423544

Modeling the interplay of multilevel risk factors for future academic and behavior problems: a person-centered approach.

PubMed

Lanza, Stephanie T; Rhoades, Brittany L; Nix, Robert L; Greenberg, Mark T

2010-05-01

This study identified profiles of 13 risk factors across child, family, school, and neighborhood domains in a diverse sample of children in kindergarten from four US locations (n = 750; 45% minority). It then examined the relation of those early risk profiles to externalizing problems, school failure, and low academic achievement in Grade 5. A person-centered approach, latent class analysis, revealed four unique risk profiles, which varied considerably across urban African American, urban White, and rural White children. Profiles characterized by several risks that cut across multiple domains conferred the highest risk for negative outcomes. Compared to a variable-centered approach, such as a cumulative risk index, these findings provide a more nuanced understanding of the early precursors to negative outcomes. For example, results suggested that urban children in single-parent homes that have few other risk factors (i.e., show at least average parenting warmth and consistency and report relatively low stress and high social support) are at quite low risk for externalizing problems, but at relatively high risk for poor grades and low academic achievement. These findings provide important information for refining and targeting preventive interventions to groups of children who share particular constellations of risk factors.

The EPA's human exposure research program for assessing cumulative risk in communities.

PubMed

Zartarian, Valerie G; Schultz, Bradley D

2010-06-01

Communities are faced with challenges in identifying and prioritizing environmental issues, taking actions to reduce their exposures, and determining their effectiveness for reducing human health risks. Additional challenges include determining what scientific tools are available and most relevant, and understanding how to use those tools; given these barriers, community groups tend to rely more on risk perception than science. The U.S. Environmental Protection Agency's Office of Research and Development, National Exposure Research Laboratory (NERL) and collaborators are developing and applying tools (models, data, methods) for enhancing cumulative risk assessments. The NERL's "Cumulative Communities Research Program" focuses on key science questions: (1) How to systematically identify and prioritize key chemical stressors within a given community?; (2) How to develop estimates of exposure to multiple stressors for individuals in epidemiologic studies?; and (3) What tools can be used to assess community-level distributions of exposures for the development and evaluation of the effectiveness of risk reduction strategies? This paper provides community partners and scientific researchers with an understanding of the NERL research program and other efforts to address cumulative community risks; and key research needs and opportunities. Some initial findings include the following: (1) Many useful tools exist for components of risk assessment, but need to be developed collaboratively with end users and made more comprehensive and user-friendly for practical application; (2) Tools for quantifying cumulative risks and impact of community risk reduction activities are also needed; (3) More data are needed to assess community- and individual-level exposures, and to link exposure-related information with health effects; and (4) Additional research is needed to incorporate risk-modifying factors ("non-chemical stressors") into cumulative risk assessments. The products of this research program will advance the science for cumulative risk assessments and empower communities with information so that they can make informed, cost-effective decisions to improve public health.

Relationship Risks in Context: A Cumulative Risk Approach to Understanding Relationship Satisfaction

PubMed Central

Rauer, Amy J.; Karney, Benjamin R.; Garvan, Cynthia W.; Hou, Wei

2009-01-01

Risks associated with less satisfying intimate relationships often co-occur within individuals, raising questions about approaches that consider only their independent impact. Utilizing the cumulative risk model, which acknowledges the natural covariation of risk factors, this study examined individuals in intimate relationships using the Florida Family Formation Survey (n = 2,876) and a replication sample (n = 1,048). Analyses confirmed that not only was relationship satisfaction lower among those with more risks, but the cumulative risk score was predictive above and beyond the individual risk factors. Furthermore, experiencing multiple risks exacerbated the negative associations between individual risks and relationship satisfaction, suggesting that the operation of a risk factor in a relationship is moderated by the presence or absence of other risks. PMID:19587840

Considering Environmental and Occupational Stressors in Cumulative Risk Assessments

EPA Science Inventory

While definitions vary across the global scientific community, cumulative risk assessments (CRAs) typically are described as exhibiting a population focus and analyzing the combined risks posed by multiple stressors. CRAs also may consider risk management alternatives as an anal...

The Effects of Cumulative Victimization on Mental Health Among Lesbian, Gay, Bisexual, and Transgender Adolescents and Young Adults.

PubMed

Mustanski, Brian; Andrews, Rebecca; Puckett, Jae A

2016-03-01

To examine the effects of the cumulative victimization experienced by lesbian, gay, bisexual, and transgender youths on mental disorders. We recruited 248 participants from the Chicago, Illinois, area in 7 waves of data collected over 4 years, beginning in 2007 (83.1% retention rate). Mean age at enrollment was 18.7 years, and 54.7% were Black. We measured depression and posttraumatic stress disorder using structured psychiatric interviews. Latent class analyses of victimization over time identified a 4-class solution. Class 1 (65.4%) had low, decreasing victimization. Class 2 (10.3%) had moderate, increasing victimization. Class 3 (5.1%) had high, steady victimization. Class 4 (19.2%) had high, decreasing victimization. Controlling for baseline diagnoses and birth sex, lesbian, gay, bisexual, and transgender youths in classes 2 and 3 were at higher risk for depression than were those in class 1; youths in classes 2, 3, and 4 were at elevated risk for posttraumatic stress disorder. Lesbian, gay, bisexual, and transgender youths with steadily high or increasing levels of victimization from adolescence to early adulthood are at higher risk for depression and posttraumatic stress disorder.

The Effects of Cumulative Victimization on Mental Health Among Lesbian, Gay, Bisexual, and Transgender Adolescents and Young Adults

PubMed Central

Andrews, Rebecca; Puckett, Jae A.

2016-01-01

Objectives. To examine the effects of the cumulative victimization experienced by lesbian, gay, bisexual, and transgender youths on mental disorders. Methods. We recruited 248 participants from the Chicago, Illinois, area in 7 waves of data collected over 4 years, beginning in 2007 (83.1% retention rate). Mean age at enrollment was 18.7 years, and 54.7% were Black. We measured depression and posttraumatic stress disorder using structured psychiatric interviews. Results. Latent class analyses of victimization over time identified a 4-class solution. Class 1 (65.4%) had low, decreasing victimization. Class 2 (10.3%) had moderate, increasing victimization. Class 3 (5.1%) had high, steady victimization. Class 4 (19.2%) had high, decreasing victimization. Controlling for baseline diagnoses and birth sex, lesbian, gay, bisexual, and transgender youths in classes 2 and 3 were at higher risk for depression than were those in class 1; youths in classes 2, 3, and 4 were at elevated risk for posttraumatic stress disorder. Conclusions. Lesbian, gay, bisexual, and transgender youths with steadily high or increasing levels of victimization from adolescence to early adulthood are at higher risk for depression and posttraumatic stress disorder. PMID:26794175

Children of Misfortune: Early Adversity and Cumulative Inequality in Perceived Life Trajectories1

PubMed Central

Schafer, Markus H.; Ferraro, Kenneth F.; Mustillo, Sarah A.

2011-01-01

Adversity early in life may alter pathways of aging, but what interpretive processes can soften the blow of early insults? Drawing from cumulative inequality theory, the authors analyze trajectories of life evaluations and then consider whether early adversity offsets favorable expectations for the future. Results reveal that early adversity contributes to more negative views of the past but rising expectations for the future. Early adversity also has enduring effects on life evaluations, offsetting the influence of buoyant expectations. The findings draw attention to the limits of human agency under the constraints of early adversity—a process described as biographical structuration. PMID:21648247

Quantitative crystalline silica exposure assessment for a historical cohort epidemiologic study in the German porcelain industry.

PubMed

Birk, Thomas; Guldner, Karlheinz; Mundt, Kenneth A; Dahmann, Dirk; Adams, Robert C; Parsons, William

2010-09-01

A time-dependent quantitative exposure assessment of silica exposure among nearly 18,000 German porcelain workers was conducted. Results will be used to evaluate exposure-response disease risks. Over 8000 historical industrial hygiene (IH) measurements with original sampling and analysis protocols from 1954-2006 were obtained from the German Berufs- genossenschaft der keramischen-und Glas-Industrie (BGGK) and used to construct a job exposure matrix (JEM). Early measurements from different devices were converted to modern gravimetric equivalent values. Conversion factors were derived from parallel historical measurements and new side-by-side measurements using historical and modern devices in laboratory dust tunnels and active workplace locations. Exposure values were summarized and smoothed using LOESS regression; estimates for early years were derived using backward extrapolation techniques. Employee work histories were merged with JEM values to determine cumulative crystalline silica exposures for cohort members. Average silica concentrations were derived for six primary similar exposure groups (SEGs) for 1938-2006. Over 40% of the cohort accumulated <0.5 mg; just over one-third accumulated >1 mg/m(3)-years. Nearly 5000 workers had cumulative crystalline silica estimates >1.5 mg/m(3)-years. Similar numbers of men and women fell into each cumulative exposure category, except for 1113 women and 1567 men in the highest category. Over half of those hired before 1960 accumulated >3 mg/m(3)-years crystalline silica compared with 4.9% of those hired after 1960. Among those ever working in the materials preparation area, half accumulated >3 mg/m(3)-year compared with 12% of those never working in this area. Quantitative respirable silica exposures were estimated for each member of this cohort, including employment periods for which sampling used now obsolete technologies. Although individual cumulative exposure estimates ranged from background to about 40 mg/m(3)-years, many of these estimates reflect long-term exposures near modern exposure limit values, allowing direct evaluation of lung cancer and silicosis risks near these limits without extrapolation. This quantitative exposure assessment is the largest to date in the porcelain industry.

Retrospective exposure assessment to airborne asbestos among power industry workers

PubMed Central

2010-01-01

Background A method of individually assessing former exposure to asbestos fibres is a precondition of risk-differentiated health surveillance. The main aims of our study were to assess former levels of airborne asbestos exposure in the power industry in Germany and to propose a basic strategy for health surveillance and the early detection of asbestos related diseases. Methods Between March 2002 and the end of 2006, we conducted a retrospective questionnaire based survey of occupational tasks and exposures with airborne asbestos fibres in a cohort of 8632 formerly asbestos exposed power industry workers. The data on exposure and occupation were entered into a specially designed computer programme, based on ambient monitoring of airborne asbestos fibre concentrations. The cumulative asbestos exposure was expressed as the product of the eight-hour time weighted average and the total duration of exposure in fibre years (fibres/cubic centimetre-years). Results Data of 7775 (90% of the total) participants working in installations for power generation, power distribution or gas supply could be evaluated. The power generation group (n = 5284) had a mean age of 56 years, were exposed for 20 years and had an average cumulative asbestos exposure of 42 fibre years. The occupational group of "metalworkers" (n = 1600) had the highest mean value of 79 fibre years. The corresponding results for the power distribution group (n = 2491) were a mean age of 45 years, a mean exposure duration of 12 years and an average cumulative asbestos exposure of only 2.5 fibre years. The gas supply workers (n = 512) had a mean age of 54 years and a mean duration of exposure of 15 years. Conclusions While the surveyed cohort as a whole was heavily exposed to asbestos dust, the power distribution group had a mean cumulative exposure of only 6% of that found in the power generation group. Based on the presented data, risk-differentiated disease surveillance focusing on metalworkers and electricians from the power generating industry seems justified. That combined with a sensitive examination technique would allow detecting asbestos related diseases early and efficiently. PMID:20579364

Are all risks equal? Early experiences of poverty-related risk and children's functioning.

PubMed

Roy, Amanda L; Raver, C Cybele

2014-06-01

Using cumulative risk and latent class analysis (LCA) models, we examined how exposure to deep poverty (income-to-needs ratio <0.50) and 4 poverty-related risks (i.e., single-parent household, residential crowding, caregiver depression, and multiple life stressors) in preschool is related to children's future difficulty in school in a longitudinal sample of 602 Head Start-enrolled, low-income families. Results from the LCA revealed 4 risk profiles: low risk, deep poverty and single, single and stressed, and deep poverty and crowded household. Tests of measurement invariance across racial/ethnic groups established that, although patterns of risk are similar across groups (i.e., risks covary in the same way), the prevalence of risk profiles differs. African American families were overrepresented in the "deep poverty and single" profile while Latino and White families were overrepresented in the "deep poverty and crowded" profile. Finally, children's third grade functioning in 3 domains (i.e., academic performance, behavior problems, and self-regulatory skills) was predicted using a cumulative risk index and LCA-identified risk profiles. Both approaches demonstrated that children who experienced higher levels of risk in preschool had worse school performance than children with low levels of risk. However, LCA also revealed that children who experienced "single and stressed" family settings had more behavior problems than low-risk children while children who experienced "deep poverty and crowded" family settings had worse academic performance. The results indicate that all risks are not equal for children's development and highlight the utility of LCA for tailoring intervention efforts to best meet the needs of target populations. PsycINFO Database Record (c) 2014 APA, all rights reserved

Are All Risks Equal? Early Experiences of Poverty-Related Risk and Children’s Functioning

PubMed Central

Roy, Amanda L.; Raver, C. Cybele

2014-01-01

Using cumulative risk and latent class analysis (LCA) models, this research examines how exposure to deep poverty (income-to-needs ratio <.50) and four poverty-related risks (single-parent household, residential crowding, caregiver depression, and multiple life stressors) in preschool is related to children’s future difficulty in school in a longitudinal sample of 602 Head-Start enrolled, low-income families. Results from the LCA revealed four risk profiles: low risk, deep poverty and single, single and stressed, and deep poverty and crowded household. Tests of measurement invariance across racial/ethnic groups established that although patterns of risk are similar across groups (i.e. risks co-vary in the same way), the prevalence of risk profiles differ. African American families were over-represented in the ‘deep poverty and single’ profile while Latino and White families were over-represented in the ‘deep poverty and crowded’ profile. Finally, children’s third grade functioning in three domains (academic performance, behavior problems, self-regulatory skills) was predicted using a cumulative risk index and LCA identified risk profiles. Both approaches demonstrated that children who experienced higher levels of risk in preschool had worse school performance than children with low levels of risk. However, the LCA also revealed that children who experienced ‘single and stressed’ family settings had more behavior problems than low risk children while children who experienced ‘deep poverty and crowded’ family settings had worse academic performance. The results indicate that all risks are not equal for children’s development and highlight the utility of LCA for tailoring intervention efforts to best meet the needs of target populations. PMID:24749652

A possible early sign of hydroxychloroquine macular toxicity.

PubMed

Brandao, Livia M; Palmowski-Wolfe, Anja M

2016-02-01

Hydroxychloroquine (HCQ) has a low risk of retinal toxicity which increases dramatically with a cumulative dose of >1000 g. Here we report a case of HCQ macular toxicity presentation in a young patient with a cumulative dose of 438 g. A 15-year-old female started attending annual consultations for retinal toxicity screening in our clinic after 3 years of HCQ treatment for juvenile idiopathic dermatomyositis. She had been diagnosed at age 12 and had been on hydroxychloroquine 200 mg/day, cyclosporin 150 mg/day and vitamin D3 since. Screening consultations included: complete ophthalmologic examination, automated perimetry (AP, M Standard, Octopus 101, Haag-Streit), multifocal electroretinogram (VERIS 6.06™, FMSIII), optical coherence tomography (OCT, fast macular protocol, Cirrus SD-OCT, Carl Zeiss), fundus autofluorescence imaging (Spectralis OCT, Heidelberg Engineering Inc.) and color testing (Farnsworth-Panel-D-15). After 5 years of treatment, AP demonstrated reduced sensibility in only one extra-foveal point in each eye (p < 0.2). Even though other exams showed no alteration and the cumulative dose was only around 353 g, consultations were increased to every 6 months. After 2-year follow-up, that is, 7 years of HCQ, a bilateral paracentral macula thinning was evident on OCT, suggestive of bull's eye maculopathy. However, the retinal pigmented epithelium appeared intact and AP was completely normal in both eyes. Further evaluation with ganglion cell analysis (GCA = ganglion cell + inner plexiform layer, Cirrus SD-OCT, Carl Zeiss) showed a concentric thinning of this layer in the same area. Although daily and cumulative doses were still under the high toxicity risk parameters, HCQ was suspended. At a follow-up 1 year later, visual acuity was 20/16 without any further changes in OCT or on any other exam. This may be the first case report of insidious bull's eye maculopathy exclusively identified using OCT thickness analysis, in a patient in whom both cumulative and daily dosages were under the high-risk parameters for screening and the averages reported in studies. As ganglion cell analysis has only recently become available, further studies are needed to understand toxicity mechanisms and maybe review screening recommendations.

Adverse experiences in childhood, adulthood neighbourhood disadvantage and health behaviours.

PubMed

Halonen, Jaana I; Vahtera, Jussi; Kivimäki, Mika; Pentti, Jaana; Kawachi, Ichiro; Subramanian, S V

2014-08-01

Early life adversities may play a role in the associations observed between neighbourhood contextual factors and health behaviours. We examined whether self-reported adverse experiences in childhood (parental divorce, long-term financial difficulties, serious conflicts, serious/chronic illness or alcohol problem in the family, and frequent fear of a family member) explain the association between adulthood neighbourhood disadvantage and co-occurrence of behavioural risk factors (smoking, moderate/heavy alcohol use, physical inactivity). Study population consisted of 31 271 public sector employees from Finland. The cross-sectional associations were analysed using two-level cumulative logistic regression models. Childhood adverse experiences were associated with the sum of risk factors (cumulative OR 1.32 (95% CI 1.25 to 1.40) among those reporting 3-6 vs 0 adversities). Adverse experiences did not attenuate the association between neighbourhood disadvantage and risk factors; this cumulative OR was 1.52 (95% CI 1.43 to 1.62) in the highest versus lowest quartile of neighbourhood disadvantage when not including adversities, and 1.50 (95% CI 1.40 to 1.60) when adjusted for childhood adversities. In adversity-stratified analyses those reporting 3-6 adversities had 1.60-fold (95% CI 1.42 to 1.80) likelihood of risk factors if living in the neighbourhood of the highest disadvantage, while in those with fewer adversities this likelihood was 1.09-1.34-fold (95% CI 0.98 to 1.53) (p interaction 0.07). Childhood adverse experiences and adulthood neighbourhood disadvantage were associated with behavioural risk factors. Childhood experiences did not explain associations between neighbourhood disadvantage and the risk factors. However, those with more adverse experiences may be susceptible for the socioeconomic conditions of neighbourhoods. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Emotion Dysregulation Mediates the Relationship between Lifetime Cumulative Adversity and Depressive Symptomatology

PubMed Central

Abravanel, Benjamin T.; Sinha, Rajita

2014-01-01

Repeated exposure to stressful events across the lifespan, referred to as cumulative adversity, is a potent risk factor for depression. Research indicates that cumulative adversity detrimentally affects emotion regulation processes, which may represent a pathway linking cumulative adversity to vulnerability to depression. However, empirical evidence that emotion dysregulation mediates the relationship between cumulative adversity and depression is limited, particularly in adult populations. We examined the direct and indirect effects of cumulative adversity on depressive symptomatology in a large community sample of adults (n = 745) who were further characterized by risk status: never-depressed (n = 638) and “at-risk” remitted mood-disordered (n = 107). All participants completed the Cumulative Adversity Inventory (CAI), the Difficulties in Emotion Regulation Scale (DERS), and the Center for Epidemiologic Studies Depression Scale (CES-D). Bootstrapped confidence intervals were computed to estimate the indirect effect of emotion dysregulation on the relationship between cumulative adversity and depressive symptomatology and to test whether this indirect effect was moderated by risk status. Emotion dysregulation partially and significantly mediated the relationship between cumulative adversity and depressive symptomatology independent of risk status. Overall, cumulative adversity and emotion dysregulation accounted for 50% of the variance in depressive symptomatology. These findings support the hypothesis that disruption of adaptive emotion regulation processes associated with repeated exposure to stressful life events represents an intrapersonal mechanism linking the experience of adverse events to depression. Our results support the utility of interventions that simultaneously emphasize stress reduction and emotion regulation to treat and prevent depressive vulnerability and pathology. PMID:25528603

Education, income and ethnic differences in cumulative biological risk profiles in a national sample of US adults: NHANES III (1988-1994).

PubMed

Seeman, Teresa; Merkin, Sharon S; Crimmins, Eileen; Koretz, Brandon; Charette, Susan; Karlamangla, Arun

2008-01-01

Data from the nationally representative US National Health and Nutrition Examination Survey (NHANES) III cohort were used to examine the hypothesis that socio-economic status is consistently and negatively associated with levels of biological risk, as measured by nine biological parameters known to predict health risks (diastolic and systolic blood pressure, pulse, HDL and total cholesterol, glycosylated hemoglobin, c-reactive protein, albumin and waist-hip ratio), resulting in greater cumulative burdens of biological risk among those of lower education and/or income. As hypothesized, consistent education and income gradients were seen for biological parameters reflecting cardiovascular, metabolic and inflammatory risk: those with lower education and income exhibiting greater prevalence of high-risk values for each of nine individual biological risk factors. Significant education and income gradients were also seen for summary indices reflecting cumulative burdens of cardiovascular, metabolic and inflammatory risks as well as overall total biological risks. Multivariable cumulative logistic regression models revealed that the education and income effects were each independently and negatively associated with cumulative biological risks, and that these effects remained significant independent of age, gender, ethnicity and lifestyle factors such as smoking and physical activity. There were no significant ethnic differences in the patterns of association between socio-economic status and biological risks, but older age was associated with significantly weaker education and income gradients.

External Validity of a Risk Stratification Score Predicting Early Distant Brain Failure and Salvage Whole Brain Radiation Therapy After Stereotactic Radiosurgery for Brain Metastases.

PubMed

Press, Robert H; Boselli, Danielle M; Symanowski, James T; Lankford, Scott P; McCammon, Robert J; Moeller, Benjamin J; Heinzerling, John H; Fasola, Carolina E; Burri, Stuart H; Patel, Kirtesh R; Asher, Anthony L; Sumrall, Ashley L; Curran, Walter J; Shu, Hui-Kuo G; Crocker, Ian R; Prabhu, Roshan S

2017-07-01

A scoring system using pretreatment factors was recently published for predicting the risk of early (≤6 months) distant brain failure (DBF) and salvage whole brain radiation therapy (WBRT) after stereotactic radiosurgery (SRS) alone. Four risk factors were identified: (1) lack of prior WBRT; (2) melanoma or breast histologic features; (3) multiple brain metastases; and (4) total volume of brain metastases <1.3 cm 3 , with each factor assigned 1 point. The purpose of this study was to assess the validity of this scoring system and its appropriateness for clinical use in an independent external patient population. We reviewed the records of 247 patients with 388 brain metastases treated with SRS between 2010 at 2013 at Levine Cancer Institute. The Press (Emory) risk score was calculated and applied to the validation cohort population, and subsequent risk groups were analyzed using cumulative incidence. The low-risk (LR) group had a significantly lower risk of early DBF than did the high-risk (HR) group (22.6% vs 44%, P=.004), but there was no difference between the HR and intermediate-risk (IR) groups (41.2% vs 44%, P=.79). Total lesion volume <1.3 cm 3  (P=.004), malignant melanoma (P=.007), and multiple metastases (P<.001) were validated as predictors for early DBF. Prior WBRT and breast cancer histologic features did not retain prognostic significance. Risk stratification for risk of early salvage WBRT were similar, with a trend toward an increased risk for HR compared with LR (P=.09) but no difference between IR and HR (P=.53). The 3-level Emory risk score was shown to not be externally valid, but the model was able to stratify between 2 levels (LR and not-LR [combined IR and HR]) for early (≤6 months) DBF. These results reinforce the importance of validating predictive models in independent cohorts. Further refinement of this scoring system with molecular information and in additional contemporary patient populations is warranted. Copyright © 2017 Elsevier Inc. All rights reserved.

Assessing Stress-Related Treatment Needs among Girls at Risk for Poor Functional Outcomes: The Impact of Cumulative Adversity, Criterion Traumas, and Non-Criterion Events

PubMed Central

Lansing, Amy E.; Plante, Wendy Y.; Beck, Audrey N.

2016-01-01

Despite growing recognition that cumulative adversity (total stressor exposure), including complex trauma, increases the risk for psychopathology and impacts development, assessment strategies lag behind: Trauma-related mental health needs (symptoms, functional impairment, maladaptive coping) are typically assessed in response to only one qualifying Criterion-A event. This is especially problematic for youth at-risk for health and academic disparities who experience cumulative adversity, including non-qualifying events (parental separations) which may produce more impairing symptomatology. Data from 118 delinquent girls demonstrate: 1) an average of 14 adverse Criterion-A and non-Criterion event exposures; 2) serious maladaptive coping strategies (self-injury) directly in response to cumulative adversity; 3) more cumulative adversity-related than worst-event related symptomatology and functional impairment; and 4) comparable symptomatology, but greater functional impairment, in response to non-Criterion events. These data support the evaluation of mental health needs in response to cumulative adversity for optimal identification and tailoring of services in high-risk populations to reduce disparities. PMID:27745922

Assessing stress-related treatment needs among girls at risk for poor functional outcomes: The impact of cumulative adversity, criterion traumas, and non-criterion events.

PubMed

Lansing, Amy E; Plante, Wendy Y; Beck, Audrey N

2017-05-01

Despite growing recognition that cumulative adversity (total stressor exposure, including complex trauma), increases the risk for psychopathology and impacts development, assessment strategies lag behind: Adversity-related mental health needs (symptoms, functional impairment, maladaptive coping) are typically assessed in response to only one qualifying Criterion-A traumatic event. This is especially problematic for youth at-risk for health and academic disparities who experience cumulative adversity, including non-qualifying events (separation from caregivers) which may produce more impairing symptomatology. Data from 118 delinquent girls demonstrate: (1) an average of 14 adverse Criterion-A and non-Criterion event exposures; (2) serious maladaptive coping strategies (self-injury) directly in response to cumulative adversity; (3) more cumulative adversity-related than worst-event related symptomatology and functional impairment; and (4) comparable symptomatology, but greater functional impairment, in response to non-Criterion events. These data support the evaluation of mental health needs in response to cumulative adversity for optimal identification and tailoring of services in high-risk populations to reduce disparities. Copyright © 2016 Elsevier Ltd. All rights reserved.

Early onset of diabetes in the proband is the major determinant of risk in HLA DR3-DQ2/DR4-DQ8 siblings.

PubMed

Gillespie, Kathleen M; Aitken, Rachel J; Wilson, Isabel; Williams, Alistair J K; Bingley, Polly J

2014-03-01

Islet autoimmunity is initiated in infancy, and primary prevention trials require children at high genetic risk to be identified before autoantibodies appear. To inform screening strategies, we evaluated risks of autoimmunity and diabetes associated with HLA DR3-DQ2/DR4-DQ8 in U.K. families. Extended HLA haplotypes were determined in 2,134 siblings from the Bart's-Oxford Study followed to a median age of 22 years. Risks of diabetes and islet autoimmunity (more than two antibodies) were estimated by survival analysis. Of 138 informative DR3-DQ2/DR4-DQ8 siblings, 63% shared both haplotypes with their diabetic proband, 29% shared one, and 8% shared neither. In HLA-identical DR3-DQ2/DR4-DQ8 siblings, the cumulative risk of diabetes by age 15 was 17% (vs. 6% in those sharing one haplotype or none; P = 0.095). Risk varied, however, with the age at the onset of diabetes in the proband; the cumulative risk of autoimmunity and/or diabetes by age 15 was 61% in siblings of probands diagnosed when younger than 10 years old compared with only 4.7% in those diagnosed after age 10 years (P < 0.001). The age of the proband at diagnosis, but not HLA haplotype sharing, was an independent determinant of sibling risk. This suggests that non-HLA genes or epigenetic/environmental factors that accelerate the progression of type 1 diabetes in the proband strongly affect risk in siblings.

Cumulative risk assessment for combined health effects from chemical and nonchemical stressors.

PubMed

Sexton, Ken; Linder, Stephen H

2011-12-01

Cumulative risk assessment is a science policy tool for organizing and analyzing information to examine, characterize, and possibly quantify combined threats from multiple environmental stressors. We briefly survey the state of the art regarding cumulative risk assessment, emphasizing challenges and complexities of moving beyond the current focus on chemical mixtures to incorporate nonchemical stressors, such as poverty and discrimination, into the assessment paradigm. Theoretical frameworks for integrating nonchemical stressors into cumulative risk assessments are discussed, the impact of geospatial issues on interpreting results of statistical analyses is described, and four assessment methods are used to illustrate the diversity of current approaches. Prospects for future progress depend on adequate research support as well as development and verification of appropriate analytic frameworks.

Cumulative Risk Assessment for Combined Health Effects From Chemical and Nonchemical Stressors

PubMed Central

Linder, Stephen H.

2011-01-01

Cumulative risk assessment is a science policy tool for organizing and analyzing information to examine, characterize, and possibly quantify combined threats from multiple environmental stressors. We briefly survey the state of the art regarding cumulative risk assessment, emphasizing challenges and complexities of moving beyond the current focus on chemical mixtures to incorporate nonchemical stressors, such as poverty and discrimination, into the assessment paradigm. Theoretical frameworks for integrating nonchemical stressors into cumulative risk assessments are discussed, the impact of geospatial issues on interpreting results of statistical analyses is described, and four assessment methods are used to illustrate the diversity of current approaches. Prospects for future progress depend on adequate research support as well as development and verification of appropriate analytic frameworks. PMID:21551386

Familial adenomatous polyposis: clinical presentation, detection and surveillance.

PubMed

Laurent, S; Franchimont, D; Coppens, J P; Leunen, K; Macken, L; Peeters, M; Plomteux, O; Polus, M; Poppe, B; Sempoux, C; Tejpar, S; Van Den Eynde, M; Van Gossum, A; Vannoote, J; Kartheuser, A; Van Cutsem, E

2011-09-01

Colorectal cancer (CRC) is a leading cause of cancer related death in the western countries. It remains an important health problem, often under-diagnosed. The symptoms can appear very late and about 25% of the patients are diagnosed at metastatic stage. Familial adenomatous polyposis (FAP) is an inherited colorectal cancer syndrome, characterized by the early onset of hundred to thousands of adenomatous polyps in the colon and rectum. Left untreated, there is a nearly 100% cumulative risk of progression to CRC by the age of 35-40 years, as well as an increased risk of various other malignancies. CRC can be prevented by the identification of the high risk population and by the timely implementation of rigid screening programs which will lead to special medico-surgical interventions.

Ethnoracial Variations in Acute PTSD Symptoms Among Hospitalized Survivors of Traumatic Injury

PubMed Central

Stephens, Kari A.; Sue, Stanley; Roy-Byrne, Peter; Unützer, Jürgen; Wang, Jin; Rivara, Frederick P.; Jurkovich, Gregory J.; Zatzick, Douglas F.

2011-01-01

Ethnoracial minority status contributes to an increased risk for posttraumatic stress disorder (PTSD) after trauma exposure, beyond other risk factors. A population-based sampling frame was used to examine the associations between ethnoracial groups and early PTSD symptoms while adjusting for relevant clinical and demographic characteristics. Acutely injured trauma center inpatients (N = 623) were screened with the PTSD Checklist. American Indian and African American patients reported the highest levels of posttraumatic stress and preinjury cumulative trauma burden. African American heritage was independently associated with an increased risk of higher acute PTSD symptom levels. Disparities in trauma history, PTSD symptoms, and event related factors emphasize the need for acute care services to incorporate culturally competent approaches for treating these diverse populations. PMID:20564368

Multi-risk infants: predicting attachment security from sociodemographic, psychosocial, and health risk among African-American preterm infants.

PubMed

Candelaria, Margo; Teti, Douglas M; Black, Maureen M

2011-08-01

Ecological and transactional theories link child outcomes to accumulated risk. This study hypothesized that cumulative risk was negatively related to attachment, and that maternal sensitivity mediated linkages between risk and attachment. One hundred and twelve high-risk African-American premature infant-mother dyads participated. Psychosocial (maternal depression, stress and self-efficacy) and sociodemographic risk (poverty, maternal education, marital status) were maternal self-report (0-4 months). Infant health risk was obtained from hospital charts. Infant-mother attachment (12 months) and maternal sensitivity (4 months) were assessed with Q-sort measures. Psychosocial and sociodemographic risk, but not infant health risk, negatively related to attachment. Both were mediated by maternal sensitivity. The impact of risk domains on attachment security was mediated by maternal sensitivity. Results emphasize the need for early intervention programs targeting premature infants to identify and address environmental and personal factors that place parenting at risk. © 2011 The Authors. Journal of Child Psychology and Psychiatry © 2011 Association for Child and Adolescent Mental Health.

Effect of protocol-related variables and women's characteristics on the cumulative false-positive risk in breast cancer screening

PubMed Central

Román, R.; Sala, M.; Salas, D.; Ascunce, N.; Zubizarreta, R.; Castells, X.

2012-01-01

Background: Reducing the false-positive risk in breast cancer screening is important. We examined how the screening-protocol and women's characteristics affect the cumulative false-positive risk. Methods: This is a retrospective cohort study of 1 565 364 women aged 45–69 years who underwent 4 739 498 screening mammograms from 1990 to 2006. Multilevel discrete hazard models were used to estimate the cumulative false-positive risk over 10 sequential mammograms under different risk scenarios. Results: The factors affecting the false-positive risk for any procedure and for invasive procedures were double mammogram reading [odds ratio (OR) = 2.06 and 4.44, respectively], two mammographic views (OR = 0.77 and 1.56, respectively), digital mammography (OR = 0.83 for invasive procedures), premenopausal status (OR = 1.31 and 1.22, respectively), use of hormone replacement therapy (OR = 1.03 and 0.84, respectively), previous invasive procedures (OR = 1.52 and 2.00, respectively), and a familial history of breast cancer (OR = 1.18 and 1.21, respectively). The cumulative false-positive risk for women who started screening at age 50–51 was 20.39% [95% confidence interval (CI) 20.02–20.76], ranging from 51.43% to 7.47% in the highest and lowest risk profiles, respectively. The cumulative risk for invasive procedures was 1.76% (95% CI 1.66–1.87), ranging from 12.02% to 1.58%. Conclusions: The cumulative false-positive risk varied widely depending on the factors studied. These findings are relevant to provide women with accurate information and to improve the effectiveness of screening programs. PMID:21430183

Growth of Korean preterm infants in a family-centered tradition during early infancy: the influence of health risks, maternal employment, and the sex of infants.

PubMed

Ahn, Youngmee; Sohn, Min; Lee, Sangmi

2014-10-01

The physical growth of mild preterm infants (<32 weeks of gestation at birth) needs to be explored in terms of bio-sociocultural factors considering the sociocultural aspects of child-care practice. A retrospective cohort study was conducted with 238 Korean mild preterm infants from birth up to 6 months of corrected age regarding four of the biological and sociocultural factors such as health risks (at birth and discharge), maternal employment status, and the infant sex. There were four noteworthy findings on growth variation in Korean mild preterm infants during early infancy: (i) the secular trend of intrauterine growth; (ii) the cumulative adverse effects of four risk factors; (iii) the possible burden of maternal employment if insufficient support; and (iv) the possibility of the cultural favoritism to male infants regardless of the modern industrialized society. The study suggests that, in a modern society, while mild preterm infants could sustain typical fetal growth, the early postnatal growth may vary based on health risks and sociocultural circumstances related to child-bearing and -rearing practices surrounding them. © 2013 The Authors. Japan Journal of Nursing Science © 2013 Japan Academy of Nursing Science.

Developmental delay and emotion dysregulation: Predicting parent-child conflict across early to middle childhood.

PubMed

Marquis, Willa A; Noroña, Amanda N; Baker, Bruce L

2017-04-01

Cumulative risk research has increased understanding of how multiple risk factors impact various socioemotional and interpersonal outcomes across the life span. However, little is known about risk factors for parent-child conflict early in development, where identifying predictors of change could be highly salient for intervention. Given their established association with parent-child conflict, child developmental delay (DD) and emotion dysregulation were examined as predictors of change in conflict across early to middle childhood (ages 3 to 7 years). Participants (n = 211) were part of a longitudinal study examining the development of psychopathology in children with or without DD. Level of parent-child conflict was derived from naturalistic home observations, whereas child dysregulation was measured using an adapted CBCL-Emotion Dysregulation Index. PROCESS was used to examine the conditional interactive effects of delay status (typically developing, DD) and dysregulation on change in conflict from child ages 3 to 5 and 5 to 7 years. Across both of these timeframes, parent-child conflict increased only for families of children with both DD and high dysregulation, providing support for an interactive risk model of parent-child conflict. Findings are considered in the context of developmental transitions, and implications for intervention are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Developmental delay and emotion dysregulation: Predicting parent-child conflict across early to middle childhood

PubMed Central

Marquis, Willa A.; Noroña, Amanda N.; Baker, Bruce L.

2016-01-01

Cumulative risk research has increased understanding of how multiple risk factors impact various socioemotional and interpersonal outcomes across the life span. However, little is known about risk factors for parent-child conflict early in development, where identifying predictors of change could be highly salient for intervention. Given their established association with parent-child conflict, child developmental delay (DD) and emotion dysregulation were examined as predictors of change in conflict across early to middle childhood (ages 3 to 7 years). Participants (n=211) were part of a longitudinal study examining the development of psychopathology in children with or without DD. Level of parent-child conflict was derived from naturalistic home observations, while child dysregulation was measured using an adapted CBCL-Emotion Dysregulation Index. PROCESS was used to examine the conditional interactive effects of delay status (typically developing, DD) and dysregulation on change in conflict from child ages 3 to 5 and 5 to 7 years. Across both of these timeframes, parent-child conflict increased only for families of children with both DD and high dysregulation, providing support for an interactive risk model of parent-child conflict. Findings are considered in the context of developmental transitions, and implications for intervention are discussed. PMID:28054804

Guidance on Cumulative Risk Assessment of Pesticide Chemicals that have a Common Mechanism of Toxicity

EPA Pesticide Factsheets

This document provides guidance to OPP scientists for evaluating and estimating the potential human risks associated with such multichemical and multipathway exposures to pesticides. This process is referred to as cumulative risk assessment.

The impact of adolescent risk behavior on partner relationships

PubMed Central

Thornberry, Terence P.; Krohn, Marvin D.; Augustyn, Megan Bears; Buchanan, Molly; Greenman, Sarah J.

2015-01-01

Prior literature suggests that involvement in adolescent risk behaviors will have short- and long-term consequences that disrupt the orderly flow of later development, including impacts on patterns of partner relationships. In this study, we explore how adolescent involvement in delinquency, drug use, and sexual behavior at an early age affects the likelihood and timing of both marriage and cohabitation using a sample from the Rochester Youth Development Study. We also examine the direct effects of dropping out of high school, teenage parenthood, and financial stress during emerging adulthood as well as their potential role as mediators of the relationships between adolescent risk behaviors and partnering for both males and females. Overall, there is not very strong support for a direct relationship between adolescent delinquency, drug use, or early sexual behavior and patterns of partner formation. In contrast, the more proximal relationships, indicated by precocious transitions to adulthood and financial instability, are more consistently related to partner formation. These findings support models of cumulative disadvantage: early adolescent problem behaviors are weakly related to partner formation, but appear to set in motion cascading consequences that influence the transition to adulthood and, in turn, these more proximal variables are more consistently related to partner formation. PMID:27429604

The impact of adolescent risk behavior on partner relationships.

PubMed

Thornberry, Terence P; Krohn, Marvin D; Augustyn, Megan Bears; Buchanan, Molly; Greenman, Sarah J

2016-06-01

Prior literature suggests that involvement in adolescent risk behaviors will have short- and long-term consequences that disrupt the orderly flow of later development, including impacts on patterns of partner relationships. In this study, we explore how adolescent involvement in delinquency, drug use, and sexual behavior at an early age affects the likelihood and timing of both marriage and cohabitation using a sample from the Rochester Youth Development Study. We also examine the direct effects of dropping out of high school, teenage parenthood, and financial stress during emerging adulthood as well as their potential role as mediators of the relationships between adolescent risk behaviors and partnering for both males and females. Overall, there is not very strong support for a direct relationship between adolescent delinquency, drug use, or early sexual behavior and patterns of partner formation. In contrast, the more proximal relationships, indicated by precocious transitions to adulthood and financial instability, are more consistently related to partner formation. These findings support models of cumulative disadvantage: early adolescent problem behaviors are weakly related to partner formation, but appear to set in motion cascading consequences that influence the transition to adulthood and, in turn, these more proximal variables are more consistently related to partner formation.

Detailed assessments of childhood adversity enhance prediction of central obesity independent of gender, race, adult psychosocial risk and health behaviors.

PubMed

Davis, Cynthia R; Dearing, Eric; Usher, Nicole; Trifiletti, Sarah; Zaichenko, Lesya; Ollen, Elizabeth; Brinkoetter, Mary T; Crowell-Doom, Cindy; Joung, Kyoung; Park, Kyung Hee; Mantzoros, Christos S; Crowell, Judith A

2014-02-01

This study examined whether a novel indicator of overall childhood adversity, incorporating number of adversities, severity, and chronicity, predicted central obesity beyond contributions of "modifiable" risk factors including psychosocial characteristics and health behaviors in a diverse sample of midlife adults. The study also examined whether the overall adversity score (number of adversities × severity × chronicity) better predicted obesity compared to cumulative adversity (number of adversities), a more traditional assessment of childhood adversity. 210 Black/African Americans and White/European Americans, mean age=45.8; ±3.3 years, were studied cross-sectionally. Regression analysis examined overall childhood adversity as a direct, non-modifiable risk factor for central obesity (waist-hip ratio) and body mass index (BMI), with and without adjustment for established adult psychosocial risk factors (education, employment, social functioning) and heath behavior risk factors (smoking, drinking, diet, exercise). Overall childhood adversity was an independent significant predictor of central obesity, and the relations between psychosocial and health risk factors and central obesity were not significant when overall adversity was in the model. Overall adversity was not a statistically significant predictor of BMI. Overall childhood adversity, incorporating severity and chronicity and cumulative scores, predicts central obesity beyond more contemporaneous risk factors often considered modifiable. This is consistent with early dysregulation of metabolic functioning. Findings can inform practitioners interested in the impact of childhood adversity and personalizing treatment approaches of obesity within high-risk populations. Prevention/intervention research is necessary to discover and address the underlying causes and impact of childhood adversity on metabolic functioning. © 2013.

Risk of lung cancer in relation to contiguous windows of endotoxin exposure among female textile workers in Shanghai

PubMed Central

Costello, Sadie; Applebaum, Katie M.; Ray, Roberta M.; Astrakianakis, George; Gao, Dao Li; Thomas, David B.; Checkoway, Harvey; Eisen, Ellen A.

2012-01-01

Objective Exposure to endotoxin has been consistently associated with a reduced risk of lung cancer. However, there is a paucity of information regarding temporal aspects of this relationship. The objective of this study was to investigate the associations between contiguous windows of endotoxin exposure and risk of lung cancer. Methods Data were reanalyzed from a case-cohort study (602 cases, 3,038 subcohort) of female textile workers in Shanghai, China. Cumulative endotoxin exposure was partitioned into two windows: ≥20 and <20 years before risk. Exposure–response relations were examined using categorical and non-linear (semi-parametric) models, accounting for confounding by previous exposure windows. Results There was an inverse trend of decreasing risk of lung cancer associated with increasing levels of endotoxin exposure ≥20 years before risk (p trend = 0.02). Women in the highest two categories of cumulative exposures had hazard ratios of 0.78 (95% CI 0.60–1.03) and 0.77 (95% CI 0.58–1.02) for lung cancer, respectively, in comparison with unexposed textile workers. There was, however, a weaker association and not statistically significant between lung cancer and endotoxin exposure accumulated in the more recent window (<20 years before risk). Conclusion Results provide further evidence that endotoxin exposure that occurred 20 years or more before risk confers the strongest protection against lung cancer, indicating a possible early anti-carcinogenic effect. Further studies are needed to better understand the underlying biological mechanisms for this effect. PMID:21732048

Mortality risks during extreme temperature events (ETEs) using a distributed lag non-linear model

NASA Astrophysics Data System (ADS)

Allen, Michael J.; Sheridan, Scott C.

2018-01-01

This study investigates the relationship between all-cause mortality and extreme temperature events (ETEs) from 1975 to 2004. For 50 U.S. locations, these heat and cold events were defined based on location-specific thresholds of daily mean apparent temperature. Heat days were defined by a 3-day mean apparent temperature greater than the 95th percentile while extreme heat days were greater than the 97.5th percentile. Similarly, calculations for cold and extreme cold days relied upon the 5th and 2.5th percentiles. A distributed lag non-linear model assessed the relationship between mortality and ETEs for a cumulative 14-day period following exposure. Subsets for season and duration effect denote the differences between early- and late-season as well as short and long ETEs. While longer-lasting heat days resulted in elevated mortality, early season events also impacted mortality outcomes. Over the course of the summer season, heat-related risk decreased, though prolonged heat days still had a greater influence on mortality. Unlike heat, cold-related risk was greatest in more southerly locations. Risk was highest for early season cold events and decreased over the course of the winter season. Statistically, short episodes of cold showed the highest relative risk, suggesting unsettled weather conditions may have some relationship to cold-related mortality. For both heat and cold, results indicate higher risk to the more extreme thresholds. Risk values provide further insight into the role of adaptation, geographical variability, and acclimatization with respect to ETEs.

Cumulative risk of breast cancer screening outcomes according to the presence of previous benign breast disease and family history of breast cancer: supporting personalised screening.

PubMed

Román, M; Quintana, M J; Ferrer, J; Sala, M; Castells, X

2017-05-23

Our aim was to assess the cumulative risk of false-positive screening results, screen-detected cancer, and interval breast cancer in mammography screening among women with and without a previous benign breast disease and a family history of breast cancer. The cohort included 42 928 women first screened at the age of 50-51 years at three areas of the Spanish Screening Programme (Girona, and two areas in Barcelona) between 1996 and 2011, and followed up until December 2012. We used discrete-time survival models to estimate the cumulative risk of each screening outcome over 10 biennial screening exams. The cumulative risk of false-positive results, screen-detected breast cancer, and interval cancer was 36.6, 5.3, and 1.4 for women with a previous benign breast disease, 24.1, 6.8, and 1.6% for women with a family history of breast cancer, 37.9, 9.0, and 3.2%; for women with both a previous benign breast disease and a family history, and 23.1, 3.2, and 0.9% for women without either of these antecedents, respectively. Women with a benign breast disease or a family history of breast cancer had an increased cumulative risk of favourable and unfavourable screening outcomes than women without these characteristics. A family history of breast cancer did not increase the cumulative risk of false-positive results. Identifying different risk profiles among screening participants provides useful information to stratify women according to their individualised risk when personalised screening strategies are discussed.

Cumulative iron dose and resistance to erythropoietin.

PubMed

Rosati, A; Tetta, C; Merello, J I; Palomares, I; Perez-Garcia, R; Maduell, F; Canaud, B; Aljama Garcia, P

2015-10-01

Optimizing anemia treatment in hemodialysis (HD) patients remains a priority worldwide as it has significant health and financial implications. Our aim was to evaluate in a large cohort of chronic HD patients in Fresenius Medical Care centers in Spain the value of cumulative iron (Fe) dose monitoring for the management of iron therapy in erythropoiesis-stimulating agent (ESA)-treated patients, and the relationship between cumulative iron dose and risk of hospitalization. Demographic, clinical and laboratory parameters from EuCliD(®) (European Clinical Dialysis Database) on 3,591 patients were recorded including ESA dose (UI/kg/week), erythropoietin resistance index (ERI) [U.I weekly/kg/gr hemoglobin (Hb)] and hospitalizations. Moreover the cumulative Fe dose (mg/kg of bodyweight) administered over the last 2 years was calculated. Univariate and multivariate analyses were performed to identify the main predictors of ESA resistance and risk of hospitalization. Patients belonging to the 4th quartile of ERI were defined as hypo-responders. The 2-year iron cumulative dose was significantly higher in the 4th quartile of ERI. In hypo-responders, 2-year cumulative iron dose was the only iron marker associated with ESA resistance. At case-mix adjusted multivariate analysis, 2-year iron cumulative dose was an independent predictor of hospitalization risk. In ESA-treated patients cumulative Fe dose could be a useful tool to monitor the appropriateness of Fe therapy and to prevent iron overload. To establish whether the associations between cumulative iron dose, ERI and hospitalization risk are causal or attributable to selection bias by indication, clinical trials are necessary.

Incorporating Nonchemical Stressors Into Cumulative Risk Assessments

PubMed Central

Rider, Cynthia V.; Dourson, Michael L.; Hertzberg, Richard C.; Mumtaz, Moiz M.; Price, Paul S.; Simmons, Jane Ellen

2012-01-01

The role of nonchemical stressors in modulating the human health risk associated with chemical exposures is an area of increasing attention. On 9 March 2011, a workshop titled “Approaches for Incorporating Nonchemical Stressors into Cumulative Risk Assessment” took place during the 50th Anniversary Annual Society of Toxicology Meeting in Washington D.C. Objectives of the workshop included describing the current state of the science from various perspectives (i.e., regulatory, exposure, modeling, and risk assessment) and presenting expert opinions on currently available methods for incorporating nonchemical stressors into cumulative risk assessments. Herein, distinct frameworks for characterizing exposure to, joint effects of, and risk associated with chemical and nonchemical stressors are discussed. PMID:22345310

CNS relapses in patients with HER2-positive early breast cancer who have and have not received adjuvant trastuzumab: a retrospective substudy of the HERA trial (BIG 1-01).

PubMed

Pestalozzi, Bernhard C; Holmes, Eileen; de Azambuja, Evandro; Metzger-Filho, Otto; Hogge, Laurence; Scullion, Matt; Láng, István; Wardley, Andrew; Lichinitser, Mikhail; Sanchez, Roberto I Lopez; Müller, Volkmar; Dodwell, David; Gelber, Richard D; Piccart-Gebhart, Martine J; Cameron, David

2013-03-01

Several randomised trials have confirmed the benefit of adjuvant trastuzumab for patients with HER2-positive early breast cancer. However, concern has been expressed that adjuvant trastuzumab might be associated with an increased frequency of CNS relapses. We assessed the frequency and course of CNS relapses, either as first event or at any time, using data from the HERA trial. We estimated the cumulative incidence of first disease-free survival (DFS) events in the CNS versus other sites by competing risks analysis in patients with HER2-positive early breast cancer who had been randomly assigned to receive 1 year of trastuzumab or to observation in the HERA trial after a median follow-up of 4 years (IQR 3·5-4·8). To obtain further information about CNS relapse at any time before death, we circulated a data collection form to investigators to obtain standardised information about CNS events that occurred in all patients who had died before July, 2009. We estimated the cumulative incidence of CNS relapse at any time with a competing risks analysis. Of 3401 patients who had been assigned to receive 1 year of trastuzumab or to observation, 69 (2%) had a CNS relapse as first DFS event and 747 (22%) had a first DFS event not in the CNS. The frequency of CNS relapses as first DFS event did not differ between the group given 1 year of trastuzumab (37 [2%] of 1703 patients) and the observation group (32 [2%] of 1698; p=0·55 [Gray's test]). 481 data collection forms were distributed, of which 413 (86%) were returned. The proportion of patients who had died and experienced a CNS relapse was numerically higher in the observation group (129 [57%] of 227) than in the group given trastuzumab for 1 year (88 [47%] of 186; p=0·06 [Gray's test]). Most CNS relapses were symptomatic (189 [87%] of 217). Adjuvant trastuzumab does not increase the risk of CNS relapse in patients with HER2-positive early breast cancer. None. Copyright © 2013 Elsevier Ltd. All rights reserved.

Phthalates and Cumulative Risk Assessment (NAS Final Report)

EPA Science Inventory

On December 18, 2008, the National Academy of Sciences' National Research Council released a final report, requested and sponsored by the EPA, entitled Phthalates and Cumulative Risk Assessment: The Task Ahead.

Risk assessment has become a dominant public policy ...

CUMULATIVE RISK ANALYSIS FOR ORGANOPHOSPHORUS PESTICIDES

EPA Science Inventory

Cumulative Risk Analysis for Organophosphorus Pesticides
R. Woodrow Setzer, Jr. NHEERL MD-74, USEPA, RTP, NC 27711

The US EPA has recently completed a risk assessment of the effects of exposure to 33 organophosphorous pesticides (OPs) through the diet, water, and resi...

Radiation Exposure and Attributable Cancer Risk in Patients With Esophageal Atresia.

PubMed

Yousef, Yasmine; Baird, Robert

2018-02-01

Cases of esophageal carcinoma have been documented in survivors of esophageal atresia (EA). Children with EA undergo considerable amounts of diagnostic imaging and consequent radiation exposure potentially increasing their lifetime cancer mortality risk. This study evaluates the radiological procedures performed on patients with EA and estimates their cumulative radiation exposure and attributable lifetime cancer mortality risk. Medical records of patients with EA managed at a tertiary care center were reviewed for demographics, EA subtype, and number and type of radiological investigations. Existing normative data were used to estimate the cumulative radiation exposure and lifetime cancer risk per patient. The present study included 53 patients with a mean follow-up of 5.7 years. The overall median and maximum estimated effective radiation dose in the neonatal period was 5521.4 μSv/patient and 66638.6 μSv/patient, respectively. This correlates to a median and maximum estimated cumulative lifetime cancer mortality risk of 1:1530 and 1:130, respectively. Hence, radiation exposure in the neonatal period increased the cumulative cancer mortality risk a median of 130-fold and a maximum of 1575-fold in EA survivors. Children with EA are exposed to significant amounts of radiation and an increased estimated cumulative cancer mortality risk. Efforts should be made to eliminate superfluous imaging.

Widespread pain following whiplash-associated disorders: incidence, course, and risk factors.

PubMed

Holm, Lena W; Carroll, Linda J; Cassidy, J David; Skillgate, Eva; Ahlbom, Anders

2007-01-01

To investigate the incidence and course of widespread pain (WP) subsequent to localized pain in subjects with whiplash-associated disorders (WAD); and to investigate the influence of depressive symptoms, neck pain intensity, number of whiplash-associated symptoms, and number of painful body areas on such conditions. From a large prospective cohort of injury claimants who reported WAD after motor vehicle collision (MVC; n = 7462), we identified a subgroup with only localized head/neck/back pain, and who responded to one or more followup questionnaires mailed at 6 weeks and 4, 6, and 12 months after the MVC (n = 266). Pain drawings were distributed at the followup, and we defined WP as having 9 or more painful areas, including posterior neck, at any of these occasions. Depressive symptoms were assessed with the Center for Epidemiological Studies Depression Scale and pain intensity with on a visual analog scale (VAS). The cumulative incidence of WP was 21%, and it occurred early after the injury. Continuous WP over the 12 months was rare. The odds for developing WP were greater in those with depressive symptoms (OR 3.2, 95% CI 1.6-6.3), VAS pain intensity 55-100 (OR 3.2, 95% CI 1.3-8.0), reporting > or = 3 pain-associated symptoms (OR 1.9, 95% CI 0.9-3.8), and those reporting 4 or 5 painful body areas (OR 2.6, 95% CI 1.3-5.4). WP occurred early in the course. Even though the cumulative incidence was 21%, continuous WP was rare. Subjects with WAD who report early depressive symptoms and more severe neck injury symptoms are at risk of developing WP after MVC.

The risk of central nervous system relapses in patients with peripheral T-cell lymphoma

PubMed Central

Fanale, Michelle A.; Miranda, Roberto N.; Noorani, Mansoor; Westin, Jason R.; Nastoupil, Loretta J.; Hagemeister, Fredrick B.; Fayad, Luis E.; Romaguera, Jorge E.; Samaniego, Felipe; Turturro, Francesco; Lee, Hun J.; Neelapu, Sattva S.; Rodriguez, M. Alma; Wang, Michael; Fowler, Nathan H.; Davis, Richard E.; Medeiros, L. Jeffrey; Oki, Yasuhiro

2018-01-01

We performed a retrospective analysis to identify risk factors and survival outcome for central nervous system (CNS) relapse of peripheral T-cell lymphoma (PTCL) by histologic type. Records of 600 PTCL patients diagnosed between 1999 and 2014 were analyzed including PTCL not otherwise specified (PTCL-NOS, 174 patients), angoimmunoblastic T-cell lymphoma (AITL, 144), ALK+anaplastic large cell lymphoma (ALCL, 74), ALK-ALCL (103), extranodal NK-cell lymphoma (ENKL, 54), or others (51). With a median follow up of 57 months, 13 patients (4 PTCL-NOS, 1 AITL, 4 ALK+ALCL, 2 ALK-ALCL, 2 ENKL) experienced CNS relapse. One-year and 5-year cumulative incidence of CNS relapse were 1.5% (95%CI: 0.7–2.8%) and 2.1% (95%CI: 1.1–3.5%), respectively. The 5-year cumulative incidence of CNS relapse was 1.8% in PTCL-NOS, 0.7% in AITL, 5.4% in ALK+ALCL, 2.1% in ALK-ALCL and 3.7% in ENKL. Extranodal involvement >1 site was the only significant factor associated with higher chance of CNS relapse (HR: 4.9, 95%CI: 1.6–15.0, p = 0.005). Patients with ALK+ALCL who had extranodal involvement >1 (N = 19) had very high risk of CNS relapse with one year cumulative incidence of 17% (95%CI: 4%-37%), all occurring within six months after diagnosis. All patients with CNS relapse eventually died (median, 1.5 months; range, 0.1–10.1 months). CNS relapse in patients with PTCL is rare event but the risk varies by subtype. ALK+ALCL patients with extranodal involvement >1 site have a very high risk of early CNS relapse, and thus evaluation of CNS involvement at the time of diagnosis and possible CNS-directed prophylaxis may be considered. PMID:29538376

Association of Lifecourse Socioeconomic Status with Chronic Inflammation and Type 2 Diabetes Risk: The Whitehall II Prospective Cohort Study

PubMed Central

Stringhini, Silvia; Batty, G. David; Bovet, Pascal; Shipley, Martin J.; Marmot, Michael G.; Kumari, Meena; Tabak, Adam G.; Kivimäki, Mika

2013-01-01

Background Socioeconomic adversity in early life has been hypothesized to “program” a vulnerable phenotype with exaggerated inflammatory responses, so increasing the risk of developing type 2 diabetes in adulthood. The aim of this study is to test this hypothesis by assessing the extent to which the association between lifecourse socioeconomic status and type 2 diabetes incidence is explained by chronic inflammation. Methods and Findings We use data from the British Whitehall II study, a prospective occupational cohort of adults established in 1985. The inflammatory markers C-reactive protein and interleukin-6 were measured repeatedly and type 2 diabetes incidence (new cases) was monitored over an 18-year follow-up (from 1991–1993 until 2007–2009). Our analytical sample consisted of 6,387 non-diabetic participants (1,818 women), of whom 731 (207 women) developed type 2 diabetes over the follow-up. Cumulative exposure to low socioeconomic status from childhood to middle age was associated with an increased risk of developing type 2 diabetes in adulthood (hazard ratio [HR] = 1.96, 95% confidence interval: 1.48–2.58 for low cumulative lifecourse socioeconomic score and HR = 1.55, 95% confidence interval: 1.26–1.91 for low-low socioeconomic trajectory). 25% of the excess risk associated with cumulative socioeconomic adversity across the lifecourse and 32% of the excess risk associated with low-low socioeconomic trajectory was attributable to chronically elevated inflammation (95% confidence intervals 16%–58%). Conclusions In the present study, chronic inflammation explained a substantial part of the association between lifecourse socioeconomic disadvantage and type 2 diabetes. Further studies should be performed to confirm these findings in population-based samples, as the Whitehall II cohort is not representative of the general population, and to examine the extent to which social inequalities attributable to chronic inflammation are reversible. Please see later in the article for the Editors' Summary PMID:23843750

Integrating human health and ecological data into cumulative risk assessment through the Aggregate Exposure Pathway and Adverse Outcome Pathway frameworks

EPA Science Inventory

Cumulative risk assessment (CRA) methods promote the use of a conceptual site model (CSM) to apportion exposures and integrate risk from relevant stressors across different species. Integration is important to provide a more complete assessment of risk, but evaluating endpoints a...

Fetal Substance Exposure and Cumulative Environmental Risk in an African American Cohort

ERIC Educational Resources Information Center

Yumoto, Chie; Jacobson, Sandra W.; Jacobson, Joseph L.

2008-01-01

Two models of vulnerability to socioenvironmental risk were examined in 337 African American children (M = 7.8 years) recruited to overrepresent prenatal alcohol or cocaine exposure: The cumulative risk model predicted synergistic effects from exposure to multiple risk factors, and the fetal patterning of disease model predicted that prenatal…

EPA Peer Consultation Workshop on Cumulative Risk Assessment of Phthalates: Potential Options and Methods for Evaluating the Cumulative Hazard Associated with Six Selected Phthalates

EPA Science Inventory

EPA held a 2-day workshop on December 8 and 9, 2010 at the Doubletree Hotel Washington DC-Crystal City in Arlington, Viriginia. The goal of this workshop was to evaulate methods of determining cumulative risk associated with exposure to mulitple phthalates for inclusion in the EP...

Drought early warning and risk management in a changing environment

NASA Astrophysics Data System (ADS)

Pulwarty, R. S.

2011-12-01

Drought has long been recognized as falling into the category of incremental but long-term and cumulative environmental changes, also termed slow-onset or creeping events. These event types would include: air and water quality decline, desertification processes, deforestation and forest fragmentation, loss of biodiversity and habitats, and nitrogen overloading, among others. Climate scientists continue to struggle with recognizing the onset of drought and scientists and policy makers continue to debate the basis (i.e., criteria) for declaring an end to a drought. Risk-based management approaches to drought planning at the national and regional levels have been recommended repeatedly over the years but their prototyping, testing and operational implementation have been limited. This presentation will outline two avenues for disaster risk reduction in the context of drought (1) integrated early warning information systems, and (2) linking disaster risk reduction to climate change adaptation strategies. Adaptation involves not only using operational facilities and infrastructure to cope with the immediate problems but also leaving slack or reserve for coping with multiple stress problems that produce extreme impacts and surprise. Increasing the 'anticipatability' of an event, involves both monitoring of key indicators from appropriate baseline data, and observing early warning signs that assumptions in risk management plans are failing and critical transitions are occurring. Illustrative cases will be drawn from the IPCC Special Report on Managing the Risks of Extreme Events and Disasters (2011), the UN Global Assessment of Disaster Risk Reduction (2011) and implementation activities in which the author has been engaged. Most drought early warning systems have tended to focus on the development and use of physical system indicators and forecasts of trends and thresholds. We show that successful early warning systems that meet expectations of risk management also have explicit foci on (1) integrating physical and social vulnerability indicators across timescales, (2) analytical capacity to generate local scenarios of risk using both analogs and projections, (3) the communication of risk-based information, and (4) the support and governance of a collaborative framework for early warning structures across spatial scales.

Implications of applying cumulative risk assessment to the workplace.

PubMed

Fox, Mary A; Spicer, Kristen; Chosewood, L Casey; Susi, Pam; Johns, Douglas O; Dotson, G Scott

2018-06-01

Multiple changes are influencing work, workplaces and workers in the US including shifts in the main types of work and the rise of the 'gig' economy. Work and workplace changes have coincided with a decline in unions and associated advocacy for improved safety and health conditions. Risk assessment has been the primary method to inform occupational and environmental health policy and management for many types of hazards. Although often focused on one hazard at a time, risk assessment frameworks and methods have advanced toward cumulative risk assessment recognizing that exposure to a single chemical or non-chemical stressor rarely occurs in isolation. We explore how applying cumulative risk approaches may change the roles of workers and employers as they pursue improved health and safety and elucidate some of the challenges and opportunities that might arise. Application of cumulative risk assessment should result in better understanding of complex exposures and health risks with the potential to inform more effective controls and improved safety and health risk management overall. Roles and responsibilities of both employers and workers are anticipated to change with potential for a greater burden of responsibility on workers to address risk factors both inside and outside the workplace that affect health at work. A range of policies, guidance and training have helped develop cumulative risk assessment for the environmental health field and similar approaches are available to foster the practice in occupational safety and health. Copyright © 2018 Elsevier Ltd. All rights reserved.

A Topical Overview of Cumulative Risk Assessment Concepts, Methods, and Applications (2007–2016)

EPA Science Inventory

Cumulative risk assessments (CRAs) address combined risks from exposures to multiple chemical and nonchemical stressors and may focus on vulnerable communities or populations. Significant contributions have been made to the development of concepts, methods, and applications for C...

Modeling Joint Exposures and Health Outcomes for Cumulative Risk Assessment: the Case of Radon and Smoking

EPA Science Inventory

Community-based cumulative risk assessment requires characterization of exposures to multiple chemical and non-chemical stressors, with consideration of how the non-chemical stressors may influence risks from chemical stressors. Residential radon provides an interesting case exam...

Cumulative Risk Exposure and Mental Health Symptoms among Maltreated Youth Placed in Out-of-Home Care

ERIC Educational Resources Information Center

Raviv, Tali; Taussig, Heather N.; Culhane, Sara E.; Garrido, Edward F.

2010-01-01

Objective: Maltreated children placed in out-of-home care are at high risk for exhibiting symptoms of psychopathology by virtue of their exposure to numerous risk factors. Research examining cumulative risk has consistently found that the accumulation of risk factors increases the likelihood of mental health problems. The goal of the current study…

Ecological correlates of multiple sexual partnerships among adolescents and young adults in urban Cape Town: a cumulative risk factor approach.

PubMed

Muchiri, Evans; Odimegwu, Clifford; Banda, Pamela; Ntoimo, Lorreta; Adedini, Sunday

2017-07-01

Studies in South Africa have reported unsafe levels of risky sexual behvaiours among adolescents and young adults, with the country reporting the highest burden of HIV/AIDS globally, as well as a high rate of teenage pregnancy. While determinants of risky sexual behaviours have been investigated for factors occurring at the individual and household levels, not fully explored in the literature is the effect of community level factors. Furthermore, it is unclear whether risk factors occurring within the ecology of adolescents and young adults act cumulatively to influence their sexual practices. This article aims to address this knowledge gap using a case study of the Cape Area Panel Study of adolescents and young adults in urban Cape Town, South Africa. The ecological framework was adopted to guide the selection of risk factors at the individual, household, and community levels. Multivariate linear discriminant function analyses were used to select significant risk factors for multiple sexual partnerships and used to produce risk indices for the respondents. The cumulative risk approach was applied to test whether significant risk factors acted cumulatively. Findings point to the importance of ecological factors in influencing outcomes of multiple sexual partnerships among respondents and further demonstrate that ecological risk factors may act cumulatively. These findings are important for South Africa that is grappling with teenage pregnancy and disproportionate HIV epidemic among the youth.

Self-injury, aggression and destruction in children with severe intellectual disability: Incidence, persistence and novel, predictive behavioural risk markers.

PubMed

Davies, L E; Oliver, C

2016-01-01

A risk informed, early intervention strategy for self-injurious, aggressive and destructive behaviours in children with severe intellectual disability is gaining support. The aims of this study were to establish the cumulative incidence and persistence of self-injury, aggression and destruction and the relationship between these behaviours and two potentially predictive behavioural risk markers (repetitive behaviour, and impulsivity and overactivity) in children at high risk. In a longitudinal design self-injury, aggression and destruction were assessed by teachers of 417 children with severe intellectual disability on two occasions separated by 15-18 months. Aggression, destruction and self-injury were persistent (69%, 57% and 58% respectively). Repetitive and restricted behaviours and interests (RRBI) and overactivity/impulsivity (O/I) were significantly associated with aggression (O/I OR=1.291, p<.001), destruction (RRBI OR 1.201, p=.013; O/I OR 1.278, p<.001) and/or self-injury (RRBI, OR 1.25, p=.004; O/I OR=1.117, p<.001). The relative risk of the cumulative incidence of self-injury, aggression and destruction was significantly increased by repetitive and restricted behaviours and interests (self-injury 2.66, destruction 2.16) and/or overactivity/impulsivity (aggression 2.42, destruction 2.07). The results provide evidence that repetitive and restricted behaviours and interests, and overactivity/impulsivity, are risk markers for the onset of self-injury, aggression and destruction within the already high risk group of children with severe intellectual disability. Copyright © 2015 Elsevier Ltd. All rights reserved.

Aging and Cumulative Inequality: How Does Inequality Get Under the Skin?

ERIC Educational Resources Information Center

Ferraro, Kenneth F.; Shippee, Tetyana Pylypiv

2009-01-01

Purpose: This article draws from cumulative disadvantage and life course theories to develop a new theory for the social scientific study of aging. Design and Methods: Five axioms of "cumulative inequality (CI) theory" are articulated to identify how life course trajectories are influenced by early and accumulated inequalities but can be modified…

Breast cancer epidemic in the early twenty-first century: evaluation of risk factors, cumulative questionnaires and recommendations for preventive measures.

PubMed

Golubnitschaja, Olga; Debald, Manuel; Yeghiazaryan, Kristina; Kuhn, Walther; Pešta, Martin; Costigliola, Vincenzo; Grech, Godfrey

2016-10-01

Rapidly increasing incidence of breast cancer is a new social challenge resulting from a spectrum of internal and external risk factors which appear to be well accepted as an attribute of the early twenty-first century, being, however, new for female sub-populations compared to the past. These include altered socio-economical conditions such as occupational exposure, rotating shift work, specific environmental factors (increased pollution and environmental toxicity, altered dietary habits, quality and composition of meal) as well as consequently shifted and/or adapted physiologic factors such as lower age at menarche, late age of first full-term pregnancy, if any, shorter periods of breastfeeding and later menopause. Consolidated expert statements suggest that over 50 % of all breast cancer cases may be potentially prevented by risk reduction strategy such as regulation of modifiable risk factors. Currently available risk assessment models may estimate potential breast cancer predisposition, in general; however, they are not able to predict the disease manifestation individually. Further, current deficits in risk assessment and effective breast cancer prevention have been recently investigated and summarised as follows: gaps in risk estimation, preventive therapy, lifestyle prevention, understanding of the biology of breast cancer risk and implementation of known preventive measures. This paper overviews the most relevant risk factors, provides recommendations for improved risk assessment and proposes an extended questionnaire for effective preventive measures.

EFFECTS-BASED CUMULATIVE RISK ASSESSMENT IN A LOW-INCOME URBAN COMMUNITY NEAR A SUPERFUND SITE

EPA Science Inventory

We will introduce into the cumulative risk assessment framework novel methods for non-cancer risk assessment, techniques for dose-response modeling that extend insights from chemical mixtures frameworks to non-chemical stressors, multilevel statistical methods used to address ...

The Effect of Cumulative Risk on Paternal Engagement: Examining Differences among Adolescent and Older Couples

ERIC Educational Resources Information Center

Farrie, Danielle; Lee, Yookyong; Fagan, Jay

2011-01-01

This study examined the association between fathers' and mothers' risk factors and paternal engagement 1 and 3 years postbirth. Distinguishing between new and persistent risk factors, we tested whether cumulative risk has unique effects on couples where one or both parents are adolescents at birth. Results indicated that although fathers' and…

Very late stent thrombosis and late target lesion revascularization after sirolimus-eluting stent implantation: five-year outcome of the j-Cypher Registry.

PubMed

Kimura, Takeshi; Morimoto, Takeshi; Nakagawa, Yoshihisa; Kawai, Kazuya; Miyazaki, Shunichi; Muramatsu, Toshiya; Shiode, Nobuo; Namura, Masanobu; Sone, Takahito; Oshima, Shigeru; Nishikawa, Hideo; Hiasa, Yoshikazu; Hayashi, Yasuhiko; Nobuyoshi, Masakiyo; Mitudo, Kazuaki

2012-01-31

There is a scarcity of long-term data from large-scale drug-eluting stent registries with a large enough sample to evaluate low-frequency events such as stent thrombosis (ST). Five-year outcomes were evaluated in 12 812 consecutive patients undergoing sirolimus-eluting stent (SES) implantation in the j-Cypher registry. Cumulative incidence of definite ST was low (30 day, 0.3%; 1 year, 0.6%; and 5 years, 1.6%). However, late and very late ST continued to occur without attenuation up to 5 years after sirolimus-eluting stent implantation (0.26%/y). Cumulative incidence of target lesion revascularization within the first year was low (7.3%). However, late target lesion revascularization beyond 1 year also continued to occur without attenuation up to 5 years (2.2%/y). Independent risk factors of ST were completely different according to the timing of ST onset, suggesting the presence of different pathophysiological mechanisms of ST according to the timing of ST onset: acute coronary syndrome and target of proximal left anterior descending coronary artery for early ST; side-branch stenting, diabetes mellitus, and end-stage renal disease with or without hemodialysis for late ST; and current smoking and total stent length >28 mm for very late ST. Independent risk factors of late target lesion revascularization beyond 1 year were generally similar to those risk factors identified for early target lesion revascularization. Late adverse events such as very late ST and late target lesion revascularization are continuous hazards, lasting at least up to 5 years after implantation of the first-generation drug-eluting stents (sirolimus-eluting stents), which should be the targets for developing improved coronary stents.

Kaplan-Meier Survival Analysis Overestimates the Risk of Revision Arthroplasty: A Meta-analysis.

PubMed

Lacny, Sarah; Wilson, Todd; Clement, Fiona; Roberts, Derek J; Faris, Peter D; Ghali, William A; Marshall, Deborah A

2015-11-01

Although Kaplan-Meier survival analysis is commonly used to estimate the cumulative incidence of revision after joint arthroplasty, it theoretically overestimates the risk of revision in the presence of competing risks (such as death). Because the magnitude of overestimation is not well documented, the potential associated impact on clinical and policy decision-making remains unknown. We performed a meta-analysis to answer the following questions: (1) To what extent does the Kaplan-Meier method overestimate the cumulative incidence of revision after joint replacement compared with alternative competing-risks methods? (2) Is the extent of overestimation influenced by followup time or rate of competing risks? We searched Ovid MEDLINE, EMBASE, BIOSIS Previews, and Web of Science (1946, 1980, 1980, and 1899, respectively, to October 26, 2013) and included article bibliographies for studies comparing estimated cumulative incidence of revision after hip or knee arthroplasty obtained using both Kaplan-Meier and competing-risks methods. We excluded conference abstracts, unpublished studies, or studies using simulated data sets. Two reviewers independently extracted data and evaluated the quality of reporting of the included studies. Among 1160 abstracts identified, six studies were included in our meta-analysis. The principal reason for the steep attrition (1160 to six) was that the initial search was for studies in any clinical area that compared the cumulative incidence estimated using the Kaplan-Meier versus competing-risks methods for any event (not just the cumulative incidence of hip or knee revision); we did this to minimize the likelihood of missing any relevant studies. We calculated risk ratios (RRs) comparing the cumulative incidence estimated using the Kaplan-Meier method with the competing-risks method for each study and used DerSimonian and Laird random effects models to pool these RRs. Heterogeneity was explored using stratified meta-analyses and metaregression. The pooled cumulative incidence of revision after hip or knee arthroplasty obtained using the Kaplan-Meier method was 1.55 times higher (95% confidence interval, 1.43-1.68; p < 0.001) than that obtained using the competing-risks method. Longer followup times and higher proportions of competing risks were not associated with increases in the amount of overestimation of revision risk by the Kaplan-Meier method (all p > 0.10). This may be due to the small number of studies that met the inclusion criteria and conservative variance approximation. The Kaplan-Meier method overestimates risk of revision after hip or knee arthroplasty in populations where competing risks (such as death) might preclude the occurrence of the event of interest (revision). Competing-risks methods should be used to more accurately estimate the cumulative incidence of revision when the goal is to plan healthcare services and resource allocation for revisions.

Cumulative risk effects for the development of behaviour difficulties in children and adolescents with special educational needs and disabilities.

PubMed

Oldfield, Jeremy; Humphrey, Neil; Hebron, Judith

2015-01-01

Research has identified multiple risk factors for the development of behaviour difficulties. What have been less explored are the cumulative effects of exposure to multiple risks on behavioural outcomes, with no study specifically investigating these effects within a population of young people with special educational needs and disabilities (SEND). Furthermore, it is unclear whether a threshold or linear risk model better fits the data for this population. The sample included 2660 children and 1628 adolescents with SEND. Risk factors associated with increases in behaviour difficulties over an 18-month period were summed to create a cumulative risk score, with this explanatory variable being added into a multi-level model. A quadratic term was then added to test the threshold model. There was evidence of a cumulative risk effect, suggesting that exposure to higher numbers of risk factors, regardless of their exact nature, resulted in increased behaviour difficulties. The relationship between risk and behaviour difficulties was non-linear, with exposure to increasing risk having a disproportionate and detrimental impact on behaviour difficulties in child and adolescent models. Interventions aimed at reducing behaviour difficulties need to consider the impact of multiple risk variables. Tailoring interventions towards those exposed to large numbers of risks would be advantageous. Copyright © 2015 Elsevier Ltd. All rights reserved.

Childhood trauma and metabolic syndrome in men and women.

PubMed

Lee, Chioun; Tsenkova, Vera; Carr, Deborah

2014-03-01

The long-term effects of childhood trauma on health are well-documented, but few population-based studies have explored how childhood trauma affects the risk of developing metabolic syndrome (MetS) in adulthood. Using data from 1234 adults in the second wave of Midlife in the United States (MIDUS), we investigate (1) the extent to which childhood abuse affects the risk of developing MetS in adulthood; (2) how the severity of different types of abuse (emotional, physical, sexual, or cumulative abuse) affects this risk; and (3) the extent to which adult socioeconomic status (SES), maladaptive stress responses, and unhealthy behaviors mediate the association. We also test whether these associations differ significantly by sex. We find that emotional and physical abuse increase the risk of developing MetS for both sexes, whereas sexual abuse is a predictor for women only. For both sexes, individuals who experienced more cumulative abuse have a greater risk of developing MetS. Adult SES partially explains the association between childhood abuse and MetS. Maladaptive stress responses and unhealthy behaviors further explain the association. Among the potential mediators, poor sleep quality was a significant pathway for men and women, while stress-induced eating was a significant pathway for women only. Our findings suggest that the well-documented health consequences of early life trauma may vary by the nature of the trauma, the victim's sex, and the coping mechanisms that he or she employs. Copyright © 2014 Elsevier Ltd. All rights reserved.

78 FR 25440 - Request for Information and Citations on Methods for Cumulative Risk Assessment

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-01

... Citations on Methods for Cumulative Risk Assessment AGENCY: Office of the Science Advisor, Environmental... requesting information and citations on approaches and methods for the planning, analysis, assessment, and... approaches to understanding risks to human health and the environment. For example, in Science & Decisions...

Cumulative incidence of cancer after solid organ transplantation.

PubMed

Hall, Erin C; Pfeiffer, Ruth M; Segev, Dorry L; Engels, Eric A

2013-06-15

Solid organ transplantation recipients have elevated cancer incidence. Estimates of absolute cancer risk after transplantation can inform prevention and screening. The Transplant Cancer Match Study links the US transplantation registry with 14 state/regional cancer registries. The authors used nonparametric competing risk methods to estimate the cumulative incidence of cancer after transplantation for 2 periods (1987-1999 and 2000-2008). For recipients from 2000 to 2008, the 5-year cumulative incidence, stratified by organ, sex, and age at transplantation, was estimated for 6 preventable or screen-detectable cancers. For comparison, the 5-year cumulative incidence was calculated for the same cancers in the general population at representative ages using Surveillance, Epidemiology, and End Results data. Among 164,156 recipients, 8520 incident cancers were identified. The absolute cancer risk was slightly higher for recipients during the period from 2000 to 2008 than during the period from 1987 to 1999 (5-year cumulative incidence: 4.4% vs. 4.2%; P = .006); this difference arose from the decreasing risk of competing events (5-year cumulative incidence of death, graft failure, or retransplantation: 26.6% vs. 31.9%; P < .001). From 2000 to 2008, the 5-year cumulative incidence of non-Hodgkin lymphoma was highest at extremes of age, especially in thoracic organ recipients (ages 0-34 years: range, 1.74%-3.28%; aged >50 years; range, 0.36%-2.22%). For recipients aged >50 years, the 5-year cumulative incidence was higher for colorectal cancer (range, 0.33%-1.94%) than for the general population at the recommended screening age (aged 50 years: range, 0.25%-0.33%). For recipients aged >50 years, the 5-year cumulative incidence was high for lung cancer among thoracic organ recipients (range, 1.16%-3.87%) and for kidney cancer among kidney recipients (range, 0.53%-0.84%). The 5-year cumulative incidence for prostate cancer and breast cancer was similar or lower in transplantation recipients than at the recommended ages of screening in the general population. Subgroups of transplantation recipients have a high absolute risk of some cancers and may benefit from targeted prevention or screening. Copyright © 2013 American Cancer Society.

Predictors of early stent occlusion among plastic biliary stents.

PubMed

Khashab, Mouen A; Kim, Katherine; Hutfless, Susan; Lennon, Anne Marie; Kalloo, Anthony N; Singh, Vikesh K

2012-09-01

A major disadvantage of plastic biliary stents is their short patency rates. The aim of this study was to identify predictors of early stent occlusion among patients receiving conventional plastic biliary stents. Early stent occlusion was defined as worsening cholestatic liver test results of a severity sufficiently significant to warrant ERCP with stent exchange prior to the planned stent exchange, or as symptoms of cholangitis. The association of cumulative stent diameter, demographics, stricture location, procedure indication, Charlson comorbidity index, history of prior early stent occlusion, presence of gallbladder, and performance of sphincteromy with the occurrence of early stent occlusion was studied using logistic regression and multivariate analysis. Our patient cohort comprised 343 patients (mean age 59.3 years) who underwent 561 ERCP procedures with the placement of one or more plastic biliary stents (mean number of stents per procedure 1.2, mean total diameter of stents per procedure 12 Fr). Early stent occlusion occurred in 73 (13 %) procedures. Female gender was protective against early stent occlusion (adjusted OR 0.54, 95 % CI 0.32-0.90, p = 0.02), while hilar stricture location was independently associated with a significantly increased risk of early stent occlusion (adjusted OR 3.41, 95 % CI 1.68-6.90, p = 0.0007). Early occlusion of conventional biliary stents occurred in 13 % of cases. While female gender decreased the risk of early stent occlusion, hilar stricture location was a significant predictor of early stent occlusion. Our results suggest that physicians should consider early elective stent exchange in patients with hilar strictures.

Relevance of the hygiene hypothesis to early vs. late onset allergic rhinitis.

PubMed

Matheson, M C; Walters, E H; Simpson, J A; Wharton, C L; Ponsonby, A-L; Johns, D P; Jenkins, M A; Giles, G G; Hopper, J L; Abramson, M J; Dharmage, S C

2009-03-01

The hygiene hypothesis proposes that reduced exposure to infections in early life increases the risk of developing allergic conditions including allergic rhinitis. We examined the association between markers of the hygiene hypothesis and allergic rhinitis that developed before 7 years of age and allergic rhinitis that developed after 7 years of age. The Tasmanian Longitudinal Health Study (TAHS) is a population-based cohort (n=8583) study of respiratory disease. Participants have been followed from 7 to 44 years of age. Information on potential risk factors, allergies and respiratory symptoms was collected longitudinally. Using multi-nomial logistic regression, exposure to siblings, infections, tonsillectomy and farm residence during childhood were examined as risk factors for allergic rhinitis that developed before or after 7 years of age. All analyses were adjusted for gender, maternal and paternal atopy, mother's age at participant's birth, paternal socio-economic status in 1968 and personal socio-economic status in 2004. Greater cumulative exposure to siblings before the age of 2 years was strongly inversely associated with early onset allergic rhinitis (<1 year sib exposure: OR=0.6, 95% CI 0.3-1.0; 1-3 years sib exposure: OR=0.6, 95% CI 0.4-0.9; >3 years sib exposure: OR=0.4, 95% CI 0.3-0.8) less so with later onset allergic rhinitis. The risk of early onset allergic rhinitis decreased with increasing viral infections (OR=0.7, 95% CI 0.5-0.9) during childhood. Having a tonsillectomy before 7 years of age increased the risk of early onset allergic rhinitis (OR=1.7, 95% CI 1.2-2.5). None of these factors was associated with later onset allergic rhinitis. Exposures relevant to the hygiene hypothesis were important predictors for the development of early onset but less so for later onset allergic rhinitis. The exact mechanisms by which siblings and infections protect against allergic rhinitis are unclear. The stronger findings for earlier onset allergic rhinitis suggest that family structure and infections have most impact on disease risk in early life. Further research should focus on early onset allergic rhinitis when exploring causal explanations for any sibling effect.

Non-Chemical Stressors and Cumulative Risk Assessment: An Overview of Current Initiatives and Potential Air Pollutant Interactions

PubMed Central

Lewis, Ari S.; Sax, Sonja N.; Wason, Susan C.; Campleman, Sharan L.

2011-01-01

Regulatory agencies are under increased pressure to consider broader public health concerns that extend to multiple pollutant exposures, multiple exposure pathways, and vulnerable populations. Specifically, cumulative risk assessment initiatives have stressed the importance of considering both chemical and non-chemical stressors, such as socioeconomic status (SES) and related psychosocial stress, in evaluating health risks. The integration of non-chemical stressors into a cumulative risk assessment framework has been largely driven by evidence of health disparities across different segments of society that may also bear a disproportionate risk from chemical exposures. This review will discuss current efforts to advance the field of cumulative risk assessment, highlighting some of the major challenges, discussed within the construct of the traditional risk assessment paradigm. Additionally, we present a summary of studies of potential interactions between social stressors and air pollutants on health as an example of current research that supports the incorporation of non-chemical stressors into risk assessment. The results from these studies, while suggestive of possible interactions, are mixed and hindered by inconsistent application of social stress indicators. Overall, while there have been significant advances, further developments across all of the risk assessment stages (i.e., hazard identification, exposure assessment, dose-response, and risk characterization) are necessary to provide a scientific basis for regulatory actions and effective community interventions, particularly when considering non-chemical stressors. A better understanding of the biological underpinnings of social stress on disease and implications for chemical-based dose-response relationships is needed. Furthermore, when considering non-chemical stressors, an appropriate metric, or series of metrics, for risk characterization is also needed. Cumulative risk assessment research will benefit from coordination of information from several different scientific disciplines, including, for example, toxicology, epidemiology, nutrition, neurotoxicology, and the social sciences. PMID:21776216

A case study to illustrate the utility of the Aggregate Exposure Pathway and Adverse Outcome Pathway frameworks for integrating human health and ecological data into cumulative risk assessment

EPA Science Inventory

Cumulative risk assessment (CRA) methods, which evaluate the risk of multiple adverse outcomes (AOs) from multiple chemicals, promote the use of a conceptual site model (CSM) to integrate risk from relevant stressors. The Adverse Outcome Pathway (AOP) framework can inform these r...

Language Delay in Severely Neglected Children: A Cumulative or Specific Effect of Risk Factors?

ERIC Educational Resources Information Center

Sylvestre, Audette; Merette, Chantal

2010-01-01

Objectives: This research sought to determine if the language delay (LD) of severely neglected children under 3 years old was better explained by a cumulative risk model or by the specificity of risk factors. The objective was also to identify the risk factors with the strongest impact on LD among various biological, psychological, and…

Predicting Academic Achievement from Cumulative Home Risk: The Mediating Roles of Effortful Control, Academic Relationships, and School Avoidance

ERIC Educational Resources Information Center

Swanson, Jodi; Valiente, Carlos; Lemery-Chalfant, Kathryn

2012-01-01

Components of the home environment are associated with children's academic functioning. The accumulation of risks in the home are expected to prove more detrimental to achievement than any one risk alone, but the processes accounting for this relation are unclear. Using an index of cumulative home risk (CHR) inclusive of protective factors, as…

Pesticide Cumulative Risk Assessment: Framework for Screening Analysis

EPA Pesticide Factsheets

This document provides guidance on how to screen groups of pesticides for cumulative evaluation using a two-step approach: begin with evaluation of available toxicological information and, if necessary, follow up with a risk-based screening approach.

Risk Factors for Diabetes Mellitus in Chronic Pancreatitis: A Cohort of 2011 Patients.

PubMed

Pan, Jun; Xin, Lei; Wang, Dan; Liao, Zhuan; Lin, Jin-Huan; Li, Bai-Rong; Du, Ting-Ting; Ye, Bo; Zou, Wen-Bin; Chen, Hui; Ji, Jun-Tao; Zheng, Zhao-Hong; Hu, Liang-Hao; Li, Zhao-Shen

2016-04-01

Diabetes mellitus (DM) is a common complication of chronic pancreatitis (CP) and increases the mortality. The identification of risk factors for DM development may contribute to the early detection and potential risk reduction of DM in patients with CP.Patients with CP admitted to Changhai Hospital (Shanghai, China) from January 2000 to December 2013 were enrolled. Cumulative rates of DM after the onset of CP were calculated by Kaplan-Meier method. Risk factors for DM development after the diagnosis of CP were identified by Cox proportional hazards regression model.A total of 2011 patients with CP were enrolled. During follow-up (median duration, 22.0 years), 564 patients developed DM. Cumulative rates of DM 20 and 50 years after the onset of CP were 45.8% (95% confidence interval [CI], 41.8%-50.0%) and 90.0% (95% CI, 75.4%-97.7%), respectively. Five risk factors for DM development after the diagnosis of CP were identified: male sex (hazard ratio [HR], 1.51; 95% CI, 1.08-2.11), alcohol abuse (HR, 2.00; 95% CI, 1.43-2.79), steatorrhea (HR, 1.46; 95% CI, 1.01-2.11), biliary stricture (HR, 2.25; 95% CI, 1.43-3.52), and distal pancreatectomy (HR, 3.41; 95% CI, 1.80-6.44).In conclusion, the risk of developing DM in patients with CP is not only influenced by the development of biliary stricture and steatorrhea indicating disease progression, and inherent nature of study subjects such as male sex, but also by modifiable factors including alcohol abuse and distal pancreatectomy .

Risk Factors for Diabetes Mellitus in Chronic Pancreatitis: A Cohort of 2,011 Patients.

PubMed

Pan, Jun; Xin, Lei; Wang, Dan; Liao, Zhuan; Lin, Jin-Huan; Li, Bai-Rong; Du, Ting-Ting; Ye, Bo; Zou, Wen-Bin; Chen, Hui; Ji, Jun-Tao; Zheng, Zhao-Hong; Hu, Liang-Hao; Li, Zhao-Shen

2016-04-01

Diabetes mellitus (DM) is a common complication of chronic pancreatitis (CP) and increases the mortality. The identification of risk factors for DM development may contribute to the early detection and potential risk reduction of DM in patients with CP.Patients with CP admitted to Changhai Hospital (Shanghai, China) from January 2000 to December 2013 were enrolled. Cumulative rates of DM after the onset of CP were calculated by Kaplan-Meier method. Risk factors for DM development after the diagnosis of CP were identified by Cox proportional hazards regression model.A total of 2011 patients with CP were enrolled. During follow-up (median duration, 22.0 years), 564 patients developed DM. Cumulative rates of DM 20 and 50 years after the onset of CP were 45.8% (95% confidence interval [CI], 41.8%-50.0%) and 90.0% (95% CI, 75.4%-97.7%), respectively. Five risk factors for DM development after the diagnosis of CP were identified: male sex (hazard ratio [HR], 1.51; 95% CI, 1.08-2.11), alcohol abuse (HR, 2.00; 95% CI, 1.43-2.79), steatorrhea (HR, 1.46; 95% CI, 1.01-2.11), biliary stricture (HR, 2.25; 95% CI, 1.43-3.52), and distal pancreatectomy (HR, 3.41; 95% CI, 1.80-6.44).In conclusion, the risk of developing DM in patients with CP is not only influenced by the development of biliary stricture and steatorrhea indicating disease progression, and inherent nature of study subjects such as male sex, but also by modifiable factors including alcohol abuse and distal pancreatectomy.

Detailed Assessments of Childhood AdversityEnhance Prediction of Central Obesity Independent of Gender, Race, Adult Psychosocial Risk and Health Behaviors

PubMed Central

Davis, Cynthia R.; Dearing, Eric; Usher, Nicole; Trifiletti, Sarah; Zaichenko, Lesya; Ollen, Elizabeth; Brinkoetter, Mary T.; Crowell-Doom, Cindy; Joung, Kyoung; Park, Kyung Hee; Mantzoros, Christos S.; Crowell, Judith A.

2017-01-01

Objective This study examined whether a novel indicator of overall childhood adversity, incorporating number of adversities, severity, and chronicity, predicted central obesity beyond contributions of “modifiable” risk factors including psychosocial characteristics and health behaviors in a diverse sample of midlife adults. The study also examined whether the overall adversity score (number of adversities X severity X chronicity) better predicted obesity compared to cumulative adversity (number of adversities), a more traditional assessment of childhood adversity. Materials/Methods 210 Black/African Americans and White/European Americans, mean age = 45.8; ±3.3 years, were studied cross-sectionally. Regression analysis examined overall childhood adversity as a direct, non-modifiable risk factor for central obesity (waist-hip ratio) and body mass index (BMI), with and without adjustment for established adult psychosocial risk factors (education, employment, social functioning) and heath behavior risk factors (smoking, drinking, diet, exercise). Results Overall childhood adversity was an independent significant predictor of central obesity, and the relations between psychosocial and health risk factors and central obesity were not significant when overall adversity was in the model. Overall adversity was not a statistically significant predictor of BMI. Conclusions Overall childhood adversity, incorporating severity and chronicity and cumulative scores, predicts central obesity beyond more contemporaneous risk factors often considered modifiable. This is consistent with early dysregulation of metabolic functioning. Findings can inform practitioners interested in the impact of childhood adversity and personalizing treatment approaches of obesity within high-risk populations. Prevention/intervention research is necessary to discover and address the underlying causes and impact of childhood adversity on metabolic functioning. PMID:24211017

Cumulative risk effects in the bullying of children and young people with autism spectrum conditions.

PubMed

Hebron, Judith; Oldfield, Jeremy; Humphrey, Neil

2017-04-01

Students with autism are more likely to be bullied than their typically developing peers. However, several studies have shown that their likelihood of being bullied increases in the context of exposure to certain risk factors (e.g. behaviour difficulties and poor peer relationships). This study explores vulnerability to bullying from a cumulative risk perspective, where the number of risks rather than their nature is considered. A total of 722 teachers and 119 parents of young people with autism spectrum conditions participated in the study. Established risk factors were summed to form a cumulative risk score in teacher and parent models. There was evidence of a cumulative risk effect in both models, suggesting that as the number of risks increased, so did exposure to bullying. A quadratic effect was found in the teacher model, indicating that there was a disproportionate increase in the likelihood of being bullied in relation to the number of risk factors to which a young person was exposed. In light of these findings, it is proposed that more attention needs to be given to the number of risks to which children and young people with autism spectrum conditions are exposed when planning interventions and providing a suitable educational environment.

Interaction between smoking and depressive symptoms with subclinical heart disease in the Coronary Artery Risk Development in Young Adults (CARDIA) study.

PubMed

Carroll, Allison J; Carnethon, Mercedes R; Liu, Kiang; Jacobs, David R; Colangelo, Laura A; Stewart, Jesse C; Carr, J Jeffrey; Widome, Rachel; Auer, Reto; Hitsman, Brian

2017-02-01

Evaluate whether smoking exposure and depressive symptoms accumulated over 25 years are synergistically associated with subclinical heart disease, measured by coronary artery calcification (CAC). Participants (baseline: 54.5% women; 51.5% Black; age range = 18-30 years) were followed prospectively from 1985 to 2010 in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Smoking status was queried yearly from Year 0 to Year 25 to compute packyears of smoking exposure. Depressive symptoms were measured on the Center for Epidemiologic Studies Depression (CES-D) scale every 5 years to compute cumulative scores from Year 5 to Year 25. A three-level multinomial logistic regression was used to evaluate the association between cumulative smoking, cumulative depressive symptoms, and their interaction with moderate-risk CAC (score 1-99) and higher-risk CAC (score ≥100) compared with no CAC (score = 0) at Year 25. Models were adjusted for sociodemographic, clinical, and behavioral covariates. Among 3,189 adults, the cumulative Smoking × Depressive Symptoms interaction was not significant for moderate-risk CAC (p = .057), but was significant for higher-risk CAC (p = .001). For adults with a 30-packyear smoking history, average CES-D scores 2, 10, and 16 were, respectively, associated with odds ratios (95% confidence intervals) 3.40 (2.36-4.90), 4.82 (3.03-7.66), and 6.25 (3.31-11.83) for higher-risk CAC (all ps < .05). Cumulative smoking exposure and cumulative depressive symptoms have a synergistic association with subclinical heart disease, where higher lifetime smoking exposure and depressive symptoms are associated with greater odds of CAC. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Cumulative radiation exposure and cancer risk estimation in children with heart disease.

PubMed

Johnson, Jason N; Hornik, Christoph P; Li, Jennifer S; Benjamin, Daniel K; Yoshizumi, Terry T; Reiman, Robert E; Frush, Donald P; Hill, Kevin D

2014-07-08

Children with heart disease are frequently exposed to imaging examinations that use ionizing radiation. Although radiation exposure is potentially carcinogenic, there are limited data on cumulative exposure and the associated cancer risk. We evaluated the cumulative effective dose of radiation from all radiation examinations to estimate the lifetime attributable risk of cancer in children with heart disease. Children ≤6 years of age who had previously undergone 1 of 7 primary surgical procedures for heart disease at a single institution between 2005 and 2010 were eligible for the study. Exposure to radiation-producing examinations was tabulated, and cumulative effective dose was calculated in millisieverts. These data were used to estimate lifetime attributable risk of cancer above baseline using the approach of the Committee on Biological Effects of Ionizing Radiation VII. The cohort included 337 children exposed to 13 932 radiation examinations. Conventional radiographs represented 92% of examinations, whereas cardiac catheterization and computed tomography accounted for 81% of cumulative exposure. Overall median cumulative effective dose was 2.7 mSv (range, 0.1-76.9 mSv), and the associated lifetime attributable risk of cancer was 0.07% (range, 0.001%-6.5%). Median lifetime attributable risk of cancer ranged widely depending on surgical complexity (0.006%-1.6% for the 7 surgical cohorts) and was twice as high in females per unit exposure (0.04% versus 0.02% per 1-mSv effective dose for females versus males, respectively; P<0.001). Overall radiation exposures in children with heart disease are relatively low; however, select cohorts receive significant exposure. Cancer risk estimation highlights the need to limit radiation dose, particularly for high-exposure modalities. © 2014 American Heart Association, Inc.

Estimation and comparison of cumulative incidences of biliary self-expandable metallic stent dysfunction accounting for competing risks.

PubMed

Hamada, Tsuyoshi; Nakai, Yousuke; Isayama, Hiroyuki; Togawa, Osamu; Kogure, Hirofumi; Kawakubo, Kazumichi; Tsujino, Takeshi; Sasahira, Naoki; Hirano, Kenji; Yamamoto, Natsuyo; Ito, Yukiko; Sasaki, Takashi; Mizuno, Suguru; Toda, Nobuo; Tada, Minoru; Koike, Kazuhiko

2014-03-01

Self-expandable metallic stent (SEMS) placement is widely carried out for distal malignant biliary obstruction, and survival analysis is used to evaluate the cumulative incidences of SEMS dysfunction (e.g. the Kaplan-Meier [KM] method and the log-rank test). However, these statistical methods might be inappropriate in the presence of 'competing risks' (here, death without SEMS dysfunction), which affects the probability of experiencing the event of interest (SEMS dysfunction); that is, SEMS dysfunction can no longer be observed after death. A competing risk analysis has rarely been done in studies on SEMS. We introduced the concept of a competing risk analysis and illustrated its impact on the evaluation of SEMS outcomes using hypothetical and actual data. Our illustrative study included 476 consecutive patients who underwent SEMS placement for unresectable distal malignant biliary obstruction. A significant difference between cumulative incidences of SEMS dysfunction in male and female patients via theKM method (P = 0.044 by the log-rank test) disappeared after applying a competing risk analysis (P = 0.115 by Gray's test). In contrast, although cumulative incidences of SEMS dysfunction via the KM method were similar with and without chemotherapy (P = 0.647 by the log-rank test), cumulative incidence of SEMS dysfunction in the non-chemotherapy group was shown to be significantly lower (P = 0.031 by Gray's test) in a competing risk analysis. Death as a competing risk event needs to be appropriately considered in estimating a cumulative incidence of SEMS dysfunction, otherwise analytical results may be biased. © 2013 The Authors. Digestive Endoscopy © 2013 Japan Gastroenterological Endoscopy Society.

Cumulative Risk and Teacher Well-Being in the Democratic Republic of the Congo

ERIC Educational Resources Information Center

Wolf, Sharon; Torrente, Catalina; McCoy, Marissa; Rasheed, Damira; Aber, J. Lawrence

2015-01-01

Remarkably little systematic research has examined the living and working conditions for teachers in sub-Saharan Africa and how such conditions predict teacher well-being. This study assesses how various risks across several domains of teachers' lives--measured as a "cumulative risk index"--predict motivation, burnout, and job…

The multicentre south European study 'Helios'. II: Different sun exposure patterns in the aetiology of basal cell and squamous cell carcinomas of the skin.

PubMed Central

Rosso, S.; Zanetti, R.; Martinez, C.; Tormo, M. J.; Schraub, S.; Sancho-Garnier, H.; Franceschi, S.; Gafà, L.; Perea, E.; Navarro, C.; Laurent, R.; Schrameck, C.; Talamini, R.; Tumino, R.; Wechsler, J.

1996-01-01

The role of sun exposure in development of basal cell and squamous cell carcinomas among different populations from south Europe was investigated. Between 1989 and 1993 we interviewed incident cases and a random population sample of controls from five centres where a cancer registry was operating, whereas we selected a sample of hospital-based cases and controls from the other three centres. We gathered information on life-long exposure to sunlight during different activities. Results are analysed for 1549 basal cell carcinoma (BCC) cases and 228 squamous cell carcinoma (SCC) cases compared with 1795 controls. We observed a statistically significant increase of risk of SCC with increasing sun exposure beyond a threshold of 70,000 cumulated hours of exposure in a lifetime. Sun exposures during work and holidays were, however, inversely correlated. Odds ratios (ORs) of SCC were up to eight or nine times the reference for the highest exposures (200,000 cumulated hours or more). BCC exhibited a 2-fold increase of risk for lower exposure (8000-10,000 cumulated hours in a lifetime) with a plateau and a slight decrease of risk for the highest exposures (100,000 cumulated hours or more). Outdoor work showed a significantly increased risk of SCC (OR 1.6 for more than 54,000 cumulated hours of exposure in a lifetime), whereas recreational activities such as sun exposure during holidays at the beach (OR 1.6 for more than 2600 cumulated hours of exposure in a lifetime) or during water sports (OR 1.6 for more than 2600 cumulated hours of exposure in a lifetime) were associated with an increased risk of BCC. Risk patterns were different in poor or good tanners with a significant risk trend for good tanners, whereas poor tanners were on a plateau of increased risk at any level of exposure. Solar radiation is associated with a risk of BCC even for relatively short periods of exposure such as during holidays and sports, whereas SCC develops later if exposure continues. The skin's ability to tan modulates the risk of BCC; subjects who tan poorly have a steady risk increase, whereas people who tan easily develop cancer only after prolonged exposures. PMID:8645596

Editorial: The effects of early trauma and deprivation on human development - from measuring cumulative risk to characterizing specific mechanisms.

PubMed

Zeanah, Charles H; Sonuga-Barke, Edmund J S

2016-10-01

Science is not a linear process of accumulating knowledge. To the contrary, progress in understanding is most likely to occur, especially in less 'mature' disciplines, when healthy debate between opposing points of view create a dialectic in which thesis and antithesis force a new synthesis. In developmental psychopathology, such tension between opposing schools of thought continue to play a vital role in driving discovery across a wide range of topics. © 2016 Association for Child and Adolescent Mental Health.

Tools to Assess Community-Based Cumulative Risk and Exposures

EPA Science Inventory

Multiple agents and stressors can interact in a given community to adversely affect human and ecological conditions. A cumulative risk assessment (CRA) analyzes, characterizes, and potentially quantifies the effects from multiple stressors, which include chemical agents (for exam...

Psychotic-spectrum symptoms, cumulative adversity exposure and substance use among high-risk girls.

PubMed

Lansing, Amy E; Plante, Wendy Y; Fennema-Notestine, Christine; Golshan, Shahrokh; Beck, Audrey N

2018-02-01

Psychotic-spectrum symptoms are linked to trauma, substance/alcohol use (SAU), criminality/violence and poor functional outcomes, supporting the need for early detection in vulnerable populations. To better understand high-risk girls' mental health, we assessed: (1) psychotic-spectrum symptoms; (2) cumulative trauma, adversity and loss exposures (C-TALE) and adversity-indicators (symptoms, maladaptive coping, stressor-reactivity); and SAU risk-factors; and (3) relationships among psychotic-spectrum symptoms, adversity-indicators and SAU risk-factors. We administered the Structured Clinical Interviews for Psychotic Spectrum, and Trauma and Loss Spectrum to 158 adolescent delinquent girls. Girls' psychotic-spectrum profiles were similar to previously reported adult psychotic patients and characterized by typical symptoms (hallucinations/delusions, reported largely SAU-independent), interpersonal sensitivity, schizoid traits and paranoia (over-interpretation, anger over-reactivity, hypervigilance). Auditory/visual hallucinations (55.7%), delusions (92.4%), ideas of reference (96.8%) and adversity (90.0% ≥10/24 C-TALE-types) were common. Mean loss (4) and trauma (8) onset-age occurred before SAU-onset (12). Significant positive correlations were found among psychotic-spectrum symptoms, stressor-reactivity, C-TALE, adversity-indicators; and number of SAU-types; and a negative correlation occurred between psychotic-spectrum symptoms and earlier alcohol use onset. After controlling for number of SAU-types, stressor-reactivity and adversity-related numbing individually had the largest associations with total psychotic-spectrum symptoms (b = 2.6-4.3). Girls averaged more than 4 maladaptive coping strategies (e.g., 24.8% attempted suicide) in response to adversity, amplifying potential health-disparities. No racial/ethnic differences emerged on psychotic-spectrum symptoms. This symptom constellation during adolescence likely interferes with social and academic functioning. Whether representing a prodromal phase, trauma-response or cross-diagnostic psychopathology, accurate early detection and appropriate treatment of psychotic-spectrum symptoms are warranted to improve functional outcomes in vulnerable populations. © 2017 John Wiley & Sons Australia, Ltd.

Birth order and risk of nasopharyngeal carcinoma in multiplex families from Taiwan.

PubMed

Liu, Zhiwei; Coghill, Anna E; Pfeiffer, Ruth M; Hsu, Wan-Lun; Lou, Pei-Jen; Wang, Cheng-Ping; Yu, Kelly J; Niwa, Shelley; Brotzman, Michelle; Ye, Weimin; Chen, Chien-Jen; Hildesheim, Allan

2016-12-01

A small proportion of individuals infected with Epstein-Barr virus (EBV) develop nasopharyngeal carcinoma (NPC). Timing of initial exposure could alter immunological responses to primary EBV infection and explain variation in cancer risk later in life. We measured early life family structure as a proxy for the timing of primary EBV infection to examine whether earlier age at infection alters NPC risk. We utilized data from 480 NPC cases and 1,291 unaffected siblings from Taiwanese NPC multiplex families (≥ 2 family members with NPC, N = 2,921). Information on birth order within the family was derived from questionnaires. We utilized logistic regression models to examine the association between birth order and NPC, accounting for correlations between relatives. Within these high-risk families, older siblings had an elevated risk of NPC. Compared with being a first-born child, the risk (95% CIs) of NPC associated with a birth order of two, three, four and five or more was 1.00 (0.71, 1.40), 0.88 (0.62, 1.24), 0.74 (0.53, 1.05) and 0.60 (0.43, 0.82), respectively (P for trend = 0.002). We observed no associations between NPC risk and the number of younger siblings or cumulative infant-years exposure. These associations were not modified by underlying genetic predisposition or family size. We observed that early life family structure was important for NPC risk in NPC multiplex families, with older siblings having a greater risk of disease. Future studies focusing on more direct measures of the immune response to EBV in early childhood could elucidate the underlying mechanisms. © 2016 UICC.

Novel coronary heart disease risk factors at 60–64 years and life course socioeconomic position: The 1946 British birth cohort

PubMed Central

Jones, Rebecca; Hardy, Rebecca; Sattar, Naveed; Deanfield, John E.; Hughes, Alun; Kuh, Diana; Murray, Emily T.; Whincup, Peter H.; Thomas, Claudia

2015-01-01

Social disadvantage across the life course is associated with a greater risk of coronary heart disease (CHD) and with established CHD risk factors, but less is known about whether novel CHD risk factors show the same patterns. The Medical Research Council National Survey of Health and Development was used to investigate associations between occupational socioeconomic position during childhood, early adulthood and middle age and markers of inflammation (C-reactive protein, interleukin-6), endothelial function (E-selectin, tissue-plasminogen activator), adipocyte function (leptin, adiponectin) and pancreatic beta cell function (proinsulin) measured at 60–64 years. Life course models representing sensitive periods, accumulation of risk and social mobility were compared with a saturated model to ascertain the nature of the relationship between social class across the life course and each of these novel CHD risk factors. For interleukin-6 and leptin, low childhood socioeconomic position alone was associated with high risk factor levels at 60–64 years, while for C-reactive protein and proinsulin, cumulative effects of low socioeconomic position in both childhood and early adulthood were associated with higher (adverse) risk factor levels at 60–64 years. No associations were observed between socioeconomic position at any life period with either endothelial marker or adiponectin. Associations for C-reactive protein, interleukin-6, leptin and proinsulin were reduced considerably by adjustment for body mass index and, to a lesser extent, cigarette smoking. In conclusion, socioeconomic position in early life is an important determinant of several novel CHD risk factors. Body mass index may be an important mediator of these relationships. PMID:25437893

Longitudinal study of parental smoking habits and development of asthma in early childhood.

PubMed

Kanoh, Miki; Kaneita, Yoshitaka; Hara, Megumi; Harada, Shohei; Gon, Yasuhiro; Kanamaru, Hiroshi; Ohida, Takashi

2012-01-01

This study examined the association between parental smoking habits and the development of asthma in early childhood by using representative samples. The survey subjects included all of the 53,575 babies born in Japan during the periods January 10-17 and July 10-17, 2001. The families of the subjects were asked to complete questionnaires that were delivered by post at 6 months, 1 year 6 months, 2 years 6 months, 3 years 6 months, and 4 years 6 months postpartum. The first survey contained questions regarding the smoking habits of the parents. The second to fifth surveys asked if the child had needed medical attention for the treatment of asthma. Data from 36,888 subjects (collection rate: 68.9%) were analyzed. The 4-year cumulative incidence of asthma was 12.0%. Maternal indoor smoking significantly increased the risk of asthma development in children, 4-year risk 14.4% vs. 11.7%, risk ratio=1.24, 95% CI: 1.11 to 1.38. No statistically significant association was found between paternal smoking and asthma development in children. In order to prevent the development of asthma in early childhood, it is necessary to formulate measures to stop or discourage maternal smoking. Copyright © 2011. Published by Elsevier Inc.

Environmental determinants of allergy and asthma in early life.

PubMed

Burbank, Allison J; Sood, Amika K; Kesic, Matthew J; Peden, David B; Hernandez, Michelle L

2017-07-01

Allergic disease prevalence has increased significantly in recent decades. Primary prevention efforts are being guided by study of the exposome (or collective environmental exposures beginning during the prenatal period) to identify modifiable factors that affect allergic disease risk. In this review we explore the evidence supporting a relationship between key components of the external exposome in the prenatal and early-life periods and their effect on atopy development focused on microbial, allergen, and air pollution exposures. The abundance and diversity of microbial exposures during the first months and years of life have been linked with risk of allergic sensitization and disease. Indoor environmental allergen exposure during early life can also affect disease development, depending on the allergen type, dose, and timing of exposure. Recent evidence supports the role of ambient air pollution in allergic disease inception. The lack of clarity in the literature surrounding the relationship between environment and atopy reflects the complex interplay between cumulative environmental factors and genetic susceptibility, such that no one factor dictates disease development in all subjects. Understanding the effect of the summation of environmental exposures throughout a child's development is needed to identify cost-effective interventions that reduce atopy risk in children. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Social Determinants of Health in Environmental Justice Communities: Examining Cumulative Risk in Terms of Environmental Exposures and Social Determinants of Health

PubMed Central

Prochaska, John D.; Nolen, Alexandra B.; Kelley, Hilton; Sexton, Ken; Linder, Stephen H.; Sullivan, John

2014-01-01

Residents of environmental justice (EJ) communities may bear a disproportionate burden of environmental health risk, and often face additional burdens from social determinants of health. Accounting for cumulative risk should include measures of risk from both environmental sources and social determinants. This study sought to better understand cumulative health risk from both social and environmental sources in a disadvantaged community in Texas. Key outcomes were determining what data are currently available for this assessment, clarifying data needs, identifying data gaps, and considering how those gaps could be filled. Analyses suggested that the traditionally defined EJ community in Port Arthur may have a lower environmental risk from air toxics than the rest of the City of Port Arthur (although the entire city has a higher risk than the average for the state), but may have a larger burden from social determinants of health. However, the results should be interpreted in light of the availability of data, the definitions of community boundaries, and the areal unit utilized. Continued focus on environmental justice communities and the cumulative risks faced by their residents is critical to protecting these residents and, ultimately, moving towards a more equitable distribution and acceptable level of risk throughout society. PMID:24771993

Social Determinants of Health in Environmental Justice Communities: Examining Cumulative Risk in Terms of Environmental Exposures and Social Determinants of Health.

PubMed

Prochaska, John D; Nolen, Alexandra B; Kelley, Hilton; Sexton, Ken; Linder, Stephen H; Sullivan, John

2014-01-01

Residents of environmental justice (EJ) communities may bear a disproportionate burden of environmental health risk, and often face additional burdens from social determinants of health. Accounting for cumulative risk should include measures of risk from both environmental sources and social determinants. This study sought to better understand cumulative health risk from both social and environmental sources in a disadvantaged community in Texas. Key outcomes were determining what data are currently available for this assessment, clarifying data needs, identifying data gaps, and considering how those gaps could be filled. Analyses suggested that the traditionally defined EJ community in Port Arthur may have a lower environmental risk from air toxics than the rest of the City of Port Arthur (although the entire city has a higher risk than the average for the state), but may have a larger burden from social determinants of health. However, the results should be interpreted in light of the availability of data, the definitions of community boundaries, and the areal unit utilized. Continued focus on environmental justice communities and the cumulative risks faced by their residents is critical to protecting these residents and, ultimately, moving towards a more equitable distribution and acceptable level of risk throughout society.

Descriptive characteristics of colon and rectal cancer recurrence in a Danish population-based study.

PubMed

Holmes, Ashley C; Riis, Anders H; Erichsen, Rune; Fedirko, Veronika; Ostenfeld, Eva Bjerre; Vyberg, Mogens; Thorlacius-Ussing, Ole; Lash, Timothy L

2017-08-01

Recurrence is a common outcome among patients that have undergone an intended curative resection for colorectal cancer. However, data on factors that influence colorectal cancer recurrence are sparse. We report descriptive characteristics of both colon and rectal cancer recurrence in an unselected population. We identified 21,152 patients with colorectal cancer diagnosed between May 2001 and December 2011 and registered with the Danish Colorectal Cancer Group. Recurrences were identified in 3198 colon and 1838 rectal cancer patients during follow-up. We calculated the frequency, proportion, and incidence rates of colon and rectal cancer recurrence within descriptive categories, and the cumulative five- and ten-year incidences of recurrence, treating death as a competing risk. We used a Cox proportional hazard model to calculate hazard ratios (HR) and 95% confidence intervals (CI). Recurrence risk was highest in the first three years of follow-up. Patients <55 years old at initial diagnosis (incidence rate for colon: 7.2 per 100 person-years; 95% CI: 6.5-7.9; rectum: 8.1 per 100 person-years; 95% CI: 7.2-9.0) and patients diagnosed with stage III cancer (colon HR: 5.70; 95% CI: 4.61-7.06; rectal HR: 7.02; 95% CI: 5.58-8.82) had increased risk of recurrence. Patients diagnosed with stage III cancer from 2009 to 2011 had a lower incidence of recurrence than those diagnosed with stage III cancer in the years before. Cumulative incidences of colon and rectal cancer recurrence were similar for both cancer types among each descriptive category. In this population, increases in colorectal cancer recurrence risk were associated with younger age and increasing stage at diagnosis. Cumulative incidence of recurrence did not differ by cancer type. Descriptive characteristics of colon and rectal cancer recurrence may help to inform patient-physician decision-making, and could be used to determine adjuvant therapies or tailor surveillance strategies so that recurrence may be identified early, particularly within the first 3 years of follow-up.

Comments on the Causation of Malignant Mesothelioma: Rebutting the False Concept That Recent Exposures to Asbestos Do Not Contribute to Causation of Mesothelioma.

PubMed

Landrigan, Phillip J

2016-01-01

European asbestos manufacturers and their expert witnesses have advanced the claim that recent exposures to asbestos are not of significance in the causation of malignant mesothelioma. They argue that in cases of prolonged exposure to asbestos only the earliest exposures contribute to mesothelioma induction. The Collegium Ramazzini examined this claim and compared it with the findings of the Epidemiology and Public Health Working Group of the Second Italian Consensus Conference on Pleural Mesothelioma. This independent Working Group noted that earlier exposures are more effective in inducing mesothelioma, but that subsequent exposures also contribute and cannot be excluded. They found convincing evidence to support the conclusion that mesothelioma incidence is proportional to cumulative asbestos exposure. The Collegium Ramazzini concludes that risk of malignant mesothelioma is proportional to cumulative exposure to asbestos in which all exposures - early as well as late - contribute to the totality of risk. The Collegium Ramazzini rejects as false and scientifically unfounded the notion that only the earliest exposures to asbestos contribute to mesothelioma induction. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

Cumulative childhood risk and adult functioning in abused and neglected children grown up

PubMed Central

HORAN, JACQUELINE M.; WIDOM, CATHY SPATZ

2017-01-01

This paper examines the relationship between childhood exposure to cumulative risk and three indicators of psychosocial adjustment in adulthood (educational attainment, mental health, and criminal behavior) and tests three different models (linear, quadratic, and interaction). Data were collected over several time points from individuals who were part of a prospective cohort design study that matched children with documented cases of abuse and/or neglect with children without such histories and followed them into adulthood. Hierarchical multiple regressions compared linear and quadratic models and then examined potential moderating effects of child abuse/neglect and gender. Exposure to a greater number of childhood risk factors was significantly related to fewer years of education, more anxiety and depression symptomatology, and more criminal arrests in adulthood. The relationship between cumulative risk and years of education demonstrated a curvilinear pattern, whereas the relationship between cumulative risk and both mental health and criminal arrests was linear. Child abuse/neglect did not moderate these relationships, although there were direct effects for both child abuse/neglect and gender on criminal arrests, with more arrests for abused/neglected individuals than controls and more for males than females. Gender interacted with cumulative risk to impact educational attainment and criminal behavior, suggesting that interventions may be more effective if tailored differently for males and females. Interventions may need to be multifaceted and designed to address these different domains of functioning. PMID:25196178

Cumulative childhood risk and adult functioning in abused and neglected children grown up.

PubMed

Horan, Jacqueline M; Widom, Cathy Spatz

2015-08-01

This paper examines the relationship between childhood exposure to cumulative risk and three indicators of psychosocial adjustment in adulthood (educational attainment, mental health, and criminal behavior) and tests three different models (linear, quadratic, and interaction). Data were collected over several time points from individuals who were part of a prospective cohort design study that matched children with documented cases of abuse and/or neglect with children without such histories and followed them into adulthood. Hierarchical multiple regressions compared linear and quadratic models and then examined potential moderating effects of child abuse/neglect and gender. Exposure to a greater number of childhood risk factors was significantly related to fewer years of education, more anxiety and depression symptomatology, and more criminal arrests in adulthood. The relationship between cumulative risk and years of education demonstrated a curvilinear pattern, whereas the relationship between cumulative risk and both mental health and criminal arrests was linear. Child abuse/neglect did not moderate these relationships, although there were direct effects for both child abuse/neglect and gender on criminal arrests, with more arrests for abused/neglected individuals than controls and more for males than females. Gender interacted with cumulative risk to impact educational attainment and criminal behavior, suggesting that interventions may be more effective if tailored differently for males and females. Interventions may need to be multifaceted and designed to address these different domains of functioning.

Advances in the management of PML: focus on natalizumab.

PubMed

Fox, Robert

2011-11-01

Progressive multifocal leukoencephalopathy (PML), a rare opportunistic infection of the central nervous system, occurs mainly in the setting of broad-based and selective immunosuppression. The immunomodulatory agent most often implicated in the development of PML is the monoclonal antibody natalizumab. Management of PML begins with risk stratification. Factors that predict the risk of PML are JC virus (JCV) antibody status, history of chemotherapy use, and cumulative exposure to natalizumab. The risk of natalizumab-related PML increases up to a duration of 36 months of therapy, after which the risk appears to level off. If suspicious for PML, the use of a sensitive JCV polymerase chain reaction assay permits early diagnosis. Immune reconstitution represents the mainstay of treatment for PML. With rapid reversal of immunosuppression followed by immunologic recovery, almost all patients suffer clinical deterioration termed immune reconstitution inflammatory syndrome (IRIS). High-dose corticosteroids are often recommended if a clinical and imaging syndrome resembling IRIS develops after immune restoration.

Impact of Early Versus Late Diuretic Exposure on Metabolic Bone Disease and Growth in Premature Neonates.

PubMed

Orth, Lucas E; O'Mara, Keliana L

2018-01-01

This study aimed to determine whether there are differences in the incidence of metabolic bone disease (MBD) between preterm neonates first exposed to diuretics prior to 2 weeks of life versus those exposed after 2 weeks. This study was a retrospective analysis of premature neonates born at a tertiary care center between 2011 and 2015 who received either furosemide or chlorothiazide. The primary outcome was incidence of MBD. Secondary outcomes included growth, electrolyte disturbances, oxygen requirement, and length of stay. A total of 147 patients were included. Early initiation (n = 90) and late initiation (n = 57) arms were balanced with respect to birth weight and gestational age. There was no difference in incidence of MBD in the early group (76%) versus the late group (65%; p = 0.164). Stratification by cumulative dose showed incidence of 85% in patients receiving ≥8 mg/kg of furosemide, compared with 68% and 64% of those in the <4 mg/kg and 4 to 7.9 mg/kg strata, respectively (p = 0.06). The early group experienced greater reductions in length-for-age growth during diuretic therapy (-70% versus -40%; p = 0.009). Electrolyte abnormalities were more prevalent in the early group. Although there was no difference in duration of mechanical ventilation, duration of supplemental oxygen requirement was reduced in the late group (75 versus 89 days; p = 0.003). Timing of diuretic initiation did not affect incidence of MBD. Increased cumulative furosemide exposure may be associated with higher incidence. Patients first exposed to diuretics within 2 weeks of life are at higher risk for electrolyte abnormalities and reduced growth velocity.

HUMAN EXPOSURE MODELING FOR CUMULATIVE RISK

EPA Science Inventory

US EPA's Office of Research and Development (ORD) has identified cumulative risk assessment as a priority research area. This is because humans and other organisms are exposed to a multitude of chemicals, physical agents, and other stressors through multiple pathways, routes, an...

Cumulative Risk: Toxicity and Interactions of Physical and Chemical Stressors

EPA Science Inventory

ABSTRACT Recent efforts to update cumulative risk assessment procedures to incorporate nonchemical stressors ranging from physical to psychosocial, reflect increased interest in consideratio of the totality of variables affecting human health and the growing desire to develop co...

PERMETHRIN BUT NOT DELTAMETHRIN INCREASES SPONTANEOUS GLUTAMATE RELEASE FROM HIPPOCAMPAL NEURONS IN CULTURE.

EPA Science Inventory

This manuscript provides important information relevant to the cumulative risk assessment of pyrethroid insecticides. Others have proposed that pyrethroid effects on voltage-gated calcium channels contribute the neurotoxicity and must be considered in cumulative risk assessments ...

Methods to Assess Adverse Childhood Experiences of Children and Families: Toward Approaches to Promote Child Well-being in Policy and Practice.

PubMed

Bethell, Christina D; Carle, Adam; Hudziak, James; Gombojav, Narangerel; Powers, Kathleen; Wade, Roy; Braveman, Paula

Advances in human development sciences point to tremendous possibilities to promote healthy child development and well-being across life by proactively supporting safe, stable and nurturing family relationships (SSNRs), teaching resilience, and intervening early to promote healing the trauma and stress associated with disruptions in SSNRs. Assessing potential disruptions in SSNRs, such as adverse childhood experiences (ACEs), can contribute to assessing risk for trauma and chronic and toxic stress. Asking about ACEs can help with efforts to prevent and attenuate negative impacts on child development and both child and family well-being. Many methods to assess ACEs exist but have not been compared. The National Survey of Children's Health (NSCH) now measures ACEs for children, but requires further assessment and validation. We identified and compared methods to assess ACEs among children and families, evaluated the acceptability and validity of the new NSCH-ACEs measure, and identified implications for assessing ACEs in research and practice. Of 14 ACEs assessment methods identified, 5 have been used in clinical settings (vs public health assessment or research) and all but 1 require self or parent report (3 allow child report). Across methods, 6 to 20 constructs are assessed, 4 of which are common to all: parental incarceration, domestic violence, household mental illness/suicide, household alcohol or substance abuse. Common additional content includes assessing exposure to neighborhood violence, bullying, discrimination, or parental death. All methods use a numeric, cumulative risk scoring methodology. The NSCH-ACEs measure was acceptable to respondents as evidenced by few missing values and no reduction in response rate attributable to asking about children's ACEs. The 9 ACEs assessed in the NSCH co-occur, with most children with 1 ACE having additional ACEs. This measure showed efficiency and confirmatory factor analysis as well as latent class analysis supported a cumulative risk scoring method. Formative as well as reflective measurement models further support cumulative risk scoring and provide evidence of predictive validity of the NSCH-ACEs. Common effects of ACEs across household income groups confirm information distinct from economic status is provided and suggest use of population-wide versus high-risk approaches to assessing ACEs. Although important variations exist, available ACEs measurement methods are similar and show consistent associations with poorer health outcomes in absence of protective factors and resilience. All methods reviewed appear to coincide with broader goals to facilitate health education, promote health and, where needed, to mitigate the trauma, chronic stress, and behavioral and emotional sequelae that can arise with exposure to ACEs. Assessing ACEs appears acceptable to individuals and families when conducted in population-based and clinical research contexts. Although research to date and neurobiological findings compel early identification and health education about ACEs in clinical settings, further research to guide use in pediatric practice is required, especially as it relates to distinguishing ACEs assessment from identifying current family psychosocial risks and child abuse. The reflective as well as formative psychometric analyses conducted in this study confirm use of cumulative risk scoring for the NSCH-ACEs measure. Even if children have not been exposed to ACEs, assessing ACEs has value as an educational tool for engaging and educating families and children about the importance of SSNRs and how to recognize and manage stress and learn resilience. Copyright © 2017 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Cumulative psychosocial risk, parental socialization, and child cognitive functioning: A longitudinal cascade model.

PubMed

Wade, Mark; Madigan, Sheri; Plamondon, Andre; Rodrigues, Michelle; Browne, Dillon; Jenkins, Jennifer M

2018-06-01

Previous studies have demonstrated that various psychosocial risks are associated with poor cognitive functioning in children, and these risks frequently cluster together. In the current longitudinal study, we tested a model in which it was hypothesized that cumulative psychosocial adversity of mothers would have deleterious effects on children's cognitive functioning by compromising socialization processes within families (i.e., parental competence). A prospective community birth cohort of 501 families was recruited when children were newborns. At this time, mothers reported on their current psychosocial circumstances (socioeconomic status, teen parenthood, depression, etc.), which were summed into a cumulative risk score. Families were followed up at 18 months and 3 years, at which point maternal reflective capacity and cognitive sensitivity were measured, respectively. Child cognition (executive functioning, theory of mind, and language ability) was assessed at age 4.5 using age-appropriate observational and standardized tasks. Analyses controlled for child age, gender, number of children in the home, number of years married, and mothers' history of adversity. The results revealed significant declines in child cognition as well as maternal reflective capacity and cognitive sensitivity as the number of psychosocial risks increased. Moreover, longitudinal path analysis showed significant indirect effects from cumulative risk to all three cognitive outcomes via reflective capacity and cognitive sensitivity. Findings suggest that cumulative risk of mothers may partially account for child cognitive difficulties in various domains by disrupting key parental socialization competencies. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Multiple imputation methods for nonparametric inference on cumulative incidence with missing cause of failure

PubMed Central

Lee, Minjung; Dignam, James J.; Han, Junhee

2014-01-01

We propose a nonparametric approach for cumulative incidence estimation when causes of failure are unknown or missing for some subjects. Under the missing at random assumption, we estimate the cumulative incidence function using multiple imputation methods. We develop asymptotic theory for the cumulative incidence estimators obtained from multiple imputation methods. We also discuss how to construct confidence intervals for the cumulative incidence function and perform a test for comparing the cumulative incidence functions in two samples with missing cause of failure. Through simulation studies, we show that the proposed methods perform well. The methods are illustrated with data from a randomized clinical trial in early stage breast cancer. PMID:25043107

Cumulative biomedical risk and social cognition in the second year of life: prediction and moderation by responsive parenting.

PubMed

Wade, Mark; Madigan, Sheri; Akbari, Emis; Jenkins, Jennifer M

2015-01-01

At 18 months, children show marked variability in their social-cognitive skill development, and the preponderance of past research has focused on constitutional and contextual factors in explaining this variability. Extending this literature, the current study examined whether cumulative biomedical risk represents another source of variability in social cognition at 18 months. Further, we aimed to determine whether responsive parenting moderated the association between biomedical risk and social cognition. A prospective community birth cohort of 501 families was recruited at the time of the child's birth. Cumulative biomedical risk was measured as a count of 10 prenatal/birth complications. Families were followed up at 18 months, at which point social-cognitive data was collected on children's joint attention, empathy, cooperation, and self-recognition using previously validated tasks. Concurrently, responsive maternal behavior was assessed through observational coding of mother-child interactions. After controlling for covariates (e.g., age, gender, child language, socioeconomic variables), both cumulative biomedical risk and maternal responsivity significantly predicted social cognition at 18 months. Above and beyond these main effects, there was also a significant interaction between biomedical risk and maternal responsivity, such that higher biomedical risk was significantly associated with compromised social cognition at 18 months, but only in children who experienced low levels of responsive parenting. For those receiving comparatively high levels of responsive parenting, there was no apparent effect of biomedical risk on social cognition. This study shows that cumulative biomedical risk may be one source of inter-individual variability in social cognition at 18 months. However, positive postnatal experiences, particularly high levels of responsive parenting, may protect children against the deleterious effects of these risks on social cognition.

The Impact of Ecological Risk and Perceived Discrimination on the Psychological Adjustment of African American and European American Youth

ERIC Educational Resources Information Center

Prelow, Hazel M.; Danoff-Burg, Sharon; Swenson, Rebecca R.; Pulgiano, Dana

2004-01-01

The purpose of the present study was to examine the role of cumulative ecological risk (i.e., neighborhood disadvantage and ecologically salient stressful events) and perceived discrimination on the psychological adjustment of urban African American and European American youth. Findings indicated that both cumulative ecological risk and perceived…

Metabolic Risk Factors and Type 2 Diabetes Incidence in American Indian Children.

PubMed

Wheelock, Kevin M; Sinha, Madhumita; Knowler, William C; Nelson, Robert G; Fufaa, Gudeta D; Hanson, Robert L

2016-04-01

Data are lacking on how metabolic risk factors during childhood affect the long-term risk of type 2 diabetes. Assess four metabolic risk factors as predictors of type 2 diabetes and determine whether the risk differs between younger and older children. In a prospective cohort study conducted between 1965 and 2007, participants were followed for development of diabetes. Baseline measurements included body mass index (BMI), blood pressure, serum cholesterol, and 2-hour plasma glucose after an oral glucose tolerance test. Additional analyses divided subjects into two groups according to baseline age, 5–11 and 12–19 years. Gila River Indian Community in Arizona. A total of 5532 nondiabetic Pima Indian children 5–19 years old. A total of 1281 children developed diabetes (median follow-up, 12.4 years). Diabetes incidence was higher in overweight children (BMI ≥ 85th percentile) than in nonoverweight children. Nonoverweight children had the lowest risk of diabetes (20-year cumulative incidence, 9.5%), whereas overweight children with impaired glucose tolerance (2-hour glucose ≥ 140 mg/dL) had the highest (79.0%). The relative risk for children with metabolic abnormalities compared with their healthy counterparts was higher in younger children than in older children early in follow-up. BMI and 2-hour glucose were related to incident diabetes in multivariable models (predicted 15-year cumulative incidence for the highest vs lowest quartile was 3.9 and 1.8 times as high for BMI and 2-hour glucose, respectively; P < .001), whereas blood pressure and cholesterol were not. BMI and impaired glucose tolerance in children are strong predictors of type 2 diabetes. Other components of the “metabolic syndrome” are not.

The effect of start and stop age at screening on the risk of being diagnosed with prostate cancer

PubMed Central

Arnsrud Godtman, Rebecka; Carlsson, Sigrid; Holmberg, Erik; Stranne, Johan; Hugosson, Jonas

2016-01-01

Purpose The aim of this study was to investigate the effect of age and number of screens on the risk of prostate cancer (PCa) diagnosis. Materials and Methods The Göteborg randomized population-based PCa screening trial has, since 1995, invited men biennially for prostate-specific antigen (PSA)-testing, until the upper age limit 70 years. Men with a PSA-level above the threshold ≥2.5 ng/ml were recommended further work-up including 10-core biopsy (sextant before 2009). The present study comprises 9,065 men born 1930–43 (1944 excluded due to different screening algorithm). Complete attendees were defined as men who accepted all screening invitations (maximum 3–9 invitations). Cumulative incidence of PCa was calculated using standard methods. Results Of the 3,488 (38%) complete attendees, 667 were diagnosed with PCa (follow-up 1995–30 Jun 2014). At the age 70, there was no significant difference in PCa risk between those who started screening at the age of 52 (9 screens), 55 (7 screens) or 60 (5 screens) years. However, the cumulative risk of PCa diagnosis increased dramatically with age and was 7.9% at age 60, 15% at age 65 and 21% at age 70, for men who had been screened ≥4 times. Conclusion There was no clear association between risk of PCa and the number of screens. Starting screening at an early age appears to advance the time of PCa diagnosis but does not seem to increase the risk of being diagnosed with the disease. Age at termination of screening is strongly associated with the risk of being diagnosed with PCa. PMID:26678954

Identifying important life stages for monitoring and assessing risks from exposures to environmental contaminants: results of a World Health Organization review.

PubMed

Cohen Hubal, Elaine A; de Wet, Thea; Du Toit, Lilo; Firestone, Michael P; Ruchirawat, Mathuros; van Engelen, Jacqueline; Vickers, Carolyn

2014-06-01

In this paper, we summarize exposure-related issues to consider in determining the most appropriate age ranges and life stages for risk assessment. We then propose a harmonized set of age bins for monitoring and assessing risks from exposures to chemicals for global use. The focus is on preconception through adolescence, though the approach should be applicable to additional life stages. A two-tiered set of early life age groups is recommended. The first tier involves the adoption of guidance similar to the childhood age groups recommended by the U.S. Environmental Protection Agency, whereas the second tier consolidates some of those age groups to reduce the burden of developing age-specific exposure factors for different regions. While there is no single "correct" means of choosing a common set of age groups to use internationally in assessing early life exposure and risk, use of a set of defined age groups is recommended to facilitate comparisons of potential exposures and risks around the globe, the collection of data and analyses of aggregate exposure and cumulative risk. Application of these age groups for robust assessment of exposure and risk for specific populations will require region-specific exposure factors as well as local environmental monitoring data. Copyright © 2013 World Health Organization. Published by Elsevier Inc. All rights reserved.

Early Restoration PEIS Public Meeting | NOAA Gulf Spill Restoration

Science.gov Websites

, or PEIS, to evaluate the potential environmental effects of types of early restoration actions, as Early Restoration Plan. The PEIS also will evaluate the cumulative effects of early restoration. We are

Tools Available to Communities for Conducting Cumulative Exposure and Risk Assessments

EPA Science Inventory

This paper summarizes and assesses over 70 tools that could aid with gathering information and taking action on environmental issues related to community-based cumulative risk assessments (CBCRA). Information on tool use, development and research needs, was gathered from websites...

A Summary of Publications on Methods and Tools for Assessing Cumulative Risk, Project Summary

EPA Science Inventory

This collection of eight publications on cumulative risk assessment was developed collaboratively among scientists within EPA’s Office of Research and Development and three other organizations. These include scientific collaborations through an Interagency Agreement with Argonne...

Participant selection for lung cancer screening by risk modelling (the Pan-Canadian Early Detection of Lung Cancer [PanCan] study): a single-arm, prospective study.

PubMed

Tammemagi, Martin C; Schmidt, Heidi; Martel, Simon; McWilliams, Annette; Goffin, John R; Johnston, Michael R; Nicholas, Garth; Tremblay, Alain; Bhatia, Rick; Liu, Geoffrey; Soghrati, Kam; Yasufuku, Kazuhiro; Hwang, David M; Laberge, Francis; Gingras, Michel; Pasian, Sergio; Couture, Christian; Mayo, John R; Nasute Fauerbach, Paola V; Atkar-Khattra, Sukhinder; Peacock, Stuart J; Cressman, Sonya; Ionescu, Diana; English, John C; Finley, Richard J; Yee, John; Puksa, Serge; Stewart, Lori; Tsai, Scott; Haider, Ehsan; Boylan, Colm; Cutz, Jean-Claude; Manos, Daria; Xu, Zhaolin; Goss, Glenwood D; Seely, Jean M; Amjadi, Kayvan; Sekhon, Harmanjatinder S; Burrowes, Paul; MacEachern, Paul; Urbanski, Stefan; Sin, Don D; Tan, Wan C; Leighl, Natasha B; Shepherd, Frances A; Evans, William K; Tsao, Ming-Sound; Lam, Stephen

2017-11-01

Results from retrospective studies indicate that selecting individuals for low-dose CT lung cancer screening on the basis of a highly predictive risk model is superior to using criteria similar to those used in the National Lung Screening Trial (NLST; age, pack-year, and smoking quit-time). We designed the Pan-Canadian Early Detection of Lung Cancer (PanCan) study to assess the efficacy of a risk prediction model to select candidates for lung cancer screening, with the aim of determining whether this approach could better detect patients with early, potentially curable, lung cancer. We did this single-arm, prospective study in eight centres across Canada. We recruited participants aged 50-75 years, who had smoked at some point in their life (ever-smokers), and who did not have a self-reported history of lung cancer. Participants had at least a 2% 6-year risk of lung cancer as estimated by the PanCan model, a precursor to the validated PLCOm2012 model. Risk variables in the model were age, smoking duration, pack-years, family history of lung cancer, education level, body-mass index, chest x-ray in the past 3 years, and history of chronic obstructive pulmonary disease. Individuals were screened with low-dose CT at baseline (T0), and at 1 (T1) and 4 (T4) years post-baseline. The primary outcome of the study was incidence of lung cancer. This study is registered with ClinicalTrials.gov, number NCT00751660. 7059 queries came into the study coordinating centre and were screened for PanCan risk. 15 were duplicates, so 7044 participants were considered for enrolment. Between Sept 24, 2008, and Dec 17, 2010, we recruited and enrolled 2537 eligible ever-smokers. After a median follow-up of 5·5 years (IQR 3·2-6·1), 172 lung cancers were diagnosed in 164 individuals (cumulative incidence 0·065 [95% CI 0·055-0·075], incidence rate 138·1 per 10 000 person-years [117·8-160·9]). There were ten interval lung cancers (6% of lung cancers and 6% of individuals with cancer): one diagnosed between T0 and T1, and nine between T1 and T4. Cumulative incidence was significantly higher than that observed in NLST (4·0%; p<0·0001). Compared with 593 (57%) of 1040 lung cancers observed in NLST, 133 (77%) of 172 lung cancers in the PanCan Study were early stage (I or II; p<0·0001). The PanCan model was effective in identifying individuals who were subsequently diagnosed with early, potentially curable, lung cancer. The incidence of cancers detected and the proportion of early stage cancers in the screened population was higher than observed in previous studies. This approach should be considered for adoption in lung cancer screening programmes. Terry Fox Research Institute and Canadian Partnership Against Cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Phthalates and Cumulative Risk Assessment (NAS Final ...

EPA Pesticide Factsheets

On December 18, 2008, the National Academy of Sciences' National Research Council released a final report, requested and sponsored by the EPA, entitled Phthalates and Cumulative Risk Assessment: The Task Ahead. Risk assessment has become a dominant public policy tool for making choices, based on limited resources, to protect public health and the environment. It has been instrumental to the mission of the U.S. Environmental Protection Agency (EPA) as well as other federal agencies in evaluating public health concerns, informing regulatory and technological decisions, prioritizing research needs and funding, and in developing approaches for cost-benefit analysis. People are exposed to a variety of chemicals throughout their daily lives. To protect public health, regulators use risk assessments to examine the effects of chemical exposures. This book provides guidance for assessing the risk of phthalates, chemicals found in many consumer products that have been shown to affect the development of the male reproductive system of laboratory animals. Because people are exposed to multiple phthalates and other chemicals that affect male reproductive development, a cumulative risk assessment should be conducted that evaluates the combined effects of exposure to all these chemicals. The book suggests an approach for cumulative risk assessment that can serve as a model for evaluating the health risks of other types of chemicals.

Projected lifetime risks and hospital care expenditure for traumatic injury.

PubMed

Chang, David C; Anderson, Jamie E; Kobayashi, Leslie; Coimbra, Raul; Bickler, Stephen W

2012-08-01

The lifetime risk and expected cost of trauma care would be valuable for health policy planners, but this information is currently unavailable. The cumulative incidence rates methodology, based on a cross-sectional population analysis, offers an alternative approach to prohibitively costly prospective cohort studies. Retrospective analysis of the California Office of Statewide Health Planning and Development (OSHPD) database was performed for 2008. Trauma admissions were identified by ICD-9 primary diagnosis codes 800-959, with certain exclusions. Cumulative incidence rates were calculated as the cumulative summation of incidence risks sequentially across age groups. A total of 2.2 million admissions were identified, with mean age of 63.8 y, 49.6% men, 82.8% Whites, 5.7% Blacks, 11.3% Hispanics, and 3.1% Asians. The cumulative incidence rate for patients older than age 85 y was 1119 per 10,000 people, with the majority of risk in the elderly, compared with 24,325 per 10,000 people for all-cause hospitalizations. The rates were 946 for men, 1079 for women, 999 for non-Hispanic Whites, 568 for Blacks, 577 for Hispanics, and 395 for Asians, per 10,000 population. The cumulative expected hospital charge was $6538, compared with $81,257 for all-cause hospitalizations. The cumulative lifetime risk of trauma/injury requiring hospitalization for a person living to age 85 y in California is 11.2%, accounting for 4.6% of expected lifetime hospitalizations, but accounting for 8.0% of expected lifetime hospital expenditures. Risk of trauma is significant in the elderly. The total expenditure for all trauma hospitalizations in California was $7.62 billion in 2008. Copyright © 2012 Elsevier Inc. All rights reserved.

Childhood poverty and health: cumulative risk exposure and stress dysregulation.

PubMed

Evans, Gary W; Kim, Pilyoung

2007-11-01

A massive literature documents the inverse association between poverty or low socioeconomic status and health, but little is known about the mechanisms underlying this robust relation. We examined longitudinal relations between duration of poverty exposure since birth, cumulative risk exposure, and physiological stress in two hundred seven 13-year-olds. Chronic stress was assessed by basal blood pressure and overnight cortisol levels; stress regulation was assessed by cardiovascular reactivity to a standard acute stressor and recovery after exposure to this stressor. Cumulative risk exposure was measured by multiple physical (e.g., substandard housing) and social (e.g., family turmoil) risk factors. The greater the number of years spent living in poverty, the more elevated was overnight cortisol and the more dysregulated was the cardiovascular response (i.e., muted reactivity). Cardiovascular recovery was not affected by duration of poverty exposure. Unlike the duration of poverty exposure, concurrent poverty (i.e., during adolescence) did not affect these physiological stress outcomes. The effects of childhood poverty on stress dysregulation are largely explained by cumulative risk exposure accompanying childhood poverty.

The effects of cumulative risks and promotive factors on urban adolescent alcohol and other drug use: a longitudinal study of resiliency.

PubMed

Ostaszewski, Krzysztof; Zimmerman, Marc A

2006-12-01

Resiliency theory provides a conceptual framework for studying why some youth exposed to risk factors do not develop the negative behaviors they predict. The purpose of this study was to test compensatory and protective models of resiliency in a longitudinal sample of urban adolescents (80% African American). The data were from Years 1 (9th grade) and 4 (12th grade). The study examined effects of cumulative risk and promotive factors on adolescent polydrug use including alcohol, tobacco and marijuana. Cumulative measures of risk/promotive factors represented individual characteristics, peer influence, and parental/familial influences. After controlling for demographics, results of multiple regression of polydrug use support the compensatory model of resiliency both cross-sectionally and longitudinally. Promotive factors were also found to have compensatory effects on change in adolescent polydrug use. The protective model of resiliency evidenced cross-sectionally was not supported in longitudinal analysis. The findings support resiliency theory and the use of cumulative risk/promotive measures in resiliency research. Implications focused on utilizing multiple assets and resources in prevention programming are discussed.

Prospective assessment of bone turnover and clinical bone diseases after allogeneic hematopoietic stem-cell transplantation.

PubMed

Petropoulou, Anna D; Porcher, Raphael; Herr, Andrée-Laure; Devergie, Agnès; Brentano, Thomas Funck; Ribaud, Patricia; Pinto, Fernando O; Rocha, Vanderson; Peffault de Latour, Régis; Orcel, Philippe; Socié, Gérard; Robin, Marie

2010-06-15

Bone complications after hematopoietic stem-cell transplantation (HSCT) are relatively frequent. Evaluation of biomarkers of bone turnover and dual energy x-ray absorptiometry (DEXA) are not known in this context. We prospectively evaluated bone mineral density, biomarkers of bone turnover, and the cumulative incidence of bone complications after allogeneic HSCT. One hundred forty-six patients were included. Bone mineral density was measured by DEXA 2-month and 1-year post-HSCT. The markers of bone turnover were serum C-telopeptide (C-TP), 5 tartrate-resistant acid phosphatase (bone resorption), and osteocalcin (bone formation) determined pre-HSCT and 2 months and 1 year thereafter. Potential association between osteoporosis at 2 months, osteoporotic fracture or avascular necrosis and, individual patient's characteristics and biologic markers were tested. C-TP was high before and 2 months after transplant. At 2 months, DEXA detected osteoporosis in more than half the patients tested. Male sex, median age less than or equal to 15 years, and abnormal C-TP before HSCT were risk factors significantly associated with osteoporosis. Three-year cumulative incidences of fractures and avascular necrosis were 8% and 11%, respectively. Children were at higher risk of fracture, whereas corticosteroid treatment duration was a significant risk factor for developing a clinical bone complication post-HSCT. Bone complications and osteoporosis are frequent after HSCT. Bone biologic markers and DEXA showed that subclinical bone abnormalities appeared early post-HSCT. The risk factors, age, gender, and C-TP easily available at the time of transplantation were identified. Biphosphonates should probably be given to patients with those risk factors.

Economic assessment of home-based COPD management programs.

PubMed

Liu, Sheena Xin; Lee, Michael C; Atakhorrami, Maryam; Tatousek, Jan; McCormack, Meredith; Yung, Rex; Hart, Nicholas; White, David P

2013-12-01

Home-based exacerbation management programs have been proposed as an approach to reducing the clinical and financial burden of COPD. We demonstrate a framework to evaluate such programs in order to guide program design and performance decisions towards optimizing cost and clinical outcomes. This study models the impact of hypothetical exacerbation management programs through probabilistic Markov simulations. Patients were stratified by risk using exacerbation rates from the ECLIPSE study and expert opinion. Three scenarios were modeled, using base, worst and best case parameters to suggest potential telehealth program performance. In these scenarios, acute exacerbations could be detected early, with sensitivity and specificity ranging from 60-90%. Detected acute exacerbations could be diverted to either a sub-acute pathway (12.5-50% probability), thus entirely avoiding hospitalization, or a lower cost pathway through length-of-stay reduction (14-28% reduction). For a cohort of patients without prior hospitalization, the base case telehealth scenario results in a cumulative per-patient lifetime savings of $2.9 K over ≈ 12 years. For a higher risk cohort of patients with a prior admission and 1 to 2 acute exacerbations per year, a cumulative $16K per patient was saved during the remaining ≈ 3 life-years. Acceptable prices for home-based exacerbation detection testing were highly dependent on patient risk and scenario, but ranged from $290-$1263 per month for the highest risk groups. These results suggest the economic viability of exacerbation management programs and highlight the importance of risk stratification in such programs. The presented model can further be adapted to model specific programs as trial data becomes available.

DOSE-RESPONSE MODELING FOR THE ASSESSMENT OF CUMULATIVE RISK DUE TO EXPOSURE TO N-METHYL CARBAMATE PESTICIDES

EPA Science Inventory

The US EPAs N-Methyl Carbamate Cumulative Risk Assessment (NMCRA) assesses the effect on acetylcholine esterase (AChE) activity of exposure to 10 N-methyl carbamate (NMC) pesticides through dietary, drinking water, and residential exposures.

CUMULATIVE RISK ASSESSMENT FOR QUANTITATIVE RESPONSE DATA

EPA Science Inventory

The Relative Potency Factor approach (RPF) is used to normalize and combine different toxic potencies among a group of chemicals selected for cumulative risk assessment. The RPF method assumes that the slopes of the dose-response functions are all equal; but this method depends o...

Community, State, and Federal Approaches to Cumulative Risk Assessment: Challenges and Opportunities for Integration

EPA Science Inventory

Community, state, and federal approaches to conventional and cumulative risk assessment (CRA) were described and compared to assess similarities and differences, and develop recommendations for a consistent CRA approach, acceptable across each level as a rigorous scientific metho...

Repeated exposure to high-frequency spanking and child externalizing behavior across the first decade: a moderating role for cumulative risk.

PubMed

MacKenzie, Michael J; Nicklas, Eric; Brooks-Gunn, Jeanne; Waldfogel, Jane

2014-12-01

This study used the Fragile Families and Child Well-Being Study to examine the effects of repeated exposure to harsh parenting on child externalizing behavior across the first decade of life, and a moderating role for cumulative ecological risk. Maternal report of harsh parenting, defined as high frequency spanking, was assessed at age 1, 3, 5, and 9, along with child externalizing at age 9 (N=2,768). Controlling for gender, race, maternal nativity, and city of residence, we found a cumulative risk index to significantly moderate the effects of repeated harsh parenting on child behavior, with the effects of repeated high-frequency spanking being amplified for those experiencing greater levels of cumulative risk. Harsh parenting, in the form of high frequency spanking, remains a too common experience for children, and results demonstrate that the effects of repeated exposure to harsh parenting across the first decade are amplified for those children already facing the most burden. Copyright © 2014. Published by Elsevier Ltd.

Repeated exposure to high-frequency spanking and child externalizing behavior across the first decade: A moderating role for cumulative risk

PubMed Central

MacKenzie, Michael J.; Nicklas, Eric; Brooks-Gunn, Jeanne; Waldfogel, Jane

2016-01-01

This study used the Fragile Families and Child Well-being study to examine the effects of repeated exposure to harsh parenting on child externalizing behavior across the first decade of life, and a moderating role for cumulative ecological risk. Maternal report of harsh parenting, defined as high frequency spanking, was assessed at age 1, 3, 5, and 9, along with child externalizing at age 9 (N=2768). Controlling for gender, race, maternal nativity, and city of residence, we found a cumulative risk index to significantly moderate the effects of repeated harsh parenting on child behavior, with the effects of repeated high-frequency spanking being amplified for those experiencing greater levels of cumulative risk. Harsh parenting, in the form of high frequency spanking, remains a too common experience for children, and results demonstrate that the effects of repeated exposure to harsh parenting across the first decade are amplified for those children already facing the most burden. PMID:25465318

Mismatch or cumulative stress: toward an integrated hypothesis of programming effects.

PubMed

Nederhof, Esther; Schmidt, Mathias V

2012-07-16

This paper integrates the cumulative stress hypothesis with the mismatch hypothesis, taking into account individual differences in sensitivity to programming. According to the cumulative stress hypothesis, individuals are more likely to suffer from disease as adversity accumulates. According to the mismatch hypothesis, individuals are more likely to suffer from disease if a mismatch occurs between the early programming environment and the later adult environment. These seemingly contradicting hypotheses are integrated into a new model proposing that the cumulative stress hypothesis applies to individuals who were not or only to a small extent programmed by their early environment, while the mismatch hypothesis applies to individuals who experienced strong programming effects. Evidence for the main effects of adversity as well as evidence for the interaction between adversity in early and later life is presented from human observational studies and animal models. Next, convincing evidence for individual differences in sensitivity to programming is presented. We extensively discuss how our integrated model can be tested empirically in animal models and human studies, inviting researchers to test this model. Furthermore, this integrated model should tempt clinicians and other intervenors to interpret symptoms as possible adaptations from an evolutionary biology perspective. Copyright © 2011 Elsevier Inc. All rights reserved.

[Theoretical evaluation of the risk of decompression illness during simulated extravehicular activity].

PubMed

Nikolaev, V P

2008-01-01

Theoretical analysis of the risk of decompression illness (DI) during extravehicular activity following the Russian and NASA decompression protocols (D-R and D-US, respectively) was performed. In contrast to the tradition approach to decompression stress evaluation by the factor of tissue supersaturation with nitrogen, our probabilistic theory of decompression safety provides a completely reasoned evaluation and comparison of the levels of hazard of these decompression protocols. According to this theory, the function of cumulative DI risk is equal to the sum of functions of cumulative risk of lesion of all body tissues by gas bubbles and their supersaturation by solute gases. Based on modeling of dynamics of these functions, growth of the DI cumulative risk in the course of D-R and D-US follows essentially similar trajectories within the time-frame of up to 330 minutes. However, further extension of D-US but not D-R raises the risk of DI drastically.

USING DOSE ADDITION TO ESTIMATE CUMULATIVE RISKS FROM EXPOSURES TO MULTIPLE CHEMICALS

EPA Science Inventory

The Food Quality Protection Act (FQPA) of 1996 requires the EPA to consider the cumulative risk from exposure to multiple chemicals that have a common mechanism of toxicity. Three methods, hazard index (HI), point-of-departure index (PODI), and toxicity equivalence factor (TEF), ...

CUMULATIVE RISK ASSESSMENT: GETTING FROM TOXICOLOGY TO QUANTITATIVE ANALYSIS

EPA Science Inventory

INTRODUCTION: GETTING FROM TOXICOLOGY TO QUANTITATIVE ANALYSIS FOR CUMULATIVE RISK

Hugh A. Barton1 and Carey N. Pope2
1US EPA, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC
2Department of...

Consideration of the FQPA Safety Factor and Other Uncertainty Factors in Cumulative Risk Assessment of Chemicals Sharing a Common Mechanism of Toxicity

EPA Pesticide Factsheets

This guidance document provides OPP's current thinking on application of the provision in FFDCA about an additional safety factor for the protection of infants and children in the context of cumulative risk assessments.

TESTING STRATEGIES TO ESTIMATE NEUROTOXIC RISK FOR CUMULATIVE EXPOSURE TO PYRETHROID MIXTURES.

EPA Science Inventory

The Food Quality Protection Act requires EPA to consider the cumulative risk of pesticides with

a common mechanism-of-toxicity. Evidence supports a mechanistic commonality for pyrethroid

insecticides: these chemicals all act on neuronal sodium channels. The lack of ...

Identification and Quantification of Cumulative Factors that Increase Environmental Exposures and Impacts

EPA Science Inventory

Evaluating the combined adverse effects of multiple stressors upon human health is an imperative component of cumulative risk assessment (CRA)1. In addition to chemical stressors, other non-chemical factors are also considered. For examples, smoking will elevate the risks of havi...

Avoiding the Major Causes of Death: Does Childhood Misfortune Reduce the Likelihood of Being Disease Free in Later Life?

PubMed

Williams, Monica M; Kemp, Blakelee R; Ferraro, Kenneth F; Mustillo, Sarah A

2018-04-03

Although previous research reveals the detrimental effects of early misfortune on the development of chronic diseases in later life, few studies have investigated its effects on remaining disease free. This study draws on cumulative inequality theory to investigate whether experiencing childhood misfortune reduces the likelihood of remaining disease free over time. This study utilizes five waves of data from the Health and Retirement Study to test whether five domains of childhood misfortune predict being disease free at baseline (2004) and developing disease over time (2004-2012). Respondents reporting risky parental behaviors during childhood were less likely to be disease free at baseline and had an increased risk of disease onset over time, the latter driven by having a guardian who smoked in combination with more pack-years smoked in adulthood. Furthermore, we find that adult resources, i.e. wealth, help to mitigate the noxious effects of other misfortunes, notably poor socioeconomic conditions. Consistent with cumulative inequality theory, these findings reveal that experiencing multiple types of misfortune during childhood decreases the likelihood of remaining disease free in later life, but engaging in health behaviors, such as physical activity, can help to ameliorate some of the noxious effects of early misfortune.

Asbestos-related lung cancer and malignant mesothelioma of the pleura: selected current issues.

PubMed

Markowitz, Steven

2015-06-01

Asbestos-related diseases persist, because millions of workers have had prior exposure and many industrializing countries continue to use asbestos. Globally, an estimated 107,000 people die annually from lung cancer, malignant mesothelioma, and asbestosis due to occupational asbestos exposure. Malignant mesothelioma and lung cancer are caused by all major types of asbestos. Asbestos causes more lung cancer deaths than malignant mesothelioma of the pleura; most cases of the latter are due to asbestos exposure. The cancer risk increases with cumulative asbestos exposure, with increased risk even at low levels of exposure to asbestos. Based on empirical studies, an estimated cumulative occupational exposure to asbestos of 1 fiber/mL-year substantially raises malignant mesothelioma risk. No safe threshold for asbestos exposure has been established for lung cancer and mesothelioma. The validity of fiber-type risk assessments depends critically on the quality of exposure assessments, which vary considerably, leading to a high degree of uncertainty. Asbestos exposure without asbestosis and smoking increases the risk of lung cancer. The joint effect of asbestos and smoking is supra-additive, which may depend in part on the presence of asbestosis. Asbestos workers who cease smoking experience a dramatic drop in lung cancer risk, which approaches that of nonsmokers after 30 years. Studies to date show that longer, thinner fibers have a stronger association with lung cancer than shorter, less thin fibers, but the latter nonetheless also show an association with lung cancer and mesothelioma. Low-dose chest computed tomographic scanning offers an unprecedented opportunity to detect early-stage lung cancers in asbestos-exposed workers. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Epidemiology of estrogen and dementia in women with Down syndrome.

PubMed

Schupf, Nicole; Lee, Joseph H; Pang, Deborah; Zigman, Warren B; Tycko, Benjamin; Krinsky-McHale, Sharon; Silverman, Wayne

2018-01-01

Several lines of investigation have shown a protective role for estrogen in Alzheimer's disease through a number of biological actions. This review examines studies of the role of estrogen-related factors in age at onset and risk for Alzheimer's disease in women with Down syndrome, a population at high risk for early onset of dementia. The studies are consistent in showing that early age at menopause and that low levels of endogenous bioavailable estradiol in postmenopausal women with Down syndrome are associated with earlier age at onset and overall risk for dementia. Polymorphisms in genes associated with estrogen receptor activity and in genes for estrogen biosynthesis affecting endogenous estrogen are related to age at onset and cumulative incidence of dementia, and may serve as biomarkers of risk. To date, no clinical trials of estrogen or hormone replacement therapy (ERT/HRT) have been published for women with Down syndrome. While findings from clinical trials of ERT or HRT for dementia have generally been negative among women in the neurotypical population, the short interval between menopause and onset of cognitive decline, together with a more positive balance between potential benefits and risks, suggests an opportunity to evaluate the efficacy of ERT/HRT for delaying or preventing dementia in this high risk population, although questions concerning the optimal formulation and timing of the hormone therapy are not yet resolved. Copyright © 2017 Elsevier Inc. All rights reserved.

Estimating the burden of recurrent events in the presence of competing risks: the method of mean cumulative count.

PubMed

Dong, Huiru; Robison, Leslie L; Leisenring, Wendy M; Martin, Leah J; Armstrong, Gregory T; Yasui, Yutaka

2015-04-01

Cumulative incidence has been widely used to estimate the cumulative probability of developing an event of interest by a given time, in the presence of competing risks. When it is of interest to measure the total burden of recurrent events in a population, however, the cumulative incidence method is not appropriate because it considers only the first occurrence of the event of interest for each individual in the analysis: Subsequent occurrences are not included. Here, we discuss a straightforward and intuitive method termed "mean cumulative count," which reflects a summarization of all events that occur in the population by a given time, not just the first event for each subject. We explore the mathematical relationship between mean cumulative count and cumulative incidence. Detailed calculation of mean cumulative count is described by using a simple hypothetical example, and the computation code with an illustrative example is provided. Using follow-up data from January 1975 to August 2009 collected in the Childhood Cancer Survivor Study, we show applications of mean cumulative count and cumulative incidence for the outcome of subsequent neoplasms to demonstrate different but complementary information obtained from the 2 approaches and the specific utility of the former. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Subsequent neoplasms in survivors of childhood central nervous system tumors: risk after modern multimodal therapy.

PubMed

Tsui, Karen; Gajjar, Amar; Li, Chenghong; Srivastava, Deokumar; Broniscer, Alberto; Wetmore, Cynthia; Kun, Larry E; Merchant, Thomas E; Ellison, David W; Orr, Brent A; Boop, Frederick A; Klimo, Paul; Ross, Jordan; Robison, Leslie L; Armstrong, Gregory T

2015-03-01

Multimodal therapy has improved survival for some childhood CNS tumors. However, whether risk for subsequent neoplasms (SNs) also increases is unknown. We report the cumulative incidence of, and risk factors for, SNs after a childhood primary CNS tumor and determine whether treatment that combines radiation therapy (RT) with chemotherapy increases risk for SNs. Analyses included 2779 patients with a primary CNS tumor treated at St Jude Children's Research Hospital between 1985 and 2012. Cumulative incidence and standardized incidence ratios (SIRs) were estimated for SNs confirmed by pathology report. Cumulative incidence among the 237 five-year medulloblastoma survivors treated with multimodal therapy (RT + chemotherapy) was compared with a historical cohort of 139 five-year survivors treated with RT but no chemotherapy in the Childhood Cancer Survivor Study. Eighty-one survivors had 97 SNs. The cumulative incidence of first SN was 3.0% (95% CI: 2.3%-3.9%) at 10 years, and 6.0% (95% CI: 4.6%-7.7%) at 20 years from diagnosis. Risks were highest for subsequent glioma, all grades (SIR = 57.2; 95% CI: 36.2-85.8) and acute myeloid leukemia (SIR = 31.8; 95% CI: 10.2-74.1). Compared with RT alone, RT + chemotherapy did not increase risk for SNs (hazard ratio: 0.64; 95% CI: 0.38-1.06). Among five-year survivors of medulloblastoma treated with multimodal therapy, cumulative incidence of SN was 12.0% (95% CI: 6.4%-19.5%) at 20 years, no different than survivors treated with RT alone (11.3%, P = .44). The cumulative incidence of SNs continues to increase with time from treatment with no obvious plateau, but the risk does not appear to be higher after exposure to multimodal therapy compared with RT alone. Continued follow-up of survivors as they age is essential. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Adenosine triphosphate stress myocardial perfusion imaging for risk stratification of patients aged 70 years and older with suspected coronary artery disease.

PubMed

Yao, Zhiming; Zhu, Hui; Li, Wenchan; Chen, Congxia; Wang, Hua; Shi, Lei; Zhang, Wenjie

2017-04-01

We investigated the cardiac risk stratification value of adenosine triphosphate stress myocardial perfusion imaging (ATP-MPI) in patients aged 70 years and older with suspected coronary artery disease (CAD). We identified a series of 415 consecutive patients aged 70 years and older with suspected CAD, who had undergone ATP-MPI with 99m Tc-MIBI. The presence of a fixed and/or reversible perfusion defect was considered as an abnormal MPI. Follow-up was available in 399 patients (96.1%) over 3.45 ± 1.71 years after excluding 16 patients who underwent early coronary revascularization <60 days after MPI. The major adverse cardiac events (MACE), including cardiac death, nonfatal infarction, and late coronary revascularization, were recorded. One hundred twenty-five (31.3%) patients had abnormal MPI and the remaining had normal MPI. A multivariable analysis using Cox regression demonstrated that abnormal MPI was independently associated with MACE (hazard ratio 19.50 and 95% confidence interval 5.91-64.31, P value .000). The patients with SSS > 8 had significantly higher cumulative MACE rate than patients with SSS ≤ 8 had (37.8% vs 5.2%, respectively, P < .001). The Kaplan-Meier cumulative MACE-free survival in patients with abnormal MPI (57.0%) was significantly lower than that in patients with normal MPI (89.6%), P < .0001. Among patients with SSS > 8, the Kaplan-Meier cumulative MACE-free survival were 36.9% in patients ≥80 years old and 49.5% in patients 70-79 years old, respectively, P < .05. However, among patients with SSS ≤ 8, there was no difference between the Kaplan-Meier cumulative MACE-free survivals of these two age groups. ATP-MPI data are useful for the prediction of major adverse cardiac events in patients aged 70 years and older with suspected CAD.

Is Cumulative Exposure to Suicide Attempts and Deaths A Risk Factor for Suicidal Behavior among Firefighters? A Preliminary Study

PubMed Central

Kimbrel, Nathan A.; Pennington, Michelle L.; Cammarata, Claire M.; Leto, Frank; Ostiguy, William J.; Gulliver, Suzy B.

2016-01-01

The present study examined the association between cumulative exposure to suicide attempts and deaths and suicidal behavior in a sample of 61 professional firefighters. On average, firefighters reported 13.1 (SD=16.6) exposures over the course of their lifetime. Cumulative exposure to suicide attempts and deaths was positively correlated with suicidal behavior (r = 0.38, p = 0.004). Moreover, firefighters with 12+ exposures were more likely to screen positive for risk of suicidal behavior (OR = 7.885, p = 0.02). Additional research on the potential impact of cumulative exposure to suicide attempts and deaths on firefighters’ health and safety is needed. PMID:27371810

A Case Study Application of the Aggregate Exposure Pathway (AEP) and Adverse Outcome Pathway (AOP) Frameworks to Facilitate the Integration of Human Health and Ecological End Points for Cumulative Risk Assessment (CRA)

EPA Science Inventory

Cumulative risk assessment (CRA) methods promote the use of a conceptual site model (CSM) to apportion exposures and integrate risk from multiple stressors. While CSMs may encompass multiple species, evaluating end points across taxa can be challenging due to data availability an...

Estimating Greenspace Exposure and Benefits for Cumulative Risk Assessment Applications (Summary Report)

EPA Science Inventory

This document provides a summary of the technical meeting on greenspace (GS) and cumulative risk assessment convened May 4−5, 2015 in Cincinnati, OH, by the U.S. Environmental Protection Agency (EPA) Office of Research and Development (ORD) National Center for Environmental As...

PHYSIOLOGICALLY-BASED PHARMACOKINETICS/PHARMACODYNAMIC MODELING AND CUMULATIVE RISK ASSESSMENT: CASE STUDY FOR THE N-METHYL CARBMATE PESTICIDES

EPA Science Inventory

The Food Quality Protection Act of 1996 [PL 104-170: 110 STAT. 1513] requires EPA to consider potential cumulative human health risks resulting from aggregate exposure to pesticide chemicals acting through a common mechanism of toxicity. This includes all anticipated dietary e...

Cumulative Experiences of Violence among High-Risk Urban Youth

ERIC Educational Resources Information Center

Taylor, Catherine A.; Boris, Neil W.; Heller, Sherryl Scott; Clum, Gretchen A.; Rice, Janet C.; Zeanah, Charles H.

2008-01-01

This study examines type-specific and cumulative experiences of violence among a vulnerable population of youth. Sixty high-risk, shelter-dwelling, urban youth were interviewed regarding their history of childhood maltreatment, exposure to community violence (ECV), and experience with intimate partner violence (IPV). Results show a high prevalence…

75 FR 52360 - Upper Truckee River Restoration and Golf Course Reconfiguration Project, El Dorado County, CA

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-25

...: Short-term risk of surface water or groundwater degradation during construction and short-term risk of surface water or groundwater degradation following construction. In addition, the cumulative effects of... cumulative beneficial effects: Long-term modified groundwater levels and flow patterns, long- term stream...

Considerations for Developing a Dosimetry-Based Cumulative Risk Assessment Approach for Mixtures of Environmental Contaminants (Final Report)

EPA Science Inventory

EPA announced the availability of the final report, Considerations for Developing a Dosimetry-Based Cumulative Risk Assessment Approach for Mixtures of Environmental Contaminants. This report describes a process that can be used to determine the potential value of develop...

Mothering and Peer Associations Mediate Cumulative Risk Effects for Latino Youth

ERIC Educational Resources Information Center

Loukas, Alexandra; Prelow, Hazel M.; Suizzo, Marie-Anne; Allua, Shane

2008-01-01

The present study examined whether positive parenting and deviant peer associations mediated the relations between a cumulative risk composite comprising financial strain, neighborhood problems, and maternal psychological distress and subsequent youth adjustment problems. Drawn from the Welfare, Children, and Families: A Three City Study, the…

HESI EXPOSURE FACTORS DATABASE FOR AGGREGATE AND CUMULATIVE RISK ASSESSMENT

EPA Science Inventory

In recent years, the risk analysis community has broadened its use of complex aggregate and cumulative residential exposure models (e.g., to meet the requirements of the 1996 Food Quality Protection Act). The value of these models is their ability to incorporate a range of inp...

Cumulative HIV viremia during highly active antiretroviral therapy is a strong predictor of AIDS-related lymphoma.

PubMed

Zoufaly, Alexander; Stellbrink, Hans-Jürgen; Heiden, Matthias An der; Kollan, Christian; Hoffmann, Christian; van Lunzen, Jan; Hamouda, Osamah

2009-07-01

AIDS-related lymphoma contributes to significant morbidity and mortality among human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART). We assessed the predictive role of cumulative HIV viremia and other risk factors in the development of AIDS-related non-Hodgkin lymphoma. Data from the Clinical Surveillance of HIV Disease (ClinSurv) study, an ongoing, observational, open cohort study of HIV-infected patients from different urban areas in Germany, were analyzed using a Cox proportional hazards model. In the Cox model, which comprised 6022 patients and 27,812 patient-years of follow-up while patients were receiving HAART from 1999 through 2006, cumulative HIV viremia was found to be independently associated with the risk of lymphoma (hazard ratio, [HR], 1.67 [95% confidence interval {CI}, 1.27-2.20]) (P < .001]). This association differed markedly between lymphoma subtypes. Although the association was more pronounced for Burkitt-type lymphoma (HR, 3.45 [95% CI, 1.52-7.85]) (P = .003), there was no association between cumulative HIV viremia and the incidence of primary central nervous system lymphoma (HR, 1.00 [95% CI, 0.39-2.57]) (P = .997). Other risk factors associated with an increased risk in a multivariable analysis included the latest CD4 T cell count as well as age per 10-year increment. Cumulative HIV viremia is an independent and strong predictor of AIDS-related lymphoma among patients receiving HAART. The influence of cumulative HIV viremia may differ between lymphoma subtypes.

Risk-reducing Surgery in Women at Risk for Familial Breast or Ovarian Cancer

PubMed Central

Rhiem, K.; Pfeifer, K.; Schmutzler, R. K.; Kiechle, M.

2012-01-01

An estimated 5 % of breast cancers and 10 % of ovarian cancers may be due to inherited autosomal dominant breast and ovarian cancer alleles BRCA1 und BRCA2. According to population-based studies 1 or 2 women per 1000 carry such a risk allele. The cumulative cancer risk for healthy women with a BRCA-mutation is between 60 and 85 % for breast cancer and between 20 and 60 % for ovarian cancer. Recent studies have reported an increased risk for contralateral breast cancer in women after unilateral breast cancer. Since 1997 the German Cancer Aid has supported an interdisciplinary approach for high-risk women consisting of genetic testing, counselling and prevention in 12 specialised centres. Since 2005 this concept has received additional support from health insurance companies, and results have been assessed with regard to outcomes (e.g. reduced mortality due to more intensive early diagnosis). The number of centres has increased to 15 at various university hospitals. These interdisciplinary centres offer women the opportunity to participate in a structured screening programme for the early diagnosis of breast cancer and provide non-directive counselling on the options for risk-reducing surgery, e.g., prophylactic bilateral salpingo-oophorectomy, prophylactic bilateral mastectomy or contralateral prophylactic mastectomy after unilateral breast cancer. Such surgical interventions can significantly reduce the risk of disease, the respective disease-specific mortality and – particularly prophylactic bilateral salpingo-oophorectomy – total mortality in BRCA-mutation carriers. PMID:26640291

Predictors of re-entry into the child protection system in Singapore: a cumulative ecological-transactional risk model.

PubMed

Li, Dongdong; Chu, Chi Meng; Ng, Wei Chern; Leong, Wai

2014-11-01

This study examines the risk factors of re-entry for 1,750 child protection cases in Singapore using a cumulative ecological-transactional risk model. Using administrative data, the present study found that the overall percentage of Child Protection Service (CPS) re-entry in Singapore is 10.5% based on 1,750 cases, with a range from 3.9% (within 1 year) to 16.5% (within 8 years after case closure). One quarter of the re-entry cases were observed to occur within 9 months from case closure. Seventeen risk factors, as identified from the extant literature, were tested for their utility to predict CPS re-entry in this study using a series of Cox regression analyses. A final list of seven risk factors (i.e., children's age at entry, case type, case closure result, duration of case, household income, family size, and mother's employment status) was used to create a cumulative risk score. The results supported the cumulative risk model in that higher risk score is related to higher risk of CPS re-entry. Understanding the prevalence of CPS re-entry and the risk factors associated with re-entry is the key to informing practice and policy in a culturally relevant way. The results from this study could then be used to facilitate critical case management decisions in order to enhance positive outcomes of families and children in Singapore's care system. Copyright © 2014 Elsevier Ltd. All rights reserved.

The relationship between herd level disease incidence and a return over feed index in Ontario dairy herds.

PubMed

McLaren, Chris J; Lissemore, Kerry D; Duffield, Todd F; Leslie, Ken E; Kelton, David F; Grexton, Bill

2006-08-01

The objective of the current research was to examine the association of herd level disease incidence with the return over feed (ROF) (milk income minus feed cost) herd profit index offered through Canwest Dairy Herd Improvement. The lactational incidence risks (LIR) for displaced abomasum, retained placenta, clinical mastitis, milk fever, clinical ketosis, and lameness submitted by producers (n = 48) were similar to previous reports. However, there was no negative association of clinical disease LIR's with ROE Subclinical ketosis and subclinical mastitis cumulative incidence were determined during the early postpartum period by using a cow-side test for betahydroxybutyrate in milk and the California Mastitis Test, respectively. Subclinical mastitis was not associated with ROE However, a unit increase in the cumulative incidence of subclinical ketosis was associated with a decrease of dollars 0.015/cow/day in the ROE The results highlight the economic significance that subclinical ketosis may have in Ontario dairy herds.

Surgery for left ventricular aneurysm: early and late survival after simple linear repair and endoventricular patch plasty.

PubMed

Lundblad, Runar; Abdelnoor, Michel; Svennevig, Jan Ludvig

2004-09-01

Simple linear resection and endoventricular patch plasty are alternative techniques to repair postinfarction left ventricular aneurysm. The aim of the study was to compare these 2 methods with regard to early mortality and long-term survival. We retrospectively reviewed 159 patients undergoing operations between 1989 and 2003. The epidemiologic design was of an exposed (simple linear repair, n = 74) versus nonexposed (endoventricular patch plasty, n = 85) cohort with 2 endpoints: early mortality and long-term survival. The crude effect of aneurysm repair technique versus endpoint was estimated by odds ratio, rate ratio, or relative risk and their 95% confidence intervals. Stratification analysis by using the Mantel-Haenszel method was done to quantify confounders and pinpoint effect modifiers. Adjustment for multiconfounders was performed by using logistic regression and Cox regression analysis. Survival curves were analyzed with the Breslow test and the log-rank test. Early mortality was 8.2% for all patients, 13.5% after linear repair and 3.5% after endoventricular patch plasty. When adjusted for multiconfounders, the risk of early mortality was significantly higher after simple linear repair than after endoventricular patch plasty (odds ratio, 4.4; 95% confidence interval, 1.1-17.8). Mean follow-up was 5.8 +/- 3.8 years (range, 0-14.0 years). Overall 5-year cumulative survival was 78%, 70.1% after linear repair and 91.4% after endoventricular patch plasty. The risk of total mortality was significantly higher after linear repair than after endoventricular patch plasty when controlled for multiconfounders (relative risk, 4.5; 95% confidence interval, 2.0-9.7). Linear repair dominated early in the series and patch plasty dominated later, giving a possible learning-curve bias in favor of patch plasty that could not be adjusted for in the regression analysis. Postinfarction left ventricular aneurysm can be repaired with satisfactory early and late results. Surgical risk was lower and long-term survival was higher after endoventricular patch plasty than simple linear repair. Differences in outcome should be interpreted with care because of the retrospective study design and the chronology of the 2 repair methods.

Aggregate Exposure and Cumulative Risk Assessment—Integrating Occupational and Non-occupational Risk Factors

PubMed Central

Lentz, T. J.; Dotson, G. S.; Williams, P. R.D.; Maier, A.; Gadagbui, B.; Pandalai, S. P.; Lamba, A.; Hearl, F.; Mumtaz, M.

2015-01-01

Occupational exposure limits have traditionally focused on preventing morbidity and mortality arising from inhalation exposures to individual chemical stressors in the workplace. While central to occupational risk assessment, occupational exposure limits have limited application as a refined disease prevention tool because they do not account for all of the complexities of the work and non-occupational environments and are based on varying health endpoints. To be of greater utility, occupational exposure limits and other risk management tools could integrate broader consideration of risks from multiple exposure pathways and routes (aggregate risk) as well as the combined risk from exposure to both chemical and non-chemical stressors, within and beyond the workplace, including the possibility that such exposures may cause interactions or modify the toxic effects observed (cumulative risk). Although still at a rudimentary stage in many cases, a variety of methods and tools have been developed or are being used in allied risk assessment fields to incorporate such considerations in the risk assessment process. These approaches, which are collectively referred to as cumulative risk assessment, have potential to be adapted or modified for occupational scenarios and provide a tangible path forward for occupational risk assessment. Accounting for complex exposures in the workplace and the broader risks faced by the individual also requires a more complete consideration of the composite effects of occupational and non-occupational risk factors to fully assess and manage worker health problems. Barriers to integrating these different factors remain, but new and ongoing community-based and worker health-related initiatives may provide mechanisms for identifying and integrating risk from aggregate exposures and cumulative risks from all relevant sources, be they occupational or non-occupational. PMID:26583907

Aggregate Exposure and Cumulative Risk Assessment--Integrating Occupational and Non-occupational Risk Factors.

PubMed

Lentz, T J; Dotson, G S; Williams, P R D; Maier, A; Gadagbui, B; Pandalai, S P; Lamba, A; Hearl, F; Mumtaz, M

2015-01-01

Occupational exposure limits have traditionally focused on preventing morbidity and mortality arising from inhalation exposures to individual chemical stressors in the workplace. While central to occupational risk assessment, occupational exposure limits have limited application as a refined disease prevention tool because they do not account for all of the complexities of the work and non-occupational environments and are based on varying health endpoints. To be of greater utility, occupational exposure limits and other risk management tools could integrate broader consideration of risks from multiple exposure pathways and routes (aggregate risk) as well as the combined risk from exposure to both chemical and non-chemical stressors, within and beyond the workplace, including the possibility that such exposures may cause interactions or modify the toxic effects observed (cumulative risk). Although still at a rudimentary stage in many cases, a variety of methods and tools have been developed or are being used in allied risk assessment fields to incorporate such considerations in the risk assessment process. These approaches, which are collectively referred to as cumulative risk assessment, have potential to be adapted or modified for occupational scenarios and provide a tangible path forward for occupational risk assessment. Accounting for complex exposures in the workplace and the broader risks faced by the individual also requires a more complete consideration of the composite effects of occupational and non-occupational risk factors to fully assess and manage worker health problems. Barriers to integrating these different factors remain, but new and ongoing community-based and worker health-related initiatives may provide mechanisms for identifying and integrating risk from aggregate exposures and cumulative risks from all relevant sources, be they occupational or non-occupational.

Analyzing risks of adverse pregnancy outcomes.

PubMed

Kramer, Michael S; Zhang, Xun; Platt, Robert W

2014-02-01

Approaches for analyzing the risks of adverse pregnancy outcomes have been the source of much debate and many publications. Much of the problem, in our view, is the conflation of time at risk with gestational age at birth (or birth weight, a proxy for gestational age). We consider the causal questions underlying such analyses with the help of a generic directed acyclic graph. We discuss competing risks and populations at risk in the context of appropriate numerators and denominators, respectively. We summarize 3 different approaches to quantifying risks with respect to gestational age, each of which addresses a distinct etiological or prognostic question (i.e., cumulative risk, prospective risk, or instantaneous risk (hazard)) and suggest the appropriate denominators for each. We show how the gestational age-specific risk of perinatal death (PND) can be decomposed as the product of the gestational age-specific risk of birth and the risk of PND conditional on birth at a given gestational age. Finally, we demonstrate how failure to consider the first of these 2 risks leads to selection bias. This selection bias creates the well-known crossover paradox, thus obviating the need to posit common causes of early birth and PND other than the study exposure.

Lifespan adversity and later adulthood telomere length in the nationally representative US Health and Retirement Study

PubMed Central

Gemmill, Alison; Weir, David; Adler, Nancy E.; Prather, Aric A.

2016-01-01

Stress over the lifespan is thought to promote accelerated aging and early disease. Telomere length is a marker of cell aging that appears to be one mediator of this relationship. Telomere length is associated with early adversity and with chronic stressors in adulthood in many studies. Although cumulative lifespan adversity should have bigger impacts than single events, it is also possible that adversity in childhood has larger effects on later life health than adult stressors, as suggested by models of biological embedding in early life. No studies have examined the individual vs. cumulative effects of childhood and adulthood adversities on adult telomere length. Here, we examined the relationship between cumulative childhood and adulthood adversity, adding up a range of severe financial, traumatic, and social exposures, as well as comparing them to each other, in relation to salivary telomere length. We examined 4,598 men and women from the US Health and Retirement Study. Single adversities tended to have nonsignificant relations with telomere length. In adjusted models, lifetime cumulative adversity predicted 6% greater odds of shorter telomere length. This result was mainly due to childhood adversity. In adjusted models for cumulative childhood adversity, the occurrence of each additional childhood event predicted 11% increased odds of having short telomeres. This result appeared mainly because of social/traumatic exposures rather than financial exposures. This study suggests that the shadow of childhood adversity may reach far into later adulthood in part through cellular aging. PMID:27698131

Lifespan adversity and later adulthood telomere length in the nationally representative US Health and Retirement Study.

PubMed

Puterman, Eli; Gemmill, Alison; Karasek, Deborah; Weir, David; Adler, Nancy E; Prather, Aric A; Epel, Elissa S

2016-10-18

Stress over the lifespan is thought to promote accelerated aging and early disease. Telomere length is a marker of cell aging that appears to be one mediator of this relationship. Telomere length is associated with early adversity and with chronic stressors in adulthood in many studies. Although cumulative lifespan adversity should have bigger impacts than single events, it is also possible that adversity in childhood has larger effects on later life health than adult stressors, as suggested by models of biological embedding in early life. No studies have examined the individual vs. cumulative effects of childhood and adulthood adversities on adult telomere length. Here, we examined the relationship between cumulative childhood and adulthood adversity, adding up a range of severe financial, traumatic, and social exposures, as well as comparing them to each other, in relation to salivary telomere length. We examined 4,598 men and women from the US Health and Retirement Study. Single adversities tended to have nonsignificant relations with telomere length. In adjusted models, lifetime cumulative adversity predicted 6% greater odds of shorter telomere length. This result was mainly due to childhood adversity. In adjusted models for cumulative childhood adversity, the occurrence of each additional childhood event predicted 11% increased odds of having short telomeres. This result appeared mainly because of social/traumatic exposures rather than financial exposures. This study suggests that the shadow of childhood adversity may reach far into later adulthood in part through cellular aging.

Postprandial Metabolism of Macronutrients and Cardiometabolic Risk: Recent Developments, Emerging Concepts, and Future Directions.

PubMed

Jacome-Sosa, Miriam; Parks, Elizabeth J; Bruno, Richard S; Tasali, Esra; Lewis, Gary F; Schneeman, Barbara O; Rains, Tia M

2016-03-01

Cardiovascular disease (CVD) is the leading cause of death in the United States. Although the role of habitual lifestyle factors such as physical activity and dietary patterns in increasing CVD risk has long been appreciated, less is known about how acute daily activities may cumulatively contribute to long-term disease risk. Here, the term acute refers to metabolic responses occurring in a short period of time after eating, and the goal of this article is to review recently identified stressors that can occur after meals and during the sleep-wake cycle to affect macronutrient metabolism. It is hypothesized that these events, when repeated on a regular basis, contribute to the observed long-term behavioral risks identified in population studies. In this regard, developments in research methods have supported key advancements in 3 fields of macronutrient metabolism. The first of these research areas is the focus on the immediate postmeal metabolism, spanning from early intestinal adsorptive events to the impact of incretin hormones on these events. The second topic is a focus on the importance of meal components on postprandial vasculature function. Finally, some of the most exciting advances are being made in understanding dysregulation in metabolism early in the day, due to insufficient sleep, that may affect subsequent processing of nutrients throughout the day. Key future research questions are highlighted which will lead to a better understanding of the relations between nocturnal, basal (fasting), and early postmeal events, and aid in the development of optimal sleep and targeted dietary patterns to reduce cardiometabolic risk. © 2016 American Society for Nutrition.

The Use of Glyburide Compared With Other Sulfonylureas and the Risk of Cancer in Patients With Type 2 Diabetes.

PubMed

Tuccori, Marco; Wu, Jennifer W; Yin, Hui; Majdan, Agnieszka; Azoulay, Laurent

2015-11-01

To determine whether the use of glyburide is associated with an increased risk of cancer compared with the use of other second-generation sulfonylureas among patients with type 2 diabetes. The U.K. Clinical Practice Research Datalink was used to conduct a cohort study among 52,600 patients newly prescribed glyburide or other second-generation sulfonylureas between 1 January 1988 and 31 July 2013. A time-dependent Cox proportional hazards model was used to estimate adjusted hazard ratios (HRs) and 95% CIs of any cancer associated with the use of glyburide compared with the use of second-generation sulfonylureas. Secondary analyses were conducted to determine whether the association varied with cumulative duration of use and cumulative dose (expressed as defined daily dose [DDD]). During 280,288 person-years of follow-up, 4,105 patients were given a new diagnosis of cancer (incidence rate 14.6 per 1,000 person-years). Overall, when compared with the use of other second-generation sulfonylureas, the use of glyburide was associated with a nonsignificant increased risk of any cancer (HR 1.09 [95% CI 0.98-1.22]). In secondary analyses, duration- and dose-response relationships were observed, with longer cumulative durations and cumulative doses associated with an increased risk of any cancer (>36 months: HR 1.21 [95% CI: 1.03-1.42]; >1,096 DDDs: HR 1.27 [95% CI 1.06-1.51]). In this population-based cohort study, longer cumulative durations and higher cumulative doses of glyburide were associated with an increased risk of cancer. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Early Antiretroviral Therapy Initiation and Mortality Among Infants Diagnosed With HIV in the First 12 Weeks of Life: Experiences From Kinshasa, DR Congo and Blantyre, Malawi.

PubMed

Sheahan, Anna; Feinstein, Lydia; Dube, Queen; Edmonds, Andrew; Chirambo, Chawanangwa Mahebere; Smith, Emily; Behets, Frieda; Heyderman, Robert; Van Rie, Annelies

2017-07-01

Based on clinical trial results, the World Health Organization recommends infant HIV testing at age 4-6 weeks and immediate antiretroviral therapy (ART) initiation in all HIV-infected infants. Little is known about the outcomes of HIV-infected infants diagnosed with HIV in the first weeks of life in resource-limited settings. We assessed ART initiation and mortality in the first year of life among infants diagnosed with HIV by 12 weeks of age. Cohort of HIV-infected infants in Kinshasa and Blantyre diagnosed before 12 weeks to estimate 12-month cumulative incidences of ART initiation and mortality, accounting for competing risks. Multivariate models were used to estimate associations between infant characteristics and timing of ART initiation. One hundred and twenty-one infants were diagnosed at a median age of 7 weeks (interquartile range, 6-8). The cumulative incidence of ART initiation was 46% [95% confidence interval (CI), 36%, 55%] at 6 months and 70% (95% CI 60%, 78%) at 12 months. Only age at HIV diagnosis was associated with ART initiation by age 6 months, with a subdistribution hazard ratio of 0.70 (95% CI 0.52, 0.91) for each week increase in age at DNA polymerase chain reaction test. The 12-month cumulative incidence of mortality was 20% (95% CI 13%, 28%). Despite early diagnosis of HIV, ART initiation was slow and mortality remained high, underscoring the complexity in translating clinical trial findings and World Health Organization's guidance into real-life practice. Novel and creative health system interventions will be required to ensure that all HIV-infected infants achieve optimal treatment outcomes under routine care settings.

+Gz Exposure and Spinal Injury-Induced Flight Duty Limitations.

PubMed

Honkanen, Tuomas; Sovelius, Roope; Mäntysaari, Matti; Kyröläinen, Heikki; Avela, Janne; Leino, Tuomo K

2018-06-01

The present study aimed to find out if possible differences in early military flight career +Gz exposure level could predict permanent flight duty limitations (FDL) due to spinal disorders during a pilot's career. The study population consisted of 23 pilots flying with Gz limitation (max limitation ranging from +2 Gz to +5 Gz) due to spinal disorders and 50 experienced (+1000 flight hours) symptomless controls flying actively in operative missions in the Finnish Air Force. Data obtained for all subjects included the level of cumulative Gz exposure measured sortie by sortie with fatigue index (FI) recordings and flight hours during the first 5 yr of the pilot's career. The mean (± SD) accumulation of FI in the first 5 yr of flying high-performance aircraft was 8.0 ± 1.8 among the pilots in the FDL group and 7.7 ± 1.7 in the non-FDL group. There was no association between flight duty limitations and early career cumulative +Gz exposure level measured with FI or flight hours. According to the present findings, it seems that the amount of cumulative +Gz exposure during the first 5 yr of a military pilot's career is not an individual risk factor for spinal disorders leading to flight duty limitation. Future studies conducted with FI recordings should be addressed to reveal the relationship between the actual level of +Gz exposure and spinal disorders, with a longer follow-up period and larger sample sizes.Honkanen T, Sovelius R, Mäntysaari M, Kyröläinen H, Avela J, Leino TK. +Gz exposure and spinal injury-induced flight duty limitations. Aerosp Med Hum Perform. 2018; 89(6):552-556.

Effect of Cumulating Exposure to Abacavir on the Risk of Cardiovascular Disease Events in Patients From the Swiss HIV Cohort Study.

PubMed

Young, Jim; Xiao, Yongling; Moodie, Erica E M; Abrahamowicz, Michal; Klein, Marina B; Bernasconi, Enos; Schmid, Patrick; Calmy, Alexandra; Cavassini, Matthias; Cusini, Alexia; Weber, Rainer; Bucher, Heiner C

2015-08-01

Patients with HIV exposed to the antiretroviral drug abacavir may have an increased risk of cardiovascular disease (CVD). There is concern that this association arises because of a channeling bias. Even if exposure is a risk, it is not clear how that risk changes as exposure cumulates. We assess the effect of exposure to abacavir on the risk of CVD events in the Swiss HIV Cohort Study. We use a new marginal structural Cox model to estimate the effect of abacavir as a flexible function of past exposures while accounting for risk factors that potentially lie on a causal pathway between exposure to abacavir and CVD. A total of 11,856 patients were followed for a median of 6.6 years; 365 patients had a CVD event (4.6 events per 1000 patient-years). In a conventional Cox model, recent--but not cumulative--exposure to abacavir increased the risk of a CVD event. In the new marginal structural Cox model, continued exposure to abacavir during the past 4 years increased the risk of a CVD event (hazard ratio = 2.06; 95% confidence interval: 1.43 to 2.98). The estimated function for the effect of past exposures suggests that exposure during the past 6-36 months caused the greatest increase in risk. Abacavir increases the risk of a CVD event: the effect of exposure is not immediate, rather the risk increases as exposure cumulates over the past few years. This gradual increase in risk is not consistent with a rapidly acting mechanism, such as acute inflammation.

Conceptual models for cumulative risk assessment.

PubMed

Linder, Stephen H; Sexton, Ken

2011-12-01

In the absence of scientific consensus on an appropriate theoretical framework, cumulative risk assessment and related research have relied on speculative conceptual models. We argue for the importance of theoretical backing for such models and discuss 3 relevant theoretical frameworks, each supporting a distinctive "family" of models. Social determinant models postulate that unequal health outcomes are caused by structural inequalities; health disparity models envision social and contextual factors acting through individual behaviors and biological mechanisms; and multiple stressor models incorporate environmental agents, emphasizing the intermediary role of these and other stressors. The conclusion is that more careful reliance on established frameworks will lead directly to improvements in characterizing cumulative risk burdens and accounting for disproportionate adverse health effects.

Conceptual Models for Cumulative Risk Assessment

PubMed Central

Sexton, Ken

2011-01-01

In the absence of scientific consensus on an appropriate theoretical framework, cumulative risk assessment and related research have relied on speculative conceptual models. We argue for the importance of theoretical backing for such models and discuss 3 relevant theoretical frameworks, each supporting a distinctive “family” of models. Social determinant models postulate that unequal health outcomes are caused by structural inequalities; health disparity models envision social and contextual factors acting through individual behaviors and biological mechanisms; and multiple stressor models incorporate environmental agents, emphasizing the intermediary role of these and other stressors. The conclusion is that more careful reliance on established frameworks will lead directly to improvements in characterizing cumulative risk burdens and accounting for disproportionate adverse health effects. PMID:22021317

Cumulative early life adversity predicts longevity in wild baboons

PubMed Central

Tung, Jenny; Archie, Elizabeth A.; Altmann, Jeanne; Alberts, Susan C.

2016-01-01

In humans and other animals, harsh circumstances in early life predict morbidity and mortality in adulthood. Multiple adverse conditions are thought to be especially toxic, but this hypothesis has rarely been tested in a prospective, longitudinal framework, especially in long-lived mammals. Here we use prospective data on 196 wild female baboons to show that cumulative early adversity predicts natural adult lifespan. Females who experience ≥3 sources of early adversity die a median of 10 years earlier than females who experience ≤1 adverse circumstances (median lifespan is 18.5 years). Females who experience the most adversity are also socially isolated in adulthood, suggesting that social processes partially explain the link between early adversity and adult survival. Our results provide powerful evidence for the developmental origins of health and disease and indicate that close ties between early adversity and survival arise even in the absence of health habit and health care-related explanations. PMID:27091302

Noninvasive assessment of arterial function in children: clinical applications

PubMed Central

Aggoun, Y; Beghetti, M

2002-01-01

Non invasive methods to assess arterial function are widely used in adults. The development and progression of arterial vascular disease is a multifactorial process that can start early in life, thus even in a pediatric population. Risk factors for cardiovascular disease mediate their effects by altering the structure, properties and function of wall and endothelial components of the arterial blood vessels. The ability to detect and monitor sub-clinical damage, representing the cumulative and integrated influence of risk factors in impairing arterial wall integrity, holds potential to further refine cardiovascular risk stratification and enable early intervention to prevent or attenuate disease progression. Measurements that provide more direct information in relation to changes in arterial wall integrity clearly hold predictive and therapeutic potential. The aim of this current review will be to describe the non-invasive procedure used in children to investigate the mechanical properties of a great elastic artery, the common carotid, and the endothelial function of the brachial artery. The accuracy of recording noninvasively the blood pressure wave contour along the arterial tree has been improved by the technique of applanation tonometry. The results obtained with these methods in previous studies are described. PMID:22368620

Cumulative Small Effect Genetic Markers and the Risk of Colorectal Cancer in Poland, Estonia, Lithuania, and Latvia

PubMed Central

Serrano-Fernandez, Pablo; Dymerska, Dagmara; Kurzawski, Grzegorz; Derkacz, Róża; Sobieszczańska, Tatiana; Banaszkiewicz, Zbigniew; Roomere, Hanno; Oitmaa, Eneli; Metspalu, Andres; Janavičius, Ramūnas; Elsakov, Pavel; Razumas, Mindaugas; Petrulis, Kestutis; Irmejs, Arvīds; Miklaševičs, Edvīns; Scott, Rodney J.; Lubiński, Jan

2015-01-01

The continued identification of new low-penetrance genetic variants for colorectal cancer (CRC) raises the question of their potential cumulative effect among compound carriers. We focused on 6 SNPs (rs380284, rs4464148, rs4779584, rs4939827, rs6983267, and rs10795668), already described as risk markers, and tested their possible independent and combined contribution to CRC predisposition. Material and Methods. DNA was collected and genotyped from 2330 unselected consecutive CRC cases and controls from Estonia (166 cases and controls), Latvia (81 cases and controls), Lithuania (123 cases and controls), and Poland (795 cases and controls). Results. Beyond individual effects, the analysis revealed statistically significant linear cumulative effects for these 6 markers for all samples except of the Latvian one (corrected P value = 0.018 for the Estonian, corrected P value = 0.0034 for the Lithuanian, and corrected P value = 0.0076 for the Polish sample). Conclusions. The significant linear cumulative effects demonstrated here support the idea of using sets of low-risk markers for delimiting new groups with high-risk of CRC in clinical practice that are not carriers of the usual CRC high-risk markers. PMID:26101521

Cumulative Small Effect Genetic Markers and the Risk of Colorectal Cancer in Poland, Estonia, Lithuania, and Latvia.

PubMed

Serrano-Fernandez, Pablo; Dymerska, Dagmara; Kurzawski, Grzegorz; Derkacz, Róża; Sobieszczańska, Tatiana; Banaszkiewicz, Zbigniew; Roomere, Hanno; Oitmaa, Eneli; Metspalu, Andres; Janavičius, Ramūnas; Elsakov, Pavel; Razumas, Mindaugas; Petrulis, Kestutis; Irmejs, Arvīds; Miklaševičs, Edvīns; Scott, Rodney J; Lubiński, Jan

2015-01-01

The continued identification of new low-penetrance genetic variants for colorectal cancer (CRC) raises the question of their potential cumulative effect among compound carriers. We focused on 6 SNPs (rs380284, rs4464148, rs4779584, rs4939827, rs6983267, and rs10795668), already described as risk markers, and tested their possible independent and combined contribution to CRC predisposition. Material and Methods. DNA was collected and genotyped from 2330 unselected consecutive CRC cases and controls from Estonia (166 cases and controls), Latvia (81 cases and controls), Lithuania (123 cases and controls), and Poland (795 cases and controls). Results. Beyond individual effects, the analysis revealed statistically significant linear cumulative effects for these 6 markers for all samples except of the Latvian one (corrected P value = 0.018 for the Estonian, corrected P value = 0.0034 for the Lithuanian, and corrected P value = 0.0076 for the Polish sample). Conclusions. The significant linear cumulative effects demonstrated here support the idea of using sets of low-risk markers for delimiting new groups with high-risk of CRC in clinical practice that are not carriers of the usual CRC high-risk markers.

Silicosis among gold miners: exposure--response analyses and risk assessment.

PubMed

Steenland, K; Brown, D

1995-10-01

This study sought to estimate the risk of silicosis by cumulative exposure-years in a cohort of miners exposed to silica, as well as the lifetime risk of silicosis under the current Occupational Safety and Health Administration (OSHA) standard (0.09 mg/m3). In a cohort study of 3330 gold miners who worked at least 1 year underground from 1940 to 1965 (average 9 years) and were exposed to a median silica level of 0.05 mg/m3 (0.15 mg/m3 for those hired before 1930), 170 cases of silicosis were determined from either death certificates or two cross-sectional radiographic surveys. The risk of silicosis was less than 1% with a cumulative exposure under 0.5 mg/m3-years, increasing to 68% to 84% for the highest cumulative exposure category of more than 4 mg/m3-years. Cumulative exposure was the best predictor of disease, followed by duration of exposure and average exposure. After adjustment for competing risks of death, a 45-year exposure under the current OSHA standard would lead to a lifetime risk of silicosis of 35% to 47%. Almost 2 million US workers are currently exposed to silica. Our results add to a small but increasing body of literature that suggests that the current OSHA silica exposure level is unacceptably high.

Cumulative Environmental Impacts: Science and Policy to Protect Communities.

PubMed

Solomon, Gina M; Morello-Frosch, Rachel; Zeise, Lauren; Faust, John B

2016-01-01

Many communities are located near multiple sources of pollution, including current and former industrial sites, major roadways, and agricultural operations. Populations in such locations are predominantly low-income, with a large percentage of minorities and non-English speakers. These communities face challenges that can affect the health of their residents, including limited access to health care, a shortage of grocery stores, poor housing quality, and a lack of parks and open spaces. Environmental exposures may interact with social stressors, thereby worsening health outcomes. Age, genetic characteristics, and preexisting health conditions increase the risk of adverse health effects from exposure to pollutants. There are existing approaches for characterizing cumulative exposures, cumulative risks, and cumulative health impacts. Although such approaches have merit, they also have significant constraints. New developments in exposure monitoring, mapping, toxicology, and epidemiology, especially when informed by community participation, have the potential to advance the science on cumulative impacts and to improve decision making.

CUMULATIVE EFFECTS OF IN UTERO ADMINISTRATION OF MIXTURES OF "ANTIANDROGENS" ON MALE RAT REPRODUCTIVIE DEVELOPMENT.

EPA Science Inventory

Although risk assessments are typically conducted on a chemical-bychemical

basis, the 1996 Food Quality Protection Act Law requires the USEPA to

consider cumulative risk of chemicals that act via a common mode/mechanism of

action. To this end, we are conducti...

Cumulative effects of in utero administration of mixtures of "antiandrogens" on male rat reproductive development

EPA Science Inventory

Although risk assessments are typically conducted on a chemical-by-chemical basis, the 1996 Food Quality Protection Act requires the USEPA to consider cumulative risk of chemicals that act via a common mechanism of toxicity. To this end, we are conducting studies to provide a fra...

CUMULATIVE EFFECTS OF IN UTERO ADMINISTRATION OF A MIXTURE OF SEVEN ANTIANDROGENS ON MALE RAT REPRODUCTIVE DEVELOPMENT

EPA Science Inventory

Although risk assessments are typically conducted on a chemical-by-chemical basis, the 1996 FQPA requires the USEPA to consider cumulative risk from chemicals that act via a common mechanism of action. To this end, we are conducting studies with mixtures to provide a framework fo...

76 FR 34978 - Petition Supplement Requesting Cancellation of Propoxur Pet Collar Uses; Notice of Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-15

... non-dietary oral exposure pathway presented in the Revised N-methyl Carbamate (NMC) Cumulative Risk... Cumulative Risk Assessment docket EPA-HQ- OPP-2007-0935; 2. A petition supplement, dated April 23, 2009... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OPP-2009-0207; FRL-8875-1] Petition Supplement Requesting...

(BOSC) DOSE-RESPONSE MODELING FOR THE ASSESSMENT OF CUMULATIVE RISK DUE TO EXPOSURE TO N-METHYL CARBAMATE PRESTICIDES

EPA Science Inventory

THE US EPA'S N-METHYL CARBAMATE CUMULATIVE RISK ASSESSMENT (NMCRA) ASSESSES THE EFFECT ON ACETYLCHOLINE ESTERASE (AChE) ACTIVITY OF EXPOSURE TO 10 N-METHLY CARBAMATE (NMC)PESTICIDES THROUGH DIETARY, DRINKING WATER, AND RESIDENTIAL EXPOSURES. THESE DATA THUS INFORM, BUT DO NOT COM...

Benchmark Dose Analysis from Multiple Datasets: The Cumulative Risk Assessment for the N-Methyl Carbamate Pesticides

EPA Science Inventory

The US EPA’s N-Methyl Carbamate (NMC) Cumulative Risk assessment was based on the effect on acetylcholine esterase (AChE) activity of exposure to 10 NMC pesticides through dietary, drinking water, and residential exposures, assuming the effects of joint exposure to NMCs is dose-...

HEALTH AND ENVIRONMENTAL SCIENCES INSTITUTE'S EXPOSURE FACTORS DATABASE FOR AGGREGATE AND CUMULATIVE RISK ASSESSMENT

EPA Science Inventory

In recent years, the risk analysis community has broadened its use of complex aggregate and cumulative residential exposure models (e.g., to meet the requirements of the 1996 Food Quality Protection Act). The value of these models is their ability to incorporate a range of input...

Cumulative Effects of in Uetro Administration of Mixtures of "Antiandrogens" on Male Rat Reproductive Development

EPA Science Inventory

Although risk assessments are typically conducted on a chemical-by-chemical basis, the 1996 FQPA required the EPA to consider cumulative risk of chemicals that act via a common mechanism of toxicity. To this end, we are conducting studies with mixtures to provide a framework for ...

Cumulative Risk, Maternal Responsiveness, and Allostatic Load among Young Adolescents

ERIC Educational Resources Information Center

Evans, Gary W.; Kim, Pilyoung; Ting, Albert H.; Tesher, Harris B.; Shannis, Dana

2007-01-01

The purpose of this study was to examine the impact of cumulative risk exposure in concert with maternal responsiveness on physiological indicators of chronic stress in children and youth. Middle-school children exposed to greater accumulated psychosocial (e.g., family turmoil, poverty) and physical (e.g., crowding, substandard housing) risk…

Cumulative Risk Assessment (CRA): Transforming the Way We Assess Health Risks

PubMed Central

Williams, Pamela R. D.; Dotson, G. Scott; Maier, Andrew

2016-01-01

Human health risk assessments continue to evolve and now focus on the need for cumulative risk assessment (CRA). CRA involves assessing the combined risk from coexposure to multiple chemical and nonchemical stressors for varying health effects. CRAs are broader in scope than traditional chemical risk assessments because they allow for a more comprehensive evaluation of the interaction between different stressors and their combined impact on human health. Future directions of CRA include greater emphasis on local-level community-based assessments; integrating environmental, occupational, community, and individual risk factors; and identifying and implementing common frameworks and risk metrics for incorporating multiple stressors. PMID:22938698

Combined early and adult life risk factor associations for mid-life obesity in a prospective birth cohort: assessing potential public health impact.

PubMed

Pinto Pereira, Snehal M; van Veldhoven, Karin; Li, Leah; Power, Chris

2016-04-12

The combined effect of life-course influences on obesity development and thus their potential public health impact is unclear. We evaluated combined associations and predicted probabilities for early and adult life risk factors with central and general obesity in mid-adulthood. 1958 British birth cohort. 4629 males and 4670 females with data on waist circumference. 45 year obesity measured via waist circumference, waist-hip ratio (WHR) and BMI. At 45 years, approximately a third of the population were centrally obese and a quarter were generally obese. Three factors (parental overweight, maternal smoking during pregnancy and adult inactivity) were consistently associated with central and general obesity. Predicted probabilities for waist obesity increased from those with none to all three risk factors (0.15-0.33 in men; 0.19-0.39 in women (ptrend<0.001)), with a similar trend for general obesity. Additional factors (adult smoking, low fibre and heavy alcohol consumption) were associated with WHR obesity, although varying by gender. Prevalence of risk factors was higher in manual than non-manual groups: for example, in men 38% versus 25%, respectively, had ≥2 risk factors for waist and general obesity. Early-life and adult factors that are amenable to change are highly prevalent and accumulate in association with central and general obesity in mid-adulthood. The increase in probabilities for mid-adult obesity associated with cumulative levels of risk factors suggests the potential for public health impact. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Cumulative exposure to work-related traumatic events and current post-traumatic stress disorder in New York City's first responders.

PubMed

Geronazzo-Alman, Lupo; Eisenberg, Ruth; Shen, Sa; Duarte, Cristiane S; Musa, George J; Wicks, Judith; Fan, Bin; Doan, Thao; Guffanti, Guia; Bresnahan, Michaeline; Hoven, Christina W

2017-04-01

Cumulative exposure to work-related traumatic events (CE) is a foreseeable risk for psychiatric disorders in first responders (FRs). Our objective was to examine the impact of work-related CE that could serve as predictor of posttraumatic stress disorder (PTSD) and/or depression in FRs. Cross-sectional examination of previous CE and past-month PTSD outcomes and depression in 209 FRs. Logistic (probable PTSD; probable depression) and Poisson regressions (PTSD score) of the outcomes on work-related CE indexes, adjusting for demographic variables. Differences across occupational groups were also examined. Receiver operating characteristic analysis determined the sensitivity and specificity of CE indexes. All indexes were significantly and differently associated with PTSD; associations with depression were non-significant. The index capturing the sheer number of different incidents experienced regardless of frequency ('Variety') showed conceptual, practical and statistical advantages compared to other indexes. In general, the indexes showed poor to fair discrimination accuracy. Work-related CE is specifically associated with PTSD. Focusing on the variety of exposures may be a simple and effective strategy to predict PTSD in FRs. Further research on sensitivity and specificity of exposure indexes, preferably examined prospectively, is needed and could lead to early identification of individuals at risk. Copyright © 2016 Elsevier Inc. All rights reserved.

Progression of Unresected Intraductal Papillary Mucinous Neoplasms of the Pancreas to Cancer: A Systematic Review and Meta-analysis.

PubMed

Choi, Sang Hyun; Park, Seong Ho; Kim, Kyung Won; Lee, Ja Youn; Lee, Sang Soo

2017-10-01

It is not clear how best to manage patients with low-risk intraductal papillary mucinous neoplasms (IPMNs) of the pancreas because little is known about IPMN progression to cancer. We sought to determine the cumulative incidence of development of pancreatic cancer in persons with unresected IPMNs (particularly low-risk IPMNs). We performed a systematic search of the MEDLINE and Embase databases through November 30, 2016 for studies reporting the cumulative incidence of pancreatic cancer in patients with unresected IPMNs or studies that provided data in sufficient detail for us to calculate cumulative incidence values. We categorized patient series as studies on low-risk IPMNs (lesions without main pancreatic duct involvement or mural nodules) or non-low-risk IPMNs. We calculated meta-analytic cumulative incidence values for pancreatic cancer at 1, 3, 5, and 10 years of follow-up by using the inverse variance method and random-effects model. Among 1514 articles screened, we identified 10 studies of low-risk IPMNs (n = 2411) and 9 studies of non-low-risk IPMNs (n = 825). In studies of low-risk IPMNs, the meta-analytic cumulative incidence values for pancreatic cancer were 0.02% at 1 year (95% confidence interval [CI], 0.0%-0.23%; I 2 = 0.0%), 1.40% at 3 years (95% CI, 0.58%-2.48%; I 2  = 58.5%), 3.12% at 5 years (95% CI, 1.12%-5.90%; I 2  = 88.0%), and 7.77% at 10 years (95% CI, 4.09%-12.39%; I 2  = 79.8%). These values were much higher in studies of non-low-risk IPMNs; cumulative incidence values for pancreatic cancer were 1.95% at 1 year (95% CI, 0.0%-5.99%; I 2  = 84.2%), 5.69% at 3 years (95% CI, 1.10%-12.77%; I 2  = 89.9%), 9.77% at 5 years (95% CI, 3.04%-19.27%; I 2  = 92.0%), and 24.68% at 10 years (95% CI, 14.87%-35.90%; I 2  = 74.3%). The pooled cumulative incidence steadily increased linearly as the follow-up duration increased. In a systematic review and meta-analysis, we found that low-risk IPMNs have almost 8% chance of progressing to pancreatic cancer within 10 years, and higher-risk IPMNs have almost 25% chance of progressing to cancer in 10 years; incidence values increase linearly with time. Continued long-term surveillance is therefore vital for patients with low-risk IPMNs. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Cumulative childhood stress and autoimmune diseases in adults.

PubMed

Dube, Shanta R; Fairweather, DeLisa; Pearson, William S; Felitti, Vincent J; Anda, Robert F; Croft, Janet B

2009-02-01

To examine whether childhood traumatic stress increased the risk of developing autoimmune diseases as an adult. Retrospective cohort study of 15,357 adult health maintenance organization members enrolled in the Adverse Childhood Experiences (ACEs) Study from 1995 to 1997 in San Diego, California, and eligible for follow-up through 2005. ACEs included childhood physical, emotional, or sexual abuse; witnessing domestic violence; growing up with household substance abuse, mental illness, parental divorce, and/or an incarcerated household member. The total number of ACEs (ACE Score range = 0-8) was used as a measure of cumulative childhood stress. The outcome was hospitalizations for any of 21 selected autoimmune diseases and 4 immunopathology groupings: T- helper 1 (Th1) (e.g., idiopathic myocarditis); T-helper 2 (Th2) (e.g., myasthenia gravis); Th2 rheumatic (e.g., rheumatoid arthritis); and mixed Th1/Th2 (e.g., autoimmune hemolytic anemia). Sixty-four percent reported at least one ACE. The event rate (per 10,000 person-years) for a first hospitalization with any autoimmune disease was 31.4 in women and 34.4 in men. First hospitalizations for any autoimmune disease increased with increasing number of ACEs (p < .05). Compared with persons with no ACEs, persons with >or=2 ACEs were at a 70% increased risk for hospitalizations with Th1, 80% increased risk for Th2, and 100% increased risk for rheumatic diseases (p < .05). Childhood traumatic stress increased the likelihood of hospitalization with a diagnosed autoimmune disease decades into adulthood. These findings are consistent with recent biological studies on the impact of early life stress on subsequent inflammatory responses.

Incidence and risk factors for development of new-onset diabetes after kidney transplantation.

PubMed

Bee, Yong Mong; Tan, Hong Chang; Tay, Tunn Lin; Kee, Terence Ys; Goh, Su Yen; Kek, Peng Chin

2011-04-01

New-onset diabetes after transplantation (NODAT) is an increasingly recognised metabolic complication of kidney transplantation that is associated with increased morbidity and mortality. This study aimed to determine the incidence of NODAT and identify risk factors for development of NODAT among kidney allograft recipients in a single centre. We retrospectively reviewed all kidney allograft recipients in our centre between 1998 and 2007. NODAT were determined using criteria as per American Diabetes Association guidelines. Logistic regression analyses were performed to identify predictors of NODAT. Among 388 patients included in the analysis, NODAT was reported in 94 patients (24.2%) after a median follow-up time of 52.1 months. The cumulative incidence of NODAT was 15.8%, 22.8% and 24.5% at 1, 3, and 5 years following transplantation. Seven clinical factors were independent predictors of NODAT: older age, HLA B13 and B15 phenotypes, use of sirolimus, acute rejections, higher pre-transplant and post-transplant (day 1) plasma glucose levels. Patients with NODAT had poorer outcomes in both graft and patient survival. Our study demonstrates a significant risk and burden of NODAT in an Asian transplant population. Risk stratification and aggressive monitoring of blood glucose early post-transplantation is necessary to identify high-risk patients so that appropriate tailoring of immunosuppression and early institution of lifestyle modifications can be implemented.

Single and Cumulative Relations of Social Risk Factors with Children's Dental Health and Care-Utilization Within Regions of the United States.

PubMed

Yang, Alyssa J; Gromoske, Andrea N; Olson, Melissa A; Chaffin, Jeffrey G

2016-03-01

The purpose is to examine the relation of social risk factors, and the cumulative burden of social risk factors, on parent-reported dental health and dental care-seeking behavior. National Survey of Children's Health data (2011-2012) were analyzed for US children by Title V Block Grant regions. Multivariate logistic regressions were estimated for ten social risk factors, as well as a cumulative risk index, to find any associations with poor condition of teeth, presence of dental caries, and no dental care visits. Almost all of the risk factors were significantly associated with poor condition of teeth and presence of dental caries for the US. Models associating no dental care visits suggested that low family income (OR 1.58), poor maternal mental health (OR 1.54), high school education or less (OR 1.34), and multi-racial/other race (OR 1.18) were significant factors for the US. Regional variation existed for those risk factors and their association with the outcomes, but income, education, and poor maternal mental health consistently played a significant role in adverse outcomes. The cumulative risk index was strongly related to poor oral health outcomes, with a weaker relationship to dental care utilization. US children experiencing certain social risk factors, such as low family income, high school education or less, and poor maternal mental health, are likely to be at greater risk for poor dental health and low levels of dental-care seeking behavior. Children experiencing multiple social risks are at greater risk for poor oral outcomes than children who experience fewer social risks. An approach that involves the social determinants of health is needed to address these issues.

Predicting severe motor impairment in preterm children at age 5 years.

PubMed

Synnes, Anne; Anderson, Peter J; Grunau, Ruth E; Dewey, Deborah; Moddemann, Diane; Tin, Win; Davis, Peter G; Doyle, Lex W; Foster, Gary; Khairy, May; Nwaesei, Chukwuma; Schmidt, Barbara

2015-08-01

To determine whether the ability to predict severe motor impairment at age 5 years improves between birth and 18 months. Ancillary study of the Caffeine for Apnea of Prematurity Trial. International cohort of very low birth weight children who were assessed sequentially from birth to 5 years. Severe motor impairment was defined as a score <5th percentile on the Movement Assessment Battery of Children (MABC), or inability to complete the MABC because of cerebral palsy. Multivariable logistic regression cumulative risk models used four sets of predictor variables: early neonatal risk factors, risk factors at 36 weeks' postmenstrual age, risk factors at a corrected age of 18 months, and sociodemographic variables. A receiver operating characteristic curve (ROC) was generated for each model, and the four ROC curves were compared to determine if the addition of the new set of predictors significantly increased the area under the curve (AUC). Of 1469 children, 291 (19.8%) had a severe motor impairment at 5 years. The AUC increased from 0.650 soon after birth, to 0.718 (p<0.001) at 36 weeks' postmenstrual age, and to 0.797 at 18 months (p<0.001). Sociodemographic variables did not significantly improve the AUC (AUC=0.806; p=0.07). Prediction of severe motor impairment at 5 years of age using a cumulative risk model improves significantly from birth to 18 months of age in children with birth weights between 500 g and 1250 g. ClinicalTrials.gov number NCT00182312. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Second Malignant Neoplasms in Childhood Cancer Survivors Treated in a Tertiary Paediatric Oncology Centre.

PubMed

Lim, Jia Wei; Yeap, Frances Sh; Chan, Yiong Huak; Yeoh, Allen Ej; Quah, Thuan Chong; Tan, Poh Lin

2017-01-01

Introduction : One of the most feared complications of childhood cancer treatment is second malignant neoplasms (SMNs). This study evaluates the incidence, risk factors and outcomes of SMNs in a tertiary paediatric oncology centre in Singapore. Materials and Methods : A retrospective review was conducted on patients diagnosed with childhood cancer under age 21 and treated at the National University Hospital, Singapore, from January 1990 to 15 April 2012. Case records of patients with SMNs were reviewed. Results : We identified 1124 cases of childhood cancers with a median follow-up of 3.49 (0 to 24.06) years. The most common primary malignancies were leukaemia (47.1%), central nervous system tumours (11.7%) and lymphoma (9.8%). Fifteen cases developed SMNs, most commonly acute myeloid leukaemia/myelodysplastic syndrome (n = 7). Median interval between the first and second malignancy was 3.41 (0.24 to 18.30) years. Overall 20-year cumulative incidence of SMNs was 5.3% (95% CI, 0.2% to 10.4%). The 15-year cumulative incidence of SMNs following acute lymphoblastic leukaemia was 4.4% (95% CI, 0% to 8.9%), significantly lower than the risk after osteosarcoma of 14.2% (95% CI, 0.7% to 27.7%) within 5 years ( P <0.0005). Overall 5-year survival for SMNs was lower than that of primary malignancies. Conclusion : This study identified factors explaining the epidemiology of SMNs described, and found topoisomerase II inhibitor use to be a likely risk factor in our cohort. Modifications have already been made to our existing therapeutic protocols in osteosarcoma treatment. We also recognised the importance of other risk management strategies, including regular long-term surveillance and early intervention for detected SMNs, to improve outcomes of high risk patients.

Cumulative neighborhood risk of psychosocial stress and allostatic load in adolescents.

PubMed

Theall, Katherine P; Drury, Stacy S; Shirtcliff, Elizabeth A

2012-10-01

The authors examined the impact of cumulative neighborhood risk of psychosocial stress on allostatic load (AL) among adolescents as a mechanism through which life stress, including neighborhood conditions, may affect health and health inequities. They conducted multilevel analyses, weighted for sampling and propensity score-matched, among adolescents aged 12-20 years in the National Health and Nutrition Examination Survey (1999-2006). Individuals (first level, n = 11,886) were nested within families/households (second level, n = 6,696) and then census tracts (third level, n = 2,191) for examination of the contextual effect of cumulative neighborhood risk environment on AL. Approximately 35% of adolescents had 2 or more biomarkers of AL. A significant amount of variance in AL was explained at the neighborhood level. The likelihood of having a high AL was approximately 10% higher for adolescents living in medium-cumulative-risk neighborhoods (adjusted odds ratio (OR) = 1.09, 95% confidence interval (CI): 1.08, 1.09), 28% higher for those living in high-risk neighborhoods (adjusted OR = 1.28, 95% CI: 1.27, 1.30), and 69% higher for those living in very-high-risk neighborhoods (adjusted OR = 1.69, 95% CI: 1.68, 1.70) as compared with adolescents living in low-risk areas. Effect modification was observed by both individual- and neighborhood-level sociodemographic factors. These findings offer support for the hypothesis that neighborhood risks may culminate in a range of biologically mediated negative health outcomes detectable in adolescents.

Cumulative Neighborhood Risk of Psychosocial Stress and Allostatic Load in Adolescents

PubMed Central

Theall, Katherine P.; Drury, Stacy S.; Shirtcliff, Elizabeth A.

2012-01-01

The authors examined the impact of cumulative neighborhood risk of psychosocial stress on allostatic load (AL) among adolescents as a mechanism through which life stress, including neighborhood conditions, may affect health and health inequities. They conducted multilevel analyses, weighted for sampling and propensity score-matched, among adolescents aged 12–20 years in the National Health and Nutrition Examination Survey (1999–2006). Individuals (first level, n = 11,886) were nested within families/households (second level, n = 6,696) and then census tracts (third level, n = 2,191) for examination of the contextual effect of cumulative neighborhood risk environment on AL. Approximately 35% of adolescents had 2 or more biomarkers of AL. A significant amount of variance in AL was explained at the neighborhood level. The likelihood of having a high AL was approximately 10% higher for adolescents living in medium-cumulative-risk neighborhoods (adjusted odds ratio (OR) = 1.09, 95% confidence interval (CI): 1.08, 1.09), 28% higher for those living in high-risk neighborhoods (adjusted OR = 1.28, 95% CI: 1.27, 1.30), and 69% higher for those living in very-high-risk neighborhoods (adjusted OR = 1.69, 95% CI: 1.68, 1.70) as compared with adolescents living in low-risk areas. Effect modification was observed by both individual- and neighborhood-level sociodemographic factors. These findings offer support for the hypothesis that neighborhood risks may culminate in a range of biologically mediated negative health outcomes detectable in adolescents. PMID:23035140

Direct and Indirect Effects of Childhood Adversity on Depressive Symptoms in Young Adults.

ERIC Educational Resources Information Center

Turner, Heather A.; Butler, Melissa J.

2003-01-01

Examined whether cumulative trauma in childhood and adolescence is related to depressive symptoms in young adults and explored mediating factors. Results for 649 college students indicate clear differences in cumulative trauma by sociodemographic characteristics, with high trauma associated with early onset of depression and later depressive…

Observed Sensitivity during Family Interactions and Cumulative Risk: A Study of Multiple Dyads per Family

ERIC Educational Resources Information Center

Browne, Dillon T.; Leckie, George; Prime, Heather; Perlman, Michal; Jenkins, Jennifer M.

2016-01-01

The present study sought to investigate the family, individual, and dyad-specific contributions to observed cognitive sensitivity during family interactions. Moreover, the influence of cumulative risk on sensitivity at the aforementioned levels of the family was examined. Mothers and 2 children per family were observed interacting in a round robin…

An application of the Aggregate Exposure Pathway (AEP) and Adverse Outcome Pathway (AOP) frameworks to mechanistically integrate data sources across multiple species into cumulative risk assessment (CRA)

EPA Science Inventory

Toxicologists use dose-response data from both in vivo and in vitro experiments to evaluate the effects of chemical contaminants on organisms. Cumulative risk assessments (CRAs) consider the effects of multiple stressors on multiple endpoints, and utilize environmental exposure ...

Estimating greenspace exposure and benefits for cumulative risk assessment applications

Treesearch

Rebecca Gernes; Richard Hertzberg; Margaret MacDonell; Glenn Rice; J. Michael Wright; Glennon Beresin; Travis Miller; Julia Africa; Geoffrey Donovan; J. Aaron Hipp; Perry Hystad; Laura Jackson; Michelle Kondo; Richard Mitchell; Mark Nieuwenhuijsen; Patrick Ryan; William Sullivan; Matilda Annerstedt. van den Bosch

2016-01-01

This document provides a summary of the technical meeting on greenspace and cumulative risk assessment (GS-CRA) convened May 4−5, 2015 in Cincinnati, OH, by the U.S. Environmental Protection Agency (EPA) Office of Research and Development (ORD) National Center for Environmental Assessment (NCEA). This report highlights the presentations, discussions, and practical...

Effects of Cumulative Family Risk Factors on American Students' Academic Performance

ERIC Educational Resources Information Center

Dunst, Carl J.; Hamby, Deborah W.

2016-01-01

The relationships between cumulative family risk factors and American students' academic performance were examined in all 50 States and the District of Columbia. Data from the 2007 "American Community Survey" were used to ascertain the percent of birth to 18 year old children in the United States who experienced three or more risk…

Concepts, Methods, and Data Sources for Cumulative Health Risk Assessment of Multiple Chemicals, Exposures and Effects: A Resource Document (Final Report, 2008)

EPA Science Inventory

EPA announced the availability of the final report, Concepts, Methods, and Data Sources for Cumulative Health Risk Assessment of Multiple Chemicals, Exposures and Effects: A Resource Document. This report provides the concepts, methods and data sources needed to assist in...

Effect modification of the association of cumulative exposure and cancer risk by intensity of exposure and time since exposure cessation: a flexible method applied to cigarette smoking and lung cancer in the SYNERGY Study.

PubMed

Vlaanderen, Jelle; Portengen, Lützen; Schüz, Joachim; Olsson, Ann; Pesch, Beate; Kendzia, Benjamin; Stücker, Isabelle; Guida, Florence; Brüske, Irene; Wichmann, Heinz-Erich; Consonni, Dario; Landi, Maria Teresa; Caporaso, Neil; Siemiatycki, Jack; Merletti, Franco; Mirabelli, Dario; Richiardi, Lorenzo; Gustavsson, Per; Plato, Nils; Jöckel, Karl-Heinz; Ahrens, Wolfgang; Pohlabeln, Hermann; Tardón, Adonina; Zaridze, David; Field, John K; 't Mannetje, Andrea; Pearce, Neil; McLaughlin, John; Demers, Paul; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Stanescu Dumitru, Rodica; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Boffetta, Paolo; Forastiere, Francesco; Bueno-de-Mesquita, Bas; Peters, Susan; Brüning, Thomas; Kromhout, Hans; Straif, Kurt; Vermeulen, Roel

2014-02-01

The indiscriminate use of the cumulative exposure metric (the product of intensity and duration of exposure) might bias reported associations between exposure to hazardous agents and cancer risk. To assess the independent effects of duration and intensity of exposure on cancer risk, we explored effect modification of the association of cumulative exposure and cancer risk by intensity of exposure. We applied a flexible excess odds ratio model that is linear in cumulative exposure but potentially nonlinear in intensity of exposure to 15 case-control studies of cigarette smoking and lung cancer (1985-2009). Our model accommodated modification of the excess odds ratio per pack-year of cigarette smoking by time since smoking cessation among former smokers. We observed negative effect modification of the association of pack-years of cigarette smoking and lung cancer by intensity of cigarette smoke for persons who smoked more than 20-30 cigarettes per day. Patterns of effect modification were similar across individual studies and across major lung cancer subtypes. We observed strong negative effect modification by time since smoking cessation. Application of our method in this example of cigarette smoking and lung cancer demonstrated that reducing a complex exposure history to a metric such as cumulative exposure is too restrictive.

Effect Modification of the Association of Cumulative Exposure and Cancer Risk by Intensity of Exposure and Time Since Exposure Cessation: A Flexible Method Applied to Cigarette Smoking and Lung Cancer in the SYNERGY Study

PubMed Central

Vlaanderen, Jelle; Portengen, Lützen; Schüz, Joachim; Olsson, Ann; Pesch, Beate; Kendzia, Benjamin; Stücker, Isabelle; Guida, Florence; Brüske, Irene; Wichmann, Heinz-Erich; Consonni, Dario; Landi, Maria Teresa; Caporaso, Neil; Siemiatycki, Jack; Merletti, Franco; Mirabelli, Dario; Richiardi, Lorenzo; Gustavsson, Per; Plato, Nils; Jöckel, Karl-Heinz; Ahrens, Wolfgang; Pohlabeln, Hermann; Tardón, Adonina; Zaridze, David; Field, John K.; 't Mannetje, Andrea; Pearce, Neil; McLaughlin, John; Demers, Paul; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Stanescu Dumitru, Rodica; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Boffetta, Paolo; Forastiere, Francesco; Bueno-de-Mesquita, Bas; Peters, Susan; Brüning, Thomas; Kromhout, Hans; Straif, Kurt; Vermeulen, Roel

2014-01-01

The indiscriminate use of the cumulative exposure metric (the product of intensity and duration of exposure) might bias reported associations between exposure to hazardous agents and cancer risk. To assess the independent effects of duration and intensity of exposure on cancer risk, we explored effect modification of the association of cumulative exposure and cancer risk by intensity of exposure. We applied a flexible excess odds ratio model that is linear in cumulative exposure but potentially nonlinear in intensity of exposure to 15 case-control studies of cigarette smoking and lung cancer (1985–2009). Our model accommodated modification of the excess odds ratio per pack-year of cigarette smoking by time since smoking cessation among former smokers. We observed negative effect modification of the association of pack-years of cigarette smoking and lung cancer by intensity of cigarette smoke for persons who smoked more than 20–30 cigarettes per day. Patterns of effect modification were similar across individual studies and across major lung cancer subtypes. We observed strong negative effect modification by time since smoking cessation. Application of our method in this example of cigarette smoking and lung cancer demonstrated that reducing a complex exposure history to a metric such as cumulative exposure is too restrictive. PMID:24355332

Cumulative reproductive effects of in utero administration of mixtures of antiandrogens in male SD rats: synergy or additivity?

EPA Science Inventory

In 1996 the USEPA was charged under the FQPA to consider the cumulative effects of chemicals in their risk assessments. Our studies were conducted to provide a framework for assessing the cumulative effects of antiandrogens. Toxicants were administered individually or as mixtures...

17 CFR 240.17i-7 - Calculations of allowable capital and risk allowances or alternative capital assessment.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) Cumulative and non-cumulative preferred stock, except that the amount of cumulative preferred stock may not..., and credit substitutes in as follows: (1) By multiplying the credit equivalent amount of the... accordance with the following: (i) Credit equivalent amount: (A) Certain loans and loan commitments...

17 CFR 240.17i-7 - Calculations of allowable capital and risk allowances or alternative capital assessment.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) Cumulative and non-cumulative preferred stock, except that the amount of cumulative preferred stock may not..., and credit substitutes in as follows: (1) By multiplying the credit equivalent amount of the... accordance with the following: (i) Credit equivalent amount: (A) Certain loans and loan commitments...

17 CFR 240.17i-7 - Calculations of allowable capital and risk allowances or alternative capital assessment.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) Cumulative and non-cumulative preferred stock, except that the amount of cumulative preferred stock may not..., and credit substitutes in as follows: (1) By multiplying the credit equivalent amount of the... accordance with the following: (i) Credit equivalent amount: (A) Certain loans and loan commitments...

17 CFR 240.17i-7 - Calculations of allowable capital and risk allowances or alternative capital assessment.

Code of Federal Regulations, 2012 CFR

2012-04-01

...) Cumulative and non-cumulative preferred stock, except that the amount of cumulative preferred stock may not..., and credit substitutes in as follows: (1) By multiplying the credit equivalent amount of the... accordance with the following: (i) Credit equivalent amount: (A) Certain loans and loan commitments...

Early development of de novo hepatocellular carcinoma after direct-acting agent therapy: Comparison with pegylated interferon-based therapy in chronic hepatitis C patients.

PubMed

Yoo, S H; Kwon, J H; Nam, S W; Kim, H Y; Kim, C W; You, C R; Choi, S W; Cho, S H; Han, J-Y; Song, D S; Chang, U I; Yang, J M; Lee, H L; Lee, S W; Han, N I; Kim, S-H; Song, M J; Hwang, S; Sung, P S; Jang, J W; Bae, S H; Choi, J Y; Yoon, S K

2018-04-16

Patients with chronic hepatitis C who achieve a sustained viral response after pegylated interferon therapy have a reduced risk of hepatocellular carcinoma, but the risk after treatment with direct-acting antivirals is unclear. We compared the rates of early development of hepatocellular carcinoma after direct-acting antivirals and after pegylated interferon therapy. We retrospectively analysed 785 patients with chronic hepatitis C who had no history of hepatocellular carcinoma (211 treated with pegylated interferon, 574 with direct-acting antivirals) and were followed up for at least 24 weeks after antiviral treatment. De novo hepatocellular carcinoma developed in 6 of 574 patients receiving direct-acting antivirals and in 1 of 211 patients receiving pegylated interferon. The cumulative incidence of early hepatocellular carcinoma development did not differ between the treatment groups either for the whole cohort (1.05% vs 0.47%, P = .298) or for those patients with Child-Pugh Class A cirrhosis (3.73% vs 2.94%, P = .827). Multivariate analysis indicated that alpha-fetoprotein level >9.5 ng/mL at the time of end-of-treatment response was the only independent risk factor for early development of hepatocellular carcinoma in all patients (P < .0001, hazard ratio 176.174, 95% confidence interval 10.768-2882.473) and in patients treated with direct-acting agents (P < .0001, hazard ratio 128.402, 95% confidence interval 8.417-1958.680). In conclusion, the rate of early development of hepatocellular carcinoma did not differ between patients treated with pegylated interferon and those treated with direct-acting antivirals and was associated with the serum alpha-fetoprotein level at the time of end-of-treatment response. © 2018 John Wiley & Sons Ltd.

Adverse Childhood Experiences and the Risk of Criminal Justice Involvement and Victimization Among Homeless Adults With Mental Illness.

PubMed

Edalati, Hanie; Nicholls, Tonia L; Crocker, Anne G; Roy, Laurence; Somers, Julian M; Patterson, Michelle L

2017-12-01

Exposure to adverse childhood experiences (ACEs) is highly prevalent among homeless individuals and is associated with negative consequences during homelessness. This study examined the effect of ACEs on the risk of criminal justice involvement and victimization among homeless individuals with mental illness. The study used baseline data from a demonstration project (At Home/Chez Soi) that provided Housing First and recovery-oriented services to homeless adults with mental illness. The sample was recruited from five Canadian cities and included participants who provided valid responses on an ACEs questionnaire (N=1,888). Fifty percent reported more than four types of ACE, 19% reported three or four types, 19% reported one or two, and 12% reported none. Rates of criminal justice involvement and victimization were significantly higher among those with a history of ACEs. For victimization, the association was significant for all ten types of ACE, and for justice involvement, it was significant for seven types. Logistic regression models indicated that the effect of cumulative childhood adversity on the two outcomes was significant regardless of sociodemographic factors, duration of homelessness, and psychiatric diagnosis, with one exception: the relationship between cumulative childhood adversity and criminal justice involvement did not remain significant when the analysis controlled for a diagnosis of posttraumatic stress disorder and substance dependence. Findings support the need for early interventions for at-risk youths and trauma-informed practice and violence prevention policies that specifically target homeless populations.

Predictive Factors for Verbal Memory Performance Over Decades of Aging: Data from the Women's Healthy Ageing Project.

PubMed

Szoeke, Cassandra; Lehert, Philippe; Henderson, Victor W; Dennerstein, Lorraine; Desmond, Patricia; Campbell, Stephen

2016-10-01

Abnormalities in brain structure and function can occur several decades prior to the onset of cognitive decline. It is in the preceding decades that an intervention is most likely to be effective, when informed by an understanding of factors contributing to the disease prodrome. Few studies, however, have sufficient longitudinal data on relevant risks to determine the optimum targets for interventions to improve cognition in aging. In this article we examine the timing and exposure of factors contributing to verbal memory performance in later life. 387 participants from the population-based Women's Healthy Ageing Project, mean age at baseline of 49.6 years (range: 45-55 years), had complete neuropsychiatric assessments, clinical information, physical measures, and biomarkers collected at baseline, with at least three follow-up visits that included at least one cognitive reassessment. Mixed linear models were conducted to assess the significance of risk factors on later-life verbal memory. We explored the influence of early, contemporaneous, and cumulative exposures. Younger age and better education were associated with baseline memory test performance (CERAD). Over the 20 years of study follow-up, cumulative mid- to late-life physical activity had the strongest effect on better later life verbal memory (0.136 [0.058, 0.214]). The next most likely contributors to verbal memory in late life were the negative effect of cumulative hypertension (-0.033 [-0.047, -0.0.18] and the beneficial effect of HDL cholesterol (0.818 [0.042, 1.593]). Findings suggest that midlife interventions focused on physical activity, hypertension control, and achieving optimal levels of HDL cholesterol will help maintain later-life verbal memory skills. Copyright © 2016 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Refinement of arsenic attributable health risks in rural Pakistan using population specific dietary intake values.

PubMed

Rasheed, Hifza; Slack, Rebecca; Kay, Paul; Gong, Yun Yun

2017-02-01

Previous risk assessment studies have often utilised generic consumption or intake values when evaluating ingestion exposure pathways. If these values do not accurately reflect the country or scenario in question, the resulting risk assessment will not provide a meaningful representation of cancer risks in that particular country/scenario. This study sought to determine water and food intake parameters for one region in South Asia, rural Pakistan, and assess the role population specific intake parameters play in cancer risk assessment. A questionnaire was developed to collect data on sociodemographic features and 24-h water and food consumption patterns from a rural community. The impact of dietary differences on cancer susceptibility linked to arsenic exposure was evaluated by calculating cancer risks using the data collected in the current study against standard water and food intake levels for the USA, Europe and Asia. A probabilistic cancer risk was performed for each set of intake values of this study. Average daily total water intake based on drinking direct plain water and indirect water from food and beverages was found to be 3.5Lday -1 (95% CI: 3.38, 3.57) exceeding the US Environmental Protection Agency's default (2.5Lday -1 ) and World Health Organization's recommended intake value (2Lday -1 ). Average daily rice intake (469gday -1 ) was found to be lower than in India and Bangladesh whereas wheat intake (402gday -1 ) was higher than intake reported for USA, Europe and Asian sub-regions. Consequently, arsenic-associated cumulative cancer risks determined for daily water intake was found to be 17 chances in children of 3-6years (95% CI: 0.0014, 0.0017), 14 in children of age 6-16years (95% CI: 0.001, 0.0011) and 6 in adults of 16-67years (95% CI: 0.0006, 0.0006) in a population size of 10,000. This is higher than the risks estimated using the US Environmental Protection Agency and World Health Organization's default recommended water intake levels. Rice intake data showed early life cumulative cancer risks of 15 chances in 10,000 for children of 3-6years (95% CI: 0.0012, 0.0015), 14 in children of 6-16years (95% CI: 0.0011, 0.0014) and later life risk of 8 adults (95% CI: 0.0008, 0.0008) in a population of 10,000. This is lower than the cancer risks in countries with higher rice intake and elevated arsenic levels (Bangladesh and India). Cumulative cancer risk from arsenic exposure showed the relative risk contribution from total water to be 51%, from rice to be 44% and 5% from wheat intake. The study demonstrates the need to use population specific dietary information for risk assessment and risk management studies. Probabilistic risk assessment concluded the importance of dietary intake in estimating cancer risk, along with arsenic concentrations in water or food and age of exposed rural population. Copyright © 2016 Elsevier Ltd. All rights reserved.

The impact of physical activity on cumulative cardiovascular disease risk factors among Malaysian adults.

PubMed

Rasiah, Rajah; Thangiah, Govindamal; Yusoff, Khalid; Manikam, Rishya; Chandrasekaran, Sankara Kumar; Mustafa, Rujhan; Bakar, Najmin Binti Abu

2015-12-16

Numerous studies have shown the importance of physical activity in reducing the morbidity and mortality rates caused by cardiovascular disease (CVD). However, most of these studies emphasise little on the cumulative effect of CVD risk factors. Hence, this study investigates the association between physical exercise and cumulative CVD risk factors among adults in three different age groups. Using a sample of 7276 respondents drawn from community centers, the REDISCOVER team gathered information on physical activity, CVD risk factors (obesity, diabetes, hypertension, hypercholesterolemia, tobacco use) and socioeconomic and demographic variables in Malaysia. Because the study required medical examination, a convenience sampling frame was preferred in which all volunteers were included in the study. Fasting blood samples and anthropometric (height, weight and more) measurements were collected by trained staffs. Socio-demographic and physical activity variables were recorded through questionnaires. A Chi-square test was performed to identify the bivariate association between the covariates (socioeconomic variables, demographic variables and physical activity) and outcome variable. The association between the main exposure, physical activity, and the outcome variable, cumulative CVD risk factors, was assessed using an ordinal logistic regression model, controlling for socioeconomic status and demographic influences in three different age groups, 35-49, 50-64 and 65 and above. The mean age of participants is 51.8 (SD = 9.4). Respondents in the age groups of 35-49 (aORmoderate = 0.12; 95 % CI: 0.02 - 0.53 ) and 65 and above (aORhigh = 0.58; 95 % CI: 0.24, 0.78) showed a statistically significant inverse relationship between physical activity and cumulative CVD risk factors. However, this relationship was not significant among respondents in the 50-64 age group suggesting the possible influence of other variables, such as stress and environment. The statistically significant results show a negative association between physical exercise and cumulative CVD risk factors. However, the lack of a significant relationship in the 50-64 age group suggests the need to include other considerations in future studies, such as stress and environment.

Subgroups at high risk for ischaemic heart disease:identification and validation in 67 000 individuals from the general population

PubMed Central

Frikke-Schmidt, Ruth; Tybjærg-Hansen, Anne; Dyson, Greg; Haase, Christiane L; Benn, Marianne; Nordestgaard, Børge G; Sing, Charles F

2015-01-01

Background The aetiology of ischaemic heart disease (IHD) is complex and is influenced by a spectrum of environmental factors and susceptibility genes. Traditional statistical modelling considers such factors to act independently in an additive manner. The Patient Rule-Induction Method (PRIM) is a multi-model building strategy for evaluating risk attributable to context-dependent gene and environmental effects. Methods PRIM was applied to 9073 participants from the prospective Copenhagen City Heart Study (CCHS). Gender-specific cumulative incidences were estimated for subgroups defined by categories of age, smoking, hypertension, diabetes, body mass index, total cholesterol, high-density lipoprotein cholesterol and triglycerides and by 94 single nucleotide variants (SNVs).Cumulative incidences for subgroups were validated using an independently ascertained sample of 58 240 participants from the Copenhagen General Population Study (CGPS). Results In the CCHS the overall cumulative incidences were 0.17 in women and 0.21 in men. PRIM identified six and four mutually exclusive subgroups in women and men, respectively, with cumulative incidences of IHD ranging from 0.02 to 0.34. Cumulative incidences of IHD generated by PRIM in the CCHS were validated in four of the six subgroups of women and two of the four subgroups of men in the CGPS. Conclusions PRIM identified high-risk subgroups characterized by specific contexts of selected values of traditional risk factors and genetic variants. These subgroups were validated in an independently ascertained cohort study. Thus, a multi-model strategy may identify groups of individuals with substantially higher risk of IHD than the overall risk for the general population. PMID:25361584

Radiotherapy is essential after complete response to asparaginase-containing chemotherapy in early-stage extranodal nasal-type NK/T-cell lymphoma: A multicenter study from the China Lymphoma Collaborative Group (CLCG).

PubMed

Deng, Xiu-Wen; Wu, Jun-Xin; Wu, Tao; Zhu, Su-Yu; Shi, Mei; Su, Hang; Wang, Ying; He, Xia; Xu, Li-Ming; Yuan, Zhi-Yong; Zhang, Li-Ling; Wu, Gang; Qu, Bao-Lin; Qian, Li-Ting; Hou, Xiao-Rong; Zhang, Fu-Quan; Zhang, Yu-Jing; Zhu, Yuan; Cao, Jian-Zhong; Lan, Sheng-Min; Dong, Mei; Qi, Shu-Nan; Yang, Yong; Li, Ye-Xiong

2018-05-05

This study aimed to clarify the benefit of radiotherapy (RT) in patients with early-stage extranodal NK/T-cell lymphoma (NKTCL) who achieve a complete response (CR) after asparaginase-containing chemotherapy (CT). Of 240 patients achieved a CR after asparaginase-containing CT, 202 patients received additional RT (CT + RT), and 38 patients did not (CT alone). Compared to CT alone, CT + RT significantly improved overall survival (OS), disease-free survival (DFS) and locoregional control (LRC). The 5-year OS, DFS and LRC rates were 84.9%, 76.2% and 84.9% for CT + RT, compared to 58.9% (P = 0.006), 43.6% (P = 0.001) and 62.1% (P = 0.026) for CT alone. The 5-year cumulative disease recurrence rate was 18.8% for CT + RT compared to 46.9% (P = 0.003) for CT alone. High-dose RT (≥50 Gy) significantly decreased the risk of locoregional recurrence. The 5-year cumulative locoregional failure rate was 35.5% for patients receiving <50 Gy compared to 8.8% for patients receiving ≥50 Gy (P = 0.028). For patients with early-stage NKTCL who achieve a CR after asparaginase-containing CT, omission of RT results in frequent locoregional recurrence and a poor prognosis; RT is essential to improve locoregional control and survival. Copyright © 2018 Elsevier B.V. All rights reserved.

Cumulative risk hypothesis: Predicting and preventing child maltreatment recidivism.

PubMed

Solomon, David; Åsberg, Kia; Peer, Samuel; Prince, Gwendolyn

2016-08-01

Although Child Protective Services (CPS) and other child welfare agencies aim to prevent further maltreatment in cases of child abuse and neglect, recidivism is common. Having a better understanding of recidivism predictors could aid in preventing additional instances of maltreatment. A previous study identified two CPS interventions that predicted recidivism: psychotherapy for the parent, which was related to a reduced risk of recidivism, and temporary removal of the child from the parent's custody, which was related to an increased recidivism risk. However, counter to expectations, this previous study did not identify any other specific risk factors related to maltreatment recidivism. For the current study, it was hypothesized that (a) cumulative risk (i.e., the total number of risk factors) would significantly predict maltreatment recidivism above and beyond intervention variables in a sample of CPS case files and that (b) therapy for the parent would be related to a reduced likelihood of recidivism. Because it was believed that the relation between temporary removal of a child from the parent's custody and maltreatment recidivism is explained by cumulative risk, the study also hypothesized that that the relation between temporary removal of the child from the parent's custody and recidivism would be mediated by cumulative risk. After performing a hierarchical logistic regression analysis, the first two hypotheses were supported, and an additional predictor, psychotherapy for the child, also was related to reduced chances of recidivism. However, Hypothesis 3 was not supported, as risk did not significantly mediate the relation between temporary removal and recidivism. Copyright © 2016 Elsevier Ltd. All rights reserved.

A novel tool for user-friendly estimation of natural, diagnostic and professional radiation risk: Radio-Risk software.

PubMed

Carpeggiani, Clara; Paterni, Marco; Caramella, Davide; Vano, Eliseo; Semelka, Richard C; Picano, Eugenio

2012-11-01

Awareness of radiological risk is low among doctors and patients. An educational/decision tool that considers each patient' s cumulative lifetime radiation exposure would facilitate provider-patient communication. The purpose of this work was to develop user-friendly software for simple estimation and communication of radiological risk to patients and doctors as a part of the SUIT-Heart (Stop Useless Imaging Testing in Heart disease) Project of the Tuscany Region. We developed a novel software program (PC-platform, Windows OS fully downloadable at http://suit-heart.ifc.cnr.it) considering reference dose estimates from American Heart Association Radiological Imaging 2009 guidelines and UK Royal College of Radiology 2007 guidelines. Cancer age and gender-weighted risk were derived from Biological Effects of Ionising Radiation VII Committee, 2006. With simple input functions (demographics, age, gender) the user selects from a predetermined menu variables relating to natural (e.g., airplane flights and geo-tracked background exposure), professional (e.g., cath lab workers) and medical (e.g., CT, cardiac scintigraphy, coronary stenting) sources. The program provides a simple numeric (cumulative effective dose in milliSievert, mSv, and equivalent number of chest X-rays) and graphic (cumulative temporal trends of exposure, cancer cases out of 100 exposed persons) display. A simple software program allows straightforward estimation of cumulative dose (in multiples of chest X-rays) and risk (in extra % lifetime cancer risk), with simple numbers quantifying lifetime extra cancer risk. Pictorial display of radiation risk may be valuable for increasing radiological awareness in cardiologists. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Children's Executive Function in a CPS-Involved Sample: Effects of Cumulative Adversity and Specific Types of Adversity.

PubMed

Roos, Leslie E; Kim, Hyoun K; Schnabler, Simone; Fisher, Philip A

2016-12-01

Prior research has identified the presence of executive function (EF) deficits in child protective service (CPS) involved (versus non-involved) children but minimal work has examined predictors that might explain individual differences within these CPS-involved children. Here, we sought to characterize EF in a large sample (N=694) of CPS-involved children and examine how specific adversities (physical abuse, neglect, caregiver domestic violence, and caregiver substance dependence) and cumulative adversity (at ages 0-3 and 3-6 years) predict EF (at approximately 5-6 years). It was expected that the sample would exhibit low EF overall based on previous research in maltreated children. Specific adversity and cumulative adversity analyses were largely exploratory given the limited previous work in this area. Results indicated poor EF overall, with 43.5% of children performing worse than chance. Amongst children who performed greater than chance, higher cumulative adversity, physical abuse, and caregiver substance use (at ages 3-6 years) predicted better EF. These findings join literature documenting that, within CPS-involved children, the presence of certain adversities predicts variable cognitive function. Findings highlight the potential relevance of evolutionary psychology to understanding how alterations in behavior linked to harsh and unpredictable early environments may cue accelerated brain development underlying relative cognitive advantages, within at-risk, low performing samples. Longitudinal studies are critical to determine if the relative EF advantages linked to higher adversity persist over time or result in lower EF later on, reflecting a more rapid, but overall limited, trajectory of cognitive development.

Silicosis among gold miners: exposure--response analyses and risk assessment.

PubMed Central

Steenland, K; Brown, D

1995-01-01

OBJECTIVES. This study sought to estimate the risk of silicosis by cumulative exposure-years in a cohort of miners exposed to silica, as well as the lifetime risk of silicosis under the current Occupational Safety and Health Administration (OSHA) standard (0.09 mg/m3). METHODS. In a cohort study of 3330 gold miners who worked at least 1 year underground from 1940 to 1965 (average 9 years) and were exposed to a median silica level of 0.05 mg/m3 (0.15 mg/m3 for those hired before 1930), 170 cases of silicosis were determined from either death certificates or two cross-sectional radiographic surveys. RESULTS. The risk of silicosis was less than 1% with a cumulative exposure under 0.5 mg/m3-years, increasing to 68% to 84% for the highest cumulative exposure category of more than 4 mg/m3-years. Cumulative exposure was the best predictor of disease, followed by duration of exposure and average exposure. After adjustment for competing risks of death, a 45-year exposure under the current OSHA standard would lead to a lifetime risk of silicosis of 35% to 47%. CONCLUSIONS. Almost 2 million US workers are currently exposed to silica. Our results add to a small but increasing body of literature that suggests that the current OSHA silica exposure level is unacceptably high. PMID:7573620

Cumulative Risk of Guillain–Barré Syndrome Among Vaccinated and Unvaccinated Populations During the 2009 H1N1 Influenza Pandemic

PubMed Central

Iqbal, Shahed; Stewart, Brock; Tokars, Jerome; DeStefano, Frank

2014-01-01

Objectives. We sought to assess risk of Guillain–Barré syndrome (GBS) among influenza A (H1N1) 2009 monovalent (pH1N1) vaccinated and unvaccinated populations at the end of the 2009 pandemic. Methods. We applied GBS surveillance data from a US population catchment area of 45 million from October 15, 2009, through May 31, 2010. GBS cases meeting Brighton Collaboration criteria were included. We calculated the incidence density ratio (IDR) among pH1N1 vaccinated and unvaccinated populations. We also estimated cumulative GBS risk using life table analysis. Additionally, we used vaccine coverage data and census population estimates to calculate denominators. Results. There were 392 GBS cases; 64 (16%) occurred after pH1N1vaccination. The vaccinated population had lower average risk (IDR = 0.83, 95% confidence interval = 0.63, 1.08) and lower cumulative risk (6.6 vs 9.2 cases per million persons, P = .012) of GBS. Conclusions. Our findings suggest that at the end of the influenza season cumulative GBS risk was less among the pH1N1vaccinated than the unvaccinated population, suggesting the benefit of vaccination as it relates to GBS. The observed potential protective effect on GBS attributed to vaccination warrants further study. PMID:24524517

Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers.

PubMed

Kuchenbaecker, Karoline B; Hopper, John L; Barnes, Daniel R; Phillips, Kelly-Anne; Mooij, Thea M; Roos-Blom, Marie-José; Jervis, Sarah; van Leeuwen, Flora E; Milne, Roger L; Andrieu, Nadine; Goldgar, David E; Terry, Mary Beth; Rookus, Matti A; Easton, Douglas F; Antoniou, Antonis C; McGuffog, Lesley; Evans, D Gareth; Barrowdale, Daniel; Frost, Debra; Adlard, Julian; Ong, Kai-Ren; Izatt, Louise; Tischkowitz, Marc; Eeles, Ros; Davidson, Rosemarie; Hodgson, Shirley; Ellis, Steve; Nogues, Catherine; Lasset, Christine; Stoppa-Lyonnet, Dominique; Fricker, Jean-Pierre; Faivre, Laurence; Berthet, Pascaline; Hooning, Maartje J; van der Kolk, Lizet E; Kets, Carolien M; Adank, Muriel A; John, Esther M; Chung, Wendy K; Andrulis, Irene L; Southey, Melissa; Daly, Mary B; Buys, Saundra S; Osorio, Ana; Engel, Christoph; Kast, Karin; Schmutzler, Rita K; Caldes, Trinidad; Jakubowska, Anna; Simard, Jacques; Friedlander, Michael L; McLachlan, Sue-Anne; Machackova, Eva; Foretova, Lenka; Tan, Yen Y; Singer, Christian F; Olah, Edith; Gerdes, Anne-Marie; Arver, Brita; Olsson, Håkan

2017-06-20

The clinical management of BRCA1 and BRCA2 mutation carriers requires accurate, prospective cancer risk estimates. To estimate age-specific risks of breast, ovarian, and contralateral breast cancer for mutation carriers and to evaluate risk modification by family cancer history and mutation location. Prospective cohort study of 6036 BRCA1 and 3820 BRCA2 female carriers (5046 unaffected and 4810 with breast or ovarian cancer or both at baseline) recruited in 1997-2011 through the International BRCA1/2 Carrier Cohort Study, the Breast Cancer Family Registry and the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, with ascertainment through family clinics (94%) and population-based studies (6%). The majority were from large national studies in the United Kingdom (EMBRACE), the Netherlands (HEBON), and France (GENEPSO). Follow-up ended December 2013; median follow-up was 5 years. BRCA1/2 mutations, family cancer history, and mutation location. Annual incidences, standardized incidence ratios, and cumulative risks of breast, ovarian, and contralateral breast cancer. Among 3886 women (median age, 38 years; interquartile range [IQR], 30-46 years) eligible for the breast cancer analysis, 5066 women (median age, 38 years; IQR, 31-47 years) eligible for the ovarian cancer analysis, and 2213 women (median age, 47 years; IQR, 40-55 years) eligible for the contralateral breast cancer analysis, 426 were diagnosed with breast cancer, 109 with ovarian cancer, and 245 with contralateral breast cancer during follow-up. The cumulative breast cancer risk to age 80 years was 72% (95% CI, 65%-79%) for BRCA1 and 69% (95% CI, 61%-77%) for BRCA2 carriers. Breast cancer incidences increased rapidly in early adulthood until ages 30 to 40 years for BRCA1 and until ages 40 to 50 years for BRCA2 carriers, then remained at a similar, constant incidence (20-30 per 1000 person-years) until age 80 years. The cumulative ovarian cancer risk to age 80 years was 44% (95% CI, 36%-53%) for BRCA1 and 17% (95% CI, 11%-25%) for BRCA2 carriers. For contralateral breast cancer, the cumulative risk 20 years after breast cancer diagnosis was 40% (95% CI, 35%-45%) for BRCA1 and 26% (95% CI, 20%-33%) for BRCA2 carriers (hazard ratio [HR] for comparing BRCA2 vs BRCA1, 0.62; 95% CI, 0.47-0.82; P=.001 for difference). Breast cancer risk increased with increasing number of first- and second-degree relatives diagnosed as having breast cancer for both BRCA1 (HR for ≥2 vs 0 affected relatives, 1.99; 95% CI, 1.41-2.82; P<.001 for trend) and BRCA2 carriers (HR, 1.91; 95% CI, 1.08-3.37; P=.02 for trend). Breast cancer risk was higher if mutations were located outside vs within the regions bounded by positions c.2282-c.4071 in BRCA1 (HR, 1.46; 95% CI, 1.11-1.93; P=.007) and c.2831-c.6401 in BRCA2 (HR, 1.93; 95% CI, 1.36-2.74; P<.001). These findings provide estimates of cancer risk based on BRCA1 and BRCA2 mutation carrier status using prospective data collection and demonstrate the potential importance of family history and mutation location in risk assessment.

Early transcriptional changes in cardiac mitochondria during chronic doxorubicin exposure and mitigation by dexrazoxane in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vijay, Vikrant; Moland, Carrie L.; Han, Tao

Identification of early biomarkers of cardiotoxicity could help initiate means to ameliorate the cardiotoxic actions of clinically useful drugs such as doxorubicin (DOX). Since DOX has been shown to target mitochondria, transcriptional levels of mitochondria-related genes were evaluated to identify early candidate biomarkers in hearts of male B6C3F{sub 1} mice given a weekly intravenous dose of 3 mg/kg DOX or saline (SAL) for 2, 3, 4, 6, or 8 weeks (6, 9, 12, 18, or 24 mg/kg cumulative DOX doses, respectively). Also, a group of mice was pretreated (intraperitoneally) with the cardio-protectant, dexrazoxane (DXZ; 60 mg/kg) 30 min before eachmore » weekly dose of DOX or SAL. At necropsy a week after the last dose, increased plasma concentrations of cardiac troponin T (cTnT) were detected at 18 and 24 mg/kg cumulative DOX doses, whereas myocardial alterations were observed only at the 24 mg/kg dose. Of 1019 genes interrogated, 185, 109, 140, 184, and 451 genes were differentially expressed at 6, 9, 12, 18, and 24 mg/kg cumulative DOX doses, respectively, compared to concurrent SAL-treated controls. Of these, expression of 61 genes associated with energy metabolism and apoptosis was significantly altered before and after occurrence of myocardial injury, suggesting these as early genomics markers of cardiotoxicity. Much of these DOX-induced transcriptional changes were attenuated by pretreatment of mice with DXZ. Also, DXZ treatment significantly reduced plasma cTnT concentration and completely ameliorated cardiac alterations induced by 24 mg/kg cumulative DOX. This information on early transcriptional changes during DOX treatment may be useful in designing cardioprotective strategies targeting mitochondria. - Highlights: • Altered mitochondria-related gene expression before heart injury by doxorubicin • Dexrazoxane mitigated doxorubicin-induced early expression changes in mitochondria. • Dexrazoxane completely ameliorated doxorubicin-induced pathology in mouse heart.« less

Fear affects parental care, which predicts juvenile survival and exacerbates the total cost of fear on demography.

PubMed

Dudeck, Blair P; Clinchy, Michael; Allen, Marek C; Zanette, Liana Y

2018-01-01

Fear itself (perceived predation risk) can affect wildlife demography, but the cumulative impact of fear on population dynamics is not well understood. Parental care is arguably what most distinguishes birds and mammals from other taxa, yet only one experiment on wildlife has tested fear effects on parental food provisioning and the repercussions this has for the survival of dependent offspring, and only during early-stage care. We tested the effect of fear on late-stage parental care of mobile dependent offspring, by locating radio-tagged Song Sparrow fledglings and broadcasting predator or non-predator playbacks in their vicinity, measuring their parent's behavior and their own, and tracking the offspring's survival to independence. Fear significantly reduced late-stage parental care, and parental fearfulness (as indexed by their reduction in provisioning when hearing predators) significantly predicted their offspring's condition and survival. Combining results from this experiment with that on early-stage care, we project that fear itself is powerful enough to reduce late-stage survival by 24%, and cumulatively reduce the number of young reaching independence by more than half, 53%. Experiments in invertebrate and aquatic systems demonstrate that fear is commonly as important as direct killing in affecting prey demography, and we suggest focusing more on fear effects and on offspring survival will reveal the same for wildlife. © 2017 by the Ecological Society of America.

17 CFR 240.15c3-1g - Conditions for ultimate holding companies of certain brokers or dealers (Appendix G to 17 CFR 240...

Code of Federal Regulations, 2012 CFR

2012-04-01

... Commission determines, based on a review of the group-wide internal risk management control system and... regulator, all written policies and procedures concerning the group-wide internal risk management control... (as defined in 12 CFR 225, appendix A); (ii) Cumulative and non-cumulative preferred stock, except...

17 CFR 240.15c3-1g - Conditions for ultimate holding companies of certain brokers or dealers (Appendix G to 17 CFR 240...

Code of Federal Regulations, 2010 CFR

2010-04-01

... Commission determines, based on a review of the group-wide internal risk management control system and... regulator, all written policies and procedures concerning the group-wide internal risk management control... (as defined in 12 CFR 225, appendix A); (ii) Cumulative and non-cumulative preferred stock, except...

Cumulative Socioeconomic Status Risk, Allostatic Load, and Adjustment: A Prospective Latent Profile Analysis with Contextual and Genetic Protective Factors

ERIC Educational Resources Information Center

Brody, Gene H.; Yu, Tianyi; Chen, Yi-Fu; Kogan, Steven M.; Evans, Gary W.; Beach, Steven R. H.; Windle, Michael; Simons, Ronald L.; Gerrard, Meg; Gibbons, Frederick X.; Philibert, Robert A.

2013-01-01

The health disparities literature has identified a common pattern among middle-aged African Americans that includes high rates of chronic disease along with low rates of psychiatric disorders despite exposure to high levels of cumulative socioeconomic status (SES) risk. The current study was designed to test hypotheses about the developmental…

Barriers to Success in Parent Training for Young Children with Developmental Delay: The Role of Cumulative Risk

ERIC Educational Resources Information Center

Bagner, Daniel M.; Graziano, Paulo A.

2013-01-01

The purpose of this study was to examine the effect of cumulative risk on dropout and treatment outcome in parent training. Participants were 44 families of young children (mean age of 49.59 months) who presented with elevated externalizing behavior problems and developmental delay or borderline developmental delay. All families were offered to…

EPA Workshop on Epigenetics and Cumulative Risk ...

EPA Pesticide Factsheets

Agenda Download the Workshop Agenda (PDF) The workshop included presentations and discussions by scientific experts pertaining to three topics (i.e., epigenetic changes associated with diverse stressors, key science considerations in understanding epigenetic changes, and practical application of epigenetic tools to address cumulative risks from environmental stressors), to address several questions under each topic, and included an opportunity for attendees to participate in break-out groups, provide comments and ask questions. Workshop Goals The workshop seeks to examine the opportunity for use of aggregate epigenetic change as an indicator in cumulative risk assessment for populations exposed to multiple stressors that affect epigenetic status. Epigenetic changes are specific molecular changes around DNA that alter expression of genes. Epigenetic changes include DNA methylation, formation of histone adducts, and changes in micro RNAs. Research today indicates that epigenetic changes are involved in many chronic diseases (cancer, cardiovascular disease, obesity, diabetes, mental health disorders, and asthma). Research has also linked a wide range of stressors including pollution and social factors with occurrence of epigenetic alterations. Epigenetic changes have the potential to reflect impacts of risk factors across multiple stages of life. Only recently receiving attention is the nexus between the factors of cumulative exposure to environmental

CUMULATIVE REPRODUCTIVE EFFECTS OF IN UTERO ADMINISTRATION OF A MIXTURE OF TEN “ANTIANDROGENS” IN MALE SD RATS: SYNERGY OR ADDITIVITY?

EPA Science Inventory

In 1996, the USEPA was charged under FQPA to consider the cumulative effects of chemicals in their risk assessments. We are conducting studies to provide a framework for assessing the cumulative effects of antiandrogens. In the current study, ten “antiandrogenic” chemicals were a...

Predicting Time to Hospital Discharge for Extremely Preterm Infants

PubMed Central

Hintz, Susan R.; Bann, Carla M.; Ambalavanan, Namasivayam; Cotten, C. Michael; Das, Abhik; Higgins, Rosemary D.

2010-01-01

As extremely preterm infant mortality rates have decreased, concerns regarding resource utilization have intensified. Accurate models to predict time to hospital discharge could aid in resource planning, family counseling, and perhaps stimulate quality improvement initiatives. Objectives For infants <27 weeks estimated gestational age (EGA), to develop, validate and compare several models to predict time to hospital discharge based on time-dependent covariates, and based on the presence of 5 key risk factors as predictors. Patients and Methods This was a retrospective analysis of infants <27 weeks EGA, born 7/2002-12/2005 and surviving to discharge from a NICHD Neonatal Research Network site. Time to discharge was modeled as continuous (postmenstrual age at discharge, PMAD), and categorical variables (“Early” and “Late” discharge). Three linear and logistic regression models with time-dependent covariate inclusion were developed (perinatal factors only, perinatal+early neonatal factors, perinatal+early+later factors). Models for Early and Late discharge using the cumulative presence of 5 key risk factors as predictors were also evaluated. Predictive capabilities were compared using coefficient of determination (R2) for linear models, and AUC of ROC curve for logistic models. Results Data from 2254 infants were included. Prediction of PMAD was poor, with only 38% of variation explained by linear models. However, models incorporating later clinical characteristics were more accurate in predicting “Early” or “Late” discharge (full models: AUC 0.76-0.83 vs. perinatal factor models: AUC 0.56-0.69). In simplified key risk factors models, predicted probabilities for Early and Late discharge compared favorably with observed rates. Furthermore, the AUC (0.75-0.77) were similar to those of models including the full factor set. Conclusions Prediction of Early or Late discharge is poor if only perinatal factors are considered, but improves substantially with knowledge of later-occurring morbidities. Prediction using a few key risk factors is comparable to full models, and may offer a clinically applicable strategy. PMID:20008430

Thyroid peroxidase antibodies during early gestation and the subsequent risk of first-onset postpartum depression: A prospective cohort study.

PubMed

Wesseloo, Richard; Kamperman, Astrid M; Bergink, Veerle; Pop, Victor J M

2018-01-01

During the postpartum period, women are at risk for the new onset of both auto-immune thyroid disorders and depression. The presence of thyroid peroxidase antibodies (TPO-ab) during early gestation is predictive for postpartum auto-immune thyroid dysfunction. The aim of this study was to investigate the association between TPO-ab status during early gestation and first-onset postpartum depression. Prospective cohort study (n = 1075) with follow-up during pregnancy up to one year postpartum. Thyroid function and TPO-ab status were measured during early gestation. Depressive symptomatology was assessed during each trimester and at four time points postpartum with the Edinburgh Depression Scale (EDS). Women with antenatal depression were not eligible for inclusion. Self-reported postpartum depression was defined with an EDS cut-off of ≥ 13. The cumulative incidence of self-reported first-onset depression in the first postpartum year was 6.3%. A positive TPO-ab status was associated with an increased risk for self-reported first-onset depression at four months postpartum (adjusted OR 3.8; 95% CI 1.3-11.6), but not at other postpartum time points. Prevalence rates of self-reported postpartum depression declined after four months postpartum in the TPO-ab positive group, but remained constant in the TPO-ab negative group. Depression was defined with a self-rating questionnaire (EDS). Women with an increased TPO-ab titer during early gestation are at increased risk for self-reported first-onset depression. The longitudinal pattern of self-reported postpartum depression in the TPO-ab positive group was similar to the typical course of postpartum TPO-ab titers changes. This suggests overlap in the etiology of first-onset postpartum depression and auto-immune thyroid dysfunction. Thyroid function should be evaluated in women with first-onset postpartum depression. Copyright © 2017 Elsevier B.V. All rights reserved.

Non-melanoma skin cancer and risk of Alzheimer’s disease and all-cause dementia

PubMed Central

Schmidt, Sigrun A. J.; Ording, Anne G.; Horváth-Puhó, Erzsébet; Sørensen, Henrik T.; Henderson, Victor W.

2017-01-01

Cancer patients may be at decreased risk of Alzheimer’s disease. This hypothesis is best developed for non-melanoma skin cancer (NMSC), but supportive epidemiological data are sparse. We therefore conducted a nationwide cohort study of the association between NMSC and Alzheimer’s disease (main outcome) and all-cause dementia. Using Danish medical databases, we identified adults diagnosed with NMSC between 1 January 1980 and 30 November 2013 (n = 216,221) and a comparison cohort of five individuals matched to each NMSC patient by sex and birth year (n = 1,081,097). We followed individuals from the time of diagnosis, or corresponding date for matched comparators, until a dementia diagnosis, death, emigration, or 30 November 2013, whichever came first. We used stratified Cox regression adjusted for comorbidities to compute hazard ratios (HRs) associating NMSC with dementia. We computed cumulative risks of dementia, treating death as a competing risk. NMSC was associated with a HR of 0.95 (95% confidence interval [CI]: 0.92–0.98) for Alzheimer’s disease and 0.92 (95% CI: 0.90–0.94) for all-cause dementia. HRs were similar for basal cell and squamous cell carcinoma, the two most common forms of NMSC. Estimates of risk reduction were more pronounced in the beginning of follow-up, reaching null after 5–10 years. At the end of follow-up (34 years), cumulative risk of Alzheimer’s disease was 4.6% (95% CI: 4.4%–4.8%) among patients with NMSC vs. 4.7% (95% CI: 4.6%–4.9%) in the comparison cohort. In conclusion, NMSC was associated with 2%–10% reductions in relative risks of Alzheimer’s disease and all-cause dementia. However, these small inverse associations may have been caused by ascertainment bias due to decreased awareness of NMSC tumors in persons with undiagnosed early cognitive impairment or by confounding from a more neuroprotective lifestyle among persons with NMSC. PMID:28225789

Interactive Contributions of Cumulative Peer Stress and Executive Function Deficits to Depression in Early Adolescence

ERIC Educational Resources Information Center

Agoston, Anna M.; Rudolph, Karen D.

2016-01-01

Exposure to peer stress contributes to adolescent depression, yet not all youth experience these effects. Thus, it is important to identify individual differences that shape the consequences of peer stress. This research investigated the interactive contribution of cumulative peer stress during childhood (second-fifth grades) and executive…

Early Life Stress Increases Metabolic Risk, HPA Axis Reactivity, and Depressive-Like Behavior When Combined with Postweaning Social Isolation in Rats.

PubMed

Vargas, Javier; Junco, Mariana; Gomez, Carlos; Lajud, Naima

2016-01-01

Early-life stress is associated with depression and metabolic abnormalities that increase the risk of cardiovascular disease and diabetes. Such associations could be due to increased glucocorticoid levels. Periodic maternal separation in the neonate and rearing in social isolation are potent stressors that increase hypothalamus-pituitary-adrenal axis activity. Moreover, social isolation promotes feed intake and body weight gain in rats subjected to periodic maternal separation; however, its effects on metabolic risks have not been described. In the present study, we evaluated whether periodic maternal separation, social isolation rearing, and a combination of these two stressors (periodic maternal separation + social isolation rearing) impair glucose homeostasis and its relation to the hypothalamus-pituitary-adrenal axis and depressive-like behavior. Periodic maternal separation increased basal corticosterone levels, induced a passive coping strategy in the forced swimming test, and was associated with a mild (24%) increase in fasting glucose, insulin resistance, and dyslipidemia. Rearing in social isolation increased stress reactivity in comparison to both controls and in combination with periodic maternal separation, without affecting the coping strategy associated with the forced swimming test. However, social isolation also increased body weight gain, fasting glucose (120%), and insulin levels in rats subjected to periodic maternal separation. Correlation analyses showed that stress-induced effects on coping strategy on the forced swimming test (but not on metabolic risk markers) are associated with basal corticosterone levels. These findings suggest that maternal separation and postweaning social isolation affect stress and metabolic vulnerability differentially and that early-life stress-related effects on metabolism are not directly dependent on glucocorticoid levels. In conclusion, our study supports the cumulative stress hypothesis, which suggests that metabolic risk markers arise when vulnerable individuals are exposed to social challenges later in life.

Vitamin D and Age-Related Macular Degeneration.

PubMed

Layana, Alfredo Garcia; Minnella, Angelo Maria; Garhöfer, Gerhard; Aslam, Tariq; Holz, Frank G; Leys, Anita; Silva, Rufino; Delcourt, Cécile; Souied, Eric; Seddon, Johanna M

2017-10-13

In recent years, the relationship between vitamin D and health has received growing attention from the scientific and medical communities. Vitamin D deficiencies have been repeatedly associated with various acute and chronic diseases, including age-related macular degeneration (AMD). Its active metabolite, 1α,25-dihydoxy vitamin D, acts as a modulator of cell proliferation, differentiation and apoptosis, and cumulative data from experimental and observational studies suggest that relatively a lower vitamin D status could be a potential risk factor for the development of early and/or late AMD. Herein, we made a narrative review of the mechanisms linking a potential role of vitamin D with the current concepts of AMD pathophysiology.

Precarious Employment, Bad Jobs, Labor Unions, and Early Retirement

PubMed Central

Warren, John R.; Sweeney, Megan M.; Hauser, Robert M.; Ho, Jeong-Hwa

2011-01-01

Objectives. We examined the extent to which involuntary job loss, exposure to “bad jobs,” and labor union membership across the life course are associated with the risk of early retirement. Methods. Using data from the Wisconsin Longitudinal Study, a large (N = 8,609) sample of men and women who graduated from high school in 1957, we estimated discrete-time event history models for the transition to first retirement through age 65. We estimated models separately for men and women. Results. We found that experience of involuntary job loss and exposure to bad jobs are associated with a lower risk of retiring before age 65, whereas labor union membership is associated with a higher likelihood of early retirement. These relationships are stronger for men than for women and are mediated to some extent by pre-retirement differences in pension eligibility, wealth, job characteristics, and health. Discussion. Results provide some support for hypotheses derived from theories of cumulative stratification, suggesting that earlier employment experiences should influence retirement outcomes indirectly through later-life characteristics. However, midlife employment experiences remain associated with earlier retirement, net of more temporally proximate correlates, highlighting the need for further theorization and empirical evaluation of the mechanisms through which increasingly common employment experiences influence the age at which older Americans retire. PMID:21310772

Overturn of magma ocean ilmenite cumulate layer: Implications for lunar magmatic evolution and formation of a lunar core

NASA Technical Reports Server (NTRS)

Hess, P. C.; Parmentier, E. M.

1993-01-01

We explore a model for the chemical evolution of the lunar interior that explains the origin and evolution of lunar magmatism and possibly the existence of a lunar core. A magma ocean formed during accretion differentiates into the anorthositic crust and chemically stratified cumulate mantle. The cumulative mantle is gravitationally unstable with dense ilmenite cumulate layers overlying olivine-orthopyroxene cumulates with Fe/Mg that decreases with depth. The dense ilmenite layer sinks to the center of the moon forming the core. The remainder of the gravitationally unstable cumulate pile also overturns. Any remaining primitive lunar mantle rises to its level of neutral buoyancy in the cumulate pile. Perhaps melting of primitive lunar mantle due to this decompression results in early lunar Mg-rich magmatism. Because of its high concentration of incompatible heat producing elements, the ilmenite core heats the overlying orthopyroxene-bearing cumulates. As a conductively thickening thermal boundary layer becomes unstable, the resulting mantle plumes rise, decompress, and partially melt to generate the mare basalts. This model explains both the timing and chemical characteristics of lunar magmatism.

Defining subgroups of low socioeconomic status women at risk for depressive symptoms: the importance of perceived stress and cumulative risks.

PubMed

van der Waerden, Judith E B; Hoefnagels, Cees; Hosman, Clemens M H; Jansen, Maria W J

2014-12-01

Most disadvantaged women are exposed to risk factors for depression, but not all necessarily have an identical risk for this mental health problem. A better prediction of which low socioeconomic status (SES) women are most at risk for depressive symptoms can help target preventive interventions at high-risk subgroups most in need of support. Exploring which demographic, socioeconomic and psychological risk factors are associated with self-reported depressive symptoms in a sample of low-SES women and whether the number of risk factors might expose them to an accumulated risk. Between April 2005 and November 2007, 519 disadvantaged women from urban neighbourhoods in Maastricht, a southern Dutch city, participated in a cross-sectional survey on stress and depressive symptoms. Lower education levels, no current employment and lower net monthly family incomes were socioeconomic risk factors associated with higher scores for depressive symptoms. The psychological risk factor 'perceived stress' had the highest explained variance and was most strongly associated with depressive symptoms. Women exposed to multiple risk factors across domains had a cumulated risk for depressive symptomatology. Low-SES women who seem most eligible for targeted preventive action are those with cumulative risks. Depression prevention strategies for this population may benefit from focusing on perceived stress since this is an important modifiable risk factor. © The Author(s) 2014.

Effect of antiretroviral therapy use and adherence on the risk of hyperlipidemia among HIV-infected patients, in the highly active antiretroviral therapy era

PubMed Central

Tsai, Fuu-Jen; Cheng, Chi-Fung; Lai, Chih-Ho; Wu, Yang-Chang; Ho, Mao-Wang; Wang, Jen-Hsien; Tien, Ni; Liu, Xiang; Tsang, Hsinyi; Lin, Ting-Hsu; Liao, Chiu-Chu; Huang, Shao-Mei; Li, Ju-Pi; Lin, Jung-Chun; Lin, Chih-Chien; Chen, Jin-Hua; Liang, Wen-Miin; Lin, Ying-Ju

2017-01-01

HIV-infected patients exposed to antiretroviral therapy (ART) have an increased risk for hyperlipidemia and cardiovascular disease. We performed a longitudinal, comprehensive, and population-based study to investigate the cumulative effect of different types of ART regimens on hyperlipidemia risk in the Taiwanese HIV/ART cohort. A total of 13,370 HIV-infected patients (2,674 hyperlipidemia and 10,696 non-hyperlipidemia patients) were recruited after matching for age, gender, and the first diagnosis date of HIV infection by using the National Health Insurance Research Database in Taiwan. Hyperlipidemia risk associated with cumulative ART use, ART adherence, and their combination was assessed. The matched hyperlipidemia group had a larger number of patients using ART and a higher incidence of comorbidities, specifically, respiratory disease and diabetes. Patients with high ART dosage and dose-dependent manner adherence, respectively, demonstrated an increased risk of hyperlipidemia. For single ART regimens, patients receiving nucleoside reverse-transcriptase inhibitors (NRTI/NRTI)- containing regimen had the highest hyperlipidemia risk, followed by protease inhibitor (PI)- containing and non-NRTI- containing regimens. For combination ART regimens, patients receiving a NRTI/NRTI + PI regimen had the highest hyperlipidemia risk. An increased cumulative drug dose was observed in patients who received the PI, NRTI/NRTI, NRTI, and NNRTI regimens in the hyperlipidemia group, when compared to the non-hyperlipidemia group. In conclusion, ART cumulative use, adherence, and regimen may affect hyperlipidemia risk among HIV-infected patients in a dose-dependent manner. PMID:29290955

Age at adoption from institutional care as a window into the lasting effects of early experiences

PubMed Central

Julian, Megan M.

2013-01-01

One of the major questions of human development is how early experience impacts the course of development years later. Children adopted from institutional care experience varying levels of deprivation in their early life followed by qualitatively better care in an adoptive home, providing a unique opportunity to study the lasting effects of early deprivation and its timing. The effects of age at adoption from institutional care are discussed for multiple domains of social and behavioral development within the context of several prominent developmental hypotheses about the effects of early deprivation (cumulative effects, experience-expectant developmental programming, and experience-adaptive developmental programming). Age at adoption effects are detected in a majority of studies, particularly when children experienced global deprivation and were assessed in adolescence. For most outcomes, institutionalization beyond a certain age is associated with a step-like increase in risk for lasting social and behavioral problems, with the step occurring at an earlier age for children who experienced more severe levels of deprivation. Findings are discussed in terms of their concordance and discordance with our current hypotheses, and speculative explanations for the findings are offered. PMID:23576122

Cumulative psychological stress and cardiovascular disease risk in middle aged and older women: Rationale, design, and baseline characteristics.

PubMed

Albert, Michelle A; Durazo, Eva M; Slopen, Natalie; Zaslavsky, Alan M; Buring, Julie E; Silva, Ted; Chasman, Daniel; Williams, David R

2017-10-01

Although a growing body of evidence indicates strong links between psychological stress (stress) and untoward cardiovascular disease (CVD) outcomes, comprehensive examination of these effects remains lacking. The "Cumulative Psychological Stress and Cardiovascular Disease Risk in Middle Aged and Older Women" study is embedded within the landmark Women's Health Study (WHS) follow-up cohort and seeks to evaluate the individual and joint effects of stressors (cumulative stress) on incident CVD risk, including myocardial infarction, stroke, coronary revascularization and CVD death. GWAS data will be used for exploratory analyses to identify any genes associated with stress and CVD. This study prospectively follows 25,335 women (mean age 72.2 ± 6.04 years) without CVD who returned a short mailed stress questionnaire at baseline and 3 years of follow-up inquiring about their experiences with stress including perceived stress, work stress, work-family spillover, financial stress, traumatic and major life events, discrimination and neighborhood environment/stressors. Other domains ascertained were sleep, anger, cynical hostility, depression, anxiety, social support, intimate partner relations, and volunteer and social activities. Higher levels of cumulative stress were associated with younger age and black race/ethnicity, divorced or separated marital status, increased prevalence of obesity, smoking, diabetes, depression and anxiety (p<0.001 for each). Findings from this study will provide clinically important, new information about associations of cumulative stress, environmental, lifestyle and genetic factors with incident CVD risk in aging women. Copyright © 2017 Elsevier Inc. All rights reserved.

Cumulative occupational mechanical exposures during working life and risk of sickness absence and disability pension: prospective cohort study.

PubMed

Sundstrup, Emil; Hansen, Åse Marie; Mortensen, Erik Lykke; Poulsen, Otto Melchior; Clausen, Thomas; Rugulies, Reiner; Møller, Anne; Andersen, Lars L

2017-09-01

Objectives The aim of this study was to determine the prospective association of cumulative mechanical exposure during working life with health-related labor market outcomes. Methods This prospective cohort study combines data from 5076 older workers (age 49-63 years) from the Copenhagen Aging and Midlife Biobank with a job exposure matrix and a national register containing information on social transfer payment. By coding individual job histories from the Danish version of ISCO-codes (International Standard Classification of Occupations), we calculated cumulative occupational mechanical exposures from a JEM for ton-years (lifting 1000 kg each day in one year), lifting-years (lifting loads weighing ≥20 kg >10 times each day in one year), kneeling-years (kneeling for one hour each day in one year) and vibration-years (whole-body vibration for one hour each day in one year). Cox-regression analyses estimated the relative risk of register-based long-term sickness absence (LTSA) and disability pension with cumulative occupational mechanical exposures throughout working life. Analyses were censored for competing events and adjusted for multiple confounders. Results During the follow-up period, 970 persons (19.3%) had ≥1 episode of LTSA and 85 persons (1.7%) were granted a disability pension. Number of ton-, lifting- and kneeling-years showed an exposure-response association with increased risk of LTSA (P<0.0001). In addition, both long term [≥20 years; hazard ratio (HR) 1.76 95% CI 1.39-2.22] and short term (<10 years; HR 1.20 95% CI 1.02-1.41) exposure to kneeling work increased the risk of LTSA. Lifting-years, but not the other mechanical exposures, were associated with risk of disability pension (HR 1.75 95% CI 1.01-3.04). Conclusions Cumulative occupational mechanical exposures during working life - such as lifting and kneeling work - increased the risk of LTSA. Importantly, being exposed to lifting increased the risk of disability pension.

Adverse health outcomes in women exposed in utero to diethylstilbestrol.

PubMed

Hoover, Robert N; Hyer, Marianne; Pfeiffer, Ruth M; Adam, Ervin; Bond, Brian; Cheville, Andrea L; Colton, Theodore; Hartge, Patricia; Hatch, Elizabeth E; Herbst, Arthur L; Karlan, Beth Y; Kaufman, Raymond; Noller, Kenneth L; Palmer, Julie R; Robboy, Stanley J; Saal, Robert C; Strohsnitter, William; Titus-Ernstoff, Linda; Troisi, Rebecca

2011-10-06

Before 1971, several million women were exposed in utero to diethylstilbestrol (DES) given to their mothers to prevent pregnancy complications. Several adverse outcomes have been linked to such exposure, but their cumulative effects are not well understood. We combined data from three studies initiated in the 1970s with continued long-term follow-up of 4653 women exposed in utero to DES and 1927 unexposed controls. We assessed the risks of 12 adverse outcomes linked to DES exposure, including cumulative risks to 45 years of age for reproductive outcomes and to 55 years of age for other outcomes, and their relationships to the baseline presence or absence of vaginal epithelial changes, which are correlated with a higher dose of, and earlier exposure to, DES in utero. Cumulative risks in women exposed to DES, as compared with those not exposed, were as follows: for infertility, 33.3% vs. 15.5% (hazard ratio, 2.37; 95% confidence interval [CI], 2.05 to 2.75); spontaneous abortion, 50.3% vs. 38.6% (hazard ratio, 1.64; 95% CI, 1.42 to 1.88); preterm delivery, 53.3% vs. 17.8% (hazard ratio, 4.68; 95% CI, 3.74 to 5.86); loss of second-trimester pregnancy, 16.4% vs. 1.7% (hazard ratio, 3.77; 95% CI, 2.56 to 5.54); ectopic pregnancy, 14.6% vs. 2.9% (hazard ratio, 3.72; 95% CI, 2.58 to 5.38); preeclampsia, 26.4% vs. 13.7% (hazard ratio 1.42; 95% CI, 1.07 to 1.89); stillbirth, 8.9% vs. 2.6% (hazard ratio, 2.45; 95% CI, 1.33 to 4.54); early menopause, 5.1% vs. 1.7% (hazard ratio, 2.35; 95% CI, 1.67 to 3.31); grade 2 or higher cervical intraepithelial neoplasia, 6.9% vs. 3.4% (hazard ratio, 2.28; 95% CI, 1.59 to 3.27); and breast cancer at 40 years of age or older, 3.9% vs. 2.2% (hazard ratio, 1.82; 95% CI, 1.04 to 3.18). For most outcomes, the risks among exposed women were higher for those with vaginal epithelial changes than for those without such changes. In utero exposure of women to DES is associated with a high lifetime risk of a broad spectrum of adverse health outcomes. (Funded by the National Cancer Institute.).

Cumulative Risk of Bovine Mastitis Treatments in Denmark, Finland, Norway and Sweden

PubMed Central

Valde, JP; Lawson, LG; Lindberg, A; Agger, JF; Saloniemi, H; Østerås, O

2004-01-01

Data from the national dairy cow recording systems during 1997 were used to calculate lactation-specific cumulative risk of mastitis treatments and cumulative risk of removal from the herds in Denmark, Finland Norway and Sweden. Sweden had the lowest risk of recorded mastitis treatments during 305 days of lactation and Norway had the highest risk. The incidence risk of recorded mastitis treatments during 305 days of lactation in Denmark, Finland, Norway and Sweden was 0.177, 0.139, 0.215 and 0.127 for first parity cows and 0.228, 0.215, 0.358 and 0.204 for parities higher than three, respectively. The risk of a first parity cow being treated for mastitis was almost 3 times higher at calving in Norway than in Sweden. The period with the highest risk for mastitis treatments was from 2 days before calving until 14 days after calving and the highest risk for removal was from calving to 10 days after calving in all countries. The study clearly demonstrated differences in bovine mastitis treatment patterns among the Nordic countries. The most important findings were the differences in treatment risks during different lactations within each country, as well as differences in strategies with respect to the time during lactation mastitis was treated. PMID:15663080

Cumulative risk of bovine mastitis treatments in Denmark, Finland, Norway and Sweden.

PubMed

Valde, J P; Lawson, L G; Lindberg, A; Agger, J F; Saloniemi, H; Osterås, O

2004-01-01

Data from the national dairy cow recording systems during 1997 were used to calculate lactation-specific cumulative risk of mastitis treatments and cumulative risk of removal from the herds in Denmark, Finland Norway and Sweden. Sweden had the lowest risk of recorded mastitis treatments during 305 days of lactation and Norway had the highest risk. The incidence risk of recorded mastitis treatments during 305 days of lactation in Denmark, Finland, Norway and Sweden was 0.177, 0.139, 0.215 and 0.127 for first parity cows and 0.228, 0.215, 0.358 and 0.204 for parities higher than three, respectively. The risk of a first parity cow being treated for mastitis was almost 3 times higher at calving in Norway than in Sweden. The period with the highest risk for mastitis treatments was from 2 days before calving until 14 days after calving and the highest risk for removal was from calving to 10 days after calving in all countries. The study clearly demonstrated differences in bovine mastitis treatment patterns among the Nordic countries. The most important findings were the differences in treatment risks during different lactations within each country, as well as differences in strategies with respect to the time during lactation mastitis was treated.

Severe physical violence between intimate partners during pregnancy: a risk factor for early cessation of exclusive breast-feeding.

PubMed

Moraes, Claudia L; de Oliveira, Alessandra S D; Reichenheim, Michael E; Lobato, Gustavo

2011-12-01

To investigate the role of severe physical violence during pregnancy (SPVP) between intimate partners in early cessation of exclusive breast-feeding (EBF). A health services survey. The revised Conflict Tactics Scale was used to characterize SPVP; premature breast-feeding cessation was identified using a current status data approach, which was based on the information reported from food recall during the preceding 7 d. The cumulative hazard function was estimated by complementary log-log transformation models, which allowed the ensuing estimation of early breast-feeding cessation rates in different age groups and the ratio of rates of weaning between women exposed and not exposed to violence. Five large public primary health-care facilities of Rio de Janeiro, Brazil. The sample comprised 811 randomly selected mothers of children under 5 months of age who were waiting to be consulted. SPVP is an independent risk factor of cessation of EBF since, after controlling for socio-economic, demographic, reproductive and lifestyle variables, women exposed to violence presented an incidence density that was 31% higher than those who were not exposed (hazard ratio = 1·30, 95% CI 1·01, 1·69). The findings corroborate the hypothesis that SPVP is an important risk factor for EBF. This indicates the need for incentives to adequately train health-care personnel in dealing with lactating women in order to gain a broader view of breast-feeding beyond the biological aspects of lactation, including the maternal psychological dimension.

Risk factors and nomogram for pancreatic pseudocysts in chronic pancreatitis: A cohort of 1998 patients.

PubMed

Hao, Lu; Pan, Jun; Wang, Dan; Bi, Ya-Wei; Ji, Jun-Tao; Xin, Lei; Liao, Zhuan; Du, Ting-Ting; Lin, Jin-Huan; Zhang, Di; Zeng, Xiang-Peng; Ye, Bo; Zou, Wen-Bin; Chen, Hui; Xie, Ting; Li, Bai-Rong; Zheng, Zhao-Hong; Hu, Liang-Hao; Li, Zhao-Shen

2017-07-01

Pancreatic pseudocyst is a common complication of chronic pancreatitis. The identification of risk factors and development of a nomogram for pancreatic pseudocysts in chronic pancreatitis patients may contribute to the early diagnosis and intervention of pancreatic pseudocysts. Patients with chronic pancreatitis admitted to our center from January 2000 to December 2013 were enrolled. Cumulative rates of pancreatic pseudocysts after the onset of chronic pancreatitis and after the diagnosis of chronic pancreatitis were calculated. Patients were randomly assigned, in a 2:1 ratio, to the training and validation cohort. Based on the training cohort, risk factors were identified through Cox proportional hazards regression model, and nomogram was developed. Internal and external validations were performed based on the training and validation cohort, respectively. With a total of 1998 patients, pancreatic pseudocysts were detected in 228 (11.41%) patients. Age at the onset of chronic pancreatitis, smoking, and severe acute pancreatitis were identified risk factors for pancreatic pseudocysts development while steatorrhea and pancreatic stones were protective factors. Incorporating these five factors, the nomogram achieved good concordance indexes of 0.735 and 0.628 in the training and validation cohorts, respectively, with well-fitted calibration curves. The nomogram achieved an individualized prediction of pancreatic pseudocysts development in chronic pancreatitis. It may help the early diagnosis and management of pancreatic pseudocysts. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Gene-environment interaction in major depression: focus on experience-dependent biological systems.

PubMed

Lopizzo, Nicola; Bocchio Chiavetto, Luisella; Cattane, Nadia; Plazzotta, Giona; Tarazi, Frank I; Pariante, Carmine M; Riva, Marco A; Cattaneo, Annamaria

2015-01-01

Major depressive disorder (MDD) is a multifactorial and polygenic disorder, where multiple and partially overlapping sets of susceptibility genes interact each other and with the environment, predisposing individuals to the development of the illness. Thus, MDD results from a complex interplay of vulnerability genes and environmental factors that act cumulatively throughout individual's lifetime. Among these environmental factors, stressful life experiences, especially those occurring early in life, have been suggested to exert a crucial impact on brain development, leading to permanent functional changes that may contribute to lifelong risk for mental health outcomes. In this review, we will discuss how genetic variants (polymorphisms, SNPs) within genes operating in neurobiological systems that mediate stress response and synaptic plasticity, can impact, by themselves, the vulnerability risk for MDD; we will also consider how this MDD risk can be further modulated when gene × environment interaction is taken into account. Finally, we will discuss the role of epigenetic mechanisms, and in particular of DNA methylation and miRNAs expression changes, in mediating the effect of the stress on the vulnerability risk to develop MDD. Taken together, we aim to underlie the role of genetic and epigenetic processes involved in stress- and neuroplasticity-related biological systems on the development of MDD after exposure to early life stress, thereby building the basis for future research and clinical interventions.

DESIGNING STUDIES AND COLLECTING DATA USEFUL FOR CUMULATIVE RISK ASSESSMENT

EPA Science Inventory

DESIGNING STUDIES AND COLLECTING DATA USEFUL FOR CUMULATIVE RISK ASSESSMENT. J E Simmons1, C Gennings2, M Casey2, M J Plewa3, E D Wagner3, W H Carter, Jr.2, A McDonald1,Y M Sey1, L K Teuschler3 1NHEERL, ORD, U.S. EPA, RTP NC, USA; 2VCU, Richmond, VA, USA;3Univ. Illinois, Urba...

Cumulative Risk, Negative Emotionality, and Emotion Regulation as Predictors of Social Competence in Transition to School: A Mediated Moderation Model

ERIC Educational Resources Information Center

Chang, Hyein; Shelleby, Elizabeth C.; Cheong, JeeWon; Shaw, Daniel S.

2012-01-01

The goals of this study were to examine the additive and interactive effects of cumulative risk and child negative emotionality on children's social competence in the transition from preschool to school and to test whether these associations were mediated by child emotion regulation within a sample of 310 low-income, ethnically diverse boys.…

Cumulative risk of false positive test in relation to breast symptoms in mammography screening: a historical prospective cohort study.

PubMed

Singh, Deependra; Pitkäniemi, Janne; Malila, Nea; Anttila, Ahti

2016-09-01

Mammography has been found effective as the primary screening test for breast cancer. We estimated the cumulative probability of false positive screening test results with respect to symptom history reported at screen. A historical prospective cohort study was done using individual screening data from 413,611 women aged 50-69 years with 2,627,256 invitations for mammography screening between 1992 and 2012 in Finland. Symptoms (lump, retraction, and secretion) were reported at 56,805 visits, and 48,873 visits resulted in a false positive mammography result. Generalized linear models were used to estimate the probability of at least one false positive test and true positive at screening visits. The estimates were compared among women with and without symptoms history. The estimated cumulative probabilities were 18 and 6 % for false positive and true positive results, respectively. In women with a history of a lump, the cumulative probabilities of false positive test and true positive were 45 and 16 %, respectively, compared to 17 and 5 % with no reported lump. In women with a history of any given symptom, the cumulative probabilities of false positive test and true positive were 38 and 13 %, respectively. Likewise, women with a history of a 'lump and retraction' had the cumulative false positive probability of 56 %. The study showed higher cumulative risk of false positive tests and more cancers detected in women who reported symptoms compared to women who did not report symptoms at screen. The risk varies substantially, depending on symptom types and characteristics. Information on breast symptoms influences the balance of absolute benefits and harms of screening.

Association of Cumulative Childhood Adversity and Adolescent Violent Offending With Suicide in Early Adulthood.

PubMed

Björkenstam, Emma; Hjern, Anders; Björkenstam, Charlotte; Kosidou, Kyriaki

2018-02-01

Childhood adversity (CA) is associated with an increased risk of suicide in young adulthood that might be explained by maladaptive trajectories during adolescence. Although adolescent violent offending is linked with suicide, little is known about its role in the association between CA and suicide. To examine whether adolescent violent offending mediates the association between CA and suicide in early adulthood. This population-based, longitudinal cohort study with a follow-up time spanning 5 to 9 years included 476 103 individuals born in Sweden between 1984 and 1988. The study population was prospectively followed up from 20 years of age until December 31, 2013, with respect to suicide. Data analysis was performed from January 1, 1984, to December 31, 2013. Register-based CAs included parental death, parental substance abuse and psychiatric disorder, parental criminal offending, parental separation, public assistance recipiency, child welfare intervention, and residential instability. Adolescent violent offending was defined as being convicted of a violent crime between the ages of 15 and 19 years. Estimates of risk of suicide after 20 years of age (from 2004 if born in 1984 and from 2008 if born in 1988) until the end of 2013 were calculated as incidence rate ratios (IRRs) with 95% CIs using Poisson regression analysis. Adjustments were made for demographics and psychiatric disorder. In addition, binary mediation analysis with logistic regression was used. A total of 476 103 individuals (231 699 [48.7%] female) were included in the study. Those with a conviction for violent offending had been exposed to all CAs to a greater extent than those with no violent offending. Cumulative CA was associated with risk of suicide in nonconvicted (adjusted IRR, 2.4; 95% CI, 1.5-3.9) and convicted youths, who had a higher risk of suicide (adjusted IRR, 8.5; 95% CI, 4.6-15.7). Adolescent violent offending partly mediated the association between CA and suicide. Individuals with a history of CA who also engage in violent offending in adolescence have a high risk of suicide. Interventions to prevent externalizing behavior during childhood and increased support to youths with delinquent behavior may have the potential to prevent suicide related to CA.

Toward the breast screening balance sheet: cumulative risk of false positives for annual versus biennial mammograms commencing at age 40 or 50.

PubMed

Winch, Caleb J; Sherman, Kerry A; Boyages, John

2015-01-01

This study aimed to: (1) Estimate cumulative risk of recall from breast screening where no cancer is detected (a harm) in Australia; (2) Compare women screened annually versus biennially, commencing age 40 versus 50; and (3) Compare with international findings. At the no-cost metropolitan program studied, women attended biennial screening, but were offered annual screening if regarded at elevated risk for breast cancer. The cumulative risk of at least one recall was estimated using discrete-time survival analysis. Cancer detection statistics were computed. In total, 801,636 mammograms were undertaken in 231,824 women. Over 10 years, cumulative risk of recall was 13.3 % (95 % CI 12.7-13.8) for those screened biennially, and 19.9 % (CI 16.6-23.2) for those screened annually from age 50-51. Cumulative risk of complex false positive involving a biopsy was 3.1 % (CI 2.9-3.4) and 5.0 % (CI 3.4-6.6), respectively. From age 40-41, the risk of recall was 15.1 % (CI 14.3-16.0) and 22.5 % (CI 17.9-27.1) for biennial and annual screening, respectively. Corresponding rates of complex false positive were 3.3 % (CI 2.9-3.8) and 6.3 % (CI 3.4-9.1). Over 10 mammograms, invasive cancer was detected in 3.4 % (CI 3.3-3.5) and ductal carcinoma in situ in 0.7 % (CI 0.6-0.7) of women, with a non-significant trend toward a larger proportion of Tis and T1N0 cancers in women screened annually (74.5 %) versus biennially (70.1 %), χ (2) = 2.77, p = 0.10. Cancer detection was comparable to international findings. Recall risk was equal to European estimates for women screening from 50 and lower for screening from 40. Recall risk was half of United States' rates across start age and rescreening interval categories. Future benefit/harm balance sheets may be useful for communicating these findings to women.

Primary Trabeculectomy Outcomes by Glaucoma Fellows in a Tertiary Hospital in Brazil.

PubMed

Abe, Ricardo Y; Shigueoka, Leonardo S; Vasconcellos, José P C; Costa, Vital P

2017-11-01

To examine outcomes of trabeculectomy with mitomycin C for uncontrolled glaucoma when performed by glaucoma trainee surgeons. Retrospective case series of patients who underwent trabeculectomy with mitomycin C. Primary outcome was to assess the rate of failure, which was defined as intraocular pressure in 2 consecutive visits >18 or <5 mm Hg or intraocular pressure reduction <30% from baseline, additional glaucoma surgery, or loss of light perception. The secondary outcome was to investigate risk factors for failure and surgical complications. One hundred forty-three eyes from 126 glaucoma patients underwent primary trabeculectomy between 2013 and 2014 at University of Campinas. Mean follow-up time was 1.47±0.96 years. Kaplan-Meier analysis showed cumulative survival rates of 70.1%, 62.5%, and 57.8%, after 1, 2, and 3 years, respectively. Multivariate analysis with generalized estimating equations revealed that neovascular glaucoma [odd ratios (OR): 5.05, P=0.043], suture lysis (OR: 8.89, P=0.011), and early bleb leak (OR: 4.63, P=0.011) were risk factors for failure. A success rate of approximately 60% was obtained 3 years after primary trabeculectomy performed by trainees. Patients with neovascular glaucoma, who underwent suture lysis and who presented an early bleb leak had an increased risk for failure during follow-up.

Radiation dose to critical body organs for October 1989 proton event

NASA Technical Reports Server (NTRS)

Simonsen, Lisa C.; Atwell, William; Nealy, John E.; Cucinotta, Francis A.

1992-01-01

The Geostationary Operational Environmental Satellite (GOES-7) provides high-quality environmental data about the temporal development and energy characteristics of the protons emitted during a solar particle event. The GOES-7 time history of the hourly averaged integral proton flux for various particle kinetic energies are analyzed for the solar proton event occurring October 19-29, 1989. This event is similar to the August 1972 event that has been widely studied to estimate free-space and planetary radiation-protection requirements. By analyzing the time-history data, the dose rates, which can vary over many orders of magnitude in the early phases of the flare, can be estimated as well as the cumulative dose as a function of time. When basic transport results are coupled with detailed body organ thickness distributions calculated with the Computerized Anatomical Man and Computerized Anatomical Female models, the dose rates and cumulative doses to specific organs can be predicted. With these results, the risks of cancer incidence and mortality are estimated for astronauts in free space protected by various water shield thicknesses.

Incidence of cervical human papillomavirus infection in systemic lupus erythematosus women.

PubMed

Mendoza-Pinto, C; García-Carrasco, M; Vallejo-Ruiz, V; Méndez-Martínez, S; Taboada-Cole, A; Etchegaray-Morales, I; Muñóz-Guarneros, M; Reyes-Leyva, J; López-Colombo, A

2017-08-01

Objectives Our objective was to study the incidence, persistence and clearance of human papillomavirus infection in systemic lupus erythematosus women and assess risk factors for persistence of human papillomavirus infection. Methods We carried out a prospective, observational cohort study of 127 systemic lupus erythematosus women. Patients were evaluated at baseline and at three years. Traditional and systemic lupus erythematosus women-related disease risk factors were collected. Gynaecological evaluations and cervical cytology screening were made. Human papillomavirus detection and genotyping were made by polymerase chain reaction and linear array. Results The cumulative prevalence of human papillomavirus infection increased from 22.8% at baseline to 33.8% at three years; p = < 0.001: 20.1% of patients experienced 43 incident infections. The risk of any human papillomavirus infection was 10.1 per 1000 patient-months. At three years, 47 (88.6%) prevalent infections were cleared. Independent risk factors associated with incident human papillomavirus infection included more lifetime sexual partners (odds ratio = 1.8, 95% confidence interval = 1.11-3.0) and cumulative cyclophosphamide dose (odds ratio = 3.9, 95% confidence interval = 1.2-12.8). Conclusions In systemic lupus erythematosus women, the cumulative prevalence of human papillomavirus infection, including high risk-human papillomavirus and multiple human papillomavirus infections, may increase over time. Most persistent infections were low risk-human papillomavirus. The number of lifetime sexual partners and the cumulative cyclophosphamide dose were independently associated with incident human papillomavirus infection.

Improving Demographic Diversity in the U.S. Air Force Officer Corps

DTIC Science & Technology

2014-01-01

40   v Career Success Is Cumulative...early markers of career success , such as high USAFA order of merit scores, than whites. The reasons for this are not clear, but the effect builds over...for each of women, African Americans, and Hispanics. 42 Career Success Is Cumulative Methodology: Generalized Boosted Models In addition to

Cumulative adversity in childhood and emergent risk factors for long-term health.

PubMed

Slopen, Natalie; Koenen, Karestan C; Kubzansky, Laura D

2014-03-01

To examine whether and when effects of cumulative adversity in the first 7 years of life are evident in relation to 3 childhood markers of risk for poor adult physical health. The study data are from an English birth cohort. Parental reports of 8 social risk factors were obtained during the child's first 7 years, and scores were created to reflect cumulative adversity at 4 developmental periods. At age 7 and 11 years, weight, height, and blood pressure (BP) were measured by clinic staff, and caregivers reported behavior problems. Linear regression was used to estimate associations of cumulative adversity with each outcome (n = 4361) and changes in these outcomes between 7 and 11 years (n = 3348). At age 7 years, mean adversity and chronic exposure to high adversity were associated with elevated body mass index (BMI) and internalizing and externalizing symptoms (P < .05), but not elevated BP. Adversity in all developmental periods was associated with elevated numbers of internalizing and externalizing symptoms (P < .0001), but associations were less robust for BMI. Adversity did not predict change in BMI or BP between age 7 and 11 years, however, it predicted increases in internalizing and externalizing symptoms (P < .0001). Cumulative adversity was associated with BMI and behavior problems at age 7 years, and our data indicate that timing and chronicity of exposure to adversity differentially influence diverse indicators of long-term health risk commonly measured in childhood. This research suggests the hypothesis that interventions to address adversity could reduce the development of multiple chronic disease risk factors and limit their effects on health. Copyright © 2014 Mosby, Inc. All rights reserved.

Cumulative Risk of Type 2 Diabetes in a Working Population: The Japan Epidemiology Collaboration on Occupational Health Study.

PubMed

Hu, Huanhuan; Nakagawa, Tohru; Okazaki, Hiroko; Nishiura, Chihiro; Imai, Teppei; Miyamoto, Toshiaki; Sasaki, Naoko; Yamamoto, Makoto; Murakami, Taizo; Kochi, Takeshi; Eguchi, Masafumi; Tomita, Kentaro; Nagahama, Satsue; Kuwahara, Keisuke; Kabe, Isamu; Mizoue, Tetsuya; Dohi, Seitaro

2018-05-04

We estimated the cumulative risk of type 2 diabetes from age 30 to 65 years in a large working population in Japan. We used data from the Japan Epidemiology Collaboration on Occupational Health Study. Participants (46,065 men and 7,763 women) were aged 30-59 years, free of diabetes at baseline, and followed up for a maximum of 7 years. Incident type 2 diabetes was defined based on fasting and casual glucose, glycated hemoglobin, and current medical treatment for type 2 diabetes. We calculated the sex-specific cumulative risk of type 2 diabetes using the Practical Incidence Estimator macro, which was created to produce several estimates of disease incidence for prospective cohort studies based on a modified Kaplan-Meier method. During 274,349 person-years of follow-up, 3,587 individuals (3,339 men and 248 women) developed type 2 diabetes. The cumulative risk was 34.7% (95% confidence interval, 33.1-36.3%) for men and 18.6% (95% confidence interval, 15.5-21.7%) for women. In BMI-stratified analysis, obese (BMI ≥30 kg/m 2 ) and overweight (BMI 25-29.9 kg/m 2 ) men and women had a much higher cumulative risk of type 2 diabetes (obese: 77.3% for men and 64.8% for women; overweight: 49.1% and 35.7%, respectively) than those with BMI <25 kg/m 2 (26.2% and 13.4% for men and women, respectively). The present data highlight the public health burden of type 2 diabetes in the working population. There is a need for effective programs for weight management and type 2 diabetes screening, especially for young obese employees, to prevent or delay the development of type 2 diabetes.

Risk assessment of student performance in the International Foundations of Medicine Clinical Science Examination by the use of statistical modeling.

PubMed

David, Michael C; Eley, Diann S; Schafer, Jennifer; Davies, Leo

2016-01-01

The primary aim of this study was to assess the predictive validity of cumulative grade point average (GPA) for performance in the International Foundations of Medicine (IFOM) Clinical Science Examination (CSE). A secondary aim was to develop a strategy for identifying students at risk of performing poorly in the IFOM CSE as determined by the National Board of Medical Examiners' International Standard of Competence. Final year medical students from an Australian university medical school took the IFOM CSE as a formative assessment. Measures included overall IFOM CSE score as the dependent variable, cumulative GPA as the predictor, and the factors age, gender, year of enrollment, international or domestic status of student, and language spoken at home as covariates. Multivariable linear regression was used to measure predictor and covariate effects. Optimal thresholds of risk assessment were based on receiver-operating characteristic (ROC) curves. Cumulative GPA (nonstandardized regression coefficient [B]: 81.83; 95% confidence interval [CI]: 68.13 to 95.53) and international status (B: -37.40; 95% CI: -57.85 to -16.96) from 427 students were found to be statistically associated with increased IFOM CSE performance. Cumulative GPAs of 5.30 (area under ROC [AROC]: 0.77; 95% CI: 0.72 to 0.82) and 4.90 (AROC: 0.72; 95% CI: 0.66 to 0.78) were identified as being thresholds of significant risk for domestic and international students, respectively. Using cumulative GPA as a predictor of IFOM CSE performance and accommodating for differences in international status, it is possible to identify students who are at risk of failing to satisfy the National Board of Medical Examiners' International Standard of Competence.

Cumulative Risk Exposure and Waist Circumference in Preschool-Aged Children: the Mediating Role of Television and Moderating Role of Sex.

PubMed

Grummon, Anna H; Vaughn, Amber; Jones, Deborah J; Ward, Dianne S

2017-08-01

Children exposed to multiple stressors are more likely to be overweight, but little is known about the mechanisms explaining this association. This cross-sectional study examined whether children exposed to multiple stressors had higher waist circumference, and whether this association was mediated through children's television time. Participants were 319 parent-child dyads. Children were 2-5 years old and had at least one overweight parent (BMI ≥ 25 kg/m 2 ). Data were collected at baseline of a larger childhood obesity prevention study and included information on psychosocial stressors (e.g., parenting stress), demographic stressors (e.g., low income), children's television time, and children's waist circumference. Two cumulative risk scores were created by summing stressors in each domain (demographic and psychosocial). Mediation and moderated mediation analyses were conducted. Indirect effects of both cumulative risk scores on waist circumference through television time were not significant; however, moderated mediation analyses found significant moderation by gender. The indirect effects of both risk scores on waist circumference through television time were significant and positive for girls, but near-zero for boys. Reducing television time should be explored as a strategy for buffering against the negative health effects of exposure to multiple stressors among girls. Longitudinal and intervention research is needed to confirm these results and to identify mediating factors between cumulative risk and body weight among boys.

Validated Competing Event Model for the Stage I-II Endometrial Cancer Population

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carmona, Ruben; Gulaya, Sachin; Murphy, James D.

2014-07-15

Purpose/Objectives(s): Early-stage endometrial cancer patients are at higher risk of noncancer mortality than of cancer mortality. Competing event models incorporating comorbidity could help identify women most likely to benefit from treatment intensification. Methods and Materials: 67,397 women with stage I-II endometrioid adenocarcinoma after total hysterectomy diagnosed from 1988 to 2009 were identified in Surveillance, Epidemiology, and End Results (SEER) and linked SEER-Medicare databases. Using demographic and clinical information, including comorbidity, we sought to develop and validate a risk score to predict the incidence of competing mortality. Results: In the validation cohort, increasing competing mortality risk score was associated with increasedmore » risk of noncancer mortality (subdistribution hazard ratio [SDHR], 1.92; 95% confidence interval [CI], 1.60-2.30) and decreased risk of endometrial cancer mortality (SDHR, 0.61; 95% CI, 0.55-0.78). Controlling for other variables, Charlson Comorbidity Index (CCI) = 1 (SDHR, 1.62; 95% CI, 1.45-1.82) and CCI >1 (SDHR, 3.31; 95% CI, 2.74-4.01) were associated with increased risk of noncancer mortality. The 10-year cumulative incidences of competing mortality within low-, medium-, and high-risk strata were 27.3% (95% CI, 25.2%-29.4%), 34.6% (95% CI, 32.5%-36.7%), and 50.3% (95% CI, 48.2%-52.6%), respectively. With increasing competing mortality risk score, we observed a significant decline in omega (ω), indicating a diminishing likelihood of benefit from treatment intensification. Conclusion: Comorbidity and other factors influence the risk of competing mortality among patients with early-stage endometrial cancer. Competing event models could improve our ability to identify patients likely to benefit from treatment intensification.« less

Process monitoring in intensive care with the use of cumulative expected minus observed mortality and risk-adjusted P charts.

PubMed

Cockings, Jerome G L; Cook, David A; Iqbal, Rehana K

2006-02-01

A health care system is a complex adaptive system. The effect of a single intervention, incorporated into a complex clinical environment, may be different from that expected. A national database such as the Intensive Care National Audit & Research Centre (ICNARC) Case Mix Programme in the UK represents a centralised monitoring, surveillance and reporting system for retrospective quality and comparative audit. This can be supplemented with real-time process monitoring at a local level for continuous process improvement, allowing early detection of the impact of both unplanned and deliberately imposed changes in the clinical environment. Demographic and UK Acute Physiology and Chronic Health Evaluation II (APACHE II) data were prospectively collected on all patients admitted to a UK regional hospital between 1 January 2003 and 30 June 2004 in accordance with the ICNARC Case Mix Programme. We present a cumulative expected minus observed (E-O) plot and the risk-adjusted p chart as methods of continuous process monitoring. We describe the construction and interpretation of these charts and show how they can be used to detect planned or unplanned organisational process changes affecting mortality outcomes. Five hundred and eighty-nine adult patients were included. The overall death rate was 0.78 of predicted. Calibration showed excess survival in ranges above 30% risk of death. The E-O plot confirmed a survival above that predicted. Small transient variations were seen in the slope that could represent random effects, or real but transient changes in the quality of care. The risk-adjusted p chart showed several observations below the 2 SD control limits of the expected mortality rate. These plots provide rapid analysis of risk-adjusted performance suitable for local application and interpretation. The E-O chart provided rapid easily visible feedback of changes in risk-adjusted mortality, while the risk-adjusted p chart allowed statistical evaluation. Local analysis of risk-adjusted mortality data with an E-O plot and a risk-adjusted p chart is feasible and allows the rapid detection of changes in risk-adjusted outcome of intensive care patients. This complements the centralised national database, which is more archival and comparative in nature.

Personal care products that contain estrogens or xenoestrogens may increase breast cancer risk.

PubMed

Donovan, Maryann; Tiwary, Chandra M; Axelrod, Deborah; Sasco, Annie J; Jones, Lovell; Hajek, Richard; Sauber, Erin; Kuo, Jean; Davis, Devra L

2007-01-01

Established models of breast cancer risk, such as the Gail model, do not account for patterns of the disease in women under the age of 35, especially in African Americans. With the possible exceptions of ionizing radiation or inheriting a known genetic mutation, most of the known risk factors for breast cancer are related to cumulative lifetime exposure to estrogens. Increased risk of breast cancer has been associated with earlier onset of menses or later age at menopause, nulliparity or late first parity, use of hormonal contraceptives or hormone replacement therapy, shorter lactation history, exposure to light at night, obesity, and regular ingestion of alcohol, all of which increase circulating levels of unbound estradiol. Among African Americans at all ages, use of hormone-containing personal care products (PCPs) is more common than among whites, as is premature appearance of secondary sexual characteristics among infants and toddlers. We hypothesize that the use of estrogen and other hormone-containing PCPs in young African American women accounts, in part, for their increased risk of breast cancer prior to menopause, by subjecting breast buds to elevated estrogen exposure during critical windows of vulnerability in utero and in early life. These early life and continuing exposures to estrogenic and xenoestrogenic agents may also contribute to the increased lethality of breast cancer in young women in general and in African American women of all ages. Public disclosure by manufacturers of proprietary hormonally active ingredients is required for this research to move forward.

Cumulative effects of mothers' risk and promotive factors on daughters' disruptive behavior.

PubMed

van der Molen, Elsa; Hipwell, Alison E; Vermeiren, Robert; Loeber, Rolf

2012-07-01

Little is known about the ways in which the accumulation of maternal factors increases or reduces risk for girls' disruptive behavior during preadolescence. In the current study, maternal risk and promotive factors and the severity of girls' disruptive behavior were assessed annually among girls' ages 7-12 in an urban community sample (N = 2043). Maternal risk and promotive factors were operative at different time points in girls' development. Maternal warmth explained variance in girls' disruptive behavior, even after controlling for maternal risk factors and relevant child and neighborhood factors. In addition, findings supported the cumulative hypothesis that the number of risk factors increased the chance on girls' disruptive behavior disorder (DBD), while the number of promotive factors decreased this probability. Daughters of mothers with a history of Conduct Disorder (CD) were exposed to more risk factors and fewer promotive factors compared to daughters of mothers without prior CD. The identification of malleable maternal factors that can serve as targets for intervention has important implications for intergenerational intervention. Cumulative effects show that the focus of prevention efforts should not be on single factors, but on multiple factors associated with girls' disruptive behavior.

Cumulative Effects of Mothers’ Risk and Promotive Factors on Daughters’ Disruptive Behavior

PubMed Central

Hipwell, Alison E.; Vermeiren, Robert; Loeber, Rolf

2012-01-01

Little is known about the ways in which the accumulation of maternal factors increases or reduces risk for girls’ disruptive behavior during preadolescence. In the current study, maternal risk and promotive factors and the severity of girls’ disruptive behavior were assessed annually among girls’ ages 7–12 in an urban community sample (N=2043). Maternal risk and promotive factors were operative at different time points in girls’ development. Maternal warmth explained variance in girls’ disruptive behavior, even after controlling for maternal risk factors and relevant child and neighborhood factors. In addition, findings supported the cumulative hypothesis that the number of risk factors increased the chance on girls’ disruptive behavior disorder (DBD), while the number of promotive factors decreased this probability. Daughters of mothers with a history of Conduct Disorder (CD) were exposed to more risk factors and fewer promotive factors compared to daughters of mothers without prior CD. The identification of malleable maternal factors that can serve as targets for intervention has important implications for intergenerational intervention. Cumulative effects show that the focus of prevention efforts should not be on single factors, but on multiple factors associated with girls’ disruptive behavior. PMID:22127641

Association Between the Duration of Periodontitis and Increased Cardiometabolic Risk Factors: A 9-Year Cohort Study.

PubMed

Morita, Toyoko; Yamazaki, Yoji; Fujiharu, Chika; Ishii, Takanori; Seto, Misae; Nishinoue, Norihide; Sasaki, Yoshiyuki; Nakai, Kumiko; Tanaka, Hideki; Kawato, Takayuki; Maeno, Masao

2016-12-01

Epidemiological studies have reported that periodontitis and cardiometabolic disease such as cardiovascular disease and type 2 diabetes are associated; however, there have been very few prospective cohort studies on this topic. Therefore, we conducted a 9-year follow-up study to examine the relationship between the duration of periodontitis and cardiometabolic risk factors, including hypertension, hyperglycemia, dyslipidemia, and obesity. The study participants comprised 572 adult industrial workers (417 men and 155 women; mean age, 37.4 years) who had undergone annual medical and dental health examinations from 2003 to 2012; the evaluation of the four cardiometabolic risk factors in 2003 revealed normal values in all the participants. We investigated the relationship between the cumulative duration of the presence of periodontal pockets, which is a major symptom of periodontitis, and the presence of cardiometabolic risk factors after 9 years using multiple logistic regression analysis. The odds ratio (OR) for the presence of ≥1 cardiometabolic risk factor in participants with a cumulative duration of periodontal pockets for ≥6 years was significantly higher than that in participants without pockets. The ORs for the onset of obesity, hypertension, dyslipidemia, and hyperglycemia were higher in participants with a cumulative duration of periodontal pockets for ≥6 years than those in participants without pockets or in participants with a cumulative duration of periodontal pockets for ≤5 years, and all the differences, except dyslipidemia, were significant. Chronic periodontitis was significantly associated with having cardiometabolic risk factors during the 9-year observation period, suggesting that the risk of cardiometabolic disease might increase in people who have untreated periodontitis.

Assessing weather effects on dengue disease in Malaysia.

PubMed

Cheong, Yoon Ling; Burkart, Katrin; Leitão, Pedro J; Lakes, Tobia

2013-11-26

The number of dengue cases has been increasing on a global level in recent years, and particularly so in Malaysia, yet little is known about the effects of weather for identifying the short-term risk of dengue for the population. The aim of this paper is to estimate the weather effects on dengue disease accounting for non-linear temporal effects in Selangor, Kuala Lumpur and Putrajaya, Malaysia, from 2008 to 2010. We selected the weather parameters with a Poisson generalized additive model, and then assessed the effects of minimum temperature, bi-weekly accumulated rainfall and wind speed on dengue cases using a distributed non-linear lag model while adjusting for trend, day-of-week and week of the year. We found that the relative risk of dengue cases is positively associated with increased minimum temperature at a cumulative percentage change of 11.92% (95% CI: 4.41-32.19), from 25.4 °C to 26.5 °C, with the highest effect delayed by 51 days. Increasing bi-weekly accumulated rainfall had a positively strong effect on dengue cases at a cumulative percentage change of 21.45% (95% CI: 8.96, 51.37), from 215 mm to 302 mm, with the highest effect delayed by 26-28 days. The wind speed is negatively associated with dengue cases. The estimated lagged effects can be adapted in the dengue early warning system to assist in vector control and prevention plan.

Relative Importance and Additive Effects of Maternal and Infant Risk Factors on Childhood Asthma

PubMed Central

Rosas-Salazar, Christian; James, Kristina; Escobar, Gabriel; Gebretsadik, Tebeb; Li, Sherian Xu; Carroll, Kecia N.; Walsh, Eileen; Mitchel, Edward; Das, Suman; Kumar, Rajesh; Yu, Chang; Dupont, William D.; Hartert, Tina V.

2016-01-01

Background Environmental exposures that occur in utero and during early life may contribute to the development of childhood asthma through alteration of the human microbiome. The objectives of this study were to estimate the cumulative effect and relative importance of environmental exposures on the risk of childhood asthma. Methods We conducted a population-based birth cohort study of mother-child dyads who were born between 1995 and 2003 and were continuously enrolled in the PRIMA (Prevention of RSV: Impact on Morbidity and Asthma) cohort. The individual and cumulative impact of maternal urinary tract infections (UTI) during pregnancy, maternal colonization with group B streptococcus (GBS), mode of delivery, infant antibiotic use, and older siblings at home, on the risk of childhood asthma were estimated using logistic regression. Dose-response effect on childhood asthma risk was assessed for continuous risk factors: number of maternal UTIs during pregnancy, courses of infant antibiotics, and number of older siblings at home. We further assessed and compared the relative importance of these exposures on the asthma risk. In a subgroup of children for whom maternal antibiotic use during pregnancy information was available, the effect of maternal antibiotic use on the risk of childhood asthma was estimated. Results Among 136,098 singleton birth infants, 13.29% developed asthma. In both univariate and adjusted analyses, maternal UTI during pregnancy (odds ratio [OR] 1.2, 95% confidence interval [CI] 1.18, 1.25; adjusted OR [AOR] 1.04, 95%CI 1.02, 1.07 for every additional UTI) and infant antibiotic use (OR 1.21, 95%CI 1.20, 1.22; AOR 1.16, 95%CI 1.15, 1.17 for every additional course) were associated with an increased risk of childhood asthma, while having older siblings at home (OR 0.92, 95%CI 0.91, 0.93; AOR 0.85, 95%CI 0.84, 0.87 for each additional sibling) was associated with a decreased risk of childhood asthma, in a dose-dependent manner. Compared with vaginal delivery, C-section delivery increased odds of childhood asthma by 34% (OR 1.34, 95%CI 1.29, 1.39) in the univariate analysis and 11% after adjusting for other environmental exposures and covariates (AOR 1.11, 95%CI 1.06, 1.15). Maternal GBS was associated with a significant increased risk of childhood asthma in the univariate analysis (OR 1.27, 95%CI 1.19, 1.35), but not in the adjusted analysis (AOR 1.03, 95%CI 0.96, 1.10). In the subgroup analysis of children whose maternal antibiotic use information was available, maternal antibiotic use was associated with an increased risk of childhood asthma in a similar dose-dependent manner in the univariate and adjusted analyses (OR 1.13, 95%CI 1.12, 1.15; AOR 1.06, 95%CI 1.05, 1.08 for every additional course). Compared with infants with the lowest number of exposures (no UTI during pregnancy, vaginal delivery, at least five older siblings at home, no antibiotics during infancy), infants with the highest number of exposures (at least three UTIs during pregnancy, C-section delivery, no older siblings, eight or more courses of antibiotics during infancy) had a 7.77 fold increased odds of developing asthma (AOR: 7.77, 95%CI: 6.25, 9.65). Lastly, infant antibiotic use had the greatest impact on asthma risk compared with maternal UTI during pregnancy, mode of delivery and having older siblings at home. Conclusion Early-life exposures, maternal UTI during pregnancy (maternal antibiotic use), mode of delivery, infant antibiotic use, and having older siblings at home, are associated with an increased risk of childhood asthma in a cumulative manner, and for those continuous variables, a dose-dependent relationship. Compared with in utero exposures, exposures occurring during infancy have a greater impact on the risk of developing childhood asthma. PMID:27002979

Relative Importance and Additive Effects of Maternal and Infant Risk Factors on Childhood Asthma.

PubMed

Wu, Pingsheng; Feldman, Amy S; Rosas-Salazar, Christian; James, Kristina; Escobar, Gabriel; Gebretsadik, Tebeb; Li, Sherian Xu; Carroll, Kecia N; Walsh, Eileen; Mitchel, Edward; Das, Suman; Kumar, Rajesh; Yu, Chang; Dupont, William D; Hartert, Tina V

2016-01-01

Environmental exposures that occur in utero and during early life may contribute to the development of childhood asthma through alteration of the human microbiome. The objectives of this study were to estimate the cumulative effect and relative importance of environmental exposures on the risk of childhood asthma. We conducted a population-based birth cohort study of mother-child dyads who were born between 1995 and 2003 and were continuously enrolled in the PRIMA (Prevention of RSV: Impact on Morbidity and Asthma) cohort. The individual and cumulative impact of maternal urinary tract infections (UTI) during pregnancy, maternal colonization with group B streptococcus (GBS), mode of delivery, infant antibiotic use, and older siblings at home, on the risk of childhood asthma were estimated using logistic regression. Dose-response effect on childhood asthma risk was assessed for continuous risk factors: number of maternal UTIs during pregnancy, courses of infant antibiotics, and number of older siblings at home. We further assessed and compared the relative importance of these exposures on the asthma risk. In a subgroup of children for whom maternal antibiotic use during pregnancy information was available, the effect of maternal antibiotic use on the risk of childhood asthma was estimated. Among 136,098 singleton birth infants, 13.29% developed asthma. In both univariate and adjusted analyses, maternal UTI during pregnancy (odds ratio [OR] 1.2, 95% confidence interval [CI] 1.18, 1.25; adjusted OR [AOR] 1.04, 95%CI 1.02, 1.07 for every additional UTI) and infant antibiotic use (OR 1.21, 95%CI 1.20, 1.22; AOR 1.16, 95%CI 1.15, 1.17 for every additional course) were associated with an increased risk of childhood asthma, while having older siblings at home (OR 0.92, 95%CI 0.91, 0.93; AOR 0.85, 95%CI 0.84, 0.87 for each additional sibling) was associated with a decreased risk of childhood asthma, in a dose-dependent manner. Compared with vaginal delivery, C-section delivery increased odds of childhood asthma by 34% (OR 1.34, 95%CI 1.29, 1.39) in the univariate analysis and 11% after adjusting for other environmental exposures and covariates (AOR 1.11, 95%CI 1.06, 1.15). Maternal GBS was associated with a significant increased risk of childhood asthma in the univariate analysis (OR 1.27, 95%CI 1.19, 1.35), but not in the adjusted analysis (AOR 1.03, 95%CI 0.96, 1.10). In the subgroup analysis of children whose maternal antibiotic use information was available, maternal antibiotic use was associated with an increased risk of childhood asthma in a similar dose-dependent manner in the univariate and adjusted analyses (OR 1.13, 95%CI 1.12, 1.15; AOR 1.06, 95%CI 1.05, 1.08 for every additional course). Compared with infants with the lowest number of exposures (no UTI during pregnancy, vaginal delivery, at least five older siblings at home, no antibiotics during infancy), infants with the highest number of exposures (at least three UTIs during pregnancy, C-section delivery, no older siblings, eight or more courses of antibiotics during infancy) had a 7.77 fold increased odds of developing asthma (AOR: 7.77, 95%CI: 6.25, 9.65). Lastly, infant antibiotic use had the greatest impact on asthma risk compared with maternal UTI during pregnancy, mode of delivery and having older siblings at home. Early-life exposures, maternal UTI during pregnancy (maternal antibiotic use), mode of delivery, infant antibiotic use, and having older siblings at home, are associated with an increased risk of childhood asthma in a cumulative manner, and for those continuous variables, a dose-dependent relationship. Compared with in utero exposures, exposures occurring during infancy have a greater impact on the risk of developing childhood asthma.

Understanding the Relation of Low Income to HPA-Axis Functioning in Preschool Children: Cumulative Family Risk and Parenting as Pathways to Disruptions in Cortisol

ERIC Educational Resources Information Center

Zalewski, Maureen; Lengua, Liliana J.; Kiff, Cara J.; Fisher, Philip A.

2012-01-01

This study examined the relation of low income and poverty to cortisol levels, and tested potential pathways from low income to disruptions in cortisol through cumulative family risk and parenting. The sample of 306 mothers and their preschool children included 29 % families at or near poverty, 27 % families below the median income, and the…

Occupational Exposure to Magnetic Fields and Breast Cancer Among Women Textile Workers in Shanghai, China

PubMed Central

Li, Wenjin; Ray, Roberta M.; Thomas, David B.; Yost, Michael; Davis, Scott; Breslow, Norman; Gao, Dao Li; Fitzgibbons, E. Dawn; Camp, Janice E.; Wong, Eva; Wernli, Karen J.; Checkoway, Harvey

2013-01-01

Exposure to magnetic fields (MFs) is hypothesized to increase the risk of breast cancer by reducing production of melatonin by the pineal gland. A nested case-cohort study was conducted to investigate the association between occupational exposure to MFs and the risk of breast cancer within a cohort of 267,400 female textile workers in Shanghai, China. The study included 1,687 incident breast cancer cases diagnosed from 1989 to 2000 and 4,702 noncases selected from the cohort. Subjects’ complete work histories were linked to a job–exposure matrix developed specifically for the present study to estimate cumulative MF exposure. Hazard ratios and 95% confidence intervals were calculated using Cox proportional hazards modeling that was adapted for the case-cohort design. Hazard ratios were estimated in relation to cumulative exposure during a woman's entire working years. No association was observed between cumulative exposure to MFs and overall risk of breast cancer. The hazard ratio for the highest compared with the lowest quartile of cumulative exposure was 1.03 (95% confidence interval: 0.87, 1.21). Similar null findings were observed when exposures were lagged and stratified by age at breast cancer diagnosis. The findings do not support the hypothesis that MF exposure increases the risk of breast cancer. PMID:24043439

Radiofrequency ablation for hepatocellular carcinoma measuring 2 cm or smaller: results and risk factors for local recurrence.

PubMed

Kono, Masashi; Inoue, Tatsuo; Kudo, Masatoshi; Chishina, Hirokazu; Arizumi, Tadaaki; Takita, Masahiro; Kitai, Satoshi; Yada, Norihisa; Hagiwara, Satoru; Minami, Yasunori; Ueshima, Kazuomi; Nishida, Naoshi; Murakami, Takamichi

2014-01-01

The purpose of this study was to evaluate the risk factors for local recurrence with radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) measuring ≤2 cm. This study involved 234 patients with 274 HCCs measuring ≤2 cm who had undergone RFA as the initial treatment. The mean tumor diameter was 1.478 cm. The median follow-up period was 829 days. We evaluated the post-RFA cumulative local recurrence rate and analyzed the risk factors contributing to clinical outcomes. Cumulative local recurrence rates were 9, 19 and 19% at 1, 2 and 3 years, respectively. Among the 145 cases with a complete safety margin (SM) after RFA, only 4 developed local tumor recurrence and the cumulative rates of local tumor recurrence at 1, 2 and 3 years were 2, 3 and 3%, respectively. Among the 129 cases with incomplete SM, local tumor recurrence developed in 34 and the cumulative rates of local tumor progression at 1, 2 and 3 years were 14, 36 and 36%, respectively. In multivariate analysis, significant risk factors were tumor location (liver surface), irregular gross type and SM <5 mm. Even with HCC measuring ≤2 cm, location and gross type of tumor should be carefully evaluated before RFA is performed.

Risk of cardiovascular events from current, recent, and cumulative exposure to abacavir among persons living with HIV who were receiving antiretroviral therapy in the United States: a cohort study.

PubMed

Dorjee, Kunchok; Baxi, Sanjiv M; Reingold, Arthur L; Hubbard, Alan

2017-10-27

There is ongoing controversy regarding abacavir use in the treatment of HIV infection and the risk of subsequent development of cardiovascular disease. It is unclear how the risk varies as exposure accumulates. Using an administrative health-plan dataset, risk of cardiovascular disease events (CVDe), defined as the first episode of an acute myocardial infarction or a coronary intervention procedure, associated with abacavir exposure was assessed among HIV-infected individuals receiving antiretroviral therapy across the U.S. from October 2009 through December 2014. The data were longitudinal, and analyzed using marginal structural models. Over 114,470 person-years (n = 72,733) of ART exposure, 714 CVDe occurred at an incidence rate (IR) (95% CI) of 6·23 (5·80, 6·71)/1000 person-years. Individuals exposed to abacavir had a higher IR of CVDe of 9·74 (8·24, 11·52)/1000 person-years as compared to 5·75 (5·30, 6·24)/1000 person-years for those exposed to other antiretroviral agents. The hazard (HR; 95% CI) of CVDe was increased for current (1·43; 1·18, 1·73), recent (1·41; 1·16, 1·70), and cumulative [(1·18; 1·06, 1·31) per year] exposure to abacavir. The risk for cumulative exposure followed a bell-shaped dose-response curve peaking at 24-months of exposure. Risk was similarly elevated among participants free of pre-existing heart disease or history of illicit substance use at baseline. Current, recent, and cumulative use of abacavir was associated with an increased risk of CVDe. The findings were consistent irrespective of underlying cardiovascular risk factors.

Association between cumulative social risk and ideal cardiovascular health in US adults: NHANES 1999-2006.

PubMed

Caleyachetty, Rishi; Echouffo-Tcheugui, Justin B; Muennig, Peter; Zhu, Wenyi; Muntner, Paul; Shimbo, Daichi

2015-07-15

The American Heart Association developed the Life's Simple 7 metric for defining cardiovascular health. Little is known about the association of co-occurring social risk factors on ideal cardiovascular health. Using data on 11,467 adults aged ≥25 years from the National Health and Nutrition Examination Survey 1999-2006, we examined the association between cumulative social risk and ideal cardiovascular health in US adults. A cumulative risk score (range 0 to 3 or 4) was created by summing four social risk factors (low family income, low education level, minority race, and single-living status). Ideal levels for each component in Life's Simple 7 (blood pressure, cholesterol, glucose, BMI, smoking, physical activity, and diet) were used to create an ideal Life's Simple 7 score [0-1 (low), 2, 3, 4, and 5-7 (high)]. Adults with low income (odds ratio [OR]=0.30 [95% CI 0.23-0.39]), low education [0.22 (0.16-0.28)], who are non-white (0.44 [0.36-0.54]) and single-living [0.79 (0.67-0.95)] were less likely to have 5-7 versus 0 ideal Life's Simple 7 scores after adjustment for age and sex. Adults were less likely to attain 5-7 versus 0 ideal Life's Simple 7 scores as exposure to the number of social risk factors increased [OR (95% CI) of 0.58 (0.49-0.68); 0.27 (0.21-0.35); and 0.19 (0.14-0.27) for cumulative social risk scores of 1, 2, and 3 or 4, respectively, each versus 0]. US adults with an increasing number of socially risk factors, were progressively less likely to attain ideal levels of cardiovascular health factors. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

REE and Isotopic Compositions of Lunar Basalts Demonstrate Partial Melting of Hybridized Mantle Sources after Cumulate Overturn is Required

NASA Astrophysics Data System (ADS)

Dygert, N. J.; Liang, Y.

2017-12-01

Lunar basalts maintain an important record of the composition of the lunar interior. Much of our understanding of the Moon's early evolution comes from studying their petrogenesis. Recent experimental work has advanced our knowledge of major and trace element fractionation during lunar magma ocean (LMO) crystallization [e.g., 1-3], which produced heterogeneous basalt sources in the Moon's mantle. With the new experimental constraints, we can evaluate isotopic and trace element signatures in lunar basalts in unprecedented detail, refining inferences about the Moon's dynamic history. Two petrogenetic models are invoked to explain the compositions of the basalts. The assimilation model argues they formed as primitive melts of early LMO cumulates that assimilated late LMO cumulates as they migrated upward. The cumulate overturn model argues that dense LMO cumulates sank into the lunar interior, producing hybridized sources that melted to form the basalts. Here we compare predicted Ce/Yb and Hf and Nd isotopes of partial melts of LMO cumulates with measured compositions of lunar basalts to evaluate whether they could have formed by end-member petrogenetic models. LMO crystallization models suggest all LMO cumulates have chondrite normalized Ce/Yb <1. Residual liquid from the magma ocean has Ce/Yb 1.5. Many primitive lunar basalts have Ce/Yb>1.5; these could not have formed by assimilation of any LMO cumulate or residual liquid (or KREEP basalt, which has isotopically negative ɛNd and ɛHf). In contrast, basalt REE patterns and isotopes can easily be modeled assuming partial melting of hybridized mantle sources, indicating overturn may be required. A chemical requirement for overturn independently confirms that late LMO cumulates are sufficiently low in viscosity to sink into the lunar interior, as suggested by recent rock deformation experiments [4]. Overturned, low viscosity late LMO cumulates would be relatively stable around the core [5]. High Ce/Yb basalts require that overturned cumulates were mixed back into the overlying mantle by convection within a few hundred Myr. [1] Dygert et al. (2014), GCA 132, 170-186. [2] Sun et al. (2017), GCA 206, 273-295. [3] Lin et al. (2017), EPSL 471, 104-116. [4] Dygert et al. (2016), GRL 43, 10.1002/2015GL066546. [5] Zhang et al. (2017), GRL 44, 10.1002/2017GL073702.

Quantitative estimated exposure to vinyl chloride and risk of angiosarcoma of the liver and hepatocellular cancer in the US industry-wide vinyl chloride cohort: mortality update through 2013

PubMed Central

Mundt, Kenneth A; Dell, Linda D; Crawford, Lori; Gallagher, Alexa E

2017-01-01

Objective To evaluate mortality risks of angiosarcoma of the liver (ASL), primary hepatocellular carcinoma (HCC) and other cancers among 9951 men employed between 1942 and 1972 at 35 US vinyl chloride (VC) or polyvinyl chloride plants followed for mortality through 31 December 2013. Methods SMR and time-dependent Cox proportional hazards analyses were used to evaluate mortality risks by cumulative VC exposure. Results Liver cancer mortality was elevated (SMR=2.87, 95% CI 2.40 to 3.40), and ASL and HCC were strongly associated with cumulative VC exposure ≥865 parts per million-years (ppm-years) (ASL: HR=36.3, 95% CI 13.1 to 100.5; and HCC: HR=5.3, 95% CI 1.6 to 17.7 for ≥2271 ppm-years). Excess deaths due to connective and soft tissue cancers (SMR=2.43, 95% CI 1.48 to 3.75), mesothelioma (SMR=2.29, 95% CI 1.18 to 4.00) and explosions (SMR=3.43, 95% CI 1.25 to 7.47) were seen. Mortalities due to melanoma, brain cancer, lung cancer and non-Hodgkin’s lymphoma were not increased or associated with VC exposure. Conclusion The association between VC and ASL first reported in this cohort 44 years ago persisted and was strongest among workers most highly exposed. VC exposure also was associated with HCC mortality, although it remains possible that misdiagnosis of early ASLs influenced findings. PMID:28490663

Age-dependent associations between androgenetic alopecia and prostate cancer risk.

PubMed

Muller, David C; Giles, Graham G; Sinclair, Rod; Hopper, John L; English, Dallas R; Severi, Gianluca

2013-02-01

Both prostate cancer and androgenetic alopecia are strongly age-related conditions that are considered to be androgen dependent, but studies of the relationship between them have yielded inconsistent results. We aimed to assess whether androgenetic alopecia at ages 20 and 40 years are associated with risk of prostate cancer. At a follow-up of the Melbourne Collaborative Cohort Study, men were asked to assess their hair pattern at ages 20 and 40 years relative to eight categories in showcards. Cases were men notified to the Victorian Cancer Registry with prostate cancer diagnosed between cohort enrollment (1990-1994) and follow-up attendance (2003-2009). Flexible parametric survival models were used to estimate age-varying HRs and predicted cumulative probabilities of prostate cancer by androgenetic alopecia categories. Of 9,448 men that attended follow-up and provided data on androgenetic alopecia, we identified 476 prostate cancer cases during a median follow-up of 11 years four months. Cumulative probability of prostate cancer was greater at all ages up to 76 years, for men with vertex versus no androgenetic alopecia at age of 40 years. At age of 76 years, the estimated probabilities converged to 0.15. Vertex androgenetic alopecia at 40 years was also associated with younger age of diagnosis for prostate cancer cases. Vertex androgenetic alopecia at age of 40 years might be a marker of increased risk of early-onset prostate cancer. If confirmed, these results suggest that the apparently conflicting findings of previous studies might be explained by failure to adequately model the age-varying nature of the association between androgenetic alopecia and prostate cancer.

Relations of Growth in Effortful Control to Family Income, Cumulative Risk, and Adjustment in Preschool-age Children

PubMed Central

Lengua, Liliana J.; Moran, Lyndsey; Zalewski, Maureen; Ruberry, Erika; Kiff, Cara; Thompson, Stephanie

2014-01-01

The study examined growth in effortful control (executive control, delay ability) in relation to income, cumulative risk (aggregate of demographic and psychosocial risk factors), and adjustment in 306 preschool-age children (50% girls, 50% boys) from families representing a range of income (29% at- or near-poverty; 28% lower-income; 25% middle-income; 18% upper-income), with 4 assessments starting at 36–40 mos. Income was directly related to levels of executive control and delay ability. Cumulative risk accounted for the effects of income on delay ability but not executive control. Higher initial executive control and slope of executive control and delay ability predicted academic readiness, whereas levels, but not growth, of executive control and delay ability predicted social competence and adjustment problems. Low income is a marker for lower effortful control, which demonstrates additive or mediating effects in the relation of income to children’s preschool adjustment. PMID:25253079

Cumulative risk and developmental health: an argument for the importance of a family-wide science.

PubMed

Browne, Dillon T; Plamondon, Andre; Prime, Heather; Puente-Duran, Sofia; Wade, Mark

2015-01-01

A substantial body of research links social disadvantage and developmental health via a cascade running from poverty, to cumulative psychosocial risk, to disrupted family dynamics, to child biological regulatory systems and neurocognitive processing, and finally to morbidity across the lifespan. Most research in this area employs single-dyad or between-family methodology. While informative, there are limitations to this approach. Specifically, it is impossible to determine how risk alters psychosocial environments that are similar for all persons within a household, versus processes that are unique to particular children. This is important in light of literature citing the primacy of child-specific environments in driving developmental health. Methodologically speaking, there are both benefits and challenges to family-wide approaches that differentiate between- and within-family environments. This review describes literature linking cumulative risk and developmental health via family process, while articulating the importance of family-wide approaches. Areas of shortcoming and recommendations for a family-wide science are provided. © 2015 John Wiley & Sons, Ltd.

National Cohort Study of Suicidality and Violent Criminality among Danish Immigrants

PubMed Central

Webb, Roger T.; Antonsen, Sussie; Mok, Pearl L. H.; Agerbo, Esben; Pedersen, Carsten B.

2015-01-01

Background Immigrant populations in western societies have grown in their size and diversity yet evidence is incomplete for their risks of suicidality and criminal violence. We examined these correlated harmful behaviours in a national cohort. Aims (i) Compare absolute risk between first and second generation immigrants, foreign-born adoptees and native Danes by plotting cumulative incidence curves to onset of early middle age; (ii) estimate sex-specific relative risks for these immigrant type subgroups vs. native Danes; (iii) examine effect modification by higher vs. lower socio-economic status. Methods In a cohort of over two million persons, attempted suicides and violent crimes were investigated using data from multiple interlinked registers. We plotted sex-specific cumulative incidence curves and estimated incidence rate ratios. Results In the whole study cohort, 1414 people died by suicide, 46,943 attempted suicide, and 51,344 were convicted of committing a violent crime. Among all immigrant subgroups combined, compared with native Danes, relative risk of attempted suicide was greater in female immigrants (incidence rate ratio, 1.59; 95% confidence interval: CI 1.54-1.64) than in male immigrants (1.26; CI 1.20-1.32), and vice versa for relative risk of violent offending in male immigrants (2.36; CI 2.31-2.42) than in female immigrants (1.74; CI 1.62-1.87). Risk for both adverse outcomes was significantly elevated in virtually every gender-specific immigrant type subgroup examined. Violent crime risk was markedly raised in first generation immigrant males and in the Danish born male children of two immigrant parents. However, male immigrants of lower social status had lower risk of attempted suicide than their native Danish peers. Conclusion Young immigrants of both first and second generation status face serious challenges and vulnerabilities that western societies need to urgently address. Relative risk patterns for these adverse outcomes vary greatly between the genders and also by socioeconomic status. This high degree of heterogeneity points to the existence of modifiable factors that are amenable to positive change and a potential for effective intervention. PMID:26121654

National Cohort Study of Suicidality and Violent Criminality among Danish Immigrants.

PubMed

Webb, Roger T; Antonsen, Sussie; Mok, Pearl L H; Agerbo, Esben; Pedersen, Carsten B

2015-01-01

Immigrant populations in western societies have grown in their size and diversity yet evidence is incomplete for their risks of suicidality and criminal violence. We examined these correlated harmful behaviours in a national cohort. (i) Compare absolute risk between first and second generation immigrants, foreign-born adoptees and native Danes by plotting cumulative incidence curves to onset of early middle age; (ii) estimate sex-specific relative risks for these immigrant type subgroups vs. native Danes; (iii) examine effect modification by higher vs. lower socio-economic status. In a cohort of over two million persons, attempted suicides and violent crimes were investigated using data from multiple interlinked registers. We plotted sex-specific cumulative incidence curves and estimated incidence rate ratios. In the whole study cohort, 1414 people died by suicide, 46,943 attempted suicide, and 51,344 were convicted of committing a violent crime. Among all immigrant subgroups combined, compared with native Danes, relative risk of attempted suicide was greater in female immigrants (incidence rate ratio, 1.59; 95% confidence interval: CI 1.54-1.64) than in male immigrants (1.26; CI 1.20-1.32), and vice versa for relative risk of violent offending in male immigrants (2.36; CI 2.31-2.42) than in female immigrants (1.74; CI 1.62-1.87). Risk for both adverse outcomes was significantly elevated in virtually every gender-specific immigrant type subgroup examined. Violent crime risk was markedly raised in first generation immigrant males and in the Danish born male children of two immigrant parents. However, male immigrants of lower social status had lower risk of attempted suicide than their native Danish peers. Young immigrants of both first and second generation status face serious challenges and vulnerabilities that western societies need to urgently address. Relative risk patterns for these adverse outcomes vary greatly between the genders and also by socioeconomic status. This high degree of heterogeneity points to the existence of modifiable factors that are amenable to positive change and a potential for effective intervention.

Individual Impact Magnitude vs. Cumulative Magnitude for Estimating Concussion Odds.

PubMed

O'Connor, Kathryn L; Peeters, Thomas; Szymanski, Stefan; Broglio, Steven P

2017-08-01

Helmeted impact devices have allowed researchers to investigate the biomechanics of head impacts in vivo. While increased impact magnitude has been associated with greater concussion risk, a definitive concussive threshold has not been established. It is likely that concussion risk is not determined by a single impact itself, but a host of predisposing factors. These factors may include genetics, fatigue, and/or prior head impact exposure. The objective of the current paper is to investigate the association between cumulative head impact magnitude and concussion risk. It is hypothesized that increased cumulative magnitudes will be associated with greater concussion risk. This retrospective analysis included participants that were recruited from regional high-schools in Illinois and Michigan from 2007 to 2014 as part of an ongoing study on concussion biomechanics. Across seven seasons, 185 high school football athletes were instrumented with the Head Impact Telemetry system. Out of 185 athletes, 31 (17%) sustained a concussion, with two athletes sustaining two concussions over the study period, yielding 33 concussive events. The system recorded 78,204 impacts for all concussed players. Linear acceleration, rotational acceleration, and head impact telemetry severity profile (HITsp) magnitudes were summed within five timeframes: the day of injury, three days prior to injury, seven days prior to injury, 30 days prior to injury, and prior in-season exposure. Logistic regressions were modeled to explain concussive events based on the singular linear acceleration, rotational acceleration, and HITsp event along with the calculated summations over time. Linear acceleration, rotational acceleration, and HITsp all produced significant models estimating concussion (p < 0.05). The strongest estimators of a concussive impact were the linear acceleration (OR = 1.040, p < 0.05), rotational acceleration (OR = 1.001, p < 0.05), and HITsp (OR = 1.003, p < 0.05) for the singular impact rather than any of the cumulative magnitude calculations. Moreover, no cumulative count measure was significant for linear or rotational acceleration. Results from this investigation support the growing literature indicating cumulative magnitude is not related to concussion likelihood. Cumulative magnitude is a simplistic measure of the total exposure sustained by a player over a given period. However, this measure is limited as it assumes the brain is a static structure unable to undergo self-repair. Future research should consider how biological recovery between impacts may influence concussion risk.

Male chromosomal polymorphisms reduce cumulative live birth rate for IVF couples.

PubMed

Ni, Tianxiang; Li, Jing; Chen, Hong; Gao, Yuan; Gao, Xuan; Yan, Junhao; Chen, Zi-Jiang

2017-08-01

Chromosomal polymorphisms are associated with infertility, but their effects on assisted reproductive outcomes are still quite conflicting, especially after IVF treatment. This study evaluated the role of chromosomal polymorphisms of different genders in IVF pregnancy outcomes. Four hundred and twenty-five infertile couples undergoing IVF treatment were divided into three groups: 214 couples with normal chromosomes (group A, control group), 86 couples with female polymorphisms (group B), and 125 couples with male polymorphisms (group C). The pregnancy outcomes after the first and cumulative transfer cycles were analyzed, and the main outcome measures were live birth rate (LBR) after the first transfer cycle and cumulative LBR after a complete IVF cycle. Comparison of pregnancy outcomes after the first transfer cycle within group A, group B, and group C demonstrated a similar LBR as well as other rates of implantation, clinical pregnancy, early miscarriage, and ongoing pregnancy (P > 0.05). However, the analysis of cumulative pregnancy outcomes indicated that compared with group A, group C had a significantly lower LBR per cycle (80.4 vs 68.00%), for a rate ratio of 1.182 (95% CI 1.030 to 1.356, P = 0.01) and a significantly higher cumulative early miscarriage rate (EMR) among clinical pregnancies (7.2 vs 14.7%), for a rate ratio of 0.489 (95% CI 0.248 to 0.963, P = 0.035). Couples with chromosomal polymorphisms in only male partners have poor pregnancy outcomes after IVF treatment manifesting as high cumulative EMR and low LBR after a complete cycle.

Relationships between alumina and bauxite dust exposure and cancer, respiratory and circulatory disease.

PubMed

Friesen, M C; Fritschi, L; Del Monaco, A; Benke, G; Dennekamp, M; de Klerk, N; Hoving, J L; MacFarlane, E; Sim, M R

2009-09-01

To examine the associations between alumina and bauxite dust exposure and cancer incidence and circulatory and respiratory disease mortality among bauxite miners and alumina refinery workers. This cohort of 5770 males has previously been linked to national mortality and national and state cancer incidence registries (1983-2002). In this paper, Poisson regression was used to undertake internal comparisons within the cohort based on subgroups of cumulative exposure to inhalable bauxite and alumina dust. Exposure was estimated using job histories and historical air monitoring data. There was no association between ever bauxite exposure and any of the outcomes. There was a borderline significant association between ever alumina exposure and cerebrovascular disease mortality (10 deaths, RR 3.8, 95% CI 1.1 to 13). There was some evidence of an exposure-response relationship between cumulative bauxite exposure and non-malignant respiratory disease mortality (seven deaths, trend p value: 0.01) and between cumulative alumina exposure and cerebrovascular disease mortality (trend p value: 0.04). These associations were based on very few cases and for non-malignant respiratory disease the deaths represented a heterogeneous mixture of causes. There was no evidence of an excess risk for any cancer type with bauxite or alumina exposure. These preliminary findings, based on very few cases, suggest that cumulative inhalable bauxite exposure may be associated with an excess risk of death from non-malignant respiratory disease and that cumulative inhalable alumina dust exposure may be associated with an excess risk of death from cerebrovascular disease. Neither exposure appears to increase the risk of incident cancers.

Modeling Joint Exposures and Health Outcomes for Cumulative Risk Assessment: The Case of Radon and Smoking

PubMed Central

Chahine, Teresa; Schultz, Bradley D.; Zartarian, Valerie G.; Xue, Jianping; Subramanian, SV; Levy, Jonathan I.

2011-01-01

Community-based cumulative risk assessment requires characterization of exposures to multiple chemical and non-chemical stressors, with consideration of how the non-chemical stressors may influence risks from chemical stressors. Residential radon provides an interesting case example, given its large attributable risk, effect modification due to smoking, and significant variability in radon concentrations and smoking patterns. In spite of this fact, no study to date has estimated geographic and sociodemographic patterns of both radon and smoking in a manner that would allow for inclusion of radon in community-based cumulative risk assessment. In this study, we apply multi-level regression models to explain variability in radon based on housing characteristics and geological variables, and construct a regression model predicting housing characteristics using U.S. Census data. Multi-level regression models of smoking based on predictors common to the housing model allow us to link the exposures. We estimate county-average lifetime lung cancer risks from radon ranging from 0.15 to 1.8 in 100, with high-risk clusters in areas and for subpopulations with high predicted radon and smoking rates. Our findings demonstrate the viability of screening-level assessment to characterize patterns of lung cancer risk from radon, with an approach that can be generalized to multiple chemical and non-chemical stressors. PMID:22016710

Incidence and risk factors for secondary malignancy in patients with neuroblastoma after treatment with (131)I-metaiodobenzylguanidine.

PubMed

Huibregtse, Kelly E; Vo, Kieuhoa T; DuBois, Steven G; Fetzko, Stephanie; Neuhaus, John; Batra, Vandana; Maris, John M; Weiss, Brian; Marachelian, Araz; Yanik, Greg A; Matthay, Katherine K

2016-10-01

Several reports of second malignant neoplasm (SMN) in patients with relapsed neuroblastoma after treatment with (131)I-MIBG suggest the possibility of increased risk. Incidence of and risk factors for SMN after (131)I-MIBG have not been defined. This is a multi-institutional retrospective review of patients with neuroblastoma treated with (131)I-MIBG therapy. A competing risk approach was used to calculate the cumulative incidence of SMN from time of first exposure to (131)I-MIBG. A competing risk regression was used to identify potential risk factors for SMN. The analytical cohort included 644 patients treated with (131)I-MIBG. The cumulative incidence of SMN was 7.6% (95% confidence interval [CI], 4.4-13.0%) and 14.3% (95% CI, 8.3-23.9%) at 5 and 10 years from first (131)I-MIBG, respectively. No increase in SMN risk was found with increased number of (131)I-MIBG treatments or higher cumulative activity per kilogram of (131)I-MIBG received (p = 0.72 and p = 0.84, respectively). Thirteen of the 19 reported SMN were haematologic. In a multivariate analysis controlling for variables with p < 0.1 (stage, age at first (131)I-MIBG, bone disease, disease status at time of first (131)I-MIBG), patients with relapsed/progressive disease had significantly lower risk of SMN (subdistribution hazard ratio 0.3, 95% CI, 0.1-0.8, p = 0.023) compared to patients with persistent/refractory neuroblastoma. The cumulative risk of SMN after (131)I-MIBG therapy for patients with relapsed or refractory neuroblastoma is similar to the greatest published incidence for high-risk neuroblastoma after myeloablative therapy, with no dose-dependent increase. As the number of patients treated and length of follow-up time increase, it will be important to reassess this risk. Copyright © 2016 Elsevier Ltd. All rights reserved.

The natural history of adult pulmonary Langerhans cell histiocytosis: a prospective multicentre study.

PubMed

Tazi, Abdellatif; de Margerie, Constance; Naccache, Jean Marc; Fry, Stéphanie; Dominique, Stéphane; Jouneau, Stéphane; Lorillon, Gwenaël; Bugnet, Emmanuelle; Chiron, Raphael; Wallaert, Benoit; Valeyre, Dominique; Chevret, Sylvie

2015-03-14

The natural history of pulmonary Langerhans cell histiocytosis (PLCH) has been unclear due to the absence of prospective studies. The rate of patients who experience an early progression of their disease is unknown. Additionally, conflicting effects of smoking cessation on the outcome of PLCH have been reported. In this prospective, multicentre study, 58 consecutive patients with newly diagnosed PLCH were comprehensively evaluated over a two-year period. Our objectives were to estimate the incidence of early progression of the disease and to evaluate the impact of smoking status on lung function outcomes. Lung function deterioration was defined as a decrease of at least 15% in FEV1 and/or FVC and/or DLCO, compared with baseline values. At each visit, smoking status was recorded based on the patients' self-reports and urinary cotinine measurements that were blinded for the patients. The cumulative incidence of lung function outcomes over time was estimated using the non-parametric Kaplan-Meier method. Multivariate Cox models with time-dependent covariates were used to calculate the hazards ratios of the lung function deterioration associated with smoking status with adjustment for potential confounders. The cumulative incidence of lung function deterioration at 24 months was 38% (22% for FEV1 and DLCO, and 9% for FVC). In the multivariate analysis, smoking status and PaO2 at inclusion were the only factors associated with the risk of lung function deterioration. The patients' smoking statuses markedly changed over time. Only 20% of the patients quit using tobacco for the entire study period. Nevertheless, being a non-smoker was associated with a decreased risk of subsequent lung function deterioration, even after adjustment for baseline predictive factors. By serial lung computed tomography, the extent of cystic lesions increased in only 11% of patients. Serial lung function evaluation on a three- to six-month basis is essential for the follow-up of patients with recently diagnosed PLCH to identify those who experience an early progression of their disease. These patients are highly addicted to tobacco, and robust efforts should be undertaken to include them in smoking cessation programs. ClinicalTrials.gov: No: NCT01225601 .

Late Relapse of Classical Hodgkin Lymphoma: An Analysis of the German Hodgkin Study Group HD7 to HD12 Trials.

PubMed

Bröckelmann, Paul J; Goergen, Helen; Kohnhorst, Charlotte; von Tresckow, Bastian; Moccia, Alden; Markova, Jana; Meissner, Julia; Kerkhoff, Andrea; Ludwig, Wolf-Dieter; Fuchs, Michael; Borchmann, Peter; Engert, Andreas

2017-05-01

Purpose Clinical characteristics, therapeutic approaches, and prognosis of late relapse (LR) in patients with classic Hodgkin lymphoma (cHL) are poorly understood. We performed a comprehensive analysis of LR of Hodgkin lymphoma (LR-HL). Methods To estimate the incidence of LR-HL, we retrospectively analyzed 6,840 patients with cHL included in the German Hodgkin Study Group trials HD7 to HD12. Patients who experienced a relapse > 5 years into remission were compared with patients in continued remission for > 5 years and with those who experienced a relapse ≤ 5 years after first diagnosis. Results With a median observation time of 10.3 years, 141 incidences of LR-HL were observed. Cumulative incidences at 10, 15, and 20 years rose linearly and were 2.5%, 4.3%, and 6.9%, respectively. The standardized incidence ratio for HL with respect to age- and sex-matched German reference data was 84.5 (95% CI, 71.2 to 99.7). LR-HL was more frequently observed in patients with early-stage favorable than unfavorable or advanced stage at first diagnosis (15-year cumulative incidence, 5.3% v 3.9% and 3.9%, respectively; P = .01). Overall survival from first diagnosis was worse after LR compared with nonrelapse survivors (10-year estimate, 95.8% v 86.1%; hazard ratio, 2.5; 95% CI, 1.7 to 3.5; P < .001). In patients with LR-HL, survival was better compared with 466 patients with earlier relapse (hazard ratio, 0.6; 95% CI, 0.4 to 0.9, P = .01). Forty-four percent and 49% of patients with LR-HL and earlier relapse, respectively, received stem cell transplantations. Conclusion Apart from treatment-associated adverse effects, survivors after initially successful therapy for cHL are at an 85-fold risk for recurrence of disease compared with the general German population. After risk-adapted treatment strategies, especially in early-stage favorable HL, regular clinical follow-up is recommended for timely detection of LR-HL. With adequate treatment, prognosis of LR-HL is better compared with early relapses.

ORD PYRETHROIDS PROJECT

EPA Science Inventory

The Food Quality Protection Act (FQPA) of 1996 requires the Agency to consider the cumulative effects of pesticides and other substances that act by a common mechanism. Under the mandates of FQPA, the Agency conducted a cumulative risk assessment for the organophosphate pesticid...

Cumulative Exposure to Systolic Blood Pressure During Young Adulthood Through Midlife and the Urine Albumin-to-Creatinine Ratio at Midlife.

PubMed

Kramer, Holly; Colangelo, Laura; Lewis, Cora E; Jacobs, David R; Pletcher, Mark; Bibbins-Domingo, Kirstin; Chang, Alex; Siscovick, David; Shlipak, Michael; Peralta, Carmen A; Bansal, Nisha; Muntner, Paul; Liu, Kiang

2017-05-01

Higher blood pressure during young adulthood may increase cardiovascular and kidney disease risk later in life. This study examined the association of cumulative systolic blood pressure (SBP) exposure during young adulthood through midlife with urine albumin-to-creatinine ratios (ACR) measured during midlife. We used data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a biracial cohort recruited in 4 urban areas during years 1985-1986. Cumulative SBP was calculated as the average SBP between 2 exams multiplied by years between exams over 20 year years. ACR was measured 20 years after baseline when participants were age 43-50 years (midlife). A generalized additive model was used to examine the association of log ACR as a function of cumulative SBP with adjustment for covariates including SBP measured concurrently with ACR. Cumulative SBP ranged from a low of 1,671 to a high of 3,260 mm Hg. Participants in the highest cumulative SBP quartile were more likely to be male (61.4% vs. 20.7%; P < 0.001), Black (61.5% vs. 25.6%; P < 0.001) and have elevated ACR (18.7% vs. 4.8%; P < 0.001) vs. lowest quartile. Spline regression curves of ACR vs. cumulative SBP demonstrated an inflection point in ACR with cumulative SBP levels >2,350 mm Hg with linear increases in ACR above this threshold. Adjusted geometric mean ACR values were significantly higher with cumulative SBP ≥2,500 vs. <2500 (9.18 [1.06] vs. 6.92 [1.02]; P < 0.0001). Higher SBP during young adulthood through midlife is associated with higher ACR during midlife. © American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Risk of Recurrent Pancreatitis and Progression to Chronic Pancreatitis After a First Episode of Acute Pancreatitis.

PubMed

Ahmed Ali, Usama; Issa, Yama; Hagenaars, Julia C; Bakker, Olaf J; van Goor, Harry; Nieuwenhuijs, Vincent B; Bollen, Thomas L; van Ramshorst, Bert; Witteman, Ben J; Brink, Menno A; Schaapherder, Alexander F; Dejong, Cornelis H; Spanier, B W Marcel; Heisterkamp, Joos; van der Harst, Erwin; van Eijck, Casper H; Besselink, Marc G; Gooszen, Hein G; van Santvoort, Hjalmar C; Boermeester, Marja A

2016-05-01

Patients with a first episode of acute pancreatitis can develop recurrent or chronic pancreatitis (CP). However, little is known about the incidence or risk factors for these events. We performed a cross-sectional study of 669 patients with a first episode of acute pancreatitis admitted to 15 Dutch hospitals from December 2003 through March 2007. We collected information on disease course, outpatient visits, and hospital readmissions, as well as results from imaging, laboratory, and histology studies. Standardized follow-up questionnaires were sent to all available patients to collect information on hospitalizations and interventions for pancreatic disease, abdominal pain, steatorrhea, diabetes mellitus, medications, and alcohol and tobacco use. Patients were followed up for a median time period of 57 months. Primary end points were recurrent pancreatitis and CP. Risk factors were evaluated using regression analysis. The cumulative risk was assessed using Kaplan-Meier analysis. Recurrent pancreatitis developed in 117 patients (17%), and CP occurred in 51 patients (7.6%). Recurrent pancreatitis developed in 12% of patients with biliary disease, 24% of patients with alcoholic etiology, and 25% of patients with disease of idiopathic or other etiologies; CP occurred in 3%, 16%, and 10% of these patients, respectively. Etiology, smoking, and necrotizing pancreatitis were independent risk factors for recurrent pancreatitis and CP. Acute Physiology and Chronic Health Evaluation II scores at admission also were associated independently with recurrent pancreatitis. The cumulative risk for recurrent pancreatitis over 5 years was highest among smokers at 40% (compared with 13% for nonsmokers). For alcohol abusers and current smokers, the cumulative risks for CP were similar-approximately 18%. In contrast, the cumulative risk of CP increased to 30% in patients who smoked and abused alcohol. Based on a retrospective analysis of patients admitted to Dutch hospitals, a first episode of acute pancreatitis leads to recurrent pancreatitis in 17% of patients, and almost 8% of patients progress to CP within 5 years. Progression was associated independently with alcoholic etiology, smoking, and a history of pancreatic necrosis. Smoking is the predominant risk factor for recurrent disease, whereas the combination of alcohol abuse and smoking produces the highest cumulative risk for chronic pancreatitis. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Sunburn risk among children and outdoor workers in South Africa and Reunion Island coastal sites.

PubMed

Wright, Caradee Y; Brogniez, Colette; Ncongwane, Katlego P; Sivakumar, Venkataraman; Coetzee, Gerrie; Metzger, Jean-Marc; Auriol, Frédérique; Deroo, Christine; Sauvage, Béatrice

2013-01-01

To estimate potential sunburn risk for schoolchildren and outdoor workers, ground-based ambient solar ultraviolet radiation (UVR) measurements were converted into possible child (5% of ambient solar UVR) and outdoor worker (20% of ambient solar UVR) solar UVR exposures by skin type and season for three coastal sites: Durban, Cape Point (South Africa) and Saint Denis (Reunion Island, France). Cumulative daily ambient solar UVR levels were relatively high at all sites, especially during summer, with maximum values of about 67, 57 and 74 Standard Erythemal Dose (SED) (1 SED = 100 J m(-2)) at Durban, Cape Point and Saint Denis respectively. Sunburn risk was evident for both children and outdoor workers, especially those with skin types I and II (extremely to moderately sensitive) during summer, early autumn and/or late spring at all three sites. Although results need to be verified with real-time, instantaneous and nonintegrated personal solar UVR measurements, this understanding of sunburn risk is useful for initiating the development skin cancer prevention and sun protection awareness campaigns in both countries. © 2013 The American Society of Photobiology.

Cost analysis of a growth guidance system compared with traditional and magnetically controlled growing rods for early-onset scoliosis: a US-based integrated health care delivery system perspective.

PubMed

Luhmann, Scott J; McAughey, Eoin M; Ackerman, Stacey J; Bumpass, David B; McCarthy, Richard E

2018-01-01

Treating early-onset scoliosis (EOS) with traditional growing rods (TGR) is effective but requires periodic surgical lengthening, risking complications. Alternatives include magnetically controlled growing rods (MCGR) that lengthen noninvasively and the growth guidance system (GGS), which obviate the need for active, distractive lengthenings. Previous studies have reported promising clinical effectiveness for GGS; however the direct medical costs of GGS compared to TGR and MCGR have not yet been explored. To estimate the cost of GGS compared with MCGR and TGR for EOS an economic model was developed from the perspective of a US integrated health care delivery system. Using dual-rod constructs, the model estimated the cumulative costs associated with initial implantation, rod lengthenings (TGR, MCGR), revisions due to device failure, surgical-site infections, device exchange, and final spinal fusion over a 6-year episode of care. Model parameters were from peer-reviewed, published literature. Medicare payments were used as a proxy for provider costs. Costs (2016 US$) were discounted 3% annually. Over a 6-year episode of care, GGS was associated with fewer invasive surgeries per patient than TGR (GGS: 3.4; TGR: 14.4) and lower cumulative costs than MCGR and TGR, saving $25,226 vs TGR. Sensitivity analyses showed that results were sensitive to changes in construct costs, rod breakage rates, months between lengthenings, and TGR lengthening setting of care. Within the model, GGS resulted in fewer invasive surgeries and deep surgical site infections than TGR, and lower cumulative costs per patient than both MCGR and TGR, over a 6-year episode of care. The analysis did not account for family disruption, pain, psychological distress, or compromised health-related quality of life associated with invasive TGR lengthenings, nor for potential patient anxiety surrounding the frequent MCGR lengthenings. Further analyses focusing strictly on current generation technologies should be considered for future research.

Cost analysis of a growth guidance system compared with traditional and magnetically controlled growing rods for early-onset scoliosis: a US-based integrated health care delivery system perspective

PubMed Central

Luhmann, Scott J; McAughey, Eoin M; Ackerman, Stacey J; Bumpass, David B; McCarthy, Richard E

2018-01-01

Purpose Treating early-onset scoliosis (EOS) with traditional growing rods (TGR) is effective but requires periodic surgical lengthening, risking complications. Alternatives include magnetically controlled growing rods (MCGR) that lengthen noninvasively and the growth guidance system (GGS), which obviate the need for active, distractive lengthenings. Previous studies have reported promising clinical effectiveness for GGS; however the direct medical costs of GGS compared to TGR and MCGR have not yet been explored. Methods To estimate the cost of GGS compared with MCGR and TGR for EOS an economic model was developed from the perspective of a US integrated health care delivery system. Using dual-rod constructs, the model estimated the cumulative costs associated with initial implantation, rod lengthenings (TGR, MCGR), revisions due to device failure, surgical-site infections, device exchange, and final spinal fusion over a 6-year episode of care. Model parameters were from peer-reviewed, published literature. Medicare payments were used as a proxy for provider costs. Costs (2016 US$) were discounted 3% annually. Results Over a 6-year episode of care, GGS was associated with fewer invasive surgeries per patient than TGR (GGS: 3.4; TGR: 14.4) and lower cumulative costs than MCGR and TGR, saving $25,226 vs TGR. Sensitivity analyses showed that results were sensitive to changes in construct costs, rod breakage rates, months between lengthenings, and TGR lengthening setting of care. Conclusion Within the model, GGS resulted in fewer invasive surgeries and deep surgical site infections than TGR, and lower cumulative costs per patient than both MCGR and TGR, over a 6-year episode of care. The analysis did not account for family disruption, pain, psychological distress, or compromised health-related quality of life associated with invasive TGR lengthenings, nor for potential patient anxiety surrounding the frequent MCGR lengthenings. Further analyses focusing strictly on current generation technologies should be considered for future research. PMID:29588607

Kindergarten stressors and cumulative adrenocortical activation: the "first straws" of allostatic load?

PubMed

Bush, Nicole R; Obradović, Jelena; Adler, Nancy; Boyce, W Thomas

2011-11-01

Using an ethnically diverse longitudinal sample of 338 kindergarten children, this study examined the effects of cumulative contextual stressors on children's developing hypothalamic-pituitary-adrenocortical (HPA) axis regulation as an early life indicator of allostatic load. Chronic HPA axis regulation was assessed using cumulative, multiday measures of cortisol in both the fall and spring seasons of the kindergarten year. Hierarchical linear regression analyses revealed that contextual stressors related to ethnic minority status, socioeconomic status, and family adversity each uniquely predicted children's daily HPA activity and that some of those associations were curvilinear in conformation. Results showed that the quadratic, U-shaped influences of family socioeconomic status and family adversity operate in different directions to predict children's HPA axis regulation. Results further suggested that these associations differ for White and ethnic minority children. In total, this study revealed that early childhood experiences contribute to shifts in one of the principal neurobiological systems thought to generate allostatic load, confirming the importance of early prevention and intervention efforts. Moreover, findings suggested that analyses of allostatic load and developmental theories accounting for its accrual would benefit from an inclusion of curvilinear associations in tested predictive models.

Cumulative effects analysis of the water quality risk of herbicides used for site preparation in the Central North Island, New Zealand

Treesearch

Dan Neary; Brenda R. Baillie

2016-01-01

Herbicide use varies both spatially and temporally within managed forests. While information exists on the effects of herbicide use on water quality at the site and small catchment scale, little is known about the cumulative effects of herbicide use at the landscape scale. A cumulative effects analysis was conducted in the upper Rangitaiki catchment (118,345...

Long-Term Cumulative Effects of Childcare on Children's Mental Development and Socioemotional Adjustment in a Non-Risk Sample: The Moderating Effects of Gender

ERIC Educational Resources Information Center

Bornstein, Marc H.; Hahn, Chun-Shin; Gist, Nancy F.; Haynes, O. Maurice

2006-01-01

We studied the long-term cumulative effects of two common indices of childcare--the total number of hours of non-maternal care and the mean hour-weighted child-to-caregiver ratio per caregiving situation--on mental development and socioemotional adjustment from birth to 4.5 years old in a non-risk middle-class sample of girls and boys after taking…

Preventive strategies for mental health.

PubMed

Arango, Celso; Díaz-Caneja, Covadonga M; McGorry, Patrick D; Rapoport, Judith; Sommer, Iris E; Vorstman, Jacob A; McDaid, David; Marín, Oscar; Serrano-Drozdowskyj, Elena; Freedman, Robert; Carpenter, William

2018-05-14

Available treatment methods have shown little effect on the burden associated with mental health disorders. We review promising universal, selective, and indicated preventive mental health strategies that might reduce the incidence of mental health disorders, or shift expected trajectories to less debilitating outcomes. Some of these interventions also seem to be cost-effective. In the transition to mental illness, the cumulative lifetime effect of multiple small effect size risk factors progressively increases vulnerability to mental health disorders. This process might inform different levels and stages of tailored interventions to lessen risk, or increase protective factors and resilience, especially during sensitive developmental periods. Gaps between knowledge, policy, and practice need to be bridged. Future steps should emphasise mental health promotion, and improvement of early detection and interventions in clinical settings, schools, and the community, with essential support from society and policy makers. Copyright © 2018 Elsevier Ltd. All rights reserved.

A missing link in the evolution of the cumulative recorder.

PubMed

Asano, Toshio; Lattal, Kennon A

2012-09-01

A recently recovered cumulative recorder provides a missing link in the evolution of the cumulative recorder from a modified kymograph to a reliably operating, scientifically and commercially successful instrument. The recorder, the only physical evidence of such an early precommercial cumulative recorder yet found, was sent to Keio University in Tokyo, Japan, in 1952 at the behest of B. F. Skinner at Harvard University. Last used in research in the late 1960s, the cumulative recorder remained locked in a storage room until 2007, when it was found again. A historical context for the recorder is followed by a description of the recorder and a comparison between it and the commercially successful Gerbrands Model C-1 recorder. Labeled the Keio recorder, it is a testament to Skinner's persistence in developing a reliable means of quantifying the behavior of living organisms in real time.

Associations of adversity in childhood and risk factors for cardiovascular disease in mid-adulthood.

PubMed

Anderson, Emma L; Fraser, Abigail; Caleyachetty, Rishi; Hardy, Rebecca; Lawlor, Debbie A; Howe, Laura D

2018-02-01

Studies assessing associations of childhood psychosocial adversity (e.g. sexual abuse, physical neglect, parental death), as opposed to socioeconomic adversity, with cardiovascular disease (CVD) risk factors in adulthood are scarce. The aim of this study is to assess associations of various types of psychosocial adversity and cumulative adversity in childhood, with multiple CVD risk factors in mid-life. At study enrolment, women from the Avon Longitudinal Study of Parents and Children (N=3612) retrospectively reported: lack of maternal care, maternal overprotection, parental mental illness, household dysfunction, sexual abuse, physical and emotional abuse, and neglect in childhood. Approximately 23 years later, body mass index (BMI), waist circumference, systolic and diastolic blood pressure, plasma glucose, insulin, triglycerides, low and high density lipoprotein cholesterol, C-reactive protein, carotid intima-media thickness (cIMT) and arterial distensibility were assessed (mean age 51 years). We examined associations of each specific type of psychosocial adversity and cumulative adversity with CVD risk factors. No specific type of psychosocial adversity was consistently associated with the CVD risk factors. There was evidence that a one standard deviation greater cumulative psychosocial adversity was associated with 0.51cm greater waist circumference (95% confidence interval [CI]: 0.02cm, 1.00cm, p=0.04) and a lower arterial distensibility, even after adjustment for age, ethnicity and childhood and adult socioeconomic position. We found no consistent evidence that any specific type of psychosocial adversity, or cumulative psychosocial adversity in childhood, is associated with CVD risk factors in adult women. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Intravenous Infiltration Risk by Catheter Dwell Time Among Hospitalized Children.

PubMed

Jeong, Ihn Sook; Jeon, Gey Rok; Lee, Man Seop; Shin, Bum Joo; Kim, Yong-Jin; Park, Soon Mi; Hyun, Sookyung

This study was aimed to examine the cumulative risk for infiltration over IV catheter dwell time by general or catheterization-specific characteristics of pediatric patients with IV therapy. This secondary data analysis was done with the data of 1596 children who received peripheral IV therapy at least once during their hospital stay between August 1st and October 30th, 2011 and in June, 2013 in an academic medical center, Yangsan, Republic of Korea. The survival functions of infiltration were determined by using the Kaplan-Meier analysis. The cumulative risk for infiltration had rapidly increased from 1.5% after 24 hours of catheter dwell time to 17.3% after 96 hours. The survival functions were significantly different in the medical than in the surgical department (p=.005), lower extremities than upper ones (p=.001), and use of 10% dextrose (p=.001), ampicillin/sulbactam (p<.001), vancomycin (p=.024), high-concentration electrolytes (p=.001), and phenytoin (p<.001). When catheter dwell times are similar, the cumulative risk for infiltration was higher in cases wherein the patient had a risk factor. The cumulative risk for infiltration has rapidly increased after 24 hours in patients who have 10% dextrose, high-concentration electrolytes, and phenytoin. The results suggest that nurses are required to assess the IV site every hour after 24 hours of catheter dwell time for the infusion of irritants for a safer practice of IV therapy. However, this monitoring time may be modified by the age of child, previous IV complications, and/or hemodynamic issues which may impact IV integrity. Copyright © 2016 Elsevier Inc. All rights reserved.

Birth defects after use of antithyroid drugs in early pregnancy: a Swedish nationwide study.

PubMed

Andersen, Stine Linding; Lönn, Stefan; Vestergaard, Peter; Törring, Ove

2017-10-01

Antithyroid drugs (ATDs) may have teratogenic effects, but more evidence is needed on the risk and types of birth defects after the use of methimazole (MMI) and propylthiouracil (PTU). This study aimed to evaluate the association between the use of ATDs in early pregnancy and birth defects. Swedish nationwide register-based cohort study. The study included 684 340 children live-born in Sweden from 2006 to 2012. Exposure groups defined by maternal ATD use in early pregnancy were MMI ( n  = 162); PTU ( n  = 218); MMI and PTU ( n  = 66); ATD before or after, but not in pregnancy ( n  = 1551) and non-exposed (never ATD ( n  = 682 343)). Outcome was cumulative incidence of birth defects diagnosed before two years of age. The cumulative incidence of birth defects was not significantly different in children exposed to MMI (6.8%, P  = 0.6) or PTU (6.4%, P  = 0.4) vs non-exposed (8.0%). For subtypes of birth defects, MMI was associated with an increased incidence of septal heart defects ( P  = 0.02). PTU was associated with ear ( P  = 0.005) and obstructive urinary system malformations ( P  = 0.006). A case of choanal atresia was observed after exposure to both MMI and PTU. The incidence of birth defects in children born to mothers who received ATD before or after, but not in pregnancy, was 8.8% and not significantly different from non-exposed ( P  = 0.3), MMI exposed ( P  = 0.4) or PTU exposed ( P  = 0.2). MMI and PTU were associated with subtypes of birth defects previously reported, but the frequency of ATD exposure in early pregnancy was low and severe malformations described in the MMI embryopathy were rarely observed. © 2017 European Society of Endocrinology.

Head Impact Exposure in Youth Football: High School Ages 14 to 18 Years and Cumulative Impact Analysis

PubMed Central

Urban, Jillian E.; Davenport, Elizabeth M.; Golman, Adam J.; Maldjian, Joseph A.; Whitlow, Christopher T.; Powers, Alexander K.; Stitzel, Joel D.

2015-01-01

Sports-related concussion is the most common athletic head injury with football having the highest rate among high school athletes. Traditionally, research on the biomechanics of football-related head impact has been focused at the collegiate level. Less research has been performed at the high school level, despite the incidence of concussion among high school football players. The objective of this study is to twofold: to quantify the head impact exposure in high school football, and to develop a cumulative impact analysis method. Head impact exposure was measured by instrumenting the helmets of 40 high school football players with helmet mounted accelerometer arrays to measure linear and rotational acceleration. A total of 16,502 head impacts were collected over the course of the season. Biomechanical data were analyzed by team and by player. The median impact for each player ranged from 15.2 to 27.0 g with an average value of 21.7 (±2.4) g. The 95th percentile impact for each player ranged from 38.8 to 72.9 g with an average value of 56.4 (±10.5) g. Next, an impact exposure metric utilizing concussion injury risk curves was created to quantify cumulative exposure for each participating player over the course of the season. Impacts were weighted according to the associated risk due to linear acceleration and rotational acceleration alone, as well as the combined probability (CP) of injury associated with both. These risks were summed over the course of a season to generate risk weighted cumulative exposure. The impact frequency was found to be greater during games compared to practices with an average number of impacts per session of 15.5 and 9.4, respectively. However, the median cumulative risk weighted exposure based on combined probability was found to be greater for practices vs. games. These data will provide a metric that may be used to better understand the cumulative effects of repetitive head impacts, injury mechanisms, and head impact exposure of athletes in football. PMID:23864337

Pre-AIDS mortality in the Edinburgh City Hospital HIV cohort.

PubMed

Seaman, S R; Brettle, R P; Gore, S M

1997-11-15

In this paper, we look at the incidence and predictive factors of pre-AIDS mortality among HIV-infected individuals, and injecting drug users (IDUs) in particular, and compare IDUs with non-IDUs. 627 patients (73 per cent IDUs) of the Edinburgh City Hospital HIV Cohort were enrolled pre-AIDS and followed up until September 1994. Analyses were performed using cumulative hazard and cumulative incidence estimators for a competing risks model, the Cox proportional hazards model and the non-parametric hazard estimator of Fusaro et al. (1993). The effects of age and CD4 T-lymphocyte cell count, progressively depleted during HIV progression, were investigated. 60 deaths occurred in AIDS-free patients during follow-up; 25 were drug-related deaths in IDUs. Pre-AIDS mortality was higher among IDUs than non-IDUs (p = 0.07). The cumulative incidences of pre-AIDS death after five years from enrollment were 11 per cent in IDUs and 6 per cent in non-IDUs; the cumulative AIDS incidences were, respectively, 19 per cent and 32 per cent. After eight years, cumulative pre-AIDS death incidence was 15 per cent among IDUs; cumulative AIDS incidence among IDUs was 35 per cent. Both groups had similar risks of medically-related (non-AIDS)-MRNA-death. Age and CD4 count were both individually predictive of MRNA death (relative risks (RRs); 2.1 per decade of life, p < 0.01; and 1.9 for each 100 cells per 100 microliters lost, p < 0.0001), although when used together age was less significant (RR 1.6, p = 0.07). Neither was statistically significant for drug-related mortality, although hazard may be lower in older individuals and may increase with falling CD4 count. The drug-related mortality was 1.1 per cent: 2.3 per cent in the first two years after enrollment, and 0.4 per cent thereafter. We conclude that older HIV-infected individuals are at greater risk of medically-related death before AIDS. This risk increases as CD4 count declines. Drug-related hazard may be greater in younger individuals and may increase as CD4 counts fall, but neither effect was formally significant.

Cumulative childhood risk is associated with a new measure of chronic inflammation in adulthood.

PubMed

Rasmussen, Line Jee Hartmann; Moffitt, Terrie E; Eugen-Olsen, Jesper; Belsky, Daniel W; Danese, Andrea; Harrington, HonaLee; Houts, Renate M; Poulton, Richie; Sugden, Karen; Williams, Benjamin; Caspi, Avshalom

2018-05-09

Childhood risk factors are associated with elevated inflammatory biomarkers in adulthood, but it is unknown whether these risk factors are associated with increased adult levels of the chronic inflammation marker soluble urokinase plasminogen activator receptor (suPAR). We aimed to test the hypothesis that childhood exposure to risk factors for adult disease is associated with elevated suPAR in adulthood and to compare suPAR with the oft-reported inflammatory biomarker C-reactive protein (CRP). Prospective study of a population-representative 1972-1973 birth cohort; the Dunedin Multidisciplinary Health and Development Study observed participants to age 38 years. Main childhood predictors were poor health, socioeconomic disadvantage, adverse childhood experiences (ACEs), low IQ, and poor self-control. Main adult outcomes were adulthood inflammation measured as suPAR and high-sensitivity CRP (hsCRP). Participants with available plasma samples at age 38 were included (N = 837, 50.5% male). suPAR (mean 2.40 ng/ml; SD 0.91) was positively correlated with hsCRP (r 0.15, p < .001). After controlling for sex, body mass index (BMI), and smoking, children who experienced more ACEs, lower IQ, or had poorer self-control showed elevated adult suPAR. When the five childhood risks were aggregated into a Cumulative Childhood Risk index, and controlling for sex, BMI, and smoking, Cumulative Childhood Risk was associated with higher suPAR (b 0.10; SE 0.03; p = .002). Cumulative Childhood Risk predicted elevated suPAR, after controlling for hsCRP (b 0.18; SE 0.03; p < .001). Exposure to more childhood risk factors was associated with higher suPAR levels, independent of CRP. suPAR is a useful addition to studies connecting childhood risk to adult inflammatory burden. © 2018 Association for Child and Adolescent Mental Health.

Risk Factors and Outcomes of De Novo Cancers (Excluding Nonmelanoma Skin Cancer) After Liver Transplantation for Primary Sclerosing Cholangitis.

PubMed

Mouchli, Mohamad A; Singh, Siddharth; Loftus, Edward V; Boardman, Lisa; Talwalkar, Jayant; Rosen, Charles B; Heimbach, Julie K; Wiesner, Russell H; Hasan, Bashar; Poterucha, John J; Kymberly, Watt D

2017-08-01

Patients with primary sclerosing cholangitis (PSC) may be at higher risk of malignancy after liver transplantation (LT) compared to other LT recipients. We aimed to determine the cumulative incidence of/risk factors for long-term cancer-related mortality in patients with PSC after LT. All adult patients underwent LT for PSC without cholangiocarcinoma from 1984 to 2012, with follow-up through June 2015. We estimated cumulative incidence, risk factors, and mortality from de novo malignancies after LT. Two hundred ninety-three patients were identified (mean [SD] age, 47 [12] years; 63.3% males; 2.4% smoking at LT). Over a median of 11.5 years (range, 6.4-18.6 years), 64 patients (21.8%) developed 73 nonskin cancers, including 46 solid-organ cancers (renal, 11; colorectal, 11; prostate, 7; breast, 5; pancreas, 5; ovarian/endometrial/vulvar cancers, 3; and de novo cholangiocarcinoma, 4). Twenty-two patients developed hematologic malignancies (posttransplant lymphoproliferative diseases, 18; Hodgkin disease, 2; and myelodysplastic syndrome, 2). Five patients developed melanoma. The 1-, 5-, 10-, and 20-year cumulative incidences of cancer were 2.1%, 8.6%, 18.7%, and 27%, respectively. Mortality of patients with PSC who developed cancer was higher than that of patients with PSC without cancer (hazard ratio, 2.2; P < 0.01). On multivariate analysis, recipient's age and elevated pre-LT international normalized ratio were associated with increased risk of de novo (nonskin) malignancy. The 10-year cumulative risk of cancer after LT for advanced-stage PSC was 18.7%, with posttransplant lymphoproliferative diseases, colorectal cancer, and renal cell cancer being the most common. Post-LT de novo nonskin cancer decreased overall posttransplant survival. Only recipient's age and elevated international normalized ratio at LT were associated with increased nonskin cancer risk.

Health risks of children's cumulative and aggregative exposure to metals and metalloids in a typical urban environment in China.

PubMed

Cao, Suzhen; Duan, Xiaoli; Zhao, Xiuge; Chen, Yiting; Wang, Beibei; Sun, Chengye; Zheng, Binghui; Wei, Fusheng

2016-03-01

Rapid development of industrialization and urbanization results in serious environmental contamination by metal(loid)s, which would consequently cause deleterious health effects to the exposed people through multi-pathways. Therefore, total health risk assessment for the population in urban environment is very important. Unfortunately, few studies to date investigate the cumulative health risks of metal(loid)s through aggregative pathways in Children who are often susceptible population. 12 metal(loid)s including Lead(Pb), Cadmium(Cd), Arsenic(As), Chromium(Cr), Zinc(Zn), Copper(Cu), Nickel(Ni), Manganese(Mn), Cobalt(Co), Selenium(Se), Antimony(Se) and Vanadium(V), were analyzed in PM10, drinking water, food, soil and indoor dust in this study. The cumulative and aggregative risks of these metal(loid)s among the local children were then evaluated on a field sampling and questionnaire-survey basis. The results showed that the environments were heavily polluted by metal(loid)s. For most metal(loid)s, food ingestion accounted for more than 80% of the total daily exposure dose. The non-cancer risks were up to 30 times higher than the acceptable level due to the food ingestion via Pb, Cr, Cu, Zn, As, Se, Cd and Sb, and the PM10 inhalation via Cr and Mn. While, the cancer risks were mainly attributed to Cr via food ingestion and As via food and dust ingestion, and approximately 100 times of the maximum acceptable level of 1.0 × 10(-4). The study highlights the cumulative and aggregative exposure assessment, instead of pollutant investigation to evaluate the potential health risks and emphasizes concerns to improve indoor hygienic and environmental quality and to decrease the potential harmful health effects of children living in urban area. Copyright © 2016 Elsevier Ltd. All rights reserved.

Does life-course socioeconomic position influence racial inequalities in the occurrence of uterine leiomyoma? Evidence from the Pró-Saúde Study.

PubMed

Boclin, Karine de Limas Irio; Faerstein, Eduardo; Szklo, Moyses

2014-02-01

We aimed to investigate whether life-course socioeconomic position mediates the association between skin color/race and occurrence of uterine leiomyomas. We analyzed 1,475 female civil servants with baseline data (1999-2001) of the Pró-Saúde Study in Rio de Janeiro State, Brazil. Life-course socioeconomic position was determined by parental education (early life socioeconomic position), participant education (socioeconomic position in early adulthood) and their combination (cumulative socioeconomic position). Gynecological/breast exams and health insurance status were considered markers of access to health care. Hazard ratios (HR) and 95% confidence intervals (95%CI) were estimated using Cox proportional hazards models. Compared with white women, black and parda ("brown") women had higher risk of reporting uterine leiomyomas, respectively HR: 1.6, 95%CI: 1.2-2.1; HR: 1.4, 95%CI: 0.8-2.5. Estimates were virtually identical in models including different variables related to life-course socioeconomic position. This study corroborated previous evidence of higher uterine leiomyomas risk in women with darker skin color, and further suggest that life-course socioeconomic position adversity does not influence this association.

Parent figure transitions and delinquency and drug use among early adolescent children of substance abusers.

PubMed

Keller, Thomas E; Catalano, Richard F; Haggerty, Kevin P; Fleming, Charles B

2002-01-01

Children of substance abusing parents have an elevated risk for experiencing disruptions in household composition and for engaging in problem behaviors. This study investigated whether multiple parent figure transitions predicted the likelihood of delinquency and drug use among a sample of early adolescents with parents receiving methadone treatment for opiate addiction. Controlling for baseline delinquency, child characteristics, family conflict, parental depression, and parent criminal history, a greater number of parenting disruptions during the longitudinal study period was associated with a higher probability of delinquent behavior. Gender moderated the effect of parent figure transitions in a parallel analysis for drug use. After accounting for baseline drug use and potentially confounding factors, only adolescent females had a higher likelihood of drug use as the number of family disruptions increased. In contrast, age was strongly associated with drug use for males. A subgroup of youths who experienced tremendous family instability and had no single consistent parent figure during the study period were at extreme risk for delinquent behavior. The findings are interpreted in terms of cumulative stress resulting from multiple parenting disruptions over time and differential influences on the expression of problem behaviors depending on gender.

Social environmental factors and preteen health-related behaviors.

PubMed

Adelmann, Pamela K

2005-01-01

To examine associations among risk and protective factors with negative (substance use, delinquent behavior, sedentary recreation, empty calorie consumption, suicidal behavior) and positive behaviors (prosocial recreation, productive behavior, exercise, nutrition behavior, academic achievement, seatbelt use). Data were from sixth-grade public school students (n = 133,629) in 2001. Factor analysis produced five risks, five protectors, seven negative and six positive behaviors. Associations were tested among single and cumulative risks and protectors with behaviors (linear, logit regression) and combinations of high and low risks and protectors with behaviors (analysis of variance, Chi-square). Individual and cumulative risks were related to higher and protectors were related to lower negative behaviors. Protectors were associated with higher positive behaviors, with some exceptions. Risks and their sum were associated with lower academic achievement and seatbelt use, but were linked to higher, rather than lower productive behavior. Being bullied or victimized was correlated with higher levels of exercise, good nutrition, and prosocial recreation. The high risk/low protection combination had the highest negative behaviors and low risk/high protection the lowest, but for positive behaviors, high protectors with either high or low risks showed higher positive behaviors. These findings provide new information about how (a) risks and protectors are associated with negative behaviors besides substance use and delinquency, (b) cumulative protectors, as well as risks, are related to negative and positive behaviors, and (c) combinations of high and low risks and protectors are related to behaviors. The unusual findings for positive behaviors merit further exploration.

Risks and Challenges of Surgery for Aortic Prosthetic Valve Endocarditis.

PubMed

Grubitzsch, Herko; Tarar, Waharat; Claus, Benjamin; Gabbieri, Davide; Falk, Volkmar; Christ, Torsten

2018-03-01

Prosthetic valve endocarditis is the most severe form of infective endocarditis. This study assessed the risks and challenges of surgery for aortic prosthetic valve endocarditis. In total, 116 consecutive patients (98 males, age 65.2±12.7years), who underwent redo-surgery for active aortic prosthetic valve endocarditis between 2000 and 2014, were reviewed. Cox regression analysis was used to identify factors for aortic root destructions as well as for morbidity and mortality. Median follow-up was 3.8 years (0-13.9 years). Aortic root destructions (42 limited and 29 multiple lesions) were associated with early prosthetic valve endocarditis and delayed diagnosis (≥14 d), but not with mortality. There were 16 (13.8%) early (≤30 d) and 32 (27.6%) late (>30 days) deaths. Survival at 1, 5, and 10 years was 72±4.3%, 56±5.4%, and 46±6.4%, respectively. The cumulative incidence of death, reinfection, and reoperation was 19.0% at 30days and 36.2% at 1year. Delayed diagnosis, concomitant procedures, and EuroSCORE II >20% were predictors for early mortality and need for mechanical circulatory support, age >70years, and critical preoperative state were predictors for late mortality. In their absence, survival at 10 years was 70±8.4%. Reinfections and reoperations occurred more frequently if ≥1 risk factor for endocarditis and aortic root destructions were present. At 10 years, freedom from reinfection and reoperation was 89±4.2% and 91±4.0%. The risks of death, reinfection, and reoperation are significant within the first year after surgery for aortic prosthetic valve endocarditis. Early diagnosis and aortic root destructions are the most important challenges, but advanced age, critical preoperative state, and the need for mechanical circulatory support determine long-term survival. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Maternal Adverse Childhood Experience and Infant Health: Biomedical and Psychosocial Risks as Intermediary Mechanisms.

PubMed

Madigan, Sheri; Wade, Mark; Plamondon, Andre; Maguire, Jonathon L; Jenkins, Jennifer M

2017-08-01

To assess the mechanisms accounting for the transfer of risk from one generation to the next, especially as they relate to maternal adverse childhood experiences and infant physical and emotional health outcomes. Participants were 501 community mother-infant dyads recruited shortly after the birth and followed up at 18 months. Mothers retrospectively reported on their adverse childhood experiences. The main outcome measures were parent-reported infant physical health and emotional problems. Potential mechanisms of intergenerational transmission included cumulative biomedical risk (eg, prenatal and perinatal complications) and postnatal psychosocial risk (eg, maternal depression, single parenthood, marital conflict). Four or more adverse childhood experiences were related to a 2- and 5-fold increased risk of experiencing any biomedical or psychosocial risk, respectively. There was a linear association between number of adverse childhood experiences and extent of biomedical and psychosocial risk. Path analysis revealed that the association between maternal adverse childhood experiences and infant physical health operated specifically through cumulative biomedical risk, while the relationship between adverse childhood experiences and infant emotional health operated specifically through cumulative psychosocial risk. This pattern was not explained by maternal childhood disadvantage or current neighborhood poverty. Maternal adverse childhood experiences confer vulnerability to prenatal, perinatal, and postnatal psychosocial health. The association between adverse childhood experiences and offspring physical and emotional health operates through discrete intermediary mechanisms. Copyright © 2017 Elsevier Inc. All rights reserved.

Cumulative Genetic Risk Predicts Platinum/Taxane-Induced Neurotoxicity

PubMed Central

McWhinney-Glass, Sarah; Winham, Stacey J.; Hertz, Daniel L.; Revollo, Jane Yen; Paul, Jim; He, Yijing; Brown, Robert; Motsinger-Reif, Alison A.; McLeod, Howard L.

2013-01-01

Purpose The combination of a platinum and taxane are standard of care for many cancers, but the utility is often limited due to debilitating neurotoxicity. We examined whether single nucleotide polymorphisms (SNPs) from annotated candidate genes will identify genetic risk for chemotherapy-induced neurotoxicity. Patients and Methods A candidate-gene association study was conducted to validate the relevance of 1261 SNPs within 60 candidate genes in 404 ovarian cancer patients receiving platinum/taxane chemotherapy on the SCOTROC1 trial. Statistically significant variants were then assessed for replication in a separate 404 patient replication cohort from SCOTROC1. Results Significant associations with chemotherapy-induced neurotoxicity were identified and replicated for four SNPs in SOX10, BCL2, OPRM1, and TRPV1. The Population Attributable Risk for each of the four SNPs ranged from 5–35%, with a cumulative risk of 62%. According to the multiplicative model, the odds of developing neurotoxicity increase by a factor of 1.64 for every risk genotype. Patients possessing 3 risk variants have an estimated odds ratio of 4.49 (2.36–8.54) compared to individuals with 0 risk variants. Neither the four SNPs nor the risk score were associated with progression free survival or overall survival. Conclusions This study demonstrates that SNPs in four genes have a significant cumulative association with increased risk for the development of chemotherapy-induced neurotoxicity, independent of patient survival. PMID:23963862

Drivers of age-specific survival in a long-lived seabird: contributions of observed and hidden sources of heterogeneity.

PubMed

Aubry, Lise M; Cam, Emmanuelle; Koons, David N; Monnat, Jean-Yves; Pavard, Samuel

2011-03-01

1. We assessed the relative influence of variability in recruitment age, dynamic reproductive investment (time-specific reproductive states) and frailty (unobserved differences in survival abilities across individuals) on survival in the black-legged kittiwake. Furthermore, we examined whether observed variability in survival trajectories was best explained by immediate reproductive investment, cumulative investment, or both. 2. Individuals that delayed recruitment (≥ age 7) suffered a higher mortality risk than early recruits (age 3), especially later in life, suggesting that recruitment age may be an indicator of individual quality. Although recruitment age helped explain variation in survival, time-varying reproductive investment had a more substantial influence. 3. The dichotomy of attempting to breed or not explained variability in survival across life better than other parameterizations of reproductive states such as clutch size, brood size or breeding success. In the kittiwake, the sinequanon condition to initiate reproduction is to hold a nest site, which is considered a very competitive activity. This might explain why attempting to breed is the key level of investment that affects survival, independent of the outcome (failure or success). 4. Interestingly, the more individuals cumulate reproductive attempts over life, the lower their mortality risk, indicating that breeding experience may be a good indicator of parental quality as well. In contrast, attempting to breed at time t increased the risk of mortality between t and t + 1. We thus detected an immediate trade-off between attempting to breed and survival in this population; however, the earlier individuals recruited, and the more breeding experience they accumulated, the smaller the cost. 5. Lastly, unobserved heterogeneity across individuals improved model fit more (1·3 times) than fixed and dynamic sources of observed heterogeneity in reproductive investment, demonstrating that it is critical to account for both sources of individual heterogeneity when studying survival trajectories. Only after simultaneously accounting for both sources of heterogeneity were we able to detect the 'cost' of immediate reproductive investment on survival and the 'benefit' of cumulative breeding attempts (experience), a proxy to individual quality. © 2010 The Authors. Journal of Animal Ecology © 2010 British Ecological Society.

Baseline Functioning and Stress Reactivity in Maltreating Parents and At-Risk Adults

PubMed Central

Reijman, Sophie; Bakermans-Kranenburg, Marian J.; Hiraoka, Regina; Crouch, Julie L.; Milner, Joel S.; van IJzendoorn, Marinus H.

2016-01-01

We reviewed and meta-analyzed 10 studies (N = 492) that examined the association between (risk for) child maltreatment perpetration and basal autonomic activity, and 10 studies (N = 471) that examined the association between (risk for) child maltreatment and autonomic stress reactivity. We hypothesized that maltreating parents/at-risk adults would show higher basal levels of heart rate (HR) and skin conductance (SC) and lower levels of HR variability (HRV) and would show greater HR and SC stress reactivity, but blunted HRV reactivity. A narrative review showed that evidence from significance testing within and across studies was mixed. The first set of meta-analyses revealed that (risk for) child maltreatment was associated with higher HR baseline activity (g = 0.24), a possible indication of allostatic load. The second set of meta-analyses yielded no differences in autonomic stress reactivity between maltreating/at-risk participants and nonmaltreating/low-risk comparison groups. Cumulative meta-analyses showed that positive effects for sympathetic stress reactivity as a risk factor for child maltreatment were found in a few early studies, whereas each subsequently aggregated study reduced the combined effect size to a null effect, an indication of the winner’s curse. Most studies were underpowered. Future directions for research are suggested. PMID:27462035

Long-Term Outcomes Among Adult Survivors of Childhood Central Nervous System Malignancies in the Childhood Cancer Survivor Study

PubMed Central

Liu, Qi; Yasui, Yutaka; Huang, Sujuan; Ness, Kirsten K.; Leisenring, Wendy; Hudson, Melissa M.; Donaldson, Sarah S.; King, Allison A.; Stovall, Marilyn; Krull, Kevin R.; Robison, Leslie L.; Packer, Roger J.

2009-01-01

Background Adult survivors of childhood central nervous system (CNS) malignancies are at high risk for long-term morbidity and late mortality. However, patterns of late mortality, the long-term risks of subsequent neoplasms and debilitating medical conditions, and sociodemographic outcomes have not been comprehensively characterized for individual diagnostic and treatment groups. Methods We collected information on treatment, mortality, chronic medical conditions, and neurocognitive functioning of adult 5-year survivors of CNS malignancies diagnosed between 1970 and 1986 within the Childhood Cancer Survivor Study. Using competing risk framework, we calculated cumulative mortality according to cause of death and cumulative incidence of subsequent neoplasms according to exposure and dose of cranial radiation therapy (RT). Neurocognitive impairment and socioeconomic outcomes were assessed with respect to dose of CNS radiotherapy to specific brain regions. Cumulative incidence of chronic medical conditions was compared between survivors and siblings using Cox regression models. All tests of statistical significance were two-sided. Results Among all eligible 5-year survivors (n = 2821), cumulative late mortality at 30 years was 25.8% (95% confidence interval [CI] = 23.4% to 28.3%), due primarily to recurrence and/or progression of primary disease. Patients who received cranial RT of 50 Gy or more (n = 813) had a cumulative incidence of a subsequent neoplasm within the CNS of 7.1% (95% CI = 4.5% to 9.6%) at 25 years from diagnosis compared with 1.0% (95% CI = 0% to 2.3%) for patients who had no RT. Survivors had higher risk than siblings of developing new endocrine, neurological, or sensory complications 5 or more years after diagnosis. Neurocognitive impairment was high and proportional to radiation dose for specific tumor types. There was a dose-dependent association between RT to the frontal and/or temporal lobes and lower rates of employment, and marriage. Conclusions Survivors of childhood CNS malignancies are at high risk for late mortality and for developing subsequent neoplasms and chronic medical conditions. Care providers should be informed of these risks so they can provide risk-directed care and develop screening guidelines. PMID:19535780

Heat and risk of myocardial infarction: hourly level case-crossover analysis of MINAP database

PubMed Central

Armstrong, Ben; Hajat, Shakoor; Haines, Andy; Wilkinson, Paul; Smeeth, Liam

2012-01-01

Objective To quantify the association between exposure to higher temperatures and the risk of myocardial infarction at an hourly temporal resolution. Design Case-crossover study. Setting England and Wales Myocardial Ischaemia National Audit Project (MINAP) database. Participants 24 861 hospital admissions for myocardial infarction occurring in 11 conurbations during the warmest months (June to August) of the years 2003-09. Main outcome measure Odds ratio of myocardial infarction for a 1°C increase in temperature. Results Strong evidence was found for an effect of heat acting 1-6 hours after exposure to temperatures above an estimated threshold of 20°C (95% confidence interval 16°C to 25°C). For each 1°C increase in temperature above this threshold, the risk of myocardial infarction increased by 1.9% (0.5% to 3.3%, P=0.009). Later reductions in risk seemed to offset early increases in risk: the cumulative effect of a 1°C rise in temperature above the threshold was 0.2% (−2.1% to 2.5%) by the end of the third day after exposure. Conclusions Higher ambient temperatures above a threshold of 20°C seem to be associated with a transiently increased risk of myocardial infarction 1-6 hours after exposure. Reductions in risk at longer lags are consistent with heat triggering myocardial infarctions early in highly vulnerable people who would otherwise have had a myocardial infarction some time later (“short term displacement”). Policies aimed at reducing the health effects of hot weather should include consideration of effects operating at sub-daily timescales. PMID:23243290

Effects of Cumulative Frequency, but Not of Frequency Trajectory, in Lexical Decision Times of Older Adults and Patients with Alzheimer's Disease

ERIC Educational Resources Information Center

Caza, Nicole; Moscovitch, Morris

2005-01-01

The purpose of this study was to investigate the issue of age-limited learning effects on visual lexical decision in normal and pathological aging, by using words with different frequency trajectories and cumulative frequencies. We selected words that objectively changed in frequency trajectory from an early word count (Thorndike, 1921, 1932;…

Cumulative effective dose and cancer risk for pediatric population in repetitive full spine follow-up imaging: How micro dose is the EOS microdose protocol?

PubMed

Law, Martin; Ma, Wang-Kei; Lau, Damian; Cheung, Kenneth; Ip, Janice; Yip, Lawrance; Lam, Wendy

2018-04-01

To evaluate and to obtain analytic formulation for the calculation of the effective dose and associated cancer risk using the EOS microdose protocol for scoliotic pediatric patients undergoing full spine imaging at different age of exposure; to demonstrate the microdose protocol capable of delivering lesser radiation dose and hence of further reducing cancer risk induction when compared with the EOS low dose protocol; to obtain cumulative effective dose and cancer risk for both genders scoliotic pediatrics of US and Hong Kong population using the microdose protocol. Organ absorbed doses of full spine exposed scoliotic pediatric patients have been simulated with the use of EOS microdose protocol imaging parameters input to the Monte Carlo software PCXMC. Gender and age specific effective dose has been calculated with the simulated organ absorbed dose using the ICRP-103 approach. The associated radiation induced cancer risk, expressed as lifetime attributable risk (LAR), has been estimated according to the method introduced in the Biological Effects of Ionizing Radiation VII report. Values of LAR have been estimated for scoliotic patients exposed repetitively during their follow up period at different age for US and Hong Kong population. The effective doses of full spine imaging with simultaneous posteroanterior and lateral projection for patients exposed at the age between 5 and 18 years using the EOS microdose protocol have been calculated within the range of 2.54-14.75 μSv. The corresponding LAR for US and Hong Kong population was ranged between 0.04 × 10 -6 and 0.84 × 10 -6 . Cumulative effective dose and cancer risk during follow-up period can be estimated using the results and are of information to patients and their parents. With the use of computer simulation and analytic formulation, we obtained the cumulative effective dose and cancer risk at any age of exposure for pediatric patients of US and Hong Kong population undergoing repetitive microdose protocol full spine imaging. Girls would be at a statistically significant higher cumulative cancer risk than boys undergoing the same microdose full spine imaging protocol and the same follow-up schedule. Copyright © 2018 Elsevier B.V. All rights reserved.

76 FR 69726 - Pyrethrins/Pyrethroid Cumulative Risk Assessment; Notice of Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-09

... to consider available information concerning the cumulative effects on human health resulting from... stakeholders including environmental, human health, farm worker, and agricultural advocates; the chemical... factors, may have atypical or disproportionately high and adverse human health impacts or environmental...

Unprotected sex among African-American adolescents: a three-year study.

PubMed Central

Li, Xiaoming; Stanton, Bonita; Feigelman, Susan; Galbraith, Jennifer

2002-01-01

This study examined the cumulative change of unprotected sex over a period of three years among 383 African American youth ages 9 to 15 at baseline who participated in a trial of a Human Immunodeficiency Virus (HIV) risk reduction intervention. Cumulative scores of sexual intercourse and failure to use condoms were compared between intervention and control groups. The results indicate that cumulatively over the three-year period, intervention youth reported significantly lower rates of failure to use a condom. The findings indicate that face-to-face interventions may offer significant cumulative protection from unprotected sex over the long-term. PMID:12392042

Tumor grade and matrix metalloproteinase 2 expression in stromal fibroblasts help to stratify the high-risk group of patients with early breast cancer identified on the basis of st Gallen recommendations.

PubMed

Niemiec, Joanna; Adamczyk, Agnieszka; Małecki, Krzysztof; Ambicka, Aleksandra; Ryś, Janusz

2013-04-01

It is still being discussed if the assessment of basal markers or if adhesion molecules expression contributes additional prognostic information to the classic prognostic factors and hence should be included into standard morphologic reports. The aim of the study was to assess the prognostic significance of: (i) classification recommended by St Gallen experts (ii) tumor grade, expression of (iii) basal markers, (iv) adhesion molecules, and (v) matrix metalloproteinase 2 (MMP-2) in patients with T1-T2 N0M0 chemotherapy-naive ductal breast cancer. In 79 patients with tumors characterized by estrogen receptor (ER) and progesterone receptor (PgR) positive, human epidermal growth factor receptor 2 negative (HER2) phenotype and MIB-1 labeling index (MIB-l) LI ≤ 15% (low-risk group) cumulative 17-year breast cancer-specific survival probability was 100% and was significantly higher than in 95 patients from the high-risk group (ER(-)/PgR(-)/HER2(-) or HER2(+) or MIB-1 LI > 15%) (72.5%). We found that MMP-2 fibroblast expression indicated 2 subgroups with significantly different survival rates in women with grade 3 tumor (88.9% for MMP-2 positivity and 56.0% for negativity). Cox multivariate analysis revealed that both grade 3 combined with stromal fibroblast MMP-2(-) and a high-risk group according to St Gallen recommendations are independent negative prognostic factors that influence survival of patients with breast cancer. To the best of our knowledge, we have shown for the first time that MMP-2(-) in stromal fibroblasts might indicate poor survivors in the group of patients with grade 3 tumors and that the cumulative effect of both above-mentioned parameters might be helpful in selecting the high-risk individuals from the group of patients with luminal B subtype/HER2(+)/triple negative phenotype identified according to St Gallen recommendations. Copyright © 2013 Elsevier Inc. All rights reserved.

Cumulative Impact of HIV and Multiple Concurrent Human Papillomavirus Infections on the Risk of Cervical Dysplasia

PubMed Central

Adler, David H.; Wallace, Melissa; Bennie, Thola; Abar, Beau; Meiring, Tracy L.; Williamson, Anna-Lise; Bekker, Linda-Gail

2016-01-01

Infection with HIV is known to increase the risk of cervical cancer. In addition, evidence suggests that concurrent infection with multiple human papillomavirus (HPV) genotypes increases the risk of cervical dysplasia more than infection with a single HPV genotype. However, the impact of the combination of HIV coinfection and presence of multiple concurrent HPV infections on the risk of cervical dysplasia is uncertain. We compared the results of HPV testing and Pap smears between HIV-infected and HIV-uninfected young women to assess the cumulative impact of these two conditions. We found that both HIV and the presence of multiple concurrent HPV infections are associated with increased risk of associated Pap smear abnormality and that the impact of these two risk factors may be additive. PMID:26997954

Use of the Maximum Cumulative Ratio As an Approach for Prioritizing Aquatic Coexposure to Plant Protection Products: A Case Study of a Large Surface Water Monitoring Database.

PubMed

Vallotton, Nathalie; Price, Paul S

2016-05-17

This paper uses the maximum cumulative ratio (MCR) as part of a tiered approach to evaluate and prioritize the risk of acute ecological effects from combined exposures to the plant protection products (PPPs) measured in 3 099 surface water samples taken from across the United States. Assessments of the reported mixtures performed on a substance-by-substance approach and using a Tier One cumulative assessment based on the lowest acute ecotoxicity benchmark gave the same findings for 92.3% of the mixtures. These mixtures either did not indicate a potential risk for acute effects or included one or more individual PPPs that had concentrations in excess of their benchmarks. A Tier Two assessment using a trophic level approach was applied to evaluate the remaining 7.7% of the mixtures. This assessment reduced the number of mixtures of concern by eliminating the combination of endpoint from multiple trophic levels, identified invertebrates and nonvascular plants as the most susceptible nontarget organisms, and indicated that a only a very limited number of PPPs drove the potential concerns. The combination of the measures of cumulative risk and the MCR enabled the identification of a small subset of mixtures where a potential risk would be missed in substance-by-substance assessments.

Prognostic value of clinical variables and liver histology for development of fibrosis and cirrhosis in autoimmune hepatitis.

PubMed

Puustinen, Lauri; Boyd, Sonja; Mustonen, Harri; Arkkila, Perttu; Arola, Johanna; Färkkilä, Martti

2017-03-01

In autoimmune hepatitis, data on the prognostic value of baseline liver biopsy and the sequential histology is controversial. Our aim was to evaluate the prognostic value of clinical variables and biopsy at the time of diagnosis and during the disease course. All 98 patients in our hospital during 1995-2012 were included. Sequential biopsies were available in 66 patients. Analyses based on clinical and histological variables were performed to find parameters predicting the progression of fibrosis, and development of cirrhosis. At the time of diagnosis, 7% were cirrhotic. Fibrosis progressed in 28 (42%) patients, remained stable in 26 (39%) and resolved in 12 (18%) patients. Findings which predicted fibrosis progression, were baseline total inflammation (odds ratio 1.7, 95% CI 1.01-2.8), cumulative total inflammation (1.8, 95% CI 1.01-3.2, rosette formation (2.8, 95% CI 1.1-7.1), absence of pericholangitis (0.4, 95% CI 0.1-1.0) and necrosis (1.4, 95% CI 1.0-2.0). Risk factors for the development of cirrhosis were cholestasis (4.6, 95% CI 1.2-16.9), interphase inflammation (3.4, 95% CI 1.1-10.4), and necrosis (3.3, 95% CI 1.2-9.7). In a cumulative model, cumulative total inflammation (4.5, 95% CI 1.4-15.0), necrosis (6.7, 95% CI 1.3-34.6), or cumulative immunoglobulin G load (61.8, 95% CI 2.0-1954.3) were risk factors. None of the patients with histological pericholangitis or granulomas developed cirrhosis. The histology provides prognostic information regarding progression of fibrosis or the development of cirrhosis. The total cumulative inflammatory activity predicts the progression of fibrosis, whereas baseline fibrosis, interphase inflammation, cholestasis, necrosis, as well as the cumulative total inflammation and cumulative immunoglobulin G, are risk factors for cirrhosis.

Predicting the cumulative risk of death during hospitalization by modeling weekend, weekday and diurnal mortality risks.

PubMed

Coiera, Enrico; Wang, Ying; Magrabi, Farah; Concha, Oscar Perez; Gallego, Blanca; Runciman, William

2014-05-21

Current prognostic models factor in patient and disease specific variables but do not consider cumulative risks of hospitalization over time. We developed risk models of the likelihood of death associated with cumulative exposure to hospitalization, based on time-varying risks of hospitalization over any given day, as well as day of the week. Model performance was evaluated alone, and in combination with simple disease-specific models. Patients admitted between 2000 and 2006 from 501 public and private hospitals in NSW, Australia were used for training and 2007 data for evaluation. The impact of hospital care delivered over different days of the week and or times of the day was modeled by separating hospitalization risk into 21 separate time periods (morning, day, night across the days of the week). Three models were developed to predict death up to 7-days post-discharge: 1/a simple background risk model using age, gender; 2/a time-varying risk model for exposure to hospitalization (admission time, days in hospital); 3/disease specific models (Charlson co-morbidity index, DRG). Combining these three generated a full model. Models were evaluated by accuracy, AUC, Akaike and Bayesian information criteria. There was a clear diurnal rhythm to hospital mortality in the data set, peaking in the evening, as well as the well-known 'weekend-effect' where mortality peaks with weekend admissions. Individual models had modest performance on the test data set (AUC 0.71, 0.79 and 0.79 respectively). The combined model which included time-varying risk however yielded an average AUC of 0.92. This model performed best for stays up to 7-days (93% of admissions), peaking at days 3 to 5 (AUC 0.94). Risks of hospitalization vary not just with the day of the week but also time of the day, and can be used to make predictions about the cumulative risk of death associated with an individual's hospitalization. Combining disease specific models with such time varying- estimates appears to result in robust predictive performance. Such risk exposure models should find utility both in enhancing standard prognostic models as well as estimating the risk of continuation of hospitalization.

Subsite-specific colorectal cancer risk in the colorectal endoscopy era.

PubMed

Stock, Christian; Pulte, Dianne; Haug, Ulrike; Brenner, Hermann

2012-03-01

Colorectal endoscopy (sigmoidoscopy and colonoscopy) is thought to reduce colorectal cancer (CRC) risk. Since the 1980s, its use has increased in the United States, which may be a reason for decreasing CRC incidence rates. To investigate the plausibility of a contribution of colorectal endoscopy use to the decrease in CRC risk. Descriptive analysis of temporal trends. U.S. population from 1978 to 2007. Using incidence data from the Surveillance, Epidemiology and End Results Program, we assessed the subsite-specific cumulative risk of CRC developing until age 79 years. The cumulative risk of proximal CRC remained relatively stable over the observation period, varying between 2.09% (95% CI, 2.06%-2.11%) and 2.66% (95% CI,2.62%-2.69%) for men and between 1.90% (95% CI, 1.88%-1.93%) and 2.24% (95% CI, 2.21%-2.27%) for women. By contrast, the cumulative risk of distal CRC decreased from 4.68% (95% CI, 4.64%-4.73%) to 3.03% (95% CI, 3.00%-3.06%) for men and from 3.15% (95% CI, 3.11%-3.18%) to 1.93% (95% CI, 1.91%-1.95%) for women, which was largely attributable to the reduced cumulative risk of cancer in the sigmoid colon. The observed pattern was restricted to the population aged 50 to 79 years, whereas the magnitude of the decrease was greater for older age groups and similar across stages. The study is based on aggregated registry data only; therefore, no inferences about causal effects can be drawn. The results show a major reduction of CRC risk, particularly in the sigmoid colon. Increased use of colorectal endoscopy in the population aged 50 years and older along with environmental factors may have contributed to the decreasing risk. Copyright © 2012 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Synergistic effects of family history of hepatocellular carcinoma and hepatitis B virus infection on risk for incident hepatocellular carcinoma.

PubMed

Loomba, Rohit; Liu, Jessica; Yang, Hwai-I; Lee, Mei-Hsuan; Lu, Sheng-Nan; Wang, Li-Yu; Iloeje, Uchenna H; You, San-Lin; Brenner, David; Chen, Chien-Jen

2013-12-01

Little is known about the effects of family history of hepatocellular carcinoma (HCC) on hepatitis B progression or risk of HCC. We examined how family HCC history and presence or stage of hepatitis B virus (HBV) infection affect risk for HCC. We performed a population-based cohort study of 22,472 participants from 7 townships in Taiwan who underwent evaluation for liver disease from 1991 through 1992. Those who received a first diagnosis of HCC from January 1, 1991, to December 31, 2008, were identified from the Taiwanese cancer registry. There were 374 cases of incident HCC over 362,268 person-years of follow-up evaluation. The cumulative risk of HCC in hepatitis B surface antigen (HBsAg)-seronegative patients without a family history of HCC was 0.62%, in those with a family history of HCC the cumulative risk was 0.65%, in HBsAg-seropositive patients without a family history of HCC the cumulative risk was 7.5%, and in HBsAg-seropositive patients with a family history of HCC the cumulative risk was 15.8% (P < .001). The multivariate-adjusted hazard ratio for HBsAg-seropositive individuals with family history, compared with HBsAg-seronegative individuals without a family history of HCC, was 32.33 (95% confidence interval, 20.8-50.3; P < .001). The relative excess risk owing to interaction was 19, the attributable proportion was 0.59, and the synergy index value was 2.54. These findings indicate synergy between family HCC history and HBsAg serostatus. The synergy between these factors remained significant in stratification analyses by HBeAg serostatus and serum level of HBV DNA. Family history of HCC multiplies the risk of HCC at each stage of HBV infection. Patients with a family history of HCC require more intensive management of HBV infection and surveillance for liver cancer. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Perinatal Problems and Psychiatric Comorbidity Among Children with ADHD

PubMed Central

Owens, Elizabeth B.; Hinshaw, Stephen P.

2013-01-01

Objective Among two large, independent samples of girls with attention-deficit/hyperactivity disorder (ADHD), we examined associations between specific (maternal gestational smoking and drug use, early labor, low birth weight, and infant breathing problems at birth) and cumulative prenatal and perinatal risk factors and psychiatric comorbidity during childhood. Method Data from the (a) Multimodal Treatment Study of Children with ADHD, a randomized clinical trial with 579 children aged 7 to 9.9 years with combined-type ADHD, and the (b) Berkeley Girls ADHD Longitudinal Sample, a naturalistic study of 140 girls with ADHD (93 combined-type and 47 inattentive-type) who were first seen when they were 6 to 12 years old, were analyzed separately. In each sample, perinatal risk factors were assessed retrospectively by maternal report, and current childhood psychiatric comorbidity was assessed using maternal report on the Diagnostic Interview Schedule for Children. Results Consistent findings across these two studies show that infant breathing problems, early labor, and total perinatal problems predicted childhood comorbid depression but not comorbid anxiety or externalizing disorders. These associations remained significant, in both samples, with control of family SES and maternal symptoms of ADHD and depression. Results attenuated slightly with control of the number of child comorbidities plus SES and maternal symptoms. Conclusion Accumulating evidence suggests that perinatal risk factors are important precursors of childhood psychiatric comorbidity and that the association between these risk factors and detrimental psychiatric outcomes cannot be explained by maternal psychiatric symptoms or SES during childhood. PMID:23581554

Ionizing diagnostic radiation exposure in patients with Crohn's disease: A retrospective study in a medium hospital and its predictive factors.

PubMed

Merino Rodríguez, Esther; Carrera Alonso, Elisa; Torralba González de Suso, Miguel; Sánchez da Silva, Marta; Martínez López, María; Sánchez-Tembleque Zarandona, María Dolores

2018-02-01

It is estimated that diagnostic medical radiation exposure may be responsable for 0.5-2% of cancers worldwide. Because of the relapsing course of Crohn's disease (CD), these patients usually requiere multiple ionizing radiation test. Stimating the total cumulative effective dose received by our CD patients and identifying the risk factors associated with the exposure to a cumulative effective dose due to the disease (CEED) > 50mSv. Retrospective cohort study (2001-2014). patients with CD. Risk dose >50mSv. For calculating de cumulative effective dose and the CEED, all the ionizing test done were taken. For identifying predictive factors for receiving a CEDD >50mSv, an univariate and a multivariate logistic regression analyses were performed using a >50mSv dose as dependent variable. Of the 267 patients analyzed the 24.6% of them received a cumulative effective dose > 50mSv and the 15.2% a CEED>50mSv. In the multivariate analysis, the following variables were identified as independent predictors associated with a CEDD >50mSv: major surgery (OR= 2.1; IC 95% [1.1-3.8]; p=.019) and severity (OR= 20.6; IC 95% [4.5-94.8]; p<.01). Patients with CD are more at risk of receiving risk CEED, so it would be advisable to monitor the cumulative effective dose received to anticipate our intervention in order to avoid reaching that dose. The ultrasounds and abdominal resonance enterography are alternatives in these cases, although their accessibility is limited in some centers. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

The Association Between the Use of Zolpidem and the Risk of Alzheimer's Disease Among Older People.

PubMed

Cheng, Hui-Ting; Lin, Fang-Ju; Erickson, Steven R; Hong, Jin-Liern; Wu, Chung-Hsuen

2017-11-01

To evaluate the association between zolpidem use and the risk of Alzheimer's disease among older people. A retrospective cohort study using data from 2001 to 2011 from the National Health Insurance Research Database. Taiwan. A total of 6,922 patients aged 65 years or older enrolled from January 2002 to December 2004 (the enrollment period). Zolpidem users were identified as patients who used zolpidem during the enrollment period. The index date was the date of the first zolpidem prescription. Dosage of zolpidem use was defined using cumulative defined daily dose (cDDD) based on the cumulative dosage that patients took within one year after the index date (grouped as: less than 28, 28-90, 91-180, and more than 180 cDDD). The occurrence of Alzheimer's disease was defined as the time period from the end of one year after the index date to the date of the Alzheimer's disease diagnosis. The propensity score was used to adjust the measured confounders of Alzheimer's disease. Cox proportional hazards models were used to evaluate the association between zolpidem use and the incidence of Alzheimer's disease. Zolpidem users with a high cumulative dose (>180 cDDD) in the first year after initiation had a significantly greater risk of Alzheimer's disease than non-zolpidem users (HR = 2.97, 95% CI = 1.61-5.49) and low cumulative dose (<28 cDDD) users (HR = 4.18, 95% CI = 1.77-9.86). We found the use of a high cumulative dose of zolpidem was associated with an increased risk of Alzheimer's disease among older people living in Taiwan. It is advised to use caution when considering long-term use of zolpidem in older patients. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

Factors associated with reduced early survival in the Oxford phase III medial unicompartment knee replacement.

PubMed

Kuipers, Bart M; Kollen, Boudewijn J; Bots, Peter C Kaijser; Burger, Bart J; van Raay, Jos J A M; Tulp, Niek J A; Verheyen, Cees C P M

2010-01-01

The aim of this study was to determine the prognostic value of preoperative patellofemoral osteoarthritis, BMI and age for implant survival of unicompartmental knee arthroplasty (UKA) performed in patients meeting strict admission criteria. The data and radiographs of 437 unilateral Oxford phase III procedures (Biomet, Bridgend, UK) were analysed. All procedures were carried out or supervised by 13 specialised knee surgeons in three different hospitals. The study group comprised 437 patients with a median follow of 2.6 years (0.1-7.9). The cumulative standard case survival rate at 5 years, when there were still 101 patients at risk, was 84.7% (CI-95%: 80.1-89.3%). Young age (<60 years) was associated with a 2.2-fold increased adjusted risk of revision (CI: 1.08-4.43; p=0.03). The preoperative presence of radiological features of patellofemoral osteoarthritis was associated with a 0.3-fold reduced adjusted risk of revision (CI: 0.11-0.89; p=0.03). BMI>30 kg/m(2), gender, the surgeon performing the operation (either as an individual or categorised by annual surgical UKA caseload, i.e., more or less than 10 UKAs) and the hospital in which surgery took place did not predict implant survival of UKA. We conclude that young patients (<60 years) experience an increased early risk of revision for UKA when compared to older patients (>60 years). Obesity (BMI>30 kg/m(2)) and preoperative patellofemoral osteoarthritis are not associated with a decreased implant survival and therefore should not be considered risk factors in this context.

Ionizing radiation exposure as a result of diagnostic imaging in patients with lymphoma.

PubMed

Crowley, M P; O'Neill, S B; Kevane, B; O'Neill, D C; Eustace, J A; Cahill, M R; Bird, B; Maher, M M; O'Regan, K; O'Shea, D

2016-05-01

Survival rates among patients with lymphoma continue to improve. Strategies aimed at reducing potential treatment-related toxicity are increasingly prioritized. While radiological procedures play an important role, ionizing radiation exposure has been linked to an increased risk of malignancy, particularly among individuals whose cumulative radiation exposure exceeds a specific threshold (75 millisieverts). Within this retrospective study, the cumulative radiation exposure dose was quantified for 486 consecutive patients with lymphoma. The median estimated total cumulative effective dose (CED) of ionizing radiation per subject was 69 mSv (42-118). However, younger patients (under 40 years) had a median CED of 89 mSv (55-124). This study highlights the considerable radiation exposure occurring among patients with lymphoma as a result of diagnostic imaging. To limit the risk of secondary carcinogenesis, consideration should be given to monitoring cumulative radiation exposure in individual patients as well as considering imaging modalities, which do not impart an ionizing radiation dose.

Exposure-response relationship and risk assessment for cognitive deficits in early welding-induced manganism.

PubMed

Park, Robert M; Bowler, Rosemarie M; Roels, Harry A

2009-10-01

The exposure-response relationship for manganese (Mn)-induced adverse nervous system effects is not well described. Symptoms and neuropsychological deficits associated with early manganism were previously reported for welders constructing bridge piers during 2003 to 2004. A reanalysis using improved exposure, work history information, and diverse exposure metrics is presented here. Ten neuropsychological performance measures were examined, including working memory index (WMI), verbal intelligence quotient, design fluency, Stroop color word test, Rey-Osterrieth Complex Figure, and Auditory Consonant Trigram tests. Mn blood levels and air sampling data in the form of both personal and area samples were available. The exposure metrics used were cumulative exposure to Mn, body burden assuming simple first-order kinetics for Mn elimination, and cumulative burden (effective dose). Benchmark doses were calculated. Burden with a half-life of about 150 days was the best predictor of blood Mn. WMI performance declined by 3.6 (normal = 100, SD = 15) for each 1.0 mg/m3 x mo exposure (P = 0.02, one tailed). At the group mean exposure metric (burden; half-life = 275 days), WMI performance was at the lowest 17th percentile of normal, and at the maximum observed metric, performance was at the lowest 2.5 percentiles. Four other outcomes also exhibited statistically significant associations (verbal intelligence quotient, verbal comprehension index, design fluency, Stroop color word test); no dose-rate effect was observed for three of the five outcomes. A risk assessment performed for the five stronger effects, choosing various percentiles of normal performance to represent impairment, identified benchmark doses for a 2-year exposure leading to 5% excess impairment prevalence in the range of 0.03 to 0.15 mg/m3, or 30 to 150 microg/m3, total Mn in air, levels that are far below those permitted by current occupational standards. More than one-third of workers would be impaired after working 2 years at 0.2 mg/m3 Mn (the current threshold limit value).

Associations between fluorosis of permanent incisors and fluoride intake from infant formula, other dietary sources and dentifrice during early childhood

PubMed Central

Levy, Steven M.; Broffitt, Barbara; Marshall, Teresa A.; Eichenberger-Gilmore, Julie M.; Warren, John J.

2017-01-01

Objectives The authors describe associations between dental fluorosis and fluoride intakes, with an emphasis on intake from fluoride in infant formula. Methods The authors administered periodic questionnaires to parents to assess early fluoride intake sources from beverages, selected foods, dentifrice and supplements. They assessed relationships between fluorosis of the permanent maxillary incisors and fluoride intake from beverages and other sources, both for individual time points and cumulatively using area-under-the-curve (AUC) estimates. The authors determined effects associated with fluoride in reconstituted powdered infant formulas, along with risks associated with intake of fluoride from dentifrice and other sources. Results Considering only fluoride intake from age 3 to 9 months, the authors found that participants with fluorosis (97 percent of which was mild) had significantly greater cumulative fluoride intake (AUC) from reconstituted powdered infant formula, other beverages with added water or a combination of these than did those without fluorosis. For participants aged 16 to 36 months, participants with fluorosis had significantly higher fluoride intake from water by itself, dentifrice or a combination of these than did those without fluorosis. In a model combining both the 3- to 9-month and 16- to 36-months age groups, the significant variables were fluoride intake from reconstituted powder concentrate formula (by participants aged 3–9 months), other beverages with added water (also by participants aged 3–9 months) and dentifrice (by participants aged 16–36 months). Conclusions Greater fluoride intakes from reconstituted powdered formulas (when participants were aged 3–9 months) and other water-added beverages (when participants were aged 3–9 months) increased fluorosis risk as did higher dentifrice intake by participants when aged 16 to 36 months. Clinical Implications Results suggest that prevalence of mild dental fluorosis could be reduced by avoiding ingestion of large quantities of fluoride from reconstituted powdered concentrate infant formula and fluoridated dentifrice. PMID:20884921

Kaplan-Meier survival analysis overestimates cumulative incidence of health-related events in competing risk settings: a meta-analysis.

PubMed

Lacny, Sarah; Wilson, Todd; Clement, Fiona; Roberts, Derek J; Faris, Peter; Ghali, William A; Marshall, Deborah A

2018-01-01

Kaplan-Meier survival analysis overestimates cumulative incidence in competing risks (CRs) settings. The extent of overestimation (or its clinical significance) has been questioned, and CRs methods are infrequently used. This meta-analysis compares the Kaplan-Meier method to the cumulative incidence function (CIF), a CRs method. We searched MEDLINE, EMBASE, BIOSIS Previews, Web of Science (1992-2016), and article bibliographies for studies estimating cumulative incidence using the Kaplan-Meier method and CIF. For studies with sufficient data, we calculated pooled risk ratios (RRs) comparing Kaplan-Meier and CIF estimates using DerSimonian and Laird random effects models. We performed stratified meta-analyses by clinical area, rate of CRs (CRs/events of interest), and follow-up time. Of 2,192 identified abstracts, we included 77 studies in the systematic review and meta-analyzed 55. The pooled RR demonstrated the Kaplan-Meier estimate was 1.41 [95% confidence interval (CI): 1.36, 1.47] times higher than the CIF. Overestimation was highest among studies with high rates of CRs [RR = 2.36 (95% CI: 1.79, 3.12)], studies related to hepatology [RR = 2.60 (95% CI: 2.12, 3.19)], and obstetrics and gynecology [RR = 1.84 (95% CI: 1.52, 2.23)]. The Kaplan-Meier method overestimated the cumulative incidence across 10 clinical areas. Using CRs methods will ensure accurate results inform clinical and policy decisions. Copyright © 2017 Elsevier Inc. All rights reserved.

An Overview of Literature Topics Related to Current Concepts, Methods, Tools, and Applications for Cumulative Risk Assessment (2007-2016).

PubMed

Fox, Mary A; Brewer, L Elizabeth; Martin, Lawrence

2017-04-07

Cumulative risk assessments (CRAs) address combined risks from exposures to multiple chemical and nonchemical stressors and may focus on vulnerable communities or populations. Significant contributions have been made to the development of concepts, methods, and applications for CRA over the past decade. Work in both human health and ecological cumulative risk has advanced in two different contexts. The first context is the effects of chemical mixtures that share common modes of action, or that cause common adverse outcomes. In this context two primary models are used for predicting mixture effects, dose addition or response addition. The second context is evaluating the combined effects of chemical and nonchemical (e.g., radiation, biological, nutritional, economic, psychological, habitat alteration, land-use change, global climate change, and natural disasters) stressors. CRA can be adapted to address risk in many contexts, and this adaptability is reflected in the range in disciplinary perspectives in the published literature. This article presents the results of a literature search and discusses a range of selected work with the intention to give a broad overview of relevant topics and provide a starting point for researchers interested in CRA applications.

An Overview of Literature Topics Related to Current Concepts, Methods, Tools, and Applications for Cumulative Risk Assessment (2007–2016)

PubMed Central

Fox, Mary A.; Brewer, L. Elizabeth; Martin, Lawrence

2017-01-01

Cumulative risk assessments (CRAs) address combined risks from exposures to multiple chemical and nonchemical stressors and may focus on vulnerable communities or populations. Significant contributions have been made to the development of concepts, methods, and applications for CRA over the past decade. Work in both human health and ecological cumulative risk has advanced in two different contexts. The first context is the effects of chemical mixtures that share common modes of action, or that cause common adverse outcomes. In this context two primary models are used for predicting mixture effects, dose addition or response addition. The second context is evaluating the combined effects of chemical and nonchemical (e.g., radiation, biological, nutritional, economic, psychological, habitat alteration, land-use change, global climate change, and natural disasters) stressors. CRA can be adapted to address risk in many contexts, and this adaptability is reflected in the range in disciplinary perspectives in the published literature. This article presents the results of a literature search and discusses a range of selected work with the intention to give a broad overview of relevant topics and provide a starting point for researchers interested in CRA applications. PMID:28387705

Personal Control and Service Connection as Paths to Improved Mental Health and Exiting Homelessness among Severely Marginalized Homeless Youth.

PubMed

Slesnick, Natasha; Zhang, Jing; Brakenhoff, Brittany

2017-02-01

Non-service connected, continuously homeless youth are arguably one of the most vulnerable populations in the U.S. These youth reside at society's margins experiencing an accumulation of risks over time. Research concludes that as vulnerabilities increase so do poor long-term outcomes. This study tested the mediating effects of service connection and personal control as mediators of cumulative risk and housing, health and mental health outcomes. By understanding the processes associated with therapeutic change among those with the most vulnerabilities, service providers and researchers can target those factors to enhance positive outcomes. Seventy-nine, non-service connected, substance using homeless youth were offered a strengths-based outreach and engagement intervention and were assessed at baseline 3, 6 and 9 months post-baseline. Personal control mediated the effects of cumulative risk on housing stability, and service utilization mediated the effects of cumulative risk on mental health. This study specifies important targets of intervention for a population at high risk for continuing homelessness. In particular, service providers should target youths' sense of personal control and link them to needed community-based services in order to help them exit street life and improve mental health outcomes.

The 3-Year Incidence of Gout in Elderly Patients with CKD.

PubMed

Tan, Vivian S; Garg, Amit X; McArthur, Eric; Lam, Ngan N; Sood, Manish M; Naylor, Kyla L

2017-04-03

The risk of gout across CKD stages is not well described. We performed a retrospective cohort study using linked health care databases from Ontario, Canada from 2002 to 2010. The primary outcome was the 3-year cumulative incidence of gout, on the basis of diagnostic codes. We presented our results by level of kidney function (eGFR≥90 ml/min per 1.73 m 2 , 60-89, 45-59, 30-44, 15-29, and chronic dialysis) and by sex. Additional analyses examined the risk of gout adjusting for clinical characteristics, incidence of gout defined by the receipt of allopurinol or colchicine, and gout risk in a subpopulation stratified by the level of eGFR and albuminuria. Of the 282,925 adults aged ≥66 years, the mean age was 75 years and 57.9% were women. The 3-year cumulative incidence of gout was higher in older adults with a lower level of eGFR. In women, the 3-year cumulative incidence of gout was 0.6%, 0.7%, 1.3%, 2.2%, and 3.4%, and in men the values were 0.8%, 1.2%, 2.5%, 3.7%, and 4.6%, respectively. However, patients on chronic dialysis had a lower 3-year cumulative incidence of gout (women 2.0%, men 2.9%) than those with more moderate reductions in kidney function ( i.e. , eGFR 15-44 ml/min per 1.73 m 2 ). The association between a greater loss of kidney function and a higher risk of diagnosed gout was also evident after adjustment for clinical characteristics and in all additional analyses. Patients with a lower level of eGFR had a higher 3-year cumulative incidence of gout, with the exception of patients receiving dialysis. Results can be used for risk stratification. Copyright © 2017 by the American Society of Nephrology.

Cumulative incidence and risk factors of prediabetes and type 2 diabetes in a Singaporean Malay cohort.

PubMed

Man, Ryan E K; Charumathi, Sabanayagam; Gan, Alfred Tau Liang; Fenwick, Eva K; Tey, Ching Siong; Chua, Jacqueline; Wong, Tien-Yin; Cheng, Ching-Yu; Lamoureux, Ecosse L

2017-05-01

The aim of this work was to determine the cumulative incidence and independent risk factors of prediabetes and type 2 diabetes (T2DM) in a well-characterized cohort of Malays in Singapore. We included 1137 participants (mean age [SD]: 55 (10) years; 53.6% female) without diabetes (DM) at baseline from the Singapore Malay Eye Study, a population-based longitudinal study with baseline (2004-2006), and follow-up (2010-2013) examinations. Prediabetes was defined as an HbA1c between 5.7% and 6.4%, with no self-reported DM history or insulin/DM medication use. T2DM was defined as a random glucose level ≥200mg/dL or HbA1c>6.4% or use of insulin/DM medication. Age-standardized cumulative incidence was calculated as the crude 6-year cumulative incidence standardized to Singapore's Malay population census. Multivariable modified poisson regression models were utilized to determine the risk factors of incident prediabetes and T2DM. The age-standardized 6-year cumulative incidence was 11.2% (95% CI 9.5, 13.1%) for T2DM, and 20.4% (95% CI 16.4, 25.2%) for prediabetes. Hypertension, higher body mass index (BMI) and higher Hba1c levels were associated with increased risk of T2DM, while older age and higher high density lipoprotein (HDL) cholesterol were protective (all P<0.05). Only higher BMI and HbA1c levels were independently associated with incident prediabetes (all P≤0.001). While only one in ten adult Malays developed T2DM over 6-years, one in five developed prediabetes over the same time period. Our results suggest that evidence-based interventions addressing modifiable risk factors (obesity, prediabetes, hypertension, low HDL cholesterol) are needed to delay or prevent their onset. Copyright © 2017 Elsevier B.V. All rights reserved.

The 3-Year Incidence of Gout in Elderly Patients with CKD

PubMed Central

Tan, Vivian S.; Garg, Amit X.; McArthur, Eric; Lam, Ngan N.; Sood, Manish M.

2017-01-01

Background and objectives The risk of gout across CKD stages is not well described. Design, setting, participants, & measurements We performed a retrospective cohort study using linked health care databases from Ontario, Canada from 2002 to 2010. The primary outcome was the 3-year cumulative incidence of gout, on the basis of diagnostic codes. We presented our results by level of kidney function (eGFR≥90 ml/min per 1.73 m2, 60–89, 45–59, 30–44, 15–29, and chronic dialysis) and by sex. Additional analyses examined the risk of gout adjusting for clinical characteristics, incidence of gout defined by the receipt of allopurinol or colchicine, and gout risk in a subpopulation stratified by the level of eGFR and albuminuria. Results Of the 282,925 adults aged ≥66 years, the mean age was 75 years and 57.9% were women. The 3-year cumulative incidence of gout was higher in older adults with a lower level of eGFR. In women, the 3-year cumulative incidence of gout was 0.6%, 0.7%, 1.3%, 2.2%, and 3.4%, and in men the values were 0.8%, 1.2%, 2.5%, 3.7%, and 4.6%, respectively. However, patients on chronic dialysis had a lower 3-year cumulative incidence of gout (women 2.0%, men 2.9%) than those with more moderate reductions in kidney function (i.e., eGFR 15–44 ml/min per 1.73 m2). The association between a greater loss of kidney function and a higher risk of diagnosed gout was also evident after adjustment for clinical characteristics and in all additional analyses. Conclusions Patients with a lower level of eGFR had a higher 3-year cumulative incidence of gout, with the exception of patients receiving dialysis. Results can be used for risk stratification. PMID:28153936

The impact of cumulative pain/stress on neurobehavioral development of preterm infants in the NICU.

PubMed

Cong, Xiaomei; Wu, Jing; Vittner, Dorothy; Xu, Wanli; Hussain, Naveed; Galvin, Shari; Fitzsimons, Megan; McGrath, Jacqueline M; Henderson, Wendy A

2017-05-01

Vulnerable preterm infants experience repeated and prolonged pain/stress stimulation during a critical period in their development while in the neonatal intensive care unit (NICU). The contribution of cumulative pain/stressors to altered neurodevelopment remains unclear. The study purpose was to investigate the impact of early life painful/stressful experiences on neurobehavioral outcomes of preterm infants in the NICU. A prospective exploratory study was conducted with fifty preterm infants (28 0/7-32 6/7weeks gestational age) recruited at birth and followed for four weeks. Cumulative pain/stressors (NICU Infant Stressor Scale) were measured daily and neurodevelopmental outcomes (NICU Network Neurobehavioral Scale) were examined at 36-37weeks post-menstrual age. Data analyses were conducted on the distribution of pain/stressors experienced over time and the linkages among pain/stressors and neurobehavioral outcomes. Preterm infants experienced a high degree of pain/stressors in the NICU, both in numbers of daily acute events (22.97±2.30 procedures) and cumulative times of chronic/stressful exposure (42.59±15.02h). Both acute and chronic pain/stress experienced during early life significantly contributed to the neurobehavioral outcomes, particularly in stress/abstinence (p<0.05) and habituation responses (p<0.01), meanwhile, direct breastfeeding and skin-to-skin holding were also significantly associated with habituation (p<0.01-0.05). Understanding mechanisms by which early life experience alters neurodevelopment will assist clinicians in developing targeted neuroprotective strategies and individualized interventions to improve infant developmental outcomes. Copyright © 2017 Elsevier B.V. All rights reserved.

Renal cancer risk and occupational exposure to polycyclic aromatic hydrocarbons and plastics

PubMed Central

Karami, Sara; Boffetta, Paolo; Brennan, Paul; Stewart, Patricia A.; Zaridze, David; Matveev, Vsevolod; Janout, Vladimir; Kollarova, Helena; Bencko, Vladimir; Navratilova, Marie; Szeszenia-Dabrowska, Neonila; Mates, Dana; Gromiec, Jan P.; Sobotka, Roman; Chow, Wong-Ho; Rothman, Nathaniel; Moore, Lee E.

2011-01-01

Objective To investigate whether occupational exposure to polycyclic aromatic hydrocarbons and certain plastic monomers increased renal cell carcinomas (RCC) risk. Methods Unconditional logistic regression was used to calculate RCC risk in relation to exposure. Results No association between RCC risk and having ever been occupationally exposed to any polycyclic aromatic hydrocarbons or plastics was observed. Duration of exposure and average exposure also showed no association with risk. Suggestive positive associations between RCC risk and cumulative exposure to styrene (P-trend = 0.02) and acrylonitrile (P-trend = 0.06) were found. Cumulative exposure to petroleum/gasoline engine emissions was inversely associated with risk (P-trend = 0.02). Conclusions Results indicate a possible association between occupational styrene and acrylonitrile exposure and RCC risk. Additional studies are needed to replicate findings, as this is the first time these associations have been reported and they may be due to chance. PMID:21270648

Cumulative pain-related stress and developmental outcomes among low-risk preterm infants at one year corrected age.

PubMed

Morag, Iris; Rotem, Ifat; Frisch, Mor; Hendler, Israel; Simchen, Michal J; Leibovitz, Leah; Maayan-Metzger, Ayala; Strauss, Tzipora

2017-06-01

Extensive exposure of preterm infants to pain-related stress (PRS) at a time of physiological immaturity and rapid brain development may contribute to altered neurodevelopment. To examine the relationship between early PRS and neurodevelopmental outcomes among low-risk very preterm infants at the age of one year corrected age (CA). Participants included 107 infants born <32weeks gestational age (GA) and monitored prospectively at 12.5months CA. Excluded were infants with severe neonatal morbidities associated with impaired neurodevelopment. PRS documentation was performed via the number of skin-breaking procedures (SBP) and by the use of the neonatal infant stressor scale (NISS). Adjustment was made for early neonatal morbidities. Developmental outcomes among the study infants were within the norm (mean 100±11.03). Infants who underwent invasive mechanical ventilation (IMV) (n=31) were exposed to significantly more PRS than non-IMV infants (n=76) (p<0.000). Developmental outcomes were similar in both groups (99.7±11.1 vs. 100.8±11 p=0.63). Among IMV infants, increased exposure to PRS was associated with lower developmental scores independent of GA, gender or other sociodemographic factors. Increased exposure to PRS among low-risk preterm infants who underwent IMV is associated with lower developmental scores at 12.5month CA. Copyright © 2017 Elsevier B.V. All rights reserved.

[Acute risk assessment of cumulative dietary exposure to organophosphorus pesticide among people in Jiangsu province].

PubMed

Zhao, Minxian; Wang, Cannan; Li, Tingting; Yi, Nannan; He, Xiansong; Wu, Hui; Yao, Xinya

2013-09-01

To understand the cumulative dietary exposure of Jiangsu residents to organophosphorus (OPs) pesticide and make acute risk assessment. Integrated the data of the nutrition and health status of residents in Jiangsu and the data of monitoring of OPs pesticide in agricultural products. Chlorpyrifos was selected as index compound (index chemical, IC), then use relative potency factor (RPF) approach which commended by EPA and simple distribution evaluation. Caloulated the dietary cumulative exposure of OPs pesticide among Jiangsu residents and compared with acute reference dose (ARfD), then made risk assessment. The exposure of rural group of age 3-6 and 7-11 were 133.84 microg/kg BW and 154.32 microg/kg BW, exceeded ARfD. The exposure level of kids and elder was higher than adults. The exposure level of rural residents were higher than urban residents. The highest contribution to the food of each age group was greengrocery and leek. The average level of exposure was safety in Jiangsu, high exposure children were at acute poisoning risk. High contribution food such as greengrocery and leek should be strengthen monitoring.

The long-term benefits of nucleos(t)ide analogs in compensated HBV cirrhotic patients with no or small esophageal varices: A 12-year prospective cohort study.

PubMed

Lampertico, Pietro; Invernizzi, Federica; Viganò, Mauro; Loglio, Alessandro; Mangia, Giampaolo; Facchetti, Floriana; Primignani, Massimo; Jovani, Manol; Iavarone, Massimo; Fraquelli, Mirella; Casazza, Giovanni; de Franchis, Roberto; Colombo, Massimo

2015-11-01

Esophageal varices (EV) are a marker of disease severity in compensated cirrhosis due to hepatitis B virus (HBV) which predicts also the risk of hepatocellular carcinoma (HCC), clinical decompensation and anticipated liver related death. The dynamics and prognostic significance of EV in patients under long-term HBV suppression by nucleos(t)ide analogs (NUC), are poorly known. A standardized protocol (Baveno) including 414 upper gastrointestinal (GI) endoscopies was applied to 107 HBeAg-negative compensated cirrhotic patients (93% Child-Pugh A) during a median of 12 (range 2 to 17) years of NUC therapy. Patients who initially started on lamivudine (LMV) and then developed resistance (LMV-R), were rescued by early administration of adefovir, or were switched to tenofovir. Surveillance included serum HBV DNA every three months and abdominal ultrasound every six months. Twenty-seven patients had baseline F1 EV which regressed in 18, remained unchanged in eight and progressed in one patient; the 12-year cumulative incidence of EV regression was 83% (95% CI: 52-92%). De novo F1/F2 EV developed in 6/80 patients with a 12-year cumulative incidence of 10% (95% CI: 5-20%). Six of seven patients with de novo varices or progression of pre-existing varices had either a clinical breakthrough due to LMV-R and/or developed a HCC. No bleedings from ruptured EV occurred, 12 patients died (9 HCC) and 15 were transplanted (13 HCC): the 12-year cumulative incidence of HCC and overall survival was 33% (95% CI: 24-42%) and 76% (95% CI: 67-83%), respectively. Long-term pharmacological suppression of HBV in HBeAg-seronegative patients with compensated cirrhosis leads to a significant regression of pre-existing EV accompanied by a negligible risk of developing de novo EV. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

The cumulative burden of double-stranded DNA virus detection after allogeneic HCT is associated with increased mortality.

PubMed

Hill, Joshua A; Mayer, Bryan T; Xie, Hu; Leisenring, Wendy M; Huang, Meei-Li; Stevens-Ayers, Terry; Milano, Filippo; Delaney, Colleen; Sorror, Mohamed L; Sandmaier, Brenda M; Nichols, Garrett; Zerr, Danielle M; Jerome, Keith R; Schiffer, Joshua T; Boeckh, Michael

2017-04-20

Strategies to prevent active infection with certain double-stranded DNA (dsDNA) viruses after allogeneic hematopoietic cell transplantation (HCT) are limited by incomplete understanding of their epidemiology and clinical impact. We retrospectively tested weekly plasma samples from allogeneic HCT recipients at our center from 2007 to 2014. We used quantitative PCR to test for cytomegalovirus, BK polyomavirus, human herpesvirus 6B, HHV-6A, adenovirus, and Epstein-Barr virus between days 0 and 100 post-HCT. We evaluated risk factors for detection of multiple viruses and association of viruses with mortality through day 365 post-HCT with Cox models. Among 404 allogeneic HCT recipients, including 125 cord blood, 125 HLA-mismatched, and 154 HLA-matched HCTs, detection of multiple viruses was common through day 100: 90% had ≥1, 62% had ≥2, 28% had ≥3, and 5% had 4 or 5 viruses. Risk factors for detection of multiple viruses included cord blood or HLA-mismatched HCT, myeloablative conditioning, and acute graft-versus-host disease ( P values < .01). Absolute lymphocyte count of <200 cells/mm 3 was associated with greater virus exposure on the basis of the maximum cumulative viral load area under the curve (AUC) ( P = .054). The maximum cumulative viral load AUC was the best predictor of early (days 0-100) and late (days 101-365) overall mortality (adjusted hazard ratio [aHR] = 1.36, 95% confidence interval [CI] [1.25, 1.49], and aHR = 1.04, 95% CI [1.0, 1.08], respectively) after accounting for immune reconstitution and graft-versus-host disease. In conclusion, detection of multiple dsDNA viruses was frequent after allogeneic HCT and had a dose-dependent association with increased mortality. These data suggest opportunities to improve outcomes with better antiviral strategies. © 2017 by The American Society of Hematology.

No added value of age at menopause and the lifetime cumulative number of menstrual cycles for cardiovascular risk prediction in postmenopausal women.

PubMed

Atsma, Femke; van der Schouw, Yvonne T; Grobbee, Diederick E; Hoes, Arno W; Bartelink, Marie-Louise E L

2008-11-12

The aim of the present study was to investigate the added value of age at menopause and the lifetime cumulative number of menstrual cycles in cardiovascular risk prediction in postmenopausal women. This study included 971 women. The ankle-arm index was used as a proxy for cardiovascular morbidity and mortality. The ankle-arm index was calculated for each leg by dividing the highest ankle systolic blood pressure by the highest brachial systolic blood pressure. A cut-off value of 0.95 was used to differentiate between low and high risk women. Three cardiovascular risk models were constructed. In the initial model all classical predictors for cardiovascular disease were investigated. This model was then extended by age at menopause or the lifetime cumulative number of menstrual cycles to test their added value for cardiovascular risk prediction. Differences in discriminative power between the models were investigated by comparing the area under the receiver operating characteristic (ROC) curves. The mean age was 66.0 (+/-5.6) years. The 6 independent predictors for cardiovascular disease were age, systolic blood pressure, total to HDL cholesterol ratio, current smoking, glucose level, and body mass index > or =30 kg/m(2). The ROC area was 0.69 (0.64-0.73) and did not change when age at menopause or the lifetime cumulative number of menstrual cycles was added. The findings in this study among postmenopausal women did not support the view that age at menopause or a refined estimation of lifetime endogenous estrogen exposure would improve cardiovascular risk prediction as approximated by the ankle-arm index.

Cumulative Association of Obstructive Sleep Apnea Severity and Short Sleep Duration with the Risk for Hypertension

PubMed Central

Priou, Pascaline; Le Vaillant, Marc; Meslier, Nicole; Paris, Audrey; Pigeanne, Thierry; Nguyen, Xuan-Lan; Alizon, Claire; Bizieux-Thaminy, Acya; Leclair-Visonneau, Laurene; Humeau, Marie-Pierre; Gagnadoux, Frédéric

2014-01-01

Obstructive sleep apnea (OSA) and short sleep duration are individually associated with an increased risk for hypertension (HTN). The aim of this multicenter cross-sectional study was to test the hypothesis of a cumulative association of OSA severity and short sleep duration with the risk for prevalent HTN. Among 1,499 patients undergoing polysomnography for suspected OSA, 410 (27.3%) previously diagnosed as hypertensive and taking antihypertensive medication were considered as having HTN. Patients with total sleep time (TST) <6 h were considered to be short sleepers. Logistic regression procedures were performed to determine the independent association of HTN with OSA and sleep duration. Considering normal sleepers (TST ≥6 h) without OSA as the reference group, the odds ratio (OR) (95% confidence intervals) for having HTN was 2.51 (1.35–4.68) in normal sleepers with OSA and 4.37 (2.18–8.78) in short sleepers with OSA after adjustment for age, gender, obesity, diabetes, depression, current smoking, use of thyroid hormones, daytime sleepiness, poor sleep complaint, time in bed, sleep architecture and fragmentation, and study site. The risk for HTN appeared to present a cumulative association with OSA severity and short sleep duration (p<0.0001 for linear trend). The higher risk for HTN was observed in short sleepers with severe OSA (AHI ≥30) (OR, 4.29 [2.03–9.07]). In patients investigated for suspected OSA, sleep-disordered breathing severity and short sleep duration have a cumulative association with the risk for prevalent HTN. Further studies are required to determine whether interventions to optimize sleep may contribute to lower BP in patients with OSA. PMID:25531468

Sunlight exposure during leisure activities and risk of prostate cancer in Montréal, Canada, 2005-2009.

PubMed

Yu, Jennifer; Lavoué, Jérôme; Parent, Marie-Élise

2014-07-28

Prostate cancer (PCa) is the leading cause of cancer in men in many developed countries, but no modifiable risk factors have been identified. A handful of analytical studies have suggested a possible etiological role for sunlight exposure. We report here on the association between leisure-time sunlight exposure during adulthood and PCa risk in the context of a population-based case-control study. In all, 1,904 PCa cases were ascertained across Montreal French hospitals between 2005 and 2009. Concurrently, 1,962 population controls, frequency matched to cases by age (±5 years), were selected from the electoral list for French-speakers in Greater Montreal. Interviews elicited the frequency of engagement in any leisure activity during adulthood. This was used to derive cumulative sunlight exposure indices: a cumulative number of leisure activities events entailing sunlight exposure and a cumulative duration of sunlight exposure during leisure activities. Unconditional logistic regression was conducted to yield odds ratios (OR) and 95% confidence intervals (CI) for estimating the association between sunlight exposure indices and PCa risk, adjusting for age, ancestry, family history of PCa, PCa screening, education, solar protection, body mass index and physical activity. Compared with men in the upper quartile category for the number of sunlight exposure events, men never exposed during leisure time had an OR of 1.32 (95% CI: 0.82-2.14). ORs were 1.11, 0.91 and 1.00 for the first to the third quartiles of exposure, respectively. Similar results were observed for cumulative duration of exposure to sunlight, and by PCa aggressiveness. These findings provide little evidence of an association between sunlight exposure during leisure-time and PCa risk. Men with no sunlight exposure appeared at somewhat higher risks but none of the estimates achieved statistical significance.

Risk factors for end stage renal disease in non-WT1-syndromic Wilms tumor.

PubMed

Lange, Jane; Peterson, Susan M; Takashima, Janice R; Grigoriev, Yevgeny; Ritchey, Michael L; Shamberger, Robert C; Beckwith, J Bruce; Perlman, Elizabeth; Green, Daniel M; Breslow, Norman E

2011-08-01

We assessed risk factors for end stage renal disease in patients with Wilms tumor without known WT1 related syndromes. We hypothesized that patients with characteristics suggestive of a WT1 etiology (early onset, stromal predominant histology, intralobar nephrogenic rests) would have a higher risk of end stage renal disease due to chronic renal failure. We predicted a high risk of end stage renal disease due to progressive bilateral Wilms tumor in patients with metachronous bilateral disease. End stage renal disease was ascertained in 100 of 7,950 nonsyndromic patients enrolled in a National Wilms Tumor Study during 1969 to 2002. Risk factors were evaluated with cumulative incidence curves and proportional hazard regressions. The cumulative incidence of end stage renal disease due to chronic renal failure 20 years after Wilms tumor diagnosis was 0.7%. For end stage renal disease due to progressive bilateral Wilms tumor the incidence was 4.0% at 3 years after diagnosis in patients with synchronous bilateral Wilms tumor and 19.3% in those with metachronous bilateral Wilms tumor. For end stage renal disease due to chronic renal failure stromal predominant histology had a HR of 6.4 relative to mixed (95% CI 3.4, 11.9; p<0.001), intralobar rests had a HR of 5.9 relative to no rests (95% CI 2.0, 17.3; p=0.001), and Wilms tumor diagnosis at less than 24 months had a HR of 1.7 relative to 24 to 48 months and 2.8 relative to greater than 48 months (p=0.003 for trend). Metachronous bilateral Wilms tumor is associated with high rates of end stage renal disease due to surgery for progressive Wilms tumor. Characteristics associated with a WT1 etiology markedly increased the risk of end stage renal disease due to chronic renal failure despite the low risk in non-WT1 syndromic cases overall. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

On the Use of a Cumulative Distribution as a Utility Function in Educational or Employment Selection.

DTIC Science & Technology

1981-02-01

monotonic increasing function of true ability or performance score. A cumulative probability function is * then very convenient for describiny; one’s...possible outcomes such as test scores, grade-point averages or other common outcome variables. Utility is usually a monotonic increasing function of true ...r(0) is negative for 8 <i and positive for 0 > M, U(o) is risk-prone for low 0 values and risk-averse for high 0 values. This property is true for

Workshop on Magmatic Processes of Early Planetary Crusts: Magma Oceans and Stratiform Layered Intrusions

NASA Technical Reports Server (NTRS)

Walker, D. (Editor); Mccallum, I. S. (Editor)

1981-01-01

The significance of the lunar highland pristine cumulate samples were reevaluated with the aid of the additional insights provided by geologically constrained terrestrial investigations. This exercise involved a review of the state of knowledge about terrestrial and lunar cumulate rocks as well as an enumeration and reevaluation of the processes hypothesized to have been responsible for their formation, both classically and at present.

Cumulative stress in childhood is associated with blunted reward-related brain activity in adulthood

PubMed Central

Albert, Dustin; Iselin, Anne-Marie R.; Carré, Justin M.; Dodge, Kenneth A.; Hariri, Ahmad R.

2016-01-01

Early life stress (ELS) is strongly associated with negative outcomes in adulthood, including reduced motivation and increased negative mood. The mechanisms mediating these relations, however, are poorly understood. We examined the relation between exposure to ELS and reward-related brain activity, which is known to predict motivation and mood, at age 26, in a sample followed since kindergarten with annual assessments. Using functional neuroimaging, we assayed individual differences in the activity of the ventral striatum (VS) during the processing of monetary rewards associated with a simple card-guessing task, in a sample of 72 male participants. We examined associations between a cumulative measure of ELS exposure and VS activity in adulthood. We found that greater levels of cumulative stress during childhood and adolescence predicted lower reward-related VS activity in adulthood. Extending this general developmental pattern, we found that exposure to stress early in development (between kindergarten and grade 3) was significantly associated with variability in adult VS activity. Our results provide an important demonstration that cumulative life stress, especially during this childhood period, is associated with blunted reward-related VS activity in adulthood. These differences suggest neurobiological pathways through which a history of ELS may contribute to reduced motivation and increased negative mood. PMID:26443679