Dose-response Fashion Research Articles

Longitudinal associations between amygdala reactivity and cannabis use in a large sample of adolescents.

The amygdala is a key brain structure to study in relation to cannabis use as reflected by its high-density of cannabinoid receptors and functional reactivity to processes relevant to drug use. Previously, we identified a correlation between cannabis use in early adolescence and amygdala hyper-reactivity to angry faces (Spechler et al. 2015). Here, we leveraged the longitudinal aspect of the same dataset (the IMAGEN study) to determine (1) if amygdala hyper-reactivity predicts future cannabis use and (2) if amygdala reactivity is affected by prolonged cannabis exposure during adolescence. First, linear regressions predicted the level of cannabis use by age 19 using amygdala reactivity to angry faces measured at age 14 prior to cannabis exposure in a sample of 1119 participants. Next, we evaluated the time course of amygdala functional development from age 14 to 19 for angry face processing and how it might be associated with protracted cannabis use throughout this developmental window. We compared the sample from Spechler et al. 2015, the majority of whom escalated their use over the 5-year interval, to a matched sample of non-users. Right amygdala reactivity to angry faces significantly predicted cannabis use 5 years later in a dose-response fashion. Cannabis-naïve adolescents demonstrated the lowest levels of amygdala reactivity. No such predictive relationship was identified for alcohol or cigarette use. Next, follow-up analyses indicated a significant group-by-time interaction for the right amygdala. (1) Right amygdala hyper-reactivity is predictive of future cannabis use, and (2) protracted cannabis exposure during adolescence may alter the rate of neurotypical functional development.

Early life stress and HPA axis function independently predict adult depressive symptoms in metropolitan Cebu, Philippines.

Alterations in adult hypothalamic-pituitary-adrenal (HPA) axis activity have increasingly been linked with early life stress and adult depression, but a limited number of studies have used longitudinal data to explore HPA axis dysregulation as an underlying mechanism driving the long-term depressive impacts of early stressors. Here we address potential long-term impacts of early life, family-based stress on depressive symptoms among young adults in a longitudinal birth cohort study begun in 1983 in the Philippines. We relate a composite measure of family-based stressors experienced between birth and adolescence to circadian dynamics in adult salivary cortisol and depressive risk measured at 21-22 years of age. Multiple regression analyses were conducted to examine the relationship between early life stress levels and risk of adult depressive symptoms, as well as the role of adult diurnal cortisol activity in this relationship. Greater levels of early life familial stress predicted more severe depressive symptomatology at age 21-22 in a dose-response fashion (p < .0001) independent of adult diurnal cortisol patterns. Flatter diurnal cortisol slopes are directly associated with higher adult depressive symptoms, an effect mostly driven by evening cortisol levels (p = .004). When considering the cumulative effects of early life stress measures, however, exposure to more of these stressors during development is associated with even higher depressive symptoms. The long-term depressive effects of early life familial stress extend to this large sample of Cebuano young adults, and early life stress and HPA axis function may shape adult depressive symptoms through independent pathways in this sample. Our findings provide further evidence that HPA axis activity is shaped by early life conditions and is associated with depressive symptoms.

Prospective association of obstructive sleep apnea risk factors with heart failure and its subtypes in postmenopausal women: The Women's Health Initiative.

The relationship between obstructive sleep apnea (OSA) and heart failure (HF) incidence in postmenopausal women has been understudied, given the limited representation of women in heart failure studies. We investigated the relationship between OSA risk factors and HF and its subtypes in postmenopausal women. We performed a prospective analysis on the adjudicated HF outcomes in the Women's Health Initiative from enrollment (1993-1998) to September 30, 2016. HF with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF) were defined as adjudicated acute HF hospitalization with EF ≥ 45% or < 45%, respectively. We employed Cox regression to examine the association between OSA risk factors and symptoms (individually and using a summary risk score) and time to first hospitalized HF. Of 42,362 women, 2,205 (5.21%) developed all HF, 1,162 (2.74%) women developed HFpEF, and 679 (1.60%) developed HFrEF. Individual OSA risk factors and symptoms, including obesity (hazard ratio = 1.33, 95% confidence interval [CI] 1.20-1.48), snoring (hazard ratio = 1.30, 95% CI 1.16-1.46), and hypertension (HR = 1.45, 95% CI 1.35-1.56), were positively associated with risk of HF and HFpEF, but only hypertension was associated with HFrEF. When examined as a summary risk score compared with those with none of the OSA risk factors, presence of each additional factor was significantly associated with increased risk of hospitalized HF in a dose-response fashion for HFpEF (P trend < .001), but not HFrEF (P trend = .26). OSA risk factors and symptoms were associated with HFpEF, but not HFrEF, among postmenopausal women and are largely dependent on body mass index, snoring, and hypertension.

Prenatal Antidepressant Use and Risk of Adverse Neonatal Outcomes.

To estimate the risk of neonatal outcomes from patterns of prenatal antidepressant use. From the OptumLabs Data Warehouse, 226 932 singleton deliveries were identified. Antidepressant claims with coverage between the last menstrual period and 35 weeks' gestation were converted to fluoxetine equivalents, and a longitudinal cluster analysis was performed. Outcomes included major cardiac malformations (11.7 of 1000 births), preterm birth (75.7 of 1000 births), and newborn respiratory distress (54.2 of 1000 births). The lowest trajectory was the primary reference group, and depression and anxiety with no antidepressant claims served as secondary reference groups. From 15 041 (6.6%) pregnancies exposed to an antidepressant, use patterns were best described as (1) low use (∼10 mg/day) with first-trimester reduction, (2) low sustained use (∼20 mg/day), (3) moderate use (∼40 mg/day) with first-trimester reduction, (4) moderate sustained use (∼40 mg/day), and (5) high sustained use (∼75 mg/day). Moderate sustained use increased the risk of major cardiac malformations, although results included the null when compared with depression or anxiety reference groups. Moderate sustained (adjusted risk ratio [RR] 1.31; 95% confidence interval [CI] 1.16-1.49) and high sustained (adjusted RR 1.78; 95% CI 1.48-2.14) trajectories were associated with an increased risk of preterm birth. All 4 trajectories increased the risk of neonatal respiratory distress in a dose-response fashion (adjusted RRs 1.36 [95% CI 1.20-1.50] to 2.23 [95% CI 1.83-2.77]). Although findings support continuation of the lowest effective dose to treat depression or anxiety, which benefits the mother, they also highlight an increased risk for newborn respiratory distress in all groups and preterm birth at moderate to high sustained doses.

Joint association of physical and psychosocial working conditions with risk of long-term sickness absence: Prospective cohort study with register follow-up

Aims: The interplay between physical and psychosocial working conditions for the risk of developing poor health is not well understood. This study aimed to determine the joint association of physical and psychosocial working conditions with risk of long-term sickness absence (LTSA) in the general working population. Methods: Based on questionnaire responses about physical working conditions and psychosocial working conditions (influence at work, emotional demands, support from colleagues and support from managers) and two-year prospective follow-up in a national register on social transfer payments, we estimated the risk of incident LTSA of >30 days among 9544 employees without previous LTSA from the Danish Work Environment Cohort Study. The analyses were censored for all events of permanent labour market drop-out (retirement, disability pension, immigration or death) and controlled for potential confounders. Results: In the total cohort, more demanding physical working conditions were associated with risk of LTSA in a dose-response fashion (trend test, p<0.0001). The combination of poor overall psychosocial working conditions (index measure of influence at work, emotional demands, support from managers and support from colleagues) and hard physical working conditions showed the highest risk of LTSA. However, poor overall psychosocial working conditions did not interact with physical working conditions in the risk of LTSA (p=0.9677). Conclusions: The results of this study suggest that workplaces should strive to improve both psychosocial and physical work factors in order to ensure the health of workers.

Associations of Serum Retinol and α-Tocopherol Levels with Uric Acid Concentrations: Analysis of a Population-Based, Nationally Representative Sample

The effects of serum retinol and α-tocopherol on serum uric acid levels have not been established, especially in Asian people. This study evaluated the independent associations of retinol and α-tocopherol with serum uric acid levels in the Korean population. We included 6023 participants aged ≥ 19 years from the Korean National Health and Nutrition Examination Survey (KNHANES). Serum retinol and α-tocopherol levels were divided into quintiles, and a multivariate linear regression model was used to evaluate the association of serum retinol and α-tocopherol levels with uric acid concentration. Additionally, we used multivariate logistic regression to examine the relationships between the levels of these micronutrients and hyperuricemia. Serum retinol levels were positively associated with uric acid concentrations in a dose-dependent fashion in both sexes (ptrend < 0.001); the difference in serum uric acid levels between the highest and lowest quintiles of retinol levels was 0.57 mg/dL in men and 0.54 mg/dL in women. In the multivariable logistic model, the hyperuricemia risk increased linearly with the increase in serum retinol level, regardless of sex (ptrend < 0.001). Although the serum α-tocopherol level appeared to be significantly associated with increased uric acid levels, this association was nullified after adjusting for serum retinol levels. Serum retinol levels were positively associated with serum uric acid levels and hyperuricemia in a dose-response fashion. Maintaining serum retinol concentrations under sub-toxic levels might be necessary to prevent hyperuricemia-related adverse health outcomes.

Frequency and Duration of Incarceration and Mortality Among US Veterans With and Without HIV

Exposure to incarceration is associated with increased risk of mortality, and HIV is cited as a leading cause of death. Yet, few studies have examined the association between incarceration and mortality among people with HIV (PWH), specifically whether and how increasing exposure to incarceration increases risk of mortality. We compared mortality by different incarceration exposures and HIV status. We conducted a prospective cohort study of participants in the Veterans Aging Cohort Study from January 2011 to August 2017 (N = 5367). The primary exposure was incarceration by 3 measures: (1) any (ever/never); (2) frequency; and (3) cumulative duration. Stratifying by HIV status and controlling for age, race, and sex, we used Cox Proportional Hazard models to estimate adjusted hazard ratios (AHRs) and 95% confidence intervals (CIs). Incarceration was associated with increased risk of mortality compared with those never incarcerated for PWH (AHR 1.37; 95% CI: 1.13 to 1.66) and those uninfected (AHR 1.24; 95% CI: 0.99 to 1.54), but the association was only statistically significant among PWH. Increasing frequency of incarceration was associated with higher risk of mortality in both groups: for PWH, AHRs 1.13, 1.45, and 1.64 for 1, 2-5; 6+ times, respectively, for uninfected, AHRs 0.98, 1.35, and 1.70 for 1, 2-5, and 6+ times, respectively. PWH were at increased risk of mortality after incarceration, and repeated exposure to incarceration was associated with mortality in both groups in a dose-response fashion. This increased risk of mortality may be mitigated by improving transitional health care, especially HIV care, and reducing incarceration.

Late-life depression and the risk of dementia in 14 countries: a 10-year follow-up study from the Survey of Health, Ageing and Retirement in Europe

BackgroundDepression is the most common mental health problem and often co-occurs with dementia in old age. This study investigates the influence of late-life depression on risk of dementia. MethodsA total of 16210 dementia-free participants aged 60+ from the Survey of Health, Aging, and Retirement in Europe were followed up for 10 years to detect incident dementia. Depression was assessed by a 12-item Europe-depression scale, dementia was determined by physician diagnosis reported by the participants and their informants. Fine and Gray model was performed to explore the association between depression and incident dementia taking into account competing risk of death. ResultsDuring an average of 8 years follow-up, 1030 (6.35%) incident dementia were identified. Late-life depression was related to higher subdistribution hazard ratio (sHR) of dementia (sHR=1.52, 95%CI: 1.32-1.75) after adjusting for age, gender, country, education, smoking, drinking, living arrangement, BMI, chronic disease, and physical activity. Further, the risk was only existed in those below age of 80 (sHR=1.75, 95%CI: 1.47-2.07). In addition, a dose-response association was observed between the severity of depression and dementia risk (p for trend<0.001). LimitationThe ascertainment of depression and dementia was based on information reported by the participants and/or their informants, which might result in information bias. The causal relationship could not be determined because limited follow-up time. ConclusionsLate-life depression is associated with higher incidence of dementia in a dose-response fashion. Interventions targeting depression patients aged 60-79 years and those with severe depression may be effective strategies to prevent dementia.

Discrimination and Multimorbidity Among Black Americans: Findings from the National Survey of American Life.

There is a notable lack of research on the risk factors for multimorbidity, which has become more common over recent decades. Black Americans experience discrimination more often than their White counterparts, and also have significantly higher prevalence of multimorbidity. This paper examines the associations between discrimination and multimorbidity among Black Americans. We analyzed data from the National Survey of American Life to calculate the prevalence of two types of discrimination (everyday discrimination, major discriminatory events) and multimorbidity (physical, psychiatric, mixed, any). Using multivariable logistic regression, we examined the associations between discrimination and multimorbidity, adjusting for age, sex, years of education, income-to-poverty ratio, and ethnicity. The everyday discrimination scale was discretized into five categories (none, low, medium, high, very high), but was also treated as a continuous variable. The major discriminatory events were analyzed in separate adjusted models, and as a count of events. When compared with those who did not experience any discrimination, people who experienced everyday discrimination were significantly more likely to report all types of multimorbidity in a dose-response fashion at a conventional level of statistical significance. Most major discriminatory events were associated with greater odds of reporting all types of multimorbidity, as were the counts of major discriminatory events, in a dose-response fashion. We found strong evidence to suggest that discrimination was associated with greater odds of reporting multimorbidity. Future studies can expand on these findings using longitudinal data to capture the relations between discrimination and health over time, or by testing preventive interventions that allay the damaging health effects of discrimination.

Metabolic syndrome, metabolic comorbid conditions, and risk of early-onset colorectal cancer.

1571 Background: The etiology and contributors to the rising incidence of early-onset colorectal cancer (CRC diagnosed under age 50), driven largely by distal and rectal cancer, remain largely unknown. Metabolic syndrome is associated with higher risk of CRC diagnosed at older ages; however, its association with early-onset CRC remains unclear. Methods: We conducted a nested case-control study among participants aged 18-50 years with ≥2 years of enrollment and prescription drug coverage in the IBM MarketScan Commercial Databases (2006-2015). Incident CRC cases were identified using ICD-9-CM diagnosis codes. Controls without any cancer were identified using frequency matching on age, sex, geographical region, and duration of insurance enrollment. Metabolic syndrome was defined using either ICD-9-CM diagnosis codes or the presence of at least 3 of the following: obesity, hypertension, hyperlipidemia, and hyperglycemia/type 2 diabetes. In addition to ICD-9-CM codes, hypertension, hyperlipidemia, and hyperglycemia/type 2 diabetes were also defined based on regular use of medications. Multivariable logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: A total of 4,673 early-onset CRC and 40,832 controls were included. Metabolic syndrome was associated with increased risk of early-onset CRC (OR: 1.33, 95% CI 1.16-1.52), after adjusting for a range of potential confounders. The number of metabolic comorbid conditions was positively associated with risk of early-onset CRC in a dose-response fashion. Compared to individuals without any conditions, individuals with 1, 2, ≥3 metabolic conditions had a 13% (OR: 1.13, CI 1.04-1.22), 18% (OR: 1.18, CI 1.07-1.31), and 40% (OR: 1.40, CI 1.22-1.61) higher risk of early-onset CRC (Ptrend&lt;0.001), respectively. These associations were driven by proximal (OR for ≥2 vs 0 metabolic comorbid conditions: 1.40, CI 1.15-1.69) and distal colon cancer, OR ≥2 vs 0: 1.25, CI 1.03-1.53), but not rectal cancer (OR≥2 vs 0: 1.07, CI 0.92-1.24). Conclusions: Metabolic syndrome and metabolic comorbid conditions were associated with increased risk of early-onset CRC, largely driven by proximal and distal colon cancer. Metabolic dysregulations may contribute to the rising incidence of early-onset CRC.

HDL-C is associated with mortality from all causes, cardiovascular disease and cancer in a J-shaped dose-response fashion: a pooled analysis of 37 prospective cohort studies.

The association between high-density lipoprotein cholesterol (HDL-C) levels and mortality remains controversial. We aimed to investigate the potential dose-response associations between HDL-C levels and mortality from all causes, cardiovascular disease and cancer in the general population. PubMed and Embase were searched through April 2019. Prospective cohort studies reporting risk estimates of HDL-C levels and mortality were included. Linear and non-linear dose-response analyses were conducted. A random-effects model was employed to calculate pooled hazard ratio. Thirty-seven studies, involving 3,524,505 participants and more than 612,027 deaths, were included. HDL-C level was found to be associated with mortality from all causes, cardiovascular disease and cancer in a J-shaped dose-response pattern, with the lowest risk observed at HDL-C levels of 54-58 mg/dL, 68-71 mg/dL and 64-68 mg/dL, respectively. Compared with HDL-C level of 56 mg/dL, the pooled hazard ratios for all-cause mortality were 1.03 (95% confidence interval (CI) 1.01, 1.05) and 1.10 (95% CI 1.09, 1.12) for each 10-mg/dL increase and decrease in HDL-C levels, respectively; furthermore, compared with the reference category, the pooled hazard ratios for all-cause mortality were 1.21 (95% CI 1.09, 1.36) and 1.36 (95% CI 1.21, 1.53) for the highest and the lowest categories of HDL-C levels, respectively. Similar results were obtained for cardiovascular and cancer mortality. In the general population, HDL-C level is associated with mortality from all causes, cardiovascular disease and cancer in a J-shaped dose-response manner; both extremely high and low HDL-C levels are associated with an increased risk of mortality.

Vitamin D3 Supplementation Increases Long-Chain Ceramide Levels in Overweight/Obese African Americans: A Post-Hoc Analysis of a Randomized Controlled Trial.

Sphingolipid metabolism plays a critical role in cell growth regulation, lipid regulation, neurodevelopment, type 2 diabetes, and cancer. Animal experiments suggest that vitamin D may be involved in sphingolipid metabolism regulation. In this study, we tested the hypothesis that vitamin D supplementation would alter circulating long-chain ceramides and related metabolites involved in sphingolipid metabolism in humans. We carried out a post-hoc analysis of a previously conducted randomized, placebo-controlled clinical trial in 70 overweight/obese African-Americans, who were randomly assigned into four groups of 600, 2000, 4000 IU/day of vitamin D3 supplements or placebo for 16 weeks. The metabolites were measured in 64 subjects (aged 26.0 ± 9.4 years, 17% male). Serum levels of N-stearoyl-sphingosine (d18:1/18:0) (C18Cer) and stearoyl sphingomyelin (d18:1/18:0) (C18SM) were significantly increased after vitamin D3 supplementation (ps < 0.05) in a dose–response fashion. The effects of 600, 2000, and 4000 IU/day vitamin D3 supplementation on C18Cer were 0.44 (p = 0.049), 0.52 (p = 0.016), and 0.58 (p = 0.008), respectively. The effects of three dosages on C18SM were 0.30 (p = 0.222), 0.61 (p = 0.009), and 0.68 (p = 0.004), respectively. This was accompanied by the significant correlations between serum 25-hydroxyvitamin D3 [25(OH)D] concentration and those two metabolites (ps < 0.05). Vitamin D3 supplementations increase serum levels of C18Cer and C18SM in a dose–response fashion among overweight/obese African Americans.

MP21-04 THE EFFECT OF AGE ON CANCER-SPECIFIC MORTALITY IN T1A STAGE RENAL CELL CARCINOMA PATIENTS ACROSS ALL TREATMENT’S MODALITIES: A SEER-BASED STUDY

You have accessJournal of UrologyKidney Cancer: Localized: Surgical Therapy III (MP21)1 Apr 2020MP21-04 THE EFFECT OF AGE ON CANCER-SPECIFIC MORTALITY IN T1A STAGE RENAL CELL CARCINOMA PATIENTS ACROSS ALL TREATMENT’S MODALITIES: A SEER-BASED STUDY Angela Pecoraro*, Sophie Knipper, Carlotta Palumbo, Brescia Italy, Giuseppe Rosiello, Stefano Luzzago, Marina Deuker, Franciska Stolzenbach, Zhe Tian, Shahrokh F. Shariat, Fred Saad, Alberto Briganti, Cristian Fiori, Francesco Porpiglia, and Pierre I. Karakiewicz Angela Pecoraro*Angela Pecoraro* More articles by this author , Sophie KnipperSophie Knipper More articles by this author , Carlotta PalumboCarlotta Palumbo More articles by this author , Brescia ItalyBrescia Italy More articles by this author , Giuseppe RosielloGiuseppe Rosiello More articles by this author , Stefano LuzzagoStefano Luzzago More articles by this author , Marina DeukerMarina Deuker More articles by this author , Franciska StolzenbachFranciska Stolzenbach More articles by this author , Zhe TianZhe Tian More articles by this author , Shahrokh F. ShariatShahrokh F. Shariat More articles by this author , Fred SaadFred Saad More articles by this author , Alberto BrigantiAlberto Briganti More articles by this author , Cristian FioriCristian Fiori More articles by this author , Francesco PorpigliaFrancesco Porpiglia More articles by this author , and Pierre I. KarakiewiczPierre I. Karakiewicz More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000854.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The effect of age on cancer-specific mortality (CSM) is always tested in specific subgroup of patient with T1a non metastatic renal cell carcinoma (nmRCC). We tested the effect of age on CSM across all treatment modalities. METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2016), we identified 44,147 T1a nmRCC patients. Cumulative incidence plots and multivariable competing-risks regression analyses (MCR) model CSM. Separate models were fitted for each of four examined treatment modalities: partial nephrectomy [PN], radical nephrectomy [RN], local tumour ablation [LTA] and non-interventional management [NIM]. RESULTS: Patient distribution was as follows: 19602 (44.4%) <60 years; 13541 (30.7%) 60-69 years; 8637 (19.6%) 70-79 years and 2367 (5.4%) ≥ 80 years. Overall, 5- and 10-year CSM rates increased with increasing of age, across all four examined treatment modalities. In MCR focusing on PN, RN and LTA, older age independently predicted CSM in a dose-response fashion where the magnitude of CSM increased with increasing age. Conversely, in MCR for NIM the dose-response effect evidenced by a gradual increase in CSM across age categories was not recorded. In MCR models focusing on NIM patients CSM was only higher in the oldest age category, relative to three younger age categories. CONCLUSIONS: We are the first examining the effect of older age in T1a RCC across all treatment modalities, which minimize the effect of selection biases. This comprehensive analysis corroborated that more advanced age is invariably associated with increasingly higher CSM in patients treated with LTA, PN and RN. Conversely, in NIM patients the association with more advanced age with CSM was only evidenced in the highest age. In consequence, older T1a RCC patients appear to harbor more aggressive RCC phenotype than their younger counterparts. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e318-e319 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Angela Pecoraro* More articles by this author Sophie Knipper More articles by this author Carlotta Palumbo More articles by this author Brescia Italy More articles by this author Giuseppe Rosiello More articles by this author Stefano Luzzago More articles by this author Marina Deuker More articles by this author Franciska Stolzenbach More articles by this author Zhe Tian More articles by this author Shahrokh F. Shariat More articles by this author Fred Saad More articles by this author Alberto Briganti More articles by this author Cristian Fiori More articles by this author Francesco Porpiglia More articles by this author Pierre I. Karakiewicz More articles by this author Expand All Advertisement PDF downloadLoading ...

Associations of Frailty Status with Low-Mileage Driving and Driving Cessation in a Cohort of Older Drivers.

The US older adult population is projected to considerably increase in the future, and continued driving mobility is important for health aspects in populations with fewer transportation alternatives. This study evaluated whether frailty is associated with low-mileage driving (<1865 miles per year) and driving cessation among older adults. Baseline demographics and health data were collected for 2990 older drivers via in-person assessments and questionnaires, with 2964 reporting baseline frailty data. Multivariable log-binomial regression models were used to evaluate the association between baseline frailty status and low-mileage driving. Multivariable Cox proportional hazards regression were used to evaluate the association between baseline frailty status and driving cessation. For every unit increase in frailty, the estimated adjusted risk of driving fewer than 1865 miles/year increased by 138% (adjusted risk ratio: 2.38, 95% CI: 1.63–3.46). Relative to older drivers who were not frail, the adjusted hazard ratios of driving cessation were 4.15 (95% CI: 1.89–9.10) for those classified as prefrail and 6.08 (95% CI: 1.36–27.26) for those classified as frail. Frailty is positively associated with low-mileage driving status and driving cessation in a dose-response fashion. Public health interventions that reduce frailty, such as physical activity, may help older drivers maintain safe and independent mobility.

Different adiposity indices and their associations with hypertension among Chinese population from Jiangxi province

BackgroundTo date, the best adiposity index that predicts or associates strongly with hypertension remains controversial. Therefore, we aimed to compare the performance of different adiposity indices [BMI (body mass index), WC (waist circumference), WHtR (waist-to-height ratio), ABSI (a body shape index), VAI (visceral adipose index), BFP (body fat percentage)] as associates and potential predictors of risk of hypertension among Chinese population.MethodsA cross-sectional survey was conducted in Jiangxi province, China from 2013 to 2014. A total of 14,573 participants were included in the study. The physical measurements included body height, weight, WC, BFP and VAI. Multivariate logistic regression analysis was performed to assess the associations between different adiposity indices and the prevalence of hypertension. Receiver operating characteristic (ROC) analysis was also performed.ResultsAll adiposity indices were independently and positively associated with the prevalence of hypertension in a dose response fashion. The area under the curves (AUCs) for WHtR, BFP and VAI were significantly larger than those for other adiposity indices in both males and females (all P < 0.01). For males, no statistically significant difference was found in AUCs among WHtR and BFP (0.653 vs. 0.647, P = 0.4774). The AUC of WHtR was significantly higher than VAI (0.653 vs. 0.636, P < 0.01). For females, the AUCs demonstrated that WHtR was significantly more powerful than BFP and VAI (both P < 0.05) for predicting hypertension [WHtR, 0.689 (0.677–0.702); BFP, 0.677 (0.664–0.690); VAI, 0.668 (0.655–0.680)]. Whereas no significant differences were found in AUCs for hypertension among BFP and VAI in both sexes (all P > 0.1). The AUCs for hypertension associated with each adiposity index declined with age in both males and females. For subjects aged < 65 years, WHtR still had the largest AUC. However, for participants aged ≥65 years, BMI had the largest AUC.ConclusionThe findings indicated that WHtR was the best for predicting hypertension, followed by BFP and VAI, especially in younger population.

Abstract MP64: Associations of Pre-pregnancy BMI and Maternal Glycemia in Pregnancy With Maternal and Child Microbiome Five Years After Birth: Results From the Genetics of Glucose Regulation in Gestation and Growth (Gen3G) Prospective Cohort

Introduction: Maternal pre-pregnancy obesity and gestational diabetes increase future risk of obesity in the mother and child. Obesity and diabetes have been associated with lower gut microbiome diversity. To our knowledge, no studies have examined if maternal pre-pregnancy body mass index (ppBMI) and maternal glycemia during pregnancy are prospectively associated with gut microbiome diversity in mothers and their children in mid-childhood. Hypothesis: We hypothesized that higher maternal ppBMI and maternal glycemia are associated with lower gut microbiome diversity in mothers and their children 5 years after birth. Methods: Gen3G is pre-birth cohort of mother-child dyads, &gt;18 yrs who visited a pregnancy clinic in Sherbrooke, Canada. Oral glucose tolerance tests (OGTT) were administered in second trimester of pregnancy. A total of 178 mother-child pairs (not on antibiotics in the month prior to visit) provided stool, anthropometric measurements and lifestyle information 5 years after birth. Maternal overweight and obesity were defined as 25-30 kg/m 2 and &gt;=30 kg/m 2 respectively. From the stool, we extracted microbial DNA and sequenced the V4 region of the 16S ribosomal subunit. We used linear regression to model the association of ppBMI and glucose values during OGTT with maternal and child gut microbiome Shannon diversity, adjusted for confounders ( see footnote of Figure ). Results: Maternal ppBMI showed U-shaped associations with gut microbiome diversity of both mothers and children 5 years after birth ( Figure, left panels ). Higher 1h-glucose post-OGTT was associated in a dose-response fashion with lower gut microbiome diversity in mothers (p for trend &lt;0.001) and children (p for trend &lt;0.001) 5 years after birth ( Figure, right panels ). Conclusion: Higher glycemia in pregnancy, and to a lesser extent ppBMI, was prospectively associated with lower gut microbiome diversity in mother-child pairs 5 years after birth, even after adjustment for confounders and mother and child BMI measured 5 years after birth.

Association between free testosterone and hyperuricemia among pre-diabetic men

Objective: Despites earlier studies, the effects of free testosterone on serum uric acid levels and risk of hyperuricemia has not been established. The present study evaluated the association between serum free testosterone levels and hyperuricemia in Korean men. Methods: This community-based cross-sectional study include 331 male subjects having data on serum free testosterone and uric acid levels. Free testosterone levels were categorized based on the quartile distribution then general linear analysis was used to measure association of free testosterone and serum uric acid levels. Multivariate logistic regression analysis was performed to evaluate the association between free testosterone and hyperuricemia after adjustment for age, income, smoking, and alcohol consumption. Results: Free testosterone levels was positively associated with serum uric acid levels in dose-response fashion in age adjusted model (P for trend = 0.037) and multivariable adjusted model (P for trend = 0.044). Higher levels of free testosterone showed increased risk for hyperuricemia and dose response relationship between free testosterone and hyperuricemia was observed (P for trend = 0.014). Conclusion: Free testosterone had positive association with uric acid levels and hyperuricemia. Further researches are warranted to elucidate underlying mechanism of the observed findings.

Exposure to fine particulate matter (PM2.5) and pediatric rheumatic diseases

Few studies have assessed the association between fine particulate matter (PM2.5) exposure during pregnancy and infancy and pediatric rheumatic diseases (PRDs). The goal of this study was to investigate the association of PM2.5 with PRDs, and to explore sensitive windows of exposure. Therefore, we conducted a cohort-based case-control study to investigate the association between weekly exposure to PM2.5 and PRDs in Taiwan. Our birth cohort consisted of infants born in 2004–2014 (n = 1,991,592) who were followed from conception to the end of 2015. There were 2363 cases of incident PRDs in children, and 23,630 children served as controls using density matching (1:10) based on date of birth, gender, and gestational week. We used a linear mixed effect (LME) model to incorporate the aerosol optical depth (AOD), meteorological variables, and land-use data to predict daily PM2.5 concentrations. We also performed conditional logistic regression with distributed lag non-linear models (DLNMs) to assess the effects of weekly average PM2.5 on PRDs, as well as dose-response relationships. In DLNMs, exposure to PM2.5 during pregnancy (11–40 weeks) or infancy (1–14 weeks after birth) was associated with incident PRDs adjusting for potential confounding factors, and for carbon monoxide and sulfur dioxide. In the dose-response association, the odds ratios of PRDs were significantly increased for PM2.5 exposures between 26 and 54 μg/m3. In addition, exposure to PM2.5 above 81 μg/m3 dramatically increased the risk of PRDs. In conclusions, our study provides new data to suggest that PM2.5 exposure from 11–40 gestational weeks to 1–14 weeks after birth can increase the risk for PRDs in a non-linear dose-response fashion.

Adverse Childhood Experiences and Internalizing Symptoms Among American Indian Adults with Type 2 Diabetes.

Decades of evidence link adverse childhood experiences (ACEs) to worse health. Despite disproportionate rates of ACEs and health disparities in tribal communities, a gap exists in understanding the effects of ACEs on American Indian (AI) health. The purpose of this study is to estimate frequencies of eight categories of ACEs, assess the risk for internalizing symptoms by each ACE category, and determine if moderate and high levels of ACEs exposures have differential, increasing risk associated with internalizing symptoms for a sample of AI adults with T2D. Five tribal communities participated in a community-based participatory research study. Data from AI adults with T2D were analyzed (N = 192). Frequencies of eight childhood events and situations were assessed, and exposure levels of low (0-1), moderate (2-3), and high levels (4 +) of ACEs were calculated. Odds of screening positive for depression and generalized anxiety disorder (GAD) by each ACE type and moderate and high levels of ACEs were estimated using regression analyses. Relative to other studies, exposure estimates for each of the eight ACE categories and moderate and high levels of ACEs were high. Sexual and physical abuse, neglect, and household mental illness were positively associated with depressive symptoms, and physical abuse was positively associated with anxiety symptoms. Exposures to moderate and high levels of ACEs were associated with increased odds of screening positive for current depression in a dose-response fashion. A high level of ACEs exposure was also associated with an increased odds of a positive GAD screening. This research extends limited knowledge about ACEs and health among AIs. More research is needed to understand the health consequences of ACEs for a population exhibiting health inequities. Components of strategies for addressing ACEs, mental health, T2D complications, and comorbidities are proposed for AIs generally and AI adults with T2D specifically.

Abstract P3-08-28: Tissue sound speed is more strongly associated with breast cancer risk than mammographic percent density: A comparative case-control study

Abstract PURPOSE. Increased mammographic percent density (MPD) is a strong independent risk factor for developing breast cancer. Previous studies have shown that tissue sound speed, derived from ultrasound tomography, is a surrogate biomarker of MPD. We examined associations of sound speed and MPD with breast cancer risk in a case-control study. METHOD AND MATERIALS. We evaluated breast cancer risk associated with sound speed and MPD in a case-control study involving 59 participants with recent breast cancer diagnoses (cases, aged 30-70 years) and 150 participants with no history of breast cancer (controls), who were matched to cases on age, race, and menopausal status. The cases and controls were imaged with both ultrasound tomography (UST) and mammography. In cases, breast density was measured pre-treatment in the contralateral breast to avoid potential influences of tumor-related changes on MPD or sound speed. In controls, a randomly selected breast was imaged. The ultrasound tomography images were used to estimate the volume averaged sound speed of the breast, and the Cumulus software package was applied to mammograms to determine MPD. Odds Ratios (ORs) and 95% Confidence Intervals (CIs), adjusted for matching factors, were calculated for the relation of quartiles of MPD and sound speed with breast cancer risk. OR differences were tested using a bootstrap approach. RESULTS. MPD was associated with elevated breast cancer risk compared to controls, consistent with previous studies, although the trend did not reach statistical significance (OR per quartile=1.28, 95%CI: 0.95, 1.73; ptrend=0.10). In contrast, elevated sound speed was significantly associated with increased breast cancer risk in a dose-response fashion (OR per quartile=1.79, 95%CI: 1.30, 2.48; ptrend=0.0004). The OR-trend for sound speed was statistically significantly different from that observed for MPD (p=0.01). DISCUSSION. Our case-control study showed that increasing quartiles of whole breast sound speed were consistently and more strongly associated with increasing breast cancer risk than quartiles of MPD. These results show promise for UST’s role in breast cancer risk stratification. CONCLUSION. Elevated breast density strongly increases breast cancer risk. UST has the potential to provide a more accurate, non-ionizing method for assessing breast density and its associated breast cancer risk. Citation Format: Mark Sak, Neb Duric, Ruth Pfeiffer, Mark Sherman, Peter Littrup, Michael Simon, David Gorski, Teri Albrecht, Haythem Ali, Rachel Brem, Rachel Brem, Sharon Fan, Gretchen Gierach. Tissue sound speed is more strongly associated with breast cancer risk than mammographic percent density: A comparative case-control study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-28.