Standard Deviation Unit Increase Research Articles

A Prospective Analysis of Red Blood Cell Trans Fatty Acid Levels and Risk of Non-Hodgkin Lymphoma

Abstract To confirm previous reports of increased non-Hodgkin lymphoma (NHL) risk with higher intake of dietary trans fatty acids (TFA), we conducted the first prospective study of pre-diagnosis red blood cell (RBC) TFA levels and risk of NHL and common NHL histologic subtypes (diffuse large-B cell lymphoma (DLBCL), follicular lymphoma, chronic lymphocytic lymphoma/small lymphocytic leukemia, other B-cell NHL, T-cell NHL). Methods: We conducted a nested case-control study in Nurses' Health Study (NHS) and Health Professionals Follow-Up Study (HPFS) participants with archived RBC specimens and no history of cancer at sample collection (NHS: 1989–90; HPFS: 1994–5). We confirmed 583 NHL cases (332 women in NHS, 251 men in HPFS) and matched 583 controls by cohort (sex), age, race/ethnicity and blood draw date/time. We analyzed RBC TFAs using gas-liquid chromatography; individual TFA levels were expressed as a percentage of total fatty acids. We used unconditional logistic regression, adjusted for the matching factors, to estimate odds ratios (OR) and 95% confidence intervals (CI) for overall NHL risk per 1 standard deviation (SD) unit increase in TFA level. We fitted multivariate polytomous logistic regression models to assess associations for the specific subtypes listed above. Results: Total and individual RBC TFAs were not associated with overall NHL risk or risk of most histologic subtypes. However, we observed a positive association of total RBC TFA with DLBCL risk (n = 86 cases; OR [95% CI] per 1 SD: 1.29 [1.02, 1.64]), driven primarily by 18:1 TFAs (1.35 [1.07, 1.72]). Among 18:1 TFA isomers, we found a positive association for trans 18:1 n-9 (elaidic acid; 1.33 [1.05, 1.68]) but not for other isomers. Conclusions: We observed significant positive associations for RBC TFA levels with DLBCL risk. These findings are consistent with published studies of self-reported TFA intake; further, previous studies have shown that TFA levels – particularly trans 18:1n-9, which is industrially-derived – are positively correlated with biomarkers of inflammation and immune activation, supporting the biologic plausibility of our findings. Food industry and public health measures to diminish TFA intake may help to reduce risk of NHL, and particularly of DLBCL.

Corporate social responsibility and M&A uncertainty

We contribute to the corporate social responsibility (CSR) literature by investigating whether the CSR of acquirers impacts mergers and acquisitions (M&A) completion uncertainty. Using arbitrage spreads following initial acquisition announcements as a measure of deal uncertainty, we document –for an international sample of 726 M&A operations spanning the 2004–2016 period– a negative association between arbitrage spreads and acquirers' CSR. Specifically, we show arbitrage spreads are reduced by 1.10 percentage points for each standard deviation unit-increase in the acquirer's CSR score. Findings are qualitatively similar when we focus on individual CSR dimensions (environmental, social, and governance). Our results suggest the CSR of acquirers is an important determinant of the way market participants assess the outcome of M&As worldwide.

Association between Changes in Anthropometric Indices and in Fasting Insulin Levels among Healthy Korean Adolescents: The JS High School Study.

BackgroundThis study investigated the association between changes in anthropometric indices and fasting insulin levels among healthy adolescents and whether the association differed by baseline obesity status.MethodsThis analysis was based on data collected for the JS High School study; 884 healthy adolescents aged 15 to 16 years followed up for 24 to 30 months were included. Changes in anthropometric indices and fasting insulin levels were computed as the difference between baseline and follow-up values. Multivariate linear regression models were used to determine the association between changes in anthropometric indices and fasting insulin levels. Based on body mass index (BMI)-for-age and waist circumference (WC)-for-age percentiles, participants were classified as normal weight (<85th percentile), overweight (85th percentile to <95th percentile), or obese (≥95th percentile).ResultsChanges in BMI, WC, waist-hip ratio, and waist-height ratio were significantly associated with changes in fasting insulin levels in both sexes (P<0.05). In analyses stratified by baseline obesity status, the association between change in BMI and change in fasting insulin was significantly stronger in overweight (males: standardized β=1.136; females: standardized β=1.262) and obese (males: standardized β=1.817; females: standardized β=2.290) participants than in those with normal weight (males: standardized β=0.957; females: standardized β=0.976) at baseline. Results were similar for changes in WC.ConclusionChanges in anthropometric indices were positively associated with fasting insulin level increases. Moreover, those who were overweight or obese at baseline had a higher absolute increase in fasting insulin levels per one standard deviation unit increase in anthropometric indices than adolescents with normal weight.

Subjective Cognitive Decline Prediction of Mortality: Results from the Einstein Aging Study.

The relation of pre-dementia stages to mortality has not been fully explored. Previous work examining subjective cognitive decline (SCD) and mortality is limited and mixed regarding methods used and consistency of findings. To examine SCD and mortality in a longitudinal, community-based cohort, using item response theory (IRT) methodology to form a composite SCD measure. Also, to assess whether this relationship was independent of clinical cognitive status. The Einstein Aging Study is a diverse longitudinal cohort of adults aged ≥70. SCD items were extracted from baseline CERAD questionnaires and a composite score was formed using IRT methodology. A total of 1,741 participants with complete data were clinically diagnosed as cognitively normal, or as having amnestic mild cognitive impairment (aMCI), nonamnestic mild cognitive impairment (naMCI), or dementia. 645 deaths occurred over a period of 8,912 person-years of follow-up. Cox proportional hazard models predicted time to death adjusting for covariates. A one standard deviation unit increase in level of SCD was associated with >20% higher risk of mortality. However, when models were adjusted for clinical cognitive status, the association was no longer significant. Both dementia and aMCI predicted mortality. Furthermore, when analyses focused only on those without cognitive impairment, SCD level did not predict mortality. The association of SCD with mortality may be due to the association of SCD with clinical cognitive status. Thus, SCD may be used as a community-based screen to initially identify those with cognitive impairment who may be at greatest risk for death.

The relationship between ferritin and urate levels and risk of gout

BackgroundFerritin positively associates with serum urate and an interventional study suggests that iron has a role in triggering gout flares. The objective of this study was to further explore the relationship between iron/ferritin and urate/gout.MethodsEuropean (100 cases, 60 controls) and Polynesian (100 cases, 60 controls) New Zealand (NZ) males and 189 US male cases and 60 male controls participated. The 10,727 participants without gout were from the Jackson Heart (JHS; African American = 1260) and NHANES III (European = 5112; African American = 4355) studies. Regression analyses were adjusted for age, sex, body mass index and C-reactive protein. To test for a causal relationship between ferritin and urate, bidirectional two-sample Mendelian randomization analysis was performed.ResultsSerum ferritin positively associated with gout in NZ Polynesian (OR (per 10 ng ml− 1 increase) = 1.03, p = 1.8E–03) and US (OR = 1.11, p = 7.4E–06) data sets but not in NZ European (OR = 1.00, p = 0.84) data sets. Ferritin positively associated with urate in NZ Polynesian (β (mg dl− 1) = 0.014, p = 2.5E–04), JHS (β = 0.009, p = 3.2E–05) and NHANES III (European β = 0.007, p = 5.1E–11; African American β = 0.011, p = 2.1E–16) data sets but not in NZ European (β = 0.009, p = 0.31) or US (β = 0.041, p = 0.15) gout data sets. Ferritin positively associated with the frequency of gout flares in two of the gout data sets. By Mendelian randomization analysis a one standard deviation unit increase in iron and ferritin was, respectively, associated with 0.11 (p = 8E–04) and 0.19 mg dl− 1 (p = 2E–04) increases in serum urate. There was no evidence for a causal effect of urate on iron/ferritin.ConclusionsThese data replicate the association of ferritin with serum urate. Increased ferritin levels associated with gout and flare frequency. There was evidence of a causal effect of iron and ferritin on urate.

Associations between cumulative neighborhood deprivation, long-term mobility trajectories, and gestational weight gain

Existing research on neighborhood environment and gestational weight gain (GWG) focuses on point-in-time measures of neighborhood context. This precludes understanding how long-term exposure to adverse neighborhood environments influences GWG. We estimated associations between average exposure to and trajectories of long-term neighborhood socioeconomic deprivation and risk of inadequate or excessive GWG. Using data from 5690 full-term, singleton pregnancies in the 1979 National Longitudinal Survey of Youth, we estimated associations between cumulative deprivation and GWG, overall and by race/ethnicity, controlling for individual and residential covariates. A one standard deviation unit (8-point) increase in neighborhood deprivation increased risk of inadequate GWG (Relative Risk (RR): 1.08; 95% Confidence Interval (CI): 1.00–1.16) for all women and excessive GWG (RR: 1.11; 95% CI 1.02–1.21) for white women. Persistent low deprivation (RR: 0.78; 95% CI: 0.64–0.94) and upward mobility (RR: 0.76; 95% CI: 0.61–0.96), compared to persistent high deprivation, reduced risk of inadequate GWG. Persistent low deprivation also reduced risk of excessive GWG (RR: 0.84; 95% CI: 0.71–0.98). Long-term neighborhood deprivation contributes to patterns of GWG over women's life course.

ACCELERATED GROWTH IN EARLY CHILDHOOD IS ASSOCIATED WITH INCREASED SYSTOLIC AND DIASTOLIC BLOOD PRESSURE

Abstract BACKGROUND Maternal obesity, low birthweight, and accelerated growth have been shown to be associated with elevated blood pressure in children. However, it is unknown which growth periods are associated with blood pressure, and whether birthweight or maternal obesity modify the relationship between growth and blood pressure in early childhood. OBJECTIVES We examined the relationship between age- and sex-standardized body mass index (zBMI) growth trajectories with longitudinal measures of systolic (SBP) and diastolic (DBP) blood pressure in early childhood. DESIGN/METHODS We collected repeated measures of zBMI and blood pressure in 2502 children participating in the TARGet Kids! cohort. In stage 1 we used linear spline multilevel models to estimate each child’s zBMI at birth and zBMI growth trajectories in early infancy (0–3 m), late infancy (3–18 m) and toddler years (18–36 m). In stage 2 we used generalized estimating equations to examine the relationship between zBMI at birth and zBMI growth with repeated measures of SBP and DBP from 3 to 6 years of age. We tested for effect modification by birthweight and maternal obesity status by inclusion of interaction terms in each growth period. RESULTS After adjusting for confounders and prior growth, a 1 standard deviation unit increase in zBMI growth per month in early infancy (β=0.59; 95% CI 0.32,0.87) and late infancy (β=0.73; 95% CI 0.44,1.01), were associated with higher SBP. Growth in the toddler years was not significantly associated with SBP (p=0.08). Similar but smaller associations were observed for zBMI growth and DBP in early (β=0.29; 95% CI 0.04, 0.53) and late infancy (β=0.42; 95% CI 0.18, 0.66). Birthweight status modified (p=0.004) the relationship between zBMI growth and SBP during late infancy, with the strongest positive association observed in the low birthweight group. During toddler years, birthweight status modified the relationship between zBMI growth with SBP (p=0.03) and DBP (p=0.04), with the strongest positive association observed in the low birthweight group, followed by the high birthweight group. Maternal obesity status modified (p= 0.03) the relationship between zBMI growth with DBP in late infancy, with a stronger association observed among children of mothers with obesity. CONCLUSION Accelerated growth in early and late infancy are associated with increased blood pressure in early childhood. Growth during late infancy and toddler years may impact blood pressure differently in children born with high and low birthweights and high maternal BMI, suggesting prospective windows and risk groups to target interventions.

Temporal and bi-directional associations between sleep duration and physical activity/sedentary time in children: An international comparison

The purpose of this multinational and cross-sectional study was to investigate whether nighttime sleep duration was associated with physical activity (PA) and sedentary time (SED) the following day, whether daytime PA/SED were associated with sleep duration the subsequent night, and whether the associations were modified by sex and study sites. Data from 5779 children aged 9–11years were analyzed. A waist-worn Actigraph GT3X+ accelerometer was used to assess children's 24-h movement behaviours for 7days, i.e. sleep duration, total SED, light-intensity physical activity (LPA), and moderate- to vigorous-intensity physical activity (MVPA). Multilevel linear regression models were used to account for the repeated measures nested within participants (there were up to 7 sleep→PA/SED and PA/SED→sleep pairings per participant) and schools, and adjusted for covariates. To facilitate interpretation, all sleep and PA/SED variables were standardized. Results showed that the relationship between sleep and PA/SED is bi-directional in this international sample of children. Specifically, for each one standard deviation (SD) unit increase in sleep duration, SED the following day decreased by 0.04 SD units, while LPA and MVPA increased by 0.04 and 0.02 SD units, respectively. Sleep duration decreased by 0.02 SD units and increased by 0.04 SD units for each one SD unit increase in SED and MVPA, respectively. Sleep duration was not affected by changes in LPA. These associations differed across sex and study sites in both directions. However, since the observed effect sizes are subtle, public health initiatives should consider the clinical and practical relevance of these findings.

A Non-Targeted Liquid Chromatographic-Mass Spectrometric Metabolomics Approach for Association with Coronary Artery Disease: An Identification of Biomarkers for Depiction of Underlying Biological Mechanisms.

BackgroundWe performed non-targeted metabolomics analysis using liquid chromatography-mass spectrometry coupled technique to explore the biological mechanism of coronary artery disease (CAD) events for improved prediction.Material/MethodsWe studied the association of CAD events in 4092 individuals and observed the replication of sphingomyelin (28:1), lysophosphatidylcholine (18:2), lysophosphatidylcholine (18:1), and monoglyceride (18:2), which were independent of main CAD risk factors.ResultsWe found that these 4 metabolites were responsible for traditional risk factors and also contributed to the modifications related to reclassification and discrimination. Monoglycerides (MonoGs) were positively associated with C-reactive proteins and body mass index, while lysophosphatidylcholines (LPPCs), which had less evidence of subclinical CAD in an additional 1010 participants, yielded a reverse pattern. An association between monoGs and CAD independence of triglycerides (triGs) were also observed. On the basis of Mendelian randomization analysis, we observed a positive but weak irregular effect (odds ratio per unit increase in standard deviation in monoG=1.11, P-value=0.05) on CAD.ConclusionsOur work establishes the relationship of metabolome with coronary artery disease and explains the biological mechanism of CAD events, as we identified the above-mentioned metabolites along with the evidence supporting their clinical use.

Maternal depressive symptoms during pregnancy, placental expression of genes regulating glucocorticoid and serotonin function and infant regulatory behaviors.

Glucocorticoids and serotonin may mediate the link between maternal environment, fetal brain development and 'programming' of offspring behaviors. The placenta regulates fetal exposure to maternal hormonal signals in animal studies, but few data address this in humans. We measured prospectively maternal depressive symptoms during pregnancy and mRNAs encoding key gene products determining glucocorticoid and serotonin function in term human placenta and explored associations with infant regulatory behaviors. Bi-weekly self-ratings of the Center for Epidemiologic Studies Depression Scale from 12th to 13th gestational week onwards and term placental mRNAs of 11beta-hydroxysteroid dehydrogenase type 2 (HSD2B11), type 1 (HSD1B11), glucocorticoid (NR3C1), mineralocorticoid receptors (NR3C2) and serotonin transporter (SLC6A4) were obtained from 54 healthy mothers aged 32.2 ± 5.3 years with singleton pregnancies and without pregnancy complications. Infant regulatory behaviors (crying, feeding, spitting, elimination, sleeping and predictability) were mother-rated at 15.6 ± 4.2 days. Higher placental mRNA levels of HSD2B11 [0.41 standard deviation (s.d.) unit increase per s.d. unit increase; 95% confidence interval (CI) 0.13-0.69, p = 0.005], HSD1B11 (0.30, 0.03-0.57, p = 0.03), NR3C1 (0.44, 0.19-0.68, p = 0.001) and SLC6A4 (0.26, 0.00-0.53, p = 0.05) were associated with more regulatory behavioral challenges of the infant. Higher placental NR3C1 mRNA partly mediated the association between maternal depressive symptoms during pregnancy and infant regulatory behaviors (p < 0.05). Higher placental expression of genes regulating feto-placental glucocorticoid and serotonin exposure is characteristic of infants with more regulatory behavioral challenges. Maternal depression acts, at least partly, via altering glucocorticoid action in the placenta to impact on offspring regulatory behaviors.

Abstract P143: Circulating Level of Hepatocyte Growth Factor and Incidence of Diabetes Mellitus: The Multi-Ethnic Study of Atherosclerosis

Introduction: Increased levels of hepatocyte growth factor (HGF), active in cell growth, motility, and morphogenesis, are associated with the presence of obesity, poor metabolic health, and cardiovascular disease. Hypothesis: We assessed the hypothesis that higher baseline levels of HGF will be associated with increased risk of diabetes. Methods: We examined the association between HGF and incident diabetes in MESA, including 5395 men and women 45-84 years of age at enrollment (2000-02). Fasting serum HGF was measured at baseline and on a subsample of participants at exam 2 (n = 1915). From 2000-11, incidence of diabetes was ascertained over 4 follow-up examinations, determined by new use of insulin or oral hypoglycemic medication or fasting glucose ≥ 126 mg/dL. Cox regression was used to estimate hazard ratios (HR) for incident diabetes according to 1 standard deviation unit (SDU) of HGF (1 SDU =256 pg/mL), before and after adjustment for age, sex, race/ethnicity, education, study center, smoking status, alcohol consumption, BMI, WC, fasting glucose and insulin, CRP, and IL-6 levels. Similarly, hazard ratios for incident diabetes were estimated according to change in HGF levels from exam 1 to exam 2 in the subsample. Results: At baseline, older age, male sex, current smoking, and higher body mass index (BMI), waist circumference (WC), fasting glucose and insulin, C-reactive protein (CRP) and interleukin-6 (IL-6) levels were all associated with higher levels of HGF, while greater education and physical activity were associated with lower serum HGF. Incidence of diabetes in this analytic sample was 12% (n cases = 670). Per 1 SDU increase in baseline HGF level, unadjusted risk for diabetes increased 1.46 fold (95% CI=1.37, 1.56). After adjustment, diabetes risk per 1 SDU increase in HGF was attenuated but remained significantly increased (HR=1.22; 95% CI=1.12, 1.32). No association was found between change in HGF level between exam 1 and exam 2 and incidence of diabetes. There was no evidence of effect modification by race/ethnicity for either analysis. Conclusion: In conclusion, in this ethnically diverse U.S. adult population, higher levels of serum HGF were independently associated with increased incidence of diabetes.

Early life predictors of blood pressure in Afro-Caribbean young adults: The Jamaica 1986 birth cohort study

Objective: In this study we examined the effects of birth weight (BWT) and early life socioeconomic circumstances (SEC) on systolic and diastolic blood pressure (SBP, DBP) among Jamaican young adults. Study Design and Setting: Longitudinal study of 364 men and 430 women from the Jamaica 1986 Birth Cohort Study. Information on maternal SEC at birth and BWT were linked to information collected at 18-20 years old. Sex-specific multilevel linear regression models were used to examine whether adult SBP and DBP were associated with BWT and maternal SEC. Results: In unadjusted models, SBP was inversely related to BWT z-score in both men and women (beta = -0.82 and -1.18, respectively) but achieved statistical significance for women only. After adjustments for current age, current BMI, current height, maternal age and mother's occupation at child's birth, a one standard deviation (SD) unit increase in BWT was associated with 1.16 mmHg reduction in SBP among men (95%CI -2.15, -0.17; p=0.021) and a 1.34 mmHg reduction in SBP among women (95%CI -2.21, -0.47; p=0.003). High maternal occupational SEC at birth was consistently associated with lowest SBP across the standardized BWT distribution. SBP was 2-4 mmHg lower among those with high SEC mothers at birth than among those whose mothers were unemployed at birth. Conclusion: SBP at 18-20 years-old was lowest among those whose mothers had high SEC at birth and was inversely related to BWT.

Analytic morphomics corresponds to functional status in older patients

BackgroundOlder patients account for nearly half of the United States surgical volume, and age alone is insufficient to predict surgical fitness. Various metrics exist for risk stratification, but little work has been done to describe the association between measures. We aimed to determine whether analytic morphomics, a novel objective risk assessment tool, correlates with functional measures currently recommended in the preoperative evaluation of older patients. Materials and methodsWe retrospectively identified 184 elective general surgery patients aged >70 y with both a preoperative computed tomography scan and Vulnerable Elderly Surgical Pathways and outcomes Assessment within 90 d of surgery. We used analytic morphomics to calculate trunk muscle size (or total psoas area [TPA]) and univariate logistic regression to assess the relationship between TPA and domains of geriatric function mobility, basic and instrumental activities of daily living (ADLs), and cognitive ability. ResultsGreater TPA was inversely correlated with impaired mobility (odds ratio [OR] = 0.46, 95% confidence interval [CI] 0.25–0.85, P = 0.013). Greater TPA was associated with decreased odds of deficit in any basic ADLs (OR = 0.36 per standard deviation unit increase in TPA, 95% CI 0.15–0.87, P <0.03) and any instrumental ADLs (OR = 0.53, 95% CI 0.34–0.81; P <0.005). Finally, patients with larger TPA were less likely to have cognitive difficulty assessed by Mini-Cog scale (OR = 0.55, 95% CI 0.35–0.86, P <0.01). Controlling for age did not change results. ConclusionsOlder surgical candidates with greater trunk muscle size, or greater TPA, are less likely to have physical impairment, cognitive difficulty, or decreased ability to perform daily self-care. Further research linking these assessments to clinical outcomes is needed.

Surrogate safety measure for evaluating rear-end collision risk related to kinematic waves near freeway recurrent bottlenecks

This study presents a surrogate safety measure for evaluating the rear-end collision risk related to kinematic waves near freeway recurrent bottlenecks using aggregated traffic data from ordinary loop detectors. The attributes of kinematic waves that accompany rear-end collisions and the traffic conditions at detector stations spanning the collision locations were examined to develop the rear-end collision risk index (RCRI). Together with RCRI, standard deviations in occupancy were used to develop a logistic regression model for estimating rear-end collision likelihood near freeway recurrent bottlenecks in real-time. The parameters in the logistic regression models were calibrated using collision data gathered from the 6-mile study site between 2006 and 2007. Findings indicated that an additional unit increase in RCRI results in increasing the odds of rear-end collision by 21.1%, a unit increase in standard deviation of upstream occupancy increases the odds by 19.5%, and a unit increase in standard deviation of downstream occupancy increases the odds by 18.7%. The likelihood of rear-end collisions is highest when the traffic approaching from upstream is near capacity state while downstream traffic is highly congested. The paper also reports on the findings from comparing the predicted number of rear-end collisions at the study site using the proposed model with the observed traffic collision data from 2008. The proposed model's true positive rates were higher than those of existing real-time crash prediction models.

Tacrolimus Level Variability Is a Novel Measure Associated with Increased Acute Rejection in Lung Transplant (LTx) Recipients

Purpose Tacrolimus blood level variability post LTx can be due to non-adherence, intercurrent illness, concommitant medications or poor absorption. The last factor is important in cystic fibrosis recipients with exocrine pancreatic insufficiency. We hypothesize that high variability in tacrolimus level is a risk factor in early acute rejection. Methods and Materials Data was collected for consecutive LTx performed over a 16 month period. Transbronchial biopsy took place routinely on week 1, 2, 4, month 2, 3, 6, 9, and 12. Acute rejection is defined as >ISHLT Grade 2 on biopsy, absence of rejection is defined as grade 0 or 1. Standard deviation (SD), mean and the total number of tacrolimus requested were separated into time intervals post LTx. The SD of early rejectors ( Results Of 108 LTx recipients, 9 were excluded (tacrolimus cessation, death unrelated to rejection, or lack of biopsy data). Ten of 14 acute rejections occurred within 90 days post LTx (mean = 28.6 ±19.1 days). For each 1 unit increase in SD in the day 8-90 post LTx period, the risk of rejection increased by 23% (H.R.= 1.23, C.I = 1.04-1.46). The mean tacrolimus level was higher in the rejectors compared to non-rejectors during day 8-30 (12.0 vs 10.4 mcg/L, p =0.01). When the pre-rejection tacrolimus levels were compared to levels in non-rejectors in the follow-up period, variability remained higher in the rejection group (H.R.= 1.44, C.I.=1.18 – 1.76). The mean tacrolimus level pre-rejection did not predict rejection (H.R.= 0.824, C.I. = 0.55-1.250). There was a higher proportion of cystic fibrosis patients in the rejection group compared to the non-rejection group (p = 0.01). Conclusions Tacrolimus variability is a risk factor for early acute LTx rejection. The higher proportion of cystic fibrosis lung recipient in the rejection group suggests poor tacrolimus absorption might contribute to this variability.

Age of alcohol and cannabis use onset mediates the association of transmissible risk in childhood and development of alcohol and cannabis disorders: Evidence for common liability.

Age at the time of first alcohol and cannabis use was investigated in relation to a measure of transmissible (intergenerational) risk for addiction in childhood and development of alcohol use disorder (AUD) and cannabis use disorder (CUD). It was hypothesized that age at the time of first experience with either substance mediates the association between transmissible risk and subsequent diagnosis of both disorders. The Transmissible Liability Index (TLI; (Vanyukov et al., 2009) was administered to 339 10- to 12-year-old boys (n = 254) and girls (n = 85). Age at the time of first alcohol and cannabis use, and diagnosis of AUD and CUD, were prospectively tracked to age 22. Each standard deviation unit increase in TLI severity corresponded to a reduction in age of alcohol and cannabis use onset by 3.2 months and 4.6 months, respectively. Age at the time of first alcohol use mediated the association of TLI with both AUD and CUD. Parallel results were obtained for cannabis. Whereas transmissible risk is congenerous to both AUD and CUD, its magnitude was 7 times greater in youths who initiated substance use with cannabis. TLI predicts age of first use of alcohol and cannabis that is common to developing both AUD and CUD. The ramifications of these findings for prevention are discussed.

Improving Screening for Hepatocellular Carcinoma by Incorporating Data on Levels of α-Fetoprotein, Over Time

Current screening algorithms for hepatocellular carcinoma (HCC) view each testing interval independently, without considering prior test results. We investigated whether measurements of α-fetoprotein (AFP), over time, can be used to identify patients most likely to develop HCC. We performed a nested case-control study using data from subjects in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis trial; 82 patients with HCC were matched 1:3 to individuals without HCC (controls), using bootstrap methods to ensure similar follow-up times between groups. We assessed the independent association between development of HCC and the following: (1) most recent level of AFP, (2) standard deviation in level of AFP, and (3) rate of increase in AFP using a multiple logistic regression that included patient-specific risk factors such as age, platelet count, and smoking status. In bivariable analysis, all 3 AFP metrics were associated with HCC development; the most strongly associated was the standard deviation of AFP (odds ratio, 1.03 per unit increase in standard deviation; P < .001). Incorporating the standard deviation of AFP and rate of AFP increase, along with patient-specific risk factors, improved the prognostic accuracy to an area under the receiver-operating characteristic curve of 0.81, compared with 0.76 when only the most recent AFP level was used. Patterns of AFP test results can more accurately identify patients with hepatitis C and advanced fibrosis or cirrhosis most likely to develop HCC, compared with most recent AFP test results.

Non-Adherence and Graft Failure in Adult Liver Transplant Recipients

Non-adherence to medical therapy after liver transplantation is confounded by different methods of measurement. (1) To compare the performance of three different methods of measuring non-adherence: (a) biochemical (standard deviation [SD] tacrolimus levels), (b) clinician report, (c) self-report. (2) To identify pre-transplant predictors of post-transplant non-adherence. (3) To evaluate whether SD tacrolimus is an accurate predictor of graft outcomes. In this retrospective cohort study, charts of adult recipients of a liver transplant 2003-2009 (sample A, n=444) were reviewed to determine pre-transplant predictors of non-adherence and clinician report of non-adherence. SD tacrolimus levels were measured between 6 and 18months post-transplant. A subset of sample A (n=122) completed a survey on non-adherence. The three methods were compared using linear and logistic regression. Multivariable analysis was used to investigate pre-transplant predictors of non-adherence. In sample B (transplant recipients 1995-2003, n=544) Cox regression was used to determine the relationship between SD immunosuppressant level and graft failure. Non-adherence was found in 22-62% of subjects, with the highest rates indicated by self-report. Clinician report of non-adherence was associated with both self-report and SD tacrolimus. On multivariable analysis, unemployment at time of listing and chart evidence of pre-transplant non-adherence were significant predictors of higher SD of tacrolimus. History of substance abuse and pre-transplant chart evidence of non-adherence were also significant independent predictors of post-transplant chart evidence of non-adherence. Drug variability in the immediate post-transplant setting was independently associated with graft failure over time (hazard ratio 1.005 per unit increase in standard deviation, p=0.04). Non-adherence among liver transplant recipients is a common problem associated with increased risk of graft failure. SD tacrolimus can be used to measure non-adherent behavior and perhaps target patients for behavioral interventions.

How much of the paediatric core curriculum do medical students remember?

Few educational studies have investigated how well information learned by medical students is retained over time. The primary aim of this study was to investigate how much of the paediatric core curriculum undergraduates remembered a year after originally passing their paediatrics examination. In addition, we looked at whether students' repeat performance is related to their approach to learning. Medical students were presented with 8 out of a possible 46 core curriculum short answer questions (Mark 1). A year later these same students were re-tested, without prior warning, on the same 8 questions (Mark 2) and a further 8 questions (Mark 3) from the bank of 46. The participants also completed the Revised two-factor Study Process Questionnaire to characterise their approach to learning. After a year, students scores had diminished by 51.2% (95% CI 48.2-54.2%, p<0.0001) from a Mark 1 average of 89.1% (standard deviation, SD=9.2%) to a Mark 2 average of 37.9% (SD 6.1%). Students who reported a superficial approach to learning achieved higher scores for mark 1 (4.1% increase (95% CI 0.9-7.4%) per one standard deviation unit increase in Surface Approach score (p=0.01)). Neither deep nor surface approach to learning significantly predicted performance a year later (Marks 2 and 3). Students had forgotten more than half of the paediatric core curricular content that they had previously proven that they knew for their summative assessment. Adopting either a deep or superficial approach to learning did not predict ability to retain this information a year later.

Temporal Associations between Daytime Physical Activity and Sleep in Children

ObjectivesWe examined temporal associations between objectively-measured physical activity (PA) during the day and in the evening, and sleep quantity and quality.Study DesignPA and sleep were measured by actigraphs for an average of one week in an epidemiological cohort study of 275 eight-year-old children.ResultsFor each one standard deviation (SD) unit of increased PA during the day, sleep duration was decreased by 0.30, sleep efficiency by 0.16, and sleep fragmentation increased by 0.08 SD units that night. For each one SD unit increase in sleep duration and efficiency the preceding night, PA the following day decreased by 0.09 and 0.16 SD units, respectively. When we contrasted days with a high amount of moderate to vigorous activity during the day or in the evening to days with a more sedentary profile, the results were essentially similar. However, moderate to vigorous PA in the evening shortened sleep latency.ConclusionsThe relationship between a higher level of PA and poorer sleep is bidirectional. These within-person findings challenge epidemiological findings showing that more active people report better sleep. Since only a few studies using objective measurements of both PA and sleep have been conducted in children, further studies are needed to confirm/refute these results.