A method to advance adolescent sexual health research: Automated algorithm finds sexual history documentation

Background:We aimed to develop and validate a rule-based Natural Language Processing (NLP) algorithm to detect sexual history documentation and its five key components [partners, practices, past history of sexually transmitted infections (STIs), protection from STIs, and prevention of pregnancy] among adolescent encounters in the pediatric emergency and inpatient settings.MethodsWe iteratively designed a NLP algorithm using pediatric emergency department (ED) provider notes from adolescent ED visits with specific abdominal or genitourinary (GU) chief complaints. The algorithm is composed of regular expressions identifying commonly used phrases in sexual history documentation. We validated this algorithm with inpatient admission notes for adolescents. We calculated the sensitivity, specificity, negative predictive value, positive predictive value, and F1 score of the tool in each environment using manual chart review as the gold standard.ResultsIn the ED test cohort with abdominal or GU complaints, 97/179 (54%) provider notes had a sexual history documented, and the NLP algorithm correctly classified each note. In the inpatient validation cohort, 97/321 (30%) admission notes included a sexual history, and the NLP algorithm had 100% sensitivity and 98.2% specificity. The algorithm demonstrated >97% sensitivity and specificity in both settings for detection of elements of a high quality sexual history including protection used and contraception. Type of sexual practice and STI testing offered were also detected with >97% sensitivity and specificity in the ED test cohort with slightly lower performance in the inpatient validation cohort.ConclusionThis NLP algorithm automatically detects the presence of sexual history documentation and its key components in ED and inpatient settings

Adolescent individual, school, and neighborhood influences on young adult diabetes risk.

Using data from the National Longitudinal Study of Adolescent to Adult Health (Add Health), this study examines the association between adolescent school and neighborhood contexts and the likelihood of diabetes in young adulthood. We apply cross-classified multi-level modeling (CCMM) techniques to examine the simultaneous influence of non-nested school and neighborhood contexts as well as individual, school, and neighborhood-level factors (N = 14,041 participants from 128 schools, 1933 neighborhoods). Our findings suggest that individual-level factors are most associated with young adult diabetes, with small contributions from school and neighborhood factors and a small proportion of the variation explained by school and neighborhood contexts

Achieving Cardiovascular Health in Young Adulthood—Which Adolescent Factors Matter?

AbstractPurposeTo examine associations of adolescent body mass index (BMI), tobacco use, and physical activity with optimal physiologic cardiovascular health (CVH) in adulthood.MethodsData were from 12,139 participants in Waves I (1995–1996) and IV (2007–2008) of the National Longitudinal Study of Adolescent Health. We defined optimal CVH as normal blood pressure, glucose, and cholesterol without diabetes or cardiovascular disease. We used logistic regression to estimate odds of having optimal CVH at ages 24–32 years (Wave IV) according to BMI category, smoking status, and physical activity at ages 11–19 years (Wave I).ResultsFew young adults (16%) had optimal CVH. Adolescents with normal BMI were more than twice as likely to have optimal young adult CVH compared to those who were obese (adjusted odds ratio, 2.77; 95% confidence interval, 1.97–3.89). Adolescent smoking and physical activity did not predict young adult CVH.ConclusionsLower adolescent BMI is associated with young adult CVH

Sexual Orientation Disparities in BMI among US Adolescents and Young Adults in Three Race/Ethnicity Groups

Obesity is a key public health issue for US youth. Previous research with primarily white samples of youth has indicated that sexual minority females have higher body mass index (BMI) and sexual minority males have lower BMI than their same-gender heterosexual counterparts, with sexual orientation differences in males increasing across adolescence. This research explored whether gender and sexual orientation differences in BMI exist in nonwhite racial/ethnic groups. Using data from Waves I–IV (1995–2009) of the US National Longitudinal Study of Adolescent Health (N = 13,306, ages 11–34 years), we examined associations between sexual orientation and BMI (kg/m2) over time, using longitudinal linear regression models, stratified by gender and race/ethnicity. Data were analyzed in 2013. Among males, heterosexual individuals showed greater one-year BMI gains than gay males across all race/ethnicity groups. Among females, white and Latina bisexual individuals had higher BMI than same-race/ethnicity heterosexual individuals regardless of age; there were no sexual orientation differences in black/African Americans. Sexual orientation disparities in BMI are a public health concern across race/ethnicity groups. Interventions addressing unhealthy weight gain in youth must be relevant for all sexual orientations and race/ethnicities

Associations of Blood Pressure and Cholesterol Levels During Young Adulthood With Later Cardiovascular Events.

BackgroundBlood pressure (BP) and cholesterol are major modifiable risk factors for cardiovascular disease (CVD), but effects of exposures during young adulthood on later life CVD risk have not been well quantified.ObjectiveThe authors sought to evaluate the independent associations between young adult exposures to risk factors and later life CVD risk, accounting for later life exposures.MethodsThe authors pooled data from 6 U.S. cohorts with observations spanning the life course from young adulthood to later life, and imputed risk factor trajectories for low-density lipoprotein (LDL) and high-density lipoprotein cholesterols, systolic and diastolic BP starting from age 18 years for every participant. Time-weighted average exposures to each risk factor during young (age 18 to 39 years) and later adulthood (age ≥40 years) were calculated and linked to subsequent risks of coronary heart disease (CHD), heart failure (HF), or stroke.ResultsA total of 36,030 participants were included. During a median follow-up of 17 years, there were 4,570 CHD, 5,119 HF, and 2,862 stroke events. When young and later adult risk factors were considered jointly in the model, young adult LDL ≥100 mg/dl (compared with <100 mg/dl) was associated with a 64% increased risk for CHD, independent of later adult exposures. Similarly, young adult SBP ≥130 mm Hg (compared with <120 mm Hg) was associated with a 37% increased risk for HF, and young adult DBP ≥80 mm Hg (compared with <80 mm Hg) was associated with a 21% increased risk.ConclusionsCumulative young adult exposures to elevated systolic BP, diastolic BP and LDL were associated with increased CVD risks in later life, independent of later adult exposures

Application of a lifestyle-based score to predict cardiovascular risk in African Americans: The Jackson heart study

Cardiovascular disease (CVD) primordial prevention tools applicable to diverse popula-tions are scarce. Our aim was to assess the performance of a lifestyle-based tool to estimate CVD risk in an African American population. The Jackson Heart Study is a prospective cohort including 5306 African American participants in Jackson, Mississippi (2000–2004), with a mean follow up of 12 years. The Healthy Heart Score is a lifestyle-based CVD risk prediction model based on nine components: body mass index (BMI), physical activity, smoking, and a 5-component diet score. Gender-specific beta coefficients from its derivation cohorts were used to assess the performance of the Healthy Heart Score. Model discrimination was assessed using Harrell’s C-Index for survival data and time dependent Area Under the Curve. Model calibration was evaluated through calibration plots. A total of 189 CVD events occurred. The Healthy Heart Score showed high-moderate discrimination for CVD events (C-statistic 0.75 [95% CI, 0.71–0.78]) but with little improvement over the age-only model. Both the age-only and Healthy Heart Score models had better performance in participants without diabetes at baseline and showed good calibration. In African Americans, the Healthy Heart Score does not improve prediction of mid-life CVD events beyond what is obtained by age alone.This research was funded by the National Heart, Lung, and Blood Institute, and the National Institute on Minority Health and Health Disparities, contract numbers HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, HHSN268201300050C. M.S.-P. holds a Ramón y Cajal contract (RYC-2018-025069-I) from the Ministry of Science, Innovation and Universities and FEDER/FSE and a FIS grant PI20/00896 (Instituto de Salud Carlos III, State Secretary of R+D+I and FEDER/FSE). Preparation of this manuscript was supported by The Robert Wood Johnson Foundation (Harold Amos Medical Faculty Development Program ID# 76236, J.J.J.) and the National Institute of Diabetes and Digestive and Kidney Diseases (K23DK117041, J.J.J.) of the National Institutes of Healt

Optimal Lifestyle Components in Young Adulthood Are Associated With Maintaining the Ideal Cardiovascular Health Profile Into Middle Age

BACKGROUND: Middle-aged adults with ideal blood pressure, cholesterol, and glucose levels exhibit substantially lower cardiovascular mortality than those with unfavorable levels. Four healthy lifestyle components-optimal body weight, diet, physical activity, and not smoking-are recommended for cardiovascular health (CVH). This study quantified associations between combinations of healthy lifestyle components measured in young adulthood and loss of the ideal CVH profile into middle age. METHODS AND RESULTS: Analyses included 2164 young adults in the Coronary Artery Risk Development in Young Adults study with the ideal CVH profile (defined as untreated blood pressure <120/80 mm Hg, total cholesterol <200 mg/dL, fasting blood glucose <100 mg/dL, and absence of cardiovascular disease) at baseline. Cox proportional hazards regression models estimated hazard ratios for loss of the ideal CVH profile over 25 years according to 4 individual and 16 combinations of optimal healthy lifestyle components measured in young adulthood: body mass index, physical activity, nonsmoking status, and diet quality. Models were adjusted for age, sex, race, education, study center, and baseline blood pressure, cholesterol, and glucose. Eighty percent (n=1737) of participants lost the ideal CVH profile by middle age; loss was greatest for young adults with no optimal healthy lifestyle components at baseline. Relative to young adults with no optimal healthy lifestyle components, those with all 4 were less likely to lose the ideal CVH profile (hazard ratio 0.59, 95% CI 0.44-0.80). Combinations that included optimal body mass index and nonsmoking status were each associated with lower risk. CONCLUSIONS: Optimal body mass index and not smoking in young adulthood were protective against loss of the ideal CVH profile through middle age. Importance of diet and physical activity may be included through their effects on healthy weight

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival