Annual Research Review: The contributions of the RDoC research framework on understanding the neurodevelopmental origins, progression and treatment of mental illnesses.

The National Institute of Mental Health (NIMH) proposed the Research Domain Criteria (RDoC) initiative as an alternate way to organize research of mental illnesses, by looking at dimensions of functioning rather than being tied to categorical diagnoses. This paper briefly discusses the motivation for and organization of RDoC, and then explores the NIMH portfolio and recent work to monitor the utility and progress that RDoC has afforded developmental research. To examine how RDoC has influenced the NIMH developmental research portfolio over the last decade, we employed a natural language processing algorithm to identify the number of developmental science grants classified as incorporating an RDoC approach. Additional portfolio analyses examine temporal trends in funded RDoC-relevant grants, publications and citations, and research training opportunities. Reflecting on how RDoC has influenced the focus of grant applications, we highlight examples from research on Attention-Deficit Hyperactivity Disorder (ADHD), childhood irritability, and Autism Spectrum Disorder (ASD). Lastly, we consider how the dimensional and transdiagnostic approaches emphasized in RDoC have facilitated research on personalized intervention for heterogeneous disorders and preventive/early interventions targeting emergent or subthreshold psychopathology.

Objective and Perceived Weight: Associations with Risky Adolescent Sexual Behavior.

CONTEXT: Studies have shown that obesity is associated with increased sexual risk-taking, particularly among adolescent females, but the relationships between obesity, perceived weight and sexual risk behaviors are poorly understood. METHODS: Integrative data analysis was performed that combined baseline data from the 1994-1995 National Longitudinal Study of Adolescent Health (from 17,606 respondents in grades 7-12) and the 1997 National Longitudinal Survey of Youth (from 7,752 respondents aged 12-16). Using six sexual behaviors measured in both data sets (age at first intercourse, various measures of contraceptive use and number of partners), cluster analysis was conducted that identified five distinct behavior clusters. Multivariate ordinal logistic regression analysis examined associations between adolescents' weight status (categorized as underweight, normal-weight, overweight or obese) and weight perception and their cluster membership. RESULTS: Among males, being underweight, rather than normal-weight, was negatively associated with membership in increasingly risky clusters (odds ratio, 0.5), as was the perception of being overweight, as opposed to about the right weight (0.8). However, being overweight was positively associated with males' membership in increasingly risky clusters (1.3). Among females, being obese, rather than normal-weight, was negatively correlated with membership in increasingly risky clusters (0.8), while the perception of being overweight was positively correlated with such membership (1.1). CONCLUSIONS: Both objective and subjective assessments of weight are associated with the clustering of risky sexual behaviors among adolescents, and these behavioral patterns differ by gender.

The effect of framing on surrogate optimism bias: A simulation study.

PURPOSE: To explore the effect of emotion priming and physician communication behaviors on optimism bias. MATERIALS AND METHODS: We conducted a 5 × 2 between-subject randomized factorial experiment using a Web-based interactive video designed to simulate a family meeting for a critically ill spouse/parent. Eligibility included age at least 35 years and self-identifying as the surrogate for a spouse/parent. The primary outcome was the surrogate's election of code status. We defined optimism bias as the surrogate's estimate of prognosis with cardiopulmonary resuscitation (CPR) > their recollection of the physician's estimate. RESULTS: Of 373 respondents, 256 (69%) logged in and were randomized and 220 (86%) had nonmissing data for prognosis. Sixty-seven (30%) of 220 overall and 56 of (32%) 173 with an accurate recollection of the physician's estimate had optimism bias. Optimism bias correlated with choosing CPR (P < .001). Emotion priming (P = .397), physician attention to emotion (P = .537), and framing of CPR as the social norm (P = .884) did not affect optimism bias. Framing the decision as the patient's vs the surrogate's (25% vs 36%, P = .066) and describing the alternative to CPR as "allow natural death" instead of "do not resuscitate" (25% vs 37%, P = .035) decreased optimism bias. CONCLUSIONS: Framing of CPR choice during code status conversations may influence surrogates' optimism bias.

The development of youth-onset severe obesity in urban US girls.

OBJECTIVE: To understand the incidence and persistence of severe obesity (≥1.2× 95th BMI percentile-for-age) in girls across the transition to adolescence, and map developmental trajectories of adolescent severe obesity in a high-risk sample. METHODS: We examined ten years of prospectively collected data from a population sample of urban girls (n=2,226; 53% African American, aged 7-10 in 2003-2004). We determined severe obesity prevalence and incidence by age. Logistic regression evaluated for secular trend in the association between age and severe obesity prevalence. Unconditional latent growth curve models (LGCMs) compared BMI development through the adolescence transition between girls with severe obesity versus healthy BMI. RESULTS: Severe obesity prevalence was 8.3% at age 7-10 and 10.1% at age 16-19 (white: 5.9%; African American: 13.2%; p<0.001). Age-specific prevalence increased more rapidly among the latest-born, versus earliest-born, girls (p=0.034). Incidence was 1.3% to 2.4% annually. When we compared 12-15 year-old girls with severe obesity versus healthy BMI, average body weight was already distinct 5 years earlier (16.5 kg versus 25.7 kg; p<0.001) and the BMI difference between groups increased annually. LCGMs between ages 7-10 and 11-14 indicated an increase of 3.32 kg/m2 in the healthy-BMI group and 8.50 kg/m2 in the severe obesity group, a 2.6-fold difference. CONCLUSIONS: Youth-onset severe obesity warrants particular concern in urban girls due to high prevalence and an increasing secular prevalence trend. Late childhood and early adolescence may represent a key developmental window for prevention and treatment, but is too late to prevent youth-onset severe obesity entirely.

Urban Neighborhood Features and Longitudinal Weight Development in Girls.

INTRODUCTION: The literature on environment and obesity is characterized by studies that are often cross-sectional and lack racial diversity. This study examined associations between neighborhood features and BMI development over 6 years in an urban sample of 2,295 girls (56% African American; mean age at baseline, 11.2 years) in 2004. Analyses were conducted in 2011-2015. METHODS: Girls, caregivers, and study staff completed annual neighborhood questionnaires. Linear mixed-effects modeling examined annual changes in neighborhood features and BMI and assessed whether baseline neighborhood features modified BMI growth over time. RESULTS: At baseline, 40% of participants were overweight/obese. Participants' neighborhoods had few neighborhood problems, moderate levels of safety issues and inconvenient features, low levels of neighborhood disorder, few cases of loitering youth, and substantial traffic volume. Adverse neighborhood features were more common for African American than white participants. Neighborhood features were relatively stable over the follow-up period. African American girls with helpful neighbors had lower annual BMI growth (-0.09 kg/m(2)) than others. For white girls, BMI increased more for girls with helpful neighbors (+0.09 kg/m(2) annually). Regardless of race, living in a U.S. Census tract with low levels of educational achievement was linked with higher BMI growth (an additional 0.07 kg/m(2) annually). Girls living in Census tracts with high (versus low) levels of poverty gained an additional 0.08 kg/m(2) gain annually. CONCLUSIONS: Social environment features are associated with BMI change in white and African American urban girls and may be helpful for identifying girls at risk for early adolescent weight gain.

Racial and ethnic differences in contraceptive use among women who desire no future children, 2006-2010 National Survey of Family Growth.

OBJECTIVE: To evaluate racial/ethnic differences in contraceptive use among women who do not desire future pregnancy. STUDY DESIGN: We used the 2006-2010 National Survey of Family Growth to examine the associations between race/ethnicity and 1) use of any contraceptive method at last heterosexual intercourse and 2) effectiveness of contraceptive method used among women who stated that they did not desire any (more) children. We conducted multivariable logistic regression to assess the independent effect of race/ethnicity on these outcomes, adjusting for socio-demographic factors, reproductive characteristics, and indicators of healthcare access and utilization. RESULTS: The study sample consisted of 2900 women, aged 15-44 years. The vast majority of women (91.2%) used contraception at last sex, although this varied significantly by race/ethnicity (p<.01). In the fully adjusted model controlling for demographic and reproductive characteristics as well as healthcare access, compared to whites, black women were significantly less likely to use any contraception at last sex (OR: 0.43; 95% CI: 0.27-0.73), while there was no significant difference for Hispanic women (OR: 0.95; 95% CI: 0.52-1.72). Among women who used a method at last sex, the type of contraceptive method varied significantly by race/ethnicity in bivariate analysis (p<.01), although most women (59%) used a highly effective method. In the fully adjusted model, racial/ethnic differences were no longer significant. CONCLUSIONS: In this nationally representative cohort of women who report that they do not desire (more) children, black women were significantly less likely than white women to use any contraception at last intercourse; this difference did not appear to be due to differential access to health care. IMPLICATIONS: Significant racial/ethnic differences exist in contraceptive use among women who have completed childbearing, which do not appear to be explained by differential socioeconomic status, reproductive characteristics or utilization of healthcare. Other factors, including social mobility and locus of reproductive control, that may contribute to these variations should be further explored.

Hospital end-of-life treatment intensity among cancer and non-cancer cohorts.

CONTEXT: Hospitals vary substantially in their end-of-life (EOL) treatment intensity. It is unknown if patterns of EOL treatment intensity are consistent across conditions. OBJECTIVES: To explore the relationship between hospitals' cancer- and non-cancer-specific EOL treatment intensity. METHODS: We conducted a retrospective cohort analysis of Pennsylvania acute care hospital admissions for either cancer or congestive heart failure (CHF) and/or chronic obstructive pulmonary disease (COPD) between 2001 and 2007, linked to vital statistics through 2008. We calculated Bayes's shrunken case-mix standardized (observed-to-expected) ratios of intensive care and life-sustaining treatment use among two EOL cohorts: those prospectively identified at high probability of dying on admission and those retrospectively identified as terminal admissions (decedents). We then summed these to create a hospital-specific prospective and retrospective overall EOL treatment intensity index for cancer vs. CHF/COPD. RESULTS: The sample included 207,523 admissions with 15% or greater predicted probability of dying on admission among 172,041 unique adults and 120,372 terminal admissions at 166 hospitals; these two cohorts overlapped by 52,986 admissions. There was substantial variation between hospitals in their standardized EOL treatment intensity ratios among cancer and CHF/COPD admissions. Within hospitals, cancer- and CHF/COPD-specific standardized EOL treatment intensity ratios were highly correlated for intensive care unit (ICU) admission (prospective ρ = 0.81; retrospective ρ = 0.78), ICU lengths of stay (ρ = 0.76; 0.64), mechanical ventilation (ρ = 0.73; 0.73), and hemodialysis (ρ = 0.60; 0.71) and less highly correlated for tracheostomy (ρ = 0.43; 0.53) and gastrostomy (ρ = 0.29; 0.30). Hospitals' overall EOL intensity index for cancer and CHF admissions were correlated (prospective ρ = 0.75; retrospective ρ = 0.75) and had equal group means (P-value = 0.631; 0.699). CONCLUSION: Despite substantial difference between hospitals in EOL treatment intensity, within-hospital homogeneity in EOL treatment intensity for cancer- and non-cancer populations suggests the existence of condition-insensitive institutional norms of EOL treatment.

Survival after acute hemodialysis in Pennsylvania, 2005-2007: a retrospective cohort study.

BACKGROUND: Little is known about acute hemodialysis in the US. Here we describe predictors of receipt of acute hemodialysis in one state and estimate the marginal impact of acute hemodialysis on survival after accounting for confounding due to illness severity. MATERIALS AND METHODS: This is a retrospective cohort study of acute-care hospitalizations in Pennsylvania from October 2005 to December 2007 using data from the Pennsylvania Health Care Cost Containment Council. Exposure variable is acute hemodialysis; dependent variable is survival following acute hemodialysis. We used multivariable logistic regression to determine propensity to receive acute hemodialysis and then, for a Cox proportional hazards model, matched acute hemodialysis and non-acute hemodialysis patients 1∶5 on this propensity. RESULTS: In 2,131,248 admissions of adults without end-stage renal disease, there were 6,657 instances of acute hemodialysis. In analyses adjusted for predicted probability of death upon admission plus other covariates and stratified on age, being male, black, and insured were independent predictors of receipt of acute hemodialysis. One-year post-admission mortality was 43% for those receiving acute hemodialysis, compared to 13% among those not receiving acute hemodialysis. After matching on propensity to receive acute hemodialysis and adjusting for predicted probability of death upon admission, patients who received acute hemodialysis had a higher risk of death than patients who did not over at least 1 year of follow-up (hazard ratio 1·82, 95% confidence interval 1·68-1·97). CONCLUSIONS: In a populous US state, receipt of acute hemodialysis varied by age, sex, race, and insurance status even after adjustment for illness severity. In a comparison of patients with similar propensity to receive acute hemodialysis, those who did receive it were less likely to survive than those who did not. These findings raise questions about reasons for lack of benefit.

Long-term central venous access in pediatric patients at high risk: conventional versus antibiotic-impregnated catheters.

PURPOSE: To study selective use of antibiotic-impregnated catheters in children at increased risk of venous catheter-related infections (CRIs). MATERIALS AND METHODS: From December 2008 to June 2009, 428 peripherally inserted central catheters (PICCs) were placed by the interventional radiology service of a large metropolitan children's hospital. This retrospective study analyzed demographic and outcome data for the 125 patients in this group at high risk for venous CRI. Patients at high risk were those with active systemic infection, previous complicated central venous access, intensive care unit (ICU) admission, intestinal failure, transplantation, complex congenital heart disease, or renal failure. Patients (age, 7.6 y ± 7.0; 73 male and 52 female) received a conventional or antibiotic-impregnated PICC, with 17 receiving more than one catheter. RESULTS: Of the 146 of 428 qualifying patient encounters (34%), 53 patients received an antibiotic-impregnated PICC and 93 received a conventional PICC, representing 5,080 total catheter-days (CDs). The rates of CRIs per 1,000 CDs, including catheter exit site infections and catheter-related bloodstream infections, were 0.86 for antibiotic-impregnated PICCs and 5.5 for conventional PICCs (P = .036). A propensity-based model predicts 15-fold greater infection-free survival over the lifetime of the catheter in patients who receive an antibiotic-impregnated PICC (P < .001). Antibiotic-impregnated PICC recipients with active infection or ICU admission at the time of insertion had no catheter-associated infections, compared with 3.42 and 9.46 infections per 1,000 CDs, respectively, for patients who received conventional PICCs. Patients with intestinal failure had 1.49 and 10 infections per 1,000 CDs with antibiotic-impregnated versus conventional PICCs, respectively. CONCLUSIONS: Antibiotic-impregnated long-term PICCs significantly improve infection-free catheter survival in pediatric patients at high risk.

Addressing health literacy through clear health communication: a training program for internal medicine residents.

OBJECTIVE: To develop, pilot, and test the effectiveness of a clear health communication curriculum to improve resident knowledge, attitudes, and skills regarding health literacy. METHODS: Thirty-one internal medicine residents participated in a small group curriculum that included didactic teaching, practice with a standardized patient, and individualized feedback on videotaped encounters with real patients. Outcomes were assessed using a pre-post survey and a communication skills checklist. RESULTS: Mean knowledge scores increased significantly from 60.3% to 77.6% (p<0.001). Residents also reported increased familiarity with the concept of health literacy (mean response 3.2 vs. 4.5 on a 5 point scale), importance placed on health literacy (4.2 vs. 4.9), frequency of considering health literacy in patient care (3.3 vs. 4.0), and confidence in communicating with low literacy patients (3.3 vs. 4.1) (all p<0.001). Use of plain language increased significantly from 33% to 86% (p=0.023). There were nonsignificant increases in the use of teach-back (0-36%, p=0.116) and encouraging questions (0-14%, p=0.502). CONCLUSION: Training in clear health communication improves resident knowledge, attitudes, and skills regarding health literacy. PRACTICE IMPLICATIONS: The increased use of clear health communication techniques can significantly improve the care and outcomes of vulnerable patients with limited health literacy.

Shortening the Work Preference Inventory for use with physician scientists: WPI-10.

The Work Preference Inventory (WPI) is a four-factor, 30-item measure that assesses work motivation. Used to help individuals choose appropriate career paths, its length contributes to response burden, especially when combined with other measures. We aimed to develop a shortened, valid, and reliable version of the WPI. Trainees at the University of Pittsburgh's Institute for Clinical Research Education completed the 30-item WPI between 2007 and 2012. We conducted exploratory and confirmatory factor analyses to reduce the number of items. Of the 402 eligible trainees, 371 (92%) provided data for the exploratory factor analysis (EFA), and 134 of the eligible 144 trainees (93%) provided data for the confirmatory factor analysis (CFA). EFA revealed four factors that were roughly equivalent to those of the original. CFA used the three items with the highest loadings on each factor, with two items removed due to low loadings and R-squareds, resulting in a 10-item scale. Cronbach's alpha for each of the four factors ranged from 0.68 to 0.76. Factors in the WPI-10 were strongly and significantly associated with factors in the original WPI, indicating strong validity of the shortened measure. The WPI-10 shows evidence for similar validity and reliability to the original instrument while reducing respondent burden.

A shortened version of the Clinical Research Appraisal Inventory: CRAI-12.

PURPOSE: The original Clinical Research Appraisal Inventory (CRAI), which assesses the self-confidence of trainees in performing different aspects of clinical research, comprises 92 items. Completing the lengthy CRAI is time-consuming and represents a considerable burden to respondents, yet the CRAI provides useful data for evaluating research training programs. The purpose of this study is to develop a shortened version of the CRAI and to test its validity and reliability. METHOD: Trainees in clinical research degree and career development programs at the University of Pittsburgh's Institute for Clinical Research Education completed the 92-item CRAI between 2007 and 2012, inclusive. The authors conducted, first, exploratory factor analysis on a training dataset (2007-2010) to reduce the number of items and, then, confirmatory factor analyses on a testing dataset (2011-2012) to test the psychometric properties of the shortened version. RESULTS: Of 546 trainees, 394 (72%) provided study data. Exploratory factor analysis revealed six distinct factors, and confirmatory factor analysis identified the two items with the highest loadings per factor, for a total of 12 items. Cronbach alpha for the six new factors ranged from 0.80 to 0.94. Factors in the 12-item CRAI were strongly and significantly associated with factors in the 92-item CRAI; correlations ranged from 0.82 to 0.96 (P < .001 for each). CONCLUSIONS: The 12-item CRAI is faster and less burdensome to complete but retains the strong psychometric properties of the original CRAI.

Clinical decision support to promote safe prescribing to women of reproductive age: a cluster-randomized trial.

BACKGROUND: Potentially teratogenic medications are frequently prescribed without provision of contraceptive counseling. OBJECTIVE: To evaluate whether computerized clinical decision support (CDS) can increase primary care providers' (PCPs') provision of family planning services when prescribing potentially teratogenic medications. DESIGN: Cluster-randomized trial conducted in one academic and one community-based practice between October of 2008 and April of 2010. PARTICIPANTS/INTERVENTIONS: Forty-one PCPs were randomized to receive one of two types of CDS which alerted them to risks of medication-induced birth defects when ordering potentially teratogenic medications for women who may become pregnant. The 'simple' CDS provided a cautionary alert; the 'multifaceted' CDS provided tailored information and links to a structured order set designed to facilitate safe prescribing. Both CDS systems alerted PCPs about medication risk only once per encounter. MAIN MEASURES: We assessed change in documented provision of family planning services using data from 35,110 encounters and mixed-effects models. PCPs completed surveys before and after the CDS systems were implemented, allowing assessment of change in PCP-reported counseling about the risks of medication-induced birth defects and contraception. KEY RESULTS: Both CDS systems were associated with slight increases in provision of family planning services when potential teratogens were prescribed, without a significant difference in improvement by CDS complexity (p = 0.87). Because CDS was not repeated, 13% of the times that PCPs received CDS they substituted another potential teratogen. PCPs reported significant improvements in several counseling and prescribing practices. The multifaceted group reported a greater increase in the number of times per month they discussed the risks of medication use during pregnancy (multifaceted: +4.9 ± 7.0 vs. simple: +0.8 ± 3.2, p = 0.03). The simple CDS system was associated with greater clinician satisfaction. CONCLUSIONS: CDS systems hold promise for increasing provision of family planning services when fertile women are prescribed potentially teratogenic medications, but further refinement of these systems is needed.