Faculty Bibliography

We review recent findings related to the neurobiology of infant attachment, emphasizing the role of parenting quality in attachment formation and emotional development. Current findings suggest that the development of brain structures important for emotional expression and regulation (amygdala, prefrontal cortex, hippocampus) is deeply associated with the quality of care received in infancy, with sensitive caregiving providing regulation vital for programming these structures, ultimately shaping the development of emotion into adulthood. Evidence indicates that without sensitive caregiving, infants fail to develop mechanisms needed for later-life emotion and emotion regulation. Research suggests that a sensitive period exists in early life for parental shaping of emotional development, although further cross-species research is needed to discern its age limits, and thus inform interventions.

Concerns persist that individuals with substance use disorders who are under community criminal justice supervision experience circumstances that might compromise their provision of valid, informed consent for research participation. These concerns include the possibilities that desire to obtain access to treatment might lead individuals to ignore important information about research participation, including information about risks, or that cognitive impairment associated with substance use might interfere with attending to important information. We report results from a consent quiz (CQ) administered in a multisite randomized clinical trial of long-acting naltrexone to prevent relapse to opioid use disorder among adults under community criminal justice supervision-a treatment option difficult to access by this population of individuals. Participants were required to answer all 11 items correctly before randomization. On average, participants answered 9.8 items correctly (89%) at baseline first attempt (n=306). At week 21 (n=212), participants scored 87% (9.5 items correct) without review. Performance was equivalent to, or better than, published results from other populations on a basic consent quiz instrument across multiple content domains. The consent quiz is an efficient method to screen for adequate knowledge of consent information as part of the informed consent process. Clinical researchers who are concerned about these issues should consider using a consent quiz with corrected feedback to enhance the informed consent process. Overall, while primarily useful as an educational tool, employing a CQ as part of the gateway to participation in research may be particularly important as the field continues to advance and tests novel experimental treatments with significant risks and uncertain potential for benefit.

There is now an unprecedented opportunity to improve the care of the over 5 million people who are living with Alzheimer's disease and related dementias and many more with cognitive impairment due to brain injury, systemic diseases, and other causes. The introduction of a new Medicare care planning benefit-long sought openly by advocacy organizations and clinicians and badly needed by patients and families-could greatly improve health care quality, but only if widely and fully implemented. We describe the components of this new benefit and its promise of better clinical care, as well as its potential to create a new platform for clinical and health outcomes research. We highlight external factors-and some that are internal to the benefit structure itself-that challenge the full realization of its value, and we call for broad public and professional engagement to ensure that it will not fail.

Microarray studies generate a large number of p-values from many gene expression comparisons. The estimate of the proportion of the p-values sampled from the null hypothesis draws broad interest. The two-component mixture model is often used to estimate this proportion. If the data are generated under the null hypothesis, the p-values follow the uniform distribution. What is the distribution of p-values when data are sampled from the alternative hypothesis? The distribution is derived for the chi-squared test. Then this distribution is used to estimate the proportion of p-values sampled from the null hypothesis in a parametric framework. Simulation studies are conducted to evaluate its performance in comparison with five recent methods. Even in scenarios with clusters of correlated p-values and a multicomponent mixture or a continuous mixture in the alternative, the new method performs robustly. The methods are demonstrated through an analysis of a real microarray dataset.

Chronic kidney disease (CKD) is a major global public health problem with significant gaps in research, care, and policy. In order to mitigate the risks and adverse effects of CKD, the International Society of Nephrology has created a cohesive set of activities to improve the global outcomes of people living with CKD. Improving monitoring of renal disease progression can be done by screening and monitoring albuminuria and estimated glomerular filtration rate in primary care. Consensus on how many times and how often albuminuria and estimated glomerular filtration rate are measured should be defined. Meaningful changes in both renal biomarkers should be determined in order to ascertain what is clinically relevant. Increasing social awareness of CKD and partnering with the technological community may be ways to engage patients. Furthermore, improving the prediction of cardiovascular events in patients with CKD can be achieved by including the renal risk markers albuminuria and estimated glomerular filtration rate in cardiovascular risk algorithms and by encouraging uptake of assessing cardiovascular risk by general practitioners and nephrologists. Finally, examining ways to further validate and implement novel biomarkers for CKD will help mitigate the global problem of CKD. The more frequent use of renal biopsy will facilitate further knowledge into the underlying etiologies of CKD and help put new biomarkers into biological context. Real-world assessments of these biomarkers in existing cohorts is important, as well as obtaining regulatory approval to use these biomarkers in clinical practice. Collaborations among academia, physician and patient groups, industry, payer organizations, and regulatory authorities will help improve the global outcomes of people living with CKD.

OBJECTIVE: Injury related morbidity and mortality is an important emergency medicine and public health challenge in the United States (US). Here we describe the epidemiology of traumatic injury presenting to US emergency departments, define changes in types and causes of injury among the elderly and the young, characterize the role of trauma centers and teaching hospitals in providing emergency trauma care, and estimate the overall economic burden of treating such injuries. METHODS: We conducted a secondary retrospective, repeated cross-sectional study of the Nationwide Emergency Department Data Sample (NEDS), the largest all-payer emergency department survey database in the US. Main outcomes and measures were survey-adjusted counts, proportions, means, and rates with associated standard errors, and 95% confidence intervals. We plotted annual age-stratified emergency department discharge rates for traumatic injury and present tables of proportions of common injuries and external causes. We modeled the association of Level 1 or 2 trauma center care with injury fatality using a multi-variable survey-adjusted logistic regression analysis that controlled for age, gender, injury severity, comorbid diagnoses, and teaching hospital status. RESULTS: There were 181,194,431 (standard error, se = 4234) traumatic injury discharges from US emergency departments between 2006 and 2012. There was an average year-to-year decrease of 143 (95% CI -184.3, -68.5) visits per 100,000 US population during the study period. The all-age, all-cause case-fatality rate for traumatic injuries across US emergency departments during the study period was 0.17% (se = 0.001). The case-fatality rate for the most severely injured averaged 4.8% (se = 0.001), and severely injured patients were nearly four times as likely to be seen in Level 1 or 2 trauma centers (relative risk = 3.9 (95% CI 3.7, 4.1)). The unadjusted risk ratio, based on group counts, for the association of Level 1 or 2 trauma centers with mortality was RR = 4.9 (95% CI 4.5, 5.3), however, after accounting for gender, age, injury severity and comorbidities, Level 1 or 2 trauma centers were not associated with an increased risk of fatality (odds ratio = 0.96 (0.79, 1.18)). There were notable changes at the extremes of age in types and causes of emergency department discharges for traumatic injury between 2009 and 2012. Age-stratified rates of diagnoses of traumatic brain injury increased 29.5% (se = 2.6) for adults older than 85, and increased 44.9% (se = 1.3) for children younger than 18. Firearm related injuries increased 31.7% (se = 0.2) in children five years and younger. The total inflation-adjusted cost of emergency department injury care in the US between 2006 and 2012 was $99.75 billion (se = 0.03). CONCLUSIONS: Emergency departments are a sensitive barometer of the continuing impact of traumatic injury as an important cause of morbidity and mortality in the US. Level 1 or 2 trauma centers remain a bulwark against the tide of severe trauma in the US. But, the types and causes of traumatic injury in the US are changing in consequential ways, particularly at the extremes of age, with traumatic brain injuries and firearm-related trauma presenting increased challenges

Living in communities with persistent gun violence is associated with negative social, behavioral, and health outcomes, analogous to those of a natural disaster. Taking a disaster-preparedness approach may identify targets for community-based action to respond to on-going gun violence. We assessed the relevance of adapting a disaster-preparedness approach to gun violence and, specifically, the relationship between perceived collective efficacy, its subscales of social cohesion and informal social control, and exposure to gun violence. In 2014, we conducted a cross-sectional study using a community-based participatory research approach in two neighborhoods in New Haven, CT, with high violent crime rates. Participants were ≥18 years of age and English speaking. We measured exposure to gun violence by adapting the Project on Human Development in Chicago Neighborhoods Exposure to Violence Scale. We examined the association between perceived collective efficacy, measured by the Sampson Collective Efficacy Scale, and exposure to gun violence using multivariate modeling. We obtained 153 surveys (51% response rate, 14% refusal rate, and 35% non-response rate). Ninety-five percent reported hearing gunfire, 58% had friend or family member killed by gun violence, and 33% were physically present during a shooting. In the fully adjusted model, one standard deviation higher perceived collective efficacy was associated with lower reported exposure to gun violence (β = -0.91, p < 0.001). We demonstrated that it is possible to activate community members and local officials to engage in gun violence research. A novel, community-based approach adapted from disaster-preparedness literature may be an effective framework for mitigating exposure to gun violence in communities with persistent gun violence.

Hospital patients with serious mental illness (SMI) have high rates of smoking. There are few post-discharge treatment models available for this population and limited research on their treatment uptake following discharge. This study is a secondary analysis of an RCT that compared multi-session intensive telephone counseling versus referral to state quitline counseling at two safety net hospitals in New York City. For this analysis, we selected all trial participants with a history of schizophrenia, schizoaffective disorder or bipolar disorder (N = 384) and used multivariable logistic regression to compare groups on self-reported 30-day abstinence at 6 months and to identify patient factors associated with use of tobacco treatment. Analyses found no significant group differences in abstinence 6 months (28% quitline vs. 29% intervention, p > 0.05), use of cessation medications (42% quitline vs. 47% intervention, p > 0.05) or receipt of at least one counseling call (47% quitline vs. 42% intervention, p > 0.05). Patients with hazardous drinking (p = 0.04) or perceived good health (p = 0.03) were less likely to use cessation medications. Homeless patients were less likely to use counseling (p = 0.02). Most patients did not use cessation treatment after discharge, and the intensive intervention did not improve abstinence rates over quitline referral. Interventions are needed to improve use of cessation treatment and long-term abstinence in patients with SMI.