Faculty Bibliography

What is the evidence that 'pro re nata' (PRN) medication is effective for ending agitated outbursts in children and adolescents in psychiatric emergency rooms or inpatient units? Literature search was performed for studies of PRN medication use in children and adolescents that included an outcome measure. One randomised controlled trial, three prospective studies and six retrospective studies that included some outcome measure were identified. Outcome measures were heterogeneous, and frequently did not use standardised metrics assessing agitation level to measure effectiveness. The single small Randomized Controlled Trial (RTC) does not find a difference between placebo and medication, and outcomes of other studies do not control for potential placebo effect of the intervention itself as opposed to the medication. There is insufficient evidence to support the common practice of PRN medications for the management of acute agitation, and no data with which to inform clinical practice, such as which medicines and doses are helpful for specific populations or situations. Psychiatrists have no evidence-based medication interventions for acutely managing agitated outbursts in children and adolescents.

This study examined how experiences of service denial and discrimination in three health care settings-doctors' offices, emergency rooms, and mental health clinics-might contribute to attempted suicide among transgender adults. Mechanisms of this relationship were examined, including treatment receipt and the use of substances to cope with mistreatment. Perceived emotional social support was also tested as a potential protective factor against the deleterious effects of service denial and discrimination on treatment receipt, substance use, and attempted suicide. The analysis included 4190 respondents from the National Transgender Discrimination Survey. Structural equation modeling was employed to test hypothesized relationships. Being denied a greater number of services and discriminated against in more settings were associated with lower levels of treatment receipt. Service denial was also correlated with increased rates of coping-motivated substance use and elevated rates of attempted suicide. Treatment receipt mediated the relationships between service denial/discrimination and substance use. Substance use mediated the relationship between treatment receipt and attempted suicide. Higher levels of support were protective to treatment receipt when denied services in one setting, but no longer retained protective effects when denied in two or three settings. Results have critical implications for service access and delivery and policies that protect transgender help-seekers in the health care system.

The International League Against Epilepsy/American Epilepsy Society (ILAE/AES) Joint Translational Task Force created the TASK3 working groups to create common data elements (CDEs) for various aspects of preclinical epilepsy research studies, which could help improve standardization of experimental designs. This article concerns the parameters that can be measured to assess the physiologic condition of the animals that are used to study rodent models of epilepsy. Here we discuss CDEs for physiologic parameters measured in adult rats and mice such as general health status, temperature, cardiac and respiratory function, and blood constituents. We provide detailed CDE tables and case report forms (CRFs), and with this companion manuscript we discuss the monitoring of different aspects of physiology of the animals. The CDEs, CRFs, and companion paper are available to all researchers, and their use will benefit the harmonization and comparability of translational preclinical epilepsy research. The ultimate hope is to facilitate the development of biomarkers and new treatments for epilepsy.

OBJECTIVES/OBJECTIVE:This study aimed to understand if maternal interpersonal violence-related posttraumatic stress disorder (IPV-PTSD) is associated with delayed language development among very young children ("toddlers"). METHODS:Data were collected from 61 mothers and toddlers (ages 12-42 months, mean age = 25.6 months SD = 8.70). Child expressive and receptive language development was assessed by the Ages and Stages Questionnaire (ASQ) communication subscale (ASQCS) that measures language acquisition. Observed maternal caregiving behavior was coded from videos of 10-min free-play interactions via the CARE-Index. Correlations, Mann-Whitney tests, and multiple linear regression were performed. RESULTS:There was no significant association between maternal IPV-PTSD severity and the ASQCS. Maternal IPV-PTSD severity was associated with continuous maternal behavior variables (i.e. sensitive and controlling behavior on the CARE-Index) across the entire sample and regardless of child gender. Maternal sensitivity was positively and significantly associated with the ASQCS. Controlling behavior was negatively and significantly associated with the ASQCS. CONCLUSIONS:Results are consistent with the literature that while maternal IPV-PTSD severity is not associated with child language delays, the quality of maternal interactive behavior is associated both with child language development and with maternal IPV-PTSD severity. Further study is needed to understand if the level of child language development contributes to intergenerational risk or resilience for relational violence and/or victimization.

Treatment response heterogeneity poses serious challenges for selecting treatment for many diseases. To better understand this heterogeneity and to help in determining the best patient-specific treatments for a given disease, many clinical trials are collecting large amounts of patient-level data prior to administering treatment in the hope that some of these data can be used to identify moderators of treatment effect. These data can range from simple scalar values to complex functional data such as curves or images. Combining these various types of baseline data to discover "biosignatures" of treatment response is crucial for advancing precision medicine. Motivated by the problem of selecting optimal treatment for subjects with depression based on clinical and neuroimaging data, we present an approach that both (1) identifies covariates associated with differential treatment effect and (2) estimates a treatment decision rule based on these covariates. We focus on settings where there is a potentially large collection of candidate biomarkers consisting of both scalar and functional data. The validity of the proposed approach is justified via extensive simulation experiments and illustrated using data from a placebo-controlled clinical trial investigating antidepressant treatment response in subjects with depression.

Common data elements (CDEs) are becoming more common as more areas of preclinical research have generated CDEs. Herein we provide an overview of the progress to date in generating CDEs for preclinical epilepsy research. Currently there are CDEs that have been developed for Physiology (in vivo), Behavior, Pharmacology, and Electroencephalography (EEG). Together the CDEs and methodologic considerations associated with these CDEs are laid out in consecutive manuscripts published in Epilepsia Open, each describing CDEs for their respective topic area. In addition to the overview of progress for the 4 subjects, core characteristics (Core CDEs) are described and explained. Data collection using a case report form (CRF) is described, and considerations that are involved in using the CDEs and CRFs are discussed.

Structural and functional elements of biological systems are highly conserved across vertebrates. Many neurological and psychiatric conditions affect both humans and animals. A cross-species approach to the study of brain and behaviour can advance our understanding of human disorders via the identification of unrecognized natural models of spontaneous disorders, thus revealing novel factors that increase vulnerability or resilience, and via the assessment of potential therapies. Moreover, diagnostic and therapeutic advances in human neurology and psychiatry can often be adapted for veterinary patients. However, clinical and research collaborations between physicians and veterinarians remain limited, leaving this wealth of comparative information largely untapped. Here, we review pain, cognitive decline syndromes, epilepsy, anxiety and compulsions, autoimmune and infectious encephalitides and mismatch disorders across a range of animal species, looking for novel insights with translational potential. This comparative perspective can help generate novel hypotheses, expand and improve clinical trials and identify natural animal models of disease resistance and vulnerability.

BACKGROUND:Sleep problems are common and impairing in individuals with autism spectrum disorders (ASD). Evidence synthesis including both subjective (ie, measured with questionnaires) and objective (ie, quantified with neurophysiological tools) sleep alterations in youth with ASD is currently lacking. OBJECTIVE:We conducted a systematic review and meta-analysis of subjective and objective studies sleep studies in youth with ASD. METHODS:FINDINGS: From a pool of 3359 non-duplicate potentially relevant references, 47 datasets were included in the meta-analyses. Subjective and objective sleep outcome measures were extracted from 37 and 15 studies, respectively. Only five studies were based on comorbidity free, medication-naïve participants. Compared with typically developing controls, youth with ASD significantly differed in 10/14 subjective parameters and in 7/14 objective sleep parameters. The average quality score in the Newcastle-Ottawa Scale was 5.9/9. DISCUSSION AND CLINICAL IMPLICATIONS/UNASSIGNED:A number of subjective and, to a less extent, objective sleep alterations might characterise youth with ASD, but future studies should assess the impact of pharmacological treatment and psychiatric comorbidities.