Perelman School of Medicine
Perelman School of Medicine's mission is to advance knowledge and improve health through research, patient care, and the education of trainees in an inclusive culture that embraces diversity, fosters innovation, stimulates critical thinking, supports lifelong learning, and sustains our legacy of excellence.
- Center for Public Health Initiatives
- Department of Biostatistics, Epidemiology and Informatics
- Department of Family Medicine and Community Health
- Department of Medical Ethics and Health Policy
- Department of Microbiology Papers
- Department of Obstetrics and Gynecology
- Department of Psychiatry
- Department of Systems Pharmacology and Translational Therapeutics
- Botswana-UPenn Partnership
- Center for Cognitive Neuroscience
- Global Health Programs
- Medical Physics Programs
PublicationStudy Protocol: Implementation of a Computer-Assisted Intervention for Autism in Schools: A Hybrid Type II Cluster Randomized Effectiveness-Implementation Trial(2016-01-01) Pellecchia, Melanie; Beidas, Rinad S; Marcus, Steven C; Fishman, Jessica; Kimberly, John R.; Cannuscio, Carolyn C; Reisinger, Erica M; Rump, Keiran; Mandell, David SBackground: The number of children diagnosed with autism has rapidly outpaced the capacities of many public school systems to serve them, especially under-resourced, urban school districts. The intensive nature of evidence-based autism interventions, which rely heavily on one-to-one delivery, has caused schools to turn to computer-assisted interventions (CAI). There is little evidence regarding the feasibility, effectiveness, and implementation of CAI in public schools. While CAI has the potential to increase instructional time for students with autism, it may also result in unintended consequences such as reduction in the amount of interpersonal (as opposed to computerized) instruction students receive. The purpose of this study is to test the effectiveness of one such CAI—TeachTown—its implementation, and its effects on teachers’ use of other evidence-based practices. Methods:This study protocol describes a type II hybrid cluster randomized effectiveness-implementation trial. We will train and coach 70 teachers in autism support classrooms in one large school district in the use of evidence-based practices for students with autism. Half of the teachers then will be randomly selected to receive training and access to TeachTown: Basics, a CAI for students with autism, for the students in their classrooms. The study examines: (1) the effectiveness of TeachTown for students with autism; (2) the extent to which teachers implement TeachTown the way it was designed (i.e., fidelity); and (3) whether its uptake increases or reduces the use of other evidence-based practices. Discussion: This study will examine the implementation of new technology for children with ASD in public schools and will be the first to measure the effectiveness of CAI. As importantly, the study will investigate whether adding a new technology on top of existing practices increases or decreases their use. This study presents a unique method to studying both the implementation and exnovation of evidence-based practices for children with autism in school settings. Trial registration: NCT02695693. Retrospectively registered on July 8, 2016. PublicationCognitive-Behavioral Treatment of Anxious Youth with Comorbid School Refusal: Clinical Presentation and Treatment Response(2010-01-01) Beidas, Rinad S; Crawley, Sarah A; Mychailyszyn, Matthew P; Comer, Jonathan S; Kendall, Phillip CThe present study investigated the effectiveness of cognitive-behavioral therapy in youth (N = 27) diagnosed with a principal anxiety disorder and school refusal (SR; denial to attend school or difficulty remaining in school). Scant research examines the effectiveness of cognitive-behavioral therapy for treatment-seeking youth with a primary anxiety disorder and comorbid SR. Effects for youth who completed treatment (N = 12) ranged from d = .61 to 2.27 based on youth- and parent-reported anxiety and depressive symptoms, as well as independently rated global functioning. A discussion of treatment drop-out, a case illustration, and treatment recommendations are provided. PublicationEssential Role of SIRT1 Signaling in the Nucleus Accumbens in Cocain and Morphine Action(2013-10-09) Ferguson, Deveroux; Koo, Ja Wook; Feng, Jian; Heller, Elizabeth A; Rabkin, Jacqui; Heshmati, Mitra; Renthal, William; Liu, Xiaochuan; Shao, Ningyi; Sartorelli, Vittorio; Shen, Li; Nestler, Eric JSirtuins (SIRTs), class III histone deacetylases, are well characterized for their control of cellular physiology in peripheral tissues, but their influence in brain under normal and pathological conditions remains poorly understood. Here, we establish an essential role for brain reward region. We show that chronic cocain administration increases SIRT1 and SIRT2 expression in the mouse NAc, while chronic morphine administration induces SIRT1 expression alone, with no regulation of all other sirtuin family members observed. Drug induction of SIRT1 and SIRT2 is mediated in part at the transcriptional level via the drug-induced transcription factor ΔFosB and is associated with robust histone modifications at the Sirt1 and Sirt2 genes. Viral-mediated overexpression of SIRT1 or SIRT2 in the NAc enhances the rewarding effects of both cocain and morphine. In contrast, the local knockdown of SIRT1 from the NAc of floxed Sirt1 mice decreases drug reward. Such behavioral effects of SIRT1 occur in concert with its regulation of numerous synaptic proteins in NAc as well as with SIRT1-mediated induction of dendritic spines on NAc medium spiny neurons. These studies establish sirtuins as key mediators of the molecular and cellular plasticity induced by drugs of abuse in NAc, and of the associated behavioral adaptations, and point towards novel signaling pathways involved in drug action. PublicationHandoffs and Transitions in Critical Care (HATRICC): Protocol for a Mixed Methods Study of Operating Room to Intensive Care Unit Handoffs(2014-01-01) Lane-Fall, Meghan B; Beidas, Rinad S; Pascual, Jose L; Collard, Meredith L; Peifer, Hannah G; Chavez, Tyler J; Barry, Mark E; Gutsche, Jacob; Halpern, Scott D; Fleisher, Lee A; Barg, Frances KBackground: Operating room to intensive care unit handoffs are high-risk events for critically ill patients. Studies in selected patient populations show that standardizing operating room to intensive care unit handoffs improves information exchange and decreases errors. To adapt these findings to mixed surgical populations, we propose to study the implementation of a standardized operating room to intensive care unit handoff process in two intensive care units currently without an existing standard process. Methods/Design: The Handoffs and Transitions in Critical Care (HATRICC) study is a hybrid effectiveness- implementation trial of operating room to intensive care unit handoffs. We will use mixed methods to conduct a needs assessment of the current handoff process, adapt published handoff processes, and implement a new standardized handoff process in two academic intensive care units. Needs assessment: We will use non-participant observation to observe the current handoff process. Focus groups, interviews, and surveys of clinicians will elicit participants’ impressions about the current process. Adaptation and implementation: We will adapt published standardized handoff processes using the needs assessment findings. We will use small group simulation to test the new process’ feasibility. After simulation, we will incorporate the new handoff process into the clinical work of all providers in the study units. Evaluation: Using the same methods employed in the needs assessment phase, we will evaluate use of the new handoff process. Data analysis: The primary effectiveness outcome is the number of information omissions per handoff episode as compared to the pre-intervention period. Additional intervention outcomes include patient intensive care unit length of stay and intensive care unit mortality. The primary implementation outcome is acceptability of the new process. Additional implementation outcomes include feasibility, fidelity and sustainability. Discussion: The HATRICC study will examine the effectiveness and implementation of a standardized operating room to intensive care unit handoff process. Findings from this study have the potential to improve healthcare communication and outcomes for critically ill patients. Trial registration: ClinicalTrials.gov identifier: NCT02267174. Date of registration October 16, 2014. PublicationPredictors of Community Therapists' Use of Therapy Techniques in a Large Public Mental Health System(2015-04-01) Beidas, Rinad S; Marcus, Steven C; Aarons, Gregory; Hoagwood, Kimberly; Schoenwald, Sonja; Evans, Arthur C; Hurford, Matthew O; Hadley, Trevor; Barg, Frances K; Walsh, Lucia M; Adams, Danielle R; Mandell, David SImportance Few studies have examined the effects of individual and organizational characteristics on the use of evidence-based practices in mental health care. Improved understanding of these factors could guide future implementation efforts to ensure effective adoption, implementation, and sustainment of evidence-based practices. Objective To estimate the relative contribution of individual and organizational factors on therapist self-reported use of cognitive-behavioral, family, and psychodynamic therapy techniques within the context of a large-scale effort to increase use of evidence-based practices in an urban public mental health system serving youth and families. Design, Setting, and Participants In this observational, cross-sectional study of 23 organizations, data were collected from March 1 through July 25, 2013. We used purposive sampling to recruit the 29 largest child-serving agencies, which together serve approximately 80% of youth receiving publically funded mental health care. The final sample included 19 agencies with 23 sites, 130 therapists, 36 supervisors, and 22 executive administrators. Main Outcomes and Measures Therapist self-reported use of cognitive-behavioral, family, and psychodynamic therapy techniques, as measured by the Therapist Procedures Checklist–Family Revised. Results Individual factors accounted for the following percentages of the overall variation: cognitive-behavioral therapy techniques, 16%; family therapy techniques, 7%; and psychodynamic therapy techniques, 20%. Organizational factors accounted for the following percentages of the overall variation: cognitive-behavioral therapy techniques, 23%; family therapy techniques, 19%; and psychodynamic therapy techniques, 7%. Older therapists and therapists with more open attitudes were more likely to endorse use of cognitive-behavioral therapy techniques, as were those in organizations that had spent fewer years participating in evidence-based practice initiatives, had more resistant cultures, and had more functional climates. Women were more likely to endorse use of family therapy techniques, as were those in organizations employing more fee-for-service staff and with more stressful climates. Therapists with more divergent attitudes and less knowledge about evidence-based practices were more likely to use psychodynamic therapy techniques. Conclusions and Relevance This study suggests that individual and organizational factors are important in explaining therapist behavior and use of evidence-based practices, but the relative importance varies by therapeutic technique. PublicationThe Biochemical Anatomy of Cortical Inhibitory Synapses(2012-01-01) Heller, Elizabeth A; Zhang, Wenzhu; Selimi, Fekrije; Earnheart, John C; Ślimak, Marta A; Santos-Torres, Julio; Ibañez-Tallon, Ines; Aoki, Chiye; Chait, Brian T; Heintz, NathanielClassical electron microscopic studies of the mammalian brain revealed two major classes of synapses, distinguished by the presence of a large postsynaptic density (PSD) exclusively at type 1, excitatory synapses. Biochemical studies of the PSD have established the paradigm of the synapse as a complex signal-processing machine that controls synaptic plasticity. We report here the restuls of a proteomic analysis of type 2, inhibitory synaptic complexes isolated by affinity purification from the cerebral cortex. We show that these synaptic complexes contain a variety of neurotransmitter receptors, neural cell-scaffolding and adhesion molecules, but that they are entirely lacking in cell signaling proteins. This fundamental distinction between the functions of type 1 and type 2 synapses in the nervous system has far reaching implications for models of synaptic plasticity, rapid adaptations in neural circuits, and homeostatic mechanisms controlling the balance of excitation and inhibition in the mature brain. PublicationSIRT1-FOXO3a Regulate Cocain Actions in the Nucleus Accumbens(2015-02-18) Ferguson, Deveroux; Shao, Ningyi; Heller, Elizabeth A; Feng, Jian; Neve, Rachael L; Kim, Hee-Dae; Shen, Li; Nestler, Eric JPrevious studies have shown that chronic cocain administration induces SIRT1, a Class III histone deacetylase, in the nucleus accumbens (NAc), a key brain reward region, and that such induction influences the gene regulation and place conditioning effects of cocaine. To determine the mechanisms by which SIRT1 mediates cocaine-induced plasticity in NAc, we used chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-seq), 1 d after 7 daily cocain (20 mg/kg) or saline injections, to map SIRT1 binding genome-wide in mouse NAc. Our unbiased results revealed two modes of SIRT1 action. First, despite its induction in NAc, chronic cocain causes depletion of SIRT1 from most affected gene promoters in concert with enrichment of H4K16ac (itself a deacetylation target of SIRT1), which is associated with increased expression of these genes. Second, we deduced the forkhead transcription factor (FOXO) familty to be a downstream mechanis through which SIRT1 regulates cocaine action. We proceeded to demonstrate that SIRT1 induction causes the deacetylation and activation of FOXO3a in NAc, which leads to the induction of several known FOXO3a gene targets in other systems. Finally, we directly establish a role for FOXO3a in promoting cocaine-elicited behavioral responses by use of viral-mediated gene transfer: we show that overexpressing FOXO3a in NAc enhances cocaine place conditioning. The discovery of these two actions of SIRT1 in NAc in the context of behavioral adaptations to cocaine represents an important step forward in advancing our understanding of the molecular adaptations underlying cocaine action. PublicationA Complementary Marriage of Perspectives: Understanding Organizational Social Context Using Mixed Methods(2014-01-01) Beidas, Rinad S; Wolk, Courtney L B; Walsh, Lucia M; Evans, Arthur C; Hurford, Matthew O; Barg, Frances KBackground: Organizational factors impact the delivery of mental health services in community settings. Mixed-methods analytic approaches have been recommended, though little research within implementation science has explicitly compared inductive and deductive perspectives to understand their relative value in understanding the same constructs. The purpose of our study is to use two different paradigmatic approaches to deepen our understanding of organizational social context. We accomplish this by using a mixed-methods approach in an investigation of organizational social context in community mental health clinics. Methods: Nineteen agencies, representing 23 sites, participated. Enrolled participants included 130 therapists, 36 supervisors, and 22 executive administrators. Quantitative data was obtained via the Organizational Social Context (OSC) measure. Qualitative data, comprised of direct observation with spot sampling generated from agency visits, was coded using content analysis and grounded theory. The present study examined elements of organizational social context that would have been missed if only quantitative data had been obtained and utilized mixed methods to investigate if stratifying observations based on quantitative ratings from the OSC resulted in the emergence of differential themes. Results: Four of the six OSC constructs were commonly observed in field observations (i.e., proficiency, rigidity, functionality, stress), while the remaining two constructs were not frequently observed (i.e., resistance, engagement). Constructs emerged related to organizational social context that may have been missed if only quantitative measurement was employed, including those around the physical environment, commentary about evidence-based practice initiatives, leadership, cultural diversity, distrust, and affect. Stratifying agencies by “best,” “average,” and “worst” organizational social context impacted interpretation for three constructs (affect, stress, and leadership). Conclusions: Results support the additive value of integrating inductive and deductive perspectives in implementation science research. This synthesis of approaches facilitated a more comprehensive understanding and interpretation of the findings than would have been possible if either methodology had been employed in isolation. PublicationSustaining Clinician Penetration, Attitudes and Knowledge in Cognitive-Therapy for Youth Anxiety(2014-01-01) Edmunds, Julie M; Read, Kendra L; Ringle, Vanesa A; Brodman, Douglas M; Kendall, Phillip C; Beidas, Rinad SBackground: Questions remain regarding the sustainment of evidence-based practices following implementation. The present study examined the sustainment of community clinicians’ implementation (i.e., penetration) of cognitive-behavioral therapy, attitudes toward evidence-based practices, and knowledge of cognitive-behavioral therapy for youth anxiety two years following training and consultation in cognitive-behavioral therapy for youth anxiety. Methods: Of the original 115 participants, 50 individuals (43%) participated in the two-year follow-up. A t- test examined sustainment in penetration over time. Hierarchical linear modeling examined sustainment in knowledge and attitudes over time. Time spent in consultation sessions was examined as a potential moderator of the change in knowledge and attitudes. Results: Findings indicated sustained self-reported penetration of cognitive-behavioral therapy for anxious youth, with low fidelity to some key CBT components (i.e., exposure tasks). Follow-up knowledge was higher than at baseline but lower than it had been immediately following the consultation phase of the study. Belief in the utility of evidence-based practices was sustained. Willingness to implement an evidence-based practice if required to do so, appeal of evidence-based practices, and openness toward evidence-based practices were not sustained. Participation in consultation positively moderated changes in knowledge and some attitudes. Conclusions: Sustainment varied depending on the outcome examined. Generally, greater participation in consultation predicted greater sustainment. Implications for future training include higher dosages of consultation. PublicationRelationships between Clinician-Level Attributes and Fidelity-Consistent and Fidelity-Inconsistent Modifications to an Evidence-Based Psychotherapy(2015-01-01) Stirman, Shannon W; Gutner, Cassidy A; Crits-Christoph, Paul F; Edmunds, Julie; Evans, Arthur C; Beidas, Rinad SBackground: Clinicians often modify evidence-based psychotherapies (EBPs) when delivering them in routine care settings. There has been little study of factors associated with or implications of modifications to EBP protocols. This paper differentiates between fidelity-consistent and fidelity-inconsistent modifications and it examines the potential influence of two clinician characteristics, training outcomes, and attitudes toward EBPs on fidelity-consistent and fidelity-inconsistent modifications of cognitive behavioral therapy in a sample of clinicians who had been trained to deliver these treatments for children or adults. Methods: Survey and coded interview data collected 2 years after completion of training programs in cognitive behavioral therapy were used to examine associations between successful or unsuccessful completion of training, clinician attitudes, and modifications. Modifications endorsed by clinicians were categorized as fidelity-consistent or fidelity-inconsistent and entered as outcomes into separate regression models, with training success and attitudes entered as independent variables. Results: Successful completion of a training program was associated with subsequent fidelity-inconsistent modifications but not fidelity-consistent modifications. Therapists who reported greater openness to using EBPs prior to training reported more fidelity-consistent modifications at follow-up, and those who reported greater willingness to adopt EBPs if they found them appealing were more likely to make fidelity-inconsistent modifications. Conclusions: Implications of these findings for training, implementation, EBP sustainment, and future studies are discussed. Research on contextual and protocol-related factors that may impact decisions to modify EBPs will be an important future direction of study to complement to this research.