Faculty Bibliography
Searched for:
school:SOM
Department/Unit:Child and Adolescent Psychiatry
Total Results:
11550
A century of research on neuromodulation interventions: A scientometric analysis of trends and knowledge maps
Interest in neurostimulation interventions has significantly grown in recent decades, yet a scientometric analysis objectively mapping scientific knowledge and recent trends remains unpublished. Using relevant keywords, we conducted a search in the Web of Science Core Collection on September 23, 2022, retrieving a total of 47,681 documents with 987,979 references. We identified two prominent research trends: 'noninvasive brain stimulation' and 'invasive brain stimulation.' These methods have interconnected over time, forming a cluster focused on evidence synthesis. Noteworthy emerging research trends encompassed 'transcutaneous auricular vagus nerve stimulation,' 'DBS/epilepsy in the pediatric population,' 'spinal cord stimulation,' and 'brain-machine interface.' While progress has been made for various neurostimulation interventions, their approval as adjuvant treatments remains limited, and optimal stimulation parameters lack consensus. Enhancing communication between experts of both neurostimulation types and encouraging novel translational research could foster further development. These findings offer valuable insights for funding agencies and research groups, guiding future directions in the field.
PMID: 37392815
ISSN: 1873-7528
CID: 5540682
A platform trial of neoadjuvant and adjuvant antitumor vaccination alone or in combination with PD-1 antagonist and CD137 agonist antibodies in patients with resectable pancreatic adenocarcinoma
A neoadjuvant immunotherapy platform clinical trial allows for rapid evaluation of treatment-related changes in tumors and identifying targets to optimize treatment responses. We enrolled patients with resectable pancreatic adenocarcinoma into such a platform trial (NCT02451982) to receive pancreatic cancer GVAX vaccine with low-dose cyclophosphamide alone (Arm A; n = 16), with anti-PD-1 antibody nivolumab (Arm B; n = 14), and with both nivolumab and anti-CD137 agonist antibody urelumab (Arm C; n = 10), respectively. The primary endpoint for Arms A/B - treatment-related change in IL17A expression in vaccine-induced lymphoid aggregates - was previously published. Here, we report the primary endpoint for Arms B/C: treatment-related change in intratumoral CD8+ CD137+ cells and the secondary outcomes including safety, disease-free and overall survivals for all Arms. Treatment with GVAX+nivolumab+urelumab meets the primary endpoint by significantly increasing intratumoral CD8+ CD137+ cells (p = 0.003) compared to GVAX+Nivolumab. All treatments are well-tolerated. Median disease-free and overall survivals, respectively, are 13.90/14.98/33.51 and 23.59/27.01/35.55 months for Arms A/B/C. GVAX+nivolumab+urelumab demonstrates numerically-improved disease-free survival (HR = 0.55, p = 0.242; HR = 0.51, p = 0.173) and overall survival (HR = 0.59, p = 0.377; HR = 0.53, p = 0.279) compared to GVAX and GVAX+nivolumab, respectively, although not statistically significant due to small sample size. Therefore, neoadjuvant and adjuvant GVAX with PD-1 blockade and CD137 agonist antibody therapy is safe, increases intratumoral activated, cytotoxic T cells, and demonstrates a potentially promising efficacy signal in resectable pancreatic adenocarcinoma that warrants further study.
PMCID:10281953
PMID: 37339979
ISSN: 2041-1723
CID: 5538452
Examining the Rationale for Studying Psychedelic-Assisted Psychotherapy for the Treatment of Caregiver Distress
ORIGINAL:0016990
ISSN: 2831-4425
CID: 5525822
Non-pharmacological management of infant and young child procedural pain
BACKGROUND:Despite evidence of the long-term implications of unrelieved pain during infancy, it is evident that infant pain is still under-managed and unmanaged. Inadequately managed pain in infancy, a period of exponential development, can have implications across the lifespan. Therefore, a comprehensive and systematic review of pain management strategies is integral to appropriate infant pain management. This is an update of a previously published review update in the Cochrane Database of Systematic Reviews (2015, Issue 12) of the same title. OBJECTIVES:To assess the efficacy and adverse events of non-pharmacological interventions for infant and child (aged up to three years) acute pain, excluding kangaroo care, sucrose, breastfeeding/breast milk, and music. SEARCH METHODS:= 74%, substantial heterogeneity), based on low- to moderate-certainty evidence. Of these five interventions most studied, only two studies observed adverse events, specifically vomiting (one preterm neonate) and desaturation (one full-term neonate hospitalised in the NICU) following the non-nutritive sucking intervention. The presence of considerable heterogeneity limited our confidence in the findings for certain analyses, as did the preponderance of evidence of very low to low certainty based on GRADE judgements. AUTHORS' CONCLUSIONS:Overall, non-nutritive sucking, facilitated tucking, and swaddling may reduce pain behaviours in preterm born neonates. Non-nutritive sucking may also reduce pain behaviours in full-term neonates. No interventions based on a substantial body of evidence showed promise in reducing pain behaviours in older infants. Most analyses were based on very low- or low-certainty grades of evidence and none were based on high-certainty evidence. Therefore, the lack of confidence in the evidence would require further research before we could draw a definitive conclusion.
PMID: 37314064
ISSN: 1469-493x
CID: 5642042
Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection
IMPORTANCE:SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals. OBJECTIVE:To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections. DESIGN, SETTING, AND PARTICIPANTS:Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling. EXPOSURE:SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES:PASC and 44 participant-reported symptoms (with severity thresholds). RESULTS:A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months. CONCLUSIONS AND RELEVANCE:A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.
PMID: 37278994
ISSN: 1538-3598
CID: 5536662
An AAV-CRISPR/Cas9 strategy for gene editing across divergent rodent species: Targeting neural oxytocin receptors as a proof of concept
A major issue in neuroscience is the poor translatability of research results from preclinical studies in animals to clinical outcomes. Comparative neuroscience can overcome this barrier by studying multiple species to differentiate between species-specific and general mechanisms of neural circuit functioning. Targeted manipulation of neural circuits often depends on genetic dissection, and use of this technique has been restricted to only a few model species, limiting its application in comparative research. However, ongoing advances in genomics make genetic dissection attainable in a growing number of species. To demonstrate the potential of comparative gene editing approaches, we developed a viral-mediated CRISPR/Cas9 strategy that is predicted to target the oxytocin receptor (Oxtr) gene in >80 rodent species. This strategy specifically reduced OXTR levels in all evaluated species (n = 6) without causing gross neuronal toxicity. Thus, we show that CRISPR/Cas9-based tools can function in multiple species simultaneously. Thereby, we hope to encourage comparative gene editing and improve the translatability of neuroscientific research.
PMID: 37256960
ISSN: 2375-2548
CID: 5541222
The impact of medical students on work after clinic for neurology preceptors
Objective: To determine whether medical students significantly impact preceptor physicians"™ clinic volume and work after clinic (WAC), we compared the time to note completion and the number of patients seen per hour (PPH) for outpatient neurologists with and without students present in their clinic. Methods: Outpatient neurologists (n = 47) involved in the Johns Hopkins Neurology Clerkship from 2015 to 2017 were included. WAC for each patient encounter was calculated as the interval between the date and time of a scheduled patient appointment and the time of clinic note completion. The number of patient encounters per scheduled clinic hour (PPH) was also calculated for each preceptor. Measurements were compared for each preceptor, serving as their own control, to account for variability in efficiency between preceptors. Results: There was no statistically significant difference in WAC or PPH for individual preceptors with and without students (WAC p-value = 0.837; PPH p-value = 0.139). Preceptors did see significantly more patients per day with students than without (6.28 with students, 5.07 without students, p-value <0.001). Conclusions: In this study, assigning a student to an outpatient ambulatory clinic did not significantly increase work after clinic. In addition, students did not significantly alter the number of patients faculty saw per hour. Public Interest Summary: Both medical students and educators have highlighted the importance of greater student involvement in clinic in providing a valuable outpatient educational experience, but it is often difficult for academic programs to recruit physician preceptors willing to teach and actively involve students in outpatient clinics. This study shows that medical student presence in clinic does not delay physician preceptors"™ note completion and is not associated with less patients seen. To further optimize the outpatient educational and efficiency model, it is important for future investigations to evaluate training programs that enhance the efficacy of a student in clinic, particularly for students with less outpatient experience. This could encourage more preceptors to involve medical students in their clinic, potentially increasing student competence and interest in outpatient medicine.
SCOPUS:85159206214
ISSN: 2211-8837
CID: 5501532
Human CCR6+ Th Cells Show Both an Extended Stable Gradient of Th17 Activity and Imprinted Plasticity
Th17 cells have been investigated in mice primarily for their contributions to autoimmune diseases. However, the pathways of differentiation of Th17 and related Th cells (type 17 cells) and the structure of the type 17 memory population in humans are not well understood; such understanding is critical for manipulating these cells in vivo. By exploiting differences in levels of surface CCR6, we found that human type 17 memory cells, including individual T cell clonotypes, form an elongated continuum of type 17 character along which cells can be driven by increasing RORγt. This continuum includes cells preserved within the memory pool with potentials that reflect the early preferential activation of multiple over single lineages. The phenotypes and epigenomes of CCR6+ cells are stable across cell divisions under noninflammatory conditions. Nonetheless, activation in polarizing and nonpolarizing conditions can yield additional functionalities, revealing, respectively, both environmentally induced and imprinted mechanisms that contribute differentially across the type 17 continuum to yield the unusual plasticity ascribed to type 17 cells.
PMID: 37093875
ISSN: 1550-6606
CID: 5944702
Autism spectrum disorder and congenital heart disease: a narrative review of the literature
Individuals born with congenital heart disease (CHD) are at an increased risk of developing neurodevelopmental disorders. Despite this, studies are limited in their investigation of autism spectrum disorder in the context of CHD. This review provides an overview of the literature examining autism spectrum disorder in CHD and discusses strengths, limitations, and future directions. Recent efforts have been made to extrapolate the association between CHD and symptoms of autism. Findings suggest that the core features of autism spectrum disorder are also implicated in children with CHD, namely social-cognitive weaknesses, pragmatic language differences, and social problems. Compared to norm-referenced samples, separate studies have identified divergent and overlapping neuropsychological profiles among both patient groups, yet there are no studies directly comparing the two groups. There is emerging evidence of prevalence rates of autism diagnosis in CHD showing an increased odds of having autism spectrum disorder among children with CHD relative to the general population or matched controls. There also appears to be genetic links to this overlap, with several genes identified as being tied to both CHD and autism. Together, research points to potentially shared underlying mechanisms contributing to the pathophysiology of neurodevelopmental, neuropsychological, and clinical traits in CHD and autism spectrum disorder. Future investigation delineating profiles across these patient populations can fill a significant gap in the literature and aid in treatment approaches to improve clinical outcomes.
PMID: 37231612
ISSN: 1467-1107
CID: 5952862
Common and unique alterations of functional connectivity in major depressive disorder and bipolar disorder
OBJECTIVE:Major depressive disorder (MDD) and bipolar disorder (BD) are considered whole-brain disorders with some common clinical and neurobiological features. It is important to investigate neural mechanisms to distinguish between the two disorders. However, few studies have explored the functional dysconnectivity between the two disorders from the whole brain level. METHODS:In this study, 117 patients with MDD, 65 patients with BD, and 116 healthy controls completed resting-state functional magnetic resonance imaging (R-fMRI) scans. Both edge-based network construction and large-scale network analyses were applied. RESULTS:Results found that both the BD and MDD groups showed decreased FC in the whole brain network. The shared aberrant network across patients involves the visual network (VN), sensorimotor network (SMN), dorsal attention network (DAN), and ventral attention network (VAN), which is related to the processing of external stimuli. The default mode network (DMN) and the limbic network (LN) abnormalities were only found in patients with MDD. Furthermore, results showed the highest decrease in edges of patients with MDD in between-network FC in SMN-VN, whereas in VAN-VN of patients with BD. CONCLUSIONS:Our findings indicated that both MDD and BD are extensive abnormal brain network diseases, mainly aberrant in those brain networks correlated to the processing of external stimuli, especially the attention network. Specific altered functional connectivity also was found in MDD and BD groups, respectively. These results may provide possible trait markers to distinguish the two disorders.
PMID: 37161552
ISSN: 1399-5618
CID: 5509332
