Faculty Bibliography
Searched for:
school:SOM
Department/Unit:Child and Adolescent Psychiatry
Total Results:
11196
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
Intolerance of uncertainty across stress, anxiety, and depression among university students in Pakistan: A descriptive cross-sectional study
BACKGROUND/UNASSIGNED:The mental health issues due to COVID-19, such as intolerance of uncertainty (IOU), anxiety, stress, and depression, have attracted extensive attention from researchers. The challenges for Pakistani university students could be worse than developed countries due to the lack of online courses/programs and online mental health support provided by academic institutions. Therefore, the current study aims to assess the intolerance of uncertainty, depression, anxiety, and stress of Pakistani university students after the second wave of COVID-19 and the relationship among these constructs. METHODS/UNASSIGNED:A convenience cross-sectional sampling method was used to collect data from university students in Pakistan between January 2021 and April 2022 via a structured online questionnaire. The Descriptive analysis focused on frequencies, percentages, mean, and standard deviation (SD) were calculated on IOU-12 and DASS-21. Covariance for the research model and confirmatory factor analyses fit indices for the IOU-12 and DASS-21 were analyzed by AMOS statistical packages. RESULTS/UNASSIGNED:As expected, anxiety, depression, and stress persist among Pakistani university students. On average, they report mild to moderate mental health problems regarding anxiety, depression, stress, and intolerance of uncertainty. Our results indicate a strong positive relationship among the three emotional distress components - anxiety, depression, and stress. However, our results suggest no significant relationship between IOU and the three subcomponents of emotional distress (anxiety, depression, and stress). LIMITATIONS/UNASSIGNED:First, the cross-sectional survey design means we cannot conclude on the causal relations. Second, the self-report questionnaire embeds subjectivity issues. Last, the generalizability of the sample to the whole student population in Pakistan is limited, considering the sampling method. CONCLUSION/UNASSIGNED:This study expanded the current knowledge in the psychological health domain (intolerance of uncertainty, anxiety, depression, and stress) due to the COVID-19 pandemic. In practice, higher education institutions should further mitigate university students' mental health issues. For researchers, our findings inspire future studies to delve into the relationship between IOU and mental health issues due to COVID-19 since our findings display contrary evidence for various reasons.
PMCID:10238721
PMID: 37274650
ISSN: 2405-8440
CID: 5742922
World psychiatry : official journal of the World Psychiatric Association (WPA). 2023:22(2):335-337.DOI: 10.1002/wps.21097
First evidence of a general disease ("d") factor, a common factor underlying physical and mental illness [Letter]
PMCID:10168148
PMID: 37159369
ISSN: 1723-8617
CID: 5509642
Antagonistic circuits mediating infanticide and maternal care in female mice
In many species, including mice, female animals show markedly different pup-directed behaviours based on their reproductive state1,2. Naive wild female mice often kill pups, while lactating female mice are dedicated to pup caring3,4. The neural mechanisms that mediate infanticide and its switch to maternal behaviours during motherhood remain unclear. Here, on the basis of the hypothesis that maternal and infanticidal behaviours are supported by distinct and competing neural circuits5,6, we use the medial preoptic area (MPOA), a key site for maternal behaviours7-11, as a starting point and identify three MPOA-connected brain regions that drive differential negative pup-directed behaviours. Functional manipulation and in vivo recording reveal that oestrogen receptor α (ESR1)-expressing cells in the principal nucleus of the bed nucleus of stria terminalis (BNSTprESR1) are necessary, sufficient and naturally activated during infanticide in female mice. MPOAESR1 and BNSTprESR1 neurons form reciprocal inhibition to control the balance between positive and negative infant-directed behaviours. During motherhood, MPOAESR1 and BNSTprESR1 cells change their excitability in opposite directions, supporting a marked switch of female behaviours towards the young.
PMID: 37286598
ISSN: 1476-4687
CID: 5538312
Examining the Rationale for Studying Psychedelic-Assisted Psychotherapy for the Treatment of Caregiver Distress
BACKGROUND/UNASSIGNED:More than 50 million people in the United States serve as uncompensated informal caregivers to chronically ill friends or family members. Providing care to a sick loved one can contribute to personal growth but can also cause significant strain. Caregiver distress refers to a constellation of physiological, psychological, interpersonal, and spiritual impairments that typically result when an individual's own health becomes affected while caring for another. Caregiver distress is highly prevalent, affecting an estimated 30-70% of individuals across various caregiver populations. Although evidence-based treatments for caregiver distress exist, they do not sufficiently address all its components. In recent years, clinical trials have demonstrated that psychedelic-assisted psychotherapy (PAP) may have applications for treating a range of medical and psychiatric conditions that have significant overlap in symptoms to those seen in caregiver distress. While no studies to date have examined PAP for caregiver distress, this article provides a rationale for investigating PAP as a potential novel treatment for this indication. METHODS/UNASSIGNED:A narrative review on the effects and clinical applications of PAP that significantly overlap with the dimensions of caregiver distress was conducted. Safety considerations, psychedelic selection, and therapeutic structure for studying PAP in the treatment of caregiver distress were also examined. RESULTS/UNASSIGNED:Psychologically, PAP has been shown to treat anxiety, depression, and reduce suicidal ideation. Physiologically, evidence suggests that psychedelics have anti-inflammatory properties, which may aid caregivers suffering from chronic inflammation. Interpersonally, PAP has been demonstrated to enhance feelings of empathy, connectedness, and strengthen social relationships, which can often become strained while caregiving. Spiritually, PAP has been shown to ameliorate existential distress and hopelessness in cancer patients, which may similarly benefit demoralized caregivers. CONCLUSION/UNASSIGNED:PAP has the potential to comprehensively treat all biopsychosocial-spiritual dimensions of caregiver distress.
PMCID:11658675
PMID: 40046728
ISSN: 2831-4433
CID: 5835002
