Psychology Internship Training Amidst COVID-19: Balancing Training Opportunities, Patient Care, and Risk of Exposure.

The emergence of the 2019 novel coronavirus (COVID-19) has dramatically altered how psychologists deliver its training. At least for the time being, virtual care has become the primary method for delivering mental health services. This has allowed patients and clinicians to continue to access and provide services in a way that would have been impossible years ago. Not only has this shift impacted patients, but it has also impacted supervision and training. The impact has been especially profound on inpatient units where the psychiatric and medical acuity is high of patients and the therapeutic milieu is an important aspect of treatment. The purpose of this paper is to review the impact of COVID-19 on pre-doctoral psychology interns during their rotation on an inpatient psychiatry unit at the start of the pandemic (January to June of 2020) and use these experiences to onboard the next class of interns in the new academic year (July 2020 to June 2021) using a hybrid model of in-person and virtual training experiences. At the end of 2020/2021 rotation, we voluntarily asked interns to complete a questionnaire that was developed based on the qualitative experiences of the previous class to assess the effectiveness of this hybrid model. We also surveyed multi-disciplinary staff members who were essential personnel and required to work in person during this time about their experiences of safety and support. With this information, we explore and offer guidance to other inpatient training sites who are likely to encounter similar challenges during this time. In particular, we discuss the integration of virtual technology into this training experience, as well as the restructuring of clinical and supervisory experiences. We highlighted several short-term strategies that we have flexibly adapted to our inpatient unit. The lessons learned herein seek to guide supervisors and trainees alike in adapting their psychology training programs to meet the evolving demands of COVID-19.

Safety, Tolerability, and Immunogenicity of the ACI-24 Vaccine in Adults With Down Syndrome: A Phase 1b Randomized Clinical Trial.

Importance: Individuals with Down syndrome (DS) are at high risk of developing Alzheimer disease due to an increased dose of the amyloid precursor protein gene, APP, which leads to increased levels of full-length APP and its products, including amyloid-ß (Aß). The liposome-based antiamyloid ACI-24 vaccine is intended to treat neurological disorders caused by misfolded Aß pathological protein. However, the safety, tolerability, and immunogenicity of the ACI-24 vaccine among adults with DS have not been fully examined. Objective: To assess the safety and tolerability of the ACI-24 vaccine among adults with DS as well as its ability to induce immunogenicity measured by anti-Aß immunoglobulin G titers. Design, Setting, and Participants: This multicenter double-blind placebo-controlled dose-escalation phase 1b randomized clinical trial was conducted at 3 US academic medical centers with affiliated Down syndrome clinics between March 30, 2016, and June 29, 2020. A total of 20 adults with DS were screened; of those, 16 adults were eligible to participate. Eligibility criteria included men or women aged 25 to 45 years with cytogenetic diagnosis of either trisomy 21 or complete unbalanced translocation of chromosome 21. Between April 27, 2016, and July 2, 2018, participants were randomized 3:1 into 2 dose-level cohorts (8 participants per cohort, with 6 participants receiving the ACI-24 vaccine and 2 receiving placebo) in a 96-week study. Participants received 48 weeks of treatment followed by an additional 48 weeks of safety follow-up. Interventions: Participants were randomized to receive 7 subcutaneous injections of ACI-24, 300 µg or 1000 µg, or placebo. Main Outcomes and Measures: Primary outcomes were measures of safety and tolerability as well as antibody titers. Results: Among 16 enrolled participants, the mean (SD) age was 32.6 (4.4) years; 9 participants were women, and 7 were men. All participants were White, and 1 participant had Hispanic or Latino ethnicity. Treatment adherence was 100%. There were no cases of meningoencephalitis, death, or other serious adverse events (AEs) and no withdrawals as a result of AEs. Most treatment-emergent AEs were of mild intensity (110 of 132 events [83.3%]) and unrelated or unlikely to be related to the ACI-24 vaccine (113 of 132 events [85.6%]). No amyloid-related imaging abnormalities with edema or cerebral microhemorrhage and no evidence of central nervous system inflammation were observed on magnetic resonance imaging scans. Increases in anti-Aß immunoglobulin G titers were observed in 4 of 12 participants (33.3%) receiving ACI-24 (2 receiving 300 µg and 2 receiving 1000 µg) compared with 0 participants receiving placebo. In addition, a greater increase was observed in plasma Aß1-40 and Aß1-42 levels among individuals receiving ACI-24. Conclusions and Relevance: In this study, the ACI-24 vaccine was safe and well tolerated in adults with DS. Evidence of immunogenicity along with pharmacodynamic and target engagement were observed, and anti-Aß antibody titers were not associated with any adverse findings. These results support progression to clinical trials using an optimized formulation of the ACI-24 vaccine among individuals with DS. Trial Registration: ClinicalTrials.gov Identifier: NCT02738450.

Factors in the neurodevelopment of negative urgency: Findings from a community-dwelling sample.

This study investigated neuroanatomic, genetic, cognitive, sociodemographic and emotional underpinnings of the Negative Urgency subscale of the Urgency, Premeditation, Perseverance, Sensation-Seeking and Positive Urgency Impulsive Behavior Scale in a healthy developmental sample. The goal of the investigation is to contribute to the harmonisation of behavioural, brain and neurogenetic aspects of behavioural self-control. Three domains - (1) Demographic, developmental, psychiatric and cognitive ability; (2) Regional brain volumes (neurobiological); and (3) Genetic variability (single nucleotide polymorphisms) - were examined, and models with relevant predictor variables were selected. Least absolute shrinkage and selection operator and best subset regressions were used to identify sparse models predicting negative urgency scores, which revealed that variables related to emotional regulation and right cingulate volume, as well as single nucleotide polymorphisms in CADM2 and SLC6A4, were associated with negative urgency. Our results contribute to the construct and criterion validity of negative urgency and support the hypothesis that negative urgency is a result of a complex array of influences across domains whose integration furthers developmental psychopathology research.

Cross-Sectional Exploration of Plasma Biomarkers of Alzheimer's Disease in Down Syndrome: Early Data from the Longitudinal Investigation for Enhancing Down Syndrome Research (LIFE-DSR) Study.

With improved healthcare, the Down syndrome (DS) population is both growing and aging rapidly. However, with longevity comes a very high risk of Alzheimer's disease (AD). The LIFE-DSR study (NCT04149197) is a longitudinal natural history study recruiting 270 adults with DS over the age of 25. The study is designed to characterize trajectories of change in DS-associated AD (DS-AD). The current study reports its cross-sectional analysis of the first 90 subjects enrolled. Plasma biomarkers phosphorylated tau protein (p-tau), neurofilament light chain (NfL), amyloid ß peptides (Aß1-40, Aß1-42), and glial fibrillary acidic protein (GFAP) were undertaken with previously published methods. The clinical data from the baseline visit include demographics as well as the cognitive measures under the Severe Impairment Battery (SIB) and Down Syndrome Mental Status Examination (DS-MSE). Biomarker distributions are described with strong statistical associations observed with participant age. The biomarker data contributes to understanding DS-AD across the spectrum of disease. Collectively, the biomarker data show evidence of DS-AD progression beginning at approximately 40 years of age. Exploring these data across the full LIFE-DSR longitudinal study population will be an important resource in understanding the onset, progression, and clinical profiles of DS-AD pathophysiology.

Proton Radiation Therapy for Pediatric Craniopharyngioma.

BACKGROUND: Radiation therapy (RT) is used for pediatric craniopharyngioma in the definitive, adjuvant, or salvage settings. Proton RT may be useful owing to tumor proximity to eloquent anatomy. We report clinical outcomes for a large cohort treated with proton therapy. METHODS: We conducted a retrospective review of pediatric patients (≤21 years) treated with surgery and proton therapy for craniopharyngioma between August 2002 and October 2018. Clinical characteristics, treatment course, and outcomes were recorded. Acute toxicity was graded using Common Terminology Criteria for Adverse Events, version 5.0. Late toxicity was assessed using neuroendocrine, neuro-ophthalmologic, and neuropsychological testing. RESULTS: Among 77 patients, median age at diagnosis was 8.6 years (range, 1.3-20); median age at radiation was 9.6 years (range, 2.3-20.5). Most common presenting symptoms were headache (58%), visual impairment (55%), and endocrinopathy (40%). Patients underwent a median of 2 surgical interventions (range, 1-7) before protons. At initial surgery, 18% had gross total resection, 60% had subtotal resection, and 22% had biopsy/cyst decompression. Median RT dose was 52.2 Gy (relative biologic effectiveness). Common acute toxicities were headache (29%), fatigue (35%), and nausea/vomiting (12%). Only 4% developed any acute grade 3 toxicity. Nine patients experienced cyst growth requiring replanning or surgical decompression. At a median of 4.8 years from RT (range, 0.8-15.6), there were 6 local failures and 3 deaths, 2 related to disease progression. Effect of tumor and treatment contributed to late toxicity including Moyamoya syndrome (13%), visual impairment (40%), and endocrine deficiency requiring hormone replacement (94%). Subclinical decline in functional independence and adaptive skills in everyday life was detected at follow-up. CONCLUSIONS: Surgery and proton therapy results in excellent disease control for pediatric craniopharyngioma. Severe acute toxicity is rare. Late toxicities from tumor, surgery, and radiation remain prevalent. Endocrine and ophthalmology follow-up is necessary, and neuropsychological testing may identify patients at risk for treatment-related cognitive and adaptive functioning changes.

Language skills as a predictor of cognitive decline in adults with Down syndrome.

INTRODUCTION: Adults with Down syndrome (DS) are at high risk for early onset Alzheimer's disease (AD), characterized by a progressive decline in multiple cognitive domains including language, which can impact social interactions, behavior, and quality of life. This cross-sectional study examined the relationship between language skills and dementia. METHODS: A total of 168 adults with DS (mean age = 51.4 years) received neuropsychological assessments, including Vineland Communication Domain, McCarthy Verbal Fluency, and Boston Naming Test, and were categorized in one of three clinical groups: cognitively stable (CS, 57.8%); mild cognitive impairment (MCI-DS, 22.6%); and probable/definite dementia (AD-DS, 19.6%). Logistic regression was used to determine how well language measures predict group status. RESULTS: Vineland Communication, particularly receptive language, was a significant predictor of MCI-DS. Semantic verbal fluency was the strongest predictor of AD-DS. DISCUSSION: Assessment of language skills can aid in the identification of dementia in adults with DS. Clinically, indications of emerging language problems should warrant further evaluation and monitoring.

Effect of Opioid Prescribing Education for Obstetrics and Gynecology Residents in a Safety-Net Hospital.

CONTEXT: The number of deaths due to opioid overdose has steadily increased in the United States since the early 2000s. The US opioid epidemic calls for an urgent need to evaluate physician prescribing habits. OBJECTIVE: To educate obstetrics and gynecology residents about opioid abuse, the quantity typically prescribed postoperatively, and strategies to decrease adverse outcomes. METHODS: Obstetrics and gynecology residents at an urban safety-net hospital were given a preintervention evaluation to understand their opioid prescribing patterns and use of resources like prescription drug monitoring programs and opioid risk tool. Residents then attended a didactic session reviewing rates of adverse outcomes from overprescribing, resources to reduce adverse outcomes, and the number of opioids considered appropriate postoperatively. Residents completed an immediate postintervention evaluation to reevaluate prescribing patterns. RESULTS: Pre- and postintervention evaluations were completed by 13 residents. In the preintervention evaluation, all participants reported that they would prescribe at least 30 opioid pills for patients after cesarean delivery, but in the postintervention evaluation, none reported that they would prescribe more than 20 opioid pills (P=<.0001). Similar but less distinct shifts can be seen in laparoscopic hysterectomy and the use of preoperative gabapentinoids (ie, gabapentin and pregabalin). Before the intervention, 7 residents (54%) reported that they currently prescribed 20 opioid pills or more for patients after laparoscopic hysterectomy, whereas after the intervention, 1 resident (7.7%) reported that he or she would prescribe more than 20 opioid pills in (P=.0382). Before the intervention, 2 residents (15.4%) reported that they would consider gabapentinoids compared with 13 residents (100%) after the intervention. CONCLUSION: Focused opioid education can reduce the intended number of opioid pills prescribed in a postoperative setting. This study highlights the effect that educational curricula can have on physician prescribing patterns to help mitigate the current epidemic and help optimize stepwise multimodal analgesia to avoid overprescribing opioids.

A comparison study assessing neuropsychological outcome of patients with post-operative pediatric cerebellar mutism syndrome and matched controls after proton radiation therapy.

PURPOSE: Post-operative pediatric cerebellar mutism syndrome (CMS), characterized by mutism, ataxia/hypotonia, and emotional lability, can result in long-term deficits following resection of posterior fossa (PF) tumors. This longitudinal study compared neuropsychological outcomes of pediatric patients with post-operative CMS to a matched control patient group without CMS. METHODS: Fifty-eight PF tumor patients received post-surgical proton radiation therapy (PRT) and testing at baseline and at ≥ 1-year post-PRT over a 10-year period. Of these, 18 (31%) had post-operative CMS with baseline and follow-up neuropsychological test data. Those participants were matched to 18 controls by tumor location, age, gender, and handedness; no significant group differences were found at baseline for clinical/demographic variables. Total mean age at baseline was 7.26 years (SD = 4.42); mean follow-up interval was 3.26 years (SD = 2.24). Areas assessed: overall intelligence, expressive and receptive vocabulary, visuomotor integration, fine motor speed, inhibition, emotional control, depression, and anxiety. RESULTS: Patients were 52% male; 86% medulloblastoma/14% ependymoma; 86% craniospinal irradiation/14% focal radiation; and 86% chemotherapy. No group differences were found between most mean baseline scores; expressive vocabulary and fine motor speed were significantly lower in the post-operative CMS group (p < 0.05). Mean change scores revealed no significant differences for the sample; scores were within the normal range except fine motor skills were impaired for both groups. CONCLUSIONS: Longitudinal neuropsychological outcomes for post-operative pediatric CMS patients did not differ significantly from matched controls without this condition. Patients were in the normal range in all areas except fine motor speed, which was impaired for both groups independent of CMS diagnosis.

Cognitive and Adaptive Outcomes After Proton Radiation for Pediatric Patients With Brain Tumors.

PURPOSE: Radiation therapy is integral in treatment of pediatric brain tumors, but it is associated with negative long-term sequelae. Proton beam radiation therapy (PRT), which enables better focusing of radiation on tumors, may entail fewer sequelae. This prospective study examined cognitive and adaptive functioning in children and young adults treated with PRT. METHODS AND MATERIALS: A total of 155 patients were assessed using age-appropriate measures for cognitive and adaptive functioning at start of or during PRT (baseline) and at follow-up. Mean age at baseline was 8.9 years; mean follow-up interval was 3.6 years. Diagnoses included medulloblastoma, craniopharyngioma, ependymoma, glial tumors, germ cell tumors, and others. The sample was divided by age at baseline (<6 years [N = 57, or 37%] and ≥6 years [N = 98, or 63%]) and by PRT field (craniospinal irradiation [CSI; 39%] and focal irradiation [61%]). RESULTS: Scores for mean intelligence quotient (IQ) and adaptive functioning skills were in the average range at baseline and follow-up. Overall, mean IQ scores declined from 105.4 to 102.5 (P = .005); however, only the younger CSI group showed significant decline. Patients receiving CSI, regardless of age, appeared particularly vulnerable in IQ, processing speed, and working memory. Adaptive skills were stable across the 4 age-by-treatment field groups. CONCLUSIONS: At a mean of 3.6 years after PRT, IQ declined slightly for the group, largely because of significant IQ decline in younger patients treated with CSI. No significant change was seen in patients <6 years treated with focal PRT or in older patients. Adaptive skills remained stable across age and treatment type.

Left hippocampal dosimetry correlates with visual and verbal memory outcomes in survivors of pediatric brain tumors.

BACKGROUND: Radiotherapy (RT) in the pediatric brain tumor population causes late neurocognitive effects. In the current study, the authors investigated associations between clinical and dosimetric risk factors and memory outcomes in a cohort of patients treated with proton radiotherapy (PRT). METHODS: A total of 70 patients (median age at PRT, 12.1 years [range, 5.0-22.5 years]) who were treated with PRT were identified with baseline and follow-up evaluations of visual and verbal memory (Children's Memory Scale and the third edition of the Wechsler Memory Scale). Whole-brain as well as bilateral hippocampal and temporal lobe contours were delineated for the calculation of dosimetric indices. Multivariate analyses were performed to assess associations of score changes over time with clinical factors and dosimetric indices. RESULTS: The median neurocognitive follow-up was 3.0 years (range, 1.1-11.4 years). For the entire cohort, delayed and immediate verbal memory scaled scores demonstrated small declines. The mean decline for delayed verbal memory scores was 0.6 (P = .01), and that for immediate verbal memory scores was 0.5 (P = .06). Immediate and delayed visual memory scores were not found to change significantly (+0.1 and -0.3, respectively; P>.30). A higher left hippocampal V20GyE (percentage of the volume of a particular anatomical region receiving at least a 20 gray equivalent) was correlated with a score decline in all 4 measures. Female sex was found to be predictive of lower delayed verbal memory follow-up scores (P = .035). CONCLUSIONS: Only delayed verbal memory scores were found to have declined statistically significantly at follow-up after PRT, reflecting some weakness in verbal memory retrieval. Given a correlation of left hippocampal dosimetry and memory outcomes after PRT, left hippocampal-sparing PRT plans may assist patients with pediatric brain tumors in preserving memory-retrieval abilities. Cancer 2018;124:2238-45. © 2018 American Cancer Society.

Executive functioning, academic skills, and quality of life in pediatric patients with brain tumors post-proton radiation therapy.

Radiation therapy (RT) is integral in the treatment of pediatric brain tumors; however, photon RT (XRT) often results in intellectual decline, executive functioning (EF) deficits, academic underachievement/failure, and lower health-related quality of life (HRQoL). Proton RT (PRT) provides more targeted therapy, minimizing damage to the developing brain, yet few studies have examined its neuropsychological effects. This study investigated the role of EF in academic skills and HRQoL in a sample of children treated with PRT. A mediation model was proposed in which academic skills mediated relations between aspects of EF and school-based HRQoL (sHRQoL). Sixty-five children (x̅age = 12.4; 43.9% male) treated with PRT completed follow-up neuropsychological testing as part of routine care. Measures included assessment of intellectual functioning, EF, attention, and academic skills (reading, math, spelling). Parents reported on children's EF and attention problems. sHRQoL was assessed via child self-report. Children who underwent PRT demonstrated relatively intact intelligence, academics, attention, EF, and sHRQoL, but were at risk for reduced processing speed. Poorer working memory and processing speed were related to lower sHRQoL. Better EF and faster processing speed were associated with better academic skills, which were linked to higher sHRQoL. Better working memory was associated with better math performance, which was linked to higher sHRQoL; this relationship did not hold for reading or spelling. Results highlight the importance of EF skills in academic performance and sHRQoL, and the need for routine screening of EF deficits and proactive supports. Supports may include cognitive rehabilitation and in-class accommodations. Overall, results compare favorably to XRT outcomes reported in the literature.

A Randomized, Double-Blind, Placebo-Controlled, Phase II Study of Oral ELND005 (scyllo-Inositol) in Young Adults with Down Syndrome without Dementia.

BACKGROUND: ELND005 (scyllo-Inositol; cyclohexane-1,2,3,4,5,6-hexol) has been evaluated as a potential disease-modifying treatment for Alzheimer's disease (AD). Individuals with Down syndrome (DS) have an increased risk for developing AD dementia. OBJECTIVE: To evaluate the safety and tolerability of ELND005 and to determine its pharmacokinetics (PK) and relationship between PK parameters, safety outcome measures, and exploratory efficacy outcome measures in young adults with DS without dementia. METHODS: This was a prospective, randomized, double-blind, placebo-controlled, parallel-group, three-arm, multicenter Phase II study of the safety and pharmacokinetics of ELND005 administered orally for 4 weeks (ClinicalTrials.gov NCT01791725). Participants who met study eligibility criteria were randomly assigned in a 2 : 1:1 ratio to receive ELND005 at either 250 mg twice daily (BID) or 250 mg once daily (QD) or matching placebo for 4 weeks. RESULTS: There were no apparent treatment group-related trends on cognitive or behavioral measures and there were no SAEs and no deaths in the study. Overall, mean changes from baseline in clinical laboratory parameters, vital sign measurements, electrocardiogram results, and other physical findings were unremarkable. ELND005 accumulation averaged approximately 2-fold with QD dosing, and 3- to 4-fold with BID dosing. CONCLUSION: Overall, treatment of adults with DS with ELND005 at both doses was well tolerated, achieved measurable blood levels and demonstrated no safety findings. Further studies will be needed to test efficacy.