Fentanyl-Related Substance Use Patterns, Morbidity, and Mortality Among Adolescents and Young Adults: Implications for Behavioral Health Services Research.

This commentary discusses best practices for responding to fentanyl-related overdose deaths in adolescents and young adults, and it outlines the current state of knowledge about them. Various types of approaches to fentanyl-related overdoses in this age group may need to be developed based on the different risk factors that are emerging from the existing data. We describe the National Institute on Drug Abuse (NIDA) behavioral health services research priorities connected with fentanyl-related overdoses in youth. We highlight a key target for intervention and discuss research opportunities related to early intervention with youth with identifiable risk factors. NIDA's research agenda is a means of assisting communities that experience fentanyl-related overdoses by providing scientific information that can be translated into clear recommendations for public action.

Digital Media-related Problems Contributing to Psychiatric Hospitalizations Among Children and Adolescents Before and After the Onset of the COVID-19 Pandemic.

The role of digital media in crises leading to youth psychiatric admissions is understudied and digital media use increased during the COVID-19 pandemic. In this cross-sectional study, demographics, clinical characteristics, and digital media-related problems (DMRPs; sub-coded as cyberbullying, online communication problems, triggering content, and limit-setting problems) were extracted from hospital records of youth (n = 1,101) admitted to a pediatric psychiatric unit from May 2018 to November 2021. DMRPs were identified in 127 admissions (11.5%), led by the online communication problems and limit-setting subtypes (both 4-5%). Significantly more overall problems were identified following the pandemic onset (13.9% of admissions vs. 9.1% before, p < 0.05). The limit-setting subtype specifically increased post-COVID-19 (6.0% vs. 2.7%, p < 0.01), and was associated with prior admissions, suicide attempts, and impulse control/behavioral disorders. Online communication problems were significantly more common among girls and youth with a history of trauma. Interventions in acute settings to mitigate consequences of DMRPs are needed.

Predictors and Correlates of Positive Urine Drug Screening in a Retrospective Cohort Analysis of Child and Adolescent Psychiatry Inpatients Throughout the COVID-19 Pandemic.

BACKGROUND AND OBJECTIVES: Youth substance use is associated with significant psychological, neurological, and medical complications. Risk factors for substance use among children and adolescents in the general population include peer and/or parental substance use, certain psychiatric illnesses (eg, Attention-Deficit/Hyperactivity Disorder, depression), and history of maltreatment. Co-occurring substance use and psychiatric illness have been associated with increased suicidality, but few prior studies have characterized substance use among child/adolescent inpatients. As such, it remains unclear how substance use contributing to acute psychiatric presentations has changed since the start of the COVID-19 pandemic. METHODS: This is a retrospective cohort study of 816 unique child/adolescent psychiatry inpatients with urine drug screening (UDS) results from a diverse urban setting. Charts of patients hospitalized between June 1, 2018 and November 30, 2021 were reviewed for sociodemographic characteristics, indication for admission, psychiatric history, hospital course, treatment plan, and discharge diagnosis. Differences in sociodemographic and clinical characteristics, such as age, race, and diagnoses, between patients with and without positive UDS were explored throughout various periods of the COVID-19 pandemic. Descriptive and comparative statistics were performed, as well as a logistic regression model to identify the predictors of positive UDS. RESULTS: Of the study sample, 18% had a positive UDS. Older age, diagnosis of impulsive or behavioral disorder, and a history of violence were found to be predictors of positive UDS. Asian/South Asian or Hispanic/LatinX race and history of a developmental or intellectual disability were found to be negative predictors. The frequency of positive UDS in this population did not change based on COVID-19. DISCUSSION AND CONCLUSIONS: Multiple factors may predispose children and adolescents to substance use. Though no impact of COVID-19 was found in this sample, longer-term studies are needed. SCIENTIFIC SIGNIFICANCE: This study identifies independent predictors of active substance use in the child and adolescent psychiatric inpatient population.

Change in Neuropsychological Test Performance Seen in a Longitudinal Study of Patients With Post-acute Sequelae of COVID-19: A 6-Month Follow-up Study.

BACKGROUND: Post-acute sequelae of COVID-19 may include physical, psychiatric, and neurocognitive symptoms. Few studies of cognitive symptoms have been longitudinal, with many following participants briefly after infection and relying on subjective complaints, screening instruments, or computerized testing. This group previously reported diminished neuropsychological (NP) test performance in over half of 60 individuals tested in-person 7 months post-COVID-19, particularly those seeking care for cognitive complaints. The current study describes the initial and 6-month follow-up results of an expanded cohort of 75 participants. OBJECTIVE: To measure longitudinal changes in neuropsychological test performance, as well as medical and psychiatric changes, post-COVID-19. METHODS: Participants underwent NP, psychiatric, and medical assessments approximately 7 months after acute COVID-19 infection. Sixty-three (84%) returned approximately 6 months later for repeat evaluation. RESULTS: At the initial visit, 29 (38.7%) met criteria for low NP performance, and 16 (21.3%) met criteria for extremely low NP performance. At 6-month follow-up, several NP domains that were significantly below normative values at the initial visit were no longer abnormal, with the exception of language. Only measures of delayed memory and fatigue showed significant improvements between the 2 time points. CONCLUSIONS: A substantial proportion of individuals recovered from acute COVID-19 infection have persistent neuropsychiatric symptoms over 1 year after infection. While the overall sample in this study showed some improvement in NP test performance relative to norms, only fatigue and delayed memory improved significantly between times 1 and 2. No individual declined in NP test performance, though relatively few individuals made significant clinical improvement, indicating the need for serial neuropsychiatric assessment and treatment supports. Longitudinal follow-up of this cohort is in progress.

Frequency and Characteristics of Depression and Its Association with Diminished Quality of Life in a Cohort of Individuals with Post-Acute Sequelae of COVID-19.

Background: Approximately one-third of COVID-19 survivors will experience persistent symptoms, which may include neurological and psychiatric disturbances. Previous research has suggested that up to 45% of people develop clinically significant depressive symptoms post-COVID. This study sought to determine frequency, symptom profile, and clinical correlates of depression post-COVID. Methods: Seventy-five participants who had recovered from COVID-19 underwent neurocognitive, psychiatric, medical, and cognitive testing/screening. The primary measures of interest in this report included the Patient Health Questionnaire (PHQ-9), a 9-item depression-screening tool, and the Endicott Quality of Life Enjoyment and Satisfaction Questionnaire. Results: One-third of study participants screened as positive on the PHQ-9 for clinically significant depression, with the most commonly reported symptom being fatigue, followed by sleep disturbance and poor concentration. Also reported were decreased satisfaction in employment, sexual life, and mood. Depressed patients described greater illness severity during COVID-19 infection and subjective cognitive impairment, which was not found on neurocognitive testing. The only significant predictor of depression was COVID-19 illness severity. Limitations: A significant portion of participants was a clinical population with specific post-COVID complaints and was predominately comprised of white females. Formal psychiatric evaluation was not performed. Conclusion: Many individuals may experience depression after COVID-19 infection, with symptoms appearing to be predominately somatic in nature and correspond with COVID-19 illness severity.

Difference in Psychiatric Hospital Admissions Between Cisgender and Transgender and Gender Nonconforming Youth, Before and During the Start of the COVID-19 Pandemic.

This retrospective study of 1101 children and adolescents examines differences in psychiatric admissions between cisgender and transgender/gender nonconforming (TGNC) youth between June 2018 and November 2021. Sociodemographic and clinical characteristics for each admission were extracted from medical records. We compared proportion of total admissions and clinical characteristics between cisgender and TGNC youth, during specified time frames of pre-COVID-19, during quarantine, and post-quarantine. During quarantine, 294 (89.9%) youth identified as cisgender and 33 (10.1%) youth identified as TGNC. Post-quarantine, 205 (88.4%) youth identified as cisgender and 27 (11.6%) identified as TGNC. TGNC patients had more history of mood disorders (p < 0.001), self-injurious behavior (p < 0.001), and suicide attempt (p = 0.007), whereas cisgender patients had more history of Attention-deficit/Hyperactivity Disorder (ADHD) (p = 0.011) and violence (p < 0.001) across each time frame of the study. TGNC patients were more likely to be admitted due to suicidal ideation (p = 0.003), whereas cisgender patients were more often admitted for aggression (p < 0.001). There was no change across COVID-19 time periods in terms of any psychiatric history variable among patients identifying as TGNC. The proportion of admitted youth identifying as TGNC increased by 8.1% from pre-COVID-19 to post-quarantine (p < 0.001). These findings suggest that TGNC youth might be particularly vulnerable to mental health crises when faced with pandemic-related stressors. Further research on the vulnerabilities of TGNC youth during sudden and extreme social changes and how this can impact their mental health is necessary, as global pandemics could and are anticipated to repeat.

Impact of COVID-19 on employment: sociodemographic, medical, psychiatric and neuropsychological correlates.

Introduction: Given the nature of the persistent physical and neuropsychiatric symptoms reported in the literature, among individuals after acute COVID illness; there is growing concern about the functional implications of the Post-Acute Sequelae of COVID-19 (PASC). We aim to evaluate associations of sociodemographic, medical, psychiatric and neuropsychological factors with employment status post COVID-19. Methods: 59 participants were administered a neuropsychiatric assessment and queried about employment status and occupational difficulties months after quarantine. Two levels of comparison were conducted: (1) Those who took time off work (TTO) to those with no time off (NTO); (2) Those who reported occupational performance suffered (PS) to those who did not (PDNS). Results: TTO vs. NTO exhibited extensive differences across medical, psychiatric and neurocognitive domains. PS vs. PDNS differed on subjective measures of physical and cognitive symptoms, but not on objective testing. Conclusion: Individuals who took time off beyond COVID-19 quarantine experience persistent physical, psychiatric, subjective and objective neurocognitive burden. In contrast, occupational impairment appears to reflect subjective complaints, but not objective measures. Clinical implications are discussed.

Anxiety and posttraumatic stress in post-acute sequelae of COVID-19: prevalence, characteristics, comorbidity, and clinical correlates.

Background: Anxiety and post-traumatic stress symptoms have been reported in association with acute and post-acute sequelae of COVID-19 (PASC). Purpose: This study aimed to document the cross-sectional prevalence, characteristics and clinical correlates of anxiety and post-traumatic stress in a study of neuropsychiatric sequelae of COVID-19. Method: 75 participants recruited from a post-COVID-19 recovery program and the community were assessed for sociodemographic, medical, psychiatric, and neurocognitive symptoms and performance. The generalized anxiety questionnaire-7 (GAD-7) and post-traumatic stress disorder questionnaire for DSM5 (PCL5) were utilized to measure anxiety and PTSD symptoms. Established cutoff scoring for the GAD-7 and algorithm-based scoring of the PCL5 were utilized to determine clinically significant anxiety symptoms and PTSD, respectively. Results: The cohort was 71% female, 36% ethnic minority, with the main age of 43.5 years, 80% employment, 40% with the prior psychiatric treatment history and 2/3 seeking post-COVID care for PASC. Clinically significant anxiety symptoms were found in 31% and PTSD was found in 29% of the cohort. Nervousness and excessive worry were the most prominent anxiety symptoms, while changes in mood/cognition and avoidance were most frequent in PTSD. There was a high degree of comorbidity between clinically significant anxiety symptoms, PTSD, depression and fatigue. In logistic regression, acute COVID illness severity, prior psychiatric history, and memory complaints (but not objective neuropsychological performance) predicted clinically significant anxiety symptoms and/or PTSD. Conclusion: Clinically significant anxiety and PTSD are found in approximately 1 of 3 individuals after COVID-19 infection. They are highly comorbid with each other as well as with depression and fatigue. All patients seeking care for PASC should be screened for these neuropsychiatric complications. Symptoms of worry, nervousness, subjective changes in mood, and cognition as well as behavioral avoidance are particularly important targets of clinical intervention.

Cariprazine: an augmentation strategy for treatment-resistant schizophrenia with pro-cognitive and anti-hostility effects.

Schizophrenia is a chronic mental health condition treated with antipsychotics. A significant number of patients fail to respond to standard treatment and develop treatment-resistant schizophrenia (TRS). The only current treatment for TRS is clozapine, which has significant side effects and may only be effective in 40% of cases. We describe two cases of patients with TRS who have failed multiple antipsychotic trials and have had extensive hospitalization history due to aggression/hostility. Both patients responded to dual antipsychotic therapy with a long-acting injectable antipsychotic plus cariprazine. Both patients demonstrated improvement in hostility and cognition/memory. Cariprazine's novel mechanism of action may allow it to be uniquely effective in dual antipsychotic therapy for TRS. Cariprazine has a higher affinity than dopamine for D3 receptors and has a 10-fold higher affinity for D3 than D2. This may contribute to its pro-cognitive and anti-hostility effects. Further studies are warranted to determine the role of cariprazine in TRS.

When Did the Empathy Die?: Examining the Correlation Between Length of Medical Training and Level of Empathy.

Purpose: Empathy is an important skill for physicians as it can lead to improved patient outcomes and satisfaction. This study assessed self-reported empathy by medical students across all four years of medical school and potential differences in empathy across students interested in different subspecialties. Method: All medical students enrolled at New York Medical College in August 2020 were invited to participate in this study. Participants completed the student version of the Jefferson Scale of Empathy. Results: A total of 179 medical students participated. Mean empathy score in fourth-year students was significantly lower than that in first-year students. Mean empathy score was greatest among students interested in Pediatrics and was greater in participants who identified as women. Conclusions: Self-reported empathy may be lower in upper-year medical students when compared to lower-year students. The potential reasons for lower empathy in the later years of training are discussed. A systematic curriculum for teaching and maintaining empathy should be developed and uniformly implemented across medical schools to combat a potential decline in empathy.

Clinical determinants, patterns and outcomes of antipsychotic medication prescribing in the treatment of schizophrenia and schizoaffective disorder: A naturalistic cohort study.

BACKGROUND: Schizophrenia affects individuals, families, and systems, with treatment primarily being antipsychotic medications. Long-acting injectable (LAI) antipsychotics are increasingly being used. This study sought to identify predictors of antipsychotic choice, in terms of formulation (LAI vs oral) and class (FGA vs SGA), and clinical outcomes. METHODS: 123 patients who received LAI antipsychotics were diagnosis-matched to patients who received oral antipsychotics. Sociodemographic and clinical factors were extracted from the medical record, including indicators of illness severity. Groups were compared with Chi-Square and t-tests, and logistic regression models were used to identify independent predictors of antipsychotic choice. RESULTS: Patients that received LAIs had longer admissions, more complex discharges, and greater illness severity; however, there were no differences in readmission rates. Independent predictors of LAIs included younger age, being single, and longer admission. Patients who received FGA LAIs were more likely to use substances and be undomiciled compared to SGA LAIs, with the only predictor being older age. Oral FGAs were more likely than Oral SGAs to be prescribed to older and female patients, as well as those with co-occurring substance use, complex discharges, and longer admissions. CONCLUSIONS: Illness severity and duration of illness appear to drive choice of LAI vs. oral antipsychotic medication and FGA vs. SGA. While LAIs were prescribed to patients with greater illness severity, readmission rates were equivalent to those receiving oral medication, supporting the use of LAI in patients with greater illness severity. Rationales for prescribing LAIs to younger patients and FGAs to older patients are discussed.

UTAUT2-based questionnaire: cross-cultural adaptation to Canadian French.

PURPOSE: The extended version of the Unified Theory of Acceptance and Use of Technology (UTAUT2) aims to better understand acceptance of technology. The objective of this study was to translate the English UTAUT2-based questionnaire to Canadian French. METHODS: The translation included five steps: (1) Forward translation, (2) Synthesis of the translated versions, (3) Backward translation, (4) Synthesis by a multidisciplinary committee and proposal of the Pre-final Canadian French version, and (5) Cognitive debriefing. Cognitive debriefing included the assessment of the questionnaire items' clarity by (1) a sample of workers, and (2) rehabilitation professionals. Any item not reaching an 80% inter-rater agreement for clarity or relevance was re-evaluated. RESULTS: The multidisciplinary committee included six researchers and clinicians from four different backgrounds. Twelve workers and 12 experts participated in the cognitive debriefing. Each item (n = 40) was judged as "clear" by at least 92% of the worker sample. Six and four items were reviewed following clarity and relevance assessments. The final version was approved unanimously. CONCLUSION: A Canadian French version of the UTAUT2-based questionnaire has been developed. Studies are necessary to examine cultural and semantic equivalence of the original and translated versions, and the cultural appropriateness of the questionnaire.IMPLICATIONS FOR REHABILITATIONThere is an exponential growth in technology, including in the rehabilitation field.Implementing rehabilitation technology into clinical practice remains a challenge.The UTAUT model, and its extension, help to better understand the acceptance of technology before its implementation.The UTAUT2-based questionnaire evaluates the acceptability of rehabilitation technology prior to implementation.

Transmission Blocking Activity of Low-dose Tafenoquine in Healthy Volunteers Experimentally Infected With Plasmodium falciparum.

BACKGROUND: Blocking the transmission of parasites from humans to mosquitoes is a key component of malaria control. Tafenoquine exhibits activity against all stages of the malaria parasite and may have utility as a transmission blocking agent. We aimed to characterize the transmission blocking activity of low-dose tafenoquine. METHODS: Healthy adults were inoculated with Plasmodium falciparum 3D7-infected erythrocytes on day 0. Piperaquine was administered on days 9 and 11 to clear asexual parasitemia while allowing gametocyte development. A single 50-mg oral dose of tafenoquine was administered on day 25. Transmission was determined by enriched membrane feeding assays predose and at 1, 4, and 7 days postdose. Artemether-lumefantrine was administered following the final assay. Outcomes were the reduction in mosquito infection and gametocytemia after tafenoquine and safety parameters. RESULTS: Six participants were enrolled, and all were infective to mosquitoes before tafenoquine, with a median 86% (range, 22-98) of mosquitoes positive for oocysts and 57% (range, 4-92) positive for sporozoites. By day 4 after tafenoquine, the oocyst and sporozoite positivity rate had reduced by a median 35% (interquartile range [IQR]: 16-46) and 52% (IQR: 40-62), respectively, and by day 7, 81% (IQR 36-92) and 77% (IQR 52-98), respectively. The decline in gametocyte density after tafenoquine was not significant. No significant participant safety concerns were identified. CONCLUSIONS: Low-dose tafenoquine (50 mg) reduces P. falciparum transmission to mosquitoes, with a delay in effect.

Aripiprazole: examining the clinical implications of D2 affinity.

Schizophrenia is a prevalent psychiatric illness, which causes significant financial and social burden on the population overall. The development of second generation antipsychotics, such as Aripiprazole, Risperidone, and Paliperidone, has changed treatment practice for many psychiatrists. Aripiprazole has extremely high binding affinity for the dopamine D2 receptor, which is the receptor thought to be responsible for the antipsychotic effect, although Aripiprazole is not the most potent of the second generation antipsychotics. In theory, Aripiprazole could displace or outcompete other, more potent antipsychotics, prompting decreased antipsychotic effect. We describe a proposed case of this phenomenon, Ms. A. We describe how Aripiprazole may have caused a worsening of psychiatric symptoms by blocking the antipsychotic effects of Paliperidone due to its strong binding affinity for the D2 receptor. Aripiprazole has a high affinity for the D2 receptor, but may have a lesser reduction of psychotic symptoms compared to other antipsychotics. Prescribers should be aware of this potential interaction and carefully consider initiating long-acting injectable forms of Aripiprazole to avoid this phenomenon.

Frequency, Characteristics, and Correlates of Cognitive Complaints in a Cohort of Individuals with Post-Acute Sequelae of COVID-19.

BACKGROUND: Cognitive complaints are among the most frequent symptoms of post-acute sequelae of COVID-19 (PASC). This study aimed to investigate the frequency, characteristics, and clinical correlates of cognitive complaints (CC) in PASC, particularly in relation to objective neuropsychological (NP) performance. METHODS: Seventy-four participants underwent psychiatric, medical, and NP testing approximately 7 months after acute COVID-19. The Patient Assessment of Own Functioning Inventory (PAOFI) was used to characterize the frequency and severity of CC in domains of memory, language, and cognitive/executive function. The associations of CC with sociodemographic, medical, psychiatric, and NP variables were assessed utilizing correlational analysis, logistic regression, and pairwise comparisons of those categorized as having CC vs. not having CC. RESULTS: Taken together, approximately one-third of the study participants had clinically significant CC. Memory difficulty was the most frequent CC, although all categories were frequently endorsed. Memory and cognitive/executive complaints correlated with NP tests in these and multiple other NP domains. CC were more likely to be under-reported in those with diminished NP performance than over-reported in those without diminished performance. Acute COVID-19 symptom severity, elevated depressive symptoms, and NP tests of diminished attention and psychomotor processing speed were independent predictors of CC in logistic regression. CONCLUSIONS: Cognitive complaints after acute COVID-19 should be taken seriously, as they are likely to reflect diminished NP performance, as well as medical, psychiatric, and functional burdens. However, patients with PASC may not accurately identify or characterize objective cognitive difficulties, so programs offering comprehensive care for patients with PASC should offer formal neuropsychological testing.

Impact of dual tasking on gaze behaviour and locomotor strategies adopted while circumventing virtual pedestrians during a collision avoidance task.

We investigated gaze behaviour and collision avoidance strategies in 16 healthy young individuals walking towards a goal while exposed to virtual pedestrians (VRPs) approaching from different directions (left, middle, right). This locomotor task and an auditory-based cognitive task were performed under single and dual-task conditions. Longer gaze fixation durations were observed on the approaching vs. other VRPs, with longer fixations devoted to the upper trunk and head compared to other body segments. Compared to other pedestrian approaches, the middle pedestrian received longer fixations and elicited faster walking speeds, larger onset distances of trajectory devitation and smaller obstacle clearances. Gaze and locomotor behaviours were similar between single and dual-task conditions but dual-task costs were observed for the cognitive task. The longer gaze fixations on approaching vs. other pedestrians suggest that enhanced visual attention is devoted to pedestrians posing a greater risk of collision. Likewise, longer gaze fixations for the middle pedestrians may be due to the greater collision risk entailed by this condition, and/or to the fact that this pedestrian was positioned in front of the end goal. Longer fixations on approaching VRPs' trunk and head may serve the purpose of anticipating their walking trajectory. Finally, the dual-task effects that were limited to the cognitive task suggest that healthy young adults prioritize the locomotor task and associated acquisition of visual information. The healthy patterns of visuomotor behaviour characterized in this study will serve as a basis for comparison to further understand defective collision avoidance strategies in patient populations.

Screening for brain fog: Is the montreal cognitive assessment an effective screening tool for neurocognitive complaints post-COVID-19?

BACKGROUND: Cognitive complaints are one of the most frequent symptoms reported in post-acute sequelae of COVID-19 (PASC). The Montreal Cognitive Assessment (MoCA) has been used to estimate prevalence of cognitive impairment in many studies of PASC, and is commonly employed as a screening test in this population, however, its validity has not been established. OBJECTIVE: To determine the utility of the MoCA to screen for cognitive impairment in PASC. METHODS: Sixty participants underwent neuropsychological, psychiatric, and medical assessments, as well as the Montreal Cognitive Assessment, 6-8 months after acute COVID-19 infection. RESULTS: The overall sample had a mean score of 26.1 on the MoCA, with approximately one third screening below the cutoff score of 26, similar to the rate of extremely low NP test performance. MoCA score was inversely correlated with fatigue and depression measures and ethnic minority participants scored on average lower, despite similar education and estimated premorbid function. The MoCA had an accuracy of 63.3% at detecting any degree of diminished NP performance, and an accuracy of 73.3% at detecting extremely low NP performance. DISCUSSION/CONCLUSION: The MoCA may not be accurate for detecting neither mild nor more severe degrees of diminished NP test performance in PASC. Therefore, patients with persistent cognitive complaints in the setting of PASC who score in the normal range on the MoCA should be referred for formal NP assessment.