Objective
The current study assessed relations among maternal depressive symptoms, poorer youth diabetes adherence, and glycemic control. Specifically, hypothesized mediating links of lowered expectations of parental involvement, less parental monitoring and more conflict were examined.
Methods
Participants included 225 mothers and their young adolescents, aged 11–14 years (M = 12.73 years, SD = 1.2) diagnosed with T1D. Maternal depressive symptoms and outcome expectancies for maternal involvement were evaluated with self-report questionnaires. Multi-source, parent/youth, and multi-method assessment of adherence, parental monitoring, and conflict were evaluated during a baseline assessment from a larger randomized clinical trial.
Results
The first hypothesized structural equation model demonstrated a good fit and indicated that more maternal depressive symptoms were directly associated with less parental monitoring and more conflict, which in turn each were associated with poorer adherence and glycemic control. Although higher involvement expectancies were associated with more monitoring and less conflict, they were not associated with other model variables. A second alternative model also fit the data well; poorer youth adherence was associated with more conflict that in turn related to maternal depressive symptoms.
Conclusions
Two models were tested by which maternal depressive symptoms and poorer youth adherence were interrelated via less monitoring and more conflict. Follow-up longitudinal evaluation can best characterize the full extent of these relations.
Neurotoxicity associated with CAR-T cell therapy can be life-threatening. With rapid development of CAR-T therapies, a systematic method is needed to identify and monitor symptoms of neurotoxicity, elucidate potential etiologies, and compare toxicity across trials. This paper presents a systematic evaluation developed and used to prospectively assess neurotoxicity in our phase I anti-CD22 CAR-T-cell trial and describes the symptoms of neurotoxicity identified using this methodology. Central nervous system (CNS) studies included routine lumbar punctures performed for disease evaluation pretherapy and posttherapy and a baseline brain MRI. Brief cognitive evaluations, assessing 4 domains (attention, working memory, cognitive flexibility, and processing speed), were administered preinfusion and postinfusion. A newly developed CAR-T-specific neurological symptom checklist (NSC) was completed by caregivers at 3 designated time-points. Serial serum cytokine levels were compared with neurotoxicity symptoms and severity. The majority of the first 22 consecutively treated subjects (ages, 7-30) demonstrated stable or improved cognitive test scores following therapy and no irreversible neurotoxicity, despite CAR-T-related antileukemic response, cytokine release syndrome, and trafficking of CAR-T cells to the CSF. The NSC allowed us to document the type and timing of symptoms and explore the etiology of neurotoxicity associated with CD22 CAR-T therapy. Cytokine profiling demonstrated that more concerning symptoms of neurotoxicity, such as hallucination and disorientation, were significantly associated with higher serum cytokine levels, supporting the hypothesis of inflammation-driven neurotoxicity. Systematic assessments of neurotoxicity were feasible in acutely ill children and young adults and served to characterize and monitor the symptoms associated with CAR-T therapy. We recommend these evaluations be incorporated into future immunotherapy protocols.
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