Detecting High-Dose Methotrexate-Induced Brain Changes in Pediatric and Young Adult Cancer Survivors Using [18F]FDG PET/MRI: A Pilot Study.

Significant improvements in treatments for children with cancer have resulted in a growing population of childhood cancer survivors who may face long-term adverse outcomes. Here, we aimed to diagnose high-dose methotrexate-induced brain injury on [18F]FDG PET/MRI and correlate the results with cognitive impairment identified by neurocognitive testing in pediatric cancer survivors. Methods: In this prospective, single-center pilot study, 10 children and young adults with sarcoma (n = 5), lymphoma (n = 4), or leukemia (n = 1) underwent dedicated brain [18F]FDG PET/MRI and a 2-h expert neuropsychologic evaluation on the same day, including the Wechsler Abbreviated Scale of Intelligence, second edition, for intellectual functioning; Delis-Kaplan Executive Function System (DKEFS) for executive functioning; and Wide Range Assessment of Memory and Learning, second edition (WRAML), for verbal and visual memory. Using PMOD software, we measured the SUVmean, cortical thickness, mean cerebral blood flow (CBFmean), and mean apparent diffusion coefficient of 3 different cortical regions (prefrontal cortex, cingulate gyrus, and hippocampus) that are routinely involved during the above-specified neurocognitive testing. Standardized scores of different measures were converted to z scores. Pairs of multivariable regression models (one for z scores < 0 and one for z scores > 0) were fitted for each brain region, imaging measure, and test score. Heteroscedasticity regression models were used to account for heterogeneity in variances between brain regions and to adjust for clustering within patients. Results: The regression analysis showed a significant correlation between the SUVmean of the prefrontal cortex and cingulum and DKEFS-sequential tracking (DKEFS-TM4) z scores (P = 0.003 and P = 0.012, respectively). The SUVmean of the hippocampus did not correlate with DKEFS-TM4 z scores (P = 0.111). The SUVmean for any evaluated brain regions did not correlate significantly with WRAML-visual memory (WRAML-VIS) z scores. CBFmean showed a positive correlation with SUVmean (r = 0.56, P = 0.01). The CBFmean of the cingulum, hippocampus, and prefrontal cortex correlated significantly with DKEFS-TM4 (all P < 0.001). In addition, the hippocampal CBFmean correlated significantly with negative WRAML-VIS z scores (P = 0.003). Conclusion: High-dose methotrexate-induced brain injury can manifest as a reduction in glucose metabolism and blood flow in specific brain areas, which can be detected with [18F]FDG PET/MRI. The SUVmean and CBFmean of the prefrontal cortex and cingulum can serve as quantitative measures for detecting executive functioning problems. Hippocampal CBFmean could also be useful for monitoring memory problems.

Brief cognitive-behavioral intervention for maternal depression and trauma in the neonatal intensive care unit: a pilot study.

Parents of hospitalized premature infants are at risk for developing psychological symptoms. This randomized controlled pilot study examined the effectiveness of a brief cognitive-behavioral intervention in reducing traumatic and depressive symptoms in mothers 1 month after their infant's discharge from the hospital. Fifty-six mothers were randomly assigned to the intervention or control group. Results showed that mothers experienced high levels of symptoms initially and at follow-up. At follow-up, there was a trend for mothers in the intervention group to report lower levels of depression (p = .06; Cohen's f = .318), but levels of traumatic symptoms were similar for both groups. Brief psychological interventions may reduce depressive symptoms in this population. Estimates of the effect sizes can be used to inform future intervention studies.

Pivotal response group treatment program for parents of children with autism.

The number of children diagnosed with autism spectrum disorders is increasing, necessitating the development of efficient treatment models. Research has demonstrated that parent-delivered behavioral interventions are a viable treatment model; however, little research has focused on teaching parents in groups. The aim of this study was to demonstrate that parents can learn Pivotal Response Training (PRT) in group therapy, resulting in correlated gains in children's language. Baseline and post-treatment data were obtained and examined for changes in (a) parent fidelity of PRT implementation, and (b) child functional verbal utterances. Significant differences were observed for both variables. These findings suggest that parents can learn PRT in a group format, resulting in correlated child language gains, thus future controlled studies are warranted.

Is child psychiatric service different when provided by attendings versus clinicians-in-training?

OBJECTIVE: This study examines the clinical management characteristics of outpatient child and adolescent psychiatric care provided by attendings and clinicians-in-training in an academic institution. The authors hypothesized that no significant differences would exist between initial evaluations conducted by attendings and those conducted by clinicians-in-training. METHODS: The amount of information obtained during an initial evaluation and the number and type of services recommended postevaluation were assessed for 429 patients treated in the child and adolescent psychiatry clinics at Stanford University by attending psychiatrists and clinicians-in-training. RESULTS: No significant differences were found for the evaluations conducted by attendings and clinicians-in-training for the amount of data collected during an evaluation of the number or type of recommendations made postevaluation. CONCLUSION: These findings lend themselves to the conclusion that attendings and clinicians-in-training offer comparable services in the assessment of new patients. Study limitations and future areas of study are discussed.

Social support from family and friends as a buffer of low spousal support among mothers of critically ill children: A multilevel modeling approach.

OBJECTIVE: To investigate whether social support from family and friends (family/friend support) attenuated ("buffered") adverse effects of having low spouse support (spousal support) among mothers of children undergoing hematopoietic stem cell transplantation (HSCT). DESIGN: One hundred sixty-three married mothers who were their child's primary caregiver during treatment completed assessments during the child's hospitalization for HSCT and 3-, 6-, and 12-months post-HSCT. MEASURES: Family/friend support and spousal support were assessed during hospitalization. Maternal physical and mental health-related functioning (the main outcome measures) were assessed at all timepoints. RESULTS: Multilevel modeling was used to analyze trajectories of maternal functioning. Findings indicated that mothers with low spousal support and low family/friend support demonstrated the worst functioning across all timepoints. Mothers with low spousal support and high family/friend support demonstrated significantly better functioning, supporting the hypothesized buffering effect. Their functioning compared to the functioning of mothers with high spousal support. Moreover, mothers with high family/friend support demonstrated trajectories of physical health-related functioning that were more stable than the trajectories of mothers with low family/friend support. CONCLUSION: These findings have clinical implications in addition to advancing knowledge of social support processes among couples coping with the shared stressor of a child's life-threatening illness and treatment.

Amantadine treatment following traumatic brain injury in children.

PRIMARY OBJECTIVE: The focus of this paper is to review the current literature on the use of amantadine in children who have sustained a head injury. MAIN OUTCOMES AND RESULTS: A MEDLINE search was conducted and yielded five papers. They were composed of prospective, retrospective and case study designs. Dosage use and side effect profiles were consistent with expected norms. Efficacy was measures primarily by alertness and arousal and positive results were found for all studies on these dimensions. Behavioural and cognitive measures of outcome yielded mixed results. CONCLUSIONS: The studies reviewed for this paper suggest that amantadine is clinically beneficial for children who have sustained head injuries. Double blind placebo controlled trials with larger sample sizes are needed to further substantiate these findings.

Maternal perspectives on children's health-related quality of life during the first year after pediatric hematopoietic stem cell transplant.

OBJECTIVE: To assess the longitudinal health-related quality of life (HRQL) of children receiving hematopoietic stem cell transplantation (HSCT). METHODS: Mothers (N = 160) of HSCT recipients aged 5-20 at six US transplant centers completed the Child Health Ratings Inventories (CHRIs), the Disease Impairment Inventory (DSII)-HSCT module, and the Short Form (SF)-36 at baseline, 3, 6, and 12 months. RESULTS: HRQL domain scores at baseline varied by recipient age and program site. Longitudinal data over the first year post-HSCT revealed lowest functioning at baseline and 3 months, with largest improvement in functioning between the 3 and 6-months assessments and continued improvement from 6 to 12 months. Recipients of unrelated donor transplants had steepest declines in functioning at 3 months and great HSCT-specific issues at 3 and 6 months. Among children who survived the first year, functioning at 12 months was similar across transplant types and surpassed baseline scores. Children who did not survive the first year exhibited deterioration in HRQL in the months before death and trajectories were strikingly different than for survivors. CONCLUSIONS: This study offers the first glimpse of the 12-month trajectory of HRQL following pediatric HSCT from mothers' perspectives. This study also highlights the importance of and approaches to addressing missing data in longitudinal research.

Mothers' perceptions of benefit following pediatric stem cell transplantation: a longitudinal investigation of the roles of optimism, medical risk, and sociodemographic resources.

BACKGROUND: This longitudinal study investigated the course and predictors of benefit finding among 144 mothers of children undergoing hematopoietic stem cell transplantation (HSCT), a severely stressful and life-threatening medical procedure. PURPOSE: Children's medical risk and mothers' dispositional optimism and sociodemographic resources were examined as predictors of benefit finding. The association between benefit finding and mothers' psychosocial adaptation was also investigated. METHODS: Assessments occurred during hospitalization for HSCT (Time 1 [T1]) and 6 months later (Time 2 [T2]). RESULTS: Hierarchial multiple regression analyses revealed that predictors of benefit finding differed systematically across assessments, with optimism and medical risk predicting benefit finding at both time points but sociodemographic resources predicting only T2 benefit findings. Benefit finding did not predict psychosocial adaptation until optimism was considered as a moderator of their relation: T1 benefit finding was positively associated with T2 adaptation only for mothers high in optimism. CONCLUSION: The need for longitudinal research on posttrauma adaptation and the utility of considering the natural history of the trauma are discussed.

Anxiety, depressive, and posttraumatic stress disorders among mothers of pediatric survivors of hematopoietic stem cell transplantation.

OBJECTIVE: To examine the prevalence and predictors of anxiety, depression, and posttraumatic stress disorder among mothers of children who underwent hematopoietic stem cell transplantation (HSCT). METHODS: A total of 111 mothers of children who survived HSCT completed self-report measures of psychological functioning at the time of HSCT and self-report measures and a structured psychiatric interview 18 months after HSCT. Demographic data and medical data were also collected. RESULTS: Approximately 20% of mothers had clinically significant distress reactions. When subthreshold posttraumatic stress disorder was included, nearly one third of mothers met the criterion for persistent distress. Mothers with 1 of the 4 psychiatric diagnoses reported a significantly lower quality of life, suggesting that the diagnoses had an impact on their general quality of life. Mothers who had 1 of the 4 diagnoses at 18 months were younger and had higher anxiety and depressive symptoms at the time of HSCT. CONCLUSIONS: A subset of mothers of children who survive HSCT may require psychological intervention. Mothers who are most at risk are younger and evidence anxiety and depressive symptoms at the time of transplantation.

Practitioners' attitudes toward the use of treatment progress and outcomes data in child mental health services.

This study focused on practitioners' attitudes toward child mental health services data collection and outcomes measurement in university-based and community-based clinics. It is relevant to the burgeoning field of empirically based mental health therapy management because it examines one potential barrier to psychotherapy and pharmacotherapy strategies (i.e., practitioners' attitudes toward outcomes measurement) that are informed by real-time, clinically relevant data. Two site differences were noted regarding the utility of specific questionnaires and the perceived burden of conducting outcomes measurement. At both sites, practitioners held positive attitudes about outcomes measurement. Compared with psychologists and other child mental health specialists, psychiatrists had less favorable attitudes toward outcomes evaluation. Practitioners who rated outcomes evaluation as more important also perceived less burden associated with such evaluation efforts. Increased understanding of the utility of systematic clinical data collection is more likely to occur in an organizational culture in which treatment progress and outcomes measurement is integral to clinical work.

Perceived partner critical and avoidant behaviors as predictors of anxious and depressive symptoms among mothers of children undergoing hemopaietic stem cell transplantation.

This prospective study examined the role of perceived partner criticism and avoidance in the anxiety and depressive symptoms of 148 mothers of children undergoing hemopaietic stem cell transplantation (HSCT). The roles of indicators of transplantation risk and posttransplantation medical course were also examined. Perceived partner criticism (e.g., criticizing coping efforts) and perceived partner avoidance (e.g., changing the topic), objective indicators of transplantation risk, and anxiety and depressive symptoms were assessed at the time of HSCT and again 3 and 6 months later. Growth curve modeling analyses indicated that perceived partner criticism was associated with higher average depressive symptoms. However, perceived partner criticism did not predict changes in mother's anxiety. Contrary to predictions, perceived partner avoidance was associated with decreases in maternal anxiety.

Coping and the course of mother's depressive symptoms during and after pediatric bone marrow transplantation.

OBJECTIVE: To evaluate the role of maternal coping strategies in depressive symptoms experienced by mothers of children undergoing bone marrow transplantation (BMT). METHOD: A total of 207 mothers completed measures of coping and depressive symptoms at the time of the child's BMT, 3 and 6 months post-BMT. The sample was collected between 1998 and 2002. The acceptance rate was 73%. The contribution of demographic, illness and treatment parameters, and mothers' concerns about the child were also evaluated. Growth curve modeling was used to evaluate the role of coping in the course of depressive symptoms. Both main effects and interactions of coping strategies with time of assessment were evaluated. RESULTS: Acceptance and humor were associated with reductions in maternal depressive symptoms, and planning and alcohol/substance use were associated with increases in maternal depressive symptoms. Positive reframing, use of emotional support, and use of religion were associated with the course of depressive symptoms, but the magnitude of associations differed depending on the use of the coping strategies at the time of transplantation. Mothers' fears about the child also predicted depressive symptoms. CONCLUSIONS: Acceptance and humor may be targets for behavioral interventions to reduce mothers' depressive symptoms during and after pediatric BMT hospitalization.

Preferences for cocaine- or pup-associated chambers differentiates otherwise behaviorally identical postpartum maternal rats.

RATIONALE AND OBJECTIVES: Our previous work uncovered a differential preference of maternal female rats for cues associated with pups versus cues associated with cocaine at three different postpartum time points. Our current study examines the preference for these cues in conjunction with an assessment of the capacity to express the maternal behavior at one of these time points. We examined dams at day 10 postpartum using a procedure that included two additional controls, and a complete assessment of the expression of maternal behavior and locomotor activity. METHODS: A conditioned place-preference procedure was used to determine the preference for cocaine- or pup-associated cues. The two controls were (1) a preconditioning test to verify no initial chamber preference and (2) a separate control group of postpartum day-10 dams exposed to chambers and cues but not to unconditioned stimuli. The expression of maternal behavior was determined by measurement of maternal nest building, retrieval of pups to the nest, grooming, crouching over pups, nursing, and maternal aggression. Locomotor activity was measured with an automated apparatus. RESULTS: Dams conditioned with cocaine or pups showed a preference for either the cocaine-associated chamber or the pup-associated chamber, confirming the existence of two similar-sized preference groups at this time point. Regardless of preference, dams had equal and robust expression of maternal behavior and similar locomotor capacity. The pre-conditioning test showed no initial chamber preferences and did not alter the conditioned preference response. The use of unconditioned stimuli in the place-preference conditioning procedure was effective and necessary for the preference response. CONCLUSION: Our current study has revealed that differences in the motivational state of the maternal dam emerge even while the expression of maternal behavior is constant and substantial. The data suggest that the difference in preference is a very specific appetitive response that is not linked to expression of maternal behavior or locomotor capacity.