Background: Prior research on trauma-exposed preschool children has found various levels of trauma-related stress symptoms depending on age, which might be explained by developmental factors.
...Objective: This study uses network analysis to extend prior research and compare symptom presentation in younger and older preschoolers in the acute phase (first 4 weeks) following a potentially traumatic event.
Method: Parent-reported trauma-related acute stress symptoms were assessed using the Pediatric Emotional Distress Scale - Early Screener via
www.kidtrauma.com
. First, the overall symptom severity and symptom levels were compared between younger (1-3 years) and older (4-6 years) preschoolers. Further, two Gaussian graphical models of stress symptoms in younger (n = 242; M
age
= 2.3 years; SD
age
= 0.6 years) and older preschoolers (n = 299; M
age
= 4.8 years; SD
age
= 0.7 years) were modelled and compared.
Results: Overall symptom severity did not differ between the groups. Symptom levels for developmental regression and avoidance of talking about the event were higher in older preschoolers. The network structures of the younger and the older preschoolers were largely similar. Highly central symptoms in both networks were trauma-unrelated fear and anger. The connections between fear of reminders and clinginess and trauma-unrelated fear and clinginess were stronger in the older preschoolers' network. The connections between worry and sadness and withdrawal; fear of reminders and creation of games, stories, and pictures; and whininess and clinginess were all stronger in the younger preschoolers' network.
Conclusions: Trauma-related stress symptomatology of younger and older preschoolers may not differ greatly in the acute phase. Trauma-unrelated fear and anger seem to be central symptoms in both groups. However, examining symptom-level associations across age groups revealed differential connections that might arise from developmental differences. If replicated in longitudinal and within-subject studies, these findings could help tailor interventions for trauma-exposed preschoolers in the acute phase.
Symptom-specific differences in frequency between younger and older preschoolers emerged for developmental regression (younger < older) and avoidance of talking about the event (younger < older).
Highly central symptoms in both age groups were trauma-unrelated fear and anger.
In couples dealing with health problems, we-disease appraisals can influence dyadic coping strategies to alleviate distress. This study describes the development and validation of a self-report scale ...to assess we-disease appraisals of health problems. The newly developed We-Disease Questionnaire (WDQ) was administered in three samples: parents of children with type 1 diabetes (
= 240) or cancer (
= 125) and individuals with visual impairment and their partners (
= 216). Reliability was measured by coefficient omega. To assess construct validity, correlations with other measures of individual and dyadic adjustment were examined. Descriptive statistics across all samples were compared. A 4-item version of the WDQ demonstrated good reliability and validity and showed meaningful associations with established scales. We-disease appraisals were highest among parents of children with cancer and lowest among couples with visual impairment. The WDQ is a reliable and valid measure that can be used across different health problems.
Background
The aim of this study is to provide a better understanding of the central symptoms of DSM‐5 posttraumatic stress disorder (PTSD) in children and adolescents from the perspective of the ...child and its caregiver. Identifying core symptoms of PTSD can help clinicians to understand what may be relevant targets for treatment. PTSD may present itself differently in children and adolescents compared to adults, and no study so far has investigated the DSM‐5 PTSD conceptualization using network analysis.
Methods
The network structure of DSM‐5 PTSD was investigated in a clinical sample of n = 475 self‐reports of children and adolescents and n = 424 caregiver‐reports using (a) regularized partial correlation models and (b) a Bayesian approach computing directed acyclic graphs (DAGs).
Results
(a) The 20 DSM‐5 PTSD symptoms were positively connected within the self‐report and the caregiver‐report sample. The most central symptoms were negative trauma‐related cognitions and persistent negative emotional state for the self‐report and negative trauma‐related cognitions, intrusive thoughts or memories and exaggerated startle response for the caregiver‐report. (b) Similarly, symptoms in the negative alterations in cognitions and mood cluster (NACM) have emerged as key drivers of other symptoms in traumatized children and adolescents.
Conclusions
As the symptoms in the DSM‐5 NACM cluster were central in our regularized partial correlation networks and also appeared to be the driving forces in the DAGs, these might represent important symptoms within PTSD symptomatology and may offer key targets in PTSD treatment for children and adolescents.
Background
This study aims to provide a better understanding of the individual impact of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) post-traumatic stress ...symptoms (PTSS) on functional impairment in trauma-exposed children and adolescents. Identifying PTSS that have the most impact on functional impairment can broaden our understanding of post-trauma reactions and guide the selection of treatment components and techniques required to help patients to restore functioning following trauma exposure.
Method
Utilizing relative importance analyses, unique shared variance of each DSM-5 PTSS with functional impairment were estimated in clinical samples of 3400 Norwegian (
M
age
= 14.18,
SD
age
= 2.49, range
age
= 7–17) and 747 US (
M
age
= 10.76,
SD
age
= 3.10, range
age
= 7–17) children and adolescents from naturalistic settings.
Results
Negative beliefs, detachment from others, inability to experience positive emotions, and diminished interest in activities within the symptom cluster negative alterations in cognitions and mood, and the hyperarousal symptom concentration problems accounted for the largest proportions of unique variance explained in functional impairment in both samples. Further, the hyperarousal symptom irritability showed a unique high association with functional impairment in the US sample.
Conclusion
As negative beliefs, emotional numbing symptoms, concentration problems and irritability may be especially related to functional impairment in traumatized children and adolescents, monitoring and targeting these symptoms throughout therapy might be of particular importance to restore functioning as early as possible and to facilitate overall recovery.
The Child Behavior Checklist (CBCL 1.5–5 years) posttraumatic stress disorder (PTSD) subscale by Dehon & Scheeringa (
2006
) as a screener for PTSD in trauma-exposed young children has yielded ...inconsistent results so far. Therefore, the aim of this study was to create and examine the validity of alternative CBCL-PTSD subscales and compare them to the existing CBCL-PTSD subscale based on the DSM-5 PTSD diagnostic criteria for children 6 years and younger. Further, the CBCL-PTSD subscales were examined regarding their usefulness in screening for posttraumatic stress-related functional impairment. The sample comprised 116 trauma-exposed young children (
M
age
= 3.42 years,
SD
age
= 1.21 years, female = 49.1%). The psychometric properties of the existing CBCL-PTSD subscale as well as the alternative subscales based on expert rating (
CBCL-PTSD-17
) and based on variable importance (
CBCL-PTSD-6
) were evaluated by means of receiver operating characteristic curves, sensitivity, specificity, positive predictive values, and negative predictive values. Area under the curves for all three investigated CBCL-PTSD subscales were good to excellent for PTSD and functional impairment. Further, all three CBCL-PTSD subscales showed high sensitivity for PTSD and functional impairment. Considering the length and the performance of the three investigated subscales, the CBCL-PTSD-6 appears to be a promising and clinically useful CBCL-PTSD subscale as a screener for PTSD and functional impairment due to the easiest and most practicable application. For purposes of discriminant validation of the CBCL-PTSD-6, young children without a history of trauma should be compared to young children with trauma history.
The purpose of this study was to identify and validate new putative lead drug targets in drug-resistant mesial temporal lobe epilepsy (mTLE) starting from differentially expressed genes (DEGs) ...previously identified in mTLE in humans by transcriptome analysis. We identified consensus DEGs among two independent mTLE transcriptome datasets and assigned them status as “lead target” if they (1) were involved in neuronal excitability, (2) were new in mTLE, and (3) were druggable. For this, we created a consensus DEG network in STRING and annotated it with information from the DISEASES database and the Target Central Resource Database (TCRD). Next, we attempted to validate lead targets using qPCR, immunohistochemistry, and Western blot on hippocampal and temporal lobe neocortical tissue from mTLE patients and non-epilepsy controls, respectively. Here we created a robust, unbiased list of 113 consensus DEGs starting from two lists of 3040 and 5523 mTLE significant DEGs, respectively, and identified five lead targets. Next, we showed that CACNB3, a voltage-gated Ca
2+
channel subunit, was significantly regulated in mTLE at both mRNA and protein level. Considering the key role of Ca
2+
currents in regulating neuronal excitability, this suggested a role for CACNB3 in seizure generation. This is the first time changes in CACNB3 expression have been associated with drug-resistant epilepsy in humans, and since efficient therapeutic strategies for the treatment of drug-resistant mTLE are lacking, our finding might represent a step toward designing such new treatment strategies.
We have shown previously that inhibition of small conductance Ca(2+)-activated K(+) (SK) channels is antiarrhythmic in models of acutely induced atrial fibrillation (AF). These models, however, do ...not take into account that AF derives from a wide range of predisposing factors, the most prevalent being hypertension. In this study we assessed the effects of two different SK channel inhibitors, NS8593 and UCL1684, in aging, spontaneously hypertensive rats to examine their antiarrhythmic properties in a setting of hypertension-induced atrial remodeling. Male spontaneously hypertensive rats and the normotensive Wistar-Kyoto rat strain were divided in 2×3 groups of animals aged 3, 8, and 11 months, respectively. The animals were randomly assigned to treatment with NS8593, UCL1684, or vehicle, and open chest in vivo experiments including burst pacing-induced AF were performed. The aging spontaneously hypertensive rats were more vulnerable to AF induction both by S2 stimulation and burst pacing. Vehicle affected neither the atrial effective refractory period nor AF duration. SK channel inhibition with NS8593 and UCL1684 significantly increased the atrial effective refractory period and decreased AF duration in both the normotensive and hypertensive strains with no decline in efficacy as age increased. In conclusion, SK channel inhibition with NS8593 and UCL1684 possesses antiarrhythmic properties in a rat in vivo model of paroxysmal AF with hypertension-induced atrial remodeling. The present results support the notion that SK channels may offer a promising new therapeutic target in the treatment of AF.
Purpose
To describe the management of arterial partial pressure of carbon dioxide (PaCO2) in severe traumatic brain-injured (TBI) patients, and the optimal target of PaCO2 in patients with high ...intracranial pressure (ICP).
Methods
Secondary analysis of CENTER-TBI, a multicentre, prospective, observational, cohort study. The primary aim was to describe current practice in PaCO2 management during the first week of intensive care unit (ICU) after TBI, focusing on the lowest PaCO2 values. We also assessed PaCO2 management in patients with and without ICP monitoring (ICPm), and with and without intracranial hypertension. We evaluated the effect of profound hyperventilation (defined as PaCO2 < 30 mmHg) on long-term outcome.
Results
We included 1100 patients, with a total of 11,791 measurements of PaCO2 (5931 lowest and 5860 highest daily values). The mean (± SD) PaCO2 was 38.9 (± 5.2) mmHg, and the mean minimum PaCO2 was 35.2 (± 5.3) mmHg. Mean daily minimum PaCO2 values were significantly lower in the ICPm group (34.5 vs 36.7 mmHg, p < 0.001). Daily PaCO2 nadir was lower in patients with intracranial hypertension (33.8 vs 35.7 mmHg, p < 0.001). Considerable heterogeneity was observed between centers. Management in a centre using profound hyperventilation (HV) more frequently was not associated with increased 6 months mortality (OR = 1.06, 95% CI = 0.77–1.45, p value = 0.7166), or unfavourable neurological outcome (OR 1.12, 95% CI = 0.90–1.38, p value = 0.3138).
Conclusions
Ventilation is manipulated differently among centers and in response to intracranial dynamics. PaCO2 tends to be lower in patients with ICP monitoring, especially if ICP is increased. Being in a centre which more frequently uses profound hyperventilation does not affect patient outcomes.
Objective
To compare outcomes between patients with primary external ventricular device (EVD)–driven treatment of intracranial hypertension and those with primary intraparenchymal monitor (IP)–driven ...treatment.
Methods
The CENTER-TBI study is a prospective, multicenter, longitudinal observational cohort study that enrolled patients of all TBI severities from 62 participating centers (mainly level I trauma centers) across Europe between 2015 and 2017. Functional outcome was assessed at 6 months and a year. We used multivariable adjusted instrumental variable (IV) analysis with “center” as instrument and logistic regression with covariate adjustment to determine the effect estimate of EVD on 6-month functional outcome.
Results
A total of 878 patients of all TBI severities with an indication for intracranial pressure (ICP) monitoring were included in the present study, of whom 739 (84%) patients had an IP monitor and 139 (16%) an EVD. Patients included were predominantly male (74% in the IP monitor and 76% in the EVD group), with a median age of 46 years in the IP group and 48 in the EVD group. Six-month GOS-E was similar between IP and EVD patients (adjusted odds ratio (aOR) and 95% confidence interval CI OR 0.74 and 95% CI 0.36–1.52, adjusted IV analysis). The length of intensive care unit stay was greater in the EVD group than in the IP group (adjusted rate ratio 95% CI 1.70 1.34–2.12, IV analysis). One hundred eighty-seven of the 739 patients in the IP group (25%) required an EVD due to refractory ICPs.
Conclusion
We found no major differences in outcomes of patients with TBI when comparing EVD-guided and IP monitor–guided ICP management. In our cohort, a quarter of patients that initially received an IP monitor required an EVD later for ICP control. The prevalence of complications was higher in the EVD group.
Protocol
The core study is registered with ClinicalTrials.gov, number NCT02210221, and the Resource Identification Portal (RRID: SCR_015582).
The purpose of this study was to identify and validate new putative lead drug targets in drug-resistant mesial temporal lobe epilepsy (mTLE) starting from differentially expressed genes (DEGs) ...previously identified in mTLE in humans by transcriptome analysis. We identified consensus DEGs among two independent mTLE transcriptome datasets and assigned them status as "lead target" if they (1) were involved in neuronal excitability, (2) were new in mTLE, and (3) were druggable. For this, we created a consensus DEG network in STRING and annotated it with information from the DISEASES database and the Target Central Resource Database (TCRD). Next, we attempted to validate lead targets using qPCR, immunohistochemistry, and Western blot on hippocampal and temporal lobe neocortical tissue from mTLE patients and non-epilepsy controls, respectively. Here we created a robust, unbiased list of 113 consensus DEGs starting from two lists of 3040 and 5523 mTLE significant DEGs, respectively, and identified five lead targets. Next, we showed that CACNB3, a voltage-gated Ca
channel subunit, was significantly regulated in mTLE at both mRNA and protein level. Considering the key role of Ca
currents in regulating neuronal excitability, this suggested a role for CACNB3 in seizure generation. This is the first time changes in CACNB3 expression have been associated with drug-resistant epilepsy in humans, and since efficient therapeutic strategies for the treatment of drug-resistant mTLE are lacking, our finding might represent a step toward designing such new treatment strategies.
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