Trauma-focused treatments for refugee children: study protocol for a randomized controlled trial of the effectiveness of KIDNET versus EMDR therapy versus a waitlist control group (KIEM).

BACKGROUND: Prevalence of posttraumatic stress disorder (PTSD) in refugees is reportedly higher in comparison to the general population. Refugee children specifically are often coping with trauma and loss and are at risk for mental health difficulties. With staggering numbers of people seeking refuge around the world and 50% being 18 years or younger, research examining the effects of trauma-focused therapies for refugee children with PTSD is highly needed. Both Eye Movement Desensitization and Reprocessing (EMDR) therapy and the child version of Narrative Exposure Therapy (KIDNET) have been used for refugees, although these treatment methods have not been systematically compared. The aim of the current study is to investigate the effectiveness of EMDR and KIDNET, compared to a waitlist control group and with each other, offered to refugee children. METHODS: A randomized controlled three-arm trial has been designed. The primary outcome is PTSD diagnosis and symptom severity assessed with the Clinician-Administered PTSD Scale for Children DSM5 (CAPS-CA-5) at baseline (T1), 1 month post-treatment, or after 8 weeks of waiting (T2) and 3 months follow-up (T3). Additionally, instruments to assess posttraumatic stress symptoms, behavioral and emotional problems, and quality of life perception in children aged 8-18 are conducted at T1, T2, and T3. DISCUSSION: This is the first RCT that examines the effectiveness of EMDR and KIDNET in refugee children aged 8-18 years specifically, compared to a waitlist control group intended to reduce PTSD diagnosis and severity of posttraumatic stress symptoms and comorbid complaints in a growing and challenging population. TRIAL REGISTRATION: Dutch Trial Register NL40769 . Retrospectively registered on June 16, 2021.

Neurocognitive functioning over the course of trauma-focused psychotherapy for PTSD: Changes in verbal memory and executive functioning.

OBJECTIVES: Individuals with post-traumatic stress disorder (PTSD) have neurocognitive deficits in verbal memory and executive functioning. In this study, we examined whether memory and executive functioning changed over the course of treatment and which clinical variables were associated with change. DESIGN: Neuropsychological assessments were administered at baseline and endpoint of a randomized controlled trial as secondary outcome. METHODS: Trauma survivors (n = 88) diagnosed with PTSD received trauma-focused psychotherapy within a 17-week randomized controlled trial. Neuropsychological tests were the California Verbal Learning Test, Rivermead Behavioural Memory Test, Stroop Color Word Test, and Trail Making Test. RESULTS: Significant, small- to medium-sized improvements in verbal memory, information processing speed, and executive functioning were found after trauma-focused psychotherapy (Cohen's d 0.16-0.68). Greater PTSD symptom decrease was significantly related to better post-treatment neurocognitive performance (all p < .005). Patients with comorbid depression improved more than patients with PTSD alone on interference tasks (p < .01). No differences emerged between treatment conditions and between patients on serotonergic antidepressants and those who were not. CONCLUSIONS: This study suggests that neurocognitive deficits in PTSD can improve over the course of trauma-focused psychotherapy and are therefore at least partly reversible. Improvements over treatment are in line with previous neuropsychological and neuroimaging studies and effect sizes exceed those of practice effects. Future research should determine whether these changes translate into improved functioning in the daily lives of the patients. PRACTITIONER POINTS: Patients with PTSD have difficulties performing verbal memory tasks (e.g., remembering a grocery list, recall of a story) and executive functioning tasks (e.g., shifting attention between two tasks, ignoring irrelevant information to complete a task). Verbal memory, information processing speed, and executive functioning significantly improved in patients with post-traumatic stress disorder over the course of trauma-focused psychotherapy. Improvements were equal in size for two different trauma-focused psychotherapies (Eye movement desensitization and reprocessing therapy and brief eclectic psychotherapy for PTSD). Medium-sized effects were found for recall of a story, whereas effects in other aspects of verbal memory, information processing speed, and executive functioning were small-sized. No causal attributions can be made because we could not include a control group without treatment for ethical reasons. Findings may be more reflective of patients who completed treatment than patients who prematurely dropped out as completers were overrepresented in our sample.

Liquid chromatography-tandem mass spectrometric assay for the PARP-1 inhibitor olaparib in combination with the nitrogen mustard melphalan in human plasma.

A bioanalytical assay for the new poly(ADP-ribose) polymerase-1 inhibitor olaparib in combination with melphalan was developed and validated. For the quantitative assay, human plasma samples were pre-treated on ice using protein precipitation with 2% (v/v) acetic acid in acetonitrile containing erlotinib and melphalan-d8 as internal standards. The extract was diluted with water and injected into the chromatographic system. This system consisted of a sub-2 µm particle, trifunctional bonded octadecyl silica column with an isocratic elution using 0.01% (v/v) of formic acid in a mixture of water and methanol. The eluate was transferred into the electrospray interface with positive ionization and the analyte was detected in the selected reaction monitoring mode of a triple quadrupole mass spectrometer. The assay was validated in a 10-5000 ng/ml calibration range for both drugs. The lowest level of this range corresponded to the lower limit of quantification. Within day precisions were 3.0-9.3%, between day precisions 6.0-9.8% and accuracies were between 101 and 110% for the whole calibration range. After validation the assay was used to assess the pharmacokinetics of olaparib in a patient with metastatic breast carcinoma. In addition, systemic exposure of melphalan was monitored in patients subjected to isolated hepatic perfusion with this drug. Both applications show that the new assay can be applied for human pharmacokinetic studies for both drugs.