Evaluating Effect Moderators in Cognitive Versus Behavioral Based CBT-Modules and Sequences Towards Preventing Adolescent Depression.

OBJECTIVE: The aim of this study was to investigate age group, gender, and baseline depressive symptom severity as possible effect moderators in (1) cognitive versus behavioral based CBT-modules and (2) sequences of modules that started either with cognitive or behavioral modules in indicated depression prevention in adolescents. METHOD: We conducted a pragmatic cluster-randomized trial under four parallel conditions. Each condition consisted of four CBT-modules of three sessions (cognitive restructuring, problem solving, behavioral activation, relaxation), but the sequencing of modules differed. The CBT-modules and sequences were clustered into more cognitive versus more behavioral based approaches. The sample involved 282 Dutch adolescents with elevated depressive symptoms (Mage = 13.8; 55.7% girls, 92.9% Dutch). Assessments were conducted at baseline, after three sessions, at post-intervention and 6-month follow-up with self-reported depressive symptoms as the primary outcome. RESULTS: We found no evidence for substantial moderation effects. Age group, gender, and depressive symptom severity level at baseline did not moderate the effects of cognitive versus behavioral modules after three sessions. No evidence was also found that these characteristics moderated the effectiveness of sequences of modules that started either with cognitive or behavioral modules at post-intervention and 6-month follow-up. CONCLUSION: Cognitive and behavioral based modules and sequences in the prevention of depression in adolescents might apply to a relatively wide range of adolescents in terms of age group, gender, and severity levels of depressive symptoms.Abbreviation: CDI-2:F: Children's Depression Inventory-2 Full-length version; CDI-2:S: Children's Depression Inventory-2 Short version; STARr: Solve, Think, Act, Relax, and repeat.

Relative Effectiveness of CBT-Components and Sequencing in Indicated Depression Prevention for Adolescents: A Cluster-Randomized Microtrial.

OBJECTIVE: Cognitive Behavioral Therapy (CBT) was dismantled into four modules of three sessions each: cognitive restructuring (Think), behavioral activation (Act), problem solving (Solve) and relaxation (Relax). We investigated the modules' relative effectiveness in indicated depression prevention for adolescents and examined variations in sequencing of these modules. METHOD: We performed a pragmatic cluster-randomized microtrial with four parallel conditions: (1) Think-Act-Relax-Solve (n = 14 clusters, n = 81 participants); (2) Act-Think-Relax-Solve (n = 13, n = 69); (3) Solve-Act-Think-Relax (n = 13, n = 77); and (4) Relax-Solve-Act-Think (n = 12, n = 55). The sample consisted of 282 Dutch adolescents with elevated depressive symptoms (Mage = 13.8; 55.7% girls, 92.9% Dutch). In total 52 treatment groups were randomized as a cluster. Assessments were conducted at baseline, after each module and at 6-month follow-up with depressive symptoms as primary outcome. RESULTS: None of the modules (Think, Act, Solve, Relax) was associated with a significant decrease in depressive symptoms after three sessions and no significant differences in effectiveness were found between the modules. All sequences of modules were associated with a significant decrease in depressive symptoms at post-intervention, except the sequence Relax-Solve-Act-Think. At 6-month follow-up, all sequences showed a significant decrease in depressive symptoms. No significant differences in effectiveness were found between the sequences at post-intervention and 6-month follow-up. CONCLUSIONS: Regardless of the CBT technique provided, one module of three sessions may not be sufficient to reduce depressive symptoms. The sequence in which the CBT components cognitive restructuring, behavioral activation, problem solving and relaxation are offered, does not appear to significantly influence outcomes at post- intervention or 6-month follow-up. ABBREVIATIONS: CDI-2:F: Children's Depression Inventory-2 Full-length version; CDI-2:S: Children's Depression Inventory-2 Short version; STARr: Solve, Think, Act, Relax and repeat.

Transcriptome sequencing reveals two subtypes of cortisol-secreting adrenocortical tumours in dogs and identifies CYP26B1 as a potential new therapeutic target.

Cushing's syndrome (CS) is a serious endocrine disorder that is relatively common in dogs, but rare in humans. In ~15%-20% of cases, CS is caused by a cortisol-secreting adrenocortical tumour (csACT). To identify differentially expressed genes that can improve prognostic predictions after surgery and represent novel treatment targets, we performed RNA sequencing on csACTs (n = 48) and normal adrenal cortices (NACs; n = 10) of dogs. A gene was declared differentially expressed when the adjusted p-value was <.05 and the log2 fold change was >2 or < -2. Between NACs and csACTs, 98 genes were differentially expressed. Based on the principal component analysis (PCA) the csACTs were separated in two groups, of which Group 1 had significantly better survival after adrenalectomy (p = .002) than Group 2. Between csACT Group G1 and Group 2, 77 genes were differentially expressed. One of these, cytochrome P450 26B1 (CYP26B1), was significantly associated with survival in both our canine csACTs and in a publicly available data set of 33 human cortisol-secreting adrenocortical carcinomas. In the validation cohort, CYP26B1 was also expressed significantly higher (p = .012) in canine csACTs compared with NACs. In future studies it would be interesting to determine whether CYP26B1 inhibitors could inhibit csACT growth in both dogs and humans.

Societal costs of subclinical depressive symptoms in Dutch adolescents: a cost-of-illness study.

BACKGROUND: Subclinical depressive symptoms are highly prevalent among adolescents and are associated with negative consequences, which may pose an economic burden for society. We conducted a prevalence-based cost-of-illness study using a societal perspective to investigate the cost-of-illness of subclinical depressive symptoms among adolescents. METHODS: Using a bottom-up approach, cost questionnaires were assessed to measure costs from 237 Dutch families with an adolescent aged 11-18 with subclinical depressive symptoms (of which 34 met the criteria of a depressive disorder). The study is registered in the Dutch Trial Register (Trial NL5584/NTR6176; www.trialregister.nl/trial/5584). RESULTS: Our calculations show that adolescents with subclinical depressive symptoms cost the Dutch society more than €42 million annually, expressed in costs related to depressive symptoms. Secondary analyses were performed to test the reliability and stability of the costs. When costs related to psychological problems were considered, the annual costs amounted to €67 million. The total societal costs related to physical problems amounted to approximately €126 million. All costs combined (depressive, psychological, behavioural and physical problems and other reasons) amounted to a €243 million. Total costs were highest for physical-related problems of the adolescent (52% of the total costs), followed by psychological (28%), depressive (17%) and behavioural problems (1%). Using an international prevalence rate, societal costs related to depressive symptoms resulted in €54 million a year. CONCLUSIONS: Cost-effective prevention programmes seem warranted given the high societal costs and risk of future costs as subclinical depressive symptoms could be a precursor of clinical depression later in life.

Basic Motor Skills of Children With Down Syndrome: Creating a Motor Growth Curve.

PURPOSE: To create a motor growth curve based on the Test of Basic Motor Skills for Children with Down Syndrome (BMS) and estimate the age of achieving BMS milestones. METHODS: A multilevel exponential model was applied to create a motor growth curve based on BMS data from 119 children with Down syndrome (DS) aged 2 months to 5 years. Logistic regression was applied to estimate the 50% probability of achieving BMS milestones. RESULTS: The BMS growth curve had the largest increase during infancy with smaller increases as children approached the predicted maximum score. The age at which children with DS have a 50% probability of achieving the milestone sitting was 22 months, for crawling 25 months, and for walking 38 months. CONCLUSIONS: The creation of a BMS growth curve provides a standardization of the gross motor development of children with DS. Physical therapists then may monitor a child's individual progress and improve clinical decisions.

Coping with stressful life events: Cognitive emotion regulation profiles and depressive symptoms in adolescents.

Cognitive strategies that adolescents use to cope with negative emotions might show distinct profiles of cognitive emotion regulation strategies, which could be differentially associated with depressive symptoms. In total, 411 Dutch adolescents who had experienced at least one stressful life event that required some coping strategy participated in this study, including 334 nonclinical and 77 clinically depressed adolescents (12-21 years). A person-centered approach with Latent Profile Analysis was used to identify underlying profiles of cognitive emotion regulation based on the adolescents' reports of their use of cognitive emotion regulation strategies when they were confronted with stressful life events. Nine different strategies, five adaptive and four maladaptive, were used as indicators. Four profiles with distinct features were found in the nonclinical sample, as well as in the combined sample of nonclinical and clinically depressed adolescents: Low Regulators, High Regulators, Maladaptive Regulators, and Adaptive Regulators. In both samples, the High Regulators profile was most commonly used, followed by the Adaptive, Maladaptive, and Low Regulators profile. Maladaptive Regulators endorsed higher levels of depressive symptoms relative to Low, High, and Adaptive Regulators. The findings underscore the utility of using a person-centered approach in order to identify patterns of cognitive emotion regulation deficits in psychopathology.

Dismantling the relative effectiveness of core components of cognitive behavioural therapy in preventing depression in adolescents: protocol of a cluster randomized microtrial.

BACKGROUND: Both depressive disorder and subclinical depressive symptoms during adolescence are a major public health concern. Therefore, it is important that depression is detected at an early stage and is treated preventively. Prevention based on the principles of Cognitive Behavioural Therapy (CBT) has proven to be the most effective, however research has mainly focused on the effectiveness of "prevention packages" consisting of multiple CBT-components, rather than on the distinct CBT-components. This study will evaluate the relative effectiveness of four core components of CBT (cognitive restructuring (CR), behavioural activation (BA), problem solving (PS) and relaxation (RE)). In addition the relative (cost-)effectiveness of four different sequences of these components will be evaluated: (1) CR - BA - RE - PS, (2) BA - CR - RE - PS, (3) PS - GA - CR - RE and (4) RE - PS - BA - CR. METHODS: We will perform a non-blinded multisite cluster randomized prevention microtrial with four parallel conditions consisting of the four sequences. The four sequences of components will be offered in groups of high school students with elevated depressive symptoms. For each CBT-component a module of three sessions is developed. Assessments will be conducted at baseline, after each CBT-component, prior to each session, at post-intervention and at 6-month follow-up. Potential moderators and mediators will be evaluated exploratively to shed light on for whom the (sequences of) CBT-components are most effective and how effects are mediated. DISCUSSION: The potential value of the study is insight in the relative effectiveness of the four most commonly used CBT-components and four different sequences, and possible moderators and mediators in the prevention of depression among adolescents. This knowledge can be used to optimize and personalize CBT-programs. TRIAL REGISTRATION: The study is registered in the Dutch Trial Register (Trial NL5584 / NTR6176) on October 13, 2016.

Effectiveness of CBT for children and adolescents with depression: A systematic review and meta-regression analysis.

BACKGROUND: Cognitive-behavioral therapy (CBT) is first choice of treatment for depressive symptoms and disorders in adolescents, however improvements are necessary because overall efficacy is low. Insights on CBT components and contextual and structural characteristics might increase the efficacy. The aim of our approach is to evaluate the efficacy of CBT for youth with depression and investigate the influence of specific components, contextual and structural factors that could improve effects. METHODS: A systematic review of randomized controlled trials was conducted, searches were undertaken in CINAHL, CENTRAL, EMBASE, MEDLINE/PubMed and PsycINFO. Outcomes were meta-analyzed and confidence in results was assessed using the GRADE-method. Meta-regression was used to pinpoint components or other factors that were associated with an in- or decrease of effects of CBT. RESULTS: We included 31 trials with 4335 participants. Moderate-quality evidence was found for CBT reducing depressive symptoms at the end of treatment and at follow-up, and CBT as indicated prevention resulted in 63% less risk of being depressed at follow-up. CBT containing a combination of behavioral activation and challenging thoughts component (as part of cognitive restructuring) or the involvement of caregiver(s) in intervention were associated with better outcomes for youth on the long term. CONCLUSIONS: There is evidence that CBT is effective for youth with a (subclinical) depression. Our analyses show that effects might improve when CBT contains the components behavioral activation and challenging thoughts and also when the caregiver(s) are involved. However, the influential effects of these three moderators should be further tested in RCTs.

Early body weight loss during concurrent chemo-radiotherapy for non-small cell lung cancer.

BACKGROUND AND PURPOSE: Radiation-esophagitis and weight loss are frequently observed toxicities in patients treated with concurrent chemo-radiotherapy (CT-RT) for non-small cell lung cancer (NSCLC) and might be related. The purpose was to investigate whether weight loss already starts early after initiation of CT-RT and precedes radiation-esophagitis. MATERIALS AND METHODS: In a retrospective cohort, weight and esophagitis grade ≥2 were assessed during the first weeks of (CT-)RT in patients treated with concurrent (n = 102) or sequential (n = 92) therapy. In a prospective validation study, data on body weight, esophagitis grade ≥2, nutritional intake and muscle strength were obtained before, during and following CT-RT. RESULTS: In the retrospective cohort, early weight loss was observed in concurrently treated patients (p = 0.002), independent of esophagitis ≥ grade 2. Early weight loss was also observed in the prospective cohort (p = 0.003) and was not accompanied by decreases in nutritional intake. In addition lower limb muscle strength rapidly declined (p = 0.042). In the later weeks of treatment, further body weight loss occurred (p < 0.001) despite increased nutritional supplementation and body weight was only partly recovered after 4 weeks post CT-RT (p = 0.003). CONCLUSIONS: Weight loss during concurrent CT-RT for NSCLC starts early and prior to onset of esophagitis, requiring timely and intense nutritional rehabilitation.

Perfusion of the deep inferior epigastric perforator flap measured by laser Doppler imager.

BACKGROUND: During surgery, circulation changes in the deep inferior epigastric perforator free flap (DIEP). Although blood flow is an important parameter for surgical outcome, little research has been performed on this topic, especially during the process of transplantation. This study examined the pattern of perfusion of DIEP flaps over time. METHODS: In all, 16 flaps were studied in 14 DIEP patients. Flap perfusion was measured with the laser Doppler imager at 4 different time points-before, during, and after surgery. RESULTS: Both central and peripheral perfusion did not alter after dissection, when blood supply became restricted to the abdominal vascular pedicle. After transplantation, blood flow was higher in the central part of the flap compared with the peripheral border. Central flow increased after transplantation, compared with measurements before and during surgery. Peripheral flow, however, decreased after transplantation. CONCLUSIONS: Surprisingly, flap perfusion did not alter after dissection. It only changed after flap transplantation, when central blood flow increased and peripheral flow decreased.

Review: Ischaemia-reperfusion injury in flap surgery.

Ischaemia-reperfusion injury is the mechanism underlying (partial) flap loss. This is not only a traumatic event for the patient, it also causes increased patient morbidity [Kerrigan CL, Stotland MA. Ischemia reperfusion injury: a review. Microsurgery 1993;14:165-75] as well as prolonged hospitalisation, increasing medical consumption and costs. For surgeons who perform flap surgery, it is important to have knowledge of ischaemia-reperfusion injury in order to prevent it. In this article, an update on the recent research on ischaemia-reperfusion is given. The production of reactive oxygen species, neutrophil influx, depletion of NO and apoptosis are discussed as well.

Responsiveness of the Test of Basic Motor Skills of Children with Down Syndrome.

The aim of this study was to examine the responsiveness of the Test of Basic Motor Skills for Children with Down Syndrome (BMS). Forty-one children with Down Syndrome, 3 to 36 months of age, participated in the study. Gross motor skills were assessed three times using the BMS and the Gross Motor Function Measure (GMFM) before and after a baseline period of 2 weeks (T1-T2) and after a period of 16 weeks (T2-T3). Internal and external responsiveness of the BMS was analyzed using Guyatt's Responsiveness Index (GRI) and 2 x 2 repeated measures. Change in BMS scores was compared to change in GMFM scores and parent and physiotherapist ratings of change. The responsiveness of the BMS was large (GRI = 2.55). A significant Time x Age interaction [F(1,37) = 8.87, p < .01] indicated that BMS scores increased more for children