Effectiveness and long-term stability of outpatient cognitive behavioural therapy (CBT) for children and adolescents with anxiety and depressive disorders under routine care conditions.

BACKGROUND: Randomised controlled trials (RCTs) have provided considerable evidence for the short-term efficacy of cognitive behavioural therapy (CBT) in children and adolescents with depressive and anxiety disorders. However, the effectiveness and long-term stability of treatment effects under routine care conditions remain unproven. AIMS: This observational study investigates the effectiveness and stability of CBT under routine care conditions within a large sample of clinically referred youth with depressive and anxiety disorders. METHOD: Two hundred and twenty former patients (age 6-18 years at start of treatment) underwent a follow-up assessment (follow-up interval: M=5.3 years, SD=2.47). Parent and self-ratings of behavioural and emotional problems were obtained at the beginning and end of treatment and at follow-up. Additionally, at follow-up, a telephone interview and questionnaires exploring other mental symptoms and life satisfaction were administered. RESULTS: A repeated measures ANOVA yielded statistically significant, medium to large pre- post symptom reductions (ηp2=.15 to ηp²=.47) and small to medium post-follow-up symptom reductions (ηp²=.03 to ηp²=.19). At follow-up, between 57 and 70% of the sample reported a decrease in different emotional symptoms since the end of treatment, and 80% reported improved life satisfaction. CONCLUSIONS: These findings provide evidence for the effectiveness and stability of treatment effects of CBT in youth with depressive and anxiety disorders under routine care conditions. Due to the lack of a direct control condition and a substantial proportion of missing data, the results must be interpreted with caution.

Progress feedback in children and adolescents with internalizing and externalizing symptoms in routine care (OPTIE study): study protocol of a randomized parallel-group trial.

BACKGROUND: Progress feedback provides therapists with progress notes on a regular basis through the continuous assessment of participants throughout their treatment (e.g., symptoms, therapeutic alliance). While for adults the evidence base has increased over the years, progress feedback in the therapy of children and adolescents has not been sufficiently investigated. This manuscript describes the trial protocol of the OPTIE study: a randomized trial that tests the efficacy of a progress feedback system in children and adolescents under conditions of routine care. METHODS: The study is based on a randomized parallel-group trial with two treatment groups (routine, feedback) at an outpatient unit of a university hospital. The target sample size is 439 families consisting of children and adolescents aged 6 to17 years old with internalizing and/or externalizing symptoms. Both the patients and the therapists are independently assigned to the treatment groups by stratified block randomization. In both treatment groups patients receive routine care behavioral therapy for a study-related 12 months; additionally, in the feedback group, a progress feedback system with three components is applied (monitoring, report, and supervision). For three informants (caregiver, child [≥ 11 years], therapist) surveys are conducted every 6 weeks (e.g., symptoms, goals, motivation). For both treatment groups, comparison data is collected at baseline and at six and 12 months after the beginning of the intervention (pre, inter, post), and includes five informants (blinded clinician, therapist, caregiver, child [≥ 11 years], teacher). DISCUSSION: The OPTIE study will contribute to the evidence base of progress feedback in children and adolescents and has the potential to uncover treatments' effects in the small to medium range. Noteworthy features are the inclusion of children younger than 10 years old and the consideration of a blinded clinician rating. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) DRKS00016737 ( https://www.drks.de/DRKS00016737 ). Registered 17 September, 2019.

Effectiveness of usual-care cognitive-behavioral therapy for adolescents with depressive disorders rated by parents and patients - an observational study.

BACKGROUND: Depressive disorders are common in adolescence and are associated with a wide range of negative long-term outcomes. Highly controlled randomized controlled trials (RCT) provide considerable evidence for the efficacy of cognitive-behavioral therapy (CBT) as a treatment for depression, but studies examining the effectiveness of CBT in clinical settings are very rare . METHODS: In the present observational study, the changes achieved through routine CBT in adolescents with depressive disorders treated in a clinical setting in terms of a university outpatient clinic were analyzed, and compared to a historical control group of adolescents with depressive disorders who had received treatment as usual. At the start and end of treatment (pre- and post-assessment), parent and self-ratings of the German versions of the Youth Self-Report (YSR), the Child Behavior Checklist (CBCL) and rating scales for depressive symptoms (FBB-DES, SBB-DES) were assessed. A total of 331 adolescents aged 11-18 years with complete data were assessed for the main analysis. RESULTS: The analysis yielded small to large pre-post effect sizes (Cohen's d) for the total sample (d = 0.33 to d = 0.82) and large effect sizes for adolescents who were rated in the clinical range on each (sub) scale at the start of treatment (d = 0.85 to d = 1.30). When comparing patients in the clinical range with historical controls, medium to large net effect sizes (d = 0.53 to d = 2.09) emerged for the total scores in self- and parent rating. However, a substantial proportion of the sample remained in the clinical range at the end of treatment. CONCLUSIONS: These findings suggest that CBT is effective for adolescents with depressive disorders when administered under routine care conditions, but the results must be interpreted with caution due to the lack of a direct control condition. TRIAL REGISTRATION: DRKS, DRKS00021518 . Registered 27 April 2020 - Retrospectively registered, http://drks.de.

Parent- and therapist-rated treatment satisfaction following routine child cognitive-behavioral therapy.

This observational study examined treatment satisfaction (TS) following routine outpatient cognitive-behavioral therapy (CBT) in a large sample of children (n = 795; aged 6 to 10 years). TS was investigated in parent and therapist rating. Means, standard deviations and inter-rater correlations were calculated to investigate TS. Regression analysis was conducted to examine potential correlates of TS (patient-related variables, mental disorder characteristics, socio-demographic factors and treatment variables). High TS in parent and therapist rating was found, with therapists showing a lower degree of TS than parents (completely or predominantly satisfied: parent rating 94.1%, therapist rating 69.5%). A statistically significant, moderate inter-rater correlation was found. Regression analysis explained 21.8% of the variance in parent rating and 57.2% in therapist rating. Most of the TS variance was explained by mental disorder characteristics (parent-rated symptoms and therapist-rated global impairment at treatment end) and by treatment variables (especially the therapist-rated cooperation of parents and patients), whereas socio-demographic and patient-related variables did not show any relevant associations with TS. Based on these results, to optimize TS, therapists should concentrate on establishing a sustainable cooperation of parents and children during therapy, and work to achieve a low global impairment at treatment end.

Treatment satisfaction following routine outpatient cognitive-behavioral therapy of adolescents with mental disorders: a triple perspective of patients, parents and therapists.

The present study investigates treatment satisfaction (TS) rated by multiple informants (patient, parent, therapist) following routine outpatient cognitive-behavioral therapy (CBT) within a large sample (n = 965) of clinically referred adolescents aged 11-20 years. Moreover, potential predictors of TS were analyzed (patient-related variables, mental disorder characteristics, socio-demographic factors and treatment variables). Overall, our results show a high treatment satisfaction in patient, parent and therapist ratings, with the therapists being the most critical raters (completely/predominantly satisfied: 87.8% in patient, 92.0% in parent, and 64.0% in therapist ratings). Correlations between the three raters were only small to moderate, but statistically significant. Regression analysis examining differential effects found that mental disorder characteristics (parent- and patient-reported symptoms at post) and treatment variables (especially cooperation of patients and parents as rated by therapists) explained most of the variance in TS, whereas patient-related or socio-demographic variables did not emerge as relevant predictors of TS. The amounts of explained variance were R adj. 2 = 0.594 in therapist rating, R adj. 2 = 0.322 in patient rating and R adj. 2 = 0.203 in parent rating.

Antitumor effects of curcumin, alone or in combination with cisplatin or doxorubicin, on human hepatic cancer cells. Analysis of their possible relationship to changes in NF-kB activation levels and in IAP gene expression.

The hepatic cancer HA22T/VGH cell line, which constitutively expresses activated nuclear factor-kappaB (NF-kB), was chosen as a model to examine the antitumor activity of curcumin, also in relationship to its possible influences on the activation of the transcription factor and on the expression of the inhibitory of apoptosis proteins (IAPs) and of other NF-kB target genes. Curcumin exerted cell growth inhibitory and apoptotic effects, related, at least part, to free radical generation and mainly dependent on caspase-9 and -3 activation. The combination of curcumin with cisplatin resulted in a synergistic antitumor activity and that with doxorubicin in additivity or sub-additivity. Curcumin exerted biphasic changes in the levels of NF-kB, with an increase at 8 h after its administration and a decrease at 16 h. For the combinations of curcumin with the other drugs, the levels of the transcription factor were lower than those predicted from the effects of the single agents, especially with a blunting of the remarkable increases in NF-kB activation induced by doxorubicin. Except for Bcl-2, the HA22T/VGH cells expressed different other genes, including the IAPs, implicated in cell proliferation and survival. Curcumin determined early changes in COX-2 and c-myc mRNAs, which were down-regulated, and in livin mRNA, which was up-regulated. Later it decreased Bcl-X(L) mRNA and increased Bcl-X(S) and c-IAP-2 mRNAs. Cisplatin and doxorubicin exerted distinct effects on gene expression. The cytotoxic interactions between curcumin and these agents were accompanied by synergistic (in particular with cisplatin) or additive effects of decrease in the expression of different genes, including c-myc, Bcl-X(L), c-IAP-2, NAIP and XIAP. However, the combinations attenuated also certain other influences on mRNA expression of the single agents, like, for example, the increases in Bcl-X(s) given by curcumin and doxorubicin. Overall, the effects of the drugs, alone or in combination, on tumor cell growth, cell death and gene expression did not show a simple relationship to the relative influences on NF-kB activation, inferring that they can be due also to other mechanisms.

Antiallergic and antihistaminic effect of two extracts of Capparis spinosa L. flowering buds.

The antiallergic properties of two lyophilized extracts obtained from Capparis spinosa L. flowering buds (capers) by methanol extraction, carried out at room temperature (CAP-C) or with heating at 60 degrees C (CAP-H), were investigated. The protective effects of CAP-H and CAP-C, orally administered (14.28 mg[sol ]kg), were evaluated against Oleaceae antigen challenge-induced and histamine-induced bronchospasm in anaesthetized guinea-pigs. Furthermore, the histamine skin prick test was performed on humans, applying a gel formulation containing 2% CAP-C (the only extract able to protect against histamine-induced bronchospasm) on the skin for 1 h before histamine application and monitoring the erythema by reflectance spectrophotometry. The CAP-H showed a good protective effect against the bronchospasm induced by antigen challenge in sensitized guinea-pigs; conversely, a significant decrease in the responsiveness to histamine was seen only in CAP-C pretreated animals. Finally, the CAP-C gel formulation possessed a marked inhibitory effect (46.07%) against histamine-induced skin erythema. These two caper extracts displayed marked antiallergic effectiveness; however, the protective effect of CAP-H was very likely due to an indirect mechanism (for example, inhibition of mediator release from mast cells or production of arachidonic acid metabolites); conversely, CAP-C is endowed with direct antihistaminic properties. The different mechanisms of action of CAP-H and CAP-C may be related to a difference in the extraction procedure and, thus, in their qualitative[sol ]quantitative chemical profile.