Cost-utility analysis of meaning-centered group psychotherapy for cancer survivors

Background: Meaning-centered group psychotherapy for cancer survivors (MCGP-CS) improves meaning, psychological well-being, and mental adjustment to cancer and reduces psychological distress. This randomized controlled trial was conducted to investigate the cost-utility of MCGP-CS compared with supportive group psychotherapy (SGP) and care-as-usual (CAU). Methods: In total, 170 patients were randomized to MCGP-CS, SGP, or CAU. Intervention costs, direct medical and nonmedical costs, productivity losses, and health-related quality of life were measured until 6 months follow-up, using the TIC-P, PRODISQ, data from the hospital information system, and the EQ-5D. The cost-utility was calculated by comparing mean cumulative costs and quality-adjusted life years (QALYs). Results: Mean total costs ranged from €4492 (MCGP-CS) to €5304 (CAU). Mean QALYs ranged.507 (CAU) to.540 (MCGP-CS). MCGP-CS had a probability of 74% to be both less costly and more effective than CAU, and 49% compared with SGP. Sensitivity analyses showed these findings are robust. If society is willing to pay €0 for one gained QALY, MCGP-CS has a 78% probability of being cost-effective compared with CAU. This increases to 85% and 92% at willingness-to-pay thresholds of €10 000 and €30 000, which are commonly accepted thresholds. Conclusions: MCGP-CS is highly likely a cost-effective intervention, meaning that there is a positive balance between the costs and gains of MCGP-CS, in comparison with SGP and CAU

Heterogeneous clinical phenotypes and cerebral malformations reflected by rotatin cellular dynamics

Recessive mutations in RTTN, encoding the protein rotatin, were originally identified as cause of polymicrogyria, a cortical malformation. With time, a wide variety of other brain malformations has been ascribed to RTTN mutations, including primary microcephaly. Rotatin is a centrosomal protein possibly involved in centriolar elongation and ciliogenesis. However, the function of rotatin in brain development is largely unknown and the molecular disease mechanism underlying cortical malformations has not yet been elucidated. We performed both clinical and cell biological studies, aimed at clarifying rotatin function and pathogenesis. Review of the 23 published and five unpublished clinical cases and genomic mutations, including the effect of novel deep intronic pathogenic mutations on RTTN transcripts, allowed us to extrapolate the core phenotype, consisting of intellectual disability, short stature, microcephaly, lissencephaly, periventricular heterotopia, polymicrogyria and other malformations. We show that the severity of the phenotype is related to residual function of the protein, not only the level of mRNA expression. Skin fibroblasts from eight affected individuals were studied by high resolution immunomicroscopy and flow cytometry, in parallel with in vitro expression of RTTN in HEK293T cells. We demonstrate that rotatin regulates different phases of the cell cycle and is mislocalized in affected individuals. Mutant cells showed consistent and severe mitotic failure with centrosome amplification and multipolar spindle formation, leading to aneuploidy and apoptosis, which could relate to depletion of neuronal progenitors often observed in microcephaly. We confirmed the role of rotatin in functional and structural maintenance of primary cilia and determined that the protein localized not only to the basal body, but also to the axoneme, proving the functional interconnectivity between ciliogenesis and cell cycle progression. Proteomics analysis of both native and exogenous rotatin uncovered that rotatin interacts with the neuronal (non-muscle) myosin heavy chain subunits, motors of nucleokinesis during neuronal migration, and in human induced pluripotent stem cell-derived bipolar mature neurons rotatin localizes at the centrosome in the leading edge. This illustrates the role of rotatin in neuronal migration. These different functions of rotatin explain why RTTN mutations can lead to heterogeneous cerebral malformations, both related to proliferation and migration defects.Genetics of disease, diagnosis and treatmen

Effectiveness of family-based therapy for depressive symptoms in children and adolescents: A systematic review and meta-analysis

Early-onset depression contributes significantly to the global health burden and has long-term negative effects. This meta-analysis collates and examines the effectiveness of family-based interventions, where family members are involved in the treatment of depression in children and adolescents. A literature search was performed up to 8th March 2023. Randomised controlled trials of family-based interventions were included for participants aged 3-18 years with a diagnosis of major depressive disorder or dysthymia, according to the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5; American Psychiatric Association, 2013) or with a score above a cut-off on a standardised self-report depression measure. The overall effect size for treatment versus active control was g = 0.22 (95% confidence interval [CI]: -0.05-0.50) (nine studies; 659 participants), and for treatment versus non-active control it was g = 0.46 (95% CI: -0.09-1.01) (four studies; 385 participants). Effect sizes were not statistically significant, and heterogeneity was high, ranging between I2 = 64.3-81.1%. Subgroup analysis comparing attachment-based family therapy with family therapy using other theoretical frameworks did not yield a significant difference between the two. The effects of family-based therapies were larger than those in the comparison groups, but family-based therapy did not demonstrate a significant treatment benefit compared to the controls. More randomised controlled trials are warranted, considering that evidence for other psychotherapies for depression in children and adolescents, indicates modest effects. Family-based therapy may be an alternative for children and adolescents whose needs are not addressed by these treatments.Study conception and design: Tanya van Aswegen, Soraya Seedat, Nadia van der Spek & Annemieke van Straten; Methodology and data collection: Tanya van Aswegen, Eleonora Samartzi, Linzette Morris, Nadia van der Spek & Ralph de Vries; analysis and interpretation of results: Tanya van Aswegen, Eleonora Samartzi; draft manuscript preparation: Tanya van Aswegen. All authors reviewed the results and approved the final version of the manuscript. This research is supported by the SA PTSD Research Programme of Excellence at the Department of Psychiatry, Stellenbosch University, and the South African Medical Research Council/Stellenbosch University Genomics of Brain Disorders Extramural Unit. SA PTSD Research Programme of Excellence at the Department of Psychiatry, Stellenbosch University.Scopu

Long‐term efficacy of meaning‐centered group psychotherapy for cancer survivors: 2‐Year follow‐up results of a randomized controlled trial

Objective: Meaning-centered group psychotherapy for cancer survivors (MCGP-CS) is an effective intervention to improve personal meaning, psychological well-being, and depressive symptoms until 6 months after the intervention. In this study, the long-term effects of MCGP-CS (i.e., at 1- and 2-year follow-up) on meaning, psychological well-being and posttraumatic growth were assessed, in comparison to supportive group psychotherapy (SGP) and care as usual (CAU). Methods: Cancer survivors (n = 170) were randomized into MCGP-CS, SGP, or CAU. Assessments were scheduled at baseline, 1 week, 3 months, 6 months, 1 year, and 2 years postintervention. Outcome measures were the Personal Meaning Profile, Ryff's Scales of Psychological Well-Being (SPWB), the Posttraumatic Growth Inventory, and their subscales. Linear mixed models (LMM) were used and results were both reported on an intention-to-treat (ITT) basis, as well as for intervention completers only. Results: LMM and post hoc analyses with Bonferroni correction revealed that MCGP-CS participants reported more improvement on positive relations (subscale of SPWB) than CAU participants of 2-year postintervention (ITT analysis, Cohen's d =.82). Completers also reported more personal growth (subscale of SPWB) after MCGP-CS than after SGP 1-year postintervention (Cohen's d =.94). No long-term effects were found on the other outcome measures. Conclusions: In the 2 years after MCGP-CS, the short-term significant effects on personal meaning and most positive effects related to psychological well-being faded. However, MCGP-CS had a long-term positive effect on positive relations with others and on survivors' sense of personal growth. Trial registration: Netherlands Trial Register: NTR3571

Long-term efficacy of meaning-centered group psychotherapy for cancer survivors: 2-Year follow-up results of a randomized controlled trial

Objective: Meaning-centered group psychotherapy for cancer survivors (MCGP-CS) is an effective intervention to improve personal meaning, psychological well-being, and depressive symptoms until 6 months after the intervention. In this study, the long-term effects of MCGP-CS (i.e., at 1- and 2-year follow-up) on meaning, psychological well-being and posttraumatic growth were assessed, in comparison to supportive group psychotherapy (SGP) and care as usual (CAU). Methods: Cancer survivors (n = 170) were randomized into MCGP-CS, SGP, or CAU. Assessments were scheduled at baseline, 1 week, 3 months, 6 months, 1 year, and 2 years postintervention. Outcome measures were the Personal Meaning Profile, Ryff's Scales of Psychological Well-Being (SPWB), the Posttraumatic Growth Inventory, and their subscales. Linear mixed models (LMM) were used and results were both reported on an intention-to-treat (ITT) basis, as well as for intervention completers only. Results: LMM and post hoc analyses with Bonferroni correction revealed that MCGP-CS participants reported more improvement on positive relations (subscale of SPWB) than CAU participants of 2-year postintervention (ITT analysis, Cohen's d =.82). Completers also reported more personal growth (subscale of SPWB) after MCGP-CS than after SGP 1-year postintervention (Cohen's d =.94). No long-term effects were found on the other outcome measures. Conclusions: In the 2 years after MCGP-CS, the short-term significant effects on personal meaning and most positive effects related to psychological well-being faded. However, MCGP-CS had a long-term positive effect on positive relations with others and on survivors' sense of personal growth. Trial registration: Netherlands Trial Register: NTR3571