RESUMEN
Introduction: In recent decades, various new psychotherapy approaches have been developed in an effort to overcome issues of non-response, referred to as "third-wave psychotherapies." How third-wave therapies perform in comparison to each other, to classical CBT, or other common comparators in the treatment of depression has not yet been systematically assessed. Methods: We firstly determined the scope of the term "third-wave" by conducting a systematic search. The identified approaches were then used as search terms for the systematic review and network meta-analysis (NMA). We searched MEDLINE, CENTRAL, PsychINFO and Web of Science from inception until 31 July 2022. We assessed randomized controlled trials comparing third-wave psychotherapies to each other, CBT, treatment as usual (TAU), medication management, active control conditions, or waitlist (WL) in adult populations with depressive disorders. The treatments included were acceptance and commitment therapy, behavioral activation, cognitive behavioral analysis system of psychotherapy, dialectical behavioral therapy, mindfulness-based cognitive therapy, meta-cognitive therapy, positive psychotherapy and schema therapy. The primary outcome was depression severity (efficacy) at study endpoint, and the secondary outcome was all-cause discontinuation (acceptability). This review was registered in PROSPERO, identifier CRD42020147535. Results: Of 7,971 search results, 55 trials were included in our NMA (5,827 patients). None of the third-wave therapies were more efficacious than CBT but most were superior to TAU [standardized mean differences (SMD) ranging between 0.42 (95% CI -0.37; 1.19) and 1.25 (0.48; 2.04)]. Meta-cognitive therapy (MCT) was more efficacious than three other third-wave therapy approaches. None of the third-wave treatments were more acceptable than WL or CBT. Twenty-seven percent of the trials were rated as low risk of bias. Confidence in the evidence was largely low according to GRADE. Inconsistency emerged for a small number of comparisons. Interpretations: Third-wave therapies are largely efficacious and acceptable alternatives to CBT when compared to TAU, with few differences between them. The evidence so far does not point toward superiority or inferiority over CBT. Patient-level research may offer possibilities for tailoring individual psychotherapies to the needs of individual patients and future trials should make this data available. The evidence base needs to be broadened by sufficiently powered trials.
RESUMEN
Large-scale gene expression analyses of microdissected primary tissue are still difficult because generally only a limited amount of mRNA can be obtained from microdissected cells. The introduction of the T7-based RNA amplification technique was an important step to reduce the amount of RNA needed for such analyses. This amplification technique produces amplified antisense RNA (aRNA), which so far has precluded its direct use for serial analysis of gene expression (SAGE) library production. We describe a method, termed 'aRNA-longSAGE', which is the first to allow the direct use of aRNA for standard longSAGE library production. The aRNA-longSAGE protocol was validated by comparing two aRNA-longSAGE libraries with two Micro-longSAGE libraries that were generated from the same RNA preparations of two different cell lines. Using a conservative validation approach, we were able to verify 68% of the differentially expressed genes identified by aRNA-longSAGE. Furthermore, the identification rate of differentially expressed genes was roughly twice as high in our aRNA-longSAGE libraries as in the standard Micro-longSAGE libraries. Using our validated aRNA-longSAGE protocol, we were able to successfully generate longSAGE libraries from as little as 40 ng of total RNA isolated from 2000-3000 microdissected pancreatic ductal epithelial cells or cells from pancreatic intraepithelial neoplasias.