7 research outputs found

    Determining what works in the treatment of PTSD

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    Many researchers accept that trauma-focused treatments are superior to non-trauma focused treatments for Post-Traumatic Stress Disorder (PTSD). However, Benish, Imel, and Wampold (2008) recently published a meta-analysis of clinical trials directly comparing 'bona fide' PTSD treatments that failed to reject the null hypothesis that PTSD treatments are similarly effective. They concluded that the results of previous meta-analysis may have been influenced by several confounds, including the use of control treatments, to make conclusions about the relative efficacy of specific PTSD treatments. Ehlers et al. (2010) claim that the selection procedures of the Benish et al. meta-analysis were biased and cite results from individual studies and previous meta-analyses that suggest trauma-focused psychological treatments are superior to non-trauma focused treatments. We first offer a review and justification of the coding criteria and procedure used in Benish et al. In addition, we discuss the appropriateness of utilizing treatments designed to control for non-specifics or common factors such as 'supportive therapy' for determining the relative efficacy of specific PTSD treatments. Finally, we note several additional confounds, such as therapist effects, allegiance, and alteration of legitimate protocols, in PTSD research and describe conceptual problems involved in the classification scheme used to determine the "trauma focus" of interventions, which lead to inappropriate conclusions about what works in the treatment of PTSD

    Targeting the Wnt signaling pathway through R-spondin 3 identifies an anti-fibrosis treatment strategy for multiple organs

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    The Wnt/β-catenin signaling pathway has been implicated in human proliferative diseases such as cancer and fibrosis. The functions of β-catenin and several other components of this pathway have been investigated in fibrosis. However, the potential role of R-spondin proteins (RSPOs), enhancers of the Wnt/β-catenin signaling, has not been described. A specific interventional strategy targeting this pathway for fibrosis remains to be defined. We developed monoclonal antibodies against members of the RSPO family (RSPO1, 2, and 3) and probed their potential function in fibrosis in vivo. We demonstrated that RSPO3 plays a critical role in the development of fibrosis in multiple organs. Specifically, an anti-RSPO3 antibody, OMP-131R10, when dosed therapeutically, attenuated fibrosis in carbon tetrachloride (CCl4)-induced liver fibrosis, bleomycin-induced pulmonary and skin fibrosis models. Mechanistically, we showed that RSPO3 induces multiple pro-fibrotic chemokines and cytokines in Kupffer cells and hepatocytes. We found that the anti-fibrotic activity of OMP-131R10 is associated with its inhibition of β-catenin activation in vivo. Finally, RSPO3 was found to be highly elevated in the active lesions of fibrotic tissues in mouse models of fibrosis and in patients with idiopathic pulmonary fibrosis (IPF) and nonalcoholic steatohepatitis (NASH). Together these data provide an anti-fibrotic strategy for targeting the Wnt/β-catenin pathway through RSPO3 blockade and support that OMP-131R10 could be an important therapeutic agent for fibrosis

    Do all psychological treatments really work the same in posttraumatic stress disorder?

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    A recent meta-analysis by Benish, Imel, and Wampold (2008, Clinical Psychology Review, 28, 746–758) concluded that all bona fide treatments are equally effective in posttraumatic stress disorder (PTSD). In contrast, seven other meta-analyses or systematic reviews concluded that there is good evidence that trauma-focused psychological treatments (trauma-focused cognitive behavior therapy and eye movement desensitization and reprocessing) are effective in PTSD; but that treatments that do not focus on the patients' trauma memories or their meanings are either less effective or not yet sufficiently studied. International treatment guidelines therefore recommend trauma-focused psychological treatments as first-line treatments for PTSD. We examine possible reasons for the discrepant conclusions and argue that (1) the selection procedure of the available evidence used in Benish et al.'s (2008)meta-analysis introduces bias, and (2) the analysis and conclusions fail to take into account the need to demonstrate that treatments for PTSD are more effective than natural recovery. Furthermore, significant increases in effect sizes of trauma-focused cognitive behavior therapies over the past two decades contradict the conclusion that content of treatment does not matter. To advance understanding of the optimal treatment for PTSD, we recommend further research into the active mechanisms of therapeutic change, including treatment elements commonly considered to be non-specific. We also recommend transparency in reporting exclusions in meta-analyses and suggest that bona fide treatments should be defined on empirical and theoretical grounds rather than by judgments of the investigators' intent
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