A Network Model of Resilience Factors for Adolescents with and without Exposure to Childhood Adversity.

Resilience factors (RFs) help prevent mental health problems after childhood adversity (CA). RFs are known to be related, but it is currently unknown how their interrelations facilitate mental health. Here, we used network analysis to examine the interrelations between ten RFs in 14-year-old adolescents exposed ('CA'; n = 638) and not exposed to CA ('no-CA'; n = 501). We found that the degree to which RFs are assumed to enhance each other is higher in the no-CA compared to the CA group. Upon correction for general distress levels, the global RF connectivity also differed between the two groups. More specifically, in the no-CA network almost all RFs were positively interrelated and thus may enhance each other, whereas in the CA network some RFs were negatively interrelated and thus may hamper each other. Moreover, the CA group showed more direct connections between the RFs and current distress. Therefore, CA seems to influence how RFs relate to each other and to current distress, potentially leading to a dysfunctional RF system. Translational research could explore whether intervening on negative RF interrelations so that they turn positive and RFs can enhance each other, may alter 'RF-mental distress' relations, resulting in a lower risk for subsequent mental health problems.EI is funded by an ERC Consolidator Grant (no. 647209). IG is funded by a Wellcome Trust Strategic Award and declares consulting to Lundbeck. ALvH is supported by the Royal Society (DH15017 & RGF\EA\180029 & RFG/RI/180064), and MQ (MQBFC/2). JF is supported by the Medical Research Council Doctoral Training/Sackler Fund and the Pinsent Darwin Fund. Funders of the authors played no role in the study conduction, analysis performance, or the reporting of the study

The importance of transdiagnostic symptom level assessment to understanding prognosis for depressed adults: analysis of data from six randomized control trials

Background: Depression is commonly perceived as a single underlying disease with a number of potential treatment options. However, patients with major depression differ dramatically in their symptom presentation and comorbidities, e.g. with anxiety disorders. There are also large variations in treatment outcomes and associations of some anxiety comorbidities with poorer prognoses, but limited understanding as to why, and little information to inform the clinical management of depression. There is a need to improve our understanding of depression, incorporating anxiety co-morbidity, and consider the association of a wide range of symptoms with treatment outcomes. / Method: Individual patient data from six RCTs of depressed patients (total n=2858) were used to estimate the differential impact symptoms have on outcomes at three post intervention timepoints using individual items and sum scores. Symptom networks (Graphical Gaussian Model) were estimated to explore the functional relations among symptoms of depression and anxiety and compare networks for treatment remitters and those with persistent symptoms to identify potential prognostic indicators. / Results: Item-level prediction performed similarly to sum scores when predicting outcomes at 3 to 4 months and 6 to 8 months, but outperformed sum scores for 9 to 12 months. Pessimism emerged as the most important predictive symptom (relative to all other symptoms), across these time points. In the network structure at study entry, symptoms clustered into physical symptoms, cognitive symptoms, and anxiety symptoms. Sadness, pessimism, and indecision acted as bridges between communities, with sadness and failure/worthlessness being the most central (i.e. interconnected) symptoms. Connectivity of networks at study entry did not differ for future remitters vs. those with persistent symptoms. / Conclusion: The relative importance of specific symptoms in association with outcomes and the interactions within the network highlight the value of transdiagnostic assessment and formulation of symptoms to both treatment and prognosis. We discuss the potential for complementary statistical approaches to improve our understanding of psychopathology

Predicting prognosis for adults with depression using individual symptom data: a comparison of modelling approaches

Aims: To develop, validate, and compare the performance of nine models predicting post-treatment outcomes for depressed adults based on pre-treatment data. / Methods: Individual patient data from all six eligible RCTs were used to develop (k=3, n=1722) and test (k=3, n=1136) nine models. Predictors included depressive and anxiety symptoms, social support, life events and alcohol use. Weighted sum-scores were developed using coefficient weights derived from network centrality statistics (Models 1-3) and factor loadings from a confirmatory factor analysis (Model 4). Unweighted sum-score models were tested using Elastic Net Regularized (ENR) and ordinary least squares (OLS) regression (Models 5-6). Individual items were then included in ENR and OLS (Models 7-8). All models were compared to one another and to a null model using the mean post-baseline BDI-II score in the training data (Model 9). Primary outcome: BDI-II scores at 3-4 months. / Results: Models 1-7 all outperformed the null model. Individual-item models (particularly Model 8) explained less variance. Model performance was very similar across models 1-6, meaning that differential weights applied to the baseline sum-scores had little impact. / Conclusions: Any of the modelling techniques (1-7) could be used to inform prognostic predictions for depressed adults with differences in the proportions of patients reaching remission based on the predicted severity of depressive symptoms post-treatment. However, the majority of variance in prognosis remained unexplained. It may be necessary to include a broader range of biopsychosocial variables to better adjudicate between competing models, and to derive models with greater clinical utility for treatment-seeking adults with depression

Treatment of substance abuse in dual diagnosis

Interventions for substance use–related problems are limited for individuals with intellectual disability (ID). This is problematic, as the lack of interventions can lead to substance use initiation, progression of substance use into substance use disorder, poorer outcomes of treatment, and stigmatization of individuals with dual diagnosis. Additionally, staff who work with individuals with ID and addiction treatment lack resources to effectively help substance use in individuals with ID. Nevertheless, there has been an increase in studies assessing the feasibility and outcomes of interventions for substance use and abuse in individuals with ID. This chapter reviews psychological and pharmacological interventions for individuals with dual diagnosis of substance abuse and ID

Differential In Vitro Effects of Intravenous versus Oral Formulations of Silibinin on the HCV Life Cycle and Inflammation

Silymarin prevents liver disease in many experimental rodent models, and is the most popular botanical medicine consumed by patients with hepatitis C. Silibinin is a major component of silymarin, consisting of the flavonolignans silybin A and silybin B, which are insoluble in aqueous solution. A chemically modified and soluble version of silibinin, SIL, has been shown to potently reduce hepatitis C virus (HCV) RNA levels in vivo when administered intravenously. Silymarin and silibinin inhibit HCV infection in cell culture by targeting multiple steps in the virus lifecycle. We tested the hepatoprotective profiles of SIL and silibinin in assays that measure antiviral and anti-inflammatory functions. Both mixtures inhibited fusion of HCV pseudoparticles (HCVpp) with fluorescent liposomes in a dose-dependent fashion. SIL inhibited 5 clinical genotype 1b isolates of NS5B RNA dependent RNA polymerase (RdRp) activity better than silibinin, with IC50 values of 40–85 µM. The enhanced activity of SIL may have been in part due to inhibition of NS5B binding to RNA templates. However, inhibition of the RdRps by both mixtures plateaued at 43–73%, suggesting that the products are poor overall inhibitors of RdRp. Silibinin did not inhibit HCV replication in subgenomic genotype 1b or 2a replicon cell lines, but it did inhibit JFH-1 infection. In contrast, SIL inhibited 1b but not 2a subgenomic replicons and also inhibited JFH-1 infection. Both mixtures inhibited production of progeny virus particles. Silibinin but not SIL inhibited NF-κB- and IFN-B-dependent transcription in Huh7 cells. However, both mixtures inhibited T cell proliferation to similar degrees. These data underscore the differences and similarities between the intravenous and oral formulations of silibinin, which could influence the clinical effects of this mixture on patients with chronic liver diseases

The relationship between doses of mindfulness-based programs and depression, anxiety, stress, and mindfulness: a dose-response meta-regression of randomized controlled trials

Abstract Objectives: Research with mindfulness-based programs (MBPs) has found participating in an MBP to predict beneficial outcomes, however, there is currently mixed research regarding the most helpful dose. This review aimed to determine whether different doses related to MBPs significantly predict outcomes. Methods: Systematic literature searches of electronic databases and trial registration sites for all randomized controlled trials of MBPs identified 203 studies (N=15,971). Depression was the primary outcome at post-program and follow-up, with secondary outcomes being mindfulness, anxiety and stress. Doses examined related to session numbers, duration and length, facilitator contact and practice. Dose-response relationships were analyzed using meta-regression in R with separate analyses for inactive and active controls. Results: Initial meta-analyses found significant between-group differences favoring MBPs for all outcomes. Meta-regression results suggested significant dose-response relationships for the mindfulness outcome for doses relating to face-to-face contact (d=0.211; C.I.[0.064,0.358]), program intensity (d=0.895; C.I.[0.315,1.474]) and actual program use (d=0.013; C.I.[0.001,0.024]). The majority of results for psychological outcomes, including depression, were not significant. Conclusions: This meta-regression examines dose-response relationships for different types and doses relating to MBPs. Considered together, MBPs appeared helpful compared to controls, supporting previous research. Based on meta-regression results, there was no evidence that larger doses are more helpful than smaller doses for predicting psychological outcomes; a finding consistent with some previous research particularly with non-clinical populations. Additionally, greater contact, intensity and actual use of MBPs predicting increased mindfulness corresponds with previous research and theory. Potential limitations and recommendations for future research are explored

What is the value and impact of quality and safety teams? A scoping review

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to conduct a scoping review of the literature about the establishment and impact of quality and safety team initiatives in acute care.</p> <p>Methods</p> <p>Studies were identified through electronic searches of Medline, Embase, CINAHL, PsycINFO, ABI Inform, Cochrane databases. Grey literature and bibliographies were also searched. Qualitative or quantitative studies that occurred in acute care, describing how quality and safety teams were established or implemented, the impact of teams, or the barriers and/or facilitators of teams were included. Two reviewers independently extracted data on study design, sample, interventions, and outcomes. Quality assessment of full text articles was done independently by two reviewers. Studies were categorized according to dimensions of quality.</p> <p>Results</p> <p>Of 6,674 articles identified, 99 were included in the study. The heterogeneity of studies and results reported precluded quantitative data analyses. Findings revealed limited information about attributes of successful and unsuccessful team initiatives, barriers and facilitators to team initiatives, unique or combined contribution of selected interventions, or how to effectively establish these teams.</p> <p>Conclusions</p> <p>Not unlike systematic reviews of quality improvement collaboratives, this broad review revealed that while teams reported a number of positive results, there are many methodological issues. This study is unique in utilizing traditional quality assessment and more novel methods of quality assessment and reporting of results (SQUIRE) to appraise studies. Rigorous design, evaluation, and reporting of quality and safety team initiatives are required.</p