Semiparametric Causal Sufficient Dimension Reduction Of High Dimensional Treatments

Cause-effect relationships are typically evaluated by comparing the outcome responses to binary treatment values, representing two arms of a hypothetical randomized controlled trial. However, in certain applications, treatments of interest are continuous and high dimensional. For example, understanding the causal relationship between severity of radiation therapy, represented by a high dimensional vector of radiation exposure values and post-treatment side effects is a problem of clinical interest in radiation oncology. An appropriate strategy for making interpretable causal conclusions is to reduce the dimension of treatment. If individual elements of a high dimensional treatment vector weakly affect the outcome, but the overall relationship between the treatment variable and the outcome is strong, careless approaches to dimension reduction may not preserve this relationship. Moreover, methods developed for regression problems do not transfer in a straightforward way to causal inference due to confounding complications between the treatment and outcome. In this paper, we use semiparametric inference theory for structural models to give a general approach to causal sufficient dimension reduction of a high dimensional treatment such that the cause-effect relationship between the treatment and outcome is preserved. We illustrate the utility of our proposal through simulations and a real data application in radiation oncology

Defining Early Positive Response to Psychotherapy: An Empirical Comparison Between Clinically Significant Change Criteria and Growth Mixture Modeling

Several different approaches have been applied to identify early positive change in response to psychotherapy so as to predict later treatment outcome and length as well as use this information for outcome monitoring and treatment planning. In this study, simple methods based on clinically significant change criteria and computationally demanding growth mixture modeling (GMM) are compared with regard to their overlap and uniqueness as well as their characteristics in terms of initial impairment, therapy outcome, and treatment length. The GMM approach identified a highly specific subgroup of early improving patients. These patients were characterized by higher average intake impairments and higher pre- to-posttreatment score differences. Although being more specific for the prediction of treatment success, GMM was much less sensitive than clinically significant and reliable change criteria. There were no differences between the groups with regard to treatment length. Because each of the approaches had specific advantages, results suggest a combination of both methods for practical use in routine outcome monitoring and treatment planning

Trauma-focused treatment outcome for complex PTSD patients: results of an intensive treatment programme

Objective The objective of the current study is to determine whether individuals classified as having CPTSD can benefit from an intensive trauma-focused treatment, resulting in decreased PTSD and CPTSD symptoms, and loss of diagnoses. Method Patients diagnosed with PTSD (N = 308) took part in an intensive 8-day treatment programme combining prolonged exposure, EMDR therapy, psycho-education, and physical activity. The treatment was not phase-based in that it did not contain a stabilization phase or skill training prior to therapy. CPTSD diagnosis was assessed by means of the International Trauma Questionnaire (ITQ) and PTSD diagnosis was assessed with both the ITQ and CAPS-5. Treatment response was measured with the CAPS-5, PCL-5, and ITQ. Results Symptoms of both PTSD and CPTSD significantly decreased from pre- to post-treatment resulting in a significant loss of CAPS-5 based PTSD (74.0%) and ITQ-based PTSD and CPTSD diagnoses (85.0% and 87.7%, respectively). No adverse events occurred in terms of suicides, suicide attempts, or hospital admissions. Conclusions The results are supportive of the notion that the majority of patients classified as having CPTSD strongly benefit from an intensive trauma-focused treatment for their PTSD

Level of impaired control predicts outcome of moderation-oriented treatment for alcohol problems

Aims To examine the ability of the Impaired Control Scale (ICS) to predict outcome of moderation-oriented treatment for alcohol problems and to compare this predictive ability directly with that of a widely used measure of alcohol dependence, the Severity of Alcohol Dependence Questionnaire (SADQ). Design Prospective follow-up study. Setting Out-patient treatment centres. Participants A combined sample 154 problem drinkers taking part in two clinical trials of Moderation-oriented Cue Exposure in the UK and Australia. Clients were followed-up 6 (UK) and 8 (Australia) months after the end of reatment. Measurements Outcome was categorized by combining drinking behaviour at follow-up with changes on the Alcohol Problems Questionnaire from before treatment to follow-up. Controlling for research site, baseline scores on Part 2 of the ICS (substitution method) and the SADQ-C were entered in logistic regression analyses with three outcome dichotomies as dependent variables. Findings Five per cent of clients were abstinent at follow-up, 13% non-problem drinkers, 25% much improved, 24% somewhat improved and 34% unimproved. Location of treatment and ICS2 scores were significant predictors of whether or not clients achieved a successful outcome (abstinence or non-problem drinking). Using a cut-point of 25 on the ICS, two-thirds of outcomes were classified correctly as either treatment successes or failures. SADQ-C score was not a significant predictor of treatment outcome. Conclusions The ICS predicts outcome of moderation-oriented treatment among moderately dependent problem drinkers recruited mainly via newspaper advertisements. The ICS should replace the SADQ as the basis for advice to clients in this population of problem drinkers regarding whether or not a moderation goal of treatment should be pursued

Expectancies, working alliance, and outcome in transdiagnostic and single diagnosis treatment for anxiety disorders: an investigation of mediation

Patients’ outcome expectancies and the working alliance are two psychotherapy process variables that researchers have found to be associated with treatment outcome, irrespective of treatment approach and problem area. Despite this, little is known about the mechanisms accounting for this association, and whether contextual factors (e.g., psychotherapy type) impact the strength of these relationships. The primary aim of this study was to examine whether patient-rated working alliance quality mediates the relationship between outcome expectancies and pre- to post-treatment change in anxiety symptoms using data from a recent randomized clinical trial comparing a transdiagnostic treatment (the Unified Protocol [UP]; Barlow et al., Unified protocol for transdiagnostic treatment of emotional disorders: Client workbook, Oxford University Press, New York, 2011a; Barlow et al., Unified protocol for transdiagnostic treatment of emotional disorders: Patient workbook. New York: Oxford University Press, 2017b) to single diagnosis protocols (SDPs) for patients with a principal heterogeneous anxiety disorder (n = 179). The second aim was to explore whether cognitive-behavioral treatment condition (UP vs. SDP) moderated this indirect relationship. Results from mediation and moderated mediation models indicated that, when collapsing across the two treatment conditions, the relationship between expectancies and outcome was partially mediated by the working alliance [B = 0.037, SE = 0.05, 95% CI (.005, 0.096)]. Interestingly, within-condition analyses showed that this conditional indirect effect was only present for SDP patients, whereas in the UP condition, working alliance did not account for the association between expectancies and outcome. These findings suggest that outcome expectancies and working alliance quality may interact to influence treatment outcomes, and that the nature and strength of the relationships among these constructs may differ as a function of the specific cognitive-behavioral treatment approach utilized.This study was funded by grant R01 MH090053 from the National Institutes of Health. (R01 MH090053 - National Institutes of Health)First author draf

Outcome measurement in functional neurological disorder: a systematic review and recommendations.

OBJECTIVES: We aimed to identify existing outcome measures for functional neurological disorder (FND), to inform the development of recommendations and to guide future research on FND outcomes. METHODS: A systematic review was conducted to identify existing FND-specific outcome measures and the most common measurement domains and measures in previous treatment studies. Searches of Embase, MEDLINE and PsycINFO were conducted between January 1965 and June 2019. The findings were discussed during two international meetings of the FND-Core Outcome Measures group. RESULTS: Five FND-specific measures were identified-three clinician-rated and two patient-rated-but their measurement properties have not been rigorously evaluated. No single measure was identified for use across the range of FND symptoms in adults. Across randomised controlled trials (k=40) and observational treatment studies (k=40), outcome measures most often assessed core FND symptom change. Other domains measured commonly were additional physical and psychological symptoms, life impact (ie, quality of life, disability and general functioning) and health economics/cost-utility (eg, healthcare resource use and quality-adjusted life years). CONCLUSIONS: There are few well-validated FND-specific outcome measures. Thus, at present, we recommend that existing outcome measures, known to be reliable, valid and responsive in FND or closely related populations, are used to capture key outcome domains. Increased consistency in outcome measurement will facilitate comparison of treatment effects across FND symptom types and treatment modalities. Future work needs to more rigorously validate outcome measures used in this population

Are Treatment Preferences Relevant in Response to Serotonergic Antidepressants and Cognitive-Behavioral Therapy in Depressed Primary Care Patients? Results from a Randomized Controlled Trial Including a Patients' Choice Arm

Background Little is known about the influence of depressed patients' preferences and expectations about treatments upon treatment outcome We investigated whether better clinical outcome in depressed primary care patients is associated with receiving their preferred treatment Methods Within a randomized placebo-controlled single-centre 10-week trial with 5 arms (sertraline, placebo, cognitive-behavioral group therapy, CBT-G, moderated self-help group control, treatment with sertraline or CBT-G according to patients' choice), outcomes for 145 primary care patients with mild-to-moderate depressive disorders according to DSM-IV criteria were investigated Preference for medication versus psychotherapy was assessed at screening using a single item Post-baseline difference scores for the Hamilton Depression Rating Scale (HAMD-17) were used to assess treatment outcome (mixed-model repeated-measures regression analysis) Results Depressed patients receiving their preferred treatment (n = 63), whether sertraline or CBT-G, responded significantly better than those who did not receive their preferred therapy (n = 54, p = 0 001) The difference in outcome between both groups was 8 0 points on the HAMD-17 for psychotherapy and 2 9 points on the HAMD-17 for treatment with antidepressants Results were not explained by differences in depression severity or dropout rates Conclusions Patients' relative preference for medication versus psychotherapy should be considered when offering a treatment because receiving the preferred treatment conveys an additional and clinically relevant benefit (HAMD-17 +2 9 points for drugs, +8 0 points for CBT-G) in outcome Copyright (C) 2010 S Karger AG Base

Virological treatment outcome under HAART : does sex matter?

Background: In Germany, 17% of 59,000 persons living with HIV/AIDS are female. Accordingly, the research focus in clinical studies as well as in cohort analyses has been almost exclusively on HIV-positive men. As a consequence, there is an urgent need to characterize and evaluate the outcome of HAART in HIV-positive women and to identify special requirements of this particular patient population. Methods: Cross-sectional multicentre (n = 31 centres) evaluation to observe characteristics of 1,557 HIV-positive women receiving medical care in Germany between June 2007 and March 2008. Data acquisition was performed using standardized questionnaires. Summary of results: Of 1,557 HIV-positive women studied, 1,191 (77%) received HAART. Mean age was 40 years and average time of known HIV-infection was 9 years. Risk of HIV transmission was: 40% heterosexual intercourse in Germany, 36% heterosexual intercourse in a high prevalence country; 17% IDU; 7% other reasons for transmission. 46% of the women had a migration background. Mean time on antiretroviral treatment was 7 years. 53% of the female participants had been treated with >2 HAART-regimens. 47% of the study subjects received a PI-based regimen, 33% a NNRTI-based regimen; 20% were on other combinations. The most commonly used PI and NNRTI were lopinavir/r and nevirapine, respectively. Only 48% of all women under HAART achieved a viral load <40 copies/ml. There was a significant difference between the PI-treated group with 44% patients <40 copies/ml and the NNRTI-treated group with 56% <40 copies/ml (p = 0.003). Conclusion: We found that HIV-positive women depicted an inferior virological response to HAART compared to those previously published in German cohort analyses dominated by men (response rates >75%). Possible differences in adherence or drug resistance may have impacted these results and are currently being evaluated in ongoing sub-analyses. Of note, the lack of a study arm with male patients is a limitation of this investigation. However, this is partly off-set by the fact that there are good comparative data in the male population found in other cohorts. We conclude that our results are in discordance to the popular assumption that there are no gender specific differences in virological treatment outcome of HAART

A meta-analysis of the relation between therapeutic alliance and treatment outcome in eating disorders.

The therapeutic alliance has demonstrated an association with favorable psychotherapeutic outcomes in the treatment of eating disorders (EDs). However, questions remain about the inter-relationships between early alliance, early symptom improvement, and treatment outcome. We conducted a meta-analysis on the relations among these constructs, and possible moderators of these relations, in psychosocial treatments for EDs. Twenty studies met inclusion criteria and supplied sufficient supplementary data. Results revealed small-to-moderate effect sizes, βs = 0.13 to 0.22 (p < .05), indicating that early symptom improvement was related to subsequent alliance quality and that alliance ratings also were related to subsequent symptom reduction. The relationship between early alliance and treatment outcome was partially accounted for by early symptom improvement. With regard to moderators, early alliance showed weaker associations with outcome in therapies with a strong behavioral component relative to nonbehavioral therapies. However, alliance showed stronger relations to outcome for younger (vs. older) patients, over and above the variance shared with early symptom improvement. In sum, early symptom reduction enhances therapeutic alliance and treatment outcome in EDs, but early alliance may require specific attention for younger patients and for those receiving nonbehaviorally oriented treatments