Using network analysis for the prediction of treatment dropout in patients with mood and anxiety disorders: a methodological proof-of-concept study

There are large health, societal, and economic costs associated with attrition from psychological services. The recently emerged, innovative statistical tool of complex network analysis was used in the present proof-of-concept study to improve the prediction of attrition. Fifty-eight patients undergoing psychological treatment for mood or anxiety disorders were assessed using Ecological Momentary Assessments four times a day for two weeks before treatment (3,248 measurements). Multilevel vector autoregressive models were employed to compute dynamic symptom networks. Intake variables and network parameters (centrality measures) were used as predictors for dropout using machine-learning algorithms. Networks for patients differed significantly between completers and dropouts. Among intake variables, initial impairment and sex predicted dropout explaining 6% of the variance. The network analysis identified four additional predictors: Expected force of being excited, outstrength of experiencing social support, betweenness of feeling nervous, and instrength of being active. The final model with the two intake and four network variables explained 32% of variance in dropout and identified 47 out of 58 patients correctly. The findings indicate that patients’ dynamic network structures may improve the prediction of dropout. When implemented in routine care, such prediction models could identify patients at risk for attrition and inform personalized treatment recommendations.This work was supported by the German Research Foundation National Institute (DFG, Grant nos. LU 660/8-1 and LU 660/10-1 to W. Lutz). The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the manuscript. The corresponding author had access to all data in the study and had final responsibility for the decision to submit for publication. Dr. Hofmann receives financial support from the Alexander von Humboldt Foundation (as part of the Humboldt Prize), NIH/NCCIH (R01AT007257), NIH/NIMH (R01MH099021, U01MH108168), and the James S. McDonnell Foundation 21st Century Science Initiative in Understanding Human Cognition - Special Initiative. (LU 660/8-1 - German Research Foundation National Institute (DFG); LU 660/10-1 - German Research Foundation National Institute (DFG); Alexander von Humboldt Foundation; R01AT007257 - NIH/NCCIH; R01MH099021 - NIH/NIMH; U01MH108168 - NIH/NIMH; James S. McDonnell Foundation 21st Century Science Initiative in Understanding Human Cognition - Special Initiative)Accepted manuscrip

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

Developing a European Psychotherapy Consortium (EPoC):Towards adopting a single-item self-report outcome measure across European countries

Background: Complementing the development of evidence-based psychological therapies, practicebased evidence has developed from patient samples collected in routine care, addressing questions relevant to patients and practitioners, and thereby expanding our knowledge of psychological therapies and their impact. Implementation of assessments in routine care allows for timely clinical decision support and the collection of multiple practice-based data sets by addressing the needs of patients and clinicians (e.g., routine outcome monitoring) and the needs of researchers (e.g., identifying the impact of therapist variables on outcomes). Method: In this article we describe an initiative developed in Europe, through the European Chapter of the Society for Psychotherapy Research, aimed at creating a consortium that has the potential for collecting data on tens of thousands of patients per year. Results: A survey identified one of the main problems in the development of a common data set to be the heterogeneity of measures used by members (e.g., 87 different pre-post outcomes). We report on the results of the survey and the initial stage of identifying a single-item – the Emotional and Psychological Outcome (EPO-1) – measure and the process of its translation into multiple European languages. Conclusions: We conclude this first stage of the overall project by discussing the future potential of the Consortium in relation to the development of procedures that allow crosswalks of outcome measures and the creation of a task force that may be consulted when new data sets are collected, aiming for new common measures to be implemented and shared.<br/

ORC-13661 protects sensory hair cells from aminoglycoside and cisplatin ototoxicity

Aminoglycoside (AG) antibiotics are widely used to prevent life-threatening infections, and cisplatin is used in the treatment of various cancers, but both are ototoxic and result in loss of sensory hair cells from the inner ear. ORC-13661 is a new drug that was derived from PROTO-1, a compound first identified as protective in a large-scale screen utilizing hair cells in the lateral line organs of zebrafish larvae. Here, we demonstrate, in zebrafish larvae and in mouse cochlear cultures, that ORC-13661 provides robust protection of hair cells against both ototoxins, the AGs and cisplatin. ORC-13661 also prevents both hearing loss in a dose-dependent manner in rats treated with amikacin and the loading of neomycin-Texas Red into lateral line hair cells. In addition, patch-clamp recordings in mouse cochlear cultures reveal that ORC-13661 is a high-affinity permeant blocker of the mechanoelectrical transducer (MET) channel in outer hair cells, suggesting that it may reduce the toxicity of AGs by directly competing for entry at the level of the MET channel and of cisplatin by a MET-dependent mechanism. ORC-13661 is therefore a promising and versatile protectant that reversibly blocks the hair cell MET channel and operates across multiple species and toxins

Improving the Efficiency of Psychological Treatment using Outcome Feedback Technology

Aims: This study evaluated the impact of applying computerized outcome feedback (OF) technology in a stepped care psychological service offering low and high intensity therapies for depression and anxiety. Methods: A group of therapists were trained to use OF based on routine outcome monitoring using depression (PHQ-9) and anxiety (GAD-7) measures. Therapists regularly reviewed expected treatment response graphs with patients and discussed cases that were “not on track” in clinical supervision. Clinical outcomes data were collected for all patients treated by this group (N = 594), six months before (controls = 349) and six months after the OF training (OF cases = 245). Symptom reductions in PHQ-9 and GAD-7 were compared between controls and OF cases using longitudinal multilevel modelling. Treatment duration and costs were compared using MANOVA. Qualitative interviews with therapists (N = 15) and patients (N = 6) were interpreted using thematic analysis. Results: OF technology was generally acceptable and feasible to integrate in routine practice. No significant between-group differences were found in post-treatment PHQ-9 or GAD-7 measures. However, OF cases had significantly lower average duration and cost of treatment compared to controls. Conclusions: After adopting OF into their practice, this group of therapists attained similar clinical outcomes but within a shorter space of time and at a reduced average cost per treatment episode. We conclude that OF can improve the efficiency of stepped care

An in vivo Biomarker to Characterize Ototoxic Compounds and Novel Protective Therapeutics

There are no approved therapeutics for the prevention of hearing loss and vestibular dysfunction from drugs like aminoglycoside antibiotics. While the mechanisms underlying aminoglycoside ototoxicity remain unresolved, there is considerable evidence that aminoglycosides enter inner ear mechanosensory hair cells through the mechanoelectrical transduction (MET) channel. Inhibition of MET-dependent uptake with small molecules or modified aminoglycosides is a promising otoprotective strategy. To better characterize mammalian ototoxicity and aid in the translation of emerging therapeutics, a biomarker is needed. In the present study we propose that neonatal mice systemically injected with the aminoglycosides G418 conjugated to Texas Red (G418-TR) can be used as a histologic biomarker to characterize in vivo aminoglycoside toxicity. We demonstrate that postnatal day 5 mice, like older mice with functional hearing, show uptake and retention of G418-TR in cochlear hair cells following systemic injection. When we compare G418-TR uptake in other tissues, we find that kidney proximal tubule cells show similar retention. Using ORC-13661, an investigational hearing protection drug, we demonstrate in vivo inhibition of aminoglycoside uptake in mammalian hair cells. This work establishes how systemically administered fluorescently labeled ototoxins in the neonatal mouse can reveal important details about ototoxic drugs and protective therapeutics

Feedback-informed treatment versus usual psychological treatment for depression and anxiety : a multisite, open-label, cluster randomised controlled trial

Background: Previous research suggests that the use of outcome feedback technology can enable psychological therapists to identify and resolve obstacles to clinical improvement. We aimed to assess the effectiveness of an outcome feedback quality assurance system applied in stepped care psychological services. Methods: This multisite, open-label, cluster randomised controlled trial was done at eight National Health Service (NHS) Trusts in England, involving therapists who were qualified to deliver evidence-based low-intensity or high-intensity psychological interventions. Adult patients (18 years or older) who accessed individual therapy with participating therapists were eligible for inclusion, except patients who accessed group therapies and those who attended less than two individual therapy sessions. Therapists were randomly assigned (1:1) to an outcome feedback intervention group or a treatment-as-usual control group by use of a computer-generated randomisation algorithm. The allocation of patients to therapists was quasi-random, whereby patients on waiting lists were allocated sequentially on the basis of therapist availability. All patients received low-intensity (less than eight sessions) or high-intensity (up to 20 sessions) psychological therapies for the duration of the 1-year study period. An automated computer algorithm alerted therapists in the outcome feedback group to patients who were not on track, and primed them to review these patients in clinical supervision. The primary outcome was symptom severity on validated depression (Patient Health Questionnaire-9 [PHQ-9]) and anxiety (Generalised Anxiety Disorder-7 [GAD-7]) measures after treatment of varying durations, which were compared between groups with multilevel modelling, controlling for cluster (therapist) effects. We used an intention-to-treat approach. This trial was prospectively registered with ISRCTN, number ISRCTN12459454. Findings: In total, 79 therapists were recruited to the study between Jan 8, 2016, and July 15, 2016, but two did not participate. Of these participants, 39 (51%) were randomly assigned to the outcome feedback group and 38 (49%) to the control group. Overall, 2233 patients were included in the trial (1176 [53%] were treated by therapists in the outcome feedback group, and 1057 [47%] by therapists in the control group). Patients classified as not on track had less severe symptoms after treatment if they were allocated to the outcome feedback group than those in the control group (PHQ-9 d=0·23, B=–1·03 [95% CI −1·84 to −0·23], p=0·012; GAD-7 d=0·19, B=–0·85 [–1·56 to −0·14], p=0·019). Interpretation: Supplementing psychological therapy with low-cost feedback technology can reduce symptom severity in patients at risk of poor response to treatment. This evidence supports the implementation of outcome feedback in stepped care psychological services. Funding: English NHS and Department of Health Sciences, University of York, York, UK

Time to get personal? The impact of researchers choices on the selection of treatment targets using the experience sampling methodology:The impact of researchers choices on the selection of treatment targets using the experience sampling methodology

OBJECTIVE: One of the promises of the experience sampling methodology (ESM) is that a statistical analysis of an individual’s emotions, cognitions and behaviors in everyday-life could be used to identify relevant treatment targets. A requisite for clinical implementation is that outcomes of such person-specific time-series analyses are not wholly contingent on the researcher performing them. METHODS: To evaluate this, we crowdsourced the analysis of one individual patient’s ESM data to 12 prominent research teams, asking them what symptom(s) they would advise the treating clinician to target in subsequent treatment. RESULTS: Variation was evident at different stages of the analysis, from preprocessing steps (e.g., variable selection, clustering, handling of missing data) to the type of statistics and rationale for selecting targets. Most teams did include a type of vector autoregressive model, examining relations between symptoms over time. Although most teams were confident their selected targets would provide useful information to the clinician, not one recommendation was similar: both the number (0–16) and nature of selected targets varied widely. CONCLUSION: This study makes transparent that the selection of treatment targets based on personalized models using ESM data is currently highly conditional on subjective analytical choices and highlights key conceptual and methodological issues that need to be addressed in moving towards clinical implementation

Reliability of Therapist Effects in Practice-Based Psychotherapy Research : A Guide for the Planning of Future Studies

This paper aims to provide researchers with practical information on sample sizes for accurate estimations of therapist effects (TEs). The investigations are based on an integrated sample of 48,648 patients treated by 1800 therapists. Multilevel modeling and resampling were used to realize varying sample size conditions to generate empirical estimates of TEs. Sample size tables, including varying sample size conditions, were constructed and study examples given. This study gives an insight into the potential size of the TE and provides researchers with a practical guide to aid the planning of future studies in this field