Practice Involves More Than Treatment: How Can Evidence‐Based Assessment Catch Up to Evidence‐Based Treatment?

[Clin Psychol Sci Prac 18: 173–177, 2011] Given the excellent work being conducted in the area of evidence‐based treatments (EBTs), it is important to consider whether other forms of evidence‐based practice are receiving concomitant attention. While significant progress has been made in the last five years to generate reviews of evidence‐based assessment (EBA) practices, this work lags behind efforts to identify EBTs. This commentary describes available data on assessment practices in clinical care settings, discusses the importance of and current status of EBA, and considers how the next generation of EBA reviews might move beyond consideration of psychometric properties to the inclusion of “effectiveness” parameters.     

Skipping along: an exon skipping therapy shows promise for Duchenne muscular dystrophy

References 1.Cirak S, Arechavala‐Gomeza V, Guglieri M et al. Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open‐label, phase 2, dose‐escalation study . Lancet 2011 : 378 (9791): 595–605. 2.Bushby K, Finkel R, Birnkrant DJ et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management . Lancet Neurol 2010 : 9 (1): 77–93. 3.Nakamura A, Takeda S. Exon‐skipping therapy for Duchenne muscular dystrophy . Lancet 2011 : 378 (9791): 546–547. Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open label, phase 2, dose‐escalation study Cirak S, Arechavala‐Gomeza V, Guglieri M, et al. (2011) The Lancet 378 (9791): 595–605     

Making a Case for Treatment Integrity as a Psychosocial Treatment Quality Indicator for Youth Mental Health Care

Measures of treatment integrity are needed to advance clinical research in general and are viewed as particularly relevant for dissemination and implementation research. Although some efforts to develop such measures are underway, a conceptual and methodological framework will help guide these efforts. The purpose of this article is to demonstrate how frameworks adapted from the psychosocial treatment, therapy process, healthcare, and business literatures can be used to address this gap. We propose that components of treatment integrity (i.e., adherence, differentiation, competence, alliance, client involvement) pulled from the treatment technology and process literatures can be used as quality indicators of treatment implementation and thereby guide quality improvement efforts in practice settings. Further, we discuss how treatment integrity indices can be used in feedback systems that utilize benchmarking to expedite the process of translating evidence‐based practices to service settings.     

On the Topic of Treatment Integrity

[Clin Psychol Sci Prac 18: 148–153, 2011] Treatment integrity, also known as treatment fidelity, is integral for empirical testing of intervention efficacy, as it allows for unambiguous interpretations of the obtained results. Ensuring treatment integrity is also important for dissemination of evidence‐based practices and quality improvement of services. However, in the examination of the relationship between treatment integrity and treatment outcome, it is important to consider that treatment integrity may be a proxy variable for other variables impacting therapeutic change (e.g., characteristics of intervention, clients, setting, and therapist). Considerations on examining the association between integrity and outcome are discussed. Further, recommendations on the level to which treatment integrity needs to be addressed in psychotherapy research and clinical practice are provided.     

Kernels vs. Ears,and Other Questions for a Science of Treatment Dissemination

[Clin Psychol Sci Prac 18: 41–46, 2011] Combining intervention diffusion with change in clinical practice and public policy is an ambitious agenda. The impressive effort in Hawaii can be instructive, highlighting questions for a science of treatment dissemination. Among these questions, some of the most important are the following: (a) Who should be targeted for change? (e.g., “downstream” clinicians in practice, “upstream” clinicians in training, consumers, “brokers,” policy makers, or payers?); (b) What should be disseminated? (e.g., full evidence‐based protocols, specific treatment elements or “kernels”?); and (c) Which procedures maximize change? (e.g., what combination and duration of teaching, supervision, consultation, and other support?). Ultimately, change efforts need to assess what aspects of practice were actually altered, what measurable impact the changes had on clinical outcomes, and what changes in practices and outcomes can be sustained over time.     

Beyond Depression Commentary: Wherefore Art Thou,Depression Clinic of Tomorrow?

[Clin Psychol Sci Prac 18: 305–310, 2011] An exciting review in this issue ( Forgeard et al., 2011 ) highlights a number of emerging themes in contemporary translational research. A primary challenge for the next generation of researchers reading this work will be how to carry out the grand charges levied by Forgeard et al. on the ground, that is, to lay the foundations for moving the emerging basic science of depression into the Depression Clinic of Tomorrow. Addressing these challenges could suggest changes in the nature of the basic science, and the questions that are being asked, and employed approaches in contemporary depression research. Preconditions for clinical adoption discussed in the review include (a) beginning to hold neuroscience‐based measures of features of depression to the same standards held for other depression measures in the clinic, (b) attending to how the proposed methods might actually end up being feasibly imported into the clinic, and (c) what interventions targeted at mechanisms of depression might look like in the next decade.     

Training in Empirically Supported Treatments Using Alternative Learning Modalities

[Clin Psychol Sci Prac 18: 84–88, 2011] Godley, Garner, Smith, Meyers, and Godley (2011) describe an intensive dissemination and implementation program for empirically supported substance use treatment in a community setting. Among the many procedures employed by this dissemination program is the integration of in‐person and alternate learning modalities (web‐based training.) The use of alternate learning modalities to aid treatment dissemination is relatively new, and much needs to be learned about how to best use these methodologies. Early research suggests that, at a minimum, these training aids may be an effective adjunct to more traditional approaches and potentially may become an invaluable tool for large‐scale treatment dissemination.     

Evidence‐Based Treatments for Children and Adolescents: An Updated Review of Indicators of Efficacy and Effectiveness

[Clin Psychol Sci Prac 18: 154–172, 2011] This updated review of evidence‐based treatments follows the original review performed by the Hawaii Task Force. Over 750 treatment protocols from 435 studies were coded and rated on a 5‐level strength of evidence system. Results showed large numbers of evidence‐based treatments applicable to anxiety, attention, autism, depression, disruptive behavior, eating problems, substance use, and traumatic stress. Treatments were reviewed in terms of diversity of client characteristics, treatment settings and formats, therapist characteristics, and other variables potentially related to feasibility and generalizability. Overall, the literature has expanded considerably since the previous review, yielding a growing list of options and information available to guide decisions about treatment selection.     

A Large‐Scale Dissemination and Implementation Model for Evidence‐Based Treatment and Continuing Care

[Clin Psychol Sci Prac 18: 67–83, 2011] Multiple evidence‐based treatments for adolescents with substance use disorders are available; however, the diffusion of these treatments in practice remains minimal. A dissemination and implementation model incorporating research‐based training components for simultaneous implementation across 33 dispersed sites and over 200 clinical staff is described. Key elements for the diffusion of the Adolescent Community Reinforcement Approach and Assertive Continuing Care were as follows: (a) 3 years of funding to support local implementation; (b) comprehensive training, including a 3.5‐day workshop, biweekly coaching calls, and ongoing performance feedback facilitated by a web tool; (c) a clinician certification process; (d) a supervisor certification process to promote long‐term sustainability; and (e) random fidelity reviews after certification. Process data are summarized for 167 clinicians and 64 supervisors.     

Treatment satisfaction, perceived treatment effectiveness, and dropout among older users of mental health services

Objectives: To examine the rates and correlates of treatment satisfaction, perceived treatment effectiveness, and dropout among older users of mental health services. Method: We used data from the Canadian Community Health Survey‐Mental Health and Well‐Being (CCHS‐1.2), which includes 12,792 individuals aged ≥55 years. The average age of these participants was 67 years and 53.2% were female. We examined the rates of treatment satisfaction, perceived treatment effectiveness, and dropout for those who had used mental health services in the past year, and used logistic regression to examine the correlates of these outcomes. Results: Of the older adults included in the CCHS‐1.2, 664 (5.3%) had used mental health services in the past year. The majority of these were satisfied with services (88.5%) and perceived treatment to be effective (83.6%), which is likely why only 15.5% dropped out in the past year. In logistic regression models, social support was significantly and positively related to both treatment satisfaction and perceived effectiveness. Perceived treatment effectiveness was the only variable related to dropout, with lower levels of perceived effectiveness associated with greater odds of dropping out of treatment. Conclusions: Results from this study indicate that older adults have very good self‐reported treatment outcomes. The modest influence of individual characteristics on treatment outcomes suggests the potential importance of contextual characteristics. © 2011 Wiley Periodicals, Inc. J Clin Psychol 67:1197–1209, 2011.     

Predicting patient deterioration in youth mental health services: community mental health vs. managed care settings

Objective: To examine differences across a community mental health system and a private managed care system in the accuracy of a warning system designed to identify youth at risk for deterioration in mental health services. Design: Longitudinal outcome data from the Youth Outcome Questionnaire (Y‐OQ) were examined using multilevel modeling for 2,310 youth ages 4–17 who received outpatient treatment. Results: The warning system correctly identified 69% of cases that ultimately ended in deterioration in the community mental health setting, compared to 61% in the managed care setting. The overall hit rate (overall accuracy in classifying cases as deteriorators/non‐deteriorators) was the same in the two settings (75%). Conclusions: Results are consistent with previous research demonstrating that patient‐focused warning systems can be reasonably accurate in identifying youth cases at risk for treatment failure. © 2011 Wiley Periodicals, Inc. J Clin Psychol 67:1–17, 2011.     

Distinguishing Scientific From Pseudoscientific Psychotherapies: Evaluating the Role of Theoretical Plausibility,With a Little Help From Reverend Bayes

[Clin Psychol Sci Prac 18: 105–112, 2011] In their stimulating article, David and Montgomery (2011) underscore the importance of identifying pseudoscientific and potentially harmful psychotherapies, and observe that the criteria for empirically supported therapies neglect to take into account the theoretical support for treatment packages. They propose a framework for evidence‐based therapies that includes empirical support for both the efficacy of the treatment and the theory that spawned it. I discuss several challenges to this and similar frameworks, including (a) the absence of convincing data regarding how most current therapies work, (b) the underdetermination of theory by data, making it difficult to strongly corroborate models of therapeutic change mechanisms using only a small number of studies, and (c) the risk of false negatives, viz., efficacious treatments derived from nonexistent or flawed theories. As a friendly amendment, I propose a Bayesian alternative to David and Montgomery’s classification that incorporates the role of theoretical plausibility while minimizing the aforementioned difficulties.     

Correlation of serum hepatitis B surface antigen level with response to entecavir in naïve patients with chronic hepatitis B

Recent studies have suggested that quantifying the serum HBsAg levels can predict the response to pegylated interferon. We aimed to determine the change in serum HBsAg levels during entecavir (ETV) treatment and the correlation with treatment response in chronic HBeAg‐positive and HBeAg‐negative hepatitis B patients. Serial HBsAg levels were measured using the Architect assay (Abbott Laboratories, Abbott Park, IL) in sera from 101 treatment‐naive chronic hepatitis B (CHB) patients receiving ETV. During treatment, in HBeAg‐positive patients, the mean HBsAg level was 3.51, 3.22, 3.34, 3.36, and 3.40 log₁₀ IU/ml at baseline, 3, 6, 12, and 24 months, respectively, and there was no significant change compared with the baseline level, except the decline at 3 months (P = 0.009). In HBeAg‐negative patients, the mean level of serum HBsAg showed increase with 3.06, 3.09, 3.20, 3.26, and 3.27 log₁₀ IU/ml at baseline, 3, 6, 12, and 24 months of treatment, respectively. In HBeAg‐positive patients, HBV‐DNA negativity (<2,000 copies/ml; P = 0.010) and HBsAg level <3,000 IU/ml (P = 0.026) at 3 months were independent predictors of HBeAg loss/seroconversion at 12 months. After 24 months of treatment, the HBsAg levels at baseline (P = 0.046) was an independent factor of HBeAg loss/seroconversion. In HBeAg‐negative patients, undetectable HBV DNA at 6 months was an independent factor predicting undetectable HBV DNA after 12 months of therapy. The level of serum HBsAg before and during therapy was a good predictor of HBeAg loss/seroconversion in naïve HBeAg‐positive CHB patients receiving entecavir. J. Med. Virol. 83:1178–1186, 2011. © 2011 Wiley‐Liss, Inc.     

Mutations in the E2 and NS5A regions in patients infected with hepatitis C virus genotype 1a and their correlation with response to treatment

Heterogeneity of subgenomic regions of hepatitis C virus (HCV) may be associated with response to interferon (IFN) therapy. The amino acid sequences of the PKR/eIF‐2α phosphorylation homology domain (pePHD), IFN sensitivity determining region (ISDR), PKR binding domain (PKRBD), and variable region 3 (V3) were studied in 19 patients before and after 4 weeks of treatment. All patients were infected with HCV genotype 1a and were treated with pegylated‐IFN and ribavirin. Thirteen patients achieved sustained viral response (responders) and six failed to clear viral RNA (nonresponders). The amino acid sequences in the pePHD and ISDR were identical in responders and nonresponders. However, amino acid substitution at position 2252 of PKRBD was significantly different between responders and nonresponders (P = 0.044). A larger number of mutations were observed in the V3 region of responders (P < 0.001). In this region, the amino acid in position 2364 differed between responders and nonresponders (responders: aspartic acid and serine, nonresponders: asparagine, P = 0.018). The amino acid sequences in the regions which were studied did not change after 4 weeks of treatment. It is concluded that the presence of specific amino acids in position 2252 of PKRBD and position 2364 of V3 might be associated with clinical response to IFN. J. Med. Virol. 83:1332–1337, 2011. © 2011 Wiley‐Liss, Inc.     

Autism,mutations, and the environment: insights from exome sequencing

References 1.Hallmayer J, Cleveland S, Torres A et al. Genetic heritability and shared environmental factors among twin pairs with utism. Arch Gen Psychiatry 2011 . DOI: 10.1001/archgenpsychiatry.2011.76. . Epub 4 July 2011. 2.Barak T, Kwan KY, Louvi A et al. Recessive LAMC3 mutations cause malformations of occipital cortical development. Nat Genet 2011 : 43 (6): 590–594. Epub 15 May 2011. 3.Zweier C, de Jong EK, Orrico A et al. CNTNAP2 and NRXN1 are mutated in autosomal‐recessive Pitt Hopkins‐like mental retardation and determine the level of a common synaptic protein in Drosophila. Am J Hum Genet 2009 : 85 (5): 655–666. Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations O'Roak et al. (2011) Nature Genetics 43(6):585–589. Epub 15 May 2011     

Linkage and association on 8p21.2‐p21.1 in schizophrenia

In the past decade, we and others have consistently reported linkage to a schizophrenia (SZ) susceptibility region on chromosome 8p21. Most recently, in the largest SZ linkage sample to date, a multi‐site international collaboration performed a SNP‐based linkage scan (～6,000 SNPs; 831 pedigrees; 121 from Johns Hopkins (JHU)), that showed the strongest evidence for linkage in a 1 Mb region of chr 8p21 from rs1561817 to rs9797 (Z_max = 3.22, P = 0.0004) [Holmans et al. 2009. Mol Psychiatry]. We have investigated this 8p21 peak region further in two ways: first by linkage and family‐based association in 106 8p‐linked European‐Caucasian (EUC) JHU pedigrees using 1,402 SNPs across a 4.4 Mb region surrounding the peak; second, by an independent case‐control association study in the genetically more homogeneous Ashkenazim (AJ) (709 cases, 1,547 controls) using 970 SNPs in a further narrowed 2.8 Mb region. Family‐based association analyses in EUC pedigrees and case‐control analyses in AJ samples reveal significant associations for SNPs in and around DPYSL2 and ADRA1A, candidate genes previously associated with SZ in our work and others. Further, several independent gene expression studies have shown that DPYSL2 is differentially expressed in SZ brains [Beasley et al. 2006. Proteomics 6(11):3414–3425; Edgar et al. 2000. Mol Psychiatry 5(1):85–90; Johnston‐Wilson et al. 2000. Mol Psychiatry 5(2):142–149] or in response to psychosis‐inducing pharmaceuticals [Iwazaki et al. 2007. Proteomics 7(7):1131–1139; Paulson et al. 2004. Proteomics 4(3):819–825]. Taken together, this work further supports DPYSL2 and the surrounding genomic region as a susceptibility locus for SZ. © 2010 Wiley‐Liss, Inc.     

Four years comparative follow‐up evaluation of community‐based,step‐down,and residential specialist psychodynamic programmes for personality disorders

Although the fulcrum of service provision for personality disorder (PD) has shifted from hospital‐based to psychodynamically‐ and cognitively‐oriented outpatient programmes, very few studies have attempted to compare specialist moderate intensity outpatient programmes with specialist high‐intensity residential models, or to explore whether a period of inpatient treatment may be necessary to improve outcome and prognosis. In this article, we prospectively compare changes over a 4‐year period in 3 groups of patients with personality disorders (N  = 162) treated in a specialist community‐based (CBP, N  = 30), a step‐down (RT‐CBP, N  = 87), and a specialist residential programme (RT, N  = 45) in psychiatric distress, deliberate self‐injury, and suicide attempt using multilevel modelling and multivariate logistic regression analyses. The results showed that percentages of early‐dropout were significantly different (p  = .0001) for the 3 programmes (CBP = 13.4%, RT‐CBP = 10.2%, and RT = 41.4%). A significant interaction between treatment model and time was found for psychiatric distress (p  = .001), with CBP and RT‐CBP achieving more marked changes (g  = 1.20 and g  = 0.68, respectively) compared to RT (g  = 0.30) at 48‐month follow‐up. CBP and RT‐CBP were found to significantly reduce impulsive behaviour (deliberate self‐injury and suicide attempt) compared to RT. Severity of presentation was not found to be a significant predictor of outcome. Long‐term RT showed no advantage over long‐term CBP, either as stand‐alone or as step‐down treatment. Replication may be needed to confirm generalizability of results, and a number of limitations in the study design may moderate the inferences that can be drawn from the results.