Randomized controlled trial of full and brief cognitive-behaviour therapy and wait-list for paediatric obsessive-compulsive disorder

Background: Reviews and practice guidelines for paediatric obsessive-compulsive disorder (OCD) recommend cognitive-behaviour therapy (CBT) as the psychological treatment of choice, but note that it has not been sufficiently evaluated for children and adolescents and that more randomized controlled trials are needed. The aim of this trial was to evaluate effectiveness and optimal delivery of CBT, emphasizing cognitive interventions. Methods: A total of 96 children and adolescents with OCD were randomly allocated to the three conditions each of approximately 12 weeks duration: full CBT (average therapist contact: 12 sessions) and brief CBT (average contact: 5 sessions, with use of therapist-guided workbooks), and wait-list/delayed treatment. The primary outcome measure was the child version of the semi-structured interviewer-based Yale-Brown Obsessive Compulsive Scale. Clinical Trial registration: http://www.controlled-trials.com/ISRCTN/; unique identifier: ISRCTN29092580. Results: There was statistically significant symptomatic improvement in both treatment groups compared with the wait-list group, with no significant differences in outcomes between the two treatment groups. Controlled treatment effect sizes in intention-to-treat analyses were 2.2 for full CBT and 1.6 for brief CBT. Improvements were maintained at follow-up an average of 14 weeks later. Conclusions: The findings demonstrate the benefits of CBT emphasizing cognitive interventions for children and adolescents with OCD and suggest that relatively lower therapist intensity delivery with use of therapist-guided workbooks is an efficient mode of delivery.

Using pH abnormalities in diseased skin to trigger and target topical therapy

Abstract Purpose: The pH discrepancy between healthy and atopic dermatitis skin was identified as a site specific trigger for delivering hydrocortisone from microcapsules. Methods: Using Eudragit L100, a pH-responsive polymer which dissolves at pH 6, hydrocortisone-loaded microparticles were produced by oil-in-oil microencapsulation or spray drying. Release and permeation of hydrocortisone from microparticles alone or in gels was assessed and preliminary stability data was determined. Results: Drug release from microparticles was pH-dependent though the particles produced by spray drying also gave significant non-pH dependent burst release, resulting from their porous nature or from drug enrichment on the surface of these particles. This pH-responsive release was maintained upon incorporation of the oil-in-oil microparticles into Carbopol- and HPMC-based gel formulations. In-vitro studies showed 4 to 5-fold higher drug permeation through porcine skin from the gels at pH 7 compared to pH 5. Conclusions: Permeation studies showed that the oil-in-oil generated particles deliver essentially no drug at normal (intact) skin pH (5.0 – 5.5) but that delivery can be triggered and targeted to atopic dermatitis skin where the pH is elevated. The incorporation of these microparticles into Carbopol- and HPMC-based aqueous gel formulations demonstrated good stability and pH-responsive permeation into porcine skin.

Mapping therapy for sentence production impairments in nonfluent aphasia

This study investigated a new treatment in which sentence production abilities were trained in a small group of individuals and nonfluent aphasia. It was based upon a mapping therapy approach which holds that sentence production and comprehension impairments are due to difficulties in mapping between the meaning form (thematic roles) and the syntactic form of sentences. We trained production of both canonical and noncanonical reversible sentences.Three patients received treatment and two served as control participants. Patients who received treatment demonstrated acquisition of all trained sentence structures. They also demonstrated across-task generalisation of treated and some untreated sentence structures on two tasks of constrained sentence production, and showed some improvements on a narrative task. One control participant improved on some of these measures and the other did not. There was no noted improvement in sentence comprehension abilities following treatment. Results are discussed with reference to the heterogeneity of underlying impairments in sentence production impairments in nonfluent patients, and the possible mechanisms by which improvement in sentence production might have been achieved in treatment.

Effective elements of cognitive behaviour therapy for psychosis: results of a novel type of subgroup analysis based on principal stratification

Background. Meta-analyses show that cognitive behaviour therapy for psychosis (CBT-P) improves distressing positive symptoms. However, it is a complex intervention involving a range of techniques. No previous study has assessed the delivery of the different elements of treatment and their effect on outcome. Our aim was to assess the differential effect of type of treatment delivered on the effectiveness of CBT-P, using novel statistical methodology. Method. The Psychological Prevention of Relapse in Psychosis (PRP) trial was a multi-centre randomized controlled trial (RCT) that compared CBT-P with treatment as usual (TAU). Therapy was manualized, and detailed evaluations of therapy delivery and client engagement were made. Follow-up assessments were made at 12 and 24 months. In a planned analysis, we applied principal stratification (involving structural equation modelling with finite mixtures) to estimate intention-to-treat (ITT) effects for subgroups of participants, defined by qualitative and quantitative differences in receipt of therapy, while maintaining the constraints of randomization. Results. Consistent delivery of full therapy, including specific cognitive and behavioural techniques, was associated with clinically and statistically significant increases in months in remission, and decreases in psychotic and affective symptoms. Delivery of partial therapy involving engagement and assessment was not effective. Conclusions. Our analyses suggest that CBT-P is of significant benefit on multiple outcomes to patients able to engage in the full range of therapy procedures. The novel statistical methods illustrated in this report have general application to the evaluation of heterogeneity in the effects of treatment.

Therapygenetics: the 5HTTLPR and response to psychological therapy

Although pharmacogenetic research thrives,1 genetic determinants of response to purely psychotherapeutic treatments remain unexplored. In a sample of children undergoing cognitive behaviour therapy (CBT) for an anxiety disorder, we tested whether treatment response is associated with the serotonin transporter gene promoter region (5HTTLPR), previously shown to moderate environmental influences on depression.

Virtual reality Post Traumatic Stress Disorder (PTSD) exposure therapy results with active duty OIF/OEF service members

Posttraumatic stress disorder (PTSD) is reported to be caused by exposure to traumatic events including (but not limited to) military combat, violent personal assault, being kidnapped or taken hostage and terrorist attacks. Initial data suggest that at least 1 out of 6 Iraq War veterans are exhibiting symptoms of depression, anxiety and PTSD. Virtual reality (VR) delivered exposure therapy for PTSD has been used with reports of positive outcomes. The aim of the current paper, is to present the rationale and brief description of a Virtual Iraq/Afghanistan PTSD VR therapy application and present initial findings from its use with PTSD patients. Thus far, Virtual Iraq/Afghanistan consists of a series of customizable virtual scenarios designed to represent relevant Middle Eastern VR contexts for exposure therapy, including a city and desert road convoy environment. User-centered design feedback, needed to iteratively evolve the system, was gathered from returning Iraq War veterans in the USA and from a system deployed in Iraq and tested by an Army Combat Stress Control Team. Results from an open clinical trial at San Diego Naval Medical Center of the first 20 treatment completers indicate that 16 no longer met PTSD screening criteria at post-treatment, with only one not maintaining treatment gains at 3 month follow-up.

Neurotrophic gene polymorphisms and response to psychological therapy

Therapygenetics, the study of genetic determinants of response to psychological therapies, is in its infancy. Here, we investigate whether single-nucleotide polymorphisms in nerve growth factor (NGF) (rs6330) and brain-derived neutrotrophic factor (BDNF) (rs6265) genes predict the response to cognitive behaviour therapy (CBT). Neurotrophic genes represent plausible candidate genes: they are implicated in synaptic plasticity, response to stress, and are widely expressed in brain areas involved in mood and cognition. Allelic variation at both loci has shown associations with anxiety-related phenotypes. A sample of 374 anxiety-disordered children with white European ancestry was recruited from clinics in Reading, UK, and in Sydney, Australia. Participants received manualised CBT treatment and DNA was collected from buccal cells using cheek swabs. Treatment response was assessed at post-treatment and follow-up time points. We report first evidence that children with one or more copies of the T allele of NGF rs6330 were significantly more likely to be free of their primary anxiety diagnosis at follow-up (OR=0.60 (0.42–0.85), P=0.005). These effects remained even when other clinically relevant covariates were accounted for (OR=0.62 (0.41–0.92), P=0.019). No significant associations were observed between BDNF rs6265 and response to psychological therapy. These findings demonstrate that knowledge of genetic markers has the potential to inform clinical treatment decisions for psychotherapeutic interventions.

Cardioprotective effects of insulin: how intensive insulin therapy may benefit cardiac surgery patients

Interest in the effects of insulin on the heart came with the recognition that hyperglycemia in the context of myocardial infarction is associated with increased risks of mortality, congestive heart failure, or cardiogenic shock. More recently, instigated by research findings on stress hyperglycemia in critical illness, this interest has been extended to the influence of insulin on clinical outcome after cardiac surgery. Even in nondiabetic individuals, stress hyperglycemia commonly occurs as a key metabolic response to critical illness, eg, after surgical trauma. It is recognized as a major pathophysiological feature of organ dysfunction in the critically ill. The condition stems from insulin resistance brought about by dysregulation of key homeostatic processes, which implicates immune/inflammatory, endocrine, and metabolic pathways. It has been associated with adverse clinical outcomes, including increased mortality, increased duration of mechanical ventilation, increased intensive care unit (ICU) and hospital stay, and increased risk of infection. Hyperglycemia in critical illness is managed with exogenous insulin as standard treatment; however, there is considerable disagreement among experts in the field as to what target blood glucose level is optimal for the critically ill patient. Conventionally, the aim of insulin therapy has been to maintain blood glucose levels below the renal threshold, typically 220 mg/dL (12.2 mmol/L). In recent years, some have advocated tight glycemic control (TGC) with intensive insulin therapy (IIT) to normalize blood glucose levels to within the euglycemic range, typically 80 to 110 mg/dL (4.4–6.1 mmol/L).

Does training improve understanding of core concepts in cognitive behaviour therapy by people with intellectual disabilities? A randomized experiment

Background. People with intellectual disabilities (ID) experience similar or even higher rates of mental health problems than the general population and there is a need to develop appropriate treatments. Cognitive behaviour therapy (CBT) is effective for a wide range of disorders in the general population. However, there is some evidence that people with ID may lack the cognitive skills needed to take part in CBT. Aims. To test if people with ID can learn skills required for CBT, specifically the ability to distinguish between thoughts, feelings, and behaviours and to link thoughts and feelings (cognitive mediation). Method. A randomized independent groups design was used to examine the effect of training in CBT on two tasks measuring CBT skills. Thirty-four adults with ID were randomly allocated to the experimental condition ðN ¼ 18Þ or to the control condition ðN ¼ 16Þ. CBT skills were assessed blind at baseline and after the intervention. Results. The training led to significant improvements in participants’ ability to link thoughts and feelings, and this skill was generalized to new material. There was no effect of training on participants’ ability to distinguish amongst thoughts, feelings, and behaviours. People with ID can, therefore, learn some skills required for CBT. This implies that preparatory training for CBT might be useful for people with ID. The results might be applicable to other groups who find aspects of CBT difficult.

Cognitive behaviour therapy for low self-esteem: A preliminary randomized controlled trial in a primary care setting

Background and Objectives Low self-esteem (LSE) is associated with psychiatric disorder, and is distressing and debilitating in its own right. Hence, it is frequent target for treatment in cognitive behavioural interventions, yet it has rarely been the primary focus for intervention. This paper reports on a preliminary randomized controlled trial of cognitive behaviour therapy (CBT) for LSE using Fennell’s (1997) cognitive conceptualisation and transdiagnostic treatment approach ( [Fennell, 1997] and [Fennell, 1999]). Methods Twenty-two participants were randomly allocated to either immediate treatment (IT) (n = 11) or to a waitlist condition (WL) (n = 11). Treatment consisted of 10 sessions of individual CBT accompanied by workbooks. Participants allocated to the WL condition received the CBT intervention once the waitlist period was completed and all participants were followed up 11 weeks after completing CBT. Results The IT group showed significantly better functioning than the WL group on measures of LSE, overall functioning and depression and had fewer psychiatric diagnoses at the end of treatment. The WL group showed the same pattern of response to CBT as the group who had received CBT immediately. All treatment gains were maintained at follow-up assessment. Limitations The sample size is small and consists mainly of women with a high level of educational attainment and the follow-up period was relatively short. Conclusions These preliminary findings suggest that a focused, brief CBT intervention can be effective in treating LSE and associated symptoms and diagnoses in a clinically representative group of individuals with a range of different and co-morbid disorders.

Chronic systemic therapy with low-dose morpholino oligomers ameliorates the pathology and normalizes locomotor behavior in mdx Mice

The administration of antisense oligonucleotides (AOs) to skip one or more exons in mutated forms of the DMD gene and so restore the reading frame of the transcript is one of the most promising approaches to treat Duchenne muscular dystrophy (DMD). At present, preclinical studies demonstrating the efficacy and safety of long-term AO administration have not been conducted. Furthermore, it is essential to determine the minimal effective dose and frequency of administration. In this study, two different low doses (LDs) of phosphorodiamidate morpholino oligomer (PMO) designed to skip the mutated exon 23 in the mdx dystrophic mouse were administered for up to 12 months. Mice treated for 50 weeks showed a substantial dose-related amelioration of the pathology, particularly in the diaphragm. Moreover, the generalized physical activity was profoundly enhanced compared to untreated mdx mice showing that widespread, albeit partial, dystrophin expression restores the normal activity in mdx mice. Our results show for the first time that a chronic long-term administration of LDs of unmodified PMO, equivalent to doses in use in DMD boys, is safe, significantly ameliorates the muscular dystrophic phenotype and improves the activity of dystrophin-deficient mice, thus encouraging the further clinical translation of this approach in humans.