Brian Everitt

Cognitive Behavior Therapy for Schizophrenia: Effect Sizes, Clinical Models, and Methodological Rigor

Background: Guidance in the United States and United Kingdom has included cognitive behavior therapy for psychosis (CBTp) as a preferred therapy. But recent advances have widened the CBTp targets to other symptoms and have different methods of provision, eg, in groups. Aim: To explore the effect sizes of current CBTp trials including targeted and nontargeted symptoms, modes of action, and effect of methodological rigor. Method: Thirty-four CBTp trials with data in the public domain were used as source data for a meta-analysis and investigation of the effects of trial methodology using the Clinical Trial Assessment Measure (CTAM). Results: There were overall beneficial effects for the target symptom (33 studies; effect size = 0.400 [95% confidence interval {CI} = 0.252, 0.548]) as well as significant effects for positive symptoms (32 studies), negative symptoms (23 studies), functioning (15 studies), mood (13 studies), and social anxiety (2 studies) with effects ranging from 0.35 to 0.44. However, there was no effect on hopelessness. Improvements in one domain were correlated with improvements in others. Trials in which raters were aware of group allocation had an inflated effect size of approximately 50%–100%. But rigorous CBTp studies showed benefit (estimated effect size = 0.223; 95% CI = 0.017, 0.428) although the lower end of the CI should be noted. Secondary outcomes (eg, negative symptoms) were also affected such that in the group of methodologically adequate studies the effect sizes were not significant. Conclusions: As in other meta-analyses, CBTp had beneficial effect on positive symptoms. However, psychological treatment trials that make no attempt to mask the group allocation are likely to have inflated effect sizes. Evidence considered for psychological treatment guidance should take into account specific methodological detail.

Compliance therapy in psychotic patients: randomised controlled trial

Abstract Objective: To determine whether compliance therapy, a cognitive-behavioural intervention, could improve compliance with treatment and hence social adjustment in acutely psychotic inpatients, and if so, whether the effect persisted six months later. Design: Randomised controlled trial of compliance therapy and non-specific counselling, each comprising 4-6 sessions lasting 10-60 minutes. Setting: Acute psychiatric admissions ward serving an inner London catchment area. Subjects: 47 patients with psychosis. Main outcome measures: Informant and observer reported measure of compliance; observer assessed global functioning after intervention and three and six months later; self rated attitudes to drug treatment after the intervention and one month later; symptom scores after intervention and six months later. Results: 25 patients received compliance therapy and showed significantly greater improvements in their attitudes to drug treatment and in their insight into illness and compliance with treatment compared with the control group. These gains persisted for six months. The intervention group was 5.2 times more likely than the control group to reach a criterion level of compliance (95% confidence interval 1.5 to 18.3). Global functioning showed a tendency to improve more in the intervention group after a delay (odds ratio 3.0 (0.8 to 11.5) to reach the criterion level at six months). Four subjects given compliance therapy and six in the control group were readmitted during follow up (odds ratio 2.0 (0.48 to 8.2)). Conclusions: Compliance therapy is a pragmatic method for improving compliance with drug treatment in psychotic inpatients and its gains persist for at least six months. Overall functioning may also be enhanced. Key messages Key messages Compliance is strongly related to attitudes to treatment and to insight The study found that such attitudes may be influenced by a simple and brief intervention known as compliance therapy Compliance therapy compared with non-specific counselling leads to improved compliance The improvement is sustained for at least six months and may lead to improved social functioning

An introduction to latent variable models

1 General introduction.- 1.1 Introduction.- 1.2 Latent variables and latent variable models.- 1.3 The role of models.- 1.4 The general latent model.- 1.5 A simple latent variable model.- 1.6 Estimation and goodness-of-fit.- 1.7 Path diagrams.- 1.8 Summary.- 2 Factor analysis.- 2.1 Introduction.- 2.2 Explanatory and confirmatory factor analysis.- 2.3 The factor analysis model.- 2.4 Identifiability of the factor analysis model.- 2.5 Estimating the parameters in the factor analysis model.- 2.6 Goodness-of-fit tests.- 2.7 Rotation of factors.- 2.8 Numerical examples.- 2.9 Confirmatory factor analysis.- 2.10 Summary.- 3 The LISREL model.- 3.1 Introduction.- 3.2 The LISREL model.- 3.3 Identification.- 3.4 Estimating the parameters in the LISREL model.- 3.5 Instrumental variables.- 3.6 Numerical examples.- 3.7 Assessing goodness-of-fit.- 3.8 Multigroup analysis.- 3.9 Summary.- 4 Latent variable models for categorical data.- 4.1 Introduction.- 4.2 Factor analysis of binary variables.- 4.3 Latent structure models.- 4.4 Summary.- 5 Some final comments.- 5.1 Introduction.- 5.2 Assessing the fit of latent variable models by cross-validation procedures.- 5.3 Latent variables - fact or fiction?.- 5.4 Summary.- Appendix A Estimating the parameters in latent variable models a brief account of computational procedures.- Appendix B Computer programs for latent variable models.- Exercises.- References.

A systematic review and quantitative appraisal of fmri studies of verbal fluency : Role of the left inferior frontal gyrus

The left inferior frontal gyrus (LIFG) has consistently been associated with both phonologic and semantic operations in functional neuroimaging studies. Two main theories have proposed a different functional organization in the LIFG for these processes. One theory suggests an anatomic parcellation of phonologic and semantic operations within the LIFG. An alternative theory proposes that both processes are encompassed within a supramodal executive function in a single region in the LIFG. To test these theories, we carried out a systematic review of functional magnetic resonance imaging studies employing phonologic and semantic verbal fluency tasks. Seventeen articles meeting our pre‐established criteria were found, consisting of 22 relevant experiments with 197 healthy subjects and a total of 41 peak activations in the LIFG. We determined 95% confidence intervals of the mean location (x, y, and z coordinates) of peaks of blood oxygenation level‐dependent (BOLD) responses from published phonologic and semantic verbal fluency studies using the nonparametric technique of bootstrap analysis. Significant differences were revealed in dorsal–ventral (z‐coordinate) localizations of the peak BOLD response: phonologic verbal fluency peak BOLD response was significantly more dorsal to the peak associated with semantic verbal fluency (confidence interval of difference: 1.9–17.4 mm). No significant differences were evident in antero–posterior (x‐coordinate) or medial–lateral (y‐coordinate) positions. The results support distinct dorsal–ventral locations for phonologic and semantic processes within the LIFG. Current limitations to meta‐analytic integration of published functional neuroimaging studies are discussed. Hum Brain Mapp, 2006.

Computerized, interactive, multimedia cognitive-behavioural program for anxiety and depression in general practice

BACKGROUND Cognitive-behavioural therapy (CBT) brings about significant clinical improvement in anxiety and depression, but therapists are in short supply. We report the first phase of a randomized controlled trial of an interactive multimedia program of cognitive-behavioural techniques, Beating the Blues (BtB), in the treatment of patients in general practice with anxiety, depression or mixed anxiety/depression. METHOD One hundred and sixty-seven adults suffering from anxiety and/or depression and not receiving any form of psychological treatment or counselling were randomly allocated to receive, with or without medication, BtB or treatment as usual (TAU). Measures were taken on five occasions: prior to treatment, 2 months later, and at 1, 3 and 6 months follow-up using the Beck Depression Inventory, Beck Anxiety Inventory and Work and Social Adjustment Scale. RESULTS Patients who received BtB showed significantly greater improvement in depression and anxiety compared to TAU by the end of treatment (2 months) and to 6 months follow-up. Symptom reduction was paralleled by improvement in work and social adjustment. There were no interactions of BtB with concomitant pharmacotherapy or duration of illness, but evidence, on the Beck Anxiety Inventory only, of interaction with primary care practice. Importantly, there was no interaction between the effects of BtB and baseline severity of depression, from which we conclude that the effects of the computer program are independent of starting level of depression. CONCLUSIONS These results demonstrate that computerized interactive multimedia cognitive-behavioural techniques under minimal clinical supervision can bring about improvements in depression and anxiety, as well as in work and social adjustment, with and without pharmacotherapy and in patients with pre-treatment illness of durations greater or less than 6 months. Thus, our results indicate that wider dissemination of cognitive-behavioural techniques is possible for patients suffering from anxiety and/or depression.

Are the effects of Cognitive Remediation Therapy (CRT) durable? Results from an exploratory trial in schizophrenia.

BACKGROUND This paper investigates the durability of the effects of cognitive remediation therapy (CRT). In a randomised control trial, CRT was compared with a control therapy (intensive occupational therapy activities), matched for length of therapist contact. The main three cognitive outcomes, (i) number of categories achieved on the Wisconsin Card Sort Test, (ii) age-scaled score on the Digit Span subtest of the WAIS-R, and (iii) mean number of moves on the Tower of London test, were chosen because they are known to be problematic in schizophrenia. In addition, a wide variety of other outcomes (symptoms, social functioning, self-esteem and cognition) were assessed. At the end of treatment, CRT conferred a benefit to people with schizophrenia in cognition and self-esteem [Schizophr. Bull. 25 (1999) 291]. This study investigates these outcomes 6 months after the therapies were withdrawn. METHOD Participants were assessed at baseline, posttreatment and 6-month follow-up (n=17 for the CRT group; n=16 for the control therapy group). In addition to the functioning measures, data on use of services and cost of therapy were collected. RESULTS The effects of CRT on cognition were still apparent at follow-up, particularly in the memory domain. When these cognitive improvements reached a criterion threshold, there were also improvements in social behaviour and symptoms. The gains made in self-esteem disappeared following the withdrawal of therapy. The economic analysis showed overall reductions in the care packages of both patient groups but there was a significant increase in day-care costs for patients who have received CRT. This additional use of day care may confer further advantages to the CRT group, such as improved social functioning and quality of life. CONCLUSIONS The overall results of this first trial of a novel CRT approach have produced encouraging results which merit further investigation.

Is there a Gulf War syndrome

Summary Background UK veterans of the Gulf War report more ill health than servicemen who were not deployed to the Gulf War. We investigated whether the pattern of symptom reporting by veterans of the Gulf War differed from that in active servicemen who had not fought in the Gulf War or who had fought in other conflicts. Methods We used a population-based cross-sectional design. We sent a standardised survey that asked about 50 physical symptoms to three UK military cohorts; men who had served in the Gulf War, those who had served in the Bosnia conflict, and men who had been in active service but not deployed to the Gulf War (Era cohort). We used exploratory factor analysis to identify underlying factors and describe the factor structure of the symptoms reported in the Gulf War cohort. Confirmatory factor analysis was used to test the fit of this factor structure in the Bosnia and Era cohorts. Findings Three factors in the Gulf War cohort together accounted for about 20% of the common variance. We labelled the factors mood, respiratory system, and peripheral nervous system, according to the symptoms that loaded on to them. In the confirmatory factor analysis, the factor structure identified in the Gulf War cohort fitted reasonably well in the Bosnia and Era cohorts. Interpretation Although results from complex modelling procedures need to be interpreted with caution, our findings do not support a unique Gulf War syndrome. The mechanisms behind increased self-reporting of symptoms need further investigation. Lancet 1999; 353: 179‐82 See Commentary page ???

Statistical methods for medical investigations

Statistics in medicine the design of medical investigations - clinical trials and other methods measurement in medicine statistical inference regression analysis repeated measures analysis of variance and the analysis of covariance crossover designs the analysis of survival data multivariate data and principal components analysis statistical methods for classification - cluster analysis and assignment techniques time series analysis the analysis of observational techniques. Appendix: computers and statistics.

Post-combat syndromes from the Boer war to the Gulf war: a cluster analysis of their nature and attribution

Abstract Objectives: To discover whether post-combat syndromes have existed after modern wars and what relation they bear to each other. Design: Review of medical and military records of servicemen and cluster analysis of symptoms. Data sources: Records for 1856 veterans randomly selected from war pension files awarded from 1872 and from the Medical Assessment Programme for Gulf war veterans. Main outcome measures: Characteristic patterns of symptom clusters and their relation to dependent variables including war, diagnosis, predisposing physical illness, and exposure to combat; and servicemens changing attributions for post-combat disorders. Results: Three varieties of post-combat disorder were identified — a debility syndrome (associated with the 19th and early 20th centuries), somatic syndrome (related primarily to the first world war), and a neuropsychiatric syndrome (associated with the second world war and the Gulf conflict). The era in which the war occurred was overwhelmingly the best predictor of cluster membership. Conclusions: All modern wars have been associated with a syndrome characterised by unexplained medical symptoms. The form that these assume, the terms used to describe them, and the explanations offered by servicemen and doctors seem to be influenced by advances in medical science, changes in the nature of warfare, and underlying cultural forces.

Mixture model mapping of brain activation in functional magnetic resonance images

We report on a novel method of identifying brain regions activated by periodic experimental design in functional magnetic resonance imaging data. This involves fitting a mixture distribution with two components to a test statistic estimated at each voxel in an image. The two parameters of this distribution, the proportion of nonactivated voxels, and the effect size can be estimated using maximum likelihood methods. Standard errors of the parameters can also be estimated. The fitted distribution can be used to derive brain activation maps and two examples are described, one involving a visual stimulation task, the other an auditory stimulation task. The method appears to have some advantages over direct use of the P‐values corresponding to each voxels value of the test statistic. Hum. Brain Mapping 7:1–14, 1999.