Performing meta-analysis with incomplete statistical information in clinical trials

Background: Results from clinical trials are usually summarized in the form of sampling distributions. When full information (mean, SEM) about these distributions is given, performing meta-analysis is straightforward. However, when some of the sampling distributions only have mean values, a challenging issue is to decide how to use such distributions in meta-analysis. Currently, the most common approaches are either ignoring such trials or for each trial with a missing SEM, finding a similar trial and taking its SEM value as the missing SEM. Both approaches have drawbacks. As an alternative, this paper develops and tests two new methods, the first being the prognostic method and the second being the interval method, to estimate any missing SEMs from a set of sampling distributions with full information. A merging method is also proposed to handle clinical trials with partial information to simulate meta-analysis.

Absence of the 7-repeat variant of the DRD4 VNTR is associated with drifting sustained attention in children with ADHD but not in controls

Many genetic studies have demonstrated an association between the 7-repeat (7r) allele of a 48-base pair variable number of tandem repeats (VNTR) in exon 3 of the DRD4 gene and the phenotype of attention deficit hyperactivity disorder (ADHD). Previous studies have shown inconsistent associations between the 7r allele and neurocognitive performance in children with ADHD. We investigated the performance of 128 children with and without ADHD on the Fixed and Random versions of the Sustained Attention to Response Task (SART). We employed timeseries analyses of reaction-time data to allow a fine-grained analysis of reaction time variability, a candidate endophenotype for ADHD. Children were grouped into either the 7r-present group (possessing at least one copy of the 7r allele) or the 7r-absent group. The ADHD group made significantly more commission errors and was significantly more variable in RT in terms of fast moment-to-moment variability than the control group, but no effect of genotype was found on these measures. Children with ADHD without the 7r allele made significantly more omission errors, were significantly more variable in the slow frequency domain and showed less sensitivity to the signal (d') than those children with ADHD the 7r and control children with or without the 7r. These results highlight the utility of time-series analyses of reaction time data for delineating the neuropsychological deficits associated with ADHD and the DRD4 VNTR. Absence of the 7-repeat allele in children with ADHD is associated with a neurocognitive profile of drifting sustained attention that gives rise to variable and inconsistent performance. (c) 2008 Wiley-Liss, Inc.

Imaging the genetics of executive function

Recent advances in neuroimaging technologies have allowed ever more detailed studies of the human brain. The combination of neuroimaging techniques with genetics may provide a more sensitive measure of the influence of genetic variants on cognitive function than behavioural measures alone. Here we present a review of functional magnetic resonance imaging (fMRI) studies of genetic links to executive functions, focusing on sustained attention, working memory and response inhibition. In addition to studies in the normal population, we also address findings from three clinical populations: schizophrenia, ADHD and autism spectrum disorders. While the findings in the populations studied do not always converge, they all point to the usefulness of neuroimaging techniques such as fMRI as potential endophenotypes for parsing the genetic aetiology of executive function. (C) 2007 Elsevier B.V. All rights reserved.

Neutrophils and eosinophils: clinical implications of their appearance, presence and disappearance in asthma and COPD.

Asthma and chronic obstructive pulmonary disease (COPD) are common chronic disorders. Traditionally, asthma has been associated with an eosinophilic inflammation and COPD with neutrophilic inflammation. In this review we will highlight the maturation, recruitment, activation, action and apoptosis of these cells. In addition we will focus on the evidence for their presence in disease and suggest potential new therapeutic interventions.

An analysis of geometric uncertainty calculations for prostate radiotherapy in clinical practice.

Margins are used in radiotherapy to assist in the calculation of planning target volumes. These margins can be determined by analysing the geometric uncertainties inherent to the radiotherapy planning and delivery process. An important part of this process is the study of electronic portal images collected throughout the course of treatment. Set-up uncertainties were determined for prostate radiotherapy treatments at our previous site and the new purpose-built centre, with margins determined using a number of different methods. In addition, the potential effect of reducing the action level from 5 mm to 3 mm for changing a patient set-up, based on off-line bony anatomy-based portal image analysis, was studied. Margins generated using different methodologies were comparable. It was found that set-up errors were reduced following relocation to the new centre. Although a significant increase in the number of corrections to a patient's set-up was predicted if the action level was reduced from 5 mm to 3 mm, minimal reduction in patient set-up uncertainties would be seen as a consequence. Prescriptive geometric uncertainty analysis not only supports calculation and justification of the margins used clinically to generate planning target volumes, but may also best be used to monitor trends in clinical practice or audit changes introduced by new equipment, technology or practice. Simulations on existing data showed that a 3 mm rather than a 5 mm action level during off-line, bony anatomy-based portal imaging would have had a minimal benefit for the patients studied in this work.

Is there a role for n-3 long-chain polyunsaturated fatty acids in the regulation of mood and behaviour? A review of the evidence to date from epidemiological studies, clinical studies and intervention trials

Selected biochemical evidence suggests a potential role for n-3 long-chain PUFA (n-3PUFA) in the regulation of mood and behaviour. The present paper reviews the relevant evidence, to date, from epidemiological studies, clinical studies and intervention trials. Most evidence is available investigating a role for n-3PUFA in depression, depressive illness and suicidal behaviour, but work is also available on anxiety and anxiety-related disorders, fatigue and fatigue-related disorders, aggression, hostility and anti-social behaviour, inattention, impulsivity and attention deficit hyperactivity disorder and schizophrenic disorders. For all these aspects of mood and behaviour, the evidence available is currently limited and highly inconsistent, both in terms of study methodology and study findings. There is a clear need for further work in this area.

No clear evidence of an association between plasma concentrations of n-3 long-chain polyunsaturated fatty acids and depressed mood in a non-clinical population

Previous research suggests that low n-3 long-chain polyunsaturated fatty acid (n-3PUFA) status is associated with higher levels of depression in clinical populations. This analysis aimed to investigate the relationship between depressed mood and n-3PUFA status in a non-clinical population. The analysis was conducted on data collected as part of a large randomized controlled trial investigating the impact of n-3PUFA supplementation on depressed mood in a community-based population. On entry into the trial, data on depressed mood were collected using the Depression, Anxiety and Stress Scales (DASS) and the Beck Depression Inventory (BDI). Plasma concentrations of various n-3PUFAs and n-6 long-chain polyunsaturated fatty acids (n-6PUFAs) were obtained from fasting venous blood samples, and various demographics were also measured. Using regression, there was no evidence of an association between either measure of depressed mood and any of the measures of n-3PUFA status or of n-6PUFA: n-3PUFA ratios. Clear associations were also not found when demographic factors were included in the analyses. These findings suggest that n-3PUFAs may not have a role in the aetiology of minor depression. This is also consistent with the results of other studies that have not demonstrated an association between depressed mood and n-3PUFA status in non-clinical populations and epidemiological studies that have not demonstrated an association between depressed mood and n-3PUFA intake in these populations. (C) 2008 Elsevier Ltd. All rights reserved.

An experience of attempting to apply the randomised controlled trial (RCT) design in a ‘real world’ community-based clinical setting – one family therapist’s current journey. Context, 99, 6-9.

This paper describes an early career researcher's expereince of using randomised controlled trial methodology to investigarte the effectiveness of psychotherapeutic interventions for traumatised families in a 'real world' setting.