Should health anxiety be carved at the joint? A look at the health anxiety construct using factor mixture modeling in a non-clinical sample

Cognitive-behavioral models conceptualize health anxiety as a construct that varies in degree along a continuum rather than existing as nonpathological versus pathological classes or taxons. Only two studies have empirically evaluated the latent structure of health anxiety, both using taxometric statistical methods and both supporting its conceptualization as continuous (Ferguson, 2009; Longley et al., 2010). We sought to further evaluate the latent structure of health anxiety using factor mixture modeling (FMM), which involved a combination of exploratory factor analysis (EFA) and mixture modeling that allowed comparison of models comprising one or more latent classes. Health anxiety symptom data were obtained from the Illness Attitude Scales (IAS) administered to 1768 university undergraduate students. Indicators of health anxiety, derived from EFA of IAS item data, included disease worry, disease conviction, health-related safety behaviors, fear of death, somatic focus, interference due to symptoms, and treatment seeking. FMM of these indicators suggested that health anxiety consists of two classes: (a) an "anxious" class comprising 81.4% of the sample and characterized primarily by somatic focus and interference due to symptoms, and (b) a "nonanxious" class comprising 18.6% of the sample with low scores on all indicators. Contrary to current conceptualizations and taxometric findings, the FMM results indicate the latent structure of health anxiety to be taxonic rather than continuous. Implications for the measurement and conceptualization of health anxiety are discussed and future research directions are highlighted.     

How cautious should we be when assessing apathy with the Unified Parkinson's Disease Rating Scale?

Current practice often assesses apathy with a single item from the Unified Parkinson's Disease Rating Scale (UPDRS, item 4). Yet, the relationship between the UPDRS item 4 and the validated Apathy Scale (AS) is unknown. The purpose of this study was to evaluate the operating characteristics of UPDRS item 4 in relation to the AS. Three hundred and one patients with PD were administered the AS and the UPDRS. We compared the UPDRS item 4 to the standard AS classification of ≥14 as apathetic. A receiver operating characteristics (ROC) curve was obtained, and sensitivity, specificity, positive, and negative predictive power were calculated. The ROC curve showed area under the curve as 0.75. A cut‐off of 1 had good sensitivity (81%) but poor specificity (53%; high false positive rate). A cut‐off point of 2 had acceptable specificity (87%) but poor sensitivity (52%, high false negative rate). Continuing to increasing the cut‐off point (e.g., 3, 4) continues to increase specificity at the expense of dramatically reducing sensitivity. These findings suggest the use of caution when screening for apathy with item 4 due to its poor sensitivity in relation to the AS. © 2009 Movement Disorder Society     

Prevention of epilepsy: Should we be avoiding clinical trials?

Epilepsy prevention is one of the great unmet needs in epilepsy. Approximately 15% of all epilepsy is caused by an acute acquired CNS insult such as traumatic brain injury (TBI), stroke or encephalitis. There is a latent period between the insult and epilepsy onset that presents an opportunity to intervene with preventive treatment that is unique in neurology. Yet no phase 3 epilepsy prevention studies, and only 2 phase 2 studies have been initiated in the last 16 years. Current prevailing opinion is that the research community is not ready for clinical preventive epilepsy studies, and that animal models should first be refined and biomarkers of epileptogenesis and of epilepsy discovered before clinical studies are embarked upon. We review data to suggest that there is basis to do epilepsy prevention studies now with the current knowledge and available drugs, and that those studies are feasible with currently available tools. We suggest that a different approach is needed from the past in order to maximize chances of success, minimize the cost, and set up platform for future preventive treatment development. That approach should include close coordination of preclinical and clinical development programs in a combined PTE prevention strategy, consideration of polytherapy, and simultaneous, combined clinical development of preventive treatment and of biomarker discovery. We argue that the currently favored approach of eschewing clinical studies until biomarkers are available will delay the discovery of epilepsy prevention treatment by at least 10 years and significantly increase the cost of such discovery.     

Selective α1-adrenoreceptor blockers in the treatment of hypertension: Should we be using them more?

It has become apparent in recent years that in the treatment of essential hypertension, reduction of blood pressure alone is not sufficient to reduce significantly the morbidity and mortality from ischaemic heart disease. Since the emergence of a multifactorial approach to the prevention of cardiovascular disease, the potential interaction between antihypertensive therapy and metabolic factors, such as control of blood glucose and lipid levels, has become an important consideration. Abnormal function of the sympathetic nervous system may contribute to both the initiation, or maintenance, of hypertension and the associated metabolic disturbances. The new generation of selective ₁-adrenoreceptor blockers, besides lowering blood pressure, appear to have favourable effects on lipid and glucose metabolism. The use of these drugs and their place in the treatment of hypertension are discussed.     

Is the Beck Depression Inventory suitable for screening major depression in different phases of the disease?

This prospective study aimed to assess the suitability of the 21-item Beck Depression Inventory (BDI-21) as a screening method for current episodes of major depressive disorder in different phases of the disease. In a sample of treatment-seeking outpatients (n=125), a structured interview method (SCID) was used twice with a 2-year interval to screen whether the patient had a current episode of major depressive disorder. The validity of the BDI-21 was also analysed by means of receiver operating characteristic (ROC) curves. The results showed that with a cut-off point of 14/15 the BDI-21 can be used to indicate the presence of a major depressive episode regardless of the phase of the major depressive disorder. The sensitivity and specificity were quite satisfactory with this cut-off point. The areas under the ROC curves were large (0.81 at baseline and 0.93 at follow-up). The same BDI-21 cut-off point is suitable for screening major depression among outpatients in any phase of the disease.     

Should OCD be classified as an anxiety disorder in DSM‐V?

In DSM‐III, DSM‐III‐R, and DSM‐IV, obsessive–compulsive disorder (OCD) was classified as an anxiety disorder. In ICD‐10, OCD is classified separately from the anxiety disorders, although within the same larger category as anxiety disorders (as one of the “neurotic, stress‐related, and somatoform disorders”). Ongoing advances in our understanding of OCD and other anxiety disorders have raised the question of whether OCD should continue to be classified with the anxiety disorders in DSM‐V. This review presents a number of options and preliminary recommendations to be considered for DSM‐V. Evidence is reviewed for retaining OCD in the category of anxiety disorders, and for moving OCD to a separate category of obsessive–compulsive (OC)‐spectrum disorders, if such a category is included in DSM‐V. Our preliminary recommendation is that OCD be retained in the category of anxiety disorders but that this category also includes OC‐spectrum disorders along with OCD. If this change is made, the name of this category should be changed to reflect this proposed change. Depression and Anxiety, 2010. © 2010 Wiley‐Liss, Inc.     

Are we close to using Alzheimer blood biomarkers in clinical practice?

<正>Alzheimer’s disease(AD) is a progressive neurodegenerative disease histologically characterized by the presence of extraneuronal plaques,mainly formed by the 42-aminoacid isoform of amyloid-(Aβ_1-42),and by intraneuronal neurofibrillary to ngles,mainly formed by the tau protein and its hyperphosphorylated isoforms(p-tau).AD is the most common cause of dementia,with an estimated lifetime risk of about 1 in 10 for men and 1 in 5 for women.As     

Should coeliac disease be considered in the work up of patients with chronic peripheral neuropathy?

OBJECTIVE: To investigate whether there is an association between chronic peripheral neuropathy and coeliac disease. METHODS: The cause of chronic peripheral neuropathy was first investigated in a group of 478 patients. Published reports were then examined systematically for an association between chronic peripheral neuropathy and coeliac disease. Cases were divided into two groups: group A, polyneuropathy preceding duodenal biopsy and controls undergoing duodenal biopsies; group B, coeliac disease preceding polyneuropathy. Patients with cerebellar ataxia, small fibre neuropathy, or a cause for their neuropathy were excluded. RESULTS: In 425 of the 478 patients, a cause other than coeliac disease was established. In the patients with no determined cause for neuropathy, one had abnormally increased IgA antigliadin antibodies but duodenal biopsy was normal. Ten previous studies of patients with chronic peripheral neuropathies were reviewed. The incidence of biopsy proven coeliac disease in patients with polyneuropathy did not differ from the controls (group A). In patients with a proven coeliac disease (group B), polyneuropathy could not be diagnosed more often than in the general population. CONCLUSIONS: The results of both the clinical study and the literature review suggest that it is unlikely that chronic peripheral neuropathy without other neurological signs is associated with coeliac disease.     

Should cognition be screened in new-onset epilepsies? A study in 247 untreated patients

The aim of our study was to assess cognition in newly diagnosed and untreated patients with epilepsy in order to determine the prevalence and the determinants of cognitive deficits at this early stage of the disease. A total of 247 untreated patients with newly diagnosed epilepsy underwent a brief test battery focusing on attention and executive functions (EpiTrack^®) and memory (short form of the VLMT). In addition, the assessment included ratings of self-perceived deficits in attention and memory. Impairments in attention and executive functions were seen in 49.4 % of the patients and memory deficits in 47.8 %. Unimpaired performance in both domains was observed in 27.9 % of the cases. Self-perceived deficits in attention were only reported by 28.7 % of the patients, and 25.1 % of the patients complained of memory impairments. Lower education and a symptomatic, i.e., lesional, cause of epilepsy were associated with worse performance in attention and executive functions, whereas worse memory performance was related to generalized tonic–clonic seizures. Results indicate a high prevalence of cognitive deficits at an early stage of epilepsy, which calls for consideration in the daily clinical care. Patients appear to underreport cognitive deficits. Thus, a routine application of a brief standardized neuropsychological screening before the initiation of a pharmacological treatment would be appreciated to provide a baseline to evaluate subsequent treatment success, to eventually initiate countermeasures, and to monitor the course of the disease.     

Cognitive and behavioural assessment in clinical trials: when should they be done?

The issue of 'timing' of behavioural assessments in clinical trials can be approached in two different ways. Firstly the 'timing' during the process of drug development. As a rule, cognitive and behavioural side effects of antiepileptic drug treatment do not become an issue until the drug is marketed. At this stage a negative result has large marketing effects and this leads to a tendency to organise 'positive studies'('no-effect results'), that can be achieved by reducing power. A second approach is the 'timing' of cognitive assessment during a trial. The first and intuitive answer to the question 'when this should be done' is to perform assessments during an untreated baseline that is then compared with an endpoint during antiepileptic drug (AED) treatment. This is the 'gold standard design' for cognitive assessments in the majority of the cognitive trials. However, in patients with epilepsy, the behavioural drug effects are not independent from the effect of the epilepsy or the seizures. Recent studies have confirmed that the effect of uncontrolled seizures are often larger than the effects of drug treatment, leading to the so-called seizure confound, that is, adverse cognitive AED effects may be masked by beneficial effects of better seizure control. In such studies endpoint scores are thus improved, hiding possible negative drug effects. Other designs may have other limitations: e.g. in using adjunctive therapy the identification of the components of a treatment most responsible for any observed effects presents a difficult problem; in normal volunteers, exposure durations which are not representative of those in epilepsy patients on chronic treatment represent a major validity issue. We therefore consider the drug withdrawal study as the optimal design for assessing behavioural drug effects. In this design subjects are tested while still on medication and after withdrawal; larger gains in the epilepsy group relative to the controls are considered evidence for a reversible impairment, attributable to AED use.     

False positive rates in Voxel-based Morphometry studies of the human brain: Should we be worried?

Voxel-based Morphometry (VBM) is a widely used automated technique for the analysis of neuroanatomical images. Despite its popularity within the neuroimaging community, there are outstanding concerns about its potential susceptibility to false positive findings. Here we review the main methodological factors that are known to influence the results of VBM studies comparing two groups of subjects. We then use two large, open-access data sets to empirically estimate false positive rates and how these depend on sample size, degree of smoothing and modulation. Our review and investigation provide three main results: (i) when groups of equal size are compared false positive rate is not higher than expected, i.e. about 5%; (ii) the sample size, degree of smoothing and modulation do not appear to influence false positive rate; (iii) when they exist, false positive findings are randomly distributed across the brain. These results provide reassurance that VBM studies comparing groups are not vulnerable to the higher than expected false positive rates that are evident in single case VBM.