Internet-based indicated prevention for panic disorder: An effectiveness trial in primary care

Previous studies have shown that an internet delivered indicated prevention program for panic disorder can be effective. However, those studies were done with select populations. Most individuals who are at risk for panic disorder present to hospital emergency rooms and primary care settings. This paper reports on a study currently being undertaken in Scotland where the program is being trialed in primary care. The intervention and experimental design will be described. However the key research question is whether General Practitioners will make use of the internet-based intervention system. Preliminary results will be reported. The results of the study will have implications for the way that primary care is recruited into the prevention of mental health problems.

Hypothesis: is Alzheimer's disease a metal-induced immune disorder?

A hypothesis that a metal-induced immune disorder may be involved in the pathogenesis of some forms of Alzheimer's disease (AD) is presented. The classical complement pathway is activated in AD and T cells and reactive microglia appear in the brain. Studies of metal induced autoimmunity and the use of compounds containing aluminium as vaccine adjuvants suggest that metals can activate complement and can be taken up by antigen presenting cells. The consequent immune response could contribute to neuronal damage, beta-amyloid deposition and cell death. The strengths and weaknesses of this hypothesis are discussed and tests of some aspects are proposed.

Investigation of chaotic mixing in laminar fluid systems by the use of computational fluid dynamics

This work presents significant development into chaotic mixing induced through periodic boundaries and twisting flows. Three-dimensional closed and throughput domains are shown to exhibit chaotic motion under both time periodic and time independent boundary motions, A property is developed originating from a signature of chaos, sensitive dependence to initial conditions, which successfully quantifies the degree of disorder withjn the mixing systems presented and enables comparisons of the disorder throughout ranges of operating parameters, This work omits physical experimental results but presents significant computational investigation into chaotic systems using commercial computational fluid dynamics techniques. Physical experiments with chaotic mixing systems are, by their very nature, difficult to extract information beyond the recognition that disorder does, does not of partially occurs. The initial aim of this work is to observe whether it is possible to accurately simulate previously published physical experimental results through using commercial CFD techniques. This is shown to be possible for simple two-dimensional systems with time periodic wall movements. From this, and subsequent macro and microscopic observations of flow regimes, a simple explanation is developed for how boundary operating parameters affect the system disorder. Consider the classic two-dimensional rectangular cavity with time periodic velocity of the upper and lower walls, causing two opposing streamline motions. The degree of disorder within the system is related to the magnitude of displacement of individual particles within these opposing streamlines. The rationale is then employed in this work to develop and investigate more complex three-dimensional mixing systems that exhibit throughputs and time independence and are therefore more realistic and a significant advance towards designing chaotic mixers for process industries. Domains inducing chaotic motion through twisting flows are also briefly considered. This work concludes by offering possible advancements to the property developed to quantify disorder and suggestions of domains and associated boundary conditions that are expected to produce chaotic mixing.

Elevated left and reduced right orbitomedial prefrontal fractional anisotropy in adults with bipolar disorder revealed by tract-based spatial statistics

Context - Diffusion tensor imaging (DTI) studies in adults with bipolar disorder (BD) indicate altered white matter (WM) in the orbitomedial prefrontal cortex (OMPFC), potentially underlying abnormal prefrontal corticolimbic connectivity and mood dysregulation in BD. Objective - To use tract-based spatial statistics (TBSS) to examine WM skeleton (ie, the most compact whole-brain WM) in subjects with BD vs healthy control subjects. Design - Cross-sectional, case-control, whole-brain DTI using TBSS. Setting - University research institute. Participants - Fifty-six individuals, 31 having a DSM-IV diagnosis of BD type I (mean age, 35.9 years [age range, 24-52 years]) and 25 controls (mean age, 29.5 years [age range, 19-52 years]). Main Outcome Measures - Fractional anisotropy (FA) longitudinal and radial diffusivities in subjects with BD vs controls (covarying for age) and their relationships with clinical and demographic variables. Results - Subjects with BD vs controls had significantly greater FA (t > 3.0, P = .05 corrected) in the left uncinate fasciculus (reduced radial diffusivity distally and increased longitudinal diffusivity centrally), left optic radiation (increased longitudinal diffusivity), and right anterothalamic radiation (no significant diffusivity change). Subjects with BD vs controls had significantly reduced FA (t > 3.0, P = .05 corrected) in the right uncinate fasciculus (greater radial diffusivity). Among subjects with BD, significant negative correlations (P < .01) were found between age and FA in bilateral uncinate fasciculi and in the right anterothalamic radiation, as well as between medication load and FA in the left optic radiation. Decreased FA (P < .01) was observed in the left optic radiation and in the right anterothalamic radiation among subjects with BD taking vs those not taking mood stabilizers, as well as in the left optic radiation among depressed vs remitted subjects with BD. Subjects having BD with vs without lifetime alcohol or other drug abuse had significantly decreased FA in the left uncinate fasciculus. Conclusions - To our knowledge, this is the first study to use TBSS to examine WM in subjects with BD. Subjects with BD vs controls showed greater WM FA in the left OMPFC that diminished with age and with alcohol or other drug abuse, as well as reduced WM FA in the right OMPFC. Mood stabilizers and depressed episode reduced WM FA in left-sided sensory visual processing regions among subjects with BD. Abnormal right vs left asymmetry in FA in OMPFC WM among subjects with BD, likely reflecting increased proportions of left-sided longitudinally aligned and right-sided obliquely aligned myelinated fibers, may represent a biologic mechanism for mood dysregulation in BD.

Functional neuroimaging studies of bipolar disorder:examining the wide clinical spectrum in the search for disease endophenotypes

Bipolar disorder (BP) is among the top ten most disabling illnesses worldwide. This review includes findings from recent studies employing functional neuroimaging to examine functional abnormalities in neural systems underlying core domains of the psychopathology in BP: emotion processing, emotion regulation and executive control, and common comorbid features of BP, that are relevant to the wide spectrum of BP rather than focused on the more traditional BPI subtype, and that may facilitate future identification of diagnostically-relevant biomarkers of the disorder. In addition, an emerging number of studies are reviewed that demonstrate the use of neuroimaging to elucidate biomarkers whose identification may help to (1) identify at-risk individuals who will subsequently develop the illness to facilitate early intervention, (2) identify targets for treatment and markers of treatment response. The use of newer neuroimaging techniques and potential confounds of psychotropic medication upon neuroimaging findings in BP are also examined. These approaches will help to improve diagnosis and the mental well-being of all individuals with BP.

Prefrontal cortical and striatal activity to happy and fear faces in bipolar disorder is associated with comorbid substance abuse and eating disorder

Background: The spectrum approach was used to examine contributions of comorbid symptom dimensions of substance abuse and eating disorder to abnormal prefrontal-cortical and subcortical-striatal activity to happy and fear faces previously demonstrated in bipolar disorder (BD). Method: Fourteen remitted BD-type I and sixteen healthy individuals viewed neutral, mild and intense happy and fear faces in two event-related fMRI experiments. All individuals completed Substance-Use and Eating-Disorder Spectrum measures. Region-of-Interest analyses for bilateral prefrontal and subcortical-striatal regions were performed. Results: BD individuals scored significantly higher on these spectrum measures than healthy individuals (p < 0.05), and were distinguished by activity in prefrontal and subcortical-striatal regions. BD relative to healthy individuals showed reduced dorsal prefrontal-cortical activity to all faces. Only BD individuals showed greater subcortical-striatal activity to happy and neutral faces. In BD individuals, negative correlations were shown between substance use severity and right PFC activity to intense happy faces (p < 0.04), and between substance use severity and right caudate nucleus activity to neutral faces (p < 0.03). Positive correlations were shown between eating disorder and right ventral putamen activity to intense happy (p < 0.02) and neutral faces (p < 0.03). Exploratory analyses revealed few significant relationships between illness variables and medication upon neural activity in BD individuals. Limitations: Small sample size of predominantly medicated BD individuals. Conclusion: This study is the first to report relationships between comorbid symptom dimensions of substance abuse and eating disorder and prefrontal-cortical and subcortical-striatal activity to facial expressions in BD. Our findings suggest that these comorbid features may contribute to observed patterns of functional abnormalities in neural systems underlying mood regulation in BD.

Psychiatric adverse effects of zonisamide in patients with epilepsy and mental disorder comorbidities

Over the last few years, zonisamide has been proposed as a potentially useful medication for patients with focal seizures, with or without secondary generalization. Since psychiatric adverse effects, including mania, psychosis, and suicidal ideation, have been associated with its use, it was suggested that the presence of antecedent psychiatric disorders is an important factor associated with the discontinuation of zonisamide therapy in patients with epilepsy. We, therefore, set out to assess the tolerability profile of zonisamide in a retrospective chart review of 23 patients with epilepsy and comorbid mental disorders, recruited from two specialist pediatric (n=11) and adult (n=12) neuropsychiatry clinics. All patients had a clinical diagnosis of treatment-refractory epilepsy after extensive neurophysiological and neuroimaging investigations. The vast majority of patients (n=22/23, 95.7%) had tried previous antiepileptic medications, and most adult patients (n=9/11, 81.8%) were on concomitant medication for epilepsy. In the majority of cases, the psychiatric adverse effects of zonisamide were not severe. Four patients (17.4%) discontinued zonisamide because of lack of efficacy, whereas only one patient (4.3%) discontinued it because of the severity of psychiatric adverse effects (major depressive disorder). The low discontinuation rate of zonisamide in a selected population of patients with epilepsy and neuropsychiatric comorbidity suggests that this medication is safe and reasonably well-tolerated for use in patients with treatment-refractory epilepsy. Given the limitations of the present study, including the relatively small sample size, further research is warranted to confirm this finding. © 2013 Elsevier Inc.

Efficacy and safety of second-generation antipsychotic long-acting injections (SGA LAIs) in maintenance treatment of bipolar disorder:protocol for a systematic review and meta-analysis

INTRODUCTION: Bipolar disorder requires long-term treatment but non-adherence is a common problem. Antipsychotic long-acting injections (LAIs) have been suggested to improve adherence but none are licensed in the UK for bipolar. However, the use of second-generation antipsychotics (SGA) LAIs in bipolar is not uncommon albeit there is a lack of systematic review in this area. This study aims to systematically review safety and efficacy of SGA LAIs in the maintenance treatment of bipolar disorder. METHODS AND ANALYSIS: The protocol is based on Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and will include only randomised controlled trials comparing SGA LAIs in bipolar. PubMed, EMBASE, CINAHL, Cochrane Library (CENTRAL), PsychINFO, LiLACS, http://www.clinicaltrials.gov will be searched, with no language restriction, from 2000 to January 2016 as first SGA LAIs came to the market after 2000. Manufacturers of SGA LAIs will also be contacted. Primary efficacy outcome is relapse rate or delayed time to relapse or reduction in hospitalisation and primary safety outcomes are drop-out rates, all-cause discontinuation and discontinuation due to adverse events. Qualitative reporting of evidence will be based on 21 items listed on standards for reporting qualitative research (SRQR) focusing on study quality (assessed using the Jadad score, allocation concealment and data analysis), risk of bias and effect size. Publication bias will be assessed using funnel plots. If sufficient data are available meta-analysis will be performed with primary effect size as relative risk presented with 95% CI. Sensitivity analysis, conditional on number of studies and sample size, will be carried out on manic versus depressive symptoms and monotherapy versus adjunctive therapy.

The use of topiramate in mood stabilization

OBJECTIVE: To review data on the effectiveness of topiramate as a mood stabilizer. DATA SOURCES: Clinical literature accessed through MEDLINE (1985-September 2001) and the manufacturer. Key search terms included topiramate, mania, mood stabilizer, and bipolar disorder. DATA SYNTHESIS: The traditional standard therapy for bipolar disorder has been lithium. Other mood stabilizers are increasingly being used to manage this complex disorder. Studies that used topiramate in bipolar disorders were evaluated. CONCLUSIONS: The present data from open trials suggest that topiramate may possibly possess antimanic properties. Controlled, double-blind studies are required to confirm this efficacy

DSM-5 Autism Spectrum Disorder:in search of essential behaviours for diagnosis

Background: Despite initial concerns about the sensitivity of the proposed diagnostic criteria for DSM-5 Autism Spectrum Disorder (ASD; e.g. Gibbs et al., 2012; McPartland et al., 2012), evidence is growing that the DSM-5 criteria provides an inclusive description with both good sensitivity and specificity (e.g. Frazier et al., 2012; Kent, Carrington et al., 2013). The capacity of the criteria to provide high levels of sensitivity and specificity comparable with DSM-IV-TR however relies on careful measurement to ensure that appropriate items from diagnostic instruments map onto the new DSM-5 descriptions.Objectives: To use an existing DSM-5 diagnostic algorithm (Kent, Carrington et .al., 2013) to identify a set of ‘essential’ behaviors sufficient to make a reliable and accurate diagnosis of DSM-5 Autism Spectrum Disorder (ASD) across age and ability level. Methods: Specific behaviors were identified and tested from the recently published DSM-5 algorithm for the Diagnostic Interview for Social and Communication Disorders (DISCO). Analyses were run on existing DISCO datasets, with a total participant sample size of 335. Three studies provided step-by-step development towards identification of a minimum set of items. Study 1 identified the most highly discriminating items (p<.0001). Study 2 used a lower selection threshold than in Study 1 (p<.05) to facilitate better representation of the full DSM-5 ASD profile. Study 3 included additional items previously reported as significantly more frequent in individuals with higher ability. The discriminant validity of all three item sets was tested using Receiver Operating Characteristic curves. Finally, sensitivity across age and ability was investigated in a subset of individuals with ASD (n=190).Results: Study 1 identified an item set (14 items) with good discriminant validity, but which predominantly measured social-communication behaviors (11/14). The Study 2 item set (48 items) better represented the DSM-5 ASD and had good discriminant validity, but the item set lacked sensitivity for individuals with higher ability. The final Study 3 adjusted item set (54 items) improved sensitivity for individuals with higher ability and performance and was comparable to the published DISCO DSM-5 algorithm.Conclusions: This work represents a first attempt to derive a reduced set of behaviors for DSM-5 directly from an existing standardized ASD developmental history interview. Further work involving existing ASD diagnostic tools with community-based and well characterized research samples will be required to replicate these findings and exploit their potential to contribute to a more efficient and focused ASD diagnostic process.

Corporate coalitions and policy making in the European Union:how and why British American tobacco promoted "better regulation"

Over the past fifteen years, an interconnected set of regulatory reforms, knownas Better Regulation, has been adopted across Europe, marking a significant shift in theway that European Union policies are developed. There has been little exploration of the origins of these reforms, which include mandatory ex ante impact assessment. Drawing on documentary and interview data, this article discusses how and why large corporations, notably British American Tobacco (BAT), worked to influence and promote these reforms. Our analysis highlights (1) howpolicy entrepreneurs with sufficient resources (such as large corporations) can shape the membership and direction of advocacy coalitions; (2) the extent to which "think tanks" may be prepared to lobby on behalf of commercial clients; and (3) why regulated industries (including tobacco) may favor the use of "evidence tools," such as impact assessments, in policy making. We argue that a key aspect of BAT's ability to shape regulatory reform involved the deliberate construction of a vaguely defined idea that could be strategically adapted to appeal to diverse constituencies.We discuss the theoretical implications of this finding for the Advocacy Coalition Framework, as well as the practical implications of the findings for efforts to promote transparency and public health in the European Union.

DSM-5 Autism Spectrum Disorder:in search of essential behaviours for diagnosis

The objective of this study was to identify a set of 'essential' behaviours sufficient for diagnosis of DSM-5 Autism Spectrum Disorder (ASD). Highly discriminating, 'essential' behaviours were identified from the published DSM-5 algorithm developed for the Diagnostic Interview for Social and Communication Disorders (DISCO). Study 1 identified a reduced item set (48 items) with good predictive validity (as measured using receiver operating characteristic curves) that represented all symptom sub-domains described in the DSM-5 ASD criteria but lacked sensitivity for individuals with higher ability. An adjusted essential item set (54 items; Study 2) had good sensitivity when applied to individuals with higher ability and performance was comparable to the published full DISCO DSM-5 algorithm. Investigation at the item level revealed that the most highly discriminating items predominantly measured social-communication behaviours. This work represents a first attempt to derive a reduced set of behaviours for DSM-5 directly from an existing standardised ASD developmental history interview and has implications for the use of DSM-5 criteria for clinical and research practice. © 2014 The Authors.

Signposting for diagnosis of Autism Spectrum Disorder using the Diagnostic Interview for Social and Communication Disorders (DISCO)

Recent research has investigated the capability of the Diagnostic and Statistical Manual for Mental Disorders (DSM-5) descriptions to identify individuals who should receive a diagnosis of Autism Spectrum Disorder (ASD) using standardised diagnostic instruments. Building on previous research investigating behaviours essential for the diagnosis of DSM-5 ASD, the current study investigated the sensitivity and specificity of a set of 14 items derived from the Diagnostic Interview for Social and Communication Disorders (DISCO Signposting set) that have potential for signposting the diagnosis of autism according to both the new DSM-5 criteria for ASD and ICD-10 criteria for Childhood Autism. An algorithm threshold for the Signposting set was calculated in Sample 1 (n = 67), tested in an independent validation sample (Sample 2; n = 78), and applied across age and ability sub-groups in Sample 3 (n = 190). The algorithm had excellent predictive validity according to best estimate clinical diagnosis (Samples 1 and 2) and excellent agreement with established algorithms for both DSM-5 and ICD-10 (all samples). The signposting set has potential to inform our understanding of the profile of ASD in relation to other neurodevelopmental disorders and to form the basis of a Signposting Interview for use in clinical practice.

Smoke rings:towards a comprehensive tobacco free policy for the Olympic Games

Background The tobacco industry has long sought affiliation with major sporting events, including the Olympic Games, for marketing, advertising and promotion purposes. Since 1988, each Olympic Games has adopted a tobacco-free policy. Limited study of the effectiveness of the smoke-free policy has been undertaken to date, with none examining the tobacco industry's involvement with the Olympics or use of the Olympic brand. Methods and Findings A comparison of the contents of Olympic tobacco-free policies from 1988 to 2014 was carried out by searching the websites of the IOC and host NOCs. The specific tobacco control measures adopted for each Games were compiled and compared with measures recommended by the WHO Tobacco Free Sports Initiative and Article 13 of the Framework Convention on Tobacco Control (FCTC). This was supported by semi-structured interviews of key informants involved with the adoption of tobacco-free policies for selected games. To understand the industry's interests in the Olympics, the Legacy Tobacco Documents Library (http://legacy.library.ucsf.edu) was systematically searched between June 2013 and August 2014. Company websites, secondary sources and media reports were also searched to triangulate the above data sources. This paper finds that, while most direct associations between tobacco and the Olympics have been prohibited since 1988, a variety of indirect associations undermine the Olympic tobacco-free policy. This is due to variation in the scope of tobacco-free policies, limited jurisdiction and continued efforts by the industry to be associated with Olympic ideals. Conclusions The paper concludes that, compatible with the IOC's commitment to promoting healthy lifestyles, a comprehensive tobacco-free policy with standardized and binding measures should be adopted by the International Olympic Committee and all national Olympic committees.

The devil is in the detail:tobacco industry political influence in the Dutch implementation of the 2001 EU Tobacco Products Directive

Introduction - The Dutch implementation of the black border provision in the 2001 European Union Tobacco Products Directive (TPD) is studied to examine the implications of tobacco industry involvement in the implementation phase of the policy process. Methods - A qualitative analysis was conducted of Dutch government documents obtained through Freedom of Information Act requests, triangulated with in-depth interviews with key informants and secondary data sources (publicly available government documents, scientific literature, and news articles). Results - Tobacco manufacturers’ associations were given the opportunity to set implementation specifications via a fast-track deal with the government. The offer of early implementation of the labelling section of the TPD was used as political leverage by the industry, and underpinned by threats of litigation and arguments highlighting the risks of additional public costs and the benefits to the government of expediency and speed. Ultimately, the government agreed to the industry's interpretation, against the advice of the European Commission. Conclusions - The findings highlight the policy risks associated with corporate actors’ ability to use interactions over technical product specifications to influence the implementation of health policy and illustrate the difficulties in limiting industry interference in accordance with Article 5.3 of the Framework Convention on Tobacco Control (FCTC). The implementation phase is particularly vulnerable to industry influence, where negotiation with industry actors may be unavoidable and the practical implications of relatively technical considerations are not always apparent to policymakers. During the implementation of the new TPD 2014/40/EU, government officials are advised to take a proactive role in stipulating technical specifications.