Cognitive behavioral therapy of socially phobic children focusing on cognition: a randomised wait-list control study

BACKGROUND: Although literature provides support for cognitive behavioral therapy (CBT) as an efficacious intervention for social phobia, more research is needed to improve treatments for children. METHODS: Forty four Caucasian children (ages 8-14) meeting diagnostic criteria of social phobia according to the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; APA, 1994) were randomly allocated to either a newly developed CBT program focusing on cognition according to the model of Clark and Wells (n = 21) or a wait-list control group (n = 23). The primary outcome measure was clinical improvement. Secondary outcomes included improvements in anxiety coping, dysfunctional cognitions, interaction frequency and comorbid symptoms. Outcome measures included child report and clinican completed measures as well as a diagnostic interview. RESULTS: Significant differences between treatment participants (4 dropouts) and controls (2 dropouts) were observed at post test on the German version of the Social Phobia and Anxiety Inventory for Children. Furthermore, in the treatment group, significantly more children were free of diagnosis than in wait-list group at post-test. Additional child completed and clinician completed measures support the results. DISCUSSION: The study is a first step towards investigating whether CBT focusing on cognition is efficacious in treating children with social phobia. Future research will need to compare this treatment to an active treatment group. There remain the questions of whether the effect of the treatment is specific to the disorder and whether the underlying theoretical model is adequate. CONCLUSION: Preliminary support is provided for the efficacy of the cognitive behavioral treatment focusing on cognition in socially phobic children. Active comparators should be established with other evidence-based CBT programs for anxiety disorders, which differ significantly in their dosage and type of cognitive interventions from those of the manual under evaluation (e.g. Coping Cat)

Oral Thromboprophylaxis Following Total Hip or Knee Replacement: Review and Multicentre Experience with Dabigatran Etexilate

The risk of venous thromboembolism (VTE) in patients undergoing total knee or hip replacement surgery is high. As a result, thromboprophylaxis is highly recommended. While current thromboprophylactic agents, such as low molecular weight heparins (LMWH) and vitamin K antagonists, are safe and effective their use can be problematic. Therefore, there is a need for alternative anticoagulants that are as safe and effective as conventional agents, but are more convenient and easier to use. Dabigatran etexilate, a direct thrombin inhibitor, is one such anticoagulant. For VTE prevention following major orthopaedic surgery, dabigatran etexilate shows similar efficacy and safety to the LMWH enoxaparin, and is approved for use in more than 75 countries, including Europe and Canada. Here, we summarize and discuss the experiences of four German clinics that have recently introduced dabigatran etexilate into clinical practice. Overall, dabigatran etexilate was well received by patients, surgeons and nurses, and compared favourably with enoxaparin. Staff appreciated the oral, single-dose administration of dabigatran etexilate. Patient satisfaction was high, especially in those individuals who had previously used LMWHs. In this review, we also address a number of questions that were asked by patients or staff; this will be of relevance to orthopaedic surgeons and nurses. We conclude that, in these four German clinics, dabigatran etexilate offered an effective oral alternative to existing thromboprophylactic agents in patients undergoing major orthopaedic surgery

New Synthetic Thrombin Inhibitors: Molecular Design and Experimental Verification

BACKGROUND: The development of new anticoagulants is an important goal for the improvement of thromboses treatments. OBJECTIVES: The design, synthesis and experimental testing of new safe and effective small molecule direct thrombin inhibitors for intravenous administration. METHODS: Computer-aided molecular design of new thrombin inhibitors was performed using our original docking program SOL, which is based on the genetic algorithm of global energy minimization in the framework of a Merck Molecular Force Field. This program takes into account the effects of solvent. The designed molecules with the best scoring functions (calculated binding energies) were synthesized and their thrombin inhibitory activity evaluated experimentally in vitro using a chromogenic substrate in a buffer system and using a thrombin generation test in isolated plasma and in vivo using the newly developed model of hemodilution-induced hypercoagulation in rats. The acute toxicities of the most promising new thrombin inhibitors were evaluated in mice, and their stabilities in aqueous solutions were measured. RESULTS: New compounds that are both effective direct thrombin inhibitors (the best K(I) was <1 nM) and strong anticoagulants in plasma (an IC(50) in the thrombin generation assay of approximately 100 nM) were discovered. These compounds contain one of the following new residues as the basic fragment: isothiuronium, 4-aminopyridinium, or 2-aminothiazolinium. LD(50) values for the best new inhibitors ranged from 166.7 to >1111.1 mg/kg. A plasma-substituting solution supplemented with one of the new inhibitors prevented hypercoagulation in the rat model of hemodilution-induced hypercoagulation. Activities of the best new inhibitors in physiological saline (1 µM solutions) were stable after sterilization by autoclaving, and the inhibitors remained stable at long-term storage over more than 1.5 years at room temperature and at 4°C. CONCLUSIONS: The high efficacy, stability and low acute toxicity reveal that the inhibitors that were developed may be promising for potential medical applications

Transfer of manualized Short Term Psychodynamic Psychotherapy (STPP) for social phobia into clinical practice: study protocol for a cluster-randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Psychodynamic psychotherapy is frequently applied in the treatment of social phobia. Nevertheless, there has been a lack of studies on the transfer of manualized treatments to routine psychodynamic practice. Our study is the first one to examine the effects of additional training in a manualized Short Term Psychodynamic Psychotherapy (STPP) procedure on outcome in routine psychotherapy for social phobia. This study is an extension to a large multi-site RCT (N = 512) comparing the efficacy of STPP to Cognitive-Behavioral Therapy (CBT) of Social Phobia.</p> <p>Methods/Design</p> <p>The manualized treatment is designed for a time limited approach with 25 individual sessions of STPP over 6 months. Private practitioners will be randomized to training in manualized STPP vs. treatment as usual without a specific training (control condition). We plan to enrol a total of 105 patients (84 completers). Assessments will be conducted before treatment starts, after 8 and 15 weeks, after 25 treatment sessions, at the end of treatment, 6 months and 12 months after termination of treatment. The primary outcome measure is the Liebowitz Social Anxiety Scale. Remission from social phobia is defined scoring with 30 or less points on this scale.</p> <p>Discussion</p> <p>We will investigate how the treatment can be transferred from a controlled trial into the less structured setting of routine clinical care. This question represents Phase IV of psychotherapy research. It combines the benefits of randomized controlled and naturalistic research. The study is genuinely designed to promote faster and more widespread dissemination of effective interventions. It will answer the questions whether manualized STPP can be implemented into routine outpatient care, whether the new methods improve treatment courses and outcomes and whether treatment effects reached in routine psychotherapeutic treatments are comparable to those of the controlled, strictly manualized treatment of the main study.</p> <p>Trial Registration</p> <p>German Clinical Trials Register (DRKS) DRKS00000570</p

Transcriptome Analysis of the Desert Locust Central Nervous System: Production and Annotation of a Schistocerca gregaria EST Database

) displays a fascinating type of phenotypic plasticity, designated as ‘phase polyphenism’. Depending on environmental conditions, one genome can be translated into two highly divergent phenotypes, termed the solitarious and gregarious (swarming) phase. Although many of the underlying molecular events remain elusive, the central nervous system (CNS) is expected to play a crucial role in the phase transition process. Locusts have also proven to be interesting model organisms in a physiological and neurobiological research context. However, molecular studies in locusts are hampered by the fact that genome/transcriptome sequence information available for this branch of insects is still limited. EST information is highly complementary to the existing orthopteran transcriptomic data. Since many novel transcripts encode neuronal signaling and signal transduction components, this paper includes an overview of these sequences. Furthermore, several transcripts being differentially represented in solitarious and gregarious locusts were retrieved from this EST database. The findings highlight the involvement of the CNS in the phase transition process and indicate that this novel annotated database may also add to the emerging knowledge of concomitant neuronal signaling and neuroplasticity events. EST data constitute an important new source of information that will be instrumental in further unraveling the molecular principles of phase polyphenism, in further establishing locusts as valuable research model organisms and in molecular evolutionary and comparative entomology