Assessment of daily profiles of ADHD and ODD symptoms, and symptomatology related to ADHD medication, by parent and teacher ratings

DAYAS is a new two-part rating scale that assesses: (1) ADHD and ODD symptoms (externalising symptom ratings) and (2) symptomatology potentially related to ADHD medication (potentially medication-related symptoms) in real-world settings at different time periods throughout a normal school day. Data from a proof-of-concept study and two observational trials (Medikinet® retard [methylphenidate] and the Equasym XL® [methylphenidate] OBSEER study) evaluated: (1) validity of weekly externalising symptom ratings using DAYAS, in place of daily ratings; (2) reliability and internal consistency of DAYAS ratings for externalising symptoms and potentially medication-related symptoms; and (3) convergent and divergent validity of the externalising symptom ratings with existing validated scales. From the proof-of-concept study, daily scores by period of day and during the whole day correlated strongly with equivalent weekly scores (r = 0.83–0.92). Internal consistency of externalising symptom rating scales calculated from pooled data were acceptable or good by period of day (Cronbach’s alpha = 0.68–0.90) and very high for whole day scores (Cronbach’s alpha = 0.88–0.95). Internal consistency of the rating scale for potentially medication-related symptoms was also good for both teacher and parent ratings. From OBSEER data, correlations between FBB-ADHD total symptom scores and ratings on both parent and teacher versions of DAYAS were high (r = 0.73 and r = 0.84, respectively). Correlations between DAYAS and SDQ were highest for the SDQ subscales hyperactivity and conduct problems and substantially lower for pro-social behaviour, peers and emotional problems. The DAYAS rating scale had good internal consistency, and DAYAS scores correlated well with existing validated scales and the SDQ subscales hyperactivity and conduct problems. Weekly DAYAS scores (whole day and by period of day) could be considered a suitable replacement for daily assessment scores

An observational study of once-daily modified-release methylphenidate in ADHD: effectiveness on symptoms and impairment, and safety

ADHD affects over 5% of children worldwide. It is typically treated with stimulant medications, and methylphenidate (MPH) is the most commonly prescribed. This study investigated the effectiveness, on symptoms and impairment, and safety of Equasym XL®, a combination of 30% immediate-release and 70% modified-release MPH, in the treatment of ADHD in daily clinical practice. This open-label, observational, post-marketing surveillance study was conducted in 169 centres in Germany. Eligible patients, aged 6–17 years, were diagnosed with ADHD and about to begin treatment with Equasym XL®. Effectiveness was assessed by physicians using the clinical global impression (CGI) severity and improvement scales; teachers and parents completed questionnaires evaluating ADHD symptoms and behavioural problems (DAYAS, FBB-ADHD and SDQ-P). Assessments were carried out at baseline, after 1–3 and 6–12 weeks of treatment. Of 852 enrolled patients, 822 were evaluable; 25.30% were treatment naïve, 69.84% had previously received different MPH formulations, and 4.87% had received other medications. ADHD symptoms improved from baseline to last visit for the majority of patients for all outcome measures. According to physician ratings of core ADHD symptoms, 75.73% of patients showed improvements on the CGI-Improvement scale, 17.77% had no change, and 6.50% worsened. In teacher and parent ratings, the effectiveness of Equasym XL® was rated better than prior therapy at all measured time points across the day, particularly late morning (teachers) and early afternoon (parents). Equasym XL® was generally well tolerated; only 3.16% of patients permanently discontinued treatment due to adverse events. Equasym XL® is effective and well tolerated in daily clinical practice

Id1 Interacts and Stabilizes the Epstein-Barr Virus Latent Membrane Protein 1 (LMP1) in Nasopharyngeal Epithelial Cells

The EBV-encoded latent membrane protein 1 (LMP1) functions as a constitutive active form of tumor necrosis factor receptor (TNFR) and activates multiple downstream signaling pathways similar to CD40 signaling in a ligand-independent manner. LMP1 expression in EBV-infected cells has been postulated to play an important role in pathogenesis of nasopharyngeal carcinoma. However, variable levels of LMP1 expression were detected in nasopharyngeal carcinoma. At present, the regulation of LMP1 levels in nasopharyngeal carcinoma is poorly understood. Here we show that LMP1 mRNAs are transcribed in an EBV-positive nasopharyngeal carcinoma (NPC) cell line (C666-1) and other EBV-negative nasopharyngeal carcinoma cells stably re-infected with EBV. The protein levels of LMP1 could readily be detected after incubation with proteasome inhibitor, MG132 suggesting that LMP1 protein is rapidly degraded via proteasome-mediated proteolysis. Interestingly, we observed that Id1 overexpression could stabilize LMP1 protein in EBV-infected cells. In contrary, Id1 knockdown significantly reduced LMP1 levels in cells. Co-immunoprecipitation studies revealed that Id1 interacts with LMP1 by binding to the CTAR1 domain of LMP1. N-terminal region of Id1 is required for the interaction with LMP1. Furthermore, binding of Id1 to LMP1 suppressed polyubiquitination of LMP1 and may be involved in stabilization of LMP1 in EBV-infected nasopharyngeal epithelial cells

Missed injuries in trauma patients: A literature review

<p>Abstract</p> <p>Background</p> <p>Overlooked injuries and delayed diagnoses are still common problems in the treatment of polytrauma patients. Therefore, ongoing documentation describing the incidence rates of missed injuries, clinically significant missed injuries, contributing factors and outcome is necessary to improve the quality of trauma care. This review summarizes the available literature on missed injuries, focusing on overlooked muscoloskeletal injuries.</p> <p>Methods</p> <p>Manuscripts dealing with missed injuries after trauma were reviewed. The following search modules were selected in PubMed: Missed injuries, Delayed diagnoses, Trauma, Musculoskeletal injuires. Three time periods were differentiated: (n = 2, 1980–1990), (n = 6, 1990–2000), and (n = 9, 2000-Present).</p> <p>Results</p> <p>We found a wide spread distribution of missed injuries and delayed diagnoses incidence rates (1.3% to 39%). Approximately 15 to 22.3% of patients with missed injuries had clinically significant missed injuries. Furthermore, we observed a decrease of missed pelvic and hip injuries within the last decade.</p> <p>Conclusion</p> <p>The lack of standardized studies using comparable definitions for missed injuries and clinically significant missed injuries call for further investigations, which are necessary to produce more reliable data. Furthermore, improvements in diagnostic techniques (e.g. the use of multi-slice CT) may lead to a decreased incidence of missed pelvic injuries. Finally, the standardized tertiary trauma survey is vitally important in the detection of clinically significant missed injuries and should be included in trauma care.</p

The history of attention deficit hyperactivity disorder

The contemporary concept of attention deficit hyperactivity disorder (ADHD) as defined in the DSM-IV-TR (American Psychiatric Association 2000) is relatively new. Excessive hyperactive, inattentive, and impulsive children have been described in the literature since the nineteenth century. Some of the early depictions and etiological theories of hyperactivity were similar to current descriptions of ADHD. Detailed studies of the behavior of hyperactive children and increasing knowledge of brain function have changed the concepts of the fundamental behavioral and neuropathological deficits underlying the disorder. This article presents an overview of the conceptual history of modern-day ADHD

Epstein-Barr Virus-Encoded LMP1 Interacts with FGD4 to Activate Cdc42 and Thereby Promote Migration of Nasopharyngeal Carcinoma Cells

Epstein-Barr virus (EBV) is closely associated with nasopharyngeal carcinoma (NPC), a human malignancy notorious for its highly metastatic nature. Among EBV-encoded genes, latent membrane protein 1 (LMP1) is expressed in most NPC tissues and exerts oncogenicity by engaging multiple signaling pathways in a ligand-independent manner. LMP1 expression also results in actin cytoskeleton reorganization, which modulates cell morphology and cell motility— cellular process regulated by RhoGTPases, such as Cdc42. Despite the prominent association of Cdc42 activation with tumorigenesis, the molecular basis of Cdc42 activation by LMP1 in NPC cells remains to be elucidated. Here using GST-CBD (active Cdc42-binding domain) as bait in GST pull-down assays to precipitate active Cdc42 from cell lysates, we demonstrated that LMP1 acts through its transmembrane domains to preferentially induce Cdc42 activation in various types of epithelial cells, including NPC cells. Using RNA interference combined with re-introduction experiments, we identified FGD4 (FYVE, RhoGEF and PH domain containing 4) as the GEF (guanine nucleotide exchange factor) responsible for the activation of Cdc42 by LMP1. Serial deletion experiments and co-immunoprecipitation assays further revealed that ectopically expressed FGD4 modulated LMP1-mediated Cdc42 activation by interacting with LMP1. Moreover, LMP1, through its transmembrane domains, directly bound FGD4 and enhanced FGD4 activity toward Cdc42, leading to actin cytoskeleton rearrangement and increased motility of NPC cells. Depletion of FGD4 or Cdc42 significantly reduced (∼50%) the LMP1-stimulated cell motility, an effect that was partially reversed by expression of a constitutively active mutant of Cdc42. Finally, quantitative RT-PCR and immunohistochemistry analyses showed that FGD4 and LMP1 were expressed in NPC tissues, supporting the potential physiologically relevance of this mechanism in NPC. Collectively, our results not only uncover a novel mechanism underlying LMP1-mediated Cdc42 activation, namely LMP1 interaction with FGD4, but also functionally link FGD4 to NPC tumorigenesis

European clinical guidelines for Tourette syndrome and other tic disorders. Part II: pharmacological treatment

To develop a European guideline on pharmacologic treatment of Tourette syndrome (TS) the available literature was thoroughly screened and extensively discussed by a working group of the European Society for the Study of Tourette syndrome (ESSTS). Although there are many more studies on pharmacotherapy of TS than on behavioral treatment options, only a limited number of studies meets rigorous quality criteria. Therefore, we have devised a two-stage approach. First, we present the highest level of evidence by reporting the findings of existing Cochrane reviews in this field. Subsequently, we provide the first comprehensive overview of all reports on pharmacological treatment options for TS through a MEDLINE, PubMed, and EMBASE search for all studies that document the effect of pharmacological treatment of TS and other tic disorders between 1970 and November 2010. We present a summary of the current consensus on pharmacological treatment options for TS in Europe to guide the clinician in daily practice. This summary is, however, rather a status quo of a clinically helpful but merely low evidence guideline, mainly driven by expert experience and opinion, since rigorous experimental studies are scarce