Cetuximab for the treatment of metastatic and/or recurrent squamous cell carcinoma of the head and neck: appraisal consultation

Appraisal consultation document - Cetuximab for the treatment of recurrent and/or metastatic squamous cell cancer of the head and neck.To take part in the 'Cetuximab for the treatment of metastatic and/or recurrent squamous cell carcinoma of the head and neck: appraisal consultation'

Trends in self-reported prevalence and management of hypertension, dyslipidaemia and diabetes in adults in Switzerland, 1992-2007

Purpose: to assess the trends of self-reported prevalence of cardiovascular risk factors (CV RFs: hypertension, dyslipidaemia, diabetes) and their management for period 1992 to 2007 in the Swiss population. Methods: four National health interview surveys conducted between 1992 and 2007 in representative samples of the Swiss population (63,782 subjects overall). Self-reported CV RFs prevalence, treatment and controllevels were computed after weighting. Weights were calculated by raking ratio such that the marginal distribution of the weighted totals conforms to the marginal distribution of the targeted population. Multivariate analysis adjusted on age, sex, education, nationality and SMI was conducted using logistic regression. Results: prevalence of ail CV RFs increased between 1992 and 2007, see table. Although the self-reported prevalence of treatment among subjects with CV RFs increased, and this was confirmed by multivariate analysis: OR for hypocholesterolaemic treatment relative to 1992: 0.64 [0.52-0.78]; 1.39 [1.18-1.65] and 2.00 [1.69-2.36] for 1997, 2002 and 2007, respectively. Still, in 2007, circa 40% of hypertensive, 60% of dyslipidaemic and 50% of diabetic subjects weren't treated. Conversely, an adequate control of CV RFs was reported by treated subjects, with an increase during the study period. This increase was confirmed by multivariate analysis (not shown). Conclusion: the self-reported prevalence of hypertension, dyslipidaemia and diabetes increased between 1992 and 2007 in the Swiss population. Despite a good control of treated subjects, still a significant percentage of subjects with CV RFs are not treated.

Media guidelines for reporting suicide and self-harm

These guidelines are for those in the media who have involvement with the reporting or portrayal of suicide and represent an important source of information to help ensure that the quality of reporting and portrayal on this important and sensitive topic is of a high standard.

Dialogism and dialogicality in the study of the self

This article stems from the statement that dialogical approaches to a study of the self face a double challenge: that of developing a conception of the self that both avoids social reductionism and accounts for the stability of the self. In discussing this double challenge, we identify three much debated issues: (a) To what does the notion of "Alter" exactly refer? (b) How could we conceptualize the fact that Subject-Alter interactions are not only interpersonal but entail larger social entities, in particular institutions? (c)What importance should we attach to the materiality of objects? We discuss these three questions from two standpoints - that of linguistics and that of psychology - and illustrate our theoretical proposals with an analysis of an excerpt taken from a focus-group discussion. In conclusion, we argue that the dialogism of discourse provides us with some clues about the dialogicality of the mind, whereas the latter invites us to develop a theory showing the importance of interactions in the construction of the self, to pay more attention to the transpersonal dimension of the social, and to consider that the material world contributes to the construction of the self.

Variant within the promoter region of the CHRNA3 gene associated with FTN dependence is not related to self-reported willingness to quit smoking.

INTRODUCTION: Common variation in the CHRNA5-CHRNA3-CHRNB4 gene region is robustly associated with smoking quantity. Conversely, the association between one of the most significant single nucleotide polymorphisms (SNPs; rs1051730 within the CHRNA3 gene) with perceived difficulty or willingness to quit smoking among current smokers is unknown. METHODS: Cross-sectional study including current smokers, 502 women, and 552 men. Heaviness of smoking index (HSI), difficulty, attempting, and intention to quit smoking were assessed by questionnaire. RESULTS: The rs1051730 SNP was associated with increased HSI (age, gender, and education-adjusted mean ± SE: 2.6 ± 0.1, 2.2 ± 0.1, and 2.0 ± 0.1 for AA, AG, and GG genotypes, respectively, p < .01). Multivariate logistic regression adjusting for gender, age, education, leisure-time physical activity, and personal history of cardiovascular or lung disease showed rs1051730 to be associated with higher smoking dependence (odds ratio [OR] and 95% CI for each additional A-allele: 1.38 [1.11-1.72] for smoking more than 20 cigarette equivalents/day; 1.31 [1.00-1.71] for an HSI ≥5 and 1.32 [1.05-1.65] for smoking 5 min after waking up) and borderline associated with difficulty to quit (OR = 1.29 [0.98-1.70]), but this relationship was no longer significant after adjusting for nicotine dependence. Also, no relationship was found with willingness (OR = 1.03 [0.85-1.26]), attempt (OR = 1.00 [0.83-1.20]), or preparation (OR = 0.95 [0.38-2.38]) to quit. Similar findings were obtained for other SNPs, but their effect on nicotine dependence was no longer significant after adjusting for rs1051730. Conclusions: These data confirm the effect of rs1051730 on nicotine dependence but failed to find any relationship with difficulty, willingness, and motivation to quit.

Accident & Emergency Nursing Assessment of Deliberate Self Harm. Exploring the Impact of Introducing a Suicide Education Programme and a Suicide Intent Scale into A&E/MAU Nursing Practice: A Pilot Study

A proposal to pilot nursing assessment of self harm in Accident and Emergency Departments (A&E) was developed by key stakeholders in nurse education and suicide prevention in the South East and submitted to the National Council for the Professional Development of Nursing and Midwifery in April 2002.The proposal included the introduction of a suicide intent scale. Following an initial training programme, a suicide intent scale was utilised by nursing staff in A&E and the Medical Assessment Unit (MAU),Wexford General Hospital and evaluated over a period of nine months. Four months into the study the National Suicide Research Foundation (NSRF) was invited to collaboratively prepare a successful submission to the Health Research Board (HRB) as part of ‘Building Partnerships for a Healthier Future Research Awards 2004’. The NSRF undertook independent scientific evaluation of the outcomes of the suicide awareness programme. The study is in line with priorities determined by Reach Out, the National Strategy for Action on Suicide Prevention 2005-2014 (HSE, 2005) and the HSE-South East Suicide Prevention Programme through raising nursing staff awareness of the public health issue of suicide/deliberate self harm and by improving the efficiency and quality of nursing services offered to persons who present to acute hospitals with deliberate self harm. The study findings indicate evidence to positively support nursing assessment of DSH using a suicide intent scale in terms of assessing behavioural characteristics of individual clients and their suicide risk. Enhanced confidence levels of nursing personnel in caring for suicidal clients was demonstrated by staff who participated in an education programme related to risk assessment and specifically the use of a suicide intent scale.This resource was contributed by The National Documentation Centre on Drug Use.

Cysteine-rich Domain 1 of CD40 Mediates Receptor Self-assembly.

The activation of CD40 on B cells, macrophages, and dendritic cells by its ligand CD154 (CD40L) is essential for the development of humoral and cellular immune responses. CD40L and other TNF superfamily ligands are noncovalent homotrimers, but the form under which CD40 exists in the absence of ligand remains to be elucidated. Here, we show that both cell surface-expressed and soluble CD40 self-assemble, most probably as noncovalent dimers. The cysteine-rich domain 1 (CRD1) of CD40 participated to dimerization and was also required for efficient receptor expression. Modelization of a CD40 dimer allowed the identification of lysine 29 in CRD1, whose mutation decreased CD40 self-interaction without affecting expression or response to ligand. When expressed alone, recombinant CD40-CRD1 bound CD40 with a KD of 0.6 μm. This molecule triggered expression of maturation markers on human dendritic cells and potentiated CD40L activity. These results suggest that CD40 self-assembly modulates signaling, possibly by maintaining the receptor in a quiescent state.

Neurochemical profile of the developing mouse cortex determined by in vivo 1H NMR spectroscopy at 14.1 T and the effect of recurrent anaesthesia.

The neurochemical profile of the cortex develops in a region and time specific manner, which can be distorted by psychiatric and other neurological pathologies. Pre-clinical studies often involve experimental mouse models. In this study, we determined the neurochemical profile of C57BL/6 mice in a longitudinal study design to provide a reference frame for the normal developing mouse cortex. Using in vivo proton NMR spectroscopy at 14 T, we measured the concentrations of 18 metabolites in the anterior and posterior cortex on postnatal days (P) 10, 20, 30, 60 and 90. Cortical development was marked by alterations of highly concentrated metabolites, such as N-acetylaspartate, glutamate, taurine and creatine. Regional specificity was represented by early variations in the concentration of glutamine, aspartate and choline. In adult animals, regional concentration differences were found for N-acetylaspartate, creatine and myo-inositol. In this study, animals were exposed to recurrent isoflurane anaesthesia. Additional experiments showed that the latter was devoid of major effects on behaviour or cortical neurochemical profile. In conclusion, the high sensitivity and reproducibility of the measurements achieved at 14 T allowed us to identify developmental variations of cortical areas within the mouse cortex.

A prospective, randomized, open label, phase iii clinical trial of novottf-100a vs best standard of care chemotherapy in patients with recurrent glioblastoma

BACKGROUND: Glioblastoma, the most common adult primary malignant brain tumor, confers poor prognosis (median survival of 15 months) notwithstanding aggressive treatment. Combination chemotherapy including carmustine (BCNU) or temozolomide (TMZ) with the MGMT inhibitor O6-benzylguanine (O6BG) has been used, but has been associated with dose-limiting hematopoietic toxicity. OBJECTIVE: To assess safety and efficacy of a retroviral vector encoding the O6BG-resistant MGMTP140K gene for transduction and autologous transplantation of hematopoietic stem cells (HSCs) in MGMT unmethylated, newly diagnosed glioblastoma patients in an attempt to chemoprotect bone marrowduring combination O6BG/TMZ therapy. METHODS: Three patients have been enrolled in the first cohort. Patients underwent standard radiation therapy without TMZ followed by G-CSF mobilization, apheresis, and conditioning with 600 mg/m2 BCNU prior to infusion of gene-modified cells. Posttransplant, patients were treated with 28-day cycles of single doseTMZ (472 mg/m2) with 48-hour intravenous O6BG (120 mg/m2 bolus, then 30 mg/m2/d). RESULTS: The BCNU dose was nonmyeloablative with ANC ,500/mL for ≤3 d and nadir thrombocytopenia of 28,000/mL. Gene marking in pre-infusion colony forming units (CFUs) was 70.6%, 79.0%, and 74.0% in Patients 1, 2, and 3, respectively, by CFU-PCR. Following engraftment, gene marking in white blood cells and sorted granulocytes ranged between 0.37-0.84 and 0.33-0.83 provirus copies, respectively, by real-time PCR. Posttransplant gene marking in CFUs from CD34-selected cells ranged from 28.5% to 47.4%. Patients have received 4, 3, and 2 cycles of O6BG/TMZ, respectively, with evidence for selection of gene-modified cells. One patient has received a single dose-escalated cycle at 590 mg/m2 TMZ. No additional extra-hematopoietic toxicity has been observed thus far and all three patients exhibit stable disease at 7-8 months since diagnosis CONCLUSIONS: We believe that these data demonstrate the feasibility of achieving significant engraftment of MGMTP140K-modified cells with a well-tolerated dose of BCNU. Further follow-up will determine whether this approach will allow for further dose escalation of TMZ and improved survival.

24-hour ambulatory electrocardiographic monitoring is unhelpful in the investigation of older persons with recurrent falls

Although frequently used in the assessment of patients with falls, it is unclear whether 24-hour ambulatory electrocardiography contributes to their assessment in older persons. The aim of this study is to identify electrocardiographic abnormalities in patients with recurrent falls and case controls, and determine whether 24-hour ambulatory electrocardiography identifies causal arrhythmias for falls. 24-hour ambulatory electrocardiography recordings were compared for the type and prevalence of arrhythmias and symptom correlation in consecutive older subjects with recurrent falls attending the accident and emergency department and in case controls (no previous falls or syncope).

Ecological components and evolution of selfing in the freshwater snail Galba truncatula.

The reproductive assurance hypothesis emphasizes that self-fertilization should evolve in species with reduced dispersal capability, low population size or experiencing recurrent bottlenecks. Our work investigates the ecological components of the habitats colonized by the snail, Galba truncatula, that may influence the evolution of selfing. Galba truncatula is a preferential selfer inhabiting freshwater habitats, which vary with respect to the degree of permanence. We considered with a population genetic approach the spatial and the temporal degree of isolation of populations of G. truncatula. We showed that patches at distances of only a few meters are highly structured. The effective population sizes appear quite low, in the order of 10 individuals or less. This study indicates that individuals of the species G. truncatula are likely to be alone in a site and have a low probability of finding a partner from a nearby site to reproduce. These results emphasize the advantage of selfing in this species.