No association between thickening fraction of the diaphragm and extubation success in ventilated children

Introduction: In mechanically ventilated adults, thickening fraction of diaphragm (dTF) measured by ultrasound is used to predict extubation success. Whether dTF can also predict extubation success in children is unclear. Aim: To investigate the association between dTF and extubation success in children. Second, to assess diaphragm thickness during ventilation and the correlation between dTF, diaphragm thickness (Tdi), age and body surface. Method: Prospective observational cohort study in children aged 0–18 years old with expected invasive ventilation for &gt;48 h. Ultrasound was performed on day 1 after intubation (baseline), day 4, day 7, day 10, at pre-extubation, and within 24 h after extubation. Primary outcome was the association between dTF pre-extubation and extubation success. Secondary outcome measures were Tdi end-inspiratory and Tdi end-expiratory and atrophy defined as &lt;10% decrease of Tdi end-expiratory versus baseline at pre-extubation. Correlations were calculated with Spearman correlation coefficients. Inter-rater reliability was calculated with intraclass correlation (ICC). Results: Fifty-three patients, with median age 3.0 months (IQR 0.1–66.0) and median duration of invasive ventilation of 114.0 h (IQR 55.5–193.5), were enrolled. Median dTF before extubation with Pressure Support 10 above 5 cmH2O was 15.2% (IQR 9.7–19.3). Extubation failure occurred in six children, three of whom were re-intubated and three then received non-invasive ventilation. There was no significant association between dTF and extubation success; OR 0.33 (95% CI; 0.06–1.86). Diaphragmatic atrophy was observed in 17/53 cases, in three of extubation failure occurred. Children in the extubation failure group were younger: 2.0 months (IQR 0.81–183.0) vs. 3.0 months (IQR 0.10–48.0); p = 0.045. At baseline, pre-extubation and post-extubation there was no significant correlation between age and BSA on the one hand and dTF, Tdi- insp and Tdi-exp on the other hand. The ICC representing the level of inter-rater reliability between the two examiners performing the ultrasounds was 0.994 (95% CI 0.970–0.999). The ICC of the inter-rater reliability between the raters in 36 paired assessments was 0.983 (95% CI 0.974–0.990). Conclusion: There was no significant association between thickening fraction of the diaphragm and extubation success in ventilated children.</p

Development and psychometric properties of a pain-related problem list for adolescents (PPL)

Instruments for measuring pain-related problems in adolescents with chronic pain are sparse, especially those based on the personal experiences of these adolescents. This study aimed to develop and test such an instrument, the pain-related problem list for adolescents (PPL). A sample of 129 adolescents with chronic pain without documented physiological etiology completed the 57-item problem list, which was based on interviews with a similar group of adolescents with chronic pain. Principal components analysis yielded four domains: problems related to (1) concentration; (2) mobility; (3) adaptability; and (4) mood. The questionnaire was shortened to 18 items and has good reliability (total α = 0.82; concentration α = 0.86; mobility α = 0.77; adaptability α = 0.71; and mood α = 0.78); the validity also proved to be adequate, especially in the general population sample. The PPL provides a tool to assess the impact of chronic pain in adolescents. Future research should focus on further validation of the PPL in a large clinical population and establishing its test-retest reliability

A cognitive-behavioural program for adolescents with chronic pain - A pilot study

The purpose of this pilot study is to evaluate the feasibility of a cognitive-behavioural training program for adolescents with chronic pain irrespective of pain localisation. A secondary aim was to give an impression of the effect of the program on pain and quality of life. Eight adolescents (14-18 years) with chronic non-organic pain recruited from the general population (and their parents) participated in this pilot study. The intervention included five group meetings alternated with four telephone contacts (during the self-management weeks) over a period of 9 weeks. The training aimed to change pain behaviour through pain education, relaxation strategies, problem-solving techniques, assertiveness training, cognitive restructuring and by stimulating the adolescent's physical activity level. The training further addresses the social context of pain by inviting parents to attend two meetings for the parents only, and by asking the adolescents to bring a peer to one of the meetings. Adolescents and their parents were positive about the program. Adolescents felt they were more in control of their pain and parents valued the support they experienced in helping their children to master the pain. The training was considered to be feasible in daily life. Further, the preliminary data showed an effect on pain and quality of life in the expected direction. The results underline the need for a definitive study with a larger sample size and a random controlled design

Comparison between children and adolescents with and without chronic benign pain: consultation rate and pain characteristics

The aim of the study was to determine whether children with chronic benign pain are in contact with their general practitioner (GP) more frequently than those without chronic benign pain. A random sample of children and adolescents aged between 0 and 18 years of age was drawn from the records of ten general practices. According to their responses to a pain questionnaire, subjects were assigned to the chronic benign pain group (n = 95) if they had pain of more than three months' duration, or to the control group (n = 105) if they had pain of less than three months' duration or no pain at all. All the subjects had an average GP consultation rate of 2.6 contacts per year. No significant age and sex differences were found. Chronic benign pain in childhood and adolescence is not related to increased use of healthcare services, suggesting that somatisation does not play a major role in children with chronic benign pain

First-in-Human Phase I Clinical Trial of an SFV-Based RNA Replicon Cancer Vaccine against HPV-Induced Cancers

A first-in-human phase I trial of Vvax001, an alphavirus-based therapeutic cancer vaccine against human papillomavirus (HPV)-induced cancers was performed assessing immunological activity, safety, and tolerability. Vvax001 consists of replication-incompetent Semliki Forest virus replicon particles encoding HPV16-derived antigens E6 and E7. Twelve participants with a history of cervical intraepithelial neoplasia were included. Four cohorts of three participants were treated per dose level, ranging from 5 × 105 to 2.5 × 108 infectious particles per immunization. The participants received three immunizations with a 3-week interval. For immune monitoring, blood was drawn before immunization and 1 week after the second and third immunization. Immunization with Vvax001 was safe and well tolerated, with only mild injection site reactions, and resulted in both CD4+ and CD8+ T cell responses against E6 and E7 antigens. Even the lowest dose of 5 × 105 infectious particles elicited E6/E7-specific interferon (IFN)-γ responses in all three participants in this cohort. Overall, immunization resulted in positive vaccine-induced immune responses in 12 of 12 participants in one or more assays performed. In conclusion, Vvax001 was safe and induced immune responses in all participants. These data strongly support further clinical evaluation of Vvax001 as a therapeutic vaccine in patients with HPV-related malignancies

Proteomics, ultrastructure, and physiology of hippocampal synapses in a fragile X syndrome mouse model reveal presynaptic phenotype

Fragile X syndrome (FXS), the most common form of hereditary mental retardation, is caused by a loss-of-function mutation of the Fmr1 gene, which encodes fragile X mental retardation protein (FMRP). FMRP affects dendritic protein synthesis, thereby causing synaptic abnormalities. Here, we used a quantitative proteomics approach in an FXS mouse model to reveal changes in levels of hippocampal synapse proteins. Sixteen independent pools of Fmr1 knock-out mice and wild type mice were analyzed using two sets of 8-plex iTRAQ experiments. Of 205 proteins quantified with at least three distinct peptides in both iTRAQ series, the abundance of 23 proteins differed between Fmr1 knock-out and wild type synapses with a false discovery rate (q-value) <5%. Significant differences were confirmed by quantitative immunoblotting. A group of proteins that are known to be involved in cell differentiation and neurite outgrowth was regulated; they included Basp1 and Gap43, known PKC substrates, and Cend1. Basp1 and Gap43 are predominantly expressed in growth cones and presynaptic terminals. In line with this, ultrastructural analysis in developing hippocampal FXS synapses revealed smaller active zones with corresponding postsynaptic densities and smaller pools of clustered vesicles, indicative of immature presynaptic maturation. A second group of proteins involved in synaptic vesicle release was up-regulated in the FXS mouse model. In accordance, paired-pulse and short-term facilitation were significantly affected in these hippocampal synapses. Together, the altered regulation of presynaptically expressed proteins, immature synaptic ultrastructure, and compromised short-term plasticity points to presynaptic changes underlying glutamatergic transmission in FXS at this stage of development. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc