Viewpoints of adolescents with overweight and obesity attending lifestyle obesity treatment interventions: a qualitative systematic review.

BACKGROUND: Current UK guidance recommends that adolescents with obesity attend a family-based multi-component obesity intervention. However, these programmes suffer from low recruitment and high rates of attrition. Understanding the views of adolescents is necessary for developing future interventions. The aim of this systematic review was to synthesize and explore the views of adolescents who have attended an obesity intervention. METHODS: Published literature was identified by searching six databases. Studies of adolescents (12-17 years) who attended an obesity intervention were examined. Only studies that collected and analysed data qualitatively were included. Full texts were analysed using thematic synthesis. RESULTS: Twenty-eight studies were included. Thirty-five analytical themes were developed that were broadly divided into seven domains. Key themes included ensuring adolescents receive a 'tailored intervention' that involves 'active engagement'. Support from professionals, family and peers were valued highly. Adolescents expressed 'prior fears of attending interventions' and wanted 'longer term support'. 'Enjoyment of sport and physical activity' was evident, and adolescents were strongly motivated by improving body image and social desirability. DISCUSSION: Considering the views of adolescents attending obesity interventions may help to inform policy makers in the development of future interventions. This may lead to an improvement in recruitment and attrition rates.

Assessing the Impact of Tissue Target Concentration Data on Uncertainty in In Vivo Target Coverage Predictions.

Understanding pharmacological target coverage is fundamental in drug discovery and development as it helps establish a sequence of research activities, from laboratory objectives to clinical doses. To this end, we evaluated the impact of tissue target concentration data on the level of confidence in tissue coverage predictions using a site of action (SoA) model for antibodies. By fitting the model to increasing amounts of synthetic tissue data and comparing the uncertainty in SoA coverage predictions, we confirmed that, in general, uncertainty decreases with longitudinal tissue data. Furthermore, a global sensitivity analysis showed that coverage is sensitive to experimentally identifiable parameters, such as baseline target concentration in plasma and target turnover half-life and fixing them reduces uncertainty in coverage predictions. Overall, our computational analysis indicates that measurement of baseline tissue target concentration reduces the uncertainty in coverage predictions and identifies target-related parameters that greatly impact the confidence in coverage predictions.

Physiologically based pharmacokinetic modeling in drug discovery and development: a pharmaceutical industry perspective.

The application of physiologically based pharmacokinetic (PBPK) modeling has developed rapidly within the pharmaceutical industry and is becoming an integral part of drug discovery and development. In this study, we provide a cross pharmaceutical industry position on "how PBPK modeling can be applied in industry" focusing on the strategies for application of PBPK at different stages, an associated perspective on the confidence and challenges, as well as guidance on interacting with regulatory agencies and internal best practices.

Controlling the action of chlorine radical: from lab to environment.

The strength of Bz-Cl˙ complexation has been explored using density functional theory (DFT) calculations, including dispersion-corrected (DFT-D) calculations. Of the methods tested, the ωB97X-D method seems the best performing, along with the previously tested MPW1K method. The effect of substituent (X = NO(2), F, Cl, Br, H, CH(3), OCH(3), OH, NH(2) and N(CH(3))(2)) on the stabilities of the Ar-Cl˙π-like intermediates show a good correlation with the linear free energy relationships used experimentally, but this is not the case for Ar-Cl˙σ-complexes, suggesting the transition state of abstraction as being π-like in nature. The role of PAH and lignin derivatives in mediating chlorination reactions in nature is explored. Stable π-complexes were identified for lignin derivatives, indicating humic substances may mediate chlorine atom reactivity at the marine boundary layer, in addition to forming chlorolignins.

Chlorine--benzene complexes--the reliability of density functionals for non-covalent radical complexes.

The structure of the chlorine atom-benzene complex has been a topic of significant controversy for more than 50 years. We have reexamined the structure of this complex with new density functional methods especially designed for non-covalent complexes, and compared the structures and energetics to those obtained using standard DFT and high accuracy composite methods. We find that the popular B3LYP functional fails to identify stationary points revealed by other functionals, and that the eta(1)-sigma complex appears to be more stable than the eta(1)-pi complex, contrary to other recent work, highlighting the careful selection of methods required in non-covalent radical systems.

Impact of end-product inhibition on the determination of in vitro metabolic clearance.

End-product inhibition was explored as a mechanism for the lower clearance determination obtained from microsomes compared with hepatocytes. Triazolam, diazepam and phenytoin microsomal substrate depletion was reduced by 23, 34 and 39%, respectively, when incubated with their primary metabolites. Ki values of 28+/-6 and 11+/-1 microM were obtained when 4'-hydroxydiazepam and p-hydroxyphenytoin where incubated with diazepam and phenytoin, respectively. Alamethicin (a glucuronidation activator) was unsuccessful in alleviating these effects. IC50 values of 17, 32 and 18 microM for phenytoin and 83, 110 and 97 microM for diazepam were observed with salicylamide- (a glucuronidation inhibitor) treated hepatocytes, control hepatocytes and microsomes, respectively, when incubated with their primary metabolites. These differences suggest that metabolite concentrations in the vicinity of the enzyme are lower in hepatocytes compared with microsomes, reducing the likelihood of end-product inhibition in the former system. In conclusion, end-product inhibition may be more prominent in microsomes (in particular for substrate depletion assays where metabolism tends to be more extensive); results suggest that this phenomenon may contribute to the observed variations in metabolism characteristics and intrinsic clearance (CLint) between hepatocytes and microsomes.

In vivo 5-HT2A receptor blockade by quetiapine: an R91150 single photon emission tomography study.

BACKGROUND: Atypical antipsychotic drugs are thought to show a high degree of 5-HT2A receptor blockade, which may prevent the emergence of extrapyramidal symptoms. METHOD: 5-HT2A binding was estimated using 123I-5-I-R91150 and single photon emission tomography (SPET) in six schizophrenic subjects treated with quetiapine at a mean (+/-SD) daily dose of 350+/-123 mg for at least 5 weeks and a matched sample of six healthy volunteers. Clinical and side-effect ratings were performed at baseline and at the time of SPET scanning. The reference region approach was used to define a 5-HT2A binding index in the frontal and temporal cortex. RESULTS: Quetiapine treatment resulted in a significant decline in 5-HT2A receptor availability in the frontal cortex (mean 0.98+/-0.09) relative to healthy volunteers (mean 1.33+/-0.16). All patients showed improvements in clinical symptom or side-effect ratings. The mean frontal cortex:cerebellum ratio after quetiapine treatment was significantly negatively correlated with reduction in the Abnormal Involuntary Rating scale and Simpson-Angus scores (P<0.05 Bonferroni corrected), but not with the reduction in the scores from the scale for the assessment of positive symptoms, the scale for the assessment of negative symptoms, the Montgomery-Asberg depression rating scale or patient age. CONCLUSION: Quetiapine treatment results in significant in vivo blockade of cortical 5-HT2A, similar to other atypical antipsychotic drugs. This effect may contribute to its placebo level extrapyramidal side-effect profile.

VACUTEX capillary action dressing: a multicentre, randomized trial.

This article describes a preliminary study comparing the effect of VACUTEX capillary action wound dressing vs standard protocol for the treatment of sloughy and necrotic wounds. The study was carried out over a period of 5 months. Randomization was computer generated and batches of trial numbers and dressing allocation were delivered to each of the three study sites, sealed in opaque envelopes to ensure blinding of allocation. A total of 35 patient participants were recruited (17 VACUTEX 14, standard protocol, three withdrew, one died). All participants gave their consent to enter the study. All participants were assessed and photographs were taken on days 1, 8, 15, 22 and 29. Nursing assessments of size, site, depth, severity, tissue type of wound and causation were collected, as were demographic factors including mental status, primary/associated medical history, weight, height, and ethnic origin.

Design, expression and functional characterization of a synthetic gene encoding the Chlamydia trachomatis major outer membrane protein.

A synthetic gene coding for the Chlamydia trachomatis serovar L2 major outer membrane protein (MOMP) was designed, constructed and expressed in Escherichia coli. The native amino acid sequence was reverse translated and the resulting nucleotide combinations manipulated in order to evenly distribute 25 unique restriction sites along the length of the gene while retaining the native amino acid sequence. The synthetic gene was cloned into a T7 promoter-controlled plasmid (pET-3a) and the expressed product was analyzed to assess antigenicity, cellular localization and function. Monoclonal antibodies specific for native MOMP reacted to the expressed product by immunoblot. Outer membrane fractionation confirmed that the processed protein was located in the outer membrane. MOMP expressed in E. coli and present in the outer membrane was shown to function as a general diffusion porin. This system provides the means to produce readily modifiable MOMP either in purified form or as a membrane-associated protein, and so facilitate the investigation of its functional, structural and antigenic properties.

Striatal and extra-striatal D(2)/D(3) dopamine receptor occupancy by quetiapine in vivo. [(123)I]-epidepride single photon emission tomography(SPET) study.

BACKGROUND: Selective action at limbic cortical dopamine D(2)-like receptors could mediate atypical antipsychotic efficacy with few extrapyramidal side-effects. AIMS: To test the hypothesis that quetiapine has 'limbic selective' D(2)/D(3) receptor occupancy in vivo. METHOD: The high-affinity D(2)/D(3) ligand [(123)I]-epidepride and single photon emission tomography were used to estimate D(2)/D(3) specific binding and an index of relative percentage D(2)/D(3) occupancy in striatal and temporal cortical regions for quetiapine-treated patients (n=6). Quetiapine-, and previously studied typical-antipsychotic- and clozapine-treated patients were compared. RESULTS: Mean (s.d.) relative percentage D(2)/D(3) receptor occupancy by quetiapine was 32.0% (14.6) in striatum and 60.1% (17.2) in temporal cortex (mean daily dose 450 mg: range 300-700 mg/day). Quetiapine treatment resulted in limbic selective D(2)/D(3) blockade similar to clozapine and significantly higher than typical antipsychotics. CONCLUSIONS: Preliminary data suggest that limbic selective D(2)/D(3) receptor blockade is important for atypical drug action.

Experienced nurses learning with medical students: a case study.

Although there are successful examples of interdisciplinary education this generally relates to pre-registration health-care professionals. Post-registration projects are usually confined to skills workshops or social science subjects, which rarely include medical staff. This project was unusual in its attempt to combine the needs of experienced practitioners with those of medical students. There are practical issues for this form of learning such as, the organization of modules into 'systems' when health-care professionals (as part of a parallel project) indicated their interests lay in courses that related to clinical practice organized around disease processes/conditions. This case study demonstrates that concerns related to the potential mismatch of clinical expertise, maturity and scientific background are not insurmountable problems, and that clear benefits can be gained. It could be argued that until pre- and post-graduate medical staff are integrated with other disciplines, the real benefits of shared understanding, enhanced team work and mutual respect will remain illusive. It is not anticipated that this form of learning would be suitable for the majority of practitioners, whose core needs are generally met by existing opportunities. However, there is a need for a greater depth of academic understanding particularly for those in senior positions or in specific specialized areas (also identified in the parallel study) and for those whose roles are expanding. These practitioners are more likely to have the ability to apply their new knowledge to clinical practice, using reflective techniques with minimal facilitation to enhance their established clinical expertise. For them this model of learning offers the opportunity to tailor education to the individual needs of the practitioner without the costly establishment of complete new programmes of learning. This case study proved particularly successful for the participants as they enhanced understanding and confidence in the knowledge underpinning their practice. This enabled them to better anticipate patients needs, to identify complications and initiate action at an earlier stage. Their appreciation of rationale underpinning medical treatment has enabled them to support junior medical staff, and to promote the continuity of appropriate care. They are more active in the education of patients, relatives and staff, and have identified specific developments which will be informed by the knowledge they have gained. It also proved beneficial to junior medical staff with whom interdisciplinary working has improved. Each organization involved in facilitating the initiative also benefited by gaining mutual understanding and appreciation of systems, constraints and opportunities. Equally, relationships among them have been strengthened and key issues with practical solutions have been identified to inform future joint ventures. Indications suggest that there would be value in using this case study to inform a structured pilot project involving other modules of learning and potentially other disciplines. If successful it could benefit all health-care professionals, particularly those senior staff who are expanding their roles and have educational needs unmet by existing provision. In addition to providing complementary opportunities this format provides a mechanism to enhance the mutual understanding essential to effective teamwork.

Introducing a lecturer-practitioner: the management perspective.

The West Midlands Regional Health Authority Department of Nursing funded a 1-year study to look at 'Implementation aspects of the lecturer-practitioner role (in nursing)'. A feasibility study was carried out from November 1992 to October 1993 to address the issue and highlight areas requiring more in-depth study. Twenty-nine subjects working as or with lecturer-practitioners were interviewed using a semi-structured questionnaire. The interview was divided into two discrete parts. The first section contained a mixture of open and closed questions and the second section adopted a modified repertory grid technique. This paper provides the main results from the first half of the interview. The study describes in practical terms how managers need to plan for the introduction of a lecturer-practitioner post; the key responsibilities of the role; and a person specification. The work identifies clear prerequisite criteria for job role and gives guidance on lecturer-practitioner management and function.