A randomised controlled trial of the compuLsive Exercise Activity TheraPy (LEAP): a new approach to compulsive exercise in anorexia nervosa

Objective: To compare the efficacy of the compuLsive Exercise Activity theraPy (LEAP) programme integrated with manualised cognitive behavioural therapy for anorexia nervosa (CBT-AN) compared to CBT-AN alone. Method: Seventy-eight adults were randomised to CBT-AN, delivered with or without 8 embedded sessions of LEAP, for a total of 34 individual outpatient sessions. Participants were assessed at baseline, the end of the first phase of CBT-AN (which included LEAP), mid-therapy, end of therapy, and at 3 and 6-months follow-up. Linear mixed effects modelling was used for comparing trajectories over time by group in primary outcomes of pathological exercise cognitions and secondary outcomes of exercise frequency, BMI, eating disorder (ED) symptoms, AN stage of change, anxiety/depression, and health related quality of life. Results: There were significant improvements over time in all outcomes. There were no significant differences between treatment groups in primary outcome measures. Fidelity and end-of- treatment participant satisfaction were satisfactory across both conditions. Discussion: CBT-AN and LEAP added to CBT-AN resulted in improved attitudes and beliefs towards exercise and general improvements in BMI and eating disorder psychopathology in people with AN

Dynamic contrast-enhanced CT compared with positron emission tomography CT to characterise solitary pulmonary nodules: the SPUtNIk diagnostic accuracy study and economic modelling

BACKGROUND: Current pathways recommend positron emission tomography-computerised tomography for the characterisation of solitary pulmonary nodules. Dynamic contrast-enhanced computerised tomography may be a more cost-effective approach. OBJECTIVES: To determine the diagnostic performances of dynamic contrast-enhanced computerised tomography and positron emission tomography-computerised tomography in the NHS for solitary pulmonary nodules. Systematic reviews and a health economic evaluation contributed to the decision-analytic modelling to assess the likely costs and health outcomes resulting from incorporation of dynamic contrast-enhanced computerised tomography into management strategies. DESIGN: Multicentre comparative accuracy trial. SETTING: Secondary or tertiary outpatient settings at 16 hospitals in the UK. PARTICIPANTS: Participants with solitary pulmonary nodules of ≥ 8 mm and of ≤ 30 mm in size with no malignancy in the previous 2 years were included. INTERVENTIONS: Baseline positron emission tomography-computerised tomography and dynamic contrast-enhanced computer tomography with 2 years' follow-up. MAIN OUTCOME MEASURES: Primary outcome measures were sensitivity, specificity and diagnostic accuracy for positron emission tomography-computerised tomography and dynamic contrast-enhanced computerised tomography. Incremental cost-effectiveness ratios compared management strategies that used dynamic contrast-enhanced computerised tomography with management strategies that did not use dynamic contrast-enhanced computerised tomography. RESULTS: A total of 380 patients were recruited (median age 69 years). Of 312 patients with matched dynamic contrast-enhanced computer tomography and positron emission tomography-computerised tomography examinations, 191 (61%) were cancer patients. The sensitivity, specificity and diagnostic accuracy for positron emission tomography-computerised tomography and dynamic contrast-enhanced computer tomography were 72.8% (95% confidence interval 66.1% to 78.6%), 81.8% (95% confidence interval 74.0% to 87.7%), 76.3% (95% confidence interval 71.3% to 80.7%) and 95.3% (95% confidence interval 91.3% to 97.5%), 29.8% (95% confidence interval 22.3% to 38.4%) and 69.9% (95% confidence interval 64.6% to 74.7%), respectively. Exploratory modelling showed that maximum standardised uptake values had the best diagnostic accuracy, with an area under the curve of 0.87, which increased to 0.90 if combined with dynamic contrast-enhanced computerised tomography peak enhancement. The economic analysis showed that, over 24 months, dynamic contrast-enhanced computerised tomography was less costly (£3305, 95% confidence interval £2952 to £3746) than positron emission tomography-computerised tomography (£4013, 95% confidence interval £3673 to £4498) or a strategy combining the two tests (£4058, 95% confidence interval £3702 to £4547). Positron emission tomography-computerised tomography led to more patients with malignant nodules being correctly managed, 0.44 on average (95% confidence interval 0.39 to 0.49), compared with 0.40 (95% confidence interval 0.35 to 0.45); using both tests further increased this (0.47, 95% confidence interval 0.42 to 0.51). LIMITATIONS: The high prevalence of malignancy in nodules observed in this trial, compared with that observed in nodules identified within screening programmes, limits the generalisation of the current results to nodules identified by screening. CONCLUSIONS: Findings from this research indicate that positron emission tomography-computerised tomography is more accurate than dynamic contrast-enhanced computerised tomography for the characterisation of solitary pulmonary nodules. A combination of maximum standardised uptake value and peak enhancement had the highest accuracy with a small increase in costs. Findings from this research also indicate that a combined positron emission tomography-dynamic contrast-enhanced computerised tomography approach with a slightly higher willingness to pay to avoid missing small cancers or to avoid a 'watch and wait' policy may be an approach to consider. FUTURE WORK: Integration of the dynamic contrast-enhanced component into the positron emission tomography-computerised tomography examination and the feasibility of dynamic contrast-enhanced computerised tomography at lung screening for the characterisation of solitary pulmonary nodules should be explored, together with a lower radiation dose protocol

Hair Cortisol in Twins : Heritability and Genetic Overlap with Psychological Variables and Stress-System Genes

A. Palotie on työryhmän jäsen.Hair cortisol concentration (HCC) is a promising measure of long-term hypothalamus-pituitary-adrenal (HPA) axis activity. Previous research has suggested an association between HCC and psychological variables, and initial studies of inter-individual variance in HCC have implicated genetic factors. However, whether HCC and psychological variables share genetic risk factors remains unclear. The aims of the present twin study were to: (i) assess the heritability of HCC; (ii) estimate the phenotypic and genetic correlation between HPA axis activity and the psychological variables perceived stress, depressive symptoms, and neuroticism; using formal genetic twin models and molecular genetic methods, i.e. polygenic risk scores (PRS). HCC was measured in 671 adolescents and young adults. These included 115 monozygotic and 183 dizygotic twin-pairs. For 432 subjects PRS scores for plasma cortisol, major depression, and neuroticism were calculated using data from large genome wide association studies. The twin model revealed a heritability for HCC of 72%. No significant phenotypic or genetic correlation was found between HCC and the three psychological variables of interest. PRS did not explain variance in HCC. The present data suggest that HCC is highly heritable. However, the data do not support a strong biological link between HCC and any of the investigated psychological variables.Peer reviewe

Impact of Optimized Breastfeeding on the Costs of Necrotizing Enterocolitis in Extremely Low Birthweight Infants

To estimate risk of NEC for ELBW infants as a function of preterm formula and maternal milk (MM) intake and calculate the impact of suboptimal feeding on NEC incidence and costs

Omega-3 fatty acids and inflammation: novel interactions reveal a new step in neutrophil recruitment

Inflammation is a physiological response to tissue trauma or infection, but leukocytes, which are the effector cells of the inflammatory process, have powerful tissue remodelling capabilities. Thus, to ensure their precise localisation, passage of leukocytes from the blood into inflamed tissue is tightly regulated. Recruitment of blood borne neutrophils to the tissue stroma occurs during early inflammation. In this process, peptide agonists of the chemokine family are assumed to provide a chemotactic stimulus capable of supporting the migration of neutrophils across vascular endothelial cells, through the basement membrane of the vessel wall, and out into the tissue stroma. Here, we show that, although an initial chemokine stimulus is essential for the recruitment of flowing neutrophils by endothelial cells stimulated with the inflammatory cytokine tumour necrosis factor-?, transit of the endothelial monolayer is regulated by an additional and downstream stimulus. This signal is supplied by the metabolism of the omega-6-polyunsaturated fatty acid (n-6-PUFA), arachidonic acid, into the eicosanoid prostaglandin-D2 (PGD2) by cyclooxygenase (COX) enzymes. This new step in the neutrophil recruitment process was revealed when the dietary n-3-PUFA, eicosapentaenoic acid (EPA), was utilised as an alternative substrate for COX enzymes, leading to the generation of PGD3. This alternative series eicosanoid inhibited the migration of neutrophils across endothelial cells by antagonising the PGD2 receptor. Here, we describe a new step in the neutrophil recruitment process that relies upon a lipid-mediated signal to regulate the migration of neutrophils across endothelial cells. PGD2 signalling is subordinate to the chemokine-mediated activation of neutrophils, but without the sequential delivery of this signal, neutrophils fail to penetrate the endothelial cell monolayer. Importantly, the ability of the dietary n-3-PUFA, EPA, to inhibit this process not only revealed an unsuspected level of regulation in the migration of inflammatory leukocytes, it also contributes to our understanding of the interactions of this bioactive lipid with the inflammatory system. Moreover, it indicates the potential for novel therapeutics that target the inflammatory system with greater affinity and/or specificity than supplementing the diet with n-3-PUFA

Electrospray ionisation mass spectrometry analysis of differential turnover of phosphatidylcholine by human blood leukocytes

Synthesis and turnover of membrane phospholipids is essential for cell growth and function, and hydrolysis of membrane phospholipid is central to many intracellular signalling mechanisms. Hydrolysis of phosphatidylcholine (PC) is a major signalling mechanism of neutrophils, leukocytes that phagocytose and kill bacteria as part of the innate immune response, generating phosphatidic acid, diacylglycerol and arachidonate-derived lipid second messengers. We describe here the application of tandem MS/MS electrospray ionisation mass spectrometry to the analysis of molecular patterns of PC synthesis by blood neutrophil and lymphocyte cells from healthy volunteers. This technique combined incorporation of the headgroup choline, methyl-labelled with deuterium (methyl-d9-choline), with precursor scans of diagnostic labelled and native fragment ions. The technique was very sensitive, permitting detection of d9 enrichment <0.01%. Results showed that the two different cell types maintained distinct molecular species compositions of PC, even though they were exposed to the same nutrient supply in blood. Moreover, while the pattern of lymphocyte PC synthesis directly mirrored composition, the fractional synthesis of arachidonoyl (C204,n-6)-containing PC species in neutrophils was greatly enhanced compared with composition. This increased turnover of arachidonoyl species in neutrophils may be related to the active synthesis of eicosanoids and other arachidonoyl-derived mediators in this cell type

The impact of common gene variants on the response of biomarkers of cardiovascular disease (CVD) risk to increased fish oil fatty acids intakes

The cardioprotective actions of the fish oil (FO)-derived long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been demonstrated, and dose-response relationships have been defined. However, there is a substantial and well-recognized within-population heterogeneity in response to FO, the etiology of which is poorly understood. Genetic variation may influence responsiveness. Here we review the available literature relating to gene variants shown to influence tissue LC n-3 PUFA status and response to FO intervention. From this review we conclude that the available evidence is relatively limited. A number of individual genotype × LC-n3 PUFA × phenotype associations have been described, but few have been investigated in subsequent cohorts or confirmed in independent studies. In the context of a more stratified approach to the provision of dietary advice, there is a need for further research to refine current dietary EPA and DHA recommendations. Expected final online publication date for the Annual Review of Nutrition Volume 31 is July 17, 2011. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates

Defining sustainability in practice: views from implementing real-world innovations in health care

Abstract Background One of the key conceptual challenges in advancing our understanding of how to more effectively sustain innovations in health care is the lack of clarity and agreement on what sustainability actually means. Several reviews have helped synthesize and clarify how researchers conceptualize and operationalize sustainability. In this study, we sought to identify how individuals who implement and/or sustain evidence-informed innovations in health care define sustainability. Methods We conducted in-depth, semi-structured interviews with implementation leaders and relevant staff involved in the implementation of evidence-based innovations relevant to cancer survivorship care (n = 27). An inductive approach, using constant comparative analysis, was used for analysis of interview transcripts and field notes. Results Participants described sustainability as an ongoing and dynamic process that incorporates three key concepts and four important conditions. The key concepts were: (1) continued capacity to deliver the innovation, (2) continued delivery of the innovation, and (3) continued receipt of benefits. The key conditions related to (2) and (3), and included: (2a) innovations must continue in the absence of the champion or person/team who introduced it and (3a) adaptation is critical to ensuring relevancy and fit, and thus to delivering the intended benefits. Conclusions Participants provided a nuanced view of sustainability, with both continued delivery and continued benefits only relevant under certain conditions. The findings reveal the interconnected elements of what sustainability means in practice, providing a unique and important perspective to the academic literature