Psychological interventions for women with non-metastatic breast cancer (Review)

Background: Breast cancer is the most common cancer affecting women worldwide. It is a distressing diagnosis and, as a result, considerable research has examined the psychological sequelae of being diagnosed and treated for breast cancer. Breast cancer is associated with increased rates of depression and anxiety and reduced quality of life. As a consequence, multiple studies have explored the impact of psychological interventions on the psychological distress experienced after a diagnosis of breast cancer. Objectives: To assess the effects of psychological interventions on psychological morbidities, quality of life and survival among women with nonmetastatic breast cancer. Search methods: We searched the following databases up to 16 May 2013: the Cochrane Breast Cancer Group Specialised Register, CENTRAL, MEDLINE, EMBASE, CINAHL and PsycINFO; and reference lists of articles. We also searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) search portal and ClinicalTrials.gov for ongoing trials in addition to handsearching. Selection criteria: Randomised controlled trials that assessed the effectiveness of psychological interventions for non-metastatic breast cancer in women. Data collection and analysis: Two review authors independently appraised and extracted data from eligible trials. Any disagreement was resolved by discussion. Extracted data included information about participants, methods, the intervention and outcome. Main results: Twenty-eight randomised controlled trials comprising 3940 participants were included. The most frequent reasons for exclusion were non-randomised trials and the inclusion of women with metastatic disease. A wide range of interventions were evaluated, with 24 trials investigating a cognitive behavioural therapy and four trials investigating psychotherapy compared to control. Pooled standardised mean differences (SMD) from baseline indicated less depression (SMD -1.01, 95% confidence interval (CI) -1.83 to -0.18; P = 0.02; 7 studies, 637 participants, I2 = 95%, low quality evidence), anxiety (SMD -0.48, 95% CI -0.76 to -0.21; P = 0.0006; 8 studies, 776 participants, I2 = 64%, low quality evidence) and mood disturbance (SMD -0.28, 95% CI -0.43 to -0.13; P = 0.0003; 8 studies, 1536 participants, I2 = 47%, moderate quality evidence) for the cognitive behavioural therapy group than the control group. For quality of life, only an individually-delivered cognitive behavioural intervention showed significantly better quality of life than the control with an SMD of 0.65 (95% CI 0.07 to 1.23; P = 0.03; 3 studies, 141 participants, I2 = 41%, very low quality evidence). Pooled data from two group-delivered studies showed a non-significant overall survival benefit favouring cognitive behavioural therapy compared to control (pooled hazard ratio (HR) 0.76, 95% CI 0.25 to 2.32; P = 0.63; 530 participants, I2 = 84%, low quality evidence). Four studies compared psychotherapy to control with one to two studies reporting on each outcome. The four studies were assessed as high risk of bias and provided limited evidence of the efficacy of psychotherapy. Adverse events were not reported in any of the included studies. Authors’ conclusions: A psychological intervention, namely cognitive behavioural therapy, produced favourable effects on some psychological outcomes, in particular anxiety, depression and mood disturbance. However, the evidence for survival improvement is still lacking. These findings are open to criticism because of the notable heterogeneity across the included studies and the shortcomings of the included studies

Can we use biomarkers of coagulation to predict which patients with foot and ankle injury will develop vein thrombosis?

Background Our aim was to determine whether plasma levels of Tissue Factor (TF), Vascular Cell Adhesion Molecule 1 (VCAM-1), Interleukin 6 (IL-6) or D-dimer after foot and ankle injury could predict which patients would develop deep vein thrombosis (DVT). Methods Patients aged 18–60 years with acute foot and ankle injury had venous blood sample to measure TF, VCAM-1, IL-6 and D-dimer within 3 days of injury. Patients had bilateral lower limb venous ultrasound to assess for DVT on discharge from clinic. Results 21 of 77 patients were found to have DVT (27%). There was no statistically significant association between levels of TF, VCAM-1, IL-6 or D-dimer and subsequent development of DVT. Conclusion Tissue Factor (TF), Vascular Cell Adhesion Molecule-1 (VCAM-1), Interleukin-6 (IL-6) and D-dimer levels were not associated with development deep vein thrombosis in patients with acute foot and ankle injury

Effect of Omega-3 Fatty Acids on Lipoprotein Profile and Particle Size in Hispanic Women

The effect of increased Ω3 fatty acids on lipoprotein sub-fractions has not been well studied in Hispanic women, a group with a high prevalence of dyslipidemia and metabolic syndrome. The purpose of this randomized, placebo-controlled trial was to examine the effect of a 90-day (90D) combined EPA+DHA supplementation on lipoprotein profiles of Hispanic women. Twenty-seven non-diabetic women were randomly assigned to the Ω3 group (n=17, 1.9 g/day EPA+DHA) or the placebo group (n=10, 2 g/day oleic acid). At baseline (0D) and 90D a fasting blood sample was drawn for determination of lipoprotein profile and lipoprotein particle sub-fractions. For the Ω3 group, total cholesterol increased 6.5%, triglycerides were reduced 14.8%, LDL concentration increased 5.6%, and total LDL particle size concentration increased 8.2% (P \u3c 0.05). Large LDL particle size concentration increased 16% from 0D to 90D, this change was not significant (P = 0.051). At 90D, total cholesterol, LDLs, and LDL particle concentration were higher in the Ω3 group compared to placebo (P \u3c 0.05). Omega-3 supplementation resulted in reduced plasma TGs and an increase in large LDL particle size concentration, yet had no effect on HDL particle size or concentration. Further research is necessary to examine the effects of increased Ω3 fatty acid intake in Hispanic women on dyslipidemia and related co-morbidities

Adalimumab in combination with methotrexate for refractory uveitis associated with juvenile idiopathic arthritis: a RCT

Abstract Background Children with juvenile idiopathic arthritis (JIA) are at risk of uveitis. The role of adalimumab (Humira®; AbbVie Inc., Ludwigshafen, Germany) in the management of uveitis in children needs to be determined. Objective To compare the efficacy, safety and cost-effectiveness of adalimumab in combination with methotrexate (MTX) versus placebo with MTX alone, with regard to controlling disease activity in refractory uveitis associated with JIA. Design This was a randomised (applying a ratio of 2 : 1 in favour of adalimumab), double-blind, placebo-controlled, multicentre parallel-group trial with an integrated economic evaluation. A central web-based system used computer-generated tables to allocate treatments. A cost–utility analysis based on visual acuity was conducted and a 10-year extrapolation by Markov modelling was also carried out. Setting The setting was tertiary care centres throughout the UK. Participants Patients aged 2–18 years inclusive, with persistently active JIA-associated uveitis (despite optimised MTX treatment for at least 12 weeks). Interventions All participants received a stable dose of MTX and either adalimumab (20 mg/0.8 ml for patients weighing < 30 kg or 40 mg/0.8 ml for patients weighing ≥ 30 kg by subcutaneous injection every 2 weeks based on body weight) or a placebo (0.8 ml as appropriate according to body weight by subcutaneous injection every 2 weeks) for up to 18 months. A follow-up appointment was arranged at 6 months. Main outcome measures Primary outcome – time to treatment failure [multicomponent score as defined by set criteria based on the Standardisation of Uveitis Nomenclature (SUN) criteria]. Economic outcome – incremental cost per quality-adjusted life-year (QALY) gained from the perspective of the NHS in England and Personal Social Services providers. Full details of secondary outcomes are provided in the study protocol. Results A total of 90 participants were randomised (adalimumab, n = 60; placebo, n = 30). There were 14 (23%) treatment failures in the adalimumab group and 17 (57%) in the placebo group. The analysis of the data from the double-blind phase of the trial showed that the hazard risk (HR) of treatment failure was significantly reduced, by 75%, for participants in the adalimumab group (HR 0.25, 95% confidence interval 0.12 to 0.51; p < 0.0001 from log-rank test). The cost-effectiveness of adalimumab plus MTX was £129,025 per QALY gained. Adalimumab-treated participants had a much higher incidence of adverse and serious adverse events. Conclusions Adalimumab in combination with MTX is safe and effective in the management of JIA-associated uveitis. However, the likelihood of cost-effectiveness is < 1% at the £30,000-per-QALY threshold. Future work A clinical trial is required to define the most effective time to stop therapy. Prognostic biomarkers of early and complete response should also be identified

Cost-effectiveness analysis of adalimumab for the treatment of uveitis associated with Juvenile Idiopathic Arthritis

Purpose To investigate the cost effectiveness of adalimumab in combination with methotrexate, compared with methotrexate alone, for the management of uveitis associated with juvenile idiopathic arthritis (JIA). Design A cost-utility analysis based on a clinical trial and decision analytic model. Participants Children and adolescents 2 to 18 years of age with persistently active uveitis associated with JIA, despite optimized methotrexate treatment for at least 12 weeks. Methods The SYCAMORE (Randomised controlled trial of the clinical effectiveness, SafetY and Cost effectiveness of Adalimumab in combination with MethOtRExate for the treatment of juvenile idiopathic arthritis associated uveitis) trial (identifier, ISRCTN10065623) of methotrexate (up to 25 mg weekly) with or without fortnightly administered adalimumab (20 or 40 mg, according to body weight) provided data on resource use (based on patient self-report and electronic records) and health utilities (from the Health Utilities Index questionnaire). Surgical event rates and long-term outcomes were based on data from a 10-year longitudinal cohort. A Markov model was used to extrapolate the effects of treatment based on visual impairment. Main Outcome Measures Medical costs to the National Health Service in the United Kingdom, utility of defined health states, quality-adjusted life-years (QALYs), and incremental cost per QALY. Results Adalimumab in combination with methotrexate resulted in additional costs of £39 316, with a 0.30 QALY gain compared with methotrexate alone, resulting in an incremental cost-effectiveness ratio of £129 025 per QALY gained. The probability of cost effectiveness at a threshold of £30 000 per QALY was less than 1%. Based on a threshold analysis, a price reduction of 84% would be necessary for adalimumab to be cost effective. Conclusions Adalimumab is clinically effective in uveitis associated with JIA; however, its cost effectiveness is not demonstrated compared with methotrexate alone in the United Kingdom setting

Remote sensing for cost-effective blue carbon accounting

Blue carbon ecosystems (BCE) include mangrove forests, tidal marshes, and seagrass meadows, all of which are currently under threat, putting their contribution to mitigating climate change at risk. Although certain challenges and trade-offs exist, remote sensing offers a promising avenue for transparent, replicable, and cost-effective accounting of many BCE at unprecedented temporal and spatial scales. The United Nations Framework Convention on Climate Change (UNFCCC) has issued guidelines for developing blue carbon inventories to incorporate into Nationally Determined Contributions (NDCs). Yet, there is little guidance on remote sensing techniques for monitoring, reporting, and verifying blue carbon assets. This review constructs a unified roadmap for applying remote sensing technologies to develop cost-effective carbon inventories for BCE – from local to global scales. We summarise and discuss (1) current standard guidelines for blue carbon inventories; (2) traditional and cutting-edge remote sensing technologies for mapping blue carbon habitats; (3) methods for translating habitat maps into carbon estimates; and (4) a decision tree to assist users in determining the most suitable approach depending on their areas of interest, budget, and required accuracy of blue carbon assessment. We designed this work to support UNFCCC-approved IPCC guidelines with specific recommendations on remote sensing techniques for GHG inventories. Overall, remote sensing technologies are robust and cost-effective tools for monitoring, reporting, and verifying blue carbon assets and projects. Increased appreciation of these techniques can promote a technological shift towards greater policy and industry uptake, enhancing the scalability of blue carbon as a Natural Climate Solution worldwide

Knocking at the brain’s door: intravital two-photon imaging of autoreactive T cell interactions with CNS structures

Since the first applications of two-photon microscopy in immunology 10 years ago, the number of studies using this advanced technology has increased dramatically. The two-photon microscope allows long-term visualization of cell motility in the living tissue with minimal phototoxicity. Using this technique, we examined brain autoantigen-specific T cell behavior in experimental autoimmune encephalitomyelitis, the animal model of human multiple sclerosis. Even before disease symptoms appear, the autoreactive T cells arrive at their target organ. There they crawl along the intraluminal surface of central nervous system (CNS) blood vessels before they extravasate. In the perivascular environment, the T cells meet phagocytes that present autoantigens. This contact activates the T cells to penetrate deep into the CNS parenchyma, where the infiltrated T cells again can find antigen, be further activated, and produce cytokines, resulting in massive immune cell recruitment and clinical disease

Accuracy of genomic breeding values in multi-breed dairy cattle populations

<p>Abstract</p> <p>Background</p> <p>Two key findings from genomic selection experiments are 1) the reference population used must be very large to subsequently predict accurate genomic estimated breeding values (GEBV), and 2) prediction equations derived in one breed do not predict accurate GEBV when applied to other breeds. Both findings are a problem for breeds where the number of individuals in the reference population is limited. A multi-breed reference population is a potential solution, and here we investigate the accuracies of GEBV in Holstein dairy cattle and Jersey dairy cattle when the reference population is single breed or multi-breed. The accuracies were obtained both as a function of elements of the inverse coefficient matrix and from the realised accuracies of GEBV.</p> <p>Methods</p> <p>Best linear unbiased prediction with a multi-breed genomic relationship matrix (GBLUP) and two Bayesian methods (BAYESA and BAYES_SSVS) which estimate individual SNP effects were used to predict GEBV for 400 and 77 young Holstein and Jersey bulls respectively, from a reference population of 781 and 287 Holstein and Jersey bulls, respectively. Genotypes of 39,048 SNP markers were used. Phenotypes in the reference population were de-regressed breeding values for production traits. For the GBLUP method, expected accuracies calculated from the diagonal of the inverse of coefficient matrix were compared to realised accuracies.</p> <p>Results</p> <p>When GBLUP was used, expected accuracies from a function of elements of the inverse coefficient matrix agreed reasonably well with realised accuracies calculated from the correlation between GEBV and EBV in single breed populations, but not in multi-breed populations. When the Bayesian methods were used, realised accuracies of GEBV were up to 13% higher when the multi-breed reference population was used than when a pure breed reference was used. However no consistent increase in accuracy across traits was obtained.</p> <p>Conclusion</p> <p>Predicting genomic breeding values using a genomic relationship matrix is an attractive approach to implement genomic selection as expected accuracies of GEBV can be readily derived. However in multi-breed populations, Bayesian approaches give higher accuracies for some traits. Finally, multi-breed reference populations will be a valuable resource to fine map QTL.</p

Oxygen- and capacity-limited thermal tolerance: blurring ecology and physiology

No abstract available

Lung inflammation does not affect the clearance kinetics of lipid nanocapsules following pulmonary administration

Lipid nanocapsules (LNCs) are semi-rigid spherical capsules with a triglyceride core that present a promising formulation option for the pulmonary delivery of drugs with poor aqueous solubility. Whilst the biodistribution of LNCs of different size has been studied following intravenous administration, the fate of LNCs following pulmonary delivery has not been reported. We investigated quantitatively whether lung inflammation affects the clearance of 50nm lipid nanocapsules, or is exacerbated by their pulmonary administration. Studies were conducted in mice with lipopolysaccharide-induced lung inflammation compared to healthy controls. Particle deposition and nanocapsule clearance kinetics were measured by single photon emission computed tomography/computed tomography (SPECT/CT) imaging over 48 h. A significantly lower lung dose of (111)In-LNC50 was achieved in the lipopolysaccharide (LPS)-treated animals compared with healthy controls (p<0.001). When normalised to the delivered lung dose, the clearance kinetics of (111)In-LNC50 from the lungs fit a first order model with an elimination half-life of 10.5±0.9h (R(2)=0.995) and 10.6±0.3h (R(2)=1.000) for healthy and inflamed lungs respectively (n=3). In contrast, (111)In-diethylene triamine pentaacetic acid (DTPA), a small hydrophilic molecule, was cleared rapidly from the lungs with the majority of the dose absorbed within 20min of administration. Biodistribution to lungs, stomach-intestine, liver, trachea-throat and blood at the end of the imaging period was unaltered by lung inflammation. This study demonstrated that lung clearance and whole body distribution of lipid nanocapsules were unaffected by the presence of acute lung inflammation