Myocardial contractility pattern characterization in radiation-induced cardiotoxicity using magnetic resonance imaging: A pilot study with ContractiX

Radiation therapy (RT) plays an integral role in treating thoracic cancers, despite the risk of radiation-induced cardiotoxicity. We hypothesize that our newly developed magnetic resonance imaging (MRI)-based contractility index (ContractiX) is a sensitive marker for early detection of RT-induced cardiotoxicity in a preclinical rat model of thoracic cancer RT. Adult salt-sensitive rats received image-guided heart RT and were imaged with MRI at 8 weeks and 10 weeks post-RT or sham. The MRI exam included cine and tagging sequences to measure left-ventricular ejection fraction (LVEF), mass, myocardial strain, and ContractiX. Furthermore, ventricular torsion, diastolic strain rate, and mechanical dyssynchrony were measured. Statistical analyses were performed between the sham, 8 weeks post-RT, and 10 weeks post-RT MRI parameters. The results showed that both LVEF and myocardial mass increased post-RT. Peak systolic strain and ContractiX significantly decreased post-RT, with a more relative reduction in ContractiX compared to strain. ContractiX showed an inverse nonlinear relationship with LVEF and continuously decreased with time post-RT. While early diastolic strain rate and mechanical dyssynchrony significantly changed post-RT, ventricular torsion changes were not significant post-RT. In conclusion, ContractiX measured via non-contrast MRI is a sensitive early marker for the detection of subclinical cardiac dysfunction post-RT, and it is superior to other MRI cardiac measures

Antibiotic capture by bacterial lipocalins uncovers an extracellular mechanism of intrinsic antibiotic resistance

15 p.-6 fig.The potential for microbes to overcome antibiotics of different classes before they reach bacterial cells is largely unexplored. Here we show that a soluble bacterial lipocalin produced by Burkholderia cenocepacia upon exposure to sublethal antibiotic concentrations increases resistance to diverse antibiotics in vitro and in vivo. These phenotypes were recapitulated by heterologous expression in B. cenocepacia of lipocalin genes from Pseudomonas aeruginosa, Mycobacterium tuberculosis,and methicillin-resistant Staphylococcus aureus. Purified lipocalin bound different classes of bactericidal antibiotics and contributed to bacterial survival in vivo. Experimental and X-ray crystal structure-guided computational studies revealed that lipocalins counteract antibiotic action by capturing antibiotics in the extracellular space. We also demonstrated that fat-soluble vitamins prevent antibiotic capture by binding bacterial lipocalin with higher affinity than antibiotics. Therefore, bacterial lipocalins contribute to antimicrobial resistance by capturing diverse antibiotics in the extracellular space at the site of infection, which can be counteracted by known vitamins.This work was funded by grants from Cystic Fibrosis Canada, the European Commission,a Marie Curie Career Integration grant (projects 618095, NONANTIRES), and the Infection and Immunity Translational Research Group, Northern Ireland HSC to M.A.V.;the Spanish Ministry for Economy and Competitiveness (MINECO CTQ2011-22724 and CTQ2014-57141-R), European Commission Marie Curie grants GLYCOPHARM FP7-PITNGA-2012-317297 and TOLLerant H2020-MSC-ETN-642157 to S.M.S.; and Canadian Institutes of Health research grant MOP-49597 and a grant from Cystic Fibrosis Canada to M.E.P.M.Peer reviewe

Cost-effectiveness of financial incentives to promote adherence to depot antipsychotic medication: economic evaluation of a cluster-randomised controlled trial

Background: Offering a modest financial incentive to people with psychosis can promote adherence to depot antipsychotic medication, but the cost-effectiveness of this approach has not been examined. Methods: Economic evaluation within a pragmatic cluster-randomised controlled trial. 141 patients under the care of 73 teams (clusters) were randomised to intervention or control; 138 patients with diagnoses of schizophrenia, schizo-affective disorder or bipolar disorder participated. Intervention participants received £15 per depot injection over 12 months, additional to usual acute, mental and community primary health services. The control group received usual health services. Main outcome measures: incremental cost per 20% increase in adherence to depot antipsychotic medication; incremental cost of ‘good’ adherence (defined as taking at least 95% of the prescribed number of depot medications over the intervention period). Findings: Economic and outcome data for baseline and 12-month follow-up were available for 117 participants. The adjusted difference in adherence between groups was 12.2% (73.4% control vs. 85.6% intervention); the adjusted costs difference was £598 (95% CI -£4 533, £5 730). The extra cost per patient to increase adherence to depot medications by 20% was £982 (95% CI -£8 020, £14 000). The extra cost per patient of achieving 'good' adherence was £2 950 (CI -£19 400, £27 800). Probability of cost-effectiveness exceeded 97.5%at willingness-to-pay values of £14 000 for a 20% increase in adherence and £27 800 for good adherence. Interpretation: Offering a modest financial incentive to people with psychosis is cost-effective in promoting adherence to depot antipsychotic medication. Direct healthcare costs (including costs of the financial incentive) are unlikely to be increased by this intervention. Trial Registration: ISRCTN.com 7776928

The development and evaluation of a five-language multi-perspective standardised measure: clinical decision-making involvement and satisfaction (CDIS).

BACKGROUND: The aim of this study was to develop and evaluate a brief quantitative five-language measure of involvement and satisfaction in clinical decision-making (CDIS) - with versions for patients (CDIS-P) and staff (CDIS-S) - for use in mental health services. METHODS: An English CDIS was developed by reviewing existing measures, focus groups, semistructured interviews and piloting. Translations into Danish, German, Hungarian and Italian followed the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Task Force principles of good practice for translation and cultural adaptation. Psychometricevaluation involved testing the measure in secondary mental health services in Aalborg, Debrecen, London, Naples, Ulm and Zurich. RESULTS: After appraising 14 measures, the Control Preference Scale and Satisfaction With Decision-making English-language scales were modified and evaluated in interviews (n = 9), focus groups (n = 22) and piloting (n = 16). Translations were validated through focus groups (n = 38) and piloting (n = 61). A total of 443 service users and 403 paired staff completed CDIS. The Satisfaction sub-scale had internal consistency of 0.89 (0.86-0.89 after item-level deletion) for staff and 0.90 (0.87-0.90) for service users, both continuous and categorical (utility) versions were associated with symptomatology and both staff-rated and service userrated therapeutic alliance (showing convergent validity), and not with social disability (showing divergent validity), and satisfaction predicted staff-rated (OR 2.43, 95%CI 1.54- 3.83 continuous, OR 5.77, 95%CI 1.90-17.53 utility) and service user-rated (OR 2.21, 95%CI 1.51-3.23 continuous, OR 3.13, 95%CI 1.10-8.94 utility) decision implementation two months later. The Involvement sub-scale had appropriate distribution and no floor or ceiling effects, was associated with stage of recovery, functioning and quality of life (staff only) (showing convergent validity), and not with symptomatology or social disability (showing divergent validity), and staff-rated passive involvement by the service user predicted implementation (OR 3.55, 95%CI 1.53-8.24). Relationships remained after adjusting for clustering by staff. CONCLUSIONS: CDIS demonstrates adequate internal consistency, no evidence of item redundancy, appropriate distribution, and face, content, convergent, divergent and predictive validity. It can be recommended for research and clinical use. CDIS-P and CDIS-S in all 3 five languages can be downloaded at http://www.cedar-net.eu/instruments. TRIAL REGISTRATION: ISRCTN75841675.CEDAR study is funded by a grant from the Seventh Framework Programme (Research Area HEALTH-2007-3.1-4 Improving clinical decision making) of the European Union (Grant no. 223290)

“It’s hard to tell”. The challenges of scoring patients on standardised outcome measures by multidisciplinary teams: a case study of Neurorehabilitation

Background Interest is increasing in the application of standardised outcome measures in clinical practice. Measures designed for use in research may not be sufficiently precise to be used in monitoring individual patients. However, little is known about how clinicians and in particular, multidisciplinary teams, score patients using these measures. This paper explores the challenges faced by multidisciplinary teams in allocating scores on standardised outcome measures in clinical practice. Methods Qualitative case study of an inpatient neurorehabilitation team who routinely collected standardised outcome measures on their patients. Data were collected using non participant observation, fieldnotes and tape recordings of 16 multidisciplinary team meetings during which the measures were recited and scored. Eleven clinicians from a range of different professions were also interviewed. Data were analysed used grounded theory techniques. Results We identified a number of instances where scoring the patient was 'problematic'. In 'problematic' scoring, the scores were uncertain and subject to revision and adjustment. They sometimes required negotiation to agree on a shared understanding of concepts to be measured and the guidelines for scoring. Several factors gave rise to this problematic scoring. Team members' knowledge about patients' problems changed over time so that initial scores had to be revised or dismissed, creating an impression of deterioration when none had occurred. Patients had complex problems which could not easily be distinguished from each other and patients themselves varied in their ability to perform tasks over time and across different settings. Team members from different professions worked with patients in different ways and had different perspectives on patients' problems. This was particularly an issue in the scoring of concepts such as anxiety, depression, orientation, social integration and cognitive problems. Conclusion From a psychometric perspective these problems would raise questions about the validity, reliability and responsiveness of the scores. However, from a clinical perspective, such characteristics are an inherent part of clinical judgement and reasoning. It is important to highlight the challenges faced by multidisciplinary teams in scoring patients on standardised outcome measures but it would be unwarranted to conclude that such challenges imply that these measures should not be used in clinical practice for decision making about individual patients. However, our findings do raise some concerns about the use of such measures for performance management

Digital payments adoption research: A meta-analysis for generalising the effects of attitude, cost, innovativeness, mobility and price value on behavioural intention

yesThe rapid evolution of mobile-based technologies and applications has led to the development of several different forms of digital payment methods (DPMs) but with limited enthusiasm in consumers for adopting them. Hence, several academic studies have already been conducted to examine the role of various antecedents that determines consumers’ intention to adopt DPMs. The degree of effect and significance of several antecedents found to be inconsistent across different studies. This provided us a basis for undertaking a meta-analysis of existing research for estimating the cumulative effect of such antecedents. Therefore, this study aims to perform a meta-analysis of five antecedents (i.e. attitude, cost, mobility, price value and innovativeness) for confirming their overall influence on intentions to adopt DPMs. The results of this study suggest that the cumulative effect of four out of five antecedents found to be significant while influence of price value was found insignificant on behavioural intentions. The recommendations drawn from this research would help to decide if and when to use such antecedents for predicting consumer intention to adopt DPMs

Analysis of national data shows mixed evidence of hardening among Australian smokers

Objective : According to the hardening hypothesis, the proportion of smokers that are low-probability quitters will increase as societal disapproval of smoking increases. This paper examines whether there has been increased hardening in Australian smokers over the past decade as reflected in an increased prevalence of psychological distress and social disadvantage among current smokers. Methods: The relationship between psychological distress, living in a disadvantaged area and level of education was determined using logistic regression at two time points 7 to 10 years apart in three cross-sectional household survey series: National Drug Strategy Household Survey (NDSHS), National Health Survey (NHS) and National Survey of Mental Health and Well-being (NSMHW). Results: The relationships between smoking and living in the most disadvantaged areas and having completed less than 12 years of schooling strengthened between 2001 and 2010 in the NDSHS, but there were no significant changes between survey years in the NHS and NSMHW. There was no significant change in the relationship between smoking and psychological distress between survey years in any of the survey series. Conclusion: Social disadvantage may be increasing among current smokers, but the results were inconsistent between survey series, presenting weak evidence that the population of Australian smokers hardened as smoking prevalence declined by approximately 4% over the last decade. Implications: A greater focus on intensive individual-level tobacco cessation interventions does not appear warranted at this time

Short-Term Exercise Training Inconsistently Influences Basel Testosterone in Older Men: A Systematic Review and Meta-Analysis

Background The age-associated decrease in testosterone is one mechanism suggested to accelerate the aging process in males. Therefore, approaches to increase endogenous testosterone may be of benefit. The aim of this paper was to undertake a Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-accordant meta-analysis concerning the effect of exercise on total (TT), bioavailable (bio-T), free (free-T), and salivary (sal-T) testosterone in older males. Methods Databases were searched up to and including 20th February 2018 for the terms ‘testosterone AND exercise AND aging AND males’, ‘testosterone AND exercise AND old AND males’, ‘testosterone AND training AND aging AND males’ and ‘testosterone AND training AND old AND males’. From 1259 originally identified titles, 22 studies (randomized controlled trials; RCTs; n=9, and uncontrolled trials; UCTs; n=13) were included which had a training component, participants ≥60 years of age, and salivary or serum testosterone as an outcome measure. Meta-analyses were conducted on change to testosterone following training using standardised difference in means (SDM) and random effects models. Results The overall SDM for endurance training, resistance training, and interval training was 0.398 (95% CI = 0.034 – 0.761; P = 0.010), -0.003 (95% CI = -0.330 – 0.324; P = 0.986), and 0.283 (95% CI = 0.030 – 0.535; P = 0.028) respectively. Resistance training exhibited a qualitative effect of hormone fraction whereby free-T resulted in the greatest SDM (0.253; 95% CI = -0.043 – 0.549; P = 0.094), followed by TT (0.028; 95% CI = -0.204 – 0.260; P = 0.813), and resistance training negatively influenced bio-T (-0.373; 95% CI = -0.789 – 0.042; P = 0.078). Due to the small number of studies, subgroup analysis was not possible for endurance training and interval training studies. Conclusions Data from the present investigation suggests that resistance training does not significantly influence basal testosterone in older men. Magnitude of effect was influenced by hormone fraction, even within the same investigation. Aerobic training and interval training did result in small, significant increases in basal testosterone. The magnitude of effect is small but the existing data are encouraging and may be an avenue for further research

The Main Belt Comets and ice in the Solar System

We review the evidence for buried ice in the asteroid belt; specifically the questions around the so-called Main Belt Comets (MBCs). We summarise the evidence for water throughout the Solar System, and describe the various methods for detecting it, including remote sensing from ultraviolet to radio wavelengths. We review progress in the first decade of study of MBCs, including observations, modelling of ice survival, and discussion on their origins. We then look at which methods will likely be most effective for further progress, including the key challenge of direct detection of (escaping) water in these bodies