Tryptophan and Non-Tryptophan Fluorescence of the Eye Lens Proteins Provides Diagnostics of Cataract at the Molecular Level

The chemical nature of the non-tryptophan (non-Trp) fluorescence of porcine and human eye lens proteins was identified by Mass Spectrometry (MS) and Fluorescence Steady-State and Lifetime spectroscopy as post-translational modifications (PTM) of Trp and Arg amino acid residues. Fluorescence intensity profiles measured along the optical axis of human eye lenses with age-related nuclear cataract showed increasing concentration of fluorescent PTM towards the lens centre in accord with the increased optical density in the lens nucleolus. Significant differences between fluorescence lifetimes of “free” Trp derivatives hydroxytryptophan (OH-Trp), N-formylkynurenine (NFK), kynurenine (Kyn), hydroxykynurenine (OH-Kyn) and their residues were observed. Notably, the lifetime constants of these residues in a model peptide were considerably greater than those of their “free” counterparts. Fluorescence of Trp, its derivatives and argpyrimidine (ArgP) can be excited at the red edge of the Trp absorption band which allows normalisation of the emission spectra of these PTMs to the fluorescence intensity of Trp, to determine semi-quantitatively their concentration. We show that the cumulative fraction of OH-Trp, NFK and ArgP emission dominates the total fluorescence spectrum in both emulsified post-surgical human cataract protein samples, as well as in whole lenses and that this correlates strongly with cataract grade and age

Understanding and using comparative healthcare information; the effect of the amount of information and consumer characteristics and skills

<p>Abstract</p> <p>Background</p> <p>Consumers are increasingly exposed to comparative healthcare information (information about the quality of different healthcare providers). Partly because of its complexity, the use of this information has been limited. The objective of this study was to examine how the amount of presented information influences the comprehension and use of comparative healthcare information when important consumer characteristics and skills are taken into account.</p> <p>Methods</p> <p>In this randomized controlled experiment, comparative information on total hip or knee surgery was used as a test case. An online survey was distributed among 800 members of the NIVEL Insurants Panel and 76 hip- or knee surgery patients. Participants were assigned to one of four subgroups, who were shown 3, 7, 11 or 15 quality aspects of three hospitals. We conducted Kruskall-Wallis tests, Chi-square tests and hierarchical multiple linear regression analyses to examine relationships between the amount of information and consumer characteristics and skills (literacy, numeracy, active choice behaviour) on one hand, and outcome measures related to effectively using information (comprehension, perceived usefulness of information, hospital choice, ease of making a choice) on the other hand.</p> <p>Results</p> <p>414 people (47%) participated. Regression analysis showed that the amount of information slightly influenced the comprehension and the perceived usefulness of comparative healthcare information. It did not affect consumers’ hospital choice and ease of making this choice. Consumer characteristics (especially age) and skills (especially literacy) were the most important factors affecting the comprehension of information and the ease of making a hospital choice. For the perceived usefulness of comparative information, active choice behaviour was the most influencing factor.</p> <p>Conclusion</p> <p>The effects of the amount of information were not unambiguous. It remains unclear what the ideal amount of quality information to be presented would be. Reducing the amount of information will probably not automatically result in more effective use of comparative healthcare information by consumers. More important, consumer characteristics and skills appeared to be more influential factors contributing to information comprehension and use. Consequently, we would suggest that more emphasis on improving consumers’ skills is needed to enhance the use of comparative healthcare information.</p

Barriers to ultrasound guidance for central venous access:a survey among Dutch intensivists and anaesthesiologists

\u3cp\u3eAccumulating evidence shows that ultrasound (US) guidance improves effectiveness and safety of central venous catheter (CVC) placement. Several international guidelines therefore recommend the use of US for placement of CVCs. However, surveys show that the landmark-based technique is still widely used, while the percentage of physicians using US is increasing less than expected. The goal of this study was to investigate current practice for central venous catheterization in anaesthesiology and intensive care in the Netherlands, identify barriers for further implementation of US guidance and to evaluate whether personality traits are associated with the choice of technique. We conducted a web-based national survey, distributed among members of the Dutch societies of anaesthesiology (NVA) and intensive care (NVIC). The survey contained questions regarding physician and hospital characteristics, frequency of US use and reasons for use or non-use, as well as the NEO-FFI-3, a validated, translated questionnaire to characterize personality traits according to the ‘Big Five’ concept. Response rate was 22% (506/2291), of which 400 had also the personality questionnaire complete. Ultrasound guidance was used always or almost always in 68%; barriers for US use were working in a non-academic non-teaching hospital, providing cardiac anaesthesia and more years of physician experience. Reasons for not using US were perceived lack of benefit, increased procedure time, lack of US equipment and fear of loss of landmark technique skills. 13% of respondents had never experienced a complication during CVC placement, and 67% knew of a complication occurring the past year at their department. Ultrasound was thought not to be able to prevent the complication in half of these cases. Of the personality traits, only neuroticism and extraversion showed a minor positive association with US guidance. A majority of anaesthesiologists and intensivists uses US guidance for CVC placement, but a significant proportion of physicians still prefers the landmark technique. Most arguments from respondents against US guidance can be challenged. Personality traits most likely do not play a major role in the acceptance of US guidance for central venous catheterization. A potential intervention to increase US use could be formalizing local hospital policies mandating compliance with US guidance. Future research can perhaps focus on cognitive biases that currently limit more widespread use of US guidance.\u3c/p\u3

The predictive value of cumulative toxicity for quality of life in patients with metastatic colorectal cancer during first-line palliative chemotherapy

Claudia SEW Schuurhuizen,1,2 Henk MW Verheul,1 Annemarie MJ Braamse,3 Laurien M Buffart,1&ndash;4 Haiko J Bloemendal,5 Joost Dekker,2,6,* Inge RHM Konings1,* 1Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands; 2Department of Psychiatry, Amsterdam Public Health Research Institute, VU University Medical Center, Amsterdam, The Netherlands; 3Department of Medical Psychology, Academic Medical Center Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands; 4Department of Epidemiology and Biostatistics, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands; 5Department of Medical Oncology, Meander Medical Center, Amersfoort, The Netherlands; 6Department of Rehabilitation Medicine, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands *These authors contributed equally to this work Background: Studies evaluating new systemic agents tend to report severe toxicities only, while the cumulative effect of multiple lower grade adverse events (AEs) may have an additional negative impact on patient quality of life (QOL). In the current observational cohort study, we evaluated whether, in patients with metastatic colorectal cancer receiving first-line chemotherapy, cumulative toxicity comprising all grades of AEs is more predictive for QOL than cumulative toxicity due to only high-grade AEs.Methods: One hundred and five patients starting treatment completed the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) questionnaire at baseline and 10 weeks. AEs, clinical outcomes, and demographics were retrieved from patient records. Cumulative toxicity scores were calculated in three ways: total number of high-grade AEs, total number of all-grade AEs, and total number of AEs multiplied by their grade (the severity score). Relations between cumulative toxicity scores and QOL were studied using multivariable linear regression analyses.Results: The mean age of patients was 65 years, 68% were male, and 84% received oxaliplatin-based chemotherapy. A higher total number of AEs of all grades (B=&minus;2.4, 95% CI=&ndash;3.9; &ndash;0.9) and the severity score (B=&ndash;1.4, 95% CI=&ndash;2.3; &ndash;0.5) were predictive for clinically relevant changes in physical QOL, whereas the total high-grade AEs was not. None of the cumulative toxicity scores were predictive for global QOL.Conclusion: Cumulative toxicity scores comprising all grades of AEs provide a better measure of treatment burden than a toxicity score comprising high-grade AEs only. Physical QOL seems to be more affected by AEs than global QOL. Our results emphasize that future clinical trials should present cumulative toxicity scores comprising all AE grades as well as physical QOL instead of global QOL. Keywords: cumulative toxicity, treatment-related toxicity, adverse events, quality of life, metastatic colorectal cance

Cost-effectiveness analysis of an 18-week exercise programme for patients with breast and colon cancer undergoing adjuvant chemotherapy: the randomised PACT study.

OBJECTIVE: Meta-analyses show that exercise interventions during cancer treatment reduce cancer-related fatigue. However, little is known about the cost-effectiveness of such interventions. Here we aim to assess the cost-effectiveness of the 18-week physical activity during cancer treatment (PACT) intervention for patients with breast and colon cancer. The PACT trial showed beneficial effects for fatigue and physical fitness. DESIGN: Cost-effectiveness analyses with a 9-month time horizon (18 weeks of intervention and 18 weeks of follow-up) within the randomised controlled multicentre PACT study. SETTING: Outpatient clinics of 7 hospitals in the Netherlands (1 academic and 6 general hospitals) PARTICIPANTS: 204 patients with breast cancer and 33 with colon cancer undergoing adjuvant treatment including chemotherapy. INTERVENTION: Supervised 1-hour aerobic and resistance exercise (twice per week for 18 weeks) or usual care. MAIN OUTCOME MEASURES: Costs, quality-adjusted life years (QALY) and the incremental cost-effectiveness ratio. RESULTS: For colon cancer, the cost-effectiveness analysis showed beneficial effects of the exercise intervention with incremental costs savings of €4321 and QALY improvements of 0.03. 100% of bootstrap simulations indicated that the intervention is dominant (ie, cheaper and more effective). For breast cancer, the results did not indicate that the exercise intervention was cost-effective. Incremental costs were €2912, and the incremental effect was 0.01 QALY. At a Dutch threshold value of €20 000 per QALY, the probability that the intervention is cost-effective was 2%. CONCLUSIONS: Our results suggest that the 18-week exercise programme was cost-effective for colon cancer, but not for breast cancer