"We Want to Talk about Death, Dying and Grief and to Learn about End-of-Life Care"-Lessons Learned from a Multi-Center Mixed-Methods Study on Last Aid Courses for Kids and Teens.

BACKGROUND: Last Aid Courses (LAC) for adults have been established in 21 countries in Europe, Australia and America to improve the public discussion about death and dying and to empower people to participate in end-of-life care provision. In 2018, the first Last Aid Courses for kids and teens (LAC-KT) were introduced. The aim of the study was to explore the views and experiences of the course participants and Last Aid Course instructors on the LAC-KT. METHODS: A mixed-methods approach was used. The views of the LAC-KT participants, aged 7 to 17 years, on the LAC-KT were collected using a questionnaire. In addition, the experiences of the Last Aid Course instructors were explored in focus group interviews. RESULTS: The results show that 84% of the participants had experiences with death and dying and 91% found the LAC-KT helpful for everyone. The majority of the participants appreciate the opportunity to talk and learn about death, dying, grief and palliative care. CONCLUSIONS: The LAC-KT is feasible, very well accepted and a welcome opportunity for exchanging and obtaining information about dying, grief and palliative care. The findings of the study indicate that the LAC-KT should be offered to all interested children and teenagers and included in the school curriculum.

Towards personalized medicine by mathematical modeling of tumors.

In this open letter, we give some insights on the potential use of mathematical modeling in understanding cancer research. The article is written in a form that can be understood by a larger public, not only by specialists.

[Mathematical and computational methods to model chemotherapy- induced resistance]. / Matematikai és számítógépes módszerek a kemoterápiás kezelések során kialakuló rezisztencia modellezésére.

Chemotherapy plays an important role in the treatment of cancer. While clinical chemotherapy protocols can lead to remission in some patients, in many cases tumor progression occurs despite continued treatment. In the present study we summarize mathematical approaches to model tumor growth and response to treatment, focusing on anticancer therapy resistance. We present results obtained at the recently founded Cybermedical Competence Center at Óbuda University, focusing on the development of a new therapy optimization concept that aims to optimize traditional chemotherapy.

Impact of reduction of tinnitus intensity on patients' quality of life.

OBJECTIVE: Assess the impact of a reduction of tinnitus intensity achieved through sound stimulation during sleep on the improvement in the patients' quality of life. DESIGN: Acoustic stimuli consisted of a highly customized sound that reproduced the spectral and intensity characteristics of the tinnitus in each patient. This stimulus was uploaded into a portable electronic device and delivered through customized ear buds during sleep, every night for three months. STUDY SAMPLE: Twelve patients with subjective idiopathic chronic tinnitus were studied. RESULTS: Results were assessed through: (1) the measurement in dB SPL of tinnitus intensity reduction over time; (2) the results of three psychometric tests: Tinnitus handicap inventory (THI), Tinnitus reaction questionnaire (TRQ), Tinnitus functional index (TFI); and (3) a Visual analog scale (VAS) for tinnitus annoyance. After three months of treatment, we observed an average decrease in tinnitus intensity of 14.1 dB SPL (p < 0.001), implying a 62% reduction of the perceived sound. This improvement was followed by a statistically significant decrease of TRQ (78%), THI (65%), and TFI (77%). CONCLUSIONS: These results suggested that the intensity reduction achieved through the protocol used in this study had a direct impact on the improvement in the patients' quality of life.

Tumor Volume Estimation and Quasi-Continuous Administration for Most Effective Bevacizumab Therapy.

BACKGROUND: Bevacizumab is an exogenous inhibitor which inhibits the biological activity of human VEGF. Several studies have investigated the effectiveness of bevacizumab therapy according to different cancer types but these days there is an intense debate on its utility. We have investigated different methods to find the best tumor volume estimation since it creates the possibility for precise and effective drug administration with a much lower dose than in the protocol. MATERIALS AND METHODS: We have examined C38 mouse colon adenocarcinoma and HT-29 human colorectal adenocarcinoma. In both cases, three groups were compared in the experiments. The first group did not receive therapy, the second group received one 200 µg bevacizumab dose for a treatment period (protocol-based therapy), and the third group received 1.1 µg bevacizumab every day (quasi-continuous therapy). Tumor volume measurement was performed by digital caliper and small animal MRI. The mathematical relationship between MRI-measured tumor volume and mass was investigated to estimate accurate tumor volume using caliper-measured data. A two-dimensional mathematical model was applied for tumor volume evaluation, and tumor- and therapy-specific constants were calculated for the three different groups. The effectiveness of bevacizumab administration was examined by statistical analysis. RESULTS: In the case of C38 adenocarcinoma, protocol-based treatment did not result in significantly smaller tumor volume compared to the no treatment group; however, there was a significant difference between untreated mice and mice who received quasi-continuous therapy (p = 0.002). In the case of HT-29 adenocarcinoma, the daily treatment with one-twelfth total dose resulted in significantly smaller tumors than the protocol-based treatment (p = 0.038). When the tumor has a symmetrical, solid closed shape (typically without treatment), volume can be evaluated accurately from caliper-measured data with the applied two-dimensional mathematical model. CONCLUSION: Our results provide a theoretical background for a much more effective bevacizumab treatment using optimized administration.

Model-based angiogenic inhibition of tumor growth using modern robust control method.

Cancer is one of the most destructive and lethal illnesses of the modern civilization. In the last decades, clinical cancer research shifted toward molecular targeted therapies which have limited side effects in comparison to conventional chemotherapy and radiation therapy. Antiangiogenic therapy is one of the most promising cancer treatment methods. The dynamical model for tumor growth under angiogenic stimulator/inhibitor control was posed by Hahnfeldt et al. in 1999; it was investigated and partly modified many times. In this paper, a modified version of the originally published model is used to describe a continuous infusion therapy. In order to generalize individualized therapies a robust control method is proposed using H(∞) methodology. Uncertainty weighting functions are determined based on the real pathophysiological case and simulations are performed on different tumor volumes to demonstrate the robustness of the proposed method.

Cochlear microphonic changes after noise exposure and gentamicin administration during sleep and waking.

These experiments were designed to investigate the effect of noise, sleep, and gentamicin on the cochlear microphonic (CM) of the guinea pigs. Are the changes observed due to intrinsic cochlear phenomena or to efferent system actions? To answer this question, noise exposure together with efferent system blockade by gentamicin administration was performed. In the normal (non-treated) animal, noise exposure decreased both variability and amplitude of the tone evoked CM in about the first 10 min while the physiological modulation of slow wave sleep increasing the CM is not present. Following administration of gentamicin, noise no longer affect the CM in about the first 10 min, although it produces amplitude and variability increments. The influence of slow wave sleep on the CM is not altered. Thus, gentamicin does not block the CM sleep/wakefulness related shifts. The data were discussed in terms of the influence of gentamicin on the olivo-cochlear bundle. It was hypothesized that the effects of noise on the CM is a result of both peripheral and central influences.