Bevacizumab for metachronous metastatic colorectal cancer: A reflection of community based practice

Background: Although the efficacy of bevacizumab has been established in patients with metastatic colorectal cancer (mCRC), population-based studies are needed to gain insight into the actual implementation of bevacizumab in daily practice. Since these studies are lacking for patients with metachronous metastases, the aim of this study is to evaluate the current role of bevacizumab in the treatment of metachronous metastases of CRC. Methods: Data on the use of bevacizumab as palliative treatment of metachronous metastases were collected for patients diagnosed with M0 CRC between 2003 and 2008 in the Eindhoven Cancer Registry (n = 361). Median follow up was 5.3years. Results: One hundred eighty-five patients received bevacizumab in addition to first-line palliative chemotherapy (51%), ranging from 36% to 80% between hospitals of diagnosis (p < 0.0001). Combined cytostatic regimens (CAPOX/FOLFOX in 97%) were prescribed in the majority of patients (63%) and were associated with a higher odds for additional treatment with bevacizumab than single-agent cytostatic regimens (OR 9.9, 95% CI 5.51-18.00). Median overall survival (OS) rates were 21.6 and 13.9months with and without the addition of bevacizumab to palliative systemic treatment respectively (p < 0.0001). The addition of bevacizumab to palliative chemotherapy was associated with a reduced hazard ratio for death (HR 0.6, 95% CI 0.45-0.73) after adjustment for patient- and tumor characteristics and the prescribed chemotherapeutic regimen. Conclusion: Bevacizumab is adopted as a therapeutic option for metachronous metastasized CRC mainly in addition to first-line oxaliplatin-based regimens, and was associated with a reduced risk of death. The presence of inter-hospital differences in the prescription of bevacizumab reflected important differences in attitude and policies in clinical practice. Ongoing efforts should be made to further define the position of targeted agents in the treatment of metastatic colorectal cancer

Las políticas arancelarias aplicadas en el ecuador como medida de protección de la balanza de pagos

El presente proyecto de tesis fue realizado tomando en cuenta q a finales del 2008 en medio de una crisis económica mundial, como registran datos de la Organización Mundial del Comercio (OMC), el volumen del comercio global registró una contracción del 12.2% y es considerado el descenso económico más fuerte desde la Segunda Guerra Mundial, y cuando las cuentas del País con el resto del mundo estaban disminuyendo, el Gobierno Nacional tomó la decisión de levantar una barrera arancelaria a las importaciones

Determination of the prebiotic activity of wheat arabinogalactan peptide (AGP) using batch culture fermentation

Purpose To test the prebiotic activity of wheat arabinogalactan-peptide (AGP), which is a soluble dietary fibre composed of arabinogalactan polysaccharide linked to a 15-residue peptide, which accounts for up to 0.4% of the dry weight of wheat flour. Methods The prebiotic activity of AGP prepared from white wheat flour was tested using in-vitro fermentation by colonic bacteria in automated pH controlled anaerobic stirred batch cultures and compared to fructooligosaccharide (FOS) and wheat flour arabinoxylan (AX). Bacterial populations were measured using fluorescence in-situ hybridisation (flow-FISH) and short-chain fatty acid (SCFA) concentrations were measured using HPLC. Results Fermentation of AGP resulted in a significant bifidogenic activity and increased concentrations of SCFAs, mainly acetate after 24 h of fermentation. Conclusions These results were comparable to those obtained with AX and confirm the prebiotic potential of AGP. Furthermore, fermentation of a mixture of AGP and AX was faster compared to the single substrates and more similar to FOS, indicating that combinations of fermentable carbohydrates with different structures are potentially more effective as prebiotics than single substrates

Assessing the Effects of Time Budget and Traffic Density with the Help of a Trajectory-Planning Method

In"?tex id="Q1" staff-cmt="As per style “The Nertherlands” in country name should not contain, hence we ignored the authors corrections. Please check and confirm."?" highly automated driving, the driver can engage in a nondriving task but sometimes has to take over control. We argue that current takeover quality measures, such as the maximum longitudinal acceleration, are insufficient because they ignore the criticality of the scenario. This paper proposes a novel method of quantifying how well the driver executed an automation-to-manual takeover by comparing human behaviour to optimised behaviour as computed using a trajectory planner. A human-in-the-loop study was carried out in a high-fidelity 6-DOF driving simulator with 25 participants. The takeover required a lane change to avoid roadworks on the ego-lane while taking other traffic into consideration. Each participant encountered six different takeover scenarios, with a different time budget (5 s, 7 s, or 20 s) and traffic density level (low or medium). Results showed that drivers exhibited a considerably higher longitudinal and lateral acceleration than the optimised behaviour, especially in the short time budget scenarios. In scenarios of medium traffic density, the trajectory planner showed a moderate deceleration to let a vehicle in the left lane pass; many participants, on the other hand, did not decelerate before making a lane change, resulting in a dangerous emergency brake of the left-lane vehicle. In conclusion, our results illustrate the value of assessing human takeover behaviour relative to optimised behaviour. Using the trajectory planner, we showed that human drivers are unable to behave optimally in urgent scenarios and that, in some conditions, a medium deceleration, as opposed to a maximal or minimal deceleration, is optimal. Document type: Articl

Importancia de la intervención psicológica en el proceso de recuperación en deportistas tras una lesión.

El trabajo de investigación se centró en el análisis y comprensión de la importancia en la intervención psicológica dentro del proceso de aceptación y posterior recuperación del deportista donde de acuerdo con la personalidad de la persona, las reacciones que pueden tener diferentes personas están vinculadas con las habilidades emocionales para enfrentar eventos fuertes de alto impacto psicológico, esto junto con técnicas de intervención psicológica de modelos previamente estudiados. Todo esto se pudo analizar dentro de los tres primeros capítulos de este trabajo para comprender el correcto proceso de apoyo por parte de profesionales de la psicología deportiva y la orientación del deportista hacia la meta de trabajar, entrenar y conseguir la victoria sobre un evento deportivo, el cual es el principal punto de inflexión y eje de concentración, por ende, la interrupción de esta meta por una lesión de leve o grave magnitud podría causar un malestar emocional, pues dependiendo de la lesión, el tiempo de recuperación puede ser de semana o meses si requiere de una operación, por lo que en aquel punto, la intervención psicológica es de vital importancia para apoyar al deportista con que permitan al lesionado visibilizar aspectos positivos del suceso, aceptar el proceso, fortalecer sus habilidades psicológicas y comprender el error en la aplicación de su técnica o estrategia deportiva. En contexto, la ausencia de la intervención psicológica dentro del proceso de recuperación puede tener consecuencias complejas de recuperación emocional enfrentándose a la depresión, ansiedad o angustia.The research work is focused on the analysis and understanding of the importance of psychological intervention within the process of acceptance and subsequent recovery of the athlete where, according to the personality of the person, the reactions that different people may have been linked to the abilities. emotional to face strong events of high psychological impact, this together with techniques of psychological intervention of previously studied models. All this can be analyzed within the first three chapters of this work to understand the correct support process by sports psychology professionals and the orientation of the athlete towards the goal of working, training and achieving victory over a sporting event. . , which is the main turning point and axis of concentration, therefore, the interruption of this goal due to a minor or serious injury could cause emotional discomfort, because depending on the injury, the recovery time can be of a week. or months if it requires an operation, so at that point, psychological intervention is of vital importance to support the athlete so that it allows the injured person to see positive aspects of the event, accept the process, strengthen their psychological abilities and understand the error in the application of his technique or sports strategy. In context, the absence of psychological intervention within the recovery process can have complex consequences for emotional recovery when dealing with depression, anxiety or anguish

Effect of alternative dosing strategies of pembrolizumab and nivolumab on health-care emissions in the Netherlands:a carbon footprint analysis

Background: Hospitals contribute substantially to greenhouse gas emissions and face a moral obligation to prioritise emission reduction. Drugs constitute an important component of the greenhouse gas emissions of hospitals. Alternative dosing strategies (ADS) have been implemented to improve the cost-effectiveness of pembrolizumab and nivolumab. However, the impact of these ADS on greenhouse gas emissions remains unknown. Therefore, we aimed to analyse the effect of ADS implementation on the carbon emissions of treatment with pembrolizumab and nivolumab. Methods: We used a process-based lifecycle assessment to quantify the environmental impact of pembrolizumab and nivolumab, focused on equivalent carbon dioxide emissions (CO2e). Lifecycle inventory and impact data from Erasmus University Medical Center (Rotterdam, Netherlands) were used to calculate the CO2e for pembrolizumab and nivolumab, their dosing intervals, and the impact of ADS on CO2e. The functional unit of the study was the administration of a single dose of pembrolizumab or nivolumab. Findings: In 2022, the annual carbon emissions related to pembrolizumab and nivolumab treatment in the Erasmus University Medical Center were 445 tons of CO2e, averaging 94 kg of CO2e per dose. Pharmaceutical production was the main driver of treatment-related carbon emissions (mean 92·9% of total emissions). Applying ADS resulted in 21–26% and 9–11% CO2e reductions for pembrolizumab and nivolumab, respectively. Interpretation: This study shows the environmental impact of pembrolizumab and nivolumab treatment and calls for further implementation of ADS for pembrolizumab, nivolumab, and other anti-PD-(L)1 monoclonal antibodies, and more sustainable pharmaceutical production processes. Our findings create environmental awareness and contribute to the promotion and understanding of health-care practices with lower carbon emissions. </p

How Does the Preparation of Rye Porridge Affect Molecular Weight Distribution of Extractable Dietary Fibers?

Extractable dietary fiber (DF) plays an important role in nutrition. This study on porridge making with whole grain rye investigated the effect of rest time of flour slurries at room temperature before cooking and amount of flour and salt in the recipe on the content of DF components and molecular weight distribution of extractable fructan, mixed linkage (1→3)(1→4)-β-d-glucan (β-glucan) and arabinoxylan (AX) in the porridge. The content of total DF was increased (from about 20% to 23% of dry matter) during porridge making due to formation of insoluble resistant starch. A small but significant increase in the extractability of β-glucan (P = 0.016) and AX (P = 0.002) due to rest time was also noted. The molecular weight of extractable fructan and AX remained stable during porridge making. However, incubation of the rye flour slurries at increased temperature resulted in a significant decrease in extractable AX molecular weight. The molecular weight of extractable β-glucan decreased greatly during a rest time before cooking, most likely by the action of endogenous enzymes. The amount of salt and flour used in the recipe had small but significant effects on the molecular weight of β-glucan. These results show that whole grain rye porridge made without a rest time before cooking contains extractable DF components maintaining high molecular weights. High molecular weight is most likely of nutritional importance

Improvements in population-based survival of patients presenting with metastatic rectal cancer in the south of the Netherlands, 1992–2008

We analysed population-based treatment and survival data of patients who presented with metastatic rectal cancer. All patients diagnosed with primary synchronous metastatic rectal cancer between 1992 and 2008 in the Eindhoven Cancer Registry area were included. Date of diagnosis was divided into three periods (1992–1999, 2000–2004, 2005–2008) according to the availability of chemotherapy type. We assessed treatment patterns and overall survival according to period of diagnosis. The proportion of patients diagnosed with stage IV disease increased from 16% in 1992–1999 to 20% in 2005–2008 (P < 0.0001). Chemotherapy use increased from 5% in 1992 to 61% in 2008 (P < 0.0001). Resection rates of the primary tumour decreased from 65% in 1992 to 27% in 2008 (P < 0.0001), while metastasectomy rates remained constant since 1999 (9%). Median survival increased from 38 weeks (95% confidence interval (CI) 32–44) in 1992–1999 to 53 weeks (95% CI 48–61) in 2005–2008. Among patients not receiving chemotherapy median survival remained approximately 30 weeks. Multivariable analysis confirmed the lower risk of death among patients diagnosed in more recent years. Increased use of chemotherapy went together with improved median survival among patients with metastatic rectal cancer in the last two decades. Stage migration as an effect of more effective imaging procedures is likely to be partly responsible for this improved survival