Treatment of initial parenchymal central nervous system involvement in systemic aggressive B-cell lymphoma

Central nervous system (CNS) involvement in systemic B-cell non-Hodgkin lymphoma (B-NHL) at diagnosis (sysCNS) is rare. We investigated the outcome of 21 patients with sysCNS, most commonly diffuse large B-cell lymphoma, treated with high dose methotrexate (HD-MTX) and R-CHOP. The median number of cycles of HD-MTX and R-CHOP was 4 (range 1–8) and 6 (range 0–8), respectively. Consolidative whole brain radiotherapy (WBRT) was given to 33% (7/21) patients. With a median follow-up of 44 months the 3-year progression free survival (PFS) and overall survival (OS) were 45% (95%CI 34–56%) and 49% (95%CI 38–60%), respectively. Over 90% of patients had an unfavorable international prognostic index score, reflected by treatment-related mortality of 19% (4/21) and relapse-related mortality of 28% (6/21). The outcome of these patients was, however, unexpectedly good when compared to secondary CNS relapses. Prospective studies are needed to define the optimal treatment for patients with sysCNS, but its rarity might be challenging

Interim thymus and activation regulated chemokine versus interim F-18-fluorodeoxyglucose positron-emission tomography in classical Hodgkin lymphoma response evaluation

Serum thymus and activation regulated chemokine (TARC) levels reflect classical Hodgkin lymphoma (cHL) disease activity and correspond with treatment response. We compared mid-treatment interim TARC (iTARC) with interim 18 F-fluorodeoxyglucose positron-emission tomography (iPET) imaging to predict modified progression-free survival (mPFS) in a group of 95 patients with cHL. High iTARC levels were found in nine and positive iPET in 17 patients. The positive predictive value (PPV) of iTARC for a 5-year mPFS event was 88% compared to 47% for iPET. The negative predictive value was comparable at 86% for iTARC and 85% for iPET. Serum iTARC levels more accurately reflect treatment response with a higher PPV compared to iPET

Disentangling the domestic contract : understanding the everyday-life construction of acceptability -or non-acceptability- of keeping and killing animals for food

When we were children learning the names of animals, farm utensils and food products from picture books, talking about farming animals and related food products appeared simple. However, the intricate realities of modern-day farming practices differ momentously from this primary reference - the picture books. The topic brings about polarized responses, both rationally and emotionally, reflecting very diverse outlooks on the world. This dissertation reports on a research, set in the Netherlands and Turkey, that was designed to improve our understanding of the everyday-life construction of the acceptability -or non-acceptability- ofkeeping and killing animals for food, or in other words: to disentangle the domestic contract

The Pedigree Dog Breeding Debate in Ethics and Practice : Beyond Welfare Arguments

Pedigree dog breeding has been the subject of public debate due to health problems caused by breeding for extreme looks and the narrow genepool of many breeds. Our research aims to provide insights in order to further the animal-ethical, political and society-wide discussion regarding the future of pedigree dog breeding in the Netherlands. Guided by the question ‘How far are we allowed to interfere in the genetic make-up of dogs, through breeding and genetic modification?’, we carried out a multi-method case-driven research, reviewing literature as well as identifying the perceptions of pedigree dog breeding of a variety of parties in the Netherlands. We examined what moral arguments and concepts different stakeholders, including breeders, veterinarians and animal protection societies, put forward when considering this question. While welfare arguments were often used as a final justification, we also frequently encountered arguments beyond welfare in practice, in particular the arguments that certain adaptations were unnatural, that they instrumentalised animals, or that they amounted to playing God. We argue that the way these arguments are employed points to a virtue ethical approach, foregrounding the virtue of temperance, as a balance between extreme positions was sought by our respondents in a variety of ways. Moreover, we argue against a rejection of unnaturalness arguments based on the naturalistic fallacy, as philosophers tend to do. We point out that unnaturalness arguments are related to people’s worldviews, including views on the proper human–animal relationship. We argue that such arguments, which we label ‘life-ethical’, should be the subject of more public discussion and should not be relegated to the private sphere

What is careful livestock farming? Substantiating the layered meaning of the term ‘careful’ and drawing implications for the stakeholder dialogue

Modern livestock farming systems typically stand out in terms of production efficiency and chain integration. However, the legitimacy of animal production systems is currently being questioned, due to social and ecological concerns. The term ‘careful’ livestock farming has been coined to reflect a production system that addresses this broader range of concerns. In this paper we argue that although the term ‘careful’ provides a useful starting point to bind together a diversity of concerns that require further attention, it lacks action-ability unless its meaning is further substantiated. Such substantiation is important to provide more concrete action perspectives both in relation to consumers as well as the diverse group of other stakeholders involved. First, the term careful is analysed from the perspectives of consumer psychology, ethics, and organizational science, showing a high level of agreement on the underlying dynamics and layers of the concept. The resulting insights are integrated into a pragmatic map with social and temporal dimensions, combined with three basic questions: (1) what levels of psychological distance are taken into consideration when designing farming practices? (2), what are the concrete farming system/product features and their benefits?, and (3) how are the benefits distributed over the levels of psychological distance? The map and questions help to substantiate the different meanings of ‘careful’ when used in relation to animal production. We conclude with exploring actions for achieving careful livestock farming and argue that delineating and articulating concrete meanings of the term is a condition for reflection and strategy formulation in multi-stakeholder dialogues

What is careful livestock farming? Substantiating the layered meaning of the term ‘careful’ and drawing implications for the stakeholder dialogue

Modern livestock farming systems typically stand out in terms of production efficiency and chain integration. However, the legitimacy of animal production systems is currently being questioned, due to social and ecological concerns. The term ‘careful’ livestock farming has been coined to reflect a production system that addresses this broader range of concerns. In this paper we argue that although the term ‘careful’ provides a useful starting point to bind together a diversity of concerns that require further attention, it lacks action-ability unless its meaning is further substantiated. Such substantiation is important to provide more concrete action perspectives both in relation to consumers as well as the diverse group of other stakeholders involved. First, the term careful is analysed from the perspectives of consumer psychology, ethics, and organizational science, showing a high level of agreement on the underlying dynamics and layers of the concept. The resulting insights are integrated into a pragmatic map with social and temporal dimensions, combined with three basic questions: (1) what levels of psychological distance are taken into consideration when designing farming practices? (2), what are the concrete farming system/product features and their benefits?, and (3) how are the benefits distributed over the levels of psychological distance? The map and questions help to substantiate the different meanings of ‘careful’ when used in relation to animal production. We conclude with exploring actions for achieving careful livestock farming and argue that delineating and articulating concrete meanings of the term is a condition for reflection and strategy formulation in multi-stakeholder dialogues

Exploring the framing of animal farming and meat consumption : On the diversity of topics used and qualitative patterns in selected demographic contexts

In various contexts, people talk about animal farming andmeat consumption using different arguments to construct and justify their (non-)acceptability. This article presents the results of an in-depth qualitative inquiry into the content of and contextual patterns in the everyday-life framing regarding this issue, performed among consumers in various settings in two extremes in the European sphere: The Netherlands and Turkey. We describe themethodological steps of collecting, coding, and organizing the variety of encountered framing topics, as well as our search for symbolic convergence in groups of consumers from different selected demographic contexts (country, urban-rural areas, gender, age, and education level). The framing of animal farming and meat consumption in everyday-life is not a simple one-issue rational display of facts, people referred to a vast range of topics in the categories knowledge, convictions, pronounced behaviour, values, norms, interests, and feelings. Looking at framing in relation to the researched demographic contexts, most patterns were found on the level of topics, symbolic convergence in lines of reasoning and composite framing was less prominent in groups based on single demographic contexts than anticipated. An explanation for this lies in the complexity of frame construction, happening in relation withmultiple interdependent contextual features

Pharmacokinetics and Tolerability of a Higher Rifampin Dose versus the Standard Dose in Pulmonary Tuberculosis Patients▿

Rifampin is a key drug for tuberculosis (TB) treatment. The available data suggest that the currently applied 10-mg/kg of body weight dose of rifampin may be too low and that increasing the dose may shorten the treatment duration. A double-blind randomized phase II clinical trial was performed to investigate the effect of a higher dose of rifampin in terms of pharmacokinetics and tolerability. Fifty newly diagnosed adult Indonesian TB patients were randomized to receive a standard (450-mg, i.e., 10-mg/kg in Indonesian patients) or higher (600-mg) dose of rifampin in addition to other TB drugs. A full pharmacokinetic curve for rifampin, pyrazinamide, and ethambutol was recorded after 6 weeks of daily TB treatment. Tolerability was assessed during the 6-month treatment period. The geometric means of exposure to rifampin (area under the concentration-time curve from 0 to 24 h [AUC0-24]) were increased by 65% (P < 0.001) in the higher-dose group (79.7 mg·h/liter) compared to the standard-dose group (48.5 mg·h/liter). Maximum rifampin concentrations (Cmax) were 15.6 mg/liter versus 10.5 mg/liter (49% increase; P < 0.001). The percentage of patients for whom the rifampin Cmax was ≥8 mg/liter was 96% versus 79% (P = 0.094). The pharmacokinetics of pyrazinamide and ethambutol were similar in both groups. Mild (grade 1 or 2) hepatotoxicity was more common in the higher-dose group (46 versus 20%; P = 0.054), but no patient developed severe hepatotoxicity. Increasing the rifampin dose was associated with a more than dose-proportional increase in the mean AUC0-24 and Cmax of rifampin without affecting the incidence of serious adverse effects. Follow-up studies are warranted to assess whether high-dose rifampin may enable shortening of TB treatment