The use of erythropoiesis-stimulating agents with ruxolitinib in patients with myelofibrosis in COMFORT-II: an open-label, phase 3 study assessing efficacy and safety of ruxolitinib versus best available therapy in the treatment of myelofibrosis

BACKGROUND: Anemia is considered a negative prognostic risk factor for survival in patients with myelofibrosis. Most patients with myelofibrosis are anemic, and 35-54 % present with anemia at diagnosis. Ruxolitinib, a potent inhibitor of Janus kinase (JAK) 1 and JAK2, was associated with an overall survival benefit and improvements in splenomegaly and patient-reported outcomes in patients with myelofibrosis in the two phase 3 COMFORT studies. Consistent with the ruxolitinib mechanism of action, anemia was a frequently reported adverse event. In clinical practice, anemia is sometimes managed with erythropoiesis-stimulating agents (ESAs). This post hoc analysis evaluated the safety and efficacy of concomitant ruxolitinib and ESA administration in patients enrolled in COMFORT-II, an open-label, phase 3 study comparing the efficacy and safety of ruxolitinib with best available therapy for treatment of myelofibrosis. Patients were randomized (2:1) to receive ruxolitinib 15 or 20 mg twice daily or best available therapy. Spleen volume was assessed by magnetic resonance imaging or computed tomography scan.

RESULTS: Thirteen of 146 ruxolitinib-treated patients had concomitant ESA administration (+ESA). The median exposure to ruxolitinib was 114 weeks in the +ESA group and 111 weeks in the overall ruxolitinib arm; the median ruxolitinib dose intensity was 33 mg/day for each group. Six weeks before the first ESA administration, 10 of the 13 patients had grade 3/4 hemoglobin abnormalities. These had improved to grade 2 in 7 of the 13 patients by 6 weeks after the first ESA administration. The rate of packed red blood cell transfusions per month within 12 weeks before and after first ESA administration remained the same in 1 patient, decreased in 2 patients, and increased in 3 patients; 7 patients remained transfusion independent. Reductions in splenomegaly were observed in 69 % of evaluable patients (9/13) following first ESA administration.

CONCLUSIONS: Concomitant use of an ESA with ruxolitinib was well tolerated and did not affect the efficacy of ruxolitinib. Further investigations evaluating the effects of ESAs to alleviate anemia in ruxolitinib-treated patients are warranted (ClinicalTrials.gov identifier, NCT00934544; July 6, 2009).

The Monetary Value Of Meat Authenticity And Food Safety In Ready To Heat Lasagne: Implications Of The ‘Horse Meat Scandal’ Across Europe

The recent ‘horse meat scandal’ in Europe has sparked huge concerns among consumers, as horse meat was found in beef lasagne ready to be consumed. Within STARTEC, a European funded project, this study investigates consumers’ preferences, attitudes and willingness to pay (WTP) towards characteristics of ready to heat (RTH) fresh lasagne, including origin of the meat, tested for meat authenticity, safety of the lasagne, and nutritional value, using Discrete Choice Experiments in six countries - Republic of Ireland, France, Italy, Spain, Germany and Norway. Our representative sample of 4,598 European consumers makes this the largest cross country study of this kind. The questionnaire was administered online in January 2014. Results from models in WTP-space show that, on average, consumers are willing to pay considerable amount (about €4-9) for food authenticity; on this Irish and Italian are the least concerned while Spanish are the most concerned. As expected from discussing with stakeholders, food safety claims and nutritional value of the RTH lasagne are relatively less important. Consumers also value knowing the origin of ingredients preferring locally sourced meat. Primarily, the results of this study present strong evidence that consumers in Europe are highly concerned about authenticity of the meat in ready meals and strongly prefer to know that the meat is national. This evidence suggests that there is great value in providing information on these attributes, both from a consumer perspective and where this leads to an increased consumer confidence has benefits for the food industry.

Impacts of Milk Fraud on Food Safety and Nutrition with Special Emphasis on Developing Countries

Milk in its natural form has a high food value, since it is comprised of a wide variety of nutrients which are essential for proper growth and maintenance of the human body. In recent decades, there has been an upsurge in milk consumption worldwide, especially in developing countries, and it is now forming a significant part of the diet for a high proportion of the global population. As a result of the increased demand, in addition to the growth in competition in the dairy market and the increasing complexity of the supply chain, some unscrupulous producers are indulging in milk fraud. This malpractice has become a common problem in the developing countries, which lack strict vigilance by food safety authorities. Milk is often subjected to fraud (by means of adulteration) for financial gain, but it can also be adulterated due to ill-informed attempts to improve hygiene conditions. Water is the most common adulterant used, which decreases the nutritional value of milk. If the water is contaminated, for example, with chemicals or pathogens, this poses a serious health risk for consumers. To the diluted milk, inferior cheaper materials may be added such as reconstituted milk powder, urea, and cane sugar, even more hazardous chemicals including melamine, formalin, caustic soda, and detergents. These additions have the potential to cause serious health-related problems. This review aims to investigate the impacts of milk fraud on nutrition and food safety, and it points out the potential adverse human health effects associated with the consumption of adulterated milk.

Cognition, metacognition and patient safety

This article explores the factors that contribute to patient safety incidents. It highlights the importance of human factors in influencing the clinician's performance. Rather than focusing on clinical skills, the article explores the range of non-technical skills which are seen to each contribute to patient safety, including: communication, teamworking, leadership, active followership, situational awareness, decision-making, assertiveness, and workload management. It asks how cognitive processes can influence safe decision-making.

Potential impacts of climate change on agriculture and food safety within the island of Ireland

Climate and other environmental change presents a number of challenges for effective food safety. Food production, distribution and consumption takes place within functioning ecosystems but this backdrop is often ignored or treated as static and unchanging. The risks presented by environmental change include novel pests and diseases, often caused by problem species expanding their spatial distributions as they track changing conditions, toxin generation in crops, direct effects on crop and animal production, consequences for trade networks driven by shifting economic viability of production methods in changing environments and finally, wholesale transformation of ecosystems as they respond to novel climatic regimes.

A Reappraisal of the Safety and Cost-Effectiveness of Statin Therapy in Primary Prevention

Statins are among the most investigated drugs of all time. There is now a wealth of evidence supporting their use in the primary and secondary prevention arenas. The reduction in event recurrence has since been demonstrated across all levels of risk and in elderly patients. As a result, it is now accepted practice for statins to be prescribed universally in secondary prevention unless contraindicated. The extension of this policy into the primary prevention setting is more problematic, with moral and financial issues arising from the long-term treatment of many young apparently healthy individuals. For these reasons it is necessary to prove not only the financial sustainability of such a strategy but also the long-term safety of statins and the degree of benefit that might be expected.

Food Colours: Existing and Emerging Food Safety Concerns

Food colours are added to different types of commodities to increase their visual attractiveness or to compensate for natural colour variations. The use of these additives is strictly regulated in the European Union, the United States and many other countries worldwide. There is a growing concern about the safety of some commonly used legal food colourants and there is a trend to replace the synthetic forms with natural products. Additionally, a number of dyes with known or suspected genotoxic or carcinogenic properties have been shown to be added illegally to foods. Robust monitoring programs based on reliable detection methods are required to assure the food is free from harmful colours. The aim of this review is to present an up to date status of the various concerns arising from use of colour additives in food. The most important food safety concerns in the field of food colours are lack of uniform regulation concerning legal food colours worldwide, possible link of artificial colours to hyperactive behaviour, replacement of synthetic colours with natural ones and the presence of harmful illegal dyes - both known but also new, emerging ones in food. The legal status of food colour additives in the EU, US and worldwide is summarized. The reported negative health effects of both legal and illegal colours are presented. The European Rapid Alert System for Food and Feed notifications and US import alerts concerning food colours are analyzed and trends in fraudulent use of colour additives identified. The detection methods for synthetic colours are also reviewed.