Intravenous iron or placebo for anaemia in intensive care: the IRONMAN multicentre randomized blinded trial. A randomized trial of IV iron in critical illness

PURPOSE: Both anaemia and allogenic red blood cell transfusion are common and potentially harmful in patients admitted to the intensive care unit. Whilst intravenous iron may decrease anaemia and RBC transfusion requirement, the safety and efficacy of administering iron intravenously to critically ill patients is uncertain. METHODS: The multicentre, randomized, placebo-controlled, blinded Intravenous Iron or Placebo for Anaemia in Intensive Care (IRONMAN) study was designed to test the hypothesis that, in anaemic critically ill patients admitted to the intensive care unit, early administration of intravenous iron, compared with placebo, reduces allogeneic red blood cell transfusion during hospital stay and increases the haemoglobin level at the time of hospital discharge. RESULTS: Of 140 patients enrolled, 70 were assigned to intravenous iron and 70 to placebo. The iron group received 97 red blood cell units versus 136 red blood cell units in the placebo group, yielding an incidence rate ratio of 0.71 [95 % confidence interval (0.43-1.18), P = 0.19]. Overall, median haemoglobin at hospital discharge was significantly higher in the intravenous iron group than in the placebo group [107 (interquartile ratio IQR 97-115) vs. 100 g/L (IQR 89-111), P = 0.02]. There was no significant difference between the groups in any safety outcome. CONCLUSIONS: In patients admitted to the intensive care unit who were anaemic, intravenous iron, compared with placebo, did not result in a significant lowering of red blood cell transfusion requirement during hospital stay. Patients who received intravenous iron had a significantly higher haemoglobin concentration at hospital discharge. The trial was registered at http://www.anzctr.org.au as # ACTRN12612001249842

Non-beneficial pediatric research : individual and social interests

Biomedical research involving human subjects is an arena of conflicts of interests. One of the most important conflicts is between interests of participants and interests of future patients. Legal regulations and ethical guidelines are instruments designed to help find a fair balance between risks and burdens taken by research subjects and development of knowledge and new treatment. There is an universally accepted ethical principle, which states that it is not ethically allowed to sacrifice individual interests for the sake of society and science. This is the principle of precedence of individual. But there is a problem with how to interpret the principle of precedence of individual in the context of research without prospect of future benefit involving children. There are proposals trying to reconcile non-beneficial research involving children with the concept of the best interests. We assert that this reconciliation is flawed and propose an interpretation of the principle of precedence of individual as follows: not all, but only the most important interests of participants, must be guaranteed; this principle should be interpreted as the secure participant standard. In consequence, the issue of permissible risk ceiling becomes ethically crucial in research with incompetent subjects

Triple-negative breast cancers are increased in black women regardless of age or body mass index

INTRODUCTION. We investigated clinical and pathologic features of breast cancers (BC) in an unselected series of patients diagnosed in a tertiary care hospital serving a diverse population. We focused on triple-negative (Tneg) tumours (oestrogen receptor (ER), progesterone receptor (PR) and HER2 negative), which are associated with poor prognosis. METHODS. We identified female patients with invasive BC diagnosed between 1998 and 2006, with data available on tumor grade, stage, ER, PR and HER2 status, and patient age, body mass index (BMI) and self-identified racial/ethnic group. We determined associations between patient and tumour characteristics using contingency tables and multivariate logistic regression. RESULTS. 415 cases were identified. Patients were racially and ethnically diverse (born in 44 countries, 36% white, 43% black, 10% Hispanic and 11% other). 47% were obese (BMI > 30 kg/m2). 72% of tumours were ER+ and/or PR+, 20% were Tneg and 13% were HER2+. The odds of having a Tneg tumour were 3-fold higher (95% CI 1.6, 5.5; p = 0.0001) in black compared with white women. Tneg tumours were equally common in black women diagnosed before and after age 50 (31% vs 29%; p = NS), and who were obese and non-obese (29% vs 31%; p = NS). Considering all patients, as BMI increased, the proportion of Tneg tumours decreased (p = 0.08). CONCLUSIONS. Black women of diverse background have 3-fold more Tneg tumours than non-black women, regardless of age and BMI. Other factors must determine tumour subtype. The higher prevalence of Tneg tumours in black women in all age and weight categories likely contributes to black women's unfavorable breast cancer prognosis.LaPann Fund; Research Enhancement Fun

Realizing the promise of population biobanks: a new model for translation

The promise of science lies in expectations of its benefits to societies and is matched by expectations of the realisation of the significant public investment in that science. In this paper, we undertake a methodological analysis of the science of biobanking and a sociological analysis of translational research in relation to biobanking. Part of global and local endeavours to translate raw biomedical evidence into practice, biobanks aim to provide a platform for generating new scientific knowledge to inform development of new policies, systems and interventions to enhance the public’s health. Effectively translating scientific knowledge into routine practice, however, involves more than good science. Although biobanks undoubtedly provide a fundamental resource for both clinical and public health practice, their potentiating ontology—that their outputs are perpetually a promise of scientific knowledge generation—renders translation rather less straightforward than drug discovery and treatment implementation. Biobanking science, therefore, provides a perfect counterpoint against which to test the bounds of translational research. We argue that translational research is a contextual and cumulative process: one that is necessarily dynamic and interactive and involves multiple actors. We propose a new multidimensional model of translational research which enables us to imagine a new paradigm: one that takes us from bench to bedside to backyard and beyond, that is, attentive to the social and political context of translational science, and is cognisant of all the players in that process be they researchers, health professionals, policy makers, industry representatives, members of the public or research participants, amongst others

Breast cancer in young women

Although uncommon, breast cancer in young women is worthy of special attention due to the unique and complex issues that are raised. This article reviews specific challenges associated with the care of younger breast cancer patients, which include fertility preservation, management of inherited breast cancer syndromes, maintenance of bone health, secondary prevention, and attention to psychosocial issues

Model selection in historical research using approximate Bayesian computation

Formal Models and History Computational models are increasingly being used to study historical dynamics. This new trend, which could be named Model-Based History, makes use of recently published datasets and innovative quantitative methods to improve our understanding of past societies based on their written sources. The extensive use of formal models allows historians to reevaluate hypotheses formulated decades ago and still subject to debate due to the lack of an adequate quantitative framework. The initiative has the potential to transform the discipline if it solves the challenges posed by the study of historical dynamics. These difficulties are based on the complexities of modelling social interaction, and the methodological issues raised by the evaluation of formal models against data with low sample size, high variance and strong fragmentation. This work examines an alternate approach to this evaluation based on a Bayesian-inspired model selection method. The validity of the classical Lanchester's laws of combat is examined against a dataset comprising over a thousand battles spanning 300 years. Four variations of the basic equations are discussed, including the three most common formulations (linear, squared, and logarithmic) and a new variant introducing fatigue. Approximate Bayesian Computation is then used to infer both parameter values and model selection via Bayes Factors. Results indicate decisive evidence favouring the new fatigue model. The interpretation of both parameter estimations and model selection provides new insights into the factors guiding the evolution of warfare. At a methodological level, the case study shows how model selection methods can be used to guide historical research through the comparison between existing hypotheses and empirical evidence.Funding for this work was provided by the SimulPast Consolider Ingenio project (CSD2010-00034) of the former Ministry for Science and Innovation of the Spanish Government and the European Research Council Advanced Grant EPNet (340828).Peer ReviewedPostprint (published version