Quality of care for cancer patients on home parenteral nutrition: Development of key interventions and outcome indicators using a two-round Delphi approach

Purpose: Clear recommendations on how to guide patients with cancer on home parenteral nutrition (HPN) are lacking as the use of HPN in this population remains a controversial issue. Therefore, the aims of this study were to rank treatment recommendations and main outcome indicators to ensure high-quality care and to indicate differences in care concerning benign versus malignant patients. Methods: Treatment recommendations, identified from published guidelines, were used as a starting point for a two-round Delphi approach. Comments and additional interventions proposed in the first round were reevaluated in the second round. Ordinal logistic regression with SPSS 2.0 was used to identify differences in care concerning benign versus malignant patients. Results: Twenty-seven experts from five European countries completed two Delphi rounds. After the second Delphi round, the top three most important outcome indicators were (1) quality of life (QoL), (2) incidence of hospital readmission and (3) incidence of catheter-related infections. Forty-two interventions were considered as important for quality of care (28/42 based on published guidelines; 14/42 newly suggested by Delphi panel). The topics 'Liver disease' and 'Metabolic bone disease' were considered less important for cancer patients, together with use of infusion pumps (p = 0.004) and monitoring of vitamins and trace elements (p = 0.000). Monitoring of QoL is considered more important for cancer patients (p = 0.03). Conclusion: Using a two-round Delphi approach, we developed a minimal set of 42 interventions that may be used to determine quality of care in HPN patients with malignancies. This set of interventions differs from a similar set developed for benign patients. © 2012 Springer-Verlag Berlin Heidelberg.

Is the Species Flock Concept Operational? The Antarctic Shelf Case

There has been a significant body of literature on species flock definition but not so much about practical means to appraise them. We here apply the five criteria of Eastman and McCune for detecting species flocks in four taxonomic components of the benthic fauna of the Antarctic shelf: teleost fishes, crinoids (feather stars), echinoids (sea urchins) and crustacean arthropods. Practical limitations led us to prioritize the three historical criteria (endemicity, monophyly, species richness) over the two ecological ones (ecological diversity and habitat dominance). We propose a new protocol which includes an iterative fine-tuning of the monophyly and endemicity criteria in order to discover unsuspected flocks. As a result nine « full » species flocks (fulfilling the five criteria) are briefly described. Eight other flocks fit the three historical criteria but need to be further investigated from the ecological point of view (here called « core flocks »). The approach also shows that some candidate taxonomic components are no species flocks at all. The present study contradicts the paradigm that marine species flocks are rare. The hypothesis according to which the Antarctic shelf acts as a species flocks generator is supported, and the approach indicates paths for further ecological studies and may serve as a starting point to investigate the processes leading to flock-like patterning of biodiversity. © 2013 Lecointre et al.

Liver-directed lentiviral gene therapy in a dog model of hemophilia B

We investigated the efficacy of liver-directed gene therapy using lentiviral vectors in a large animal model of hemophilia B and evaluated the risk of insertional mutagenesis in tumor-prone mouse models. We showed that gene therapy using lentiviral vectors targeting the expression of a canine factor IX transgene in hepatocytes was well tolerated and provided a stable long-term production of coagulation factor IX in dogs with hemophilia B. By exploiting three different mouse models designed to amplify the consequences of insertional mutagenesis, we showed that no genotoxicity was detected with these lentiviral vectors. Our findings suggest that lentiviral vectors may be an attractive candidate for gene therapy targeted to the liver and may be potentially useful for the treatment of hemophilia.

Genome-wide hydroxymethylcytosine pattern changes in response to oxidative stress

The TET enzymes convert methylcytosine to the newly discovered base hydroxymethylcytosine. While recent reports suggest that TETs may play a role in response to oxidative stress, this role remains uncertain, and results lack in vivo models. Here we show a global decrease of hydroxymethylcytosine in cells treated with buthionine sulfoximine, and in mice depleted for the major antioxidant enzymes GPx1 and 2. Furthermore, genome-wide profiling revealed differentially hydroxymethylated regions in coding genes, and intriguingly in microRNA genes, both involved in response to oxidative stress. These results thus suggest a profound effect of in vivo oxidative stress on the global hydroxymethylome.

Cross-sectional study of 168 patients with hepatorenal tyrosinaemia and implications for clinical practice

Background: Hepatorenal tyrosinaemia (Tyr 1) is a rare inborn error of tyrosine metabolism. Without treatment, patients are at high risk of developing acute liver failure, renal dysfunction and in the long run hepatocellular carcinoma. The aim of our study was to collect cross-sectional data. Methods. Via questionnaires we collected retrospective data of 168 patients with Tyr 1 from 21 centres (Europe, Turkey and Israel) about diagnosis, treatment, monitoring and outcome. In a subsequent consensus workshop, we discussed data and clinical implications. Results: Early treatment by NTBC accompanied by diet is essential to prevent serious complications such as liver failure, hepatocellular carcinoma and renal disease. As patients may remain initially asymptomatic or develop uncharacteristic clinical symptoms in the first months of life newborn mass screening using succinylacetone (SA) as a screening parameter in dried blood is mandatory for early diagnosis. NTBC-treatment has to be combined with natural protein restriction supplemented with essential amino acids. NTBC dosage should be reduced to the minimal dose allowing metabolic control, once daily dosing may be an option in older children and adults in order to increase compliance. Metabolic control is judged by SA (below detection limit) in dried blood or urine, plasma tyrosine (<400 μM) and NTBC-levels in the therapeutic range (20-40 μM). Side effects of NTBC are mild and often transient. Indications for liver transplantation are hepatocellular carcinoma or failure to respond to NTBC. Follow-up procedures should include liver and kidney function tests, tumor markers and imaging, ophthalmological examination, blood count, psychomotor and intelligence testing as well as therapeutic monitoring (SA, tyrosine, NTBC in blood). Conclusion: Based on the data from 21 centres treating 168 patients we were able to characterize current practice and clinical experience in Tyr 1. This information could form the basis for clinical practice recommendations, however further prospective data are required to underpin some of the recommendations.