Comparison of the Hemostatic Efficacy of Pathogen-Reduced Platelets vs Untreated Platelets in Patients With Thrombocytopenia and Malignant Hematologic Diseases: A Randomized Clinical Trial

Importance: Pathogen reduction of platelet concentrates may reduce transfusion-transmitted infections but is associated with qualitative impairment, which could have clinical significance with regard to platelet hemostatic capacity. Objective: To compare the effectiveness of platelets in additive solution treated with amotosalen-UV-A vs untreated platelets in plasma or in additive solution in patients with thrombocytopenia and hematologic malignancies. Design, Setting, and Participants: The Evaluation of the Efficacy of Platelets Treated With Pathogen Reduction Process (EFFIPAP) study was a randomized, noninferiority, 3-arm clinical trial performed from May 16, 2013, through January 21, 2016, at 13 French tertiary university hospitals. Clinical signs of bleeding were assessed daily until the end of aplasia, transfer to another department, need for a specific platelet product, or 30 days after enrollment. Consecutive adult patients with bone marrow aplasia, expected hospital stay of more than 10 days, and expected need of platelet transfusions were included. Interventions: At least 1 transfusion of platelets in additive solution with amotosalen-UV-A treatment, in plasma, or in additive solution. Main Outcomes and Measures: The proportion of patients with grade 2 or higher bleeding as defined by World Health Organization criteria. Results: Among 790 evaluable patients (mean [SD] age, 55 [13.4] years; 458 men [58.0%]), the primary end point was observed in 126 receiving pathogen-reduced platelets in additive solution (47.9%; 95% CI, 41.9%-54.0%), 114 receiving platelets in plasma (43.5%; 95% CI, 37.5%-49.5%), and 120 receiving platelets in additive solution (45.3%; 95% CI, 39.3%-51.3%). With a per-protocol population with a prespecified margin of 12.5%, noninferiority was not achieved when pathogen-reduced platelets in additive solution were compared with platelets in plasma (4.4%; 95% CI, -4.1% to 12.9%) but was achieved when the pathogen-reduced platelets were compared with platelets in additive solution (2.6%; 95% CI, -5.9% to 11.1%). The proportion of patients with grade 3 or 4 bleeding was not different among treatment arms. Conclusions and Relevance: Although the hemostatic efficacy of pathogen-reduced platelets in thrombopenic patients with hematologic malignancies was noninferior to platelets in additive solution, such noninferiority was not achieved when comparing pathogen-reduced platelets with platelets in plasma. Trial Registration: clinicaltrials.gov Identifier: NCT01789762

Fungal infection-related mortality versus total mortality as an outcome in trials of antifungal agents

BACKGROUND: Disease specific mortality is often used as outcome rather than total mortality in clinical trials. This approach assumes that the classification of cause of death is unbiased. We explored whether use of fungal infection-related mortality as outcome rather than total mortality leads to bias in trials of antifungal agents in cancer patients. METHODS: As an estimate of bias we used relative risk of death in those patients the authors considered had not died from fungal infection. Our sample consisted of 69 trials included in four systematic reviews of prophylactic or empirical antifungal treatment in patients with cancer and neutropenia we have published previously. RESULTS: Thirty trials met the inclusion criteria. The trials comprised 6130 patients and 869 deaths, 220 (25%) of which were ascribed to fungal infection. The relative risk of death was 0.85 (95% CI 0.75–0.96) for total mortality, 0.57 (95% CI 0.44–0.74) for fungal mortality, and 0.95 (95% CI 0.82–1.09) for mortality among those who did not die from fungal infection. CONCLUSION: We could not support the hypothesis that use of disease specific mortality introduces bias in antifungal trials on cancer patients as our estimate of the relative risk for mortality in those who survived the fungal infection was not increased. We conclude that it seems to be reliable to use fungal mortality as the primary outcome in trials of antifungal agents. Data on total mortality should be reported as well, however, to guard against the possible introduction of harmful treatments

Interaction between Coastal and Oceanic Ecosystems of the Western and Central Pacific Ocean through Predator-Prey Relationship Studies

The Western and Central Pacific Ocean sustains the highest tuna production in the world. This province is also characterized by many islands and a complex bathymetry that induces specific current circulation patterns with the potential to create a high degree of interaction between coastal and oceanic ecosystems. Based on a large dataset of oceanic predator stomach contents, our study used generalized linear models to explore the coastal-oceanic system interaction by analyzing predator-prey relationship. We show that reef organisms are a frequent prey of oceanic predators. Predator species such as albacore (Thunnus alalunga) and yellowfin tuna (Thunnus albacares) frequently consume reef prey with higher probability of consumption closer to land and in the western part of the Pacific Ocean. For surface-caught-predators consuming reef prey, this prey type represents about one third of the diet of predators smaller than 50 cm. The proportion decreases with increasing fish size. For predators caught at depth and consuming reef prey, the proportion varies with predator species but generally represents less than 10%. The annual consumption of reef prey by the yellowfin tuna population was estimated at 0.8±0.40CV million tonnes or 2.17×1012±0.40CV individuals. This represents 6.1%±0.17CV in weight of their diet. Our analyses identify some of the patterns of coastal-oceanic ecosystem interactions at a large scale and provides an estimate of annual consumption of reef prey by oceanic predators

Exome sequencing identifies germline variants in DIS3 in familial multiple myeloma

[Excerpt] Multiple myeloma (MM) is the third most common hematological malignancy, after Non-Hodgkin Lymphoma and Leukemia. MM is generally preceded by Monoclonal Gammopathy of Undetermined Significance (MGUS) [1], and epidemiological studies have identified older age, male gender, family history, and MGUS as risk factors for developing MM [2]. The somatic mutational landscape of sporadic MM has been increasingly investigated, aiming to identify recurrent genetic events involved in myelomagenesis. Whole exome and whole genome sequencing studies have shown that MM is a genetically heterogeneous disease that evolves through accumulation of both clonal and subclonal driver mutations [3] and identified recurrently somatically mutated genes, including KRAS, NRAS, FAM46C, TP53, DIS3, BRAF, TRAF3, CYLD, RB1 and PRDM1 [3,4,5]. Despite the fact that family-based studies have provided data consistent with an inherited genetic susceptibility to MM compatible with Mendelian transmission [6], the molecular basis of inherited MM predisposition is only partly understood. Genome-Wide Association (GWAS) studies have identified and validated 23 loci significantly associated with an increased risk of developing MM that explain ~16% of heritability [7] and only a subset of familial cases are thought to have a polygenic background [8]. Recent studies have identified rare germline variants predisposing to MM in KDM1A [9], ARID1A and USP45 [10], and the implementation of next-generation sequencing technology will allow the characterization of more such rare variants. [...]French National Cancer Institute (INCA) and the Fondation Française pour la Recherche contre le Myélome et les Gammapathies (FFMRG), the Intergroupe Francophone du Myélome (IFM), NCI R01 NCI CA167824 and a generous donation from Matthew Bell. This work was supported in part through the computational resources and staff expertise provided by Scientific Computing at the Icahn School of Medicine at Mount Sinai. Research reported in this paper was supported by the Office of Research Infrastructure of the National Institutes of Health under award number S10OD018522. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors thank the Association des Malades du Myélome Multiple (AF3M) for their continued support and participation. Where authors are identified as personnel of the International Agency for Research on Cancer / World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer / World Health Organizatio

Geolocation with respect to persona privacy for the Allergy Diary app - a MASK study

Background: Collecting data on the localization of users is a key issue for the MASK (Mobile Airways Sentinel network: the Allergy Diary) App. Data anonymization is a method of sanitization for privacy. The European Commission's Article 29 Working Party stated that geolocation information is personal data. To assess geolocation using the MASK method and to compare two anonymization methods in the MASK database to find an optimal privacy method. Methods: Geolocation was studied for all people who used the Allergy Diary App from December 2015 to November 2017 and who reported medical outcomes. Two different anonymization methods have been evaluated: Noise addition (randomization) and k-anonymity (generalization). Results: Ninety-three thousand one hundred and sixteen days of VAS were collected from 8535 users and 54,500 (58. 5%) were geolocalized, corresponding to 5428 users. Noise addition was found to be less accurate than k-anonymity using MASK data to protect the users' life privacy. Discussion: k-anonymity is an acceptable method for the anonymization of MASK data and results can be used for other databases.Peer reviewe

Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018) : Change management in allergic rhinitis and asthma multimorbidity using mobile technology

Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.Peer reviewe

Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018): Change management in allergic rhinitis and asthma multimorbidity using mobile technology

Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional

Pelvic fracture in multiple trauma: A 67-case series

International audienceIntroduction: Severe pelvic trauma remains associated with elevated mortality, largely due to hemorrhagic shock. Objective: The main study objective was to test for correlation between fracture type and mortality. The secondary objective was to assess the efficacy in terms of mortality of multidisciplinary management following a decision-tree in multiple trauma victims admitted to a level 1 trauma center. Material and methods: Between July 2011 and July 2013, 534 severe trauma patients were included in a single-center continuous prospective observational study. All patients with hemorrhagic shock received early treatment by pelvic binder. Patients with active bleeding on full-body CT or persisting hemorrhagic shock underwent arteriography with or without embolization. Pelvic trauma was graded on the Tile classification. The principle end-point was mortality. Results: Median age was 40 years (range, 26-48 years), with a 79% male/female sex ratio. Thirty-two of the 67 patients with pelvic trauma (48%) were in hemorrhagic shock at admission. Median injury severity score (ISS) was 36 (range, 24-43). On the Tile classification, 22 patients (33%) were grade A, 33 (49%) grade B and 12 (18%) grade C. Overall mortality was 19%, and 42% in case of hemorrhagic shock. Mortality was significantly higher with Tile C than A or B (58% vs. 9.1% and 12.1%, respectively; P = 0.001). Conclusion: Vertical shear fracture (Tile C) was associated with greater mortality from hemorrhagic shock. (C) 2016 Elsevier Masson SAS. All rights reserved