Best practice in undertaking and reporting health technology assessments : Working Group 4 report

[Executive Summary] The aim of Working Group 4 has been to develop and disseminate best practice in undertaking and reporting assessments, and to identify needs for methodologic development. Health technology assessment (HTA) is a multidisciplinary activity that systematically examines the technical performance, safety, clinical efficacy, and effectiveness, cost, costeffectiveness, organizational implications, social consequences, legal, and ethical considerations of the application of a health technology (18). HTA activity has been continuously increasing over the last few years. Numerous HTA agencies and other institutions (termed in this report “HTA doers”) across Europe are producing an important and growing amount of HTA information. The objectives of HTA vary considerably between HTA agencies and other actors, from a strictly political decision making–oriented approach regarding advice on market licensure, coverage in benefits catalogue, or investment planning to information directed to providers or to the public. Although there seems to be broad agreement on the general elements that belong to the HTA process, and although HTA doers in Europe use similar principles (41), this is often difficult to see because of differences in language and terminology. In addition, the reporting of the findings from the assessments differs considerably. This reduces comparability and makes it difficult for those undertaking HTA assessments to integrate previous findings from other HTA doers in a subsequent evaluation of the same technology. Transparent and clear reporting is an important step toward disseminating the findings of a HTA; thus, standards that ensure high quality reporting may contribute to a wider dissemination of results. The EUR-ASSESS methodologic subgroup already proposed a framework for conducting and reporting HTA (18), which served as the basis for the current working group. New developments in the last 5 years necessitate revisiting that framework and providing a solid structure for future updates. Giving due attention to these methodologic developments, this report describes the current “best practice” in both undertaking and reporting HTA and identifies the needs for methodologic development. It concludes with specific recommendations and tools for implementing them, e.g., by providing the structure for English-language scientific summary reports and a checklist to assess the methodologic and reporting quality of HTA reports

Traitement du PTI et de l’AHAI au cours du DICV : revue systématique de la littérature

INTRODUCTION: Ten to 15% of common variable immunodeficiencies (CVID) develop auto-immune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). Treatment is based on immunosuppressants, which produce blocking effects in the CVID. Our objective was to assess their risk-benefit ratio in these immunocompromised patients. METHODS: We identified 17 articles detailing the treatment of AIHA and/or ITP in patients suffering from CVID through a systematic review of the MEDLINE database. RESULTS: The increased infectious risk with corticosteroids does not call into question their place in the first line of treatment of ITP and AIHA in CVID. High-doses immunoglobulin therapy remain reserved for ITP with a high risk of bleeding. In second-line treatment, rituximab appears to be effective, with a lower infectious risk than the splenectomy. Immunosuppressants (azathioprine, methotrexate, mycophenolate, cyclophosphamide, vincristine, ciclosporine) are moderately effective and often lead to severe infections, meaning that their use is justified only in resistant cases and steroid-sparing. Dapsone, danazol and anti-D immunoglobulins have an unfavorable risk-benefit ratio. The place of TPO receptor agonists is still to be defined. The establishment of immunoglobulin replacement in the place of immunosuppressants (except for short-term corticotherapy) or splenectomy appears to be essential to limit the risk of infections, including in the absence of previous infections. CONCLUSION: The presence of CVID does not mean that it is necessary to give up on corticosteroids as a first-line treatment and rituximab as a second-line treatment for AIHA and ITP, but it should be in addition to immunoglobulin replacement. A splenectomy should be reserved as a third-line treatment

Characterizations of how species mediate ecosystem properties require more comprehensive functional effect descriptors

The importance of individual species in mediating ecosystem process and functioning is generally accepted, but categorical descriptors that summarize species-specific contributions to ecosystems tend to reference a limited number of biological traits and underestimate the importance of how organisms interact with their environment. Here, we show how three functionally contrasting sediment-dwelling marine invertebrates affect fluid and particle transport - important processes in mediating nutrient cycling - and use high-resolution reconstructions of burrow geometry to determine the extent and nature of biogenic modification. We find that individual functional effect descriptors fall short of being able to adequately characterize how species mediate the stocks and flows of important ecosystem properties and that, in contrary to common practice and understanding, they are not substitutable with one another because they emphasize different aspects of species activity and behavior. When information derived from these metrics is combined with knowledge of how species behave and modify their environment, however, detailed mechanistic information emerges that increases the likelihood that a species functional standing will be appropriately summarized. Our study provides evidence that more comprehensive functional effect descriptors are required if they are to be of value to those tasked with projecting how altered biodiversity will influence future ecosystems

VarGoats project: a dataset of 1159 whole-genome sequences to dissect Capra hircus global diversity

Background: Since their domestication 10,500 years ago, goat populations with distinctive genetic backgrounds have adapted to a broad variety of environments and breeding conditions. The VarGoats project is an international 1000-genome resequencing program designed to understand the consequences of domestication and breeding on the genetic diversity of domestic goats and to elucidate how speciation and hybridization have modeled the genomes of a set of species representative of the genus Capra. Findings: A dataset comprising 652 sequenced goats and 507 public goat sequences, including 35 animals representing eight wild species, has been collected worldwide. We identified 74,274,427 single nucleotide polymorphisms (SNPs) and 13,607,850 insertion-deletions (InDels) by aligning these sequences to the latest version of the goat reference genome (ARS1). A Neighbor-joining tree based on Reynolds genetic distances showed that goats from Africa, Asia and Europe tend to group into independent clusters. Because goat breeds from Oceania and Caribbean (Creole) all derive from imported animals, they are distributed along the tree according to their ancestral geographic origin. Conclusions: We report on an unprecedented international effort to characterize the genome-wide diversity of domestic goats. This large range of sequenced individuals represents a unique opportunity to ascertain how the demographic and selection processes associated with post-domestication history have shaped the diversity of this species. Data generated for the project will also be extremely useful to identify deleterious mutations and polymorphisms with causal effects on complex traits, and thus will contribute to new knowledge that could be used in genomic prediction and genome-wide association studies

Organism-sediment interactions govern post-hypoxia recovery of ecosystem functioning

Hypoxia represents one of the major causes of biodiversity and ecosystem functioning loss for coastal waters. Since eutrophication-induced hypoxic events are becoming increasingly frequent and intense, understanding the response of ecosystems to hypoxia is of primary importance to understand and predict the stability of ecosystem functioning. Such ecological stability may greatly depend on the recovery patterns of communities and the return time of the system properties associated to these patterns. Here, we have examined how the reassembly of a benthic community contributed to the recovery of ecosystem functioning following experimentally-induced hypoxia in a tidal flat. We demonstrate that organism-sediment interactions that depend on organism size and relate to mobility traits and sediment reworking capacities are generally more important than recovering species richness to set the return time of the measured sediment processes and properties. Specifically, increasing macrofauna bioturbation potential during community reassembly significantly contributed to the recovery of sediment processes and properties such as denitrification, bedload sediment transport, primary production and deep pore water ammonium concentration. Such bioturbation potential was due to the replacement of the small-sized organisms that recolonised at early stages by large-sized bioturbating organisms, which had a disproportionately stronger influence on sediment. This study suggests that the complete recovery of organism-sediment interactions is a necessary condition for ecosystem functioning recovery, and that such process requires long periods after disturbance due to the slow growth of juveniles into adult stages involved in these interactions. Consequently, repeated episodes of disturbance at intervals smaller than the time needed for the system to fully recover organism-sediment interactions may greatly impair the resilience of ecosystem functioning.

Ecosystem services provided by a non-cultured shellfish species: the common cockle Cerastoderma edule

Coastal habitats provide many important ecosystem services. The substantial role of shellfish in delivering ecosystem services is increasingly recognised, usually with a focus on cultured species, but wild-harvested bivalve species have largely been ignored. This study aimed to collate evidence and data to demonstrate the substantial role played by Europe's main wild-harvested bivalve species, the common cockle Cerastoderma edule, and to assess the ecosystem services that cockles provide. Data and information are synthesised from five countries along the Atlantic European coast with a long history of cockle fisheries. The cockle helps to modify habitat and support biodiversity, and plays a key role in the supporting services on which many of the other services depend. As well as providing food for people, cockles remove nitrogen, phosphorus and carbon from the marine environment, and have a strong cultural influence in these countries along the Atlantic coast. Preliminary economic valuation of some of these services in a European context is provided, and key knowledge gaps identified. It is concluded that the cockle has the potential to become (i) an important focus of conservation and improved sustainable management practices in coastal areas and communities, and (ii) a suitable model species to study the integration of cultural ecosystem services within the broader application of ‘ecosystem services’

Monomeric Ti(IV)-based complexes incorporating luminescent nitrogen ligands: synthesis, structural characterization, emission spectroscopy and cytotoxic activities

This manuscript describes the synthesis of a series of neutral titanium(IV) monomeric complexes constructed around a TiO4N2 core. The two nitrogen atoms that compose the coordination sphere of the metallic center belong to 2,2′-bipyrimidine ligands homo-disubstituted in the 4 and 4′ positions by methyl (2a), phenylvinyl (2b), naphthylvinyl (2c) or anthrylvinyl (2d) groups. The crystal structures of these complexes named [Ti(1)2(2a)], [Ti(1)2(2b)], [Ti(1)2(2c)] and [Ti(1)2(2d)] (where 1 is a 2,2′-biphenolato ligand substituted in the 6 and 6′ positions by phenyl groups) are reported. The hydrolytic stability of the four complexes is evaluated by monitoring the evolution of the free 2a–d signals by 1H NMR spectroscopy. For the conditions tested (6 mM, DMSO-d6/D2O: 8/1), a rather good stability with t1/2 ranging from 180 to 300 min is determined for the complexes. In the presence of an acid (DCl), the hydrolysis of [Ti(1)2(2a)] is faster than without an acid. The cytotoxic activity against gastric cancer cells of the titanium-based compounds and the free disubstituted 2,2′-bipyrimidine ligands is tested, showing IC50 ranging from 6.2 ± 1.2 μM to 274 ± 56 μM. The fluorescence studies of the ligands 2a–d, and the complexes [Ti(1)2(2a–d)] reveal an important fluorescence loss of the ligands 2c and 2d upon coordination with the Ti(1)2 fragment. Frontier orbitals obtained by DFT calculations permit us to explain this fluorescence quenching.Other supports : Centre National pour la Recherche Scientifique (CNRS, France), ARC, Ligue contre le Cancer, European action COST CM1105 (C. G.

Impact of front line relative dose intensity for methotrexate and comorbidities in immunocompetent elderly patients with primary central nervous system lymphoma

Primary central nervous system lymphomas (PCNSL) are non-Hodgkin lymphomas strictly localized to the CNS, occurring mainly in elderly patients with comorbidities. Current treatment in fit patients relies on high-dose methotrexate and high-dose cytarabine. The aim of this study was to evaluate the efficacy and feasibility of this treatment in elderly patients and to assess potential prognostic factors associated with survival. We conducted a retrospective study in two centers between January 2008 and September 2015 including 35 elderly immunocompetent patients who received first-line treatment with high-dose methotrexate. With a median follow-up of 19.8 months (range: 1.7-73.4 months), median overall survival (OS) was 39.5 months (95% confidence interval (95% CI): 18.3-60.7) and median progression-free survival (PFS) was 25.8 months (95% CI: 5.2-46.4). In univariate analysis, administration of high-dose cytarabine and achieving a relative dose intensity for methotrexate > 75% were associated with increased OS (p = 0.006 and p = 0.003, respectively) and PFS (p = 0.003 and p = 0.04, respectively) whereas comorbidities, defined by a CIRS-G score ≥ 8, were associated with decreased OS and PFS (p = 0.02 and p = 0.04, respectively). A high MSKCC score was associated with decreased OS (p = 0.02). In multivariate analysis, administration of high-dose cytarabine was associated with increased OS and PFS (p = 0.02 and p = 0.007, respectively). Comorbidities and relative dose intensity for methotrexate are important for the prognosis of elderly patients with PCNSL. These results must be confirmed in prospective trials