Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

SEAwise report on the bycatch mortality risk of potentially endangered and threatened species of fish, seabirds, reptiles and mammals

The SEAwise project works to deliver a fully operational tool that will allow fishers, managers, and policy makers to easily apply Ecosystem Based Fisheries Management (EBFM) in their fisheries and bycatch of protected, endangered and threatened (PET) species is a major concern in EBFM implementation. This SEAwise report evaluates the effects of fishing on bycatch of PET species by applying a hierarchical framework that moves from qualitative to quantitative methodologies depending on species vulnerability to bycatch and data availability. By these means, this work identifies current areas of highest bycatch risk across the case studies and assesses the sustainability of bycatch levels on PET populations.The first step of this report consisted of the application of the semi-quantitative Productivity-Susceptibility Analysis (PSA) to a wide range of sensitive species across European waters, including cetaceans, bony and cartilaginous fishes and a single seabird species. PSA measures the risk of a species to over-exploitation by a fishery based on two properties; productivity, defined by the life history characteristics determining the intrinsic rate of population increase, and susceptibility, based on the interactions between population and fishing dynamics. This analysis scores species’ productivity and susceptibility attributes from 1 (low risk) to 3 (high risk) for each fishery or gear of interest, allowing a rapid screening of the species most likely affected by bycatch.Cetaceans were assessed in the Bay of Biscay and Irish waters, and in both cases, gillnets were identified as the gears with the highest bycatch risk, especially for common dolphin (Delphinus delphis) and harbour porpoise (Phocoena phocoena). Cartilaginous fishes were assessed in the Mediterranean Sea, including pelagic species such as the blue shark (Prionace glauca) and demersal species such as the longnose spurgod (Squalus blainville), the bull ray (Aetomylaeus bovinus) and the common smooth-hound (Mustelus mustelus). The blue shark, which is Critically Endangered in the Mediterranean, showed a high risk of being bycaught by pelagic longline, while demersal species were all highly threatened by bottom trawlers. A combination of elasmobranchs and teleost fishes was assessed along the North Sea, Bay of Biscay, and Celtic Seas, including common skate complex (Dipturus spp.), blonde ray (Raja brachyura), spurdog (Squalus acanthias), tope (Galeorhinus galeus), spotted ray (Raja montagui), undulate ray (Raja undulata), starry ray (Amblyraja radiata), John dory (Zeus faber), Atlantic wolffish (Anarhichas lupus) and Atlantic halibut (Hippoglossus hippoglossus). Highest bycatch risk was found for the common skate complex, spurdog and tope, showing highest bycatch risk for both beam- and otter trawls, as well as gillnets. The only seabird species analysed was the critically endangered Balearic shearwater (Puffinus mauretanicus), which showed a high risk to longlines in the Bay of Biscay.Where quantitative data were available for populations size and bycatch in e.g, ICES reports, the impact of fisheries bycatch was estimated quantitively by estimating reference points and by comparing them to total bycatch mortalities. This quantitative assessment was completed for two cetaceans and two elasmobranch species that were also included in the previous step. Bycatch impact for the common dolphin in the Northeast Atlantic and for harbour porpoise in Irish waters was found to be unsustainable, as current bycatch mortalities are above the “allowable” capture limits in both cases. For spurdog and undulate ray in the Northeast Atlantic and English Channel, respectively, the fishing pressure on the stock was sustainable, as it is below the harvest rate of Maximum Sustainable Yield (MSY). Reference points for seabirds were also estimated, but no comparison with bycatch mortality could be done due to lack of data. Additionally, quantitative assessments were produced for grey seal in the North Sea and loggerhead turtle in the Mediterranean (despite not being included in the previous step), where current bycatch rates were evaluated to be sustainable.Specific analyses were conducted for the Baltic Sea harbour porpoise with previously unused bycatch data from gillnets. Bycatch was modelled to estimate total bycatch mortality, addressing several objectives at once. On one hand, estimated total bycatch was compared with reference points, which showed that the current bycatch level was unsustainable for the population. Secondly, estimated total bycatch was compared with the results provided by previous simpler extrapolations, demonstrating that the later should not be applied when the fishery is heterogeneous due to the potential to provide biased estimates.Overall, the qualitative approaches are commonly used as a tool to identify species that are minimally affected, so the more intensive analysed are limited to high-risk species. Here, most species analysed showed-medium-high risk and therefore, all of them should have been analysed in further steps. However, many of those species lack the necessary information to conduct a quantitative assessment, and as result, the impact of bycatch at population level could only be evaluated, as seen above, for a few of them. This highlights the need for more exhaustive data collection and further research that could answer to the requirements of the EBFM.More information about the SEAwise project can be found at https://seawiseproject.org/</p

12-hr shifts in nursing: Do they remove unproductive time and information loss or do they reduce education and discussion opportunities for nurses? A cross-sectional study in 12 European countries

AIMS AND OBJECTIVES: To examine the association between registered nurses' (referred to as "nurses" for brevity) shifts of 12 hr or more and presence of continuing educational programmes; ability to discuss patient care with other nurses; assignments that foster continuity of care; and patient care information being lost during handovers. BACKGROUND: The introduction of long shifts (i.e., shifts of 12 hr or more) remains controversial. While there are claims of efficiency, studies have shown long shifts to be associated with adverse effects on quality of care. Efficiency claims are predicated on the assumption that long shifts reduce overlaps between shifts; these overlaps are believed to be unproductive and dangerous. However, there are potentially valuable educational and communication activities that occur during these overlaps. DESIGN: Cross-sectional survey of 31,627 nurses within 487 hospitals in 12 European countries. METHODS: The associations were measured through generalised linear mixed models. The study methods were compliant with the STROBE checklist. RESULTS: When nurses worked shifts of 12 hr or more, they were less likely to report having continuing educational programmes; and time to discuss patient care with other nurses, compared to nurses working 8 hr or less. Nurses working shifts of 12 hr or more were less likely to report assignments that foster continuity of care, albeit the association was not significant. Similarly, working long shifts was associated with reports of patient care information being lost during handovers, although association was not significant. CONCLUSION: Working shifts of 12 hr or more is associated with reduced educational activities and fewer opportunities to discuss patient care, with potential negative consequences for safe and effective care. RELEVANCE TO CLINICAL PRACTICE: Implementation of long shifts should be questioned, as reduced opportunity to discuss care or participate in educational activities may jeopardise the quality and safety of care for patients.status: publishe

Integrating vibrational signals, mitochondrial DNA and morphology for species determination in the genus Aphrodes (Hemiptera: Cicadellidae)

Reliable delimitation and identification of species is central not only to systematics, but also to studies of biodiversity, ecology and pest management. In the era of Internet-based biodiversity databases misidentifications are rapidly disseminated and may have far-reaching consequences. Leafhoppers from the genus Aphrodes (Hemiptera, Cicadellidae) are common and abundant, but, nevertheless, they are still a taxonomically challenging group whose members are often assessed in ecological studies and are also potential vectors of plant diseases. Previous study has shown that the syntype series for A. aestuarina (Edwards) includes also specimens of A. makarovi Zachvatkin and has suggested that misidentifications may be widespread in museum collections. We studied Aphrodes individuals collected from the U.K. and Slovenia in order to provide a more comprehensive analysis of this genus using multiple criteria. Combined work using male and female vibrational signals emitted during courtship, and a 600-bp fragment within the barcoding region of the COI mtDNA gene, provided validated specimens that we also used for morphometric study. Analyses confirmed A. aestuarina, A. bicincta, A. diminuta and A. makarovi as behaviourally, genetically and morphologically distinct species. Although any of these approaches could be used alone to distinguish between species, combining morphological and molecular approaches will help to improve reliability, especially when identifying females. Morphological investigation of validated individuals from the U.K. and Slovenia also revealed geographic differences within species. By combining several body and aedeagus morphological characters males can be reliably identified, however, morphological differences between species are, nevertheless, relatively small. By contrast, observed genetic distances between Aphrodes species are relatively large (4.2–7.0%). At about half of our collecting sites more than one Aphrodes species was found and A. makarovi was collected together with every other species, including A. aestuarina on tidal saltmarshes. Due to low morphological variation between syntopic congeners it is likely that many museum specimens of Aphrodes have been assigned to the wrong species and species identification in ecological and vector studies may also be questionable