Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Provenance of Detrital Rutiles from the Triassic–Jurassic Sandstones in Franz Josef Land (Barents Sea Region, Russian High Arctic): U-Pb Ages and Trace Element Geochemistry

Provenance study plays an important role in paleogeographic and tectonic reconstructions. Detrital zircons are commonly used to identify sediment provenance; however, a wide range of detrital zircon ages in clastic rock often represent a fingerprint of reworked older terrigenous successions rather than ages of magmatism and metamorphism in the provenance area. This study focuses on the provenance of detrital rutile grains in the Triassic–Jurassic sandstones from Franz Josef Land and shows the importance of multiproxy approaches for provenance studies. Trace element data demonstrate that most rutile grains were sourced from metapelitic rocks, with a subordinate population having a metamafic origin. The Zr-in-rutile thermometer and U-Pb geochronology suggest that detrital rutile grains were predominantly derived from rocks that underwent amphibolite facies metamorphism during the Paleozoic era, with a predominance of the Carboniferous–Permian ages. Therefore, we suggest that the provenance area for the studied sandstones on Franz Josef Land has a similar geological history to the Taimyr region and Severnaya Zemlya archipelago. We propose that this crustal domain extends across the Kara Sea and forms the basement to the north and east of FJL, representing a proximal provenance for the studied Mesozoic terrigenous rocks. This domain experienced both Middle–Late Ordovician and Carboniferous–Permian metamorphism. The comparison of U-Pb dating and the geochemistry of rutile, U-Th/He, and U-Pb dating of zircons showed that detrital rutiles are the powerful toll in provenance restoration and can give additional constrains when a provenance area locates within collisional-convergent settings

Hidden Middle Devonian Magmatism of North-Eastern Siberia: Age Constraints from Detrital Zircon U–Pb Data

We present new data on the tectonic evolution of north-eastern Siberia using an integrated provenance analysis based on U–Pb detrital zircon dating and sandstone petrography of Devonian sedimentary strata. Our petrographic data suggest that Upper Devonian sandstones of north-eastern Siberia were derived from a local provenance, supported by the widespread distribution of ca. 1900–2000 Ma magmatic events in the basement of the neighboring Ust’-Lena and Olenek uplifts. Devonian detrital zircon age distributions of the Devonian sandstones are similar to ages of Middle Paleozoic magmatic rocks of Yakutsk-Vilyui large igneous province (LIP). Therefore, we suggest that the studied sandstones were derived from proximally-located uplifted blocks composed of Proterozoic–Devonian rocks and Middle–Late Devonian volcanics. Moreover, the abundance of Middle–Late Devonian zircons is suggestive of a wider distribution of coeval magmatism across north-eastern Siberia than previously supposed. We propose that widespread Devonian magmatism associated with the Yakutsk-Vilyui LIP also occurred to the east of our study area and is now buried beneath thick Carboniferous–Jurassic sedimentary rocks of the eastern Siberian passive margin, subsequently deformed into the Late Jurassic–Cretaceous Verkhoyansk fold-and-thrust belt. We also propose that the major pulse of the Yakutsk-Vilyui LIP occurred in north-eastern Siberia during the Middle Devonian at ca. 390 Ma, some 15 million years earlier than within the Vilyui rift basin in eastern Siberia (ca. 375 Ma)

Provenance and Stratigraphy of the Upper Carboniferous—Lower Permian Strata of October Revolution Island (Severnaya Zemlya Archipelago): Implications for Geological History of the Russian High Arctic

Small depressions across the north-eastern part of October Revolution Island (Severnaya Zemlya archipelago, Kara terrane) are filled with continental terrigenous rocks, dated as Upper Carboniferous–Lower Permian in age based on palynological data. These rocks overlie Ordovician volcaniclastic rocks above a prominent angular unconformity. U-Pb dating of detrital zircons from the Late Carboniferous–Lower Permian rocks reveals that most grains are Ordovician in age, ranging between 475–455 Ma. A subordinate population of Silurian detrital zircons is also present, contributing up to 15% of the dated population, while Precambrian grains mainly yield Neo-Mesoproterozoic ages and do not form prominent peaks. The combined U-Pb and (U-Th)/He ages indicate that most zircon (U-Th)/He ages were reset and average at ca. 317 Ma, suggesting ~6–7 km of Late Carboniferous uplift within the provenance area. This provenance area, mainly comprising Ordovician magmatic and volcanic rocks, was located close to the study area based on the coarse-grained nature of Late Carboniferous–Lower Permian rocks of north-eastern October Revolution Island. Therefore, we propose that Late Paleozoic tectonism significantly affected both the southern margin of the Kara terrane, as previously supposed, and also its north-eastern part. We propose that the Late Paleozoic Uralian suture zone continued to the north-eastern October Revolution Island and was responsible for the significant tectonic uplift of the studied region. This suture zone is now hidden beneath the younger Arctic basins

Provenance and Stratigraphy of the Upper Carboniferous—Lower Permian Strata of October Revolution Island (Severnaya Zemlya Archipelago): Implications for Geological History of the Russian High Arctic

Small depressions across the north-eastern part of October Revolution Island (Severnaya Zemlya archipelago, Kara terrane) are filled with continental terrigenous rocks, dated as Upper Carboniferous–Lower Permian in age based on palynological data. These rocks overlie Ordovician volcaniclastic rocks above a prominent angular unconformity. U-Pb dating of detrital zircons from the Late Carboniferous–Lower Permian rocks reveals that most grains are Ordovician in age, ranging between 475–455 Ma. A subordinate population of Silurian detrital zircons is also present, contributing up to 15% of the dated population, while Precambrian grains mainly yield Neo-Mesoproterozoic ages and do not form prominent peaks. The combined U-Pb and (U-Th)/He ages indicate that most zircon (U-Th)/He ages were reset and average at ca. 317 Ma, suggesting ~6–7 km of Late Carboniferous uplift within the provenance area. This provenance area, mainly comprising Ordovician magmatic and volcanic rocks, was located close to the study area based on the coarse-grained nature of Late Carboniferous–Lower Permian rocks of north-eastern October Revolution Island. Therefore, we propose that Late Paleozoic tectonism significantly affected both the southern margin of the Kara terrane, as previously supposed, and also its north-eastern part. We propose that the Late Paleozoic Uralian suture zone continued to the north-eastern October Revolution Island and was responsible for the significant tectonic uplift of the studied region. This suture zone is now hidden beneath the younger Arctic basins

U–Pb Age and Hf Isotope Geochemistry of Detrital Zircons from Cambrian Sandstones of the Severnaya Zemlya Archipelago and Northern Taimyr (Russian High Arctic)

U–Pb and Lu–Hf isotope analyses of detrital zircons collected from metasedimentary rocks from the southern part of Kara Terrane (northern Taimyr and Severnaya Zemlya archipelago) provide vital information about the paleogeographic and tectonic evolution of the Russian High Arctic. The detrital zircon signatures of the seven dated samples are very similar, suggesting a common provenance for the clastic detritus. The majority of the dated grains belong to the late Neoproterozoic to Cambrian ages, which suggests the maximum depositional age of the enclosing sedimentary units to be Cambrian. The εHf(t) values indicate that juvenile magma mixed with evolved continental crust and the zircons crystallized within a continental magmatic arc setting. Our data strongly suggest that the main provenance for the studied clastics was located within the Timanian Orogen. A review of the available detrital zircon ages from late Neoproterozoic to Cambrian strata across the wider Arctic strongly suggests that Kara Terrane, Novaya Zemlya, Seward Peninsula (Arctic Alaska), Alexander Terrane, De Long Islands, and Scandinavian Caledonides all formed a single tectonic domain during the Cambrian age, with clastics predominantly sourced from the Timanian Orogen

Glendonite-Like Carbonate Aggregates from the Lower Ordovician Koporye Formation (Russian Part of the Baltic Klint): Detailed Mineralogical and Geochemical Data and Paleogeographic Implications

Stellate and plate-like carbonate bodies, traditionally called anthraconites, are found throughout the Baltic-Ladoga Klint in bituminous shale of the Koporye Formation (Tremadocian, Lower Ordovician). Although this time interval is usually considered as a greenhouse, there is some evidence for the existence of at least temporary cold conditions during the Cambrian–Ordovician. However, the origin of anthraconites is still strongly debated. We studied the mineralogical, petrographic, cathodoluminescence, geochemical, and isotopic characteristics of anthraconites from five sections of the Russian part of the Baltic paleobasin. A close similarity between the morphological, petrographic, cathodoluminescence, and isotopic characteristics of the studied anthraconites with those of glendonites allow us to suggest that these bodies formed in a similar paleo-environment and should be considered as pseudomorphs of the mineral ikaite. The oxygen and carbon isotope ratios reveal that ikaite precipitation occurred in low-temperature conditions on the seafloor. The carbon isotopic values reveal influence of inorganic seawater carbon along with organic matter decomposition and/or methane oxidation during ikaite-glendonite transformations. The oxygen isotopic composition significantly changed after deposition due to meteoric diagenesis. We propose that the studied Tremadocian anthraconites formed under a region of upwelling, where cold phosphate-rich deep waters rose to the relatively shallow part of the Baltic paleobasin, providing favorable conditions for ikaite precipitation. Based on our cathodoluminescence study, we suggest that ikaite was transformed to calcite over several stages during diagenesis. Mineralogical studies also reveal that primary calcite was transformed to sulfate (gypsum) or dolomite during late superimposed processes