The immunogenicity and safety of a reduced PRP-content DTPw-HBV/Hib vaccine when administered according to the accelerated EPI schedule

<p>Abstract</p> <p>Background</p> <p>Combination vaccines improve coverage, compliance and effectively introduce new antigens to mass vaccination programmes. This was a phase III, observer-blind, randomized study of GSK Biologicals diphtheria-tetanus-whole cell pertussis vaccine combined with hepatitis B and <it>Haemophilus influenzae </it>type b vaccines, containing a reduced amount of polyribosyl-ribitol-phosphate (PRP) and a DTPw component manufactured at a different site (DTPw-HBV/Hib_2.5[Kft]). The primary aim of this study was to demonstrate that DTPw-HBV/Hib_2.5[Kft] was not inferior to the licensed DTPw-HBV/Hib (<it>Tritanrix</it>(tm)-HepB/<it>Hiberix</it>(tm)) vaccine or the DTPw-HBV/Hib_2.5vaccine, also containing a reduced amount of PRP, with respect to the immune response to the PRP antigen, when administered to healthy infants, according to the Expanded Programme for Immunization (EPI) schedule at 6, 10 and 14 weeks of age.</p> <p>Methods</p> <p>299 healthy infants were randomised to receive either DTPw-HBV/Hib_2.5[Kft] DTPw-HBV/Hib_2.5or DTPw-HBV/Hib according to the 6-10-14 week EPI schedule. Blood samples were analysed prior to the first dose of study vaccine and one month after the third vaccine dose for the analysis of immune responses. Solicited local and general symptoms such as pain, redness and swelling at the injection site and drowsiness and fever, unsolicited symptoms (defined as any additional adverse event) and serious adverse events (SAEs) were recorded up to 20 weeks of age.</p> <p>Results</p> <p>One month after the third vaccine dose, 100% of subjects receiving DTPw-HBV/Hib_2.5[Kft] or DTPw-HBV/Hib and 98.8% of subjects receiving DTPw-HBV/Hib_2.5vaccine had seroprotective levels of anti-PRP antibodies (defined as anti-PRP antibody concentration ≥0.15 μg/ml). Seroprotective antibody concentrations were attained in over 98.9% of subjects for diphtheria, tetanus and hepatitis B. The vaccine response rate to pertussis antigen was at least 97.8% in each group. Overall, the DTPw-HBV/Hib_2.5[Kft] vaccine was well tolerated in healthy infants; no SAEs were reported in any group.</p> <p>Conclusions</p> <p>The DTPw-HBV/Hib_2.5[Kft] vaccine was immunogenic and well-tolerated when administered according to the EPI schedule to Indian infants.</p> <p>Trial registration</p> <p><url>http://www.clinicaltrials.gov</url> NCT00473668</p

Global Island Monitoring Scheme (GIMS) : a proposal for the long-term coordinated survey and monitoring of native island forest biota

Islands harbour evolutionary and ecologically unique biota, which are currently disproportionately threatened by a multitude of anthropogenic factors, including habitat loss, invasive species and climate change. Native forests on oceanic islands are important refugia for endemic species, many of which are rare and highly threatened. Long-term monitoring schemes for those biota and ecosystems are urgently needed: (i) to provide quantitative baselines for detecting changes within island ecosystems, (ii) to evaluate the effectiveness of conservation and management actions, and (iii) to identify general ecological patterns and processes using multiple island systems as repeated 'natural experiments'. In this contribution, we call for a Global Island Monitoring Scheme (GIMS) for monitoring the remaining native island forests, using bryophytes, vascular plants, selected groups of arthropods and vertebrates as model taxa. As a basis for the GIMS, we also present new, optimized monitoring protocols for bryophytes and arthropods that were developed based on former standardized inventory protocols. Effective inventorying and monitoring of native island forests will require: (i) permanent plots covering diverse ecological gradients (e.g. elevation, age of terrain, anthropogenic disturbance); (ii) a multiple-taxa approach that is based on standardized and replicable protocols; (iii) a common set of indicator taxa and community properties that are indicative of native island forests' welfare, building on, and harmonized with existing sampling and monitoring efforts; (iv) capacity building and training of local researchers, collaboration and continuous dialogue with local stakeholders; and (v) long-term commitment by funding agencies to maintain a global network of native island forest monitoring plots.Peer reviewe

Sarilumab in patients admitted to hospital with severe or critical COVID-19: a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19. Methods: We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 [death] to 7 [discharged from hospital]) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov, NCT04327388; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021. Findings: Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 [20%]), sarilumab 200 mg (n=159 [38%]), or sarilumab 400 mg (n=173 [42%]). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days [95% CI 9·0 to 15·0]) and sarilumab 200 mg (10·0 days [9·0 to 12·0]; hazard ratio [HR] 1·03 [95% CI 0·75 to 1·40]; log-rank p=0·96) or sarilumab 400 mg (10·0 days [9·0 to 13·0]; HR 1·14 [95% CI 0·84 to 1·54]; log-rank p=0·34), or in proportions of patients alive (77 [92%] of 84 patients in the placebo group; 143 [90%] of 159 patients in the sarilumab 200 mg group; difference −1·7 [−9·3 to 5·8]; p=0·63 vs placebo; and 159 [92%] of 173 patients in the sarilumab 400 mg group; difference 0·2 [−6·9 to 7·4]; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% [95% CI −7·7 to 25·5]; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 11% (17 of 159) were in the sarilumab 200 mg group, and 10% (18 of 173) were in the sarilumab 400 mg group. Interpretation: This trial did not show efficacy of sarilumab in patients admitted to hospital with COVID-19 and receiving supplemental oxygen. Adequately powered trials of targeted immunomodulatory therapies assessing survival as a primary endpoint are suggested in patients with critical COVID-19. Funding: Sanofi and Regeneron Pharmaceuticals

Selection of the silicon sensor thickness for the Phase-2 upgrade of the CMS Outer Tracker

During the operation of the CMS experiment at the High-Luminosity LHC the silicon sensors of the Phase-2 Outer Tracker will be exposed to radiation levels that could potentially deteriorate their performance. Previous studies had determined that planar float zone silicon with n-doped strips on a p-doped substrate was preferred over p-doped strips on an n-doped substrate. The last step in evaluating the optimal design for the mass production of about 200 m$^{2}$ of silicon sensors was to compare sensors of baseline thickness (about 300 μm) to thinned sensors (about 240 μm), which promised several benefits at high radiation levels because of the higher electric fields at the same bias voltage. This study provides a direct comparison of these two thicknesses in terms of sensor characteristics as well as charge collection and hit efficiency for fluences up to 1.5 × 10$^{15}$ n$_{eq}$/cm$^{2}$. The measurement results demonstrate that sensors with about 300 μm thickness will ensure excellent tracking performance even at the highest considered fluence levels expected for the Phase-2 Outer Tracker

Comparative evaluation of analogue front-end designs for the CMS Inner Tracker at the High Luminosity LHC

The CMS Inner Tracker, made of silicon pixel modules, will be entirely replaced prior to the start of the High Luminosity LHC period. One of the crucial components of the new Inner Tracker system is the readout chip, being developed by the RD53 Collaboration, and in particular its analogue front-end, which receives the signal from the sensor and digitizes it. Three different analogue front-ends (Synchronous, Linear, and Differential) were designed and implemented in the RD53A demonstrator chip. A dedicated evaluation program was carried out to select the most suitable design to build a radiation tolerant pixel detector able to sustain high particle rates with high efficiency and a small fraction of spurious pixel hits. The test results showed that all three analogue front-ends presented strong points, but also limitations. The Differential front-end demonstrated very low noise, but the threshold tuning became problematic after irradiation. Moreover, a saturation in the preamplifier feedback loop affected the return of the signal to baseline and thus increased the dead time. The Synchronous front-end showed very good timing performance, but also higher noise. For the Linear front-end all of the parameters were within specification, although this design had the largest time walk. This limitation was addressed and mitigated in an improved design. The analysis of the advantages and disadvantages of the three front-ends in the context of the CMS Inner Tracker operation requirements led to the selection of the improved design Linear front-end for integration in the final CMS readout chip

Beam test performance of a prototype module with Short Strip ASICs for the CMS HL-LHC tracker upgrade

The Short Strip ASIC (SSA) is one of the four front-end chips designed for the upgrade of the CMS Outer Tracker for the High Luminosity LHC. Together with the Macro-Pixel ASIC (MPA) it will instrument modules containing a strip and a macro-pixel sensor stacked on top of each other. The SSA provides both full readout of the strip hit information when triggered, and, together with the MPA, correlated clusters called stubs from the two sensors for use by the CMS Level-1 (L1) trigger system. Results from the first prototype module consisting of a sensor and two SSA chips are presented. The prototype module has been characterized at the Fermilab Test Beam Facility using a 120 GeV proton beam

The clinical relevance of oliguria in the critically ill patient : Analysis of a large observational database

Funding Information: Marc Leone reports receiving consulting fees from Amomed and Aguettant; lecture fees from MSD, Pfizer, Octapharma, 3 M, Aspen, Orion; travel support from LFB; and grant support from PHRC IR and his institution. JLV is the Editor-in-Chief of Critical Care. The other authors declare that they have no relevant financial interests. Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Urine output is widely used as one of the criteria for the diagnosis and staging of acute renal failure, but few studies have specifically assessed the role of oliguria as a marker of acute renal failure or outcomes in general intensive care unit (ICU) patients. Using a large multinational database, we therefore evaluated the occurrence of oliguria (defined as a urine output 16 years) patients in the ICON audit who had a urine output measurement on the day of admission were included. To investigate the association between oliguria and mortality, we used a multilevel analysis. Results: Of the 8292 patients included, 2050 (24.7%) were oliguric during the first 24 h of admission. Patients with oliguria on admission who had at least one additional 24-h urine output recorded during their ICU stay (n = 1349) were divided into three groups: transient - oliguria resolved within 48 h after the admission day (n = 390 [28.9%]), prolonged - oliguria resolved > 48 h after the admission day (n = 141 [10.5%]), and permanent - oliguria persisting for the whole ICU stay or again present at the end of the ICU stay (n = 818 [60.6%]). ICU and hospital mortality rates were higher in patients with oliguria than in those without, except for patients with transient oliguria who had significantly lower mortality rates than non-oliguric patients. In multilevel analysis, the need for RRT was associated with a significantly higher risk of death (OR = 1.51 [95% CI 1.19-1.91], p = 0.001), but the presence of oliguria on admission was not (OR = 1.14 [95% CI 0.97-1.34], p = 0.103). Conclusions: Oliguria is common in ICU patients and may have a relatively benign nature if only transient. The duration of oliguria and need for RRT are associated with worse outcome.publishersversionPeer reviewe

Effects of Climate and Atmospheric Nitrogen Deposition on Early to Mid-Term Stage Litter Decomposition Across Biomes

open263siWe acknowledge support by the German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig, funded by the German Research Foundation (FZT 118), Scientific Grant Agency VEGA(GrantNo.2/0101/18), as well as by the European Research Council under the European Union’s Horizon 2020 Research and Innovation Program (Grant Agreement No. 677232)Litter decomposition is a key process for carbon and nutrient cycling in terrestrial ecosystems and is mainly controlled by environmental conditions, substrate quantity and quality as well as microbial community abundance and composition. In particular, the effects of climate and atmospheric nitrogen (N) deposition on litter decomposition and its temporal dynamics are of significant importance, since their effects might change over the course of the decomposition process. Within the TeaComposition initiative, we incubated Green and Rooibos teas at 524 sites across nine biomes. We assessed how macroclimate and atmospheric inorganic N deposition under current and predicted scenarios (RCP 2.6, RCP 8.5) might affect litter mass loss measured after 3 and 12 months. Our study shows that the early to mid-term mass loss at the global scale was affected predominantly by litter quality (explaining 73% and 62% of the total variance after 3 and 12 months, respectively) followed by climate and N deposition. The effects of climate were not litter-specific and became increasingly significant as decomposition progressed, with MAP explaining 2% and MAT 4% of the variation after 12 months of incubation. The effect of N deposition was litter-specific, and significant only for 12-month decomposition of Rooibos tea at the global scale. However, in the temperate biome where atmospheric N deposition rates are relatively high, the 12-month mass loss of Green and Rooibos teas decreased significantly with increasing N deposition, explaining 9.5% and 1.1% of the variance, respectively. The expected changes in macroclimate and N deposition at the global scale by the end of this century are estimated to increase the 12-month mass loss of easily decomposable litter by 1.1-3.5% and of the more stable substrates by 3.8-10.6%, relative to current mass loss. In contrast, expected changes in atmospheric N deposition will decrease the mid-term mass loss of high-quality litter by 1.4-2.2% and that of low-quality litter by 0.9-1.5% in the temperate biome. Our results suggest that projected increases in N deposition may have the capacity to dampen the climate-driven increases in litter decomposition depending on the biome and decomposition stage of substrate.openKwon T.; Shibata H.; Kepfer-Rojas S.; Schmidt I.K.; Larsen K.S.; Beier C.; Berg B.; Verheyen K.; Lamarque J.-F.; Hagedorn F.; Eisenhauer N.; Djukic I.; Caliman A.; Paquette A.; Gutierrez-Giron A.; Petraglia A.; Augustaitis A.; Saillard A.; Ruiz-Fernandez A.C.; Sousa A.I.; Lillebo A.I.; Da Rocha Gripp A.; Lamprecht A.; Bohner A.; Francez A.-J.; Malyshev A.; Andric A.; Stanisci A.; Zolles A.; Avila A.; Virkkala A.-M.; Probst A.; Ouin A.; Khuroo A.A.; Verstraeten A.; Stefanski A.; Gaxiola A.; Muys B.; Gozalo B.; Ahrends B.; Yang B.; Erschbamer B.; Rodriguez Ortiz C.E.; Christiansen C.T.; Meredieu C.; Mony C.; Nock C.; Wang C.-P.; Baum C.; Rixen C.; Delire C.; Piscart C.; Andrews C.; Rebmann C.; Branquinho C.; Jan D.; Wundram D.; Vujanovic D.; Adair E.C.; Ordonez-Regil E.; Crawford E.R.; Tropina E.F.; Hornung E.; Groner E.; Lucot E.; Gacia E.; Levesque E.; Benedito E.; Davydov E.A.; Bolzan F.P.; Maestre F.T.; Maunoury-Danger F.; Kitz F.; Hofhansl F.; Hofhansl G.; De Almeida Lobo F.; Souza F.L.; Zehetner F.; Koffi F.K.; Wohlfahrt G.; Certini G.; Pinha G.D.; Gonzlez G.; Canut G.; Pauli H.; Bahamonde H.A.; Feldhaar H.; Jger H.; Serrano H.C.; Verheyden H.; Bruelheide H.; Meesenburg H.; Jungkunst H.; Jactel H.; Kurokawa H.; Yesilonis I.; Melece I.; Van Halder I.; Quiros I.G.; Fekete I.; Ostonen I.; Borovsk J.; Roales J.; Shoqeir J.H.; Jean-Christophe Lata J.; Probst J.-L.; Vijayanathan J.; Dolezal J.; Sanchez-Cabeza J.-A.; Merlet J.; Loehr J.; Von Oppen J.; Loffler J.; Benito Alonso J.L.; Cardoso-Mohedano J.-G.; Penuelas J.; Morina J.C.; Quinde J.D.; Jimnez J.J.; Alatalo J.M.; Seeber J.; Kemppinen J.; Stadler J.; Kriiska K.; Van Den Meersche K.; Fukuzawa K.; Szlavecz K.; Juhos K.; Gerhtov K.; Lajtha K.; Jennings K.; Jennings J.; Ecology P.; Hoshizaki K.; Green K.; Steinbauer K.; Pazianoto L.; Dienstbach L.; Yahdjian L.; Williams L.J.; Brigham L.; Hanna L.; Hanna H.; Rustad L.; Morillas L.; Silva Carneiro L.; Di Martino L.; Villar L.; Fernandes Tavares L.A.; Morley M.; Winkler M.; Lebouvier M.; Tomaselli M.; Schaub M.; Glushkova M.; Torres M.G.A.; De Graaff M.-A.; Pons M.-N.; Bauters M.; Mazn M.; Frenzel M.; Wagner M.; Didion M.; Hamid M.; Lopes M.; Apple M.; Weih M.; Mojses M.; Gualmini M.; Vadeboncoeur M.; Bierbaumer M.; Danger M.; Scherer-Lorenzen M.; Ruek M.; Isabellon M.; Di Musciano M.; Carbognani M.; Zhiyanski M.; Puca M.; Barna M.; Ataka M.; Luoto M.; H. Alsafaran M.; Barsoum N.; Tokuchi N.; Korboulewsky N.; Lecomte N.; Filippova N.; Hlzel N.; Ferlian O.; Romero O.; Pinto-Jr O.; Peri P.; Dan Turtureanu P.; Haase P.; Macreadie P.; Reich P.B.; Petk P.; Choler P.; Marmonier P.; Ponette Q.; Dettogni Guariento R.; Canessa R.; Kiese R.; Hewitt R.; Weigel R.; Kanka R.; Cazzolla Gatti R.; Martins R.L.; Ogaya R.; Georges R.; Gaviln R.G.; Wittlinger S.; Puijalon S.; Suzuki S.; Martin S.; Anja S.; Gogo S.; Schueler S.; Drollinger S.; Mereu S.; Wipf S.; Trevathan-Tackett S.; Stoll S.; Lfgren S.; Trogisch S.; Seitz S.; Glatzel S.; Venn S.; Dousset S.; Mori T.; Sato T.; Hishi T.; Nakaji T.; Jean-Paul T.; Camboulive T.; Spiegelberger T.; Scholten T.; Mozdzer T.J.; Kleinebecker T.; Runk T.; Ramaswiela T.; Hiura T.; Enoki T.; Ursu T.-M.; Di Cella U.M.; Hamer U.; Klaus V.; Di Cecco V.; Rego V.; Fontana V.; Piscov V.; Bretagnolle V.; Maire V.; Farjalla V.; Pascal V.; Zhou W.; Luo W.; Parker W.; Parker P.; Kominam Y.; Kotrocz Z.; Utsumi Y.Kwon T.; Shibata H.; Kepfer-Rojas S.; Schmidt I.K.; Larsen K.S.; Beier C.; Berg B.; Verheyen K.; Lamarque J.-F.; Hagedorn F.; Eisenhauer N.; Djukic I.; Caliman A.; Paquette A.; Gutierrez-Giron A.; Petraglia A.; Augustaitis A.; Saillard A.; Ruiz-Fernandez A.C.; Sousa A.I.; Lillebo A.I.; Da Rocha Gripp A.; Lamprecht A.; Bohner A.; Francez A.-J.; Malyshev A.; Andric A.; Stanisci A.; Zolles A.; Avila A.; Virkkala A.-M.; Probst A.; Ouin A.; Khuroo A.A.; Verstraeten A.; Stefanski A.; Gaxiola A.; Muys B.; Gozalo B.; Ahrends B.; Yang B.; Erschbamer B.; Rodriguez Ortiz C.E.; Christiansen C.T.; Meredieu C.; Mony C.; Nock C.; Wang C.-P.; Baum C.; Rixen C.; Delire C.; Piscart C.; Andrews C.; Rebmann C.; Branquinho C.; Jan D.; Wundram D.; Vujanovic D.; Adair E.C.; Ordonez-Regil E.; Crawford E.R.; Tropina E.F.; Hornung E.; Groner E.; Lucot E.; Gacia E.; Levesque E.; Benedito E.; Davydov E.A.; Bolzan F.P.; Maestre F.T.; Maunoury-Danger F.; Kitz F.; Hofhansl F.; Hofhansl G.; De Almeida Lobo F.; Souza F.L.; Zehetner F.; Koffi F.K.; Wohlfahrt G.; Certini G.; Pinha G.D.; Gonzlez G.; Canut G.; Pauli H.; Bahamonde H.A.; Feldhaar H.; Jger H.; Serrano H.C.; Verheyden H.; Bruelheide H.; Meesenburg H.; Jungkunst H.; Jactel H.; Kurokawa H.; Yesilonis I.; Melece I.; Van Halder I.; Quiros I.G.; Fekete I.; Ostonen I.; Borovsk J.; Roales J.; Shoqeir J.H.; Jean-Christophe Lata J.; Probst J.-L.; Vijayanathan J.; Dolezal J.; Sanchez-Cabeza J.-A.; Merlet J.; Loehr J.; Von Oppen J.; Loffler J.; Benito Alonso J.L.; Cardoso-Mohedano J.-G.; Penuelas J.; Morina J.C.; Quinde J.D.; Jimnez J.J.; Alatalo J.M.; Seeber J.; Kemppinen J.; Stadler J.; Kriiska K.; Van Den Meersche K.; Fukuzawa K.; Szlavecz K.; Juhos K.; Gerhtov K.; Lajtha K.; Jennings K.; Jennings J.; Ecology P.; Hoshizaki K.; Green K.; Steinbauer K.; Pazianoto L.; Dienstbach L.; Yahdjian L.; Williams L.J.; Brigham L.; Hanna L.; Hanna H.; Rustad L.; Morillas L.; Silva Carneiro L.; Di Martino L.; Villar L.; Fernandes Tavares L.A.; Morley M.; Winkler M.; Lebouvier M.; Tomaselli M.; Schaub M.; Glushkova M.; Torres M.G.A.; De Graaff M.-A.; Pons M.-N.; Bauters M.; Mazn M.; Frenzel M.; Wagner M.; Didion M.; Hamid M.; Lopes M.; Apple M.; Weih M.; Mojses M.; Gualmini M.; Vadeboncoeur M.; Bierbaumer M.; Danger M.; Scherer-Lorenzen M.; Ruek M.; Isabellon M.; Di Musciano M.; Carbognani M.; Zhiyanski M.; Puca M.; Barna M.; Ataka M.; Luoto M.; H. Alsafaran M.; Barsoum N.; Tokuchi N.; Korboulewsky N.; Lecomte N.; Filippova N.; Hlzel N.; Ferlian O.; Romero O.; Pinto-Jr O.; Peri P.; Dan Turtureanu P.; Haase P.; Macreadie P.; Reich P.B.; Petk P.; Choler P.; Marmonier P.; Ponette Q.; Dettogni Guariento R.; Canessa R.; Kiese R.; Hewitt R.; Weigel R.; Kanka R.; Cazzolla Gatti R.; Martins R.L.; Ogaya R.; Georges R.; Gaviln R.G.; Wittlinger S.; Puijalon S.; Suzuki S.; Martin S.; Anja S.; Gogo S.; Schueler S.; Drollinger S.; Mereu S.; Wipf S.; Trevathan-Tackett S.; Stoll S.; Lfgren S.; Trogisch S.; Seitz S.; Glatzel S.; Venn S.; Dousset S.; Mori T.; Sato T.; Hishi T.; Nakaji T.; Jean-Paul T.; Camboulive T.; Spiegelberger T.; Scholten T.; Mozdzer T.J.; Kleinebecker T.; Runk T.; Ramaswiela T.; Hiura T.; Enoki T.; Ursu T.-M.; Di Cella U.M.; Hamer U.; Klaus V.; Di Cecco V.; Rego V.; Fontana V.; Piscov V.; Bretagnolle V.; Maire V.; Farjalla V.; Pascal V.; Zhou W.; Luo W.; Parker W.; Parker P.; Kominam Y.; Kotrocz Z.; Utsumi Y

Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42\ub74% vs 44\ub72%; absolute difference \u20131\ub769 [\u20139\ub758 to 6\ub711] p=0\ub767; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5\u20138] vs 6 [5\u20138] cm H2O; p=0\ub70011). ICU mortality was higher in MICs than in HICs (30\ub75% vs 19\ub79%; p=0\ub70004; adjusted effect 16\ub741% [95% CI 9\ub752\u201323\ub752]; p&lt;0\ub70001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0\ub780 [95% CI 0\ub775\u20130\ub786]; p&lt;0\ub70001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status. Funding: No funding

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700