Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure &lt;= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Fibrates for the Treatment of Primary Biliary Cholangitis Unresponsive to Ursodeoxycholic Acid: An Exploratory Study

Aim: Up to 40% of patients with primary biliary cholangitis (PBC) will have a suboptimal biochemical response to ursodeoxycholic acid (UDCA), which can be improved by the addition of fibrates. This exploratory study aims to evaluate the long-term real-life biochemical response of different fibrates, including ciprofibrate, in subjects with UDCA-unresponsive PBC.Methods: The Brazilian Cholestasis Study Group multicenter database was reviewed to assess the response rates to UDCA plus fibrates in patients with UDCA-unresponsive PBC 1 and 2 years after treatment initiation by different validated criteria.Results: In total, 27 patients (100% women, mean age 48.9 +/- 9.2 years) with PBC were included. Overall response rates to fibrates by each validated criterion varied from 39 to 60% and 39-76% at 12 and 24 months after treatment combination, respectively. Combination therapy resulted in a significant decrease in ALT and ALP only after 2 years, while GGT significantly improved in the first year of treatment. Treatment response rates at 1 and 2 years appear to be comparable between ciprofibrate and bezafibrate using all available criteria.Conclusion: Our findings endorse the efficacy of fibrate add-on treatment in PBC patients with suboptimal response to UDCA. Ciprofibrate appears to be at least as effective as bezafibrate and should be assessed in large clinical trials as a possibly new, cheaper, and promising option for treatment of UDCA-unresponsive PBC patients

Response to Ursodeoxycholic Acid May Be Assessed Earlier to Allow Second-Line Therapy in Patients with Unresponsive Primary Biliary Cholangitis

Background Response to ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) has been traditionally assessed 1 to 2 years after treatment initiation. With the development of new drugs, some patients may benefit from an earlier introduction of second-line therapies. Aims This study aims to identify whether well-validated response criteria could correctly identify individuals likely to benefit from add-on second-line therapy at 6 months. Methods Analysis of a multicenter retrospective cohort which included only patients with clear-cut PBC. Results 206 patients with PBC (96.6% women; mean age 54 +/- 12 years) were included. Kappa concordance was substantial for Toronto (0.67), Rotterdam (0.65), Paris 1 (0.63) and 2 (0.63) criteria at 6 and 12 months, whereas Barcelona (0.47) and POISE trial (0.59) criteria exhibited moderate agreement. Non-response rates to UDCA was not statistically different when assessed either at 6 or 12 months using Toronto, Rotterdam or Paris 2 criteria. Those differences were even smaller or absent in those subjects with advanced PBC. Mean baseline alkaline phosphatase was 2.73 +/- 1.95 times the upper limit of normal (x ULN) among responders versus 5.05 +/- 3.08 x ULN in non-responders (p < 0.001). Conclusions After 6 months of treatment with UDCA, the absence of response by different criteria could properly identify patients who could benefit from early addition of second-line therapies, especially in patients with advanced disease or high baseline liver enzymes levels

Sensitivity of South American tropical forests to an extreme climate anomaly

NERC Knowledge Exchange Fellowship (NE/V018760/1) to E.N.H.C.The tropical forest carbon sink is known to be drought sensitive, but it is unclear which forests are the most vulnerable to extreme events. Forests with hotter and drier baseline conditions may be protected by prior adaptation, or more vulnerable because they operate closer to physiological limits. Here we report that forests in drier South American climates experienced the greatest impacts of the 2015–2016 El Niño, indicating greater vulnerability to extreme temperatures and drought. The long-term, ground-measured tree-by-tree responses of 123 forest plots across tropical South America show that the biomass carbon sink ceased during the event with carbon balance becoming indistinguishable from zero (−0.02 ± 0.37 Mg C ha−1 per year). However, intact tropical South American forests overall were no more sensitive to the extreme 2015–2016 El Niño than to previous less intense events, remaining a key defence against climate change as long as they are protected.Publisher PDFPeer reviewe

Sensitivity of South American tropical forests to an extreme climate anomaly

Abstract: The tropical forest carbon sink is known to be drought sensitive, but it is unclear which forests are the most vulnerable to extreme events. Forests with hotter and drier baseline conditions may be protected by prior adaptation, or more vulnerable because they operate closer to physiological limits. Here we report that forests in drier South American climates experienced the greatest impacts of the 2015–2016 El Niño, indicating greater vulnerability to extreme temperatures and drought. The long-term, ground-measured tree-by-tree responses of 123 forest plots across tropical South America show that the biomass carbon sink ceased during the event with carbon balance becoming indistinguishable from zero (−0.02 ± 0.37 Mg C ha−1 per year). However, intact tropical South American forests overall were no more sensitive to the extreme 2015–2016 El Niño than to previous less intense events, remaining a key defence against climate change as long as they are protected

Sensitivity of South American tropical forests to an extreme climate anomaly

Funder: A Moore Foundation grant, Royal Society Global Challenges grant (Sensitivity of Tropical Forest Ecosystem Services to Climate Changes), CNPq grants (441282/2016-4, 403764/2012-2 and 558244/2009-2), FAPEAM grants 1600/2006, 465/2010 and PPFOR 147/2015, CNPq grants 473308/2009-6 and 558320/2009-0. European Research Council (ERC Advanced Grant 291585 – ‘T-FORCES’), the Gordon and Betty Moore Foundation (#1656 ‘RAINFOR’, and ‘MonANPeru’), the European Union’s Fifth, Sixth and Seventh Framework Programme (EVK2-CT-1999-00023 – ‘CARBONSINK-LBA’, 283080 – ‘GEOCARBON’, 282664 – ‘AMAZALERT), the Natural Environment Research Council (NE/ D005590/1 – ‘TROBIT’, NE/F005806/1 – ‘AMAZONICA’, E/M0022021/1 - ‘PPFOR’), several NERC Urgency and New Investigators Grants, the NERC/State of São Paulo Research Foundation (FAPESP) consortium grants ‘BIO-RED’ (NE/N012542/1), ‘ECOFOR’ (NE/K016431/1, 2012/51872-5, 2012/51509-8), ‘ARBOLES’ (NE/S011811/1, FAPESP 2018/15001-6), ‘SEOSAW’ (NE/P008755/1), ‘SECO’ (NE/T01279X/1), Brazilian National Research Council (PELD/CNPq 403710/2012-0), the Royal Society (University Research Fellowships and Global challenges Awards) (ICA/R1/180100 - ‘FORAMA’), the National Geographic Society, US National Science Foundation (DEB 1754647) and Colombia’s Colciencias. We thank the National Council for Science and Technology Development of Brazil (CNPq) for support to the Cerrado/Amazonia Transition Long-Term Ecology Project (PELD/441244/2016-5), the PPBio Phytogeography of Amazonia/Cerrado Transition Project (CNPq/PPBio/457602/2012-0), PELD-RAS (CNPq, Process 441659/2016-0), RESFLORA (Process 420254/2018-8), Synergize (Process 442354/2019-3), the Empresa Brasileira de Pesquisa Agropecuária – Embrapa (SEG: 02.08.06.005.00), the Fundação de Amparo à Pesquisa do Estado de São Paulo – FAPESP (2012/51509-8 and 2012/51872-5), the Goiás Research Foundation (FAPEG/PELD: 2017/10267000329) the EcoSpace Project (CNPq 459941/2014-3) and several PVE and Productivity Grants. We also thank the “Investissement d’Avenir” program (CEBA, ref. ANR-10LABX-25-01), the São Paulo Research Foundation (FAPESP 03/12595-7) and the Sustainable Landscapes Brazil Project (through Brazilian Agricultural Research Corporation (EMBRAPA), the US Forest Service, USAID, and the US Department of State) for supporting plot inventories in the Atlantic Forest sites in Sao Paulo, Brazil. L.E.O.C.A. was supported by CNPq (processes 305054/2016-3 and 442371/2019-5). We thank to the National Council for Technological and Scientific Development (CNPq) for the financial support of the PELD project (441244/2016-5, 441572/2020-0) and FAPEMAT (0346321/2021). NE/B503384/1, NE/N012542/1 - ‘BIO-RED’, ERC Advanced Grant 291585 - ‘T-FORCES’, NE/F005806/1 - ‘AMAZONICA’, NE/N004655/1 - ‘TREMOR’, NERC New Investigators Awards, the Gordon and Betty Moore Foundation (‘RAINFOR’, ‘MonANPeru’), ERC Starter Grant 758873 -‘TreeMort’, EU Framework 6, a Royal Society University Research Fellowship, and a Leverhulme Trust Research Fellowship.The tropical forest carbon sink is known to be drought sensitive, but it is unclear which forests are the most vulnerable to extreme events. Forests with hotter and drier baseline conditions may be protected by prior adaptation, or more vulnerable because they operate closer to physiological limits. Here we report that forests in drier South American climates experienced the greatest impacts of the 2015–2016 El Niño, indicating greater vulnerability to extreme temperatures and drought. The long-term, ground-measured tree-by-tree responses of 123 forest plots across tropical South America show that the biomass carbon sink ceased during the event with carbon balance becoming indistinguishable from zero (−0.02 ± 0.37 Mg C ha−1 per year). However, intact tropical South American forests overall were no more sensitive to the extreme 2015–2016 El Niño than to previous less intense events, remaining a key defence against climate change as long as they are protected

Sensitivity of South American tropical forests to an extreme climate anomaly

Funder: A Moore Foundation grant, Royal Society Global Challenges grant (Sensitivity of Tropical Forest Ecosystem Services to Climate Changes), CNPq grants (441282/2016-4, 403764/2012-2 and 558244/2009-2), FAPEAM grants 1600/2006, 465/2010 and PPFOR 147/2015, CNPq grants 473308/2009-6 and 558320/2009-0. European Research Council (ERC Advanced Grant 291585 - 'T-FORCES'), the Gordon and Betty Moore Foundation (#1656 'RAINFOR', and 'MonANPeru'), the European Union's Fifth, Sixth and Seventh Framework Programme (EVK2-CT-1999-00023 - 'CARBONSINK-LBA', 283080 - 'GEOCARBON', 282664 - 'AMAZALERT), the Natural Environment Research Council (NE/ D005590/1 - 'TROBIT', NE/F005806/1 - 'AMAZONICA', E/M0022021/1 - 'PPFOR'), several NERC Urgency and New Investigators Grants, the NERC/State of Sao Paulo Research Foundation (FAPESP) consortium grants 'BIO-RED' (NE/N012542/1), 'ECOFOR' (NE/K016431/1, 2012/51872-5, 2012/51509-8), 'ARBOLES' (NE/S011811/1, FAPESP 2018/15001-6), 'SEOSAW' (NE/P008755/1), 'SECO' (NE/T01279X/1), Brazilian National Research Council (PELD/CNPq 403710/2012-0), the Royal Society (University Research Fellowships and Global challenges Awards) (ICA/R1/180100 - 'FORAMA'), the National Geographic Society, US National Science Foundation (DEB 1754647) and Colombia's Colciencias. We thank the National Council for Science and Technology Development of Brazil (CNPq) for support to the Cerrado/Amazonia Transition Long-Term Ecology Project (PELD/441244/2016-5), the PPBio Phytogeography of Amazonia/Cerrado Transition Project (CNPq/PPBio/457602/2012-0), PELD-RAS (CNPq, Process 441659/2016-0), RESFLORA (Process 420254/2018-8), Synergize (Process 442354/2019-3), the Empresa Brasileira de Pesquisa Agropecuaria - Embrapa (SEG: 02.08.06.005.00), the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo - FAPESP (2012/51509-8 and 2012/51872-5), the Goias Research Foundation (FAPEG/PELD: 2017/10267000329) the EcoSpace Project (CNPq 459941/2014-3) and several PVE and Productivity Grants. We also thank the "Investissement d'Avenir" program (CEBA, ref. ANR-10LABX-25-01), the Sao Paulo Research Foundation (FAPESP 03/12595-7) and the Sustainable Landscapes Brazil Project (through Brazilian Agricultural Research Corporation (EMBRAPA), the US Forest Service, USAID, and the US Department of State) for supporting plot inventories in the Atlantic Forest sites in Sao Paulo, Brazil. L.E.O.C.A. was supported by CNPq (processes 305054/2016-3 and 442371/2019-5). We thank to the National Council for Technological and Scientific Development (CNPq) for the financial support of the PELD project (441244/2016-5, 441572/2020-0) and FAPEMAT (0346321/2021). NE/B503384/1, NE/N012542/1 - 'BIO-RED', ERC Advanced Grant 291585 - 'T-FORCES', NE/F005806/1 - 'AMAZONICA', NE/N004655/1 - 'TREMOR', NERC New Investigators Awards, the Gordon and Betty Moore Foundation ('RAINFOR', 'MonANPeru'), ERC Starter Grant 758873 -'TreeMort', EU Framework 6, a Royal Society University Research Fellowship, and a Leverhulme Trust Research Fellowship.AbstractThe tropical forest carbon sink is known to be drought sensitive, but it is unclear which forests are the most vulnerable to extreme events. Forests with hotter and drier baseline conditions may be protected by prior adaptation, or more vulnerable because they operate closer to physiological limits. Here we report that forests in drier South American climates experienced the greatest impacts of the 2015–2016 El Niño, indicating greater vulnerability to extreme temperatures and drought. The long-term, ground-measured tree-by-tree responses of 123 forest plots across tropical South America show that the biomass carbon sink ceased during the event with carbon balance becoming indistinguishable from zero (−0.02 ± 0.37 Mg C ha−1 per year). However, intact tropical South American forests overall were no more sensitive to the extreme 2015–2016 El Niño than to previous less intense events, remaining a key defence against climate change as long as they are protected.</jats:p

Neotropical freshwater fisheries : A dataset of occurrence and abundance of freshwater fishes in the Neotropics

The Neotropical region hosts 4225 freshwater fish species, ranking first among the world's most diverse regions for freshwater fishes. Our NEOTROPICAL FRESHWATER FISHES data set is the first to produce a large-scale Neotropical freshwater fish inventory, covering the entire Neotropical region from Mexico and the Caribbean in the north to the southern limits in Argentina, Paraguay, Chile, and Uruguay. We compiled 185,787 distribution records, with unique georeferenced coordinates, for the 4225 species, represented by occurrence and abundance data. The number of species for the most numerous orders are as follows: Characiformes (1289), Siluriformes (1384), Cichliformes (354), Cyprinodontiformes (245), and Gymnotiformes (135). The most recorded species was the characid Astyanax fasciatus (4696 records). We registered 116,802 distribution records for native species, compared to 1802 distribution records for nonnative species. The main aim of the NEOTROPICAL FRESHWATER FISHES data set was to make these occurrence and abundance data accessible for international researchers to develop ecological and macroecological studies, from local to regional scales, with focal fish species, families, or orders. We anticipate that the NEOTROPICAL FRESHWATER FISHES data set will be valuable for studies on a wide range of ecological processes, such as trophic cascades, fishery pressure, the effects of habitat loss and fragmentation, and the impacts of species invasion and climate change. There are no copyright restrictions on the data, and please cite this data paper when using the data in publications

NEOTROPICAL CARNIVORES: a data set on carnivore distribution in the Neotropics

Mammalian carnivores are considered a key group in maintaining ecological health and can indicate potential ecological integrity in landscapes where they occur. Carnivores also hold high conservation value and their habitat requirements can guide management and conservation plans. The order Carnivora has 84 species from 8 families in the Neotropical region: Canidae; Felidae; Mephitidae; Mustelidae; Otariidae; Phocidae; Procyonidae; and Ursidae. Herein, we include published and unpublished data on native terrestrial Neotropical carnivores (Canidae; Felidae; Mephitidae; Mustelidae; Procyonidae; and Ursidae). NEOTROPICAL CARNIVORES is a publicly available data set that includes 99,605 data entries from 35,511 unique georeferenced coordinates. Detection/non-detection and quantitative data were obtained from 1818 to 2018 by researchers, governmental agencies, non-governmental organizations, and private consultants. Data were collected using several methods including camera trapping, museum collections, roadkill, line transect, and opportunistic records. Literature (peer-reviewed and grey literature) from Portuguese, Spanish and English were incorporated in this compilation. Most of the data set consists of detection data entries (n = 79,343; 79.7%) but also includes non-detection data (n = 20,262; 20.3%). Of those, 43.3% also include count data (n = 43,151). The information available in NEOTROPICAL CARNIVORES will contribute to macroecological, ecological, and conservation questions in multiple spatio-temporal perspectives. As carnivores play key roles in trophic interactions, a better understanding of their distribution and habitat requirements are essential to establish conservation management plans and safeguard the future ecological health of Neotropical ecosystems. Our data paper, combined with other large-scale data sets, has great potential to clarify species distribution and related ecological processes within the Neotropics. There are no copyright restrictions and no restriction for using data from this data paper, as long as the data paper is cited as the source of the information used. We also request that users inform us of how they intend to use the data