bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of changes in cardiopulmonary resuscitation practices and outcomes on 1005 victims of out-of-hospital cardiac arrest during the COVID-19 outbreak: registry-based study
Authors:   on behalf of the GR-RéAC, Baert Valentine , Jaeger Deborah , Hubert Hervé , Lascarrou Jean-Baptiste , Debaty Guillaume , Chouihed Tahar , Javaudin François 
Published: December 2020

Abstract
Background
The COVID-19 outbreak requires a permanent adaptation of practices. Cardiopulmonary resuscitation (CPR) is also involved and we evaluated these changes in the management of out-of-hospital cardiac arrest (OHCA).

Methods
OHCA of medical origins identified from the French National Cardiac Arrest Registry between March 1st and April 31st 2020 (COVID-19 period), were analysed. Different resuscitation characteristics were compared with the same period from the previous year (non-COVID-19 period).

Results
Overall, 1005 OHCA during the COVID-19 period and 1620 during the non-COVID-19 period were compared. During the COVID-19 period, bystanders and first aid providers initiated CPR less frequently (49.8% versus 54.9%; difference, − 5.1 percentage points [95% CI, − 9.1 to − 1.2]; and 84.3% vs. 88.7%; difference, − 4.4 percentage points [95% CI, − 7.1 to − 1.6]; respectively) as did mobile medical teams (67.3% vs. 75.0%; difference, − 7.7 percentage points [95% CI, − 11.3 to − 4.1]). First aid providers used defibrillators less often (66.0% vs. 74.1%; difference, − 8.2 percentage points [95% CI, − 11.8 to − 4.6]). Return of spontaneous circulation (ROSC) and D30 survival were lower during the COVID-19 period (19.5% vs. 25.3%; difference, − 5.8 percentage points [95% CI, − 9.0 to − 2.5]; and 2.8% vs. 6.4%; difference, − 3.6 percentage points [95% CI, − 5.2 to − 1.9]; respectively).

Conclusions
During the COVID-19 period, we observed a decrease in CPR initiation regardless of whether patients were suspected of SARS-CoV-2 infection or not. In the current atmosphere, it is important to communicate good resuscitation practices to avoid drastic and lasting reductions in survival rates after an OHCA.
Risks of ventilator-associated pneumonia and invasive pulmonary aspergillosis in patients with viral acute respiratory distress syndrome related or not to Coronavirus 19 disease
Authors: Razazi Keyvan , Arrestier Romain , Haudebourg Anne Fleur , Benelli Brice , Carteaux Guillaume , Decousser Jean‑Winoc , Fourati Slim , Woerther Paul Louis , Schlemmer Frederic , Charles-Nelson Anais , Botterel Francoise , de Prost Nicolas , Mekontso Dessap Armand 
Published: December 2020

Abstract
Background
Data on incidence of ventilator-associated pneumonia (VAP) and invasive pulmonary aspergillosis in patients with severe SARS-CoV-2 infection are limited.

Methods
We conducted a monocenter retrospective study comparing the incidence of VAP and invasive aspergillosis between patients with COVID-19-related acute respiratory distress syndrome (C-ARDS) and those with non-SARS-CoV-2 viral ARDS (NC-ARDS).

Results
We assessed 90 C-ARDS and 82 NC-ARDS patients, who were mechanically ventilated for more than 48 h. At ICU admission, there were significantly fewer bacterial coinfections documented in C-ARDS than in NC-ARDS: 14 (16%) vs 38 (48%), p < 0.01. Conversely, significantly more patients developed at least one VAP episode in C-ARDS as compared with NC-ARDS: 58 (64%) vs. 36 (44%), p = 0.007. The probability of VAP was significantly higher in C-ARDS after adjusting on death and ventilator weaning [sub-hazard ratio = 1.72 (1.14–2.52), p < 0.01]. The incidence of multi-drug-resistant bacteria (MDR)-related VAP was significantly higher in C-ARDS than in NC-ARDS: 21 (23%) vs. 9 (11%), p = 0.03. Carbapenem was more used in C-ARDS than in NC-ARDS: 48 (53%), vs 21 (26%), p < 0.01. According to AspICU algorithm, there were fewer cases of putative aspergillosis in C-ARDS than in NC-ARDS [2 (2%) vs. 12 (15%), p = 0.003], but there was no difference in Aspergillus colonization.

Conclusions
In our experience, we evidenced a higher incidence of VAP and MDR-VAP in C-ARDS than in NC-ARDS and a lower risk for invasive aspergillosis in the former group.
Role of the adaptive immune response in sepsis
Authors: Brady Jack , Horie Shahd , Laffey John G. 
Published: December 2020

AbstractSepsis is a syndrome of shock and dysfunction of multiple vital organs that is caused by an uncontrolled immune response to infection and has a high mortality rate. There are no therapies for sepsis, and it has become a global cause for concern. Advances in patient care and management now mean that most patients survive the initial hyper-inflammatory phase of sepsis but progress to a later immunosuppressed phase, where 30% of patients die due to secondary infection. Deficits in the adaptive immune response may play a major role in sepsis patient mortality. The adaptive immune response involves a number of cell types including T cells, B cells and dendritic cells, all with immunoregulatory roles aimed at limiting damage and returning immune homeostasis after infection or insult. However, in sepsis, adaptive immune cells experience cell death or exhaustion, meaning that they have defective effector and memory responses ultimately resulting in an ineffective or suppressed immune defence. CD4+ T cells seem to be the most susceptible to cell death during sepsis and have ensuing defective secretory profiles and functions. Regulatory T cells seem to evade apoptosis and contribute to the immune suppression observed with sepsis. Preclinical studies have identified a number of new targets for therapy in sepsis including anti-apoptotic agents and monoclonal antibodies aimed at reducing cell death, exhaustion and maintaining/restoring adaptive immune cell functions. While early phase clinical trials have demonstrated safety and encouraging signals for biologic effect, larger scale clinical trial testing is required to determine whether these strategies will prove effective in improving outcomes from sepsis.
Continuous external negative pressure improves oxygenation and respiratory mechanics in Experimental Lung Injury in Pigs – A pilot proof-of-concept trial
Authors: Scharffenberg Martin , Wittenstein Jakob , Herzog Moritz , Tauer Sebastian , Vivona Luigi , Theilen Raphael , Bluth Thomas , Kiss Thomas , Koch Thea , Fiorentino Giuseppe , de Abreu Marcelo Gama , Huhle Robert 
Published: December 2020

Abstract
Background
Continuous external negative pressure (CENP) during positive pressure ventilation can recruit dependent lung regions. We hypothesised that CENP applied regionally to the thorax or the abdomen only, increases the caudal end-expiratory transpulmonary pressure depending on positive end-expiratory pressure (PEEP) in lung-injured pigs. Eight pigs were anesthetised and mechanically ventilated in the supine position. Pressure sensors were placed in the left pleural space, and a lung injury was induced by saline lung lavages. A CENP shell was placed at the abdomen and thorax (randomised order), and animals were ventilated with PEEP 15, 7 and zero cmH2O (15 min each). On each PEEP level, CENP of − 40, − 30, − 20, − 10 and 0 cmH2O was applied (3 min each). Respiratory and haemodynamic variables were recorded. Electrical impedance tomography allowed assessment of centre of ventilation.

Results
Compared to positive pressure ventilation alone, the caudal transpulmonary pressure was significantly increased by CENP of ≤ 20 cmH2O at all PEEP levels. CENP of – 20 cmH2O reduced the mean airway pressure at zero PEEP (P = 0.025). The driving pressure decreased at CENP of ≤ 10 at PEEP of 0 and 7 cmH2O (P < 0.001 each) but increased at CENP of – 30 cmH2O during the highest PEEP (P = 0.001). CENP of – 30 cmH2O reduced the mechanical power during zero PEEP (P < 0.001). Both elastance (P < 0.001) and resistance (P < 0.001) were decreased at CENP ≤ 30 at PEEP of 0 and 7 cmH2O. Oxygenation increased at CENP of ≤ 20 at PEEP of 0 and 7 cmH2O (P < 0.001 each). Applying external negative pressure significantly shifted the centre of aeration towards dorsal lung regions irrespectively of the PEEP level. Cardiac output decreased significantly at CENP -20 cmH2O at all PEEP levels (P < 0.001). Effects on caudal transpulmonary pressure, elastance and cardiac output were more pronounced when CENP was applied to the abdomen compared with the thorax.

Conclusions
In this lung injury model in pigs, CENP increased the end-expiratory caudal transpulmonary pressure. This lead to a shift of lung aeration towards dependent zones as well as improved respiratory mechanics and oxygenation, especially when CENP was applied to the abdomen as compared to the thorax. CENP values ≤ 20 cmH2O impaired the haemodynamics.
Alkaline phosphatase in pulmonary inflammation—a translational study in ventilated critically ill patients and rats
Authors:   for the BASIC study investigators, Juschten Jenny , Ingelse Sarah A. , Bos Lieuwe D. J. , Girbes Armand R. J. , Juffermans Nicole P. , van der Poll Tom , Schultz Marcus J. , Tuinman Pieter Roel 
Published: December 2020

Abstract
Background
Alkaline phosphatase (AP), a dephosphorylating enzyme, is involved in various physiological processes and has been shown to have anti-inflammatory effects.

Aim
To determine the correlation between pulmonary AP activity and markers of inflammation in invasively ventilated critically ill patients with or without acute respiratory distress syndrome (ARDS), and to investigate the effect of administration of recombinant AP on pulmonary inflammation in a well-established lung injury model in rats

Methods
AP activity was determined and compared with levels of various inflammatory mediators in bronchoalveolar lavage fluid (BALF) samples obtained from critically ill patients within 2 days of start of invasive ventilation. The endpoints of this part of the study were the correlations between AP activity and markers of inflammation, i.e., interleukin (IL)-6 levels in BALF. In RccHan Wistar rats, lung injury was induced by intravenous administration of 10 mg/kg lipopolysaccharide, followed by ventilation with a high tidal volume for 4 h. Rats received either an intravenous bolus of 1500 IU/kg recombinant AP or normal saline 2 h after intravenous LPS administration, right before start of ventilation. Endpoints of this part of the study were pulmonary levels of markers of inflammation, including IL-6, and markers of endothelial and epithelial dysfunction.

Results
BALF was collected from 83 patients; 10 patients had mild ARDS, and 15 had moderate to severe ARDS. AP activity correlated well with levels of IL-6 (r = 0.70), as well as with levels of other inflammatory mediators. Pulmonary AP activity between patients with and without ARDS was comparable (0.33 [0.14–1.20] vs 0.55 [0.21–1.42] U/L; p = 0.37). Animals with acute lung injury had markedly elevated pulmonary AP activity compared to healthy controls (2.58 [2.18–3.59] vs 1.01 [0.80–1.46] U/L; p < 0.01). Intravenous administration of recombinant AP did neither affect pulmonary inflammation nor endothelial and epithelial dysfunction.

Conclusions
In ventilated critically ill patients, pulmonary AP activity correlates well with markers of pulmonary inflammation, such as IL-6 and IL-8. In animals with lung injury, pulmonary AP activity is elevated. Administration of recombinant AP does not alter pulmonary inflammation and endothelial or epithelial dysfunction in the acute phase of a murine lung injury model.
Effect of routine vs on-demand nebulization of acetylcysteine with salbutamol on accumulation of airway secretions in endotracheal tubes: substudy of a randomized clinical trial
Authors: van der Hoeven Sophia , Ball Lorenzo , Constantino Federico , van Meenen David M. , Pelosi Paolo , Beenen Ludo F. , Schultz Marcus J. , Paulus Frederique ,   for the NEBULAE-investigators
Published: December 2020

Abstract
Background
Accumulated airway secretions in the endotracheal tube increase work of breathing and may favor airway colonization eventually leading to pneumonia. The aim of this preplanned substudy of the ‘Preventive Nebulization of Mucolytic Agents and Bronchodilating Drugs in Intubated and Ventilated Intensive Care Unit Patients trial’ (NEBULAE) was to compare the effect of routine vs on-demand nebulization of acetylcysteine with salbutamol on accumulation of secretions in endotracheal tubes in critically ill patients.

Results
In this single-center substudy of a national multicenter trial, patients were randomized to a strategy of routine nebulizations of acetylcysteine with salbutamol every 6 h until end of invasive ventilation, or to a strategy with on-demand nebulizations of acetylcysteine or salbutamol applied on strict clinical indications only. The primary endpoint, the maximum reduction in cross-sectional area (CSA) of the endotracheal tube was assessed with high-resolution computed tomography. Endotracheal tubes were collected from 72 patients, 36 from patients randomized to the routine nebulization strategy and 36 of patients randomized to the on-demand nebulization strategy. The maximum cross-sectional area (CSA) of the endotracheal tube was median 12 [6 to 15]% in tubes obtained from patients in the routine nebulization group, not different from median 9 [6 to 14]% in tubes obtained from patients in the on-demand nebulization group (P = 0.33).

Conclusion
In adult critically ill patients under invasive ventilation, routine nebulization of mucolytics and bronchodilators did not affect accumulation of airway secretions in the endotracheal tube.
Trial registration Clinicaltrials.gov Identifier: NCT02159196
The effects of tidal volume size and driving pressure levels on pulmonary complement activation: an observational study in critically ill patients
Authors:   for the BASIC–study group, de Beer Friso M. , Wieske Luuk , van Mierlo Gerard , Wouters Diana , Zeerleder Sacha , Bos Lieuwe D. , Juffermans Nicole P. , Schultz Marcus J. , van der Poll Tom , Lagrand Wim K. , Horn Janneke 
Published: December 2020

Abstract
Background
Mechanical ventilation can induce or even worsen lung injury, at least in part via overdistension caused by too large volumes or too high pressures. The complement system has been suggested to play a causative role in ventilator-induced lung injury.

Aims and methods
This was a single-center prospective study investigating associations between pulmonary levels of complement activation products and two ventilator settings, tidal volume (VT) and driving pressure (ΔP), in critically ill patients under invasive ventilation. A miniature bronchoalveolar lavage (BAL) was performed for determination of pulmonary levels of C5a, C3b/c, and C4b/c. The primary endpoint was the correlation between BAL fluid (BALF) levels of C5a and VT and ΔP. Levels of complement activation products were also compared between patients with and without ARDS or with and without pneumonia.

Results
Seventy-two patients were included. Median time from start of invasive ventilation till BAL was 27 [19 to 34] hours. Median VT and ΔP before BAL were 6.7 [IQR 6.1 to 7.6] ml/kg predicted bodyweight (PBW) and 15 [IQR 11 to 18] cm H2O, respectively. BALF levels of C5a, C3b/c and C4b/c were neither different between patients with or without ARDS, nor between patients with or without pneumonia. BALF levels of C5a, and also C3b/c and C4b/c, did not correlate with VT and ΔP. Median BALF levels of C5a, C3b/c, and C4b/c, and the effects of VT and ΔP on those levels, were not different between patients with or without ARDS, and in patients with or without pneumonia.

Conclusion
In this cohort of critically ill patients under invasive ventilation, pulmonary levels of complement activation products were independent of the size of VT and the level of ΔP. The associations were not different for patients with ARDS or with pneumonia. Pulmonary complement activation does not seem to play a major role in VILI, and not even in lung injury per se, in critically ill patients under invasive ventilation.
Study protocol for Post Pregnancy Family Planning Choices, an operations research study examining the effectiveness of interventions in the public and private sectors in Indonesia and Kenya
Authors: Charurat Elaine , Kennedy Sara , Qomariyah Siti , Schuster Anne , Christofield Megan , Breithaupt Lindsay , Kariuki Emmah , Muthamia Michael , Kabue Mark , Omanga Eunice , Stekelenburg Jelle 
Published: December 2020

Background: Global evidence suggests many postpartum and postabortion women have an unmet need for family planning (FP) after delivery or receiving care following loss of a pregnancy. Post Pregnancy Family Planning Choices, an operations research study, aims to examine the effectiveness of a package of postpregnancy FP interventions, inclusive of postpartum and postabortion FP. The interventions are being implemented in selected public and private facilities in Indonesia and Kenya and focus on quality FP counseling and service provision prior to discharge. This manuscript presents the study protocol, documenting how the study team intends to determine key factors that influence uptake of postpregnancy FP. Methods: This is a multi-country, quasi-experimental three-year operations research study in Brebes and Batang Districts of Indonesia and Meru and Kilifi Counties of Kenya. Quantitative and qualitative data is collected longitudinally through interviews and health facility assessments at multiple time points. Data is gathered from 22 health facilities; 8,796 antenatal, postpartum, and postabortion clients; and key informants at national, subnational, facility, and community levels. Quantitative study data is collected and managed using REDCap (Research Electronic Data Capture). Once data are thoroughly cleaned and reviewed, regression models and multilevel analyses will explore quantitative data. Qualitative study data is collected using audio recordings and transcribed to Microsoft Word, then analyzed using ATLAS.ti. Qualitative datasets will be analyzed using grounded theory methods. Discussion: The ultimate goals of the study are to generate and disseminate actionable evidence of positive drivers, barriers, and activities that do not yield results with regard to increasing postpregnancy FP programmatic activities, and to institutionalize postpregnancy FP in the public and private sectors in Indonesia and Kenya. We hope these learnings and experience will contribute to global efforts to advance and scale up postpregnancy FP in similar settings beyond these two countries. Trial registration: ClinicalTrials.gov NCT03333473
The feasibility of implementing an exercise programme for deconditioned cancer survivors in a national cancer centre: FIXCAS Study
Authors: Devenney Kate , Murphy Niamh , Ryan Ronan , Grant Clíona , Kennedy John , Manecksha Rustom P. , Sheils Orla , McNeely Margaret L. , Hussey Juliette , Sheill Grainne 
Published: December 2020

Introduction: As both the number of cancer survivors and the length of survival time are increasing, long-term health issues related to cancer and its treatment are becoming more prevalent. Research suggests that exercise can mitigate several negative health consequences in cancer survivors and improve physical function and quality of life. Multi-modal exercise interventions have been proposed as a cornerstone for survivorship care. However, studies evaluating exercise programmes within the Irish population are lacking. Purpose: To evaluate the introduction, implementation and acceptability of a multi-modal exercise rehabilitation programme for deconditioned cancer survivors in a real-world, standard practice setting. Methods and analysis: In this single-arm prospective feasibility study, cancer survivors (n=40) will undergo a 10-week multi-modal exercise programme. The study population will comprise of cancer survivors attending outpatient services in an Irish national cancer centre. Participants will be aged 18 or older and have completed treatment with curative intent. Feasibility will be evaluated in terms of recruitment, adherence and compliance to the programme. Secondary outcomes will examine physical function and quality of life measures. In addition, the acceptability of the programme will be assessed through stakeholder feedback. Ethics and dissemination: Ethical approval through the St. James’s Hospital and Tallaght University Hospital Research and Ethics Committee is currently pending. The study results will be used to optimise the intervention content and may serve as the foundation for a larger definitive trial. Results will be disseminated through peer-review journals, congresses and relevant clinical groups. Trial registration: ClinicalTrials.gov NCT04026659 (19/07/19)
A living mapping review for COVID-19 funded research projects: three-month update
Authors: Norton Alice , Bucher Adrian , Antonio Emilia , Advani Nicole , Grund Henrike , Mburu Sheila , Clegg Emma , Scott Laura , Boily-Larouche Genevieve , Lay A. Morgan , Carson Gail , Tufet Bayona Marta 
Published: December 2020

Background:The coronavirus disease 2019 (COVID-19) has resulted in an unprecedented research response, demonstrating exceptional examples of rapid research and collaboration. There is however a need for greater coordination, with limited resources and the shifting global nature of the pandemic resulting in a proliferation of research projects underpowered and unable to achieve their aims.Methods:The UK Collaborative on Development Research (UKCDR) and Global Research Collaboration for Infectious Disease Preparedness (GloPID-R), two funder coordination groups have collaborated to develop a live database of funded research projects across the world relating to COVID-19. Drawing data continually from their members and further global funding bodies, as of 15thOctober 2020 the database contains 5,084 projects, funded by 71 funders, taking place across 134 countries representing an investment of at least $1.7 billion. To our knowledge it is one of the most comprehensive databases, covering a wide breadth of research disciplines. The database is aligned to the World Health Organisation (WHO) Global Research Roadmap: 2019 Novel Coronavirus. It is being used by the WHO, governments and multi-lateral policy makers, research funders and researchers.This living mapping review aims to supplement the database by providing an open accessible and frequently updated resource summarising the characteristics of the COVID-19 funded research portfolio. Both descriptive and thematic analysis will be presented and updated frequently to aid interpretation of the global COVID-19 funded research portfolio.Results:In this three-month update analysis we provide an updated detailed descriptive analysis of the database and focus our thematic analysis on research gaps, research areas in need of coordination, study populations and research locations (with a focus on resource-limited countries).Conclusions:This living mapping review will help both funders and researchers to prioritise resources to underfunded areas where there is greatest research need and facilitate further strategic collaboration.