Ebola outbreak in Guinea, 2021: Clinical care of patients with Ebola virus disease.

Background: Experience from the Zaire Ebolavirus epidemic in the eastern Democratic Republic of the Congo (2018-2020) demonstrates that early initiation of essential critical care and administration of Zaire Ebolavirus specific monoclonal antibodies may be associated with improved outcomes among patients with Ebola virus disease (EVD). Objectives: This series describes 13 EVD patients and 276 patients with suspected EVD treated during a Zaire Ebolavirus outbreak in Guinea in 2021. Method: Patients with confirmed or suspected EVD were treated in two Ebola treatment centres (ETC) in the region of N'zérékoré. Data were reviewed from all patients with suspected or confirmed EVD hospitalised in these two ETCs during the outbreak (14 February 2021 - 19 June 2021). Ebola-specific monoclonal antibodies, were available 2 weeks after onset of the outbreak. Results: Nine of the 13 EVD patients (age range: 22-70 years) survived. The four EVD patients who died, including one pregnant woman, presented with multi-organ dysfunction and died within 48 h of admission. All eight patients who received Ebola-specific monoclonal antibodies survived. Four of the 13 EVD patients were health workers. Improvement of ETC design facilitated implementation of WHO-recommended 'optimized supportive care for EVD'. In this context, pragmatic clinical training was integrated in routine ETC activities. Initial clinical manifestations of 13 confirmed EVD patients were similar to those of 276 patients with suspected, but subsequently non confirmed EVD. These patients suffered from other acute infections (e.g. malaria in 183 of 276 patients; 66%). Five of the 276 patients with suspected EVD died. One of these five patients had Lassa virus disease and a coronavirus disease 2019 (COVID-19) co-infection. Conclusion: Multidisciplinary outbreak response teams can rapidly optimise ETC design. Trained clinical teams can provide WHO-recommended optimised supportive care, including safe administration of Ebola-specific monoclonal antibodies. Pragmatic training in essential critical care can be integrated in routine ETC activities. Contribution: This article describes clinical realities associated with implementation of WHO-recommended standards of 'optimized supportive care' and administration of Ebola virus specific treatments. In this context, the importance of essential design principles of ETCs is underlined, which allow continuous visual contact and verbal interaction of health workers and families with their patients. Elements that may contribute to further quality of care improvements for patients with confirmed or suspected EVD are discussed.

Ebola outbreak in Guinea, 2021: Clinical care of patients with Ebola virus disease

Background: Experience from the Zaire Ebolavirus epidemic in the eastern Democratic Republic of the Congo (2018­2020) demonstrates that early initiation of essential critical care and administration of Zaire Ebolavirus specific monoclonal antibodies may be associated with improved outcomes among patients with Ebola virus disease (EVD). Objectives: This series describes 13 EVD patients and 276 patients with suspected EVD treated during a Zaire Ebolavirus outbreak in Guinea in 2021. Method: Patients with confirmed or suspected EVD were treated in two Ebola treatment centres (ETC) in the region of N'zérékoré. Data were reviewed from all patients with suspected or confirmed EVD hospitalised in these two ETCs during the outbreak (14 February 2021 ­ 19 June 2021). Ebola-specific monoclonal antibodies, were available 2 weeks after onset of the outbreak. Results: Nine of the 13 EVD patients (age range: 22­70 years) survived. The four EVD patients who died, including one pregnant woman, presented with multi-organ dysfunction and died within 48 h of admission. All eight patients who received Ebola-specific monoclonal antibodies survived. Four of the 13 EVD patients were health workers. Improvement of ETC design facilitated implementation of WHO-recommended 'optimized supportive care for EVD'. In this context, pragmatic clinical training was integrated in routine ETC activities. Initial clinical manifestations of 13 confirmed EVD patients were similar to those of 276 patients with suspected, but subsequently non confirmed EVD. These patients suffered from other acute infections (e.g. malaria in 183 of 276 patients; 66%). Five of the 276 patients with suspected EVD died. One of these five patients had Lassa virus disease and a coronavirus disease 2019 (COVID-19) co-infection. Conclusion: Multidisciplinary outbreak response teams can rapidly optimise ETC design. Trained clinical teams can provide WHO-recommended optimised supportive care, including safe administration of Ebola-specific monoclonal antibodies. Pragmatic training in essential critical care can be integrated in routine ETC activities. Contribution: This article describes clinical realities associated with implementation of WHO-recommended standards of 'optimized supportive care' and administration of Ebola virus specific treatments. In this context, the importance of essential design principles of ETCs is underlined, which allow continuous visual contact and verbal interaction of health workers and families with their patients. Elements that may contribute to further quality of care improvements for patients with confirmed or suspected EVD are discussed.

Rapid Bacteria Detection from Patients' Blood Bypassing Classical Bacterial Culturing.

Sepsis is a life-threatening condition mostly caused by a bacterial infection resulting in inflammatory reaction and organ dysfunction if not treated effectively. Rapid identification of the causing bacterial pathogen already in the early stage of bacteremia is therefore vital. Current technologies still rely on time-consuming procedures including bacterial culturing up to 72 h. Our approach is based on ultra-rapid and highly sensitive nanomechanical sensor arrays. In measurements we observe two clearly distinguishable distributions consisting of samples with bacteria and without bacteria respectively. Compressive surface stress indicates the presence of bacteria. For this proof-of-concept, we extracted total RNA from EDTA whole blood samples from patients with blood-culture-confirmed bacteremia, which is the reference standard in diagnostics. We determined the presence or absence of bacterial RNA in the sample through 16S-rRNA hybridization and species-specific probes using nanomechanical sensor arrays. Via both probes, we identified two clinically highly-relevant bacterial species i.e., Escherichia coli and Staphylococcus aureus down to an equivalent of 20 CFU per milliliter EDTA whole blood. The dynamic range of three orders of magnitude covers most clinical cases. We correctly identified all patient samples regarding the presence or absence of bacteria. We envision our technology as an important contribution to early and sensitive sepsis diagnosis directly from blood without requirement for cultivation. This would be a game changer in diagnostics, as no commercial PCR or POCT device currently exists who can do this.

Development of the PREDS score to predict in-hospital mortality of patients with Ebola virus disease under advanced supportive care: Results from the EVISTA cohort in the Democratic Republic of the Congo.

Background: As mortality remains high for patients with Ebola virus disease (EVD) despite new treatment options, the ability to level up the provided supportive care and to predict the risk of death is of major importance. This analysis of the EVISTA cohort aims to describe advanced supportive care provided to EVD patients in the Democratic Republic of the Congo (DRC) and to develop a simple risk score for predicting in-hospital death, called PREDS. Methods: In this prospective cohort (NCT04815175), patients were recruited during the 10th EVD outbreak in the DRC across three Ebola Treatment Centers (ETCs). Demographic, clinical, biological, virological and treatment data were collected. We evaluated factors known to affect the risk of in-hospital death and applied univariate and multivariate Cox proportional-hazards analyses to derive the risk score in a training dataset. We validated the score in an internal-validation dataset, applying C-statistics as a measure of discrimination. Findings: Between August 1st 2018 and December 31th 2019, 711 patients were enrolled in the study. Regarding supportive care, patients received vasopressive drug (n = 111), blood transfusion (n = 101), oxygen therapy (n = 250) and cardio-pulmonary ultrasound (n = 15). Overall, 323 (45%) patients died before day 28. Six independent prognostic factors were identified (ALT, creatinine, modified NEWS2 score, viral load, age and symptom duration). The final score range from 0 to 13 points, with a good concordance (C = 86.24%) and calibration with the Hosmer-Lemeshow test (p = 0.12). Interpretation: The implementation of advanced supportive care is possible for EVD patients in emergency settings. PREDS is a simple, accurate tool that could help in orienting early advanced care for at-risk patients after external validation. Funding: This study was funded by ALIMA.

Clinical presentation, outcomes and factors associated with mortality: A prospective study from three COVID-19 referral care centres in West Africa.

OBJECTIVES: The overall death toll from COVID-19 in Africa is reported to be low but there is little individual-level evidence on the severity of the disease. This study examined the clinical spectrum and outcome of patients monitored in COVID-19 care centres (CCCs) in two West-African countries. METHODS: Burkina Faso and Guinea set up referral CCCs to hospitalise all symptomatic SARS-CoV-2 carriers, regardless of the severity of their symptoms. Data collected from hospitalised patients by November 2020 are presented. RESULT: A total of 1,805 patients (64% men, median age 41 years) were admitted with COVID-19. Symptoms lasted for a median of 7 days (IQR 4-11). During hospitalisation, 443 (25%) had a SpO2 < 94% at least once, 237 (13%) received oxygen and 266 (15%) took corticosteroids. Mortality was 5% overall, and 1%, 5% and 14% in patients aged <40, 40-59 and ≥60 years, respectively. In multivariable analysis, the risk of death was higher in men (aOR 2.0, 95% CI 1.1; 3.6), people aged ≥60 years (aOR 2.9, 95% CI 1.7; 4.8) and those with chronic hypertension (aOR 2.1, 95% CI 1.2; 3.4). CONCLUSION: COVID-19 is as severe in Africa as elsewhere, and there must be more vigilance for common risk factors such as older age and hypertension.

Rapid and Ultrasensitive Detection of Mutations and Genes Relevant to Antimicrobial Resistance in Bacteria.

The worldwide emergence of multidrug-resistant (MDR) bacteria is associated with significant morbidity, mortality, and healthcare costs. Rapid and accurate diagnostic methods to detect antibiotic resistance are critical for antibiotic stewardship and infection control measurements. Here a cantilever nanosensor-based diagnostic assay is shown to detect single nucleotide polymorphisms (SNPs) and genes associated with antibiotic resistance in Gram negative (Pseudomonas aeruginosa) and positive (Enterococcus faecium) bacteria, representing frequent causes for MDR infections. Highly specific RNA capture probes for SNPs (ampRD135G or ampRG154R ) or resistance genes (vanA, vanB, and vanD) allow to detect the binding of bacterial RNA within less than 5 min. Serial dilutions of bacterial RNA indicate an unprecedented sensitivity of 10 fg µL-1 total RNA corresponding to less than ten bacterial cells for SNPs and 1 fg µL-1 total RNA for vanD detection equivalent to single bacterial cell sensitivity.

Challenges of implementing the Paediatric Surviving Sepsis Campaign International Guidelines 2020 in resource-limited settings: A real-world view beyond the academia.

The Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-associated Organ Dysfunction in Children was released in 2020 and is intended for use in all global settings that care for children with sepsis. However, practitioners managing children with sep sis in resource-limited settings (RLS) face several challenges and disease patterns not experienced by those in resource-rich settings. Based upon our collective experience from RLS, we aimed to reflect on the difficulties of implementing the international guidelines. We believe there is an urgent need for more evidence from RLS on feasible, efficacious approaches to the management of sepsis and septic shock that could be included in future context-specific guidelines.

International evidence-based guidelines on Point of Care Ultrasound (POCUS) for critically ill neonates and children issued by the POCUS Working Group of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC).

BACKGROUND: Point-of-care ultrasound (POCUS) is nowadays an essential tool in critical care. Its role seems more important in neonates and children where other monitoring techniques may be unavailable. POCUS Working Group of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC) aimed to provide evidence-based clinical guidelines for the use of POCUS in critically ill neonates and children. METHODS: Creation of an international Euro-American panel of paediatric and neonatal intensivists expert in POCUS and systematic review of relevant literature. A literature search was performed, and the level of evidence was assessed according to a GRADE method. Recommendations were developed through discussions managed following a Quaker-based consensus technique and evaluating appropriateness using a modified blind RAND/UCLA voting method. AGREE statement was followed to prepare this document. RESULTS: Panellists agreed on 39 out of 41 recommendations for the use of cardiac, lung, vascular, cerebral and abdominal POCUS in critically ill neonates and children. Recommendations were mostly (28 out of 39) based on moderate quality of evidence (B and C). CONCLUSIONS: Evidence-based guidelines for the use of POCUS in critically ill neonates and children are now available. They will be useful to optimise the use of POCUS, training programs and further research, which are urgently needed given the weak quality of evidence available.

International evidence-based guidelines on Point of Care Ultrasound (POCUS) for critically ill neonates and children issued by the POCUS Working Group of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC)

Point-of-care ultrasound (POCUS) is nowadays an essential tool in critical care. Its role seems more important in neonates and children where other monitoring techniques may be unavailable. POCUS Working Group of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC) aimed to provide evidence-based clinical guidelines for the use of POCUS in critically ill neonates and children. Creation of an international Euro-American panel of paediatric and neonatal intensivists expert in POCUS and systematic review of relevant literature. A literature search was performed, and the level of evidence was assessed according to a GRADE method. Recommendations were developed through discussions managed following a Quaker-based consensus technique and evaluating appropriateness using a modified blind RAND/UCLAvoting method. AGREE statement was followed to prepare this document. Panellists agreed on 39 out of 41 recommendations for the use of cardiac, lung, vascular, cerebral and abdominal POCUS in critically ill neonates and children. Recommendations were mostly (28 out of 39) based on moderate quality of evidence (B and C). Evidence-based guidelines for the use of POCUS in critically ill neonates and children are now available. They will be useful to optimise the use of POCUS, training programs and further research, which are urgently needed given the weak quality of evidence available.

Prognostic Impact of Ventral Versus Dorsal Tumor Location After Total Mesorectal Excision of Rectal Cancer.

BACKGROUND: Multidisciplinary treatment of rectal cancer, including neoadjuvant treatment, total mesorectal excision, and adjuvant chemotherapy, have improved oncological outcome. Preoperative radiation therapy is advocated by national and international guidelines in all patients with AJCC stage II and III rectal cancer. Although this treatment reduces local recurrence rates with no effect on overall survival, there are possible short- and long-term side effects of radiation exposure, so patients should be carefully selected for neoadjuvant radiation therapy. METHODS: We analyzed whether ventral or dorsal tumor location affects local recurrence rates following radical rectal resection. Patients who underwent radical rectal resection for mid or low rectal cancer in our department between October 2001 and December 2013 were included. Prognostic indicators for local recurrence were analyzed using univariate and multivariate analyses. RESULTS: Overall, 480 patients met the inclusion criteria. Univariate analysis identified surgical procedure (hazard ratio [HR] 1.9, p = 0.006), ventral tumor location (HR 3.8, p < 0.001), and a pathologic circumferential resection margin (pCRM) (HR 9.3, p < 0.001) as prognostic factors of local recurrence. Multivariate analysis revealed tumor location (HR 3.5, p < 0.001) and pCRM (HR 6.0, p = 0.002) as independent factors for local recurrence. Neoadjuvant treatment of AJCC stage II and III tumors reduced the local recurrence rate at ventral but not at dorsal tumor locations (p < 0.001). CONCLUSIONS: Ventral versus dorsal tumor location is an independent prognostic factor for local recurrence. Tumor location may aid in patient selection for neoadjuvant treatment.

Effects of saline or albumin fluid bolus in resuscitation: evidence from re-analysis of the FEAST trial.

BACKGROUND: Fluid resuscitation is the recommended management of shock, but increased mortality in febrile African children in the FEAST trial. We hypothesised that fluid bolus-induced deaths in FEAST would be associated with detectable changes in cardiovascular, neurological, or respiratory function, oxygen carrying capacity, and blood biochemistry. METHODS: We developed composite scores for respiratory, cardiovascular, and neurological function using vital sign data from the FEAST trial, and used them to compare participants from FEAST with those from four other cohorts and to identify differences between the bolus (n=2097) and no bolus (n=1044) groups of FEAST. We calculated the odds of adverse outcome for each ten-unit increase in baseline score using logistic regression for each cohort. Within FEAST participants, we also compared haemoglobin and plasma biochemistry between bolus and non-bolus patients, assessed the effects of these factors along with the vital sign scores on the contribution of bolus to mortality using Cox proportional hazard models, and used Bayesian clustering to identify subgroups that differed in response to bolus. The FEAST trial is registered with ISRCTN, number ISRCTN69856593. FINDINGS: Increasing respiratory (odds ratio 1·09, 95% CI 1·07-1·11), neurological (1·26, 1·21-1·31), and cardiovascular scores (1·09, 1·05-1·14) were associated with death in FEAST (all p<0·0001), and with adverse outcomes for specific scores in the four other cohorts. In FEAST, fluid bolus increased respiratory and neurological scores and decreased cardiovascular score at 1 h after commencement of the infusion. Fluid bolus recipients had mean 0·33 g/dL (95% CI 0·20-0·46) reduction in haemoglobin concentration after 8 h (p<0·0001), and at 24 h had a decrease of 1·41 mEq/L (95% CI 0·76-2·06; p=0·0002) in mean base excess and increase of 1·65 mmol/L (0·47-2·8; p=0·0070) in mean chloride, and a decrease of 0·96 mmol/L (0·45 to 1·47; p=0·0003) in bicarbonate. There were similar effects of fluid bolus in three patient subgroups, identified on the basis of their baseline characteristics. Hyperchloraemic acidosis and respiratory and neurological dysfunction induced by saline or albumin bolus explained the excess mortality due to bolus in Cox survival models. INTERPRETATION: In the resuscitation of febrile children, albumin and saline boluses can cause respiratory and neurological dysfunction, hyperchloraemic acidosis, and reduction in haemoglobin concentration. The findings support the notion that fluid resuscitation with unbuffered electrolyte solutions may cause harm and their use should be cautioned. The effects of lower volumes of buffered solutions should be evaluated further. FUNDING: Medical Research Council, Department for International Development, National Institute for Health Research, Imperial College Biomedical Research Centre.

Use of bubble continuous positive airway pressure (bCPAP) in the management of critically ill children in a Malawian paediatric unit: an observational study.

Introduction: In low-resource countries, respiratory failure is associated with a high mortality risk among critically ill children. We evaluated the role of bubble continuous positive airway pressure (bCPAP) in the routine care of critically ill children in Lilongwe, Malawi. Methods: We conducted an observational study between 26 February and 15 April 2014, in an urban paediatric unit with approximately 20 000 admissions/year (in-hospital mortality <5% approximately during this time period). Modified oxygen concentrators or oxygen cylinders provided humidified bCPAP air/oxygen flow. Children up to the age of 59 months with signs of severe respiratory dysfunction were recruited. Survival was defined as survival during the bCPAP-treatment and during a period of 48 hours following the end of the bCPAP-weaning process. Results: 117 children with signs of respiratory failure were included in this study and treated with bCPAP. Median age: 7 months. Malaria rapid diagnostic tests were positive in 25 (21%) cases, 15 (13%) had severe anaemia (Hb < 7.0 g/dL); 55 (47%) children had multiorgan failure (MOF); 22 (19%) children were HIV-infected/exposed. 28 (24%) were severely malnourished. Overall survival was 79/117 (68%); survival was 54/62 (87%) in children with very severe pneumonia (VSPNA) but without MOF. Among the 19 children with VSPNA (single-organ failure (SOF)) and negative HIV tests, all children survived. Survival rates were lower in children with MOF (including shock) (45%) as well as in children with severe malnutrition (36%) and proven HIV infection or exposure (45%). Conclusion: Despite the limitations of this study, the good outcome of children with signs of severe respiratory dysfunction (SOF) suggests that it is feasible to use bCPAP in the hospital management of critically ill children in resource-limited settings. The role of bCPAP and other forms of non-invasive ventilatory support as a part of an improved care package for critically ill children with MOF at tertiary and district hospital level in low-resource countries needs further evaluation. Critically ill children with nutritional deficiencies and/or HIV infection/exposure need further study to determine bCPAP efficacy.

Comprehensive Treatment and Rehabilitation of Patients With Osteosarcoma of the Mandible.

OBJECTIVE: The article studies state-of-the art physical therapeutic techniques as a high degree of relevance to minimize invalidation and improve quality of life for patients with dental osteosarcoma. MATERIALS AND METHODS: A randomized controlled clinical trial was conducted in 21 patients with osteogenic sarcoma of mandible (C41.1). There were 10 patients in the experimental group and 11 patients in the control group. RESULTS: A comprehensive treatment and rehabilitation program for patients with osteosarcoma of mandible was developed. The first part of the program comprised 3 basic phases: preop chemotherapy, surgery, and postop rehabilitation. The surgical treatment further included resection of an affected part of the mandible and primary repair of the defect with jaw fragments and an autoimplant joined together with the help of positioning devices. The postop rehabilitation included postop chemotherapy and mesodiencephalic modulation (MDM). The second part of the program comprised preop examination, modeling, using stereolytic 3-dimensional models of the mandible, corrective surgeries, including implantation into the autoimplant-a fragment of patient's fibula, and building of a removable titanium alloy-based denture. MDM sessions were administered after each invasive intervention. CONCLUSIONS: Higher psychological and physical well-being was observed in the experimental group as compared with the control group (P < 0.01) in 2 weeks after the first surgery and 2 months after scheduled corrective surgeries, which finished in denture installation.

A pediatric death audit in a large referral hospital in Malawi.

BACKGROUND: Death audits have been used to describe pediatric mortality in under-resourced settings, where record keeping is often a challenge. This information provides the cornerstone for the foundation of quality improvement initiatives. Malawi, located in sub-Saharan Africa, currently has an Under-5 mortality rate of 64/1000. Kamuzu Central Hospital, in the capital city Lilongwe, is a busy government referral hospital, which admits up to 3000 children per month. A study published in 2013 reported mortality rates as high as 9%. This is the first known audit of pediatric death files conducted at this hospital. METHODS: A retrospective chart review on all pediatric deaths that occurred at Kamuzu Central Hospital (excluding deaths in the neonatal nursery) during a 13-month period was done using a standardized death audit form. A descriptive analysis was completed, including patient demographics, HIV and nutritional status, and cause of death. Modifiable factors were identified that may have contributed to mortality, including a lack of vital sign collection, poor documentation, and delays in the procurement or results of tests, studies, and specialist review. RESULTS: Seven hundred forty three total pediatric deaths were recorded and 700 deceased patient files were reviewed. The mortality rate by month ranged from a low of 2.2% to a high of 4.4%. Forty-four percent of deaths occurred within the first 24 h of admission, and 59% occurred within the first 48 h. The most common causes of death were malaria, malnutrition, HIV-related illnesses, and sepsis. CONCLUSIONS: The mortality rate for this pediatric referral center has dramatically decreased in the 6 years since the last published mortality data, but remains high. Areas identified for continued development include improved record keeping, improved patient assessment and monitoring, and more timely and reliable provision of testing and treatment. This study demonstrates that in low-resource settings, where reliable record keeping is often difficult, death audits are useful tools to describe the sickest patient population and determine factors possibly contributing to mortality that may be amenable to quality improvement interventions.

Facing the Guilt and Commemorating the Victims: German Radiology and Radiation Oncology During National Socialism.

Whereas the scientific community is aware of atrocities committed by medical doctors like Mengele, the specifics of radiology and radiation oncology during National Socialism remain largely unknown. Starting in 2010, the German Radiology Association and the German Association of Radiation Oncology coordinated a national project looking into original archival material. A national committee convened in 2013 to discuss the project's findings, which were also the subject of a symposium at the University of Tuebingen in 2016 on radiology under National Socialism. The project identified approximately 160 radiologists who were victimized because of their Jewish descent, among them Gustav Bucky (known for the Bucky factor in x-ray diagnostics). Radiologists throughout Germany took part in forced sterilizations. The "Schutzstaffel," commonly known as SS, had a special radiology unit that was established for tuberculosis screening. Radiation was also used for sterilization experiments in the Auschwitz concentration camp with subsequent surgical procedures to enable histological analysis of the irradiated tissue. Reflection on medicine during the Holocaust will be strengthened by specific facts related to the respective medical field. Radiologists were involved in atrocious medical experiments as well as in supporting Nazi policies in Germany. These facts provoke ethical considerations about marginalized patient groups and doctor-patient communication. They also raise questions about "evidence-based" medicine as sole justification for medical procedures. In summary, historical studies will be able to help in the professional identity formation of radiologists gaining awareness to ethical issues of today.

Review of supplemental oxygen and respiratory support for paediatric emergency care in sub-Saharan Africa.

INTRODUCTION: In African countries, respiratory infections and severe sepsis are common causes of respiratory failure and mortality in children under five years of age. Mortality and morbidity in these children could be reduced with adequate respiratory support in the emergency care setting. The purpose of this review is to describe management priorities in the emergency care of critically ill children presenting with respiratory problems. Basic and advanced respiratory support measures are described for implementation according to available resources, work load and skill-levels. METHODS: We did a focused search of respiratory support for critically ill children in resource-limited settings over the past ten years, using the search tools PubMed and Google Scholar, the latest WHO guidelines, international 'Advanced Paediatric Life Support' guidelines and paediatric critical care textbooks. RESULTS: The implementation of triage and rapid recognition of respiratory distress and hypoxia with pulse oximetry is important to correctly identify critically ill children with increased risk of mortality in all health facilities in resource constrained settings. Basic, effective airway management and respiratory support are essential elements of emergency care. Correct provision of supplemental oxygen is safe and its application alone can significantly improve the outcome of critically ill children. Non-invasive ventilatory support is cost-effective and feasible, with the potential to improve emergency care packages for children with respiratory failure and other organ dysfunctions. Non-invasive ventilation is particularly important in severely under-resourced regions unable to provide intubation and invasive mechanical ventilation support. Malnutrition and HIV-infection are important co-morbid conditions, associated with increased mortality in children with respiratory dysfunction. DISCUSSION: A multi-disciplinary approach is required to optimise emergency care for critically ill children in low-resource settings. In this context, it is important to consider aspects of training of staff, technical support and pragmatic research.

Nitric oxide-fixation by non-symbiotic haemoglobin proteins in Arabidopsis thaliana under N-limited conditions.

Nitric oxide (NO) is an important signalling molecule that is involved in many different physiological processes in plants. Here, we report about a NO-fixing mechanism in Arabidopsis, which allows the fixation of atmospheric NO into nitrogen metabolism. We fumigated Arabidopsis plants cultivated in soil or as hydroponic cultures during the whole growing period with up to 3 ppmv of NO gas. Transcriptomic, proteomic and metabolomic analyses were used to identify non-symbiotic haemoglobin proteins as key components of the NO-fixing process. Overexpressing non-symbiotic haemoglobin 1 or 2 genes resulted in fourfold higher nitrate levels in these plants compared with NO-treated wild-type. Correspondingly, rosettes size and weight, vegetative shoot thickness and seed yield were 25, 40, 30, and 50% higher, respectively, than in wild-type plants. Fumigation with 250 ppbv 15 NO confirmed the importance of non-symbiotic haemoglobin 1 and 2 for the NO-fixation pathway, and we calculated a daily uptake for non-symbiotic haemoglobin 2 overexpressing plants of 250 mg N/kg dry weight. This mechanism is probably important under conditions with limited N supply via the soil. Moreover, the plant-based NO uptake lowers the concentration of insanitary atmospheric NOx, and in this context, NO-fixation can be beneficial to air quality.

Review of supplemental oxygen and respiratory support for paediatric emergency care in sub-Saharan Africa

Introduction:In African countries, respiratory infections and severe sepsis are common causes of respiratory failure and mortality in children under five years of age. Mortality and morbidity in these children could be reduced with adequate respiratory support in the emergency care setting. The purpose of this review is to describe management priorities in the emergency care of critically ill children presenting with respiratory problems. Basic and advanced respiratory support measures are described for implementation according to available resources, work load and skill-levels.Methods:We did a focused search of respiratory support for critically ill children in resource-limited settings over the past ten years, using the search tools PubMed and Google Scholar, the latest WHO guidelines, international 'Advanced Paediatric Life Support' guidelines and paediatric critical care textbooks.Results:The implementation of triage and rapid recognition of respiratory distress and hypoxia with pulse oximetry is important to correctly identify critically ill children with increased risk of mortality in all health facilities in resource constrained settings. Basic, effective airway management and respiratory support are essential elements of emergency care. Correct provision of supplemental oxygen is safe and its application alone can significantly improve the outcome of critically ill children. Non-invasive ventilatory support is cost-effective and feasible, with the potential to improve emergency care packages for children with respiratory failure and other organ dysfunctions. Non-invasive ventilation is particularly important in severely under-resourced regions unable to provide intubation and invasive mechanical ventilation support. Malnutrition and HIV-infection are important co-morbid conditions,associated with increased mortality in children with respiratory dysfunction.Discussion:A multi-disciplinary approach is required to optimise emergency care for critically ill children in low-resource settings. In this context, it is important to consider aspects of training of staff, technical support and pragmatic research