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Background: This study looked at the characteristics and outcomes of critically ill patients with confirmed influenza A (H1N1) pdm09 infection in the Western Balkans in the post-pandemic period. Materials and Methods: This retrospective observational study of medical records and associated data collected during the post-pandemic period included all mechanically ventilated adult patients of two university-affiliated hospitals of the Western Balkans between 1 January and 31 March 2019 who had influenza A (H1N1) pdm09 infection confirmed by real-time reverse transcriptase-polymerase chain reaction from nasopharyngeal swab specimens and respiratory secretions. Results: The study included 89 patients, 49 males (55.1%), aged 56.09 ± 12.64 years. The median time from shift from hospital time to intensive care unit was 1 day (range: 1–2). In the post-pandemic period, cases observed in this study were found to have the following comorbidities: cardiovascular diseases in 44 (49.4%) patients and diabetes in 21 (23.6%) patients. Thirty-one patients (34.8%) in this study were obese. All 89 patients (100%) experienced some degree of acute respiratory distress syndrome, and 39 (44%) had multiorgan failure. Eighty-three patients (93%) were intubated and mechanically ventilated, 6 (7%) received non-invasive mechanical ventilation, 12 (13%) were treated with vvECMO and 36 (40%) received renal replacement therapy. Vasoactive support was needed by 56 (63%) patients. The median duration of mechanical ventilation was 9 (6–15.5) days. The hospital mortality rate was 44%. Conclusion: Critically ill patients with confirmed influenza A (H1N1) pdm09 infection in the post-pandemic season were older, required vasoactive drugs more often, and there was a trend of higher survival compared to H1N1 infection patients in the previous pandemic seasons.

Background/Aim. Acinetobacter is one of the most common causes of nosocomial infections, especially ventilatorassociated pneumonia (VAP). Considering the increased presence of multidrug-resistant microorganisms and the lack of novel antibiotics, colistin merged as the last-resort antibiotic for life threatening nosocomial infections. Intravenous use of antibiotics is accepted as a gold standard for the treatment of pneumonia, but additional administration of inhaled antibiotics in the treatment of VAP has shown to be advantageous in some clinical trials. The aim of this study was to investigate the effect of inhalatory colistin as an adjunct to intravenous colistin on the survival of patients with VAP caused by Acinetobacter species. Methods. We conducted a retrospective study to evaluate the efficacy of combination of inhalatory and intravenous colistin vs. intravenous colistin alone in 69 patients in the Intensive Care Units (ICU) with VAP caused by Acinetobacter baumannii. The patients were treated in the ICU at the Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica (Serbia) in the period from January, 2013 to March, 2018. Baseline demographic data, severity of the disease, comorbidities, colistin regimen and length of the treatment were collected. The primary outcome was 28-day mortality. Results. Twenty seven of total 69 (39.1%) patients received combined intravenous and inhalatory colistin. Forty two (60.9%) patients received only intravenous colistin. Compared to the combined use of the drug (intravenous and inhalatory colistin), patients receiving intravenous colistin alone had a significantly increased risk of death during 28 days [25.9% vs. 61.9%, respectively; odds ratio (OR) 4.464, 95% confidence interval (CI) 1.539?2.925; p = 0.006]. Length of colistin use (> 7 days) was also associated with reduced survival (OR 0.22; 95% CI 0.080?0.606; p = 0.003). After adjusting for baseline severity of the illness (APACHE score) and length of colistin treatment, patients receiving only intravenous colistin had greater 28-day mortality rate compared to patients receiving both intravenous and inhalatory colistin (OR 6.305; 95% CI 1.795?22.153; p = 0.004). Conclusion. Our results suggest that adding inhalatory to intravenous colistin might be beneficial in the treatment of VAP caused by Acinetobacter species.

In many areas of the world, critical care providers caring for COVID-19 patients lacked specific knowledge and were exposed to the abundance of new and unfiltered information. With support from the World Health Organization, we created a multimodal tele-education intervention to rapidly share critical care knowledge related to COVID-19 targeting providers in a region of Southeastern Europe. We delivered 60-minute weekly interactive tele-education sessions over YouTube TM between March and May 2020, supplemented by a dedicated webpage. The intervention was reinforced using a secure social media platform (Viber TM) providing continuous rapid knowledge exchange among faculty and learners. A high level of engagement was observed with over 2,000 clinicians participating and actively interacting over a six-week period. Surveyed participants were highly satisfied with the intervention. Tele-education interventions using social media platforms are feasible, low-cost, and effective methods to share knowledge during the COVID-19 pandemic.

Background: The Checklist for Early Recognition and Treatment of Acute Illness and Injury (CERTAIN) study is a before-and-after clinical quality improvement study involving 20 countries. Our aim was to describe the challenges and solutions for study implementation across various intensive care units.Methods: After local institutional review board approval, each study center had a setup period before patient data were collected. Each center was required to accomplish 4 stages: baseline data collection, remote simulation training, local implementation, and postimplementation data collection and maintenance of process of care. We measured the time required to complete each study stage and used the Define, Measure, Analyze, Improve, and Control (DMAIC) framework to identify the challenges encountered during each stage and guide improvement strategies to facilitate implementation of CERTAIN.Results: Between June 2012 and December 2017, 55 centers from 20 countries were recruited to participate. The time to complete each stage at different centers varied significantly. The most common domains in which challenges occurred were 1) leadership support and team building, 2) communication, 3) work environment culture, 4) language barriers, 5) infrastructure and technology, and 6) sustainability. Obstacles in these 6 areas delayed reaching major milestones of the study. Different strategies were deployed to overcome these barriers: engaging leadership for support, using native-speaking clinicians during training sessions, using various communication platforms, providing personal computers to local hospitals, making in-person site visits, offering flexible training time, and supporting local centers’ grant applications. Centers that enrolled during the control phase, compared with those that enrolled earlier, had significantly shorter times and less variation in times for each study stage and for the total study time.Conclusions: By using the DMAIC method, we identified the predominant 6 domains in which challenges occurred during implementation of the global CERTAIN study and developed targeted strategies to overcome the challenges and shorten the duration of the study. The DMAIC method would be useful in improving the efficiency of other large-scale multinational quality improvement projects.

Pneumonia is the leading infectious cause of death worldwide. While inflammation is critically important in host response to microbial invasion, exaggerated inflammation can damage the lungs, contributing to respiratory failure and mortality. Corticosteroids are effective in reducing inflammation and can also cause immune suppression. Presently, clinicians are unable to reliably distinguish between exaggerated and appropriate immune response and thus cannot rapidly identify patients most likely to benefit from adjunctive corticosteroids. In this review, we propose a biomarker-guided, precision medicine approach to corticosteroid treatment, aimed to give these medications at appropriate dose and time and only to patients who have exaggerated inflammation.

Background: Systemic thrombolytic therapy is not recommended for patients with intermediate-risk pulmonary embolism (PE) because of major bleeding and intracranial bleeding overcomes the benefit of...

Background: Chronic obstructive pulmonary disease (COPD) is a major cause of mortality worldwide but the data on ICU outcomes are limited to high income settings. Aim: To determine the outcomes of COPD patients admitted to ICUs in middle income countries (MICs). Methods: A secondary analysis of CERTAIN (Checklist For Early Recognition And Treatment of Acute Illness) trial. The ICU patients with main discharge diagnosis of COPD in 27 ICUs from 12 MICs (9 upper-MICs and 3 lower-MICs according to World Bank classification) were included in the analysis. Results: From total 3365 admissions, 184 were diagnosed with COPD (5.5%). There were 118 (64.1%) men, mean age was 68 (±14) years and BMI 24 (IQR 22-28) kg/m2. One hundred and fifty-three patients (83%) received mechanical ventilation (median 4 days, IQR 2-12). Palliative care was provided at some point in 48 (26.6%) patients. Median number of ICU days was 6 (IQR 3-13). ICU mortality was 25% and 28-days mortality 34%. There were no differences in ICU mortality between upper-MICS and lower-MICS (31/134, 23.3% vs.15/50, 30.0%, p=0.34) but significant differences between the countries were observed (Figure 1). Conclusions: Although COPD represents minority of total ICU patients in MICs these patients have high mortality rates that are comparable to previous reports from developed countries. The mortality rates varied across different geographical regions but were not associated with income levels.

Asthma is one of the most common chronic diseases worldwide with an estimated 300 million affected individuals. Grading of asthma based on clinical presentation is going from acute severe asthma over life threatening asthma to near fatal asthma There are only a few diagnostic methods that we can use for patients with severe form of asthma because. This is because of severity of disease which disables them to complete usually used diagnostic tests. Treatment of patients with severe form of asthma is difficult. Today we have precisely defined criteria for hospital admission, so we will not waste time to decide whether patient is of general ward, high dependence unit or intensive care unit. Thanks to latest GINA recommendations we updated about treatment procedures for each patient based on severity of disease. It is extremely important to choose adequate therapy as soon as possible, because we do not have big margin for an error. Therapy should be based on latest GINA recommendation.

Additional file 1: Figure S1. Activity patterns of promoter candidates showing epidermis enriched (Figure S1.1), general cortex- or endodermis enriched (Figure S1.2), pericycle and phloem enriched (Figure S1.3) or xylem specific (Figure S1.4) expression in L. japonicus roots. Figure S1.4 g-l show roots expressing a control vector devoid of a promoter:GUS expression cassette. Agrobacterium rhizogenes induced transgenic roots were harvested three days after mock treatment (mock) with medium or inoculation with M. loti bacteria. Representative GUS stained root tips (a,d,g,j,m,p entire root mounts) and responsive zone fragments (b,e,h,k,n,q entire root mounts; c,f,i,l,o,r cross sections) are shown. Cross sections are 7-8 µm microtome sections of resin (Kulzer Technovit 7100) embedded roots stained with 0.1 % Ruthenium Red. Scale bars 50 µm. Figure S2. Root tip associated GUS signal varied with root hair emergence patterns in pLeExt1:GUS expressing roots. Where root hairs developed near the root tip, epidermal cells showed GUS activity in a distinct ring of blue encircling the root tip. GUS stained and fixed tips of Agrobacterium rhizogenes induced transgenic roots harvested a three days after mock treatment (mock) with medium or b inoculation with M. loti bacteria are shown. Scale bars 50 µm. Figure S3. Vibratome sections of pAtCortex:GUS expressing roots show strong enrichment of GUS signal in cortical cells. a–b 60-80 µm sections of the responsive zone of pAtCortex:GUS expressing L. japonicus roots. Roots were stained, fixed and embedded in 2.4 % agarose prior to sectioning. Scale bars 50 µm. Figure S4. pAtSUC2 activity pattern in transgenic L. japonicus roots. a–b roots shielded from light access show no GUS staining. c–d chloroplast-containing roots exposed to light show GUS signal in phloem cells. Arrows indicate GUS signal in chloroplast containing roots. Representative longitudinal views of GUS stained whole root mounts are shown. e cross-section of resin (Kulzer Technovit 7100) embedded root responsive zone stained with 0.1 % Ruthenium Red. Black arrows point to phloem poles, white arrows to pericycle cells showing GUS signal. The respective root had been exposed to light during development. Scale bars a–d 100 µm, e 50 µm. Figure S5. Promoter activity distribution across developmental zones of representative roots stably expressing promoter:GUS constructs. Transgenes are a pLeExt1:GUS (line LIG29-2); b pAtCortex:GUS (line CoG11-6); c pAtE29:GUS (line 29G4b-5); d pAtS13:GUS (line 13G26b-28) and e pAtS18:GUS (line XG5A-5). Transgenic plants were uninoculated and harvested as well as GUS stained at three weeks post germination. Scale bars 1 mm. Figure S6. Promoter activity distribution across developmental zones of representative nodulated roots stably expressing promoter:GUS constructs. Transgenes are a pLeExt1:GUS (line LIG29-2); b pAtCortex:GUS (line CoG11-6); c pAtE29:GUS (line 29G4b-5); d pAtS13:GUS (line 13G26b-28) and e pAtS18:GUS (line XG5A-5). Transgenic plants were harvested and GUS stained at two weeks after inoculation with M. loti. Scale bars 1 mm.

Conclusion Influenza 2009 H1N1 infection in three southeast European ICUs affected predominantly healthy young patients and was associated with rapid deterioration after hospital admission and severe respiratory and multiorgan failure. These emerging ICUs provided contemporary ICU services, resulting in case-fatality rate comparable to reports from well-established ICU settings. After the first cases of human influenza A H1N1 infection were observed in Mexico in April 2009 (1), the infection quickly spread to Europe, Asia, and both Americas, which is why the World Health Organization (WHO) declared level 6 pandemic alert on June 11, 2009 (2). Up to February 2010, influenza A H1N1 virus was confirmed in more than 212 countries and caused more than 15 000 deaths (3). Compared with seasonal influenza, pandemic 2009 H1N1 influenza A has affected a great number of young, previously healthy patients and caused significant health and economic burden even in developed countries. So far, several studies have reported their experience with critically ill patients with 2009 H1N1 influenza in North America, South America, Asia, Australia, and Europe (1,4-12). A few studies have so far reported on H1N1 patients' characteristics and outcome in low-income and developing countries with limited ICU resources (1,8-12), and none on that in the west Balkans. The ICUs in these countries are mainly run by physicians who lack formal ICU training. Furthermore, until only recently non-surgical critically ill patients in these ICUs had limited access to mechanical ventilation and other life support interventions. However, over the past five years, three university hospitals in Bosnia and Herzegovina and Serbia have established multidisciplinary medical ICUs and most of critically ill patients with H1N1 influenza A infection in the region were admitted to these units. The aim of this study was to describe characteristics and outcomes of mechanically ventilated adult patients with 2009 H1N1 influenza A infection treated in these ICUs.

Critical care is a complicated, high risk, resource-dependent environment. Developing countries face common barriers to delivering quality emergent care due to the lack of supplies, coordination, infrastructure, technology, and human resources (e.g., competency-based education, multi-disciplinary staff and access to the most recent literature).(1) More importantly, the capacity to provide care for critically ill patients in intensive care units (ICUs) of low-income countries is unknown. Most developing countries lack published data on ICU capacity.(2) Importantly, a previous observational study aimed to assess the worldwide burden of critical illness, but only an insignificant sample (2 of 730 centers) of ICUs in low-income countries was taken into account.(3) Poor access to material resources and skilled personal pose a significant barrier to care improvement. Indeed, severity-of-illness-adjusted mortality is inversely related to gross national income.(3) Nevertheless, a recent survey performed by the CERTAIN (Checklist for Early Recognition and Treatment of Acute Illness and INjury; www.icertain.org) Investigators network in 15 ICUs from 11 lowand middle-income countries showed that 77% of ICUs singled out lack of protocols and trained staff, which are the most important barriers to improving the care and outcomes of critically ill patients as opposed to cost-dependent variables, such as equipment or supplies.(1) Basic resources, such as standardized supportive care and trained personnel have been cited as instrumental in changing the outcomes for catastrophic/challenging diseases, such as the Ebola virus disease in resource-limited settings.(4)

Background: Timely and appropriate care is the key to achieving good outcomes in acutely ill patients, but the effectiveness of critical care may be limited in resource-limited settings.Objectives: This study sought to understand how to implement best practices in intensive care units (ICU) in low- and middle-income countries (LMIC) and to develop a point-of-care training and decision-support tool.Methods: An internationally representative group of clinicians performed a 22-item capacity-and-needs assessment survey in a convenience sample of 13 ICU in Eastern Europe (4), Asia (4), Latin America (3), and Africa (2), between April and July 2012. Two ICU were from low-income, 2 from low-middle-income, and 9 from upper-middle-income countries. Clinician respondents were asked about bed capacity, patient characteristics, human resources, available medications and equipment, access to education, and processes of care.Results: Thirteen clinicians from each of 13 hospitals (1 per ICU) responded. Surveyed hospitals had median of 560 (interquartile range [IQR]: 232, 1,200) beds. ICU had a median of 9 (IQR: 7, 12) beds and treated 40 (IQR: 20, 67) patients per month. Many ICU had 1 staff member with some formal critical care training (n = 9, 69%) or who completed Fundamental Critical Care Support (n = 7, 54%) or Advanced Cardiac Life Support (n = 9, 69%) courses. Only 2 ICU (15%) used any kind of checklists for acute resuscitation. Ten (77%) ICU listed lack of trained staff as the most important barrier to improving the care and outcomes of critically ill patients.Conclusions: In a convenience sample of 13 ICU from LMIC, specialty-trained staff and standardized processes of care such as checklists are frequently lacking. ICU needs-assessment evaluations should be expanded in LMIC as a global priority, with the goal of creating and evaluating context-appropriate checklists for ICU best practices.HighlightsIn intensive care units from low- and middle-income countries, trained staff and processes of care such as checklists are frequently lacking even as access to intensive care unit resources is reasonable.A better understanding of existing intensive care units' capacity and evaluation of interventions to bring context-appropriate best practices to the bedside of critically ill patients should be a global priority.

Processes to ensure world-wide best-practice for critical care delivery are likely to minimize preventable death, disability and costly complications for any healthcare system's sickest patients, but no large-scale efforts have so far been undertaken towards these goals. The advances in medical informatics and human factors engineering have provided possibility for novel and user-friendly clinical decision support tools that can be applied in a complex and busy hospital setting. To facilitate timely and accurate best-practice delivery in critically ill patients international group of intensive care unit (ICU) physicians and researchers developed a simple decision support tool: Checklist for Early Recognition and Treatment of Acute Illness (CERTAIN). The tool has been refined and tested in high fidelity simulated clinical environment and has been shown to improve performance of clinical providers faced with simulated emergencies. The aim of this international educational intervention is to implement CERTAIN into clinical practice in hospital settings with variable resources (included those in low income countries) and evaluate the impact of the tool on the care processes and patient outcomes. To accomplish our aims, CERTAIN will be uniformly available on either mobile or fixed computing devices (as well as a backup paper version) and applied in a standardized manner in the ICUs of diverse hospitals. To ensure the effectiveness of the proposed intervention, access to CERTAIN is coupled with structured training of bedside ICU providers.

Background Establishment and maintenance of mutualistic plant–microbial interactions in the rhizosphere and within plant roots involve several root cell types. The processes of host–microbe recognition and infection require complex signal exchange and activation of downstream responses. These molecular events coordinate host responses across root cell layers during microbe invasion, ultimately triggering changes of root cell fates. The progression of legume root interactions with rhizobial bacteria has been addressed in numerous studies. However, tools to globally resolve the succession of molecular events in the host root at the cell type level have been lacking. To this end, we aimed to identify promoters exhibiting cell type enriched expression in roots of the model legume Lotus japonicus, as no comprehensive set of such promoters usable in legume roots is available to date. Results Here, we use promoter:GUS fusions to characterize promoters stemming from Arabidopsis, tomato (Lycopersicon esculentum) or L.japonicus with respect to their expression in major cell types of the L.japonicus root differentiation zone, which shows molecular and morphological responses to symbiotic bacteria and fungi. Out of 24 tested promoters, 11 showed cell type enriched activity in L.japonicus roots. Covered cell types or cell type combinations are epidermis (1), epidermis and cortex (2), cortex (1), endodermis and pericycle (2), pericycle and phloem (4), or xylem (1). Activity of these promoters in the respective cell types was stable during early stages of infection of transgenic roots with the rhizobial symbiont of L.japonicus, Mesorhizobium loti. For a subset of five promoters, expression stability was further demonstrated in whole plant transgenics as well as in active nodules. Conclusions 11 promoters from Arabidopsis (10) or tomato (1) with enriched activity in major L.japonicus root and nodule cell types have been identified. Root expression patterns are independent of infection with rhizobial bacteria, providing a stable read-out in the root section responsive to symbiotic bacteria. Promoters are available as cloning vectors. We expect these tools to help provide a new dimension to our understanding of signaling circuits and transcript dynamics in symbiotic interactions of legumes with microbial symbionts. Electronic supplementary material The online version of this article (doi:10.1186/s13007-016-0105-y) contains supplementary material, which is available to authorized users.