LOX-1 and MMP-9 Inhibition Attenuates the Detrimental Effects of Delayed rt-PA Therapy and Improves Outcomes After Acute Ischemic Stroke.

BACKGROUND: Acute ischemic stroke triggers endothelial activation that disrupts vascular integrity and increases hemorrhagic transformation leading to worsened stroke outcomes. rt-PA (recombinant tissue-type plasminogen activator) is an effective treatment; however, its use is limited due to a restricted time window and hemorrhagic transformation risk, which in part may involve activation of MMPs (matrix metalloproteinases) mediated through LOX-1 (lectin-like oxLDL [oxidized low-density lipoprotein] receptor 1). This study's overall aim was to evaluate the therapeutic potential of novel MMP-9 (matrix metalloproteinase 9) ± LOX-1 inhibitors in combination with rt-PA to improve stroke outcomes. METHODS: A rat thromboembolic stroke model was utilized to investigate the impact of rt-PA delivered 4 hours poststroke onset as well as selective MMP-9 (JNJ0966) ±LOX-1 (BI-0115) inhibitors given before rt-PA administration. Infarct size, perfusion, and hemorrhagic transformation were evaluated by 9.4-T magnetic resonance imaging, vascular and parenchymal MMP-9 activity via zymography, and neurological function was assessed using sensorimotor function testing. Human brain microvascular endothelial cells were exposed to hypoxia plus glucose deprivation/reperfusion (hypoxia plus glucose deprivation 3 hours/R 24 hours) and treated with ±tPA and ±MMP-9 ±LOX-1 inhibitors. Barrier function was assessed via transendothelial electrical resistance, MMP-9 activity was determined with zymography, and LOX-1 and barrier gene expression/levels were measured using qRT-PCR (quantitative reverse transcription PCR) and Western blot. RESULTS: Stroke and subsequent rt-PA treatment increased edema, hemorrhage, MMP-9 activity, LOX-1 expression, and worsened neurological outcomes. LOX-1 inhibition improved neurological function, reduced edema, and improved endothelial barrier integrity. Elevated MMP-9 activity correlated with increased edema, infarct volume, and decreased neurological function. MMP-9 inhibition reduced MMP-9 activity and LOX-1 expression. In human brain microvascular endothelial cells, LOX-1/MMP-9 inhibition differentially attenuated MMP-9 levels, inflammation, and activation following hypoxia plus glucose deprivation/R. CONCLUSIONS: Our findings indicate that LOX-1 inhibition and ± MMP-9 inhibition attenuate negative aspects of ischemic stroke with rt-PA therapy, thus resulting in improved neurological function. While no synergistic effect was observed with simultaneous LOX-1 and MMP-9 inhibition, a distinct interaction is evident.

Therapeutic S100A8/A9 blockade inhibits myocardial and systemic inflammation and mitigates sepsis-induced myocardial dysfunction.

BACKGROUND AND AIMS: The triggering factors of sepsis-induced myocardial dysfunction (SIMD) are poorly understood and are not addressed by current treatments. S100A8/A9 is a pro-inflammatory alarmin abundantly secreted by activated neutrophils during infection and inflammation. We investigated the efficacy of S100A8/A9 blockade as a potential new treatment in SIMD. METHODS: The relationship between plasma S100A8/A9 and cardiac dysfunction was assessed in a cohort of 62 patients with severe sepsis admitted to the intensive care unit of Linköping University Hospital, Sweden. We used S100A8/A9 blockade with the small-molecule inhibitor ABR-238901 and S100A9-/- mice for therapeutic and mechanistic studies on endotoxemia-induced cardiac dysfunction in mice. RESULTS: In sepsis patients, elevated plasma S100A8/A9 was associated with left-ventricular (LV) systolic dysfunction and increased SOFA score. In wild-type mice, 5 mg/kg of bacterial lipopolysaccharide (LPS) induced rapid plasma S100A8/A9 increase and acute LV dysfunction. Two ABR-238901 doses (30 mg/kg) administered intraperitoneally with a 6 h interval, starting directly after LPS or at a later time-point when LV dysfunction is fully established, efficiently prevented and reversed the phenotype, respectively. In contrast, dexamethasone did not improve cardiac function compared to PBS-treated endotoxemic controls. S100A8/A9 inhibition potently reduced systemic levels of inflammatory mediators, prevented upregulation of inflammatory genes and restored mitochondrial function in the myocardium. The S100A9-/- mice were protected against LPS-induced LV dysfunction to an extent comparable with pharmacologic S100A8/A9 blockade. The ABR-238901 treatment did not induce an additional improvement of LV function in the S100A9-/- mice, confirming target specificity. CONCLUSION: Elevated S100A8/A9 is associated with the development of LV dysfunction in severe sepsis patients and in a mouse model of endotoxemia. Pharmacological blockade of S100A8/A9 with ABR-238901 has potent anti-inflammatory effects, mitigates myocardial dysfunction and might represent a novel therapeutic strategy for patients with severe sepsis.

Image quality of spectral brain computed tomography angiography using halved dose of iodine contrast medium.

PURPOSE: Reduction in iodinated contrast medium (CM) dose is highly motivated. Our aim was to evaluate if a 50% reduction of CM, while preserving image quality, is possible in brain CT angiography (CTA) using virtual monoenergetic images (VMI) on spectral CT. As a secondary aim, we evaluated if VMI can salvage examinations with suboptimal CM timing. METHODS: Consecutive patients older than 18 years without intracranial stenosis/occlusion were included. Three imaging protocols were used: group 1, full CM dose; group 2, 50% CM dose suboptimal timing; and group 3, 50% CM dose optimized timing. Attenuation, noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were measured in the internal carotid artery, M2 segment of the middle cerebral artery, and white matter for conventional images (CI) and VMI (40-200 keV). Qualitative image quality for CI and VMI (50 and 60 keV) was rated by 4 experienced reviewers. RESULTS: Qualitatively and quantitatively, VMI (40-60 keV) improved image quality within each group. Significantly higher attenuation and CNR was found for group 3 VMI 40-50 keV, with unchanged SNR, compared to group 1 CI. Group 3 VMI 50 keV also received significantly higher rating scores than group 1 CI. Group 2 VMI (40-50 keV) had significantly higher CNR compared to group 3 CI, but the subjective image quality was similar. CONCLUSION: VMI of 50 keV with 50% CM dose increases qualitative and quantitative image quality over CI with full CM dose. Using VMI reduces non-diagnostic examinations and may salvage CTA examinations deemed non-diagnostic due to suboptimal timing.

Comparison of image quality between a novel mobile CT scanner and current generation stationary CT scanners.

PURPOSE: Point-of-care imaging with mobile CT scanners offers several advantages, provided that the image quality is satisfactory. Our aim was to compare image quality of a novel mobile CT to stationary scanners for patients in a neurosurgical intensive care unit (ICU). METHODS: From November 2020 to April 2021, all patients above 18 years of age examined by a mobile CT scanner at a neurosurgical ICU were included if they also had a stationary head CT examination during the same hospitalization. Quantitative image quality parameters included attenuation and noise in six predefined regions of interest, as well as contrast-to-noise ratio between gray and white matter. Subjective image quality was rated on a 4-garde scale, by four radiologists blinded to scanner parameters. RESULTS: Fifty patients were included in the final study population. Radiation dose and image attenuation values were similar for mobCT and stationary CTs. There was a small statistically significant difference in subjective quality rating between mobCT and stationary CT images. Two radiologists favored the stationary CT images, one was neutral, and one favored mobCT images. For overall image quality, 14% of mobCT images were rated grade 1 (poor image quality) compared to 8% for stationary CT images. CONCLUSION: Point-of-care brain CT imaging was successfully performed on clinical neurosurgical ICU patients with small reduction in image quality, predominantly affecting the posterior fossa, compared to high-end stationary CT scanners.

The onset of sepsis as experienced by patients and family members: A qualitative interview study.

AIMS AND OBJECTIVES: To explore the onset of sepsis based on patients' and family members' experiences. BACKGROUND: Knowledge about the onset of sepsis is limited among patients and their families, which makes early recognition of sepsis difficult. Previous studies argue that their stories are important to recognising sepsis and reduced suffering and mortality. DESIGN: A descriptive design with a qualitative approach was used. METHODS: In total, 29 patients and family members participated in 24 interviews with open-ended questions, including five dyadic and 19 individual interviews. The interviews were conducted during 2021, and participants were recruited from a sepsis group on social media. A thematic analysis based on descriptive phenomenology was performed. The study followed the COREQ checklist. FINDINGS: Two themes emerged from the experiences: (1) When health changes into something unknown, including the two subthemes; Bodily symptoms and signs being vague but still tangible and Feelings of uncertainty, and (2) Turning points when warnings signs are deemed as serious, including the two subthemes Passing borders when feeling out of control and Difficulties understanding the seriousness. CONCLUSIONS: Patients' and family members' stories of the onset of sepsis indicate that symptoms and signs appeared insidiously and then noticeably worsen. The symptoms and signs seemed not be attributed to sepsis; instead, there was uncertainty about what the symptoms and signs meant. It was mainly family members who possibly understood the seriousness of the disease. IMPLICATIONS FOR THE PROFESSION AND PATIENT CARE: Patients' experiences of their symptoms and signs and family members' unique knowledge of the patient, indicate that healthcare professionals should listen and try to understand what the patient and family members are telling and take their concerns seriously. How the condition appears, and family members' concerns are important pieces of the assessment to recognise patients with sepsis. PATIENT OR PUBLIC CONTRIBUTION: Patients and family members contributed to the data collected.

Inter-modality assessment of medial temporal lobe atrophy in a non-demented population: application of a visual rating scale template across radiologists with varying clinical experience.

OBJECTIVES: To assess inter-modality agreement and accuracy for medial temporal lobe atrophy (MTA) ratings across radiologists with varying clinical experience in a non-demented population. METHODS: Four raters (two junior radiologists and two senior neuroradiologists) rated MTA on CT and MRI scans using Scheltens' MTA scale. Ratings were compared to a consensus rating by two experienced neuroradiologists for estimation of true positive and negative rates (TPR and TNR) and over- and underestimation of MTA. Inter-modality agreement expressed as Cohen's κ (dichotomized data), Cohen's κw, and two-way mixed, single measures, consistency ICC (ordinal data) were determined. Adequate agreement was defined as κ/κw ≥ 0.80 and ICC ≥ 0.80 (significance level at 95% CI ≥ 0.65). RESULTS: Forty-nine subjects (median age 72 years, 27% abnormal MTA) with cognitive impairment were included. Only junior radiologists achieved adequate agreement expressed as Cohen's κ. All raters achieved adequate agreement expressed as Cohen's κw and ICC. True positive rates varied from 69 to 100% and TNR varied from 85 to 100%. No under- or overestimation of MTA was observed. Ratings did not differ between radiologists. CONCLUSION: We conclude that radiologists with varying experience achieve adequate inter-modality agreement and similar accuracy when Scheltens' MTA scale is used to rate MTA on a non-demented population. However, TPR varied between radiologists which could be attributed to rating style differences. KEY POINTS: • Radiologists with varying experience achieve adequate inter-modality agreement with similar accuracy when Scheltens' MTA scale is used to rate MTA on a non-demented population. • Differences in rating styles might affect accuracy, this was most evident for senior neuroradiologists, and only junior radiologists achieved adequate agreement on dichotomized (abnormal/normal) ratings. • The use of an MTA scale template might compensate for varying clinical experience which could make it applicable for clinical use.

A review of the advances in composites/nanocomposites for triboelectric nanogenerators.

Material development is essential when studying triboelectric nanogenerators (TENGs). This importance is because the performance of TENGs is highly dependent on the properties of the utilized triboelectric materials. To obtain more specific properties, composites have been developed that combine the features of their components. According to Google Scholar, 55% of published papers related to triboelectric nanogenerators have utilized or mentioned composites. This number is 34.5% if one searches with the keyword nanocomposites instead of composites. The importance of composites is because they can exhibit new dielectric properties, better mechanical strength, enhanced charge affinities, etc. Therefore, the development of new composites has great importance in TENG studies. In this paper, we review the production of nanocomposites, the types of nanocomposites, and their application in TENG studies. This review gives an overview of how nanocomposites boost the performance of TENGs and provides guidance for future studies.

Identification of myocardial injury using perioperative troponin surveillance in major noncardiac surgery and net benefit over the Revised Cardiac Risk Index.

BACKGROUND: Patients with perioperative myocardial injury are at risk of death and major adverse cardiovascular and cerebrovascular events (MACCE). The primary aim of this study was to determine optimal thresholds of preoperative and perioperative changes in high-sensitivity cardiac troponin T (hs-cTnT) to predict MACCE and mortality. METHODS: Prospective, observational, cohort study in patients ≥50 yr of age undergoing elective major noncardiac surgery at seven hospitals in Sweden. The exposures were hs-cTnT measured before and days 0-3 after surgery. Two previously published thresholds for myocardial injury and two thresholds identified using receiver operating characteristic analyses were evaluated using multivariable logistic regression models and externally validated. The weighted comparison net benefit method was applied to determine the additional value of hs-cTnT thresholds when compared with the Revised Cardiac Risk Index (RCRI). The primary outcome was a composite of 30-day all-cause mortality and MACCE. RESULTS: We included 1291 patients between April 2017 and December 2020. The primary outcome occurred in 124 patients (9.6%). Perioperative increase in hs-cTnT ≥14 ng L-1 above preoperative values provided statistically optimal model performance and was associated with the highest risk for the primary outcome (adjusted odds ratio 2.9, 95% confidence interval 1.8-4.7). Validation in an independent, external cohort confirmed these findings. A net benefit over RCRI was demonstrated across a range of clinical thresholds. CONCLUSIONS: Perioperative increases in hsTnT ≥14 ng L-1 above baseline values identifies acute perioperative myocardial injury and provides a net prognostic benefit when added to RCRI for the identification of patients at high risk of death and MACCE. CLINICAL TRIAL REGISTRATION: NCT03436238.

Ethics education to support ethical competence learning in healthcare: an integrative systematic review.

BACKGROUND: Ethical problems in everyday healthcare work emerge for many reasons and constitute threats to ethical values. If these threats are not managed appropriately, there is a risk that the patient may be inflicted with moral harm or injury, while healthcare professionals are at risk of feeling moral distress. Therefore, it is essential to support the learning and development of ethical competencies among healthcare professionals and students. The aim of this study was to explore the available literature regarding ethics education that promotes ethical competence learning for healthcare professionals and students undergoing training in healthcare professions. METHODS: In this integrative systematic review, literature was searched within the PubMed, CINAHL, and PsycInfo databases using the search terms 'health personnel', 'students', 'ethics', 'moral', 'simulation', and 'teaching'. In total, 40 articles were selected for review. These articles included professionals from various healthcare professions and students who trained in these professions as subjects. The articles described participation in various forms of ethics education. Data were extracted and synthesised using thematic analysis. RESULTS: The review identified the need for support to make ethical competence learning possible, which in the long run was considered to promote the ability to manage ethical problems. Ethical competence learning was found to be helpful to healthcare professionals and students in drawing attention to ethical problems that they were not previously aware of. Dealing with ethical problems is primarily about reasoning about what is right and in the patient's best interests, along with making decisions about what needs to be done in a specific situation. CONCLUSIONS: The review identified different designs and course content for ethics education to support ethical competence learning. The findings could be used to develop healthcare professionals' and students' readiness and capabilities to recognise as well as to respond appropriately to ethically problematic work situations.

National outcomes and characteristics of patients admitted to Swedish intensive care units for COVID-19: A registry-based cohort study.

BACKGROUND: Mortality among patients admitted to intensive care units (ICUs) with COVID-19 is unclear due to variable follow-up periods. Few nationwide data are available to compare risk factors, treatment and outcomes of COVID-19 patients after ICU admission. OBJECTIVE: To evaluate baseline characteristics, treatments and 30-day outcomes of patients admitted to Swedish ICUs with COVID-19. DESIGN: Registry-based cohort study with prospective data collection. SETTING: Admissions to Swedish ICUs from 6 March to 6 May 2020 with laboratory confirmed COVID-19 disease. PARTICIPANTS: Adult patients admitted to Swedish ICUs. EXPOSURES: Baseline characteristics, intensive care treatments and organ failures. MAIN OUTCOMES AND MEASURES: The primary outcome was 30-day all-cause mortality. A multivariable model was used to determine the independent association between potential predictor variables and death. RESULTS: We identified 1563 patients with complete 30-day follow-up. The 30-day all-cause mortality was 26.7%. Median age was 61 [52 to 69], Simplified Acute Physiology Score III (SAPS III) was 53 [46 to 59] and 62.5% had at least one comorbidity. Median PaO2/FiO2 on admission was 97.5 [75.0 to 140.6] mmHg, 74.7% suffered from moderate-to-severe acute respiratory failure. Age, male sex [adjusted odds ratio (aOR) 1.5 (1.1 to 2.2)], SAPS III score [aOR 1.3 (1.2 to 1.4)], severe respiratory failure [aOR 3.0 (2.0 to 4.7)], specific COVID-19 pharmacotherapy [aOR 1.4 (1.0 to 1.9)] and continuous renal replacement therapy [aOR 2.1 (1.5 to 3.0)] were associated with increased mortality. Except for chronic lung disease, the presence of comorbidities was not independently associated with mortality. CONCLUSIONS: Thirty-day mortality rate in COVID-19 patients admitted to Swedish ICUs is generally lower than previously reported despite a severe degree of hypoxaemia on admission. Mortality was driven by age, baseline disease severity, the presence and degree of organ failure, rather than pre-existing comorbidities. TRIAL REGISTRATION NO: NCT04462393.

A Proposal of Implementation of Sitting Posture Monitoring System for Wheelchair Utilizing Machine Learning Methods.

This paper presents a posture recognition system aimed at detecting sitting postures of a wheelchair user. The main goals of the proposed system are to identify and inform irregular and improper posture to prevent sitting-related health issues such as pressure ulcers, with the potential that it could also be used for individuals without mobility issues. In the proposed monitoring system, an array of 16 screen printed pressure sensor units was employed to obtain pressure data, which are sampled and processed in real-time using read-out electronics. The posture recognition was performed for four sitting positions: right-, left-, forward- and backward leaning based on k-nearest neighbors (k-NN), support vector machines (SVM), random forest (RF), decision tree (DT) and LightGBM machine learning algorithms. As a result, a posture classification accuracy of up to 99.03 percent can be achieved. Experimental studies illustrate that the system can provide real-time pressure distribution value in the form of a pressure map on a standard PC and also on a raspberry pi system equipped with a touchscreen monitor. The stored pressure distribution data can later be shared with healthcare professionals so that abnormalities in sitting patterns can be identified by employing a post-processing unit. The proposed system could be used for risk assessments related to pressure ulcers. It may be served as a benchmark by recording and identifying individuals' sitting patterns and the possibility of being realized as a lightweight portable health monitoring device.

Assessment of patients with suspected sepsis in ambulance services: a qualitative interview study.

BACKGROUND: The initial care of patients with sepsis is commonly performed by ambulance clinicians (ACs). Early identification, care and treatment are vital for patients with sepsis to avoid adverse outcomes. However, knowledge about how patients with sepsis are assessed in ambulance services (AS) by AC is limited. Therefore, the aim of this study was to explore the meaning of ACs' lived experiences in assessing patients suspected of having sepsis. METHODS: A descriptive design with a qualitative approach was used. Fourteen ACs from three Swedish ambulance organizations participated in dyadic and individual semistructured interviews. A thematic analysis based on descriptive phenomenology was performed. RESULTS: AC experiences were grouped into four themes: (1) being influenced by previous experience; (2) searching for clues to the severity of the patient's condition; (3) feeling confident when signs and symptoms were obvious; and (4) needing health-care professionals for support and consultation. CONCLUSIONS: This study indicates that several factors are important to assessments. ACs needed to engage in an ongoing search for information, discuss the cases with colleagues and reconsider the assessment throughout the entire ambulance mission. A reflective and open stance based on professional knowledge could contribute to recognizing patients with sepsis.

High-content phenotypic assay for proliferation of human iPSC-derived cardiomyocytes identifies L-type calcium channels as targets.

Over 5 million people in the United States suffer from heart failure, due to the limited ability to regenerate functional cardiac tissue. One potential therapeutic strategy is to enhance proliferation of resident cardiomyocytes. However, phenotypic screening for therapeutic agents is challenged by the limited ability of conventional markers to discriminate between cardiomyocyte proliferation and endoreplication (e.g. polyploidy and multinucleation). Here, we developed a novel assay that combines automated live-cell microscopy and image processing algorithms to discriminate between proliferation and endoreplication by quantifying changes in the number of nuclei, changes in the number of cells, binucleation, and nuclear DNA content. We applied this assay to further prioritize hits from a primary screen for DNA synthesis, identifying 30 compounds that enhance proliferation of human induced pluripotent stem cell-derived cardiomyocytes. Among the most active compounds from the phenotypic screen are clinically approved L-type calcium channel blockers from multiple chemical classes whose activities were confirmed across different sources of human induced pluripotent stem cell-derived cardiomyocytes. Identification of compounds that stimulate human cardiomyocyte proliferation may provide new therapeutic strategies for heart failure.

Prehospital characteristics among patients with sepsis: a comparison between patients with or without adverse outcome.

BACKGROUND: The prehospital care of patients with sepsis are commonly performed by the emergency medical services. These patients may be critically ill and have high in-hospital mortality rates. Unfortunately, few patients with sepsis are identified by the emergency medical services, which can lead to delayed treatment and a worse prognosis. Therefore, early identification of patients with sepsis is important, and more information about the prehospital characteristics that can be used to identify these patients is needed. Based on this lack of information, the objectives of this study were to investigate the prehospital characteristics that are identified while patients with sepsis are being transported to the hospital by the emergency medical services, and to compare these values to those of the patients with and without adverse outcomes during their hospital stays. METHODS: This was a retrospective observational study. The patients' electronic health records were reviewed and selected consecutively based on the following: retrospectively diagnosed with sepsis and transported to an emergency department by the emergency medical services. Data were collected on demographics, prehospital characteristics and adverse outcomes, defined as the in-hospital mortality or treatment in the intensive care unit, and analysed by independent sample t-test and chi-square. Sensitivity, specificity and likelihood ratio, of prehospital characteristics for predicting or development of adverse outcome were analysed. RESULTS: In total, 327 patients were included. Of these, 50 patients had adverse outcomes. When comparing patients with or without an adverse outcome, decreased oxygen saturation and body temperature, increased serum glucose level and altered mental status during prehospital care were found to be associated with an adverse outcome. CONCLUSIONS: The findings suggests that patients having a decreased oxygen saturation and body temperature, increased serum glucose level and altered mental status during prehospital care are at risk of a poorer patient prognosis and adverse outcome. Recognizing these prehospital characteristics may help to identify patients with sepsis early and improve their long-term outcomes. However further research is required to predict limit values of saturation and serum glucose and to validate the use of prehospital characteristics for adverse outcome in patients with sepsis.

Association between the reported intensity of an acute symptom at first prehospital assessment and the subsequent outcome: a study on patients with acute chest pain and presumed acute coronary syndrome.

BACKGROUND: To decrease the morbidity burden of cardiovascular disease and to avoid the development of potentially preventable complications, early assessment and treatment of acute coronary syndrome (ACS) are important. The aim of this study has therefore been to explore the possible association between patients' estimated intensity of chest pain when first seen by the ambulance crew in suspected ACS, and the subsequent outcome before and after arrival in hospital. METHODS: Data was collected both prospectively and retrospectively. The inclusion criteria were chest pain raising suspicion of ACS and a reported intensity of pain ≥4 on the visual analogue scale. RESULTS: All in all, 1603 patients were included in the study. Increased intensity of chest pain was related to: 1) more heart-related complications before hospital admission; 2) a higher proportion of heart failure, anxiety and chest pain after hospital admission; 3) a higher proportion of acute myocardial infarction and 4) a prolonged hospitalisation. However, there was no significant association with mortality neither in 30 days nor in three years. Adjustment for possible confounders including age, a history of smoking and heart failure showed similar results. CONCLUSION: The estimated intensity of chest pain reported by the patients on admission by the ambulance team was associated with the risk of complications prior to hospital admission, heart failure, anxiety and chest pain after hospital admission, the final diagnosis and the number of days in hospital. TRIAL REGISTRATION: ClinicalTrials.gov 151:2008/4564 Identifier: NCT00792181. Registred 17 November 2008 'retrospectively registered'.

The early chain of care in bacteraemia patients: Early suspicion, treatment and survival in prehospital emergency care.

INTRODUCTION: Bacteraemia is a first stage for patients risking conditions such as septic shock. The primary aim of this study is to describe factors in the early chain of care in bacteraemia, factors associated with increased chance of survival during the subsequent 28days after admission to hospital. Furthermore, the long-term outcome was assessed. METHODS: This study has a quantitative design based on data from Emergency Medical Services (EMS) and hospital records. RESULTS: In all, 961 patients were included in the study. Of these patients, 13.5% died during the first 28days. The EMS was more frequently used by non-survivors. Among patients who used the EMS, the suspicion of sepsis already on scene was more frequent in survivors. Similarly, EMS personnel noted the ESS code "fever, infection" more frequently for survivors upon arriving on scene. The delay time from call to the EMS and admission to hospital until start of antibiotics was similar in survivors and non-survivors. The five-year mortality rate was 50.8%. Five-year mortality was 62.6% among those who used the EMS and 29.5% among those who did not (p<0.0001). CONCLUSION: This study shows that among patients with bacteraemia who used the EMS, an early suspicion of sepsis or fever/infection was associated with improved early survival whereas the delay time from call to the EMS and admission to hospital until start of treatment with antibiotics was not. 50.8% of all patients were dead after five years.

Nurses' competencies in home healthcare: an interview study.

BACKGROUND: Nurses working in Home healthcare (HHC) are facing major challenges since more advanced care and treatment are increasingly being carried out in patients' homes. The aim of this study has been to explore how nurses experience their competencies in HHC situations. METHODS: This study has a qualitative and explorative design. Ten nurses were interviewed and data was analyzed using content analysis. RESULTS: The themes "Being a capable nurse", "Being a useful nurse" and "Being a subordinate and dependent nurse" were identified. Nurses want to be capable of taking care of patients, to develop their competencies and to perform their duties in the way required. They also want their work to be useful and to provide good and safe HHC. Finally, nurses want to improve HHC care by applying their competencies. Simultaneously, they are subordinate and dependent in relation to their manager and also dependent upon their manager's interest in encouraging nurses' competence development. CONCLUSIONS: Nurses in HHC are responsible for many seriously ill patients and they want to contribute to good and safe patient care. To maintain patient safety, reduce the risk for burnout and staff turnover as well as to contribute to a sustainable development of the work, strategies for transferring competencies between nurses and efforts for competence development are needed.

Possible effects of a course in cardiovascular nursing on prehospital care of patients experiencing suspected acute coronary syndrome: a cluster randomised controlled trial.

BACKGROUND: Current research suggests that nurses can influence the outcome for patients with acute coronary syndrome (ACS). The aim of this study has been to evaluate whether a course in cardiovascular nursing (CVN) can improve ambulance nurses' (ANs') prehospital care of patients experiencing suspected ACS, related to pain intensity. METHODS: This is a cluster randomised controlled trial that was conducted in the ambulance services. Patients were allocated to one of two groups: in the first group, patients were treated by ANs who had attended the CVN course and in the second group patients were treated by ANs without this qualification. Inclusion criteria were: 1/pain raising suspicion of ACS, and 2/pain score ≥4 on a visual analogue scale (VAS). The primary outcome was the estimated intensity of pain or discomfort according to VAS 15 min after randomisation. Secondary outcomes were estimated intensity of pain or discomfort on admission to hospital and further requirement of pain treatment, as well as symptoms such as paleness and/or cold sweat; nausea and/or vomiting; anxiety, dyspnea, degree of alertness, respiratory depression and aggressiveness. A further secondary outcome measured was survival to 30 days. Lastly, a final diagnosis was made. A total of 38 ANs attended the CVN course. There were 1,747 patients who fulfilled the inclusion criteria. RESULTS: The pain score did not differ significantly between the two groups fifteen minutes after randomisation (median value of VAS was 4.0 in both groups). On admission to hospital the pain score was significantly lower for patients treated by an AN who had attended the CVN course (n = 332) compared with those treated by an AN who had not attended the course (n = 1,415) (median 2.5 and 3.0 respectively, p = 0.001). The ANs who had attended the course used higher doses of morphine. CONCLUSIONS: An educational intervention with a CVN course did not relate significantly to more efficient pain relief in suspected ACS during the first 15 min. However, this intervention was associated with more effective pain relief later on in the prehospital setting. Thus, a CVN course for ANs appears to be associated with reduced pain intensity among patients experiencing suspected ACS. This result needs however to be confirmed in further trials. TRIAL REGISTRATION: The ClinicalTrials.gov Protocol Registration System (registration number NCT00792181).

Orexin a phosphorylates the γ-Aminobutyric acid type A receptor ß2 subunit on a serine residue and changes the surface expression of the receptor in SH-SY5Y cells exposed to propofol.

Propofol activates the γ-aminobutyric acid type A receptor (GABAA R) and causes a reversible neurite retraction, leaving a thin, thread-like structure behind; it also reverses the transport of vesicles in rat cortical neurons. The awakening peptide orexin A (OA) inhibits this retraction via phospholipase D (PLD) and protein kinase Cɛ (PKCɛ). The human SH-SY5Y cells express both GABAA Rs and orexin 1 and 2 receptors. These cells are used to examine the interaction between OA and the GABAA R. The effects of OA are studied with flow cytometry and immunoblotting. This study shows that OA stimulates phosphorylation on the serine residues of the GABAA R ß2 subunit and that the phosphorylation is caused by the activation of PLD and PKCɛ. OA administration followed by propofol reduces the cell surface expression of the GABAA R, whereas propofol stimulation before OA increases the surface expression. The GABAA R ß2 subunit is important for receptor recirculation, and the effect of OA on propofol-stimulated cells may be due to a disturbed recirculation of the GABAA R.