Publications by authors named "Johan Mårtensson"

131 Publications

Cognitive interference processing in adult survivors of childhood acute lymphoblastic leukemia using functional magnetic resonance imaging.

Acta Oncol 2021 Oct 12:1-8. Epub 2021 Oct 12.

Department of Oncology, Skåne University Hospital, Lund, Sweden.

Background: Childhood acute lymphoblastic leukemia (ALL) is associated with cognitive impairment in adulthood. Cognitive interference processing and its correlated functional magnetic resonance imaging (fMRI) activity in the brain have not yet been studied in this patient group.

Material: Twenty-six adult childhood ALL survivors (median [interquartile range {IQR}] age, 40.0 [37.0-42.3] years) were investigated at median age (IQR), 35.0 (32.0-37.0) years after treatment with intrathecal and intravenous chemotherapy as well as cranial radiotherapy (24 Gy) and compared with 26 matched controls (median [IQR] age, 37.5 [33.0-41.5] years).

Methods: Cognitive interference processing was investigated in terms of behavioral performance (response times [ms] and accuracy performance [%]) and fMRI activity in the cingulo-fronto-parietal (CFP) attention network as well as other parts of the brain using the multisource interference task (MSIT).

Results: ALL survivors had longer response times and reduced accuracy performance during cognitive interference processing (median [IQR] interference effect, 371.9 [314.7-453.3] ms and 6.7 [4.2-14.7]%, respectively) comparedwith controls (303.7 [275.0-376.7] ms and 2.3 [1.6-4.3]%, respectively), but did not exhibit altered fMRI activity in the CFP attention network or elsewhere in the brain.

Conclusion: Adult childhood ALL survivors demonstrated impaired behavioral performance but no altered fMRI activity when performing cognitive interference processing when compared with controls. The results can be used to better characterize this patient group and to optimize follow-up care and support for these individuals.
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http://dx.doi.org/10.1080/0284186X.2021.1987514DOI Listing
October 2021

Rapid Evaluation of Coronavirus Illness Severity (RECOILS) in intensive care: Development and validation of a prognostic tool for in-hospital mortality.

Acta Anaesthesiol Scand 2021 Oct 8. Epub 2021 Oct 8.

Intensive Care, Reinier de Graaf Gasthuis, Delft, The Netherlands.

Background: The prediction of in-hospital mortality for ICU patients with COVID-19 is fundamental to treatment and resource allocation. The main purpose was to develop an easily implemented score for such prediction.

Methods: This was an observational, multicenter, development, and validation study on a national critical care dataset of COVID-19 patients. A systematic literature review was performed to determine variables possibly important for COVID-19 mortality prediction. Using a logistic multivariable model with a LASSO penalty, we developed the Rapid Evaluation of Coronavirus Illness Severity (RECOILS) score and compared its performance against published scores.

Results: Our development (validation) cohort consisted of 1480 (937) adult patients from 14 (11) Dutch ICUs admitted between March 2020 and April 2021. Median age was 65 (65) years, 31% (26%) died in hospital, 74% (72%) were males, average length of ICU stay was 7.83 (10.25) days and average length of hospital stay was 15.90 (19.92) days. Age, platelets, PaO2/FiO2 ratio, pH, blood urea nitrogen, temperature, PaCO2, Glasgow Coma Scale (GCS) score measured within +/-24 h of ICU admission were used to develop the score. The AUROC of RECOILS score was 0.75 (CI 0.71-0.78) which was higher than that of any previously reported predictive scores (0.68 [CI 0.64-0.71], 0.61 [CI 0.58-0.66], 0.67 [CI 0.63-0.70], 0.70 [CI 0.67-0.74] for ISARIC 4C Mortality Score, SOFA, SAPS-III, and age, respectively).

Conclusions: Using a large dataset from multiple Dutch ICUs, we developed a predictive score for mortality of COVID-19 patients admitted to ICU, which outperformed other predictive scores reported so far.
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http://dx.doi.org/10.1111/aas.13991DOI Listing
October 2021

Chronic dysglycemia and risk of SARS-CoV-2 associated respiratory failure in hospitalized patients.

Acta Anaesthesiol Scand 2021 Sep 28. Epub 2021 Sep 28.

Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden.

Background: Diabetes is common among patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced respiratory failure. We aimed to investigate the relationship between different stages of chronic dysglycemia and development of respiratory failure in hospitalized SARS-CoV-2 positive patients.

Methods: In this retrospective observational study, we included 385 hospitalized SARS-CoV-2 positive patients at Karolinska University Hospital, Sweden with an HbA1c test obtained within 3 months before admission. Based on HbA1c level and previous diabetes history, we classified patients into the following dysglycemia categories: prediabetes, unknown diabetes, controlled diabetes, or uncontrolled diabetes. We used multivariable logistic regression analysis adjusted for age, sex, and body mass index, to assess the association between dysglycemia categories and development of SARS-CoV-2-induced respiratory failure.

Results: Of the 385 study patients, 88 (22.9%) had prediabetes, 68 (17.7%) had unknown diabetes, 36 (9.4%) had controlled diabetes, and 83 (21.6%) had uncontrolled diabetes. Overall, 299 (77.7%) patients were admitted with or developed SARS-CoV-2-induced respiratory failure during hospitalization. In multivariable logistic regression analysis compared with no chronic dysglycemia, prediabetes (OR 14.41, 95% CI 5.27-39.43), unknown diabetes (OR 15.86, 95% CI 4.55-55.36), and uncontrolled diabetes (OR 17.61, 95% CI 5.77-53.74) was independently associated with increased risk of SARS-CoV-2-induced respiratory failure.

Conclusion: In our cohort of hospitalized SARS-CoV-2 positive patients with available HbA1c data, prediabetes, undiagnosed diabetes, and poorly controlled diabetes were associated with a markedly increased risk of SARS-CoV-2-associated respiratory failure.
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http://dx.doi.org/10.1111/aas.13982DOI Listing
September 2021

Nationwide case-control study of risk factors and outcomes for community-acquired sepsis.

Sci Rep 2021 07 23;11(1):15118. Epub 2021 Jul 23.

Perioperative Medicine and Intensive Care, Karolinska University Hospital Solna, 171 76, Stockholm, Sweden.

Sepsis is the main cause of death in the intensive care units (ICU) and increasing incidences of ICU admissions for sepsis are reported. Identification of patients at risk for sepsis and poor outcome is therefore of outmost importance. We performed a nation-wide case-control study aiming at identifying and quantifying the association between co-morbidity and socio-economic factors with intensive care admission for community-acquired sepsis. We also explored 30-day mortality. All adult patients (n = 10,072) with sepsis admitted from an emergency department to an intensive care unit in Sweden between 2008 and 2017 and a control population (n = 50,322), matched on age, sex and county were included. In the sepsis group, 69% had a co-morbid condition at ICU admission, compared to 31% in the control group. Multivariable conditional logistic regression analysis was performed and there was a large variation in the influence of different risk factors associated with ICU-admission, renal disease, liver disease, metastatic malignancy, substance abuse, and congestive heart failure showed the strongest associations. Low income and low education level were more common in sepsis patients compared to controls. The adjusted OR for 30-day mortality for sepsis patients was 132 (95% CI 110-159) compared to controls.
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http://dx.doi.org/10.1038/s41598-021-94558-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8302728PMC
July 2021

Cognitive interference processing in adults with childhood craniopharyngioma using functional magnetic resonance imaging.

Endocrine 2021 Jul 22. Epub 2021 Jul 22.

Department of Endocrinology, Skåne University Hospital, Lund, Sweden.

Purpose: To assess cognitive interference processing in adults with childhood craniopharyngioma (CP), with and without hypothalamic injury, respectively, in terms of behavioral performance and functional magnetic resonance imaging (fMRI) activity, using the multi-source interference task (MSIT).

Methods: Twenty-eight CP patients (median age 34.5 [29.0-39.5] years) were investigated at median 20.5 (16.3-28.8) years after treatment with surgical resection and in some cases additional radiotherapy (n = 10) and compared to 29 matched controls (median age 37.0 [32.5-42.0] years). The subjects performed the MSIT during fMRI acquisition and behavioral performance in terms of response times (ms) and accuracy performance (%) were recorded.

Results: The MSIT activated the cingulo-fronto-parietal (CFP) attention network in both CP patients and controls. No differences were found in behavioral performance nor fMRI activity between CP patients (interference effect 333.9 [287.3-367.1] ms and 3.1 [1.6-5.6]%, respectively) and controls (309.1 [276.4-361.0] ms and 2.6 [1.6-4.9]%). No differences were found in behavioral performance nor fMRI activity between the two subgroups with (332.0 [283.6-353.4] ms and 4.2 [2.3-5.7]%, respectively) and without hypothalamic injury (355.7 [293.7-388.7] ms and 2.1 [1.0-5.2]%, respectively), respectively, and controls.

Conclusion: Adults with childhood CP performed cognitive interference processing equally well as controls and demonstrated no compensatory fMRI activity in the CFP attention network compared to controls. This was also true for the two subgroups with and without hypothalamic injury. The results can be useful to better characterize this condition, and to optimize treatment and support for these individuals.
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http://dx.doi.org/10.1007/s12020-021-02824-9DOI Listing
July 2021

Spend time outdoors for your brain - an in-depth longitudinal MRI study.

World J Biol Psychiatry 2021 Jul 7:1-7. Epub 2021 Jul 7.

Clinic and Policlinic for Psychiatry and Psychotherapy, University Clinic Hamburg-Eppendorf, Hamburg, Germany.

Objectives: The effects of nature on physical and mental health are an emerging topic in empirical research with increasing influence on practical health recommendations. Here we set out to investigate the association between spending time outdoors and brain structural plasticity in conjunctions with self-reported affect.

Methods: We established the Day2day study, which includes an unprecedented in-depth assessment of variability of brain structure in a serial sequence of 40-50 structural magnetic resonance imaging (MRI) acquisitions of each of six young healthy participants for 6-8 months ( = 281 MRI scans in total).

Results: A whole-brain analysis revealed that time spent outdoors was positively associated with grey matter volume in the right dorsolateral prefrontal cortex and positive affect, also after controlling for physical activity, fluid intake, free time, and hours of sunshine.

Conclusions: Results indicate remarkable and potentially behaviorally relevant plasticity of cerebral structure within a short time frame driven by the daily time spent outdoors. This is compatible with anecdotal evidence of the health and mood-promoting effects of going for a walk. The study may provide the first evidence for underlying cerebral mechanisms of so-called green prescriptions with possible consequences for future interventions in mental disorders.
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http://dx.doi.org/10.1080/15622975.2021.1938670DOI Listing
July 2021

Clinical phenotypes and outcomes of SARS-CoV-2, influenza, RSV and seven other respiratory viruses: a retrospective study using complete hospital data.

Thorax 2021 Jul 5. Epub 2021 Jul 5.

Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.

Background: An understanding of differences in clinical phenotypes and outcomes COVID-19 compared with other respiratory viral infections is important to optimise the management of patients and plan healthcare. Herein we sought to investigate such differences in patients positive for SARS-CoV-2 compared with influenza, respiratory syncytial virus (RSV) and other respiratory viruses.

Methods: We performed a retrospective cohort study of hospitalised adults and children (≤15 years) who tested positive for SARS-CoV-2, influenza virus A/B, RSV, rhinovirus, enterovirus, parainfluenza viruses, metapneumovirus, seasonal coronaviruses, adenovirus or bocavirus in a respiratory sample at admission between 2011 and 2020.

Results: A total of 6321 adult (1721 SARS-CoV-2) and 6379 paediatric (101 SARS-CoV-2) healthcare episodes were included in the study. In adults, SARS-CoV-2 positivity was independently associated with younger age, male sex, overweight/obesity, diabetes and hypertension, tachypnoea as well as better haemodynamic measurements, white cell count, platelet count and creatinine values. Furthermore, SARS-CoV-2 was associated with higher 30-day mortality as compared with influenza (adjusted HR (aHR) 4.43, 95% CI 3.51 to 5.59), RSV (aHR 3.81, 95% CI 2.72 to 5.34) and other respiratory viruses (aHR 3.46, 95% CI 2.61 to 4.60), as well as higher 90-day mortality, ICU admission, ICU mortality and pulmonary embolism in adults. In children, patients with SARS-CoV-2 were older and had lower prevalence of chronic cardiac and respiratory diseases compared with other viruses.

Conclusions: SARS-CoV-2 is associated with more severe outcomes compared with other respiratory viruses, and although associated with specific patient and clinical characteristics at admission, a substantial overlap precludes discrimination based on these characteristics.
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http://dx.doi.org/10.1136/thoraxjnl-2021-216949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260304PMC
July 2021

Glycemic lability index and mortality in critically ill patients-A multicenter cohort study.

Acta Anaesthesiol Scand 2021 Oct 20;65(9):1267-1275. Epub 2021 May 20.

Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden.

Background: Emerging evidence indicates a relationship between glycemic variability during intensive care unit (ICU) admission and death. We assessed whether mean glucose, hypoglycemia occurrence, or premorbid glycemic control modified this relationship.

Methods: In this retrospective, multicenter cohort study, we included adult patients admitted to five ICUs in Australia and Sweden with available preadmission glycated hemoglobin A1c (HbA1c) and three or more glucose readings. We calculated the glycemic lability index (GLI), a measure of glycemic variability, and the time-weighted average blood glucose (TWA-BG) from all glucose readings. We used logistic regression analysis with adjustment for hypoglycemia and admission characteristics to assess the independent association of GLI (above vs. below cohort median) and TWA-BG (above vs. below cohort median) with hospital mortality.

Results: Among 2305 patients, 859 (37%) had diabetes, median GLI was 40 [mmol/L] /h/week, median TWA-BG was 8.2 mmol/L, 171 (7%) developed hypoglycemia, and 371 (16%) died. The adjusted odds ratio for death was 1.61 (95% CI, 1.19-2.15; P = .002) for GLI above versus below median and 1.06 (95% CI, 0.80-1.41; P = .67) for TWA-BG above versus below median. The relationship between GLI and mortality was not modified by TWA-BG (P [interaction] = 0.66), a history of diabetes (P [interaction] = 0.89) or by HbA1c ≥52 mmol/mol (vs. <52 mmol/mol) (P [interaction] = 0.29).

Conclusion: In adult patients admitted to an ICU in Sweden and Australia, a high GLI was associated with increased hospital mortality irrespective of the level of mean glycemia, hypoglycemia occurrence, or premorbid glycemic control. These findings support the assessment of interventions to reduce glycemic variability during critical illness.
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http://dx.doi.org/10.1111/aas.13843DOI Listing
October 2021

Structural Changes on MRI Demonstrate Specific Cerebellar Involvement in SLE Patients-A VBM Study.

Brain Sci 2021 Apr 16;11(4). Epub 2021 Apr 16.

Department of Clinical Sciences Lund, Diagnostic Radiology, Faculty of Medicine, Lund University, 221 00 Lund, Sweden.

The purpose of this study is to investigate possible differences in brain structure, as measured by T1-weighted MRI, between patients with systemic lupus erythematosus (SLE) and healthy controls (HC), and whether any observed differences were in turn more severe in SLE patients with neuropsychiatric manifestations (NPSLE) than those without (non-NPSLE). Structural T1-weighted MRI was performed on 69 female SLE patients (mean age = 35.8 years, range = 18-51 years) and 24 age-matched female HC (mean age = 36.8 years, range = 23-52 years) in conjunction with neuropsychological assessment using the CNS Vital Signs test battery. T1-weighted images were preprocessed and analyzed by FSL-VBM. The results show that SLE patients had lower grey matter probability values than the control group in the VIIIa of the cerebellum bilaterally, a region that has previously been implied in sensorimotor processing in human and non-human primates. No structural differences for this region were found between NPSLE and non-NPSLE patients. VBM values from the VIIIa region showed a weak positive correlation with the psychomotor speed domain from CNS Vital Signs ( = 0.05, = 0.21), which is in line with its presumed role as a sensorimotor processing area.
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http://dx.doi.org/10.3390/brainsci11040510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072619PMC
April 2021

Long-term outcome after intensive care for COVID-19: differences between men and women-a nationwide cohort study.

Crit Care 2021 02 25;25(1):86. Epub 2021 Feb 25.

Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, 171 76, Stockholm, Sweden.

Background: Questions remain about long-term outcome for COVID-19 patients in general, and differences between men and women in particular given the fact that men seem to suffer a more dramatic course of the disease. We therefore analysed outcome beyond 90 days in ICU patients with COVID-19, with special focus on differences between men and women.

Methods: We identified all patient ≥ 18 years with COVID-19 admitted between March 6 and June 30, 2020, in the Swedish Intensive Care Registry. Patients were followed until death or study end-point October 22, 2020. Association with patient sex and mortality, in addition to clinical variables, was estimated using Cox regression. We also performed a logistic regression model estimating factors associated with 90-day mortality.

Results: In total, 2354 patients with COVID-19 were included. Four patients were still in the ICU at study end-point. Median follow-up time was 183 days. Mortality at 90-days was 26.9%, 23.4% in women and 28.2% in men. After 90 days until end of follow-up, only 11 deaths occurred. On multivariable Cox regression analysis, male sex (HR 1.28, 95% CI 1.06-1.54) remained significantly associated with mortality even after adjustments. Additionally, age, COPD/asthma, immune deficiency, malignancy, SAPS3 and admission month were associated with mortality. The logistic regression model of 90-day mortality showed almost identical results.

Conclusions: In this nationwide study of ICU patients with COVID-19, men were at higher risk of poor long-term outcome compared to their female counterparts. The underlying mechanisms for these differences are not fully understood and warrant further studies.
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http://dx.doi.org/10.1186/s13054-021-03511-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906087PMC
February 2021

A Post Hoc Analysis of Osmotherapy Use in the Erythropoietin in Traumatic Brain Injury Study-Associations With Acute Kidney Injury and Mortality.

Crit Care Med 2021 04;49(4):e394-e403

Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.

Objectives: Mannitol and hypertonic saline are used to treat raised intracerebral pressure in patients with traumatic brain injury, but their possible effects on kidney function and mortality are unknown.

Design: A post hoc analysis of the erythropoietin trial in traumatic brain injury (ClinicalTrials.gov NCT00987454) including daily data on mannitol and hypertonic saline use.

Setting: Twenty-nine university-affiliated teaching hospitals in seven countries.

Patients: A total of 568 patients treated in the ICU for 48 hours without acute kidney injury of whom 43 (7%) received mannitol and 170 (29%) hypertonic saline.

Interventions: None.

Measurements And Main Results: We categorized acute kidney injury stage according to the Kidney Disease Improving Global Outcome classification and defined acute kidney injury as any Kidney Disease Improving Global Outcome stage-based changes from the admission creatinine. We tested associations between early (first 2 d) mannitol and hypertonic saline and time to acute kidney injury up to ICU discharge and death up to 180 days with Cox regression analysis. Subsequently, acute kidney injury developed more often in patients receiving mannitol (35% vs 10%; p < 0.001) and hypertonic saline (23% vs 10%; p < 0.001). On competing risk analysis including factors associated with acute kidney injury, mannitol (hazard ratio, 2.3; 95% CI, 1.2-4.3; p = 0.01), but not hypertonic saline (hazard ratio, 1.6; 95% CI, 0.9-2.8; p = 0.08), was independently associated with time to acute kidney injury. In a Cox model for predicting time to death, both the use of mannitol (hazard ratio, 2.1; 95% CI, 1.1-4.1; p = 0.03) and hypertonic saline (hazard ratio, 1.8; 95% CI, 1.02-3.2; p = 0.04) were associated with time to death.

Conclusions: In this post hoc analysis of a randomized controlled trial, the early use of mannitol, but not hypertonic saline, was independently associated with an increase in acute kidney injury. Our findings suggest the need to further evaluate the use and choice of osmotherapy in traumatic brain injury.
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http://dx.doi.org/10.1097/CCM.0000000000004853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963441PMC
April 2021

The Frequency of, and Factors Associated with Prolonged Hospitalization: A Multicentre Study in Victoria, Australia.

J Clin Med 2020 Sep 22;9(9). Epub 2020 Sep 22.

Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC 3800, Australia.

Background: Limited available evidence suggests that a small proportion of inpatients undergo prolonged hospitalization and use a disproportionate number of bed days. Understanding the factors contributing to prolonged hospitalization may improve patient care and reduce the length of stay in such patients.

Methods: We undertook a retrospective cohort study of adult (≥20 years) patients admitted for at least 24 h between 14 November 2016 and 14 November 2018 to hospitals in Victoria, Australia. Data including baseline demographics, admitting specialty, survival status and discharge disposition were obtained from the Victorian Admission Episode Dataset. Multivariable logistic regression analysis was used to identify factors independently associated with prolonged hospitalization (≥14 days). Cox proportional hazard regression model was used to examine the association between various factors and in-hospital mortality.

Results: There were almost 5 million hospital admissions over two years. After exclusions, 1,696,112 admissions lasting at least 24 h were included. Admissions with prolonged hospitalization comprised only 9.7% of admissions but utilized 44.2% of all hospital bed days. Factors independently associated with prolonged hospitalization included age, female gender, not being in a relationship, being a current smoker, level of co-morbidity, admission from another hospital, admission on the weekend, and the number of admissions in the prior 12 months. The in-hospital mortality rate was 5.0% for those with prolonged hospitalization compared with 1.8% in those without ( < 0.001). Prolonged hospitalization was also independently associated with a decreased likelihood of being discharged to home (OR 0.53, 95% CI 0.52-0.54).

Conclusions: Patients experiencing prolonged hospitalization utilize a disproportionate proportion of bed days and are at higher risk of in-hospital death and discharge to destinations other than home. Further studies are required to identify modifiable factors contributing to prolonged hospitalization as well as the quality of end-of-life care in such admissions.
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http://dx.doi.org/10.3390/jcm9093055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564707PMC
September 2020

Neuroplasticity induced by general anaesthesia: study protocol for a randomised cross-over clinical trial exploring the effects of sevoflurane and propofol on the brain - A 3-T magnetic resonance imaging study of healthy volunteers.

Trials 2020 Sep 22;21(1):805. Epub 2020 Sep 22.

Department of Neuroanaesthesiology, The Neuroscience Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark.

Background: Although used extensively worldwide, the effects of general anaesthesia on the human brain remain largely elusive. Moreover, general anaesthesia may contribute to serious conditions or adverse events such as postoperative cognitive dysfunction and delirium. To understand the basic mechanisms of general anaesthesia, this project aims to study and compare possible de novo neuroplastic changes induced by two commonly used types of general anaesthesia, i.e. inhalation anaesthesia by sevoflurane and intravenously administered anaesthesia by propofol. In addition, we wish to to explore possible associations between neuroplastic changes, neuropsychological adverse effects and subjective changes in fatigue and well-being.

Methods: This is a randomised, participant- and assessor-blinded, cross-over clinical trial. Thirty healthy volunteers (male:female ratio 1:1) will be randomised to general anaesthesia by either sevoflurane or propofol. Multimodal magnetic resonance imaging (MRI) of the brain will be performed before and after general anaesthesia and repeated after 1 and 8 days. Each magnetic resonance imaging session will be accompanied by cognitive testing and questionnaires on fatigue and well-being. After a wash-out period of 4 weeks, the volunteers will receive the other type of anaesthetic (sevoflurane or propofol), followed by the same series of tests. Primary outcomes: changes in T1-weighted 3D anatomy and diffusion tensor imaging.

Secondary Outcomes: changes in resting-state functional magnetic resonance imaging, fatigue, well-being, cognitive function, correlations between magnetic resonance imaging findings and the clinical outcomes (questionnaires and cognitive function). Exploratory outcomes: changes in cerebral perfusion and oxygen metabolism, lactate, and response to visual stimuli.

Discussion: To the best of our knowledge, this is the most extensive and advanced series of studies with head-to-head comparison of two widely used methods for general anaesthesia. Recruitment was initiated in September 2019.

Trial Registration: Approved by the Research Ethics Committee in the Capital Region of Denmark, ref. H-18028925 (6 September 2018). EudraCT and Danish Medicines Agency: 2018-001252-35 (23 March 2018). www.clinicaltrials.gov , ID: NCT04125121 . Retrospectively registered on 10 October 2019.
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http://dx.doi.org/10.1186/s13063-020-04468-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506820PMC
September 2020

Characteristics and outcomes of patients with COVID-19 admitted to ICU in a tertiary hospital in Stockholm, Sweden.

Acta Anaesthesiol Scand 2021 01 15;65(1):76-81. Epub 2020 Sep 15.

Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.

Background: Information on characteristics and outcomes of intensive care unit (ICU) patients with COVID-19 remains limited. We examined characteristics, clinical course and early outcomes of patients with COVID-19 admitted to ICU.

Methods: We included all 260 patients with COVID-19 admitted to nine ICUs at the Karolinska University Hospital (Stockholm, Sweden) between 9 March and 20 April 2020. Primary outcome was in-hospital mortality among patients with definite outcomes (discharged from ICU or death), as of 30 April 2020 (study end point). Secondary outcomes included ICU length of stay, the proportion of patients receiving mechanical ventilation and renal replacement therapy, and hospital discharge destination.

Results: Of 260 ICU patients with COVID-19, 208 (80.0%) were men, the median age was 59 (IQR 51-65) years, 154 (59.2%) had at least one comorbidity, and the median duration of symptoms preceding ICU admission was 11 (IQR 8-14) days. Sixty-two (23.8%) patients remained in ICU at study end point. Among the 198 patients with definite outcomes, ICU length of stay was 12 (IQR, 6-18) days, 163 (82.3%) received mechanical ventilation, 28 (14.1%) received renal replacement therapy, 60 (30.3%) died, 62 (31.3%) were discharged home, 47 (23.7%) were discharged to ward, and 29 (14.6%) were discharged to another health care facility. On multivariable logistic regression analysis, older age and admission from the emergency department was associated with higher mortality.

Conclusion: This study presents detailed data on clinical characteristics and early outcomes of consecutive patients with COVID-19 admitted to ICU in a large tertiary hospital in Sweden.
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http://dx.doi.org/10.1111/aas.13694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756749PMC
January 2021

Prevalence and impact of chronic dysglycemia in intensive care unit patients-A retrospective cohort study.

Acta Anaesthesiol Scand 2021 01 16;65(1):82-91. Epub 2020 Sep 16.

Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden.

Background: The prevalence of chronic dysglycemia (diabetes and prediabetes) in patients admitted to Swedish intensive care units (ICUs) is unknown. We aimed to determine the prevalence of such chronic dysglycemia and asses its impact on blood glucose control and patient-centered outcomes in critically ill patients.

Methods: In this retrospective observational cohort study, we obtained glycated hemoglobin A1c (HbA1c) in patients admitted to four tertiary ICUs in Sweden between March and August 2016. Based on previous diabetes history and HbA1c we determined the prevalence of chronic dysglycemia. We used multivariable regression analyses to study the association of chronic dysglycemia with the time-weighted average blood glucose concentration, glycemic lability index (GLI), and development of hypoglycemia (co-primary outcomes), and with ICU length of stay, mechanical ventilation duration, renal replacement therapy (RRT) use, vasopressor use, ICU-acquired infections, and mortality (exploratory clinical outcomes).

Results: Of 943 patients, 312 (33%) had chronic dysglycemia. Of these 312 patients, 84 (27%) had prediabetes, 43 (14%) had undiagnosed diabetes and 185 (59%) had known diabetes. Chronic dysglycemia was independently associated with higher time-weighted average blood glucose concentration (P < .001), higher GLI (P < .001), and hypoglycemia (P < .001). Chronic dysglycemia was independently associated with RRT use (adjusted odds ratio 1.97, 95% CI 1.24-3.13, P = .004) but not with other exploratory clinical outcomes.

Conclusions: In four tertiary Swedish ICUs, measurement of HbA1c showed that one-third of patients had chronic dysglycemia. Chronic dysglycemia was associated with marked derangements in glycemic control, and a greater need for renal replacement therapy.
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http://dx.doi.org/10.1111/aas.13695DOI Listing
January 2021

Neutrophil Gelatinase-Associated Lipocalin Measured on Clinical Laboratory Platforms for the Prediction of Acute Kidney Injury and the Associated Need for Dialysis Therapy: A Systematic Review and Meta-analysis.

Am J Kidney Dis 2020 12 15;76(6):826-841.e1. Epub 2020 Jul 15.

Columbia University Vagelos College of Physicians and Surgeons, New York, NY.

Rationale & Objective: The usefulness of measures of neutrophil gelatinase-associated lipocalin (NGAL) in urine or plasma obtained on clinical laboratory platforms for predicting acute kidney injury (AKI) and AKI requiring dialysis (AKI-D) has not been fully evaluated. We sought to quantitatively summarize published data to evaluate the value of urinary and plasma NGAL for kidney risk prediction.

Study Design: Literature-based meta-analysis and individual-study-data meta-analysis of diagnostic studies following PRISMA-IPD guidelines.

Setting & Study Populations: Studies of adults investigating AKI, severe AKI, and AKI-D in the setting of cardiac surgery, intensive care, or emergency department care using either urinary or plasma NGAL measured on clinical laboratory platforms.

Selection Criteria For Studies: PubMed, Web of Science, Cochrane Library, Scopus, and congress abstracts ever published through February 2020 reporting diagnostic test studies of NGAL measured on clinical laboratory platforms to predict AKI.

Data Extraction: Individual-study-data meta-analysis was accomplished by giving authors data specifications tailored to their studies and requesting standardized patient-level data analysis.

Analytical Approach: Individual-study-data meta-analysis used a bivariate time-to-event model for interval-censored data from which discriminative ability (AUC) was characterized. NGAL cutoff concentrations at 95% sensitivity, 95% specificity, and optimal sensitivity and specificity were also estimated. Models incorporated as confounders the clinical setting and use versus nonuse of urine output as a criterion for AKI. A literature-based meta-analysis was also performed for all published studies including those for which the authors were unable to provide individual-study data analyses.

Results: We included 52 observational studies involving 13,040 patients. We analyzed 30 data sets for the individual-study-data meta-analysis. For AKI, severe AKI, and AKI-D, numbers of events were 837, 304, and 103 for analyses of urinary NGAL, respectively; these values were 705, 271, and 178 for analyses of plasma NGAL. Discriminative performance was similar in both meta-analyses. Individual-study-data meta-analysis AUCs for urinary NGAL were 0.75 (95% CI, 0.73-0.76) and 0.80 (95% CI, 0.79-0.81) for severe AKI and AKI-D, respectively; for plasma NGAL, the corresponding AUCs were 0.80 (95% CI, 0.79-0.81) and 0.86 (95% CI, 0.84-0.86). Cutoff concentrations at 95% specificity for urinary NGAL were>580ng/mL with 27% sensitivity for severe AKI and>589ng/mL with 24% sensitivity for AKI-D. Corresponding cutoffs for plasma NGAL were>364ng/mL with 44% sensitivity and>546ng/mL with 26% sensitivity, respectively.

Limitations: Practice variability in initiation of dialysis. Imperfect harmonization of data across studies.

Conclusions: Urinary and plasma NGAL concentrations may identify patients at high risk for AKI in clinical research and practice. The cutoff concentrations reported in this study require prospective evaluation.
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http://dx.doi.org/10.1053/j.ajkd.2020.05.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283708PMC
December 2020

Comparison of Thromboelastography and Conventional Coagulation Tests in Patients With Severe Liver Disease.

Clin Appl Thromb Hemost 2020 Jan-Dec;26:1076029620925915

Department of Intensive Care, Austin Health, Heidelberg, Melbourne, Australia.

Objective: Thromboelastography (TEG) may provide rapid and clinically important coagulation information in acutely ill patients with chronic liver disease (CLD). Our objective was to describe the relationship between TEG and conventional coagulation tests (CCTs), which has not been previously explored in this population.

Methods: In acutely ill patients with severe CLD (Child-Pugh score > 9, category C), we conducted a prospective observational study investigating coagulation assessment as measured by both CCTs and TEG. We used quantile regression to explore 30 associations between TEG parameters and corresponding CCTs. We compared TEG and CCT measures of coagulation initiation, clot formation, clot strength, and fibrinolysis.

Results: We studied 34 patients on a total of 109 occasions. We observed inconsistent associations between TEG and CCT measures of coagulation initiation: TEG (citrated kaolin [CK] assay) standard reaction time and international normalized ratio: = 0.117 ( = .044). Conversely, there were strong and consistent associations between tests of clot formation: TEG (CK) kinetics time and fibrinogen: = 0.202 ( < .0001) and TEG (CK) α angle and fibrinogen 0.263 ( < .0001). We also observed strong associations between tests of clot strength, specifically TEG MA and conventional fibrinogen levels, across all TEG assays: MA (CK) and fibrinogen: = 0.485 ( < .0001). There were no associations between TEG and D-dimer levels.

Conclusions: In acutely ill patients with CLD, there are strong and consistent associations between TEG measures of clot formation and clot strength and conventional fibrinogen levels. There are weak and/or inconsistent associations between TEG and all other conventional measures of coagulation.
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http://dx.doi.org/10.1177/1076029620925915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427018PMC
February 2021

Study protocol and statistical analysis plan for the Liberal Glucose Control in Critically Ill Patients with Pre-existing Type 2 Diabetes (LUCID) trial.

Crit Care Resusc 2020 Jun;22(2):133-141

Department of Intensive Care, Royal Melbourne Hospital, Melbourne, VIC, Australia.

Background: Contemporary glucose management of intensive care unit (ICU) patients with type 2 diabetes is based on trial data derived predominantly from patients without type 2 diabetes. This is despite the recognition that patients with type 2 diabetes may be relatively more tolerant of hyperglycaemia and more susceptible to hypoglycaemia. It is uncertain whether glucose targets should be more liberal in patients with type 2 diabetes.

Objective: To detail the protocol, analysis and reporting plans for a randomised clinical trial - the Liberal Glucose Control in Critically Ill Patients with Pre-existing Type 2 Diabetes (LUCID) trial - which will evaluate the risks and benefits of targeting a higher blood glucose range in patients with type 2 diabetes.

Design, Setting, Participants And Intervention: A multicentre, parallel group, open label phase 2B randomised controlled clinical trial of 450 critically ill patients with type 2 diabetes. Patients will be randomised 1:1 to liberal blood glucose (target 10.0-14.0 mmol/L) or usual care (target 6.0-10.0 mmol/L).

Main Outcome Measures: The primary endpoint is incident hypoglycaemia (< 4.0 mmol/L) during the study intervention. Secondary endpoints include biochemical and feasibility outcomes.

Results And Conclusion: The study protocol and statistical analysis plan described will delineate conduct and analysis of the trial, such that analytical and reporting bias are minimised.

Trial Registration: This trial has been registered on the Australian New Zealand Clinical Trials Registry (ACTRN No. 12616001135404) and has been endorsed by the Australian and New Zealand Intensive Care Society Clinical Trials Group.
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June 2020

Assessing TEG6S reliability between devices and across multiple time points: A prospective thromboelastography validation study.

Sci Rep 2020 04 27;10(1):7045. Epub 2020 Apr 27.

Department of Anaesthesia, Austin Hospital, 145 Studley Rd, Heidelberg, 3084, Victoria, Australia.

The TEG6S is a novel haemostasis analyser utilising resonance technology. It offers potentially greater coagulation information and ease of use, however has not been independently validated in a clinical setting. We aimed to determine if the TEG6S is reliable between devices and across time points. We performed a prospective observational study with ethical approval. For interdevice reliability, we performed simultaneous analysis on two TEG6S devices on 25 adult ICU patients. For time point reliability, we performed repeated sampling across five different time points on 15 adult participants. Blood was collected with informed consent, or as standard care, before four-channel citrated kaolin analysis. We observed almost perfect interdevice reliability across all TEG parameters. The Lin's concordance correlation coefficients (95% CI, major axis regression slope, intercept) were R-time: 0.96 (0.92-0.99, 0.88, 0.57); K-time: 0.93 (0.87-0.98, 1.07, 0.00); Alpha Angle: 0.87 (0.78-0.96, 1.20, -14.10); Maximum Amplitude: 0.99 (0.98-0.99, 1.02, -1.38); Clot Lysis: 0.89 (0.82-0.97, 1.20, 0.07). Additionally, we observed moderate-to-high reliability across time points. Demonstrating almost perfect agreement across different devices and moderate-to-high reliability across multiple time points, suggests the TEG6S platform can be used with haemostatic accuracy and generalisability. This has potentially significant implications for clinical practice and multi-site research programs.
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http://dx.doi.org/10.1038/s41598-020-63964-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184600PMC
April 2020

Towards unconstrained compartment modeling in white matter using diffusion-relaxation MRI with tensor-valued diffusion encoding.

Magn Reson Med 2020 09 6;84(3):1605-1623. Epub 2020 Mar 6.

Clinical Sciences Lund, Radiology, Lund University, Lund, Sweden.

Purpose: To optimize diffusion-relaxation MRI with tensor-valued diffusion encoding for precise estimation of compartment-specific fractions, diffusivities, and T values within a two-compartment model of white matter, and to explore the approach in vivo.

Methods: Sampling protocols featuring different b-values (b), b-tensor shapes (b ), and echo times (TE) were optimized using Cramér-Rao lower bounds (CRLB). Whole-brain data were acquired in children, adults, and elderly with white matter lesions. Compartment fractions, diffusivities, and T values were estimated in a model featuring two microstructural compartments represented by a "stick" and a "zeppelin."

Results: Precise parameter estimates were enabled by sampling protocols featuring seven or more "shells" with unique b/b /TE-combinations. Acquisition times were approximately 15 minutes. In white matter of adults, the "stick" compartment had a fraction of approximately 0.5 and, compared with the "zeppelin" compartment, featured lower isotropic diffusivities (0.6 vs. 1.3 μm /ms) but higher T values (85 vs. 65 ms). Children featured lower "stick" fractions (0.4). White matter lesions exhibited high "zeppelin" isotropic diffusivities (1.7 μm /ms) and T values (150 ms).

Conclusions: Diffusion-relaxation MRI with tensor-valued diffusion encoding expands the set of microstructure parameters that can be precisely estimated and therefore increases their specificity to biological quantities.
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http://dx.doi.org/10.1002/mrm.28216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652211PMC
September 2020

Haemodynamic effect of a 20% albumin fluid bolus in post-cardiac surgery patients.

Crit Care Resusc 2020 Mar;22(1):15-25

Department of Intensive Care, Austin Hospital, Melbourne, VIC, Australia.

Objective: To study the cardiovascular effect over 30 minutes following the end of fluid bolus therapy (FBT) with 20% albumin in patients after cardiac surgery.

Design: Prospective observational study.

Setting: Intensive care unit of a tertiary university-affiliated hospital.

Participants: Twenty post-cardiac surgery mechanically ventilated patients with a clinical decision to administer FBT.

Intervention: FBT with a 100 mL bolus of 20% albumin.

Main Outcome Measures: Cardiac index (CI) response was defined by a ≥ 15% increase, while mean arterial pressure (MAP) response was defined by a ≥ 10% increase.

Results: The most common indication for FBT was hypotension (40%). Median duration of infusion was 7 minutes (interquartile range [IQR], 3-9 min). At the end of FBT, five patients (25%) showed a CI response, which increased to almost half in the following 30 minutes and dissipated in one patient. MAP response occurred in 11 patients (55%) and dissipated in five patients (45%) by a median of 6 minutes (IQR, 6-10 min). CI and MAP responses coexisted in four patients (20%). An intrabolus MAP response occurred in 17 patients (85%) but dissipated in 11 patients (65%) within a median of 7 minutes (IQR, 2-11 min). On regression analysis, faster fluid bolus administration predicted MAP increase at the end of the bolus.

Conclusion: In post-cardiac surgery patients, CI response to 20% albumin FBT was not congruous with MAP response over 30 minutes. Although hypotension was the main indication for FBT and a MAP response occurred in most of patients, such response was maximal during the bolus, dissipated in a few minutes, and was dissociated from the CI response.
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March 2020

Point-of-care creatinine measurements to predict acute kidney injury.

Acta Anaesthesiol Scand 2020 07 3;64(6):766-773. Epub 2020 Mar 3.

Department of Intensive Care, Austin Hospital, Austin Health, Melbourne, Vic, Australia.

Background: Plasma creatinine (Cr) is a marker of kidney function and typically measured once daily. We hypothesized that Cr measured by point-of-care technology early after ICU admission would be a good predictor of acute kidney injury (AKI) the next day in critically ill patients.

Methods: We conducted a retrospective database audit in a single tertiary ICU database. We included patients with normal first admission Cr (Cr ) and identified a Cr value (Cr ) obtained within 6-12 hours from ICU admission. We used their difference converted into percentage (delta-Cr-%) to predict subsequent AKI (based on Cr and/or need for renal replacement therapy) the next day. We assessed predictive value by calculating area under the receiver characteristic curve (AUC), logistic regression models for AKI with and without delta-Cr-%, and the category-free net reclassifying index (cfNRI).

Results: We studied 780 patients. Overall, 70 (9.0%) fulfilled the Cr AKI definition by Cr measurement. On day 2, 148 patients (19.0%) were diagnosed with AKI. AUC (95% CI) for delta-Cr-% to predict AKI on day 2 was 0.82 (95% CI 0.78-0.86), and 0.74 (95% CI 0.69-0.80) when patients with AKI based on the Cr were excluded. Using a cut-off of 17% increment, the positive likelihood ratio (95% CI) for delta-Cr-% to predict AKI was 3.5 (2.9-4.2). The cfNRI was 90.0 (74.9-106.1).

Conclusions: Among patients admitted with normal Cr, early changes in Cr help predict AKI the following day.
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http://dx.doi.org/10.1111/aas.13564DOI Listing
July 2020

The effect of mindfulness training on extinction retention.

Sci Rep 2019 12 27;9(1):19896. Epub 2019 Dec 27.

Department of Psychology, University of Southern Denmark, Odense, Denmark.

Anxiety and trauma related disorders are highly prevalent, causing suffering and high costs for society. Current treatment strategies, although effective, only show moderate effect-sizes when compared to adequate control groups demonstrating a need to develop new forms of treatment or optimize existing ones. In order to achieve this, an increased understanding of what mechanisms are involved is needed. An emerging literature indicates that mindfulness training (MFT) can be used to treat fear and anxiety related disorders, but the treatment mechanisms are unclear. One hypothesis, largely based on findings from neuroimaging studies, states that MFT may improve extinction retention, but this has not been demonstrated empirically. To investigate this question healthy subjects either completed a 4-week MFT- intervention delivered through a smart-phone app (n = 14) or were assigned to a waitlist (n = 15). Subsequently, subjects participated in a two-day experimental protocol using pavlovian aversive conditioning, evaluating acquisition and extinction of threat-related responses on day 1, and extinction retention on day 2. Results showed that the MFT group displayed reduced spontaneous recovery of threat related arousal responses, as compared to the waitlist control group, on day 2. MFT did not however, have an effect on either the acquisition or extinction of conditioned responses day 1. This clarifies the positive effect of MFT on emotional functioning and could have implications for the treatment of anxiety and trauma related disorders.
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http://dx.doi.org/10.1038/s41598-019-56167-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934560PMC
December 2019

Relative Hypoglycemia in Diabetic Patients With Critical Illness.

Crit Care Med 2020 03;48(3):e233-e240

Department of Intensive Care, Austin Hospital, Heidelberg, Melbourne, VIC, Australia.

Objectives: Relative hypoglycemia is a decrease in glucose greater than or equal to 30% below prehospital admission levels (estimated by hemoglobin A1C) but not to absolute hypoglycemia levels. It is a recognized pathophysiologic phenomenon in ambulant poorly controlled diabetic patients but remains unexamined during critical illness. We examined the frequency, characteristics, and outcome associations of relative hypoglycemia in diabetic patients with critical illness.

Design: Retrospective cohort study.

Setting: ICU of a tertiary hospital.

Patients: One-thousand five-hundred ninety-two critically ill diabetic patients between January 2013 and December 2017.

Interventions: None.

Measurements And Main Results: The median age of patients was 67 years (interquartile range, 60-75 yr). The median Acute Physiology and Chronic Health Evaluation III score was 53 (interquartile range, 40-68). Thirty-four percent of patients with diabetes experienced relative hypoglycemia (exposure) during their ICU admission. Such patients had higher glycemic lability, hemoglobin A1C levels, and Acute Physiology and Chronic Health Evaluation III scores. The hazard ratio for 28-day mortality of diabetic patients, censored at hospital discharge, for patients with relative hypoglycemia was 1.9 (95% CI, 1.3-2.8) and was essentially unchanged after adjustment for episodes of absolute hypoglycemia. After an episode of relative hypoglycemia, the hazard ratio for subsequent absolute hypoglycemia in the ICU was 3.5 (95% CI, 2.3-5.3).

Conclusions: In ICU patients with diabetes, relative hypoglycemia is common, increases with higher hemoglobin A1C levels, and is a modifiable risk factor for both mortality and subsequent absolute hypoglycemia. These findings provide the rationale for future interventional studies to explore new blood glucose management strategies and to substantiate the clinical relevance of relative hypoglycemia.
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http://dx.doi.org/10.1097/CCM.0000000000004213DOI Listing
March 2020

Laboratory-derived early warning score for the prediction of in-hospital mortality, intensive care unit admission, medical emergency team activation and cardiac arrest in general medical wards.

Intern Med J 2021 May;51(5):746-751

Data Analytics Research and Evaluation Centre, University of Melbourne and Austin Hospital, Melbourne, Victoria, Australia.

Background: General medical wards admit a varied cohort of patients from the emergency department, some of whom deteriorate during their hospital stay. Currently, we use vital signs based warning scores to predict patients at risk of imminent deterioration, but there is now a growing body of literature that commonly available laboratory results may also help to identify those at risk.

Aim: To assess whether a laboratory-based admission score can predict in hospital mortality, intensive care unit (ICU) admission, medical emergency team (MET) activation or cardiac arrest in a cohort of Australian general medical patients admitted through the emergency department (ED).

Methods: We performed a retrospective observational study of all general medical admissions to hospital through the ED in 2015. Admission pathology was used to calculate a risk score. In-patient outcomes of death, ICU transfer, MET call activation or cardiac arrest were collected from hospital records.

Results: We studied 2942 admissions derived from 2521 patients, with a median age of 81 years. There were 143 in-patient deaths, 82 ICU admissions, 277 MET calls and 14 cardiac arrest calls. The laboratory-based admission score had an area under the receiver operating characteristic curve (AUC-ROC) of 0.76 (95% confidence interval (CI): 0.72-0.80) for inpatient death, an AUC-ROC of 0.79 (95% CI: 0.66-0.93) for inpatient cardiac arrest, an AUC-ROC of 0.64 (95% CI: 0.58-0.70) for ICU transfer and an AUC-ROC of 0.59 (95% CI: 0.55-0.62) for MET call activation. When patients aged over 75 were analysed separately, the AUC-ROC for prediction of in-patient death was 0.74 (95% CI: 0.70-0.78) and increased to 0.86 (95% CI: 0.73-0.98) for the prediction of in-patient cardiac arrest.

Conclusion: A simple laboratory-derived score obtained at patient admission is a fair to good predictor of subsequent in-patient death or cardiac arrest in general medical patients and in the older patient cohort. Prospective interventional studies are required to ascertain the clinical utility of this admission score.
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http://dx.doi.org/10.1111/imj.14613DOI Listing
May 2021

Stress Levels Escalate When Repeatedly Performing Tasks Involving Threats.

Front Psychol 2019 4;10:1562. Epub 2019 Jul 4.

Lund University Humanities Lab, Lund, Sweden.

Police work may include performing repeated tasks under the influence of psychological stress, which can affect perceptual, cognitive and motor performance. However, it is largely unknown how repeatedly performing stressful tasks physically affect police officers in terms of heart rate and pupil diameter properties. Psychological stress is commonly assessed by monitoring the changes in these biomarkers. Heart rate and pupil diameter was measured in 12 male police officers when performing a sequence of four stressful tasks, each lasting between 20 and 130 s. The participants were first placed in a dimly illuminated anteroom before allowed to enter a brightly lit room where a scenario was played out. After each task was performed, the participants returned to the anteroom for about 30 s before performing the next sequential task. Performing a repeated sequence of stressful tasks caused a significant increase in heart rate ( = 0.005). The heart rate started to increase already before entering the scenario room and was significantly larger just after starting the task than just before starting the task ( < 0.001). This pattern was more marked during the first tasks ( < 0.001). Issuance of a verbal "abort" command which terminated the tasks led to a significant increase of heart rate ( = 0.002), especially when performing the first tasks ( = 0.002). The pupil diameter changed significantly during the repeated tasks during all phases but in a complex pattern where the pupil diameter reached a minimum during task 2 followed by an increase during tasks 3 and 4 ( ≤ 0.020). During the initial tasks, the pupil size ( = 0.014) increased significantly. The results suggest that being repeatedly exposed to stressful tasks can produce in itself an escalation of psychological stress, this even prior to being exposed to the task. However, the characteristics of both the heart rate and pupil diameter were complex, thus, the findings highlight the importance of studying the effects and dynamics of different stress-generating factors. Monitoring heart rate was found useful to screen for stress responses, and thus, to be a vehicle for indication if and when rotation of deployed personnel is necessary to avoid sustained high stress exposures.
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http://dx.doi.org/10.3389/fpsyg.2019.01562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6621421PMC
July 2019

Performance of plasma measurement of neutrophil gelatinase-associated lipocalin as a biomarker of bacterial infections in the intensive care unit.

J Crit Care 2019 10 2;53:264-270. Epub 2019 Jul 2.

Department of Physiology and Pharmacology, Karolinska Institutet, 171 77, Stockholm, Sweden.

Purpose: To assess the value of dimeric neutrophil-gelatinase associated lipocalin (NGAL) as an early marker of bacterial infection and its response to antibiotic therapy in intensive care unit (ICU) patients.

Materials & Methods: We measured daily plasma dNGAL in 198 patients admitted to a mixed ICU. Likelihood of infection was determined with International Sepsis Forum criteria. We measured dNGAL in 145 healthy controls to establish normal values.

Results: ICU patients had higher dNGAL than healthy controls. A suspected or confirmed infection was independently associated with 90% (95% CI 15-215%) higher dNGAL than absence of infection. We observed no association between acute kidney injury and dNGAL. Diagnostic accuracy at antibiotic treatment initiation, assessed with area under the receiver-operating characteristics curve (AUC-ROC), for dNGAL was 0.70 (95% CI 0.60-0.79). AUC-ROC for dNGAL 24 h before antibiotic treatment initiation was 0.54 (95% CI 0.41-0.66). The mean (95% CI) change of dNGAL in the first 2 days after appropriate antibiotic therapy initiation was -31 (-49,-13)%.

Conclusions: In our cohort of ICU patients, plasma dNGAL was associated with presence of bacterial infections independent of AKI but it performed poor as a predictor of infections. Following antibiotic therapy, dNGAL markedly decreased-supporting further exploration of dNGAL-guided antibiotic de-escalation.
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http://dx.doi.org/10.1016/j.jcrc.2019.07.001DOI Listing
October 2019

Fluid balance after continuous renal replacement therapy initiation and outcome in paediatric multiple organ failure.

Acta Anaesthesiol Scand 2019 09 3;63(8):1028-1036. Epub 2019 Jun 3.

Department of Paediatric Perioperative Medicine and Intensive Care, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.

Background: Patients with multiple organ failure (MOF) often receive large amounts of resuscitation fluid, making them at high risk of fluid overload (FO). Our main objective was to investigate if the ability to achieve a negative fluid balance during the first 3 continuous renal replacement therapy (CRRT) days was associated with mortality in children with MOF.

Methods: Retrospective cohort study in a tertiary multidisciplinary academic paediatric hospital. The study included 63 patients (age 0-18 years) with 3 or more failing organs receiving CRRT due to acute kidney injury and/or fluid overload.

Results: The median age was 4 months, and PICU mortality was 29%. Survivors had significantly lower degree of FO at CRRT initiation, (median 15% (Interquartile range 9-22)) than non-survivors (24% (17%-37%), P = 0.002). On PICU admission, PIM-3 score was significantly higher in non-survivors (P = 0.01), but at CRRT initiation there was no difference in PELOD-2 score (P = 0.98). Mortality in patients achieving a cumulative net negative fluid balance during the first 3 days after CRRT initiation was 12%, compared to 86% in those not achieving this (P < 0.0001). In multivariate analysis, the inability to achieve a net negative fluid balance during 3 days after CRRT initiation (P < 0.0001) and FO >20% at CRRT initiation (P = 0.0019) remained associated with mortality.

Conclusion: Our results suggest that early fluid removal is associated with improved patient outcome in critically ill children receiving CRRT, and that prompt measures should be taken to prevent fluid overload in critical illness. These results need to be verified in further, prospective studies.
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http://dx.doi.org/10.1111/aas.13389DOI Listing
September 2019

Sepsis uncouples serum C-peptide and insulin levels in critically ill patients with type 2 diabetes mellitus.

Crit Care Resusc 2019 Jun;21(2):87-95

Department of Intensive Care, Austin Hospital, Melbourne, VIC, Australia.

Objective: To assess the effects of sepsis and exogenous insulin on C-peptide levels and C-peptide to insulin ratios in intensive care unit (ICU) patients with type 2 diabetes mellitus (T2DM).

Design, Setting And Participants: In this prospective, observational, single-centre study, we enrolled 31 ICU-admitted adults with T2DM. We measured serum C-peptide and insulin levels during the first 3 days of ICU stay and recorded characteristics of exogenous insulin therapy. Patients were compared on the basis of the presence of sepsis, and their exposure to exogenous insulin therapy. C-peptide levels were also measured in eight healthy subjects.

Main Outcome Measures: Serum insulin and C-peptide levels during the first 3 days in ICU.

Results: Median C-peptide levels were higher in the ICU population compared with healthy subjects (10.9 [IQR, 8.2 -14.1] 4.8 [IQR, 4.6-5.1] nmol/L, < 0.01). Sepsis was present in 25 ICU patients (81%). Among ICU patients unexposed to exogenous insulin, the 11 patients with sepsis had higher median C-peptide levels compared with the six non-septic patients (2.5 [IQR, 1.8-3.7] 1.7 [IQR, 0.8-2.2] nmol/L, = 0.04), and a threefold higher C-peptide to insulin ratio (45 [IQR, 37-62] 13 [IQR, 11-17], = 0.03). However, septic patients exposed to exogenous insulin had lower median C-peptide levels (1.2 [IQR, 0.7-2.3] nmol/L, = 0.01) and C-peptide to insulin ratios (5 [IQR, 2-10], < 0.01) compared with insulin-free septic patients. The C-peptide to insulin ratio was significantly associated with white cell count and severity of illness in insulin-free septic patients.

Conclusion: C-peptide levels were elevated in critically ill patients with T2DM. In this population, sepsis increased C-peptide levels and uncoupled serum C-peptide and insulin levels. Exogenous insulin decreased both C-peptide levels and C-peptide to insulin ratios.
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June 2019

Conservative versus conventional oxygen therapy for cardiac surgical patients: A before-and-after study.

Anaesth Intensive Care 2019 Mar 21;47(2):175-182. Epub 2019 May 21.

1 Department of Intensive Care, Austin Hospital, Australia.

Avoiding hypoxaemia is considered crucial in cardiac surgery patients admitted to the intensive care unit (ICU). However, avoiding hyperoxaemia may also be important. A conservative approach to oxygen therapy may reduce exposure to hyperoxaemia without increasing the risk of hypoxaemia. Using a before-and-after design, we evaluated the introduction of conservative oxygen therapy (target SpO 88%-92% using the lowest FiO) for cardiac surgical patients admitted to the ICU. We studied 9041 arterial blood gas (ABG) datasets: 4298 ABGs from 245 'conventional' and 4743 ABGs from 298 'conservative' oxygen therapy patients. During mechanical ventilation (MV) and while in the ICU, compared to the conventional group, conservative group patients had significantly lower FiO exposure and PaO values ( P < 0.001 for each). Accordingly, using the mean PaO during MV, more conservative group patients were classified as normoxaemic (226 versus 62 patients, P < 0.01), fewer as hyperoxaemic (66 versus 178 patients, P < 0.01) and no patient in either group as hypoxaemic or severely hypoxaemic. Moreover, more ABG samples were hyperoxaemic or severely hyperoxaemic during conventional treatment ( P < 0.001). Finally, there was no difference in ICU or hospital length of stay, ICU or hospital mortality or 30-day mortality between the groups. Our findings support the feasibility and physiological safety of conservative oxygen therapy in patients admitted to ICU after cardiac surgery.
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http://dx.doi.org/10.1177/0310057X19838753DOI Listing
March 2019
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