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Aim Early extubation after cardiac surgery shortens paediatric intensive care unit (PICU) length of stay (LOS) and decreases complications from mechanical ventilation (MV). We explored the duration of MV in Scandinavian paediatric heart centres. Methods We retrospectively reviewed the MV duration and PICU LOS of 696 children operated for atrial septal defect (ASD), ventricular septal defect (VSD), tetralogy of Fallot (TOF) or total cavopulmonary connection (TCPC) in four Scandinavian centres in 2015-2016. Neonates (n = 90) were included regardless of heart surgery type. Results Patients with ASD were extubated at a median of 3.25 h (interquartile range [IQR] 2.00-4.83), followed by patients with TCPC (median 5.00 h, IQR 2.60-16.83), VSD (median 7.00 h, IQR 3.69-22.25) and TOF (median 18.08 h, IQR 6.00-41.38). Neonates were not extubated early (median 94.42 h, IQR 45.03-138.14). Although MV durations were reflected in PICU LOS, this was not as apparent among those extubated within 12 h. The Swedish centres had shortest MV durations and PICU LOS. Extubation failed in 24/696 (3.4%) of patients. Conclusion Scandinavian paediatric heart centres differed in the duration of postoperative MV. Deferring extubation up to 12 h postoperatively did not markedly prolong PICU LOS.

Aims Peripheral arterial disease (PAD) and coronary artery disease (CAD) are both caused by atherosclerosis. Serum lipids and lipoproteins are predictive of the development of atherosclerosis but it is not clear if they differ in the two manifestations PAD and CAD. We tested whether a more detailed characterization of the lipid and lipoprotein patterns of PAD and CAD allows a clear differentiation between the two atherosclerotic phenotypes. Methods A cohort of 274 statin-naive patients with either newly diagnosed imaging proven PAD (n = 89) or stable CAD (n = 185) was characterized using NMR- and LC-MS/MS-based advanced lipid and lipoprotein analysis. An independent cohort of 1239 patients with PAD and CAD was used for validation. Results We found a significant difference in markers of inflammation as well as ceramide and phosphatidylcholine levels between PAD and CAD patients. In contrast, basic lipid markers including total cholesterol, low density lipoprotein cholesterol, high density lipoprotein-cholesterol, lipoprotein (a) or detailed lipoprotein profiles did not differ significantly between PAD and CAD patients. Applying ratios and scores derived from ceramides and phosphatidylcholines further improved the discrimination between PAD and CAD. These significant differences were independent from body composition, from the status of smoking or T2DM, and also from apolipoprotein C-III and other inflammatory parameters which were different between CAD and PAD. Conclusion The present study clearly suggests that PAD and CAD differ in terms of their ceramide- and phosphatidylcholine-based lipid pattern but not in lipoprotein characteristics. This article is protected by copyright. All rights reserved.

AimCholesterol-based risk prediction is often insufficient in cardiovascular disease (CVD) patients. Ceramides are a new kind of biomarkers for CVD. The Coronary Event Risk Test (CERT) is a validated cardiovascular risk predictor that uses only circulating ceramide levels, determined by coupled liquid chromatography–mass spectrometry, to allocate patients into one of four risk categories. This test has recently been modified (CERT2) by additionally including phosphatidylcholine levels.Methods and resultsIn this observational cohort study, we have recruited 999 Austrian patients with CVD and followed them for up to 13 years. We found that CERT and CERT2 both predicted cardiovascular events, cardiovascular mortality, and overall mortality. CERT2 had the higher performance compared to CERT and also to the recent cardiovascular risk score of the ESC/EAS guidelines (Systematic COronary Risk Evaluation (SCORE)) for low-risk European countries. Combining CERT2 with the ESC/EAS-SCORE, predictive capacity was further increased leading to a hazard ratio of 3.58 (2.02–6.36; P ConclusionWe conclude that CERT and CERT2 are powerful predictors of cardiovascular events, cardiovascular mortality, and overall mortality in CVD patients. Including phosphatidylcholine to a ceramide-based score increases the predictive performance and is best in combination with classical risk factors as used in the ESC/EAS-SCORE.

Background There is a lack of knowledge how patients with COVID-19 disease differ from patients with similar signs or symptoms (but who will have a diagnosis other than COVID-19) in the prehospital setting. The aim of this study was to compare the characteristics of these two patient groups met by the emergency medical services. Methods All prehospital patients after the World Health Organisation (WHO) pandemic declaration 11.3.2020 until 30.6.2020 were recruited for the study. The patients were screened using modified WHO criteria for suspected COVID-19. Data from the electronic prehospital patient reporting system were linked with hospital laboratory results to check the laboratory confirmation for COVID-19. For comparison, we divided the patients into two groups: screening- and laboratory-positive patients with a hospital diagnosis of COVID-19 and screening-positive but laboratory-negative patients who eventually received a different diagnosis in hospital. Results A total of 4157 prehospital patients fulfilled the criteria for suspected COVID-19 infection during the study period. Five-hundred-thirty-six (12.9%) of the suspected cases received a laboratory confirmation for COVID-19. The proportion of positive cases in relation to suspected ones peaked during the first 2 weeks after the declaration of the pandemic. In the comparison of laboratory-positive and laboratory-negative cases, there were clinically insignificant differences between the groups in age, tympanic temperature, systolic blood pressure, heart rate, on-scene time, urgency category of the call and mode of transportation. Foreign-language-speakers were overrepresented amongst the positive cases over native language speakers (26,6% vs. 7,4%, p Conclusions In a sample of suspected COVID-19 patients, the laboratory-positive and laboratory-negative patients were clinically indistinguishable from each other during the prehospital assessment. Foreign-language-speakers had a high likelihood of having Covid-19. The modified WHO criteria still form the basis of screening of suspected COVID-19 patients in the prehospital setting.

Aim To investigate paediatric emergency room (ER) visits to evaluate the immediate health effects of COVID-19 pandemic restrictions on children. Methods We retrospectively examined paediatric ER visits in the Helsinki University Hospital (HUH) district during the first wave of the pandemic (1 March to 31 May 2020), and a 2-month period immediately before and after. These periods were compared to the corresponding time periods in 2015-2019 ('reference period'). Results The total number of ER visits decreased by 23.4% (mean 6474 during the reference period, 4960 during the pandemic period (incidence rate ratio [IRR] 0.75, 95% confidence interval 0.72-0.77; p < 0.001). This was due to a decrease in visits related to infectious diseases; visits due to surgical reasons did not decrease. The amount or proportion of patients triaged to the most urgent class (Emergency Severity Index 1) did not increase. Paediatric ER visits returned to baseline after lifting of restrictions. Conclusions Although paediatric ER visits substantially decreased during the pandemic restrictions, children seen at the ER were not more severely ill. Our results do not indicate immediate detrimental health effects of pandemic control measures on children.

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Background Emergency nurses are expected to follow recent research findings and ensure that their practice is based on evidence. Yet, during busy work-shifts in overcrowded emergency departments, evidence-based practice (EBP) is not always implemented. Aim To describe emergency nurses’ EBP attitudes, self-efficacy, knowledge, skills and behaviours at the baseline of a RCT. Methods A baseline study as a part of a randomised, single-blind controlled multicentre intervention trial (RCT). The study population consisted of 300 emergency nurses employed in two university hospitals’ emergency departments in Finland. The total sample size (n = 80) was estimated using a simulation approach. The data were collected from voluntary emergency nurses by using four structured questionnaires. Findings Emergency nurses’ EBP attitudes, self-efficacy, knowledge and skills were above the average level, and their EBP behaviour was below the average level when measured with the other of the two sum variables measuring behaviour. A significant correlation was found between age, years since graduation, the length of working experience in health care and EBP attitudes, behaviour, knowledge and self-efficacy. Younger emergency nurses who had recently graduated and had shorter work experience showed more positive attitudes towards EBP than older counterparts. No correlation was found between gender, educational background or prior exposure to EBP and EBP attitudes, self-efficacy, knowledge, skills or behaviours. Conclusions This study showed that to promote emergency nurses’ use of EBP in future, tailored educational interventions on EBP are needed. This would ensure implementation of EBP in daily clinical practice for quality and effective patient care.

Objectives Seizures seem to represent a frequent cause for pediatric emergency medical (EM) and emergency room (ER) contacts, but few population-based data are available. Our aim was to study the incidence, prehospital and ER treatment, and outcomes of pediatric seizures necessitating out-of-hospital care. Methods We studied the out-of-hospital evaluation procedures, ER treatment, diagnostics and 2-year prognosis of all cases of pediatric (0-16 years) seizures encountered by the emergency medical services (EMS) in Helsinki, Finland, in 2012 (population 603,968, pediatric population 92,742); 251 patients were encountered by the EMS, of which 220 seen at the ER. Results The yearly incidence of pediatric seizures necessitating EMS activation was 2.8/1000 in the pediatric population. Febrile seizures were responsible for 97 (44.1%) of the cases transported to the ER. Only a minority of patients required advanced life support measures out-of-hospital or complex diagnostics in the ER. Still, of the 220 patients seen at ER, 68 (30.9%) were hospitalized, and 106 (48.2%) had follow-up contacts scheduled. Conclusions Pediatric seizures were a common cause for EM and ER contacts. Advanced life support measures were seldom needed, and the prognosis was good, but seizures still required considerable resources. They often resulted in urgent EM dispatch and transport, hospitalization, follow-up visits, new medication, and complementary studies. This emphasizes the role the EMS plays in recognizing and terminating pediatric seizures and in referring these children to appropriate care.

BACKGROUND AND IMPORTANCE: Emergency Severity Index is a five-level triage tool in the emergency department that predicts the need for emergency department resources and the degree of emergency. However, it is unknown whether this is valid in patients aged greater than or equal to 65 years. OBJECTIVE: The aim of the study was to compare the accuracy of the Emergency Severity Index triage system between emergency department patients aged 18-64 and greater than or equal to 65 years. DESIGN, SETTINGS, AND PARTICIPANTS: This was a retrospective observational cohort study of adults who presented to a Finnish emergency department between 1 February 2018 and 28 February 2018. All data were collected from electronic health records. OUTCOME MEASURES AND ANALYSIS: The primary outcome was 3-day mortality. The secondary outcomes were 30-day mortality, hospital admission, high dependency unit or ICU admission, and emergency department length of stay. The area under the receiver operating characteristic curve and cutoff performances were used to investigate significant associations between triage categories and outcomes. The results of the two age groups were compared. MAIN RESULTS: There were 3141 emergency department patients aged 18-64 years and 2370 patients aged greater than or equal to 65 years. The 3-day mortality area under the curve in patients aged greater than or equal to 65 years was greater than that in patients aged 18-64 years. The Emergency Severity Index was associated with high dependency unit/ICU admissions in both groups, with moderate sensitivity [18-64 years: 61.8% (50.9-71.9%); greater than or equal to 65 years: 73.3% (63.5-81.6%)] and high specificity [18-64 years: 93.0% (92.0-93.8%); greater than or equal to 65 years: 90.9% (90.0-92.1%)]. The sensitivity was high and specificity was low for 30-day mortality and hospital admission in both age groups. The emergency department length of stay was the longest in Emergency Severity Index category 3 for both age groups. There was no significant difference in accuracy between age groups for any outcome. CONCLUSION: Emergency Severity Index performed well in predicting high dependency unit/ICU admission rates for both 18-64 years and greater than or equal to 65-year-old patients. It predicted the 3-day mortality for patients aged greater than or equal to 65 years with high accuracy. It was inaccurate in predicting 30-day mortality and hospital admission for both age groups. publishedVersion

Aims A risk score, CERT2, based on distinct ceramide and phosphatidylcholine lipid species, has shown robust performance in predicting cardiovascular risk in secondary prevention. Here, our aim was to investigate the predictive value of CERT2 in primary prevention compared to classical lipid biomarkers and its compatibility with clinical characteristics used in the SCORE risk chart. Methods and results Four ceramides [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:0), Cer(d18:1/24:1)] and three phosphatidylcholines [PC(14:0/22:6), PC(16:0/22:5), PC(16:0/16:0)] were analysed by targeted tandem liquid chromatography–mass spectrometry method in FINRISK 2002, which is a population-based risk factor survey investigating men and women aged 25–74 years. Primary prevention subjects (N = 7324) were followed up for 10 years for the following outcomes: incident coronary heart disease (CHD), cardiovascular disease (CVD), major adverse cardiovascular event (MACE), stroke, and heart failure. Hazard ratios per standard deviation obtained from adjusted Cox proportional hazard models were significant for all these endpoints, and the highest for fatal ones, i.e. fatal CHD [1.45 (95% confidence interval 1.07–1.97)], CVD [1.39 (1.06–1.83)], and MACE [1.39 (1.07–1.80)]. The categorical net reclassification improvement was 0.051 for the 10-year risk of incident CVD. Incidence of fatal events was over 10-fold more frequent in the highest CERT2 category compared to the lowest risk category and modified SCORE risk charts, utilizing CERT2 and diabetes mellitus, increased granularity of risk assessment compared to a chart utilizing total cholesterol. Conclusion CERT2 is a significant predictor of incident cardiovascular outcomes and risk charts utilizing this score provide an easy tool to estimate relative and absolute risk for incident CVD.

The recently introduced Coronary Event Risk Test version 2 (CERT2) is a validated cardiovascular risk predictor score that uses circulating ceramide and phosphatidylcholine concentrations. The purpose of this study was to investigate the power of CERT2 to predict cardiovascular mortality in 280 male and 121 female patients with type 2 diabetes (T2DM). Prospectively, we recorded 55 cardiovascular deaths in men and 19 in women during a mean follow-up time of 7.6±3.6 and 8.1±3.4 years respectively. Overall, cardiovascular survival decreased with increasing CERT2 risk categories (figure 1). In Cox regression models, CERT2 significantly predicted the incidence of cardiovascular mortality in male patients with T2DM (unadj. HR 1.82 [1.39–2.37] per standard deviation; p We conclude that sex does not significantly impact the association of CERT2 with cardiovascular mortality in patients with T2DM. Funding Acknowledgement Type of funding sources: None. Figure 1

Background Most emergency departments rely on acuity assessment, triage, to recognize critically ill patients that need urgent treatment, and to allocate resources according to need. The accuracy of commonly used triage instruments such as the Emergency Severity Index (ESI) is lower for older adults compared to young patients. We aim to examine, whether adjusting the triage category by age leads to improvement in sensitivity without excessive increase in patient numbers in the higher triage categories. The primary outcome measure was 3-day mortality and secondary outcomes were 30-day mortality, hospital admission, and HDU/ICU admissions. Methods We gathered data of all adult patients who had an unscheduled visit to any of our three emergency departments within one month. The data was analysed for 3-day mortality, 30-day mortality, hospital admission, and high dependency unit or intensive care unit (HDU/ICU) admission. The analysis was run for both the standard ESI triage method and a local 3-level Helsinki University Hospital (HUH) method. A further analysis was run for both triage methods with age adjustment. Net reclassification improvement values were calculated to demonstrate the effect of age adjustment. Results Thirteen thousand seven hundred fifty-nine patients met the study criteria, median age was 57. 3-day mortality AUCs for unadjusted HUH and ESI triage were 0.77 (0.65–0.88) and 0.72 (0.57–0.87); 30-day mortality AUCs were 0.64 (0.59–0.69) and 0.69 (0.64–0.73); hospital admission AUCs were 0.60 (0.68–0.71) and 0.66 (0.65–0.68) and HDU/ICU admission AUCs were 0.67 (0.64–0.70) and 0.82 (0.79–0.86), respectively. Age adjustment improved accuracy for 30-day mortality and hospital admission. With the threshold age of 80, AUCs for 30-day mortality were 0.73 (0.68–0.77) and 0.77 (0.73–0.81) and for hospital admission, 0.66 (0.65–0.67) and 0.72 (0.71–0.73) for the HUH and ESI triage. The effect was similar with all cut off ages. Conclusion Moving older adults into a more urgent triage category based on age, improved the triage instruments’ performance slightly in predicting 30-day mortality and hospital admission without excessive increase in patient numbers in the higher triage categories. Age adjustment did not improve HDU/ICU admission or 3-day mortality prediction.

Background The COVID-19 pandemic has had profound effects on the utilization of health care services, including Emergency Medical Services (EMS). Social distancing measures taken to prevent the spread of the disease have greatly affected the functioning of societies and reduced or halted many activities with a risk of injury. The aim of this study was to report the effects of lockdown measures on trauma-related EMS calls in the Finnish capital area. Methods We conducted a retrospective cohort study of all EMS calls in the Helsinki University Hospital (HUH) catchment area between 1 January and 31 July 2020. Calls were identified from the HUH EMS database. Calls were grouped into pre-lockdown, lockdown, and post-lockdown periods according to the restrictions set by the Finnish government and compared to the mean number of calls for the corresponding periods in 2018 and 2019. Statistical comparisons were performed using Mann-Whitney U-test for weekly numbers and percentages. Results During the study period there was a total of 70,705 EMS calls, of which 14,998 (21.2%) were related to trauma; 67,973 patients (median age 61.6 years; IQR 35.3–78.6) were met by EMS. There was no significant change in the weekly number of total or trauma-related EMS calls during the pre-lockdown period. During the lockdown period, the number of weekly total EMS calls was reduced by 12.2% (p = 0.001) and the number of trauma-related calls was reduced by 23.3% (p = 0.004). The weekly number of injured patients met by EMS while intoxicated with alcohol was reduced by 41.8% (p = 0.002). During the post-lockdown period, the number of total and trauma-related calls and the number of injured patients intoxicated by alcohol returned to previous years’ levels. Conclusions The COVID-19 pandemic and social distancing measures reduced the number of trauma-related EMS calls. Lockdown measures had an especially significant effect on the number of injured patients intoxicated by alcohol met by the EMS. Trial registration Not applicable.

The recently introduced Coronary Event Risk Test version 2 (CERT2) is a validated cardiovascular risk predictor score that uses circulating ceramide and phosphatidylcholine concentrations. We here aimed at investigating the power of CERT2 to predict cardiovascular mortality in 280 male and 121 female patients with type 2 diabetes (T2DM). Prospectively, we recorded 55 cardiovascular deaths in men and 19 in women during a mean follow-up time of 7.6±3.6 and 8.1±3.4 years respectively. Overall, cardiovascular survival decreased with increasing CERT2 risk category (Figure), and cardiovascular mortality was higher in men than in women (20.1% vs. 15.8%; p=0.321). In Cox regression models, CERT2 significantly predicted the incidence of cardiovascular mortality in male patients with T2DM (unadj. HR 1.82 [1.39-2.37] per standard deviation; p Disclosure A. Leiherer: None. M. Laaperi: None. A. Jylha: None. P. Fraunberger: None. H. Drexel: None. A. Muendlein: None. C. H. Saely: None. B. Larcher: None. A. Mader: None. M. Maechler: None. L. Sprenger: None. B. Mutschlechner: None. R. Laaksonen: None.

Background: Viral infections are a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Although immune suppression plays a central role, the literat...

The treatment of constitutional delay of growth and puberty (CDGP) is an underinvestigated area in adolescent medicine. We tested the hypothesis that peroral aromatase inhibition with letrozole is more efficacious than intramuscular injection of low-dose testosterone in inducing puberty in boys with CDGP.We did a randomised, controlled, open-label trial at four paediatric centres in Finland. Boys aged at least 14 years with CDGP who wanted medical intervention and exhibited the first signs of puberty were randomly assigned in blocks of ten to receive either six intramuscular injections of low-dose testosterone (about 1 mg/kg bodyweight) every 4 weeks for 6 months or peroral letrozole 2·5 mg once daily for 6 months. All boys were followed up for 6 months after the end of treatment. The primary outcomes were changes in testicular volume and hormonal markers of puberty at 6 months after treatment initiation, which were assessed in all participants who received the assigned treatment. All patients were included in the safety analysis. This study is registered with ClinicalTrials.gov, number NCT01797718.Between Aug 1, 2013, and Jan 30, 2017, 30 boys were randomly assigned to receive testosterone (n=15) or letrozole (n=15). One boy in the testosterone group was excluded from the primary analyses because of a protocol deviation. During treatment, boys in the letrozole group had higher serum concentrations of luteinising hormone, follicle-stimulating hormone, testosterone, and inhibin B than did boys in the testosterone group. Testicular growth from baseline to 6 months was greater in the letrozole group than in the testosterone group (7·2 mL [95% CI 5·2-9·3] vs 2·2 mL [1·4-2·9]; between-group difference per month 0·9 mL [95% CI 0·6-1·2], p0·0001). Most adverse events were mild. One boy in the testosterone group had aggressive behaviour for 1 week after each injection, and one boy in the letrozole group had increased irritability at 6 months.Letrozole might be a feasible alternative treatment to low-dose testosterone for boys with CDGP who opt for medical intervention. However, the risks and benefits of manipulating the reproductive axis during early puberty should be weighed carefully.Helsinki University Hospital, Academy of Finland, and Finnish Foundation for Pediatric Research.

Background Viral infections may trigger type 1 diabetes (T1D), and recent reports suggest an increased incidence of paediatric T1D and/or diabetic ketoacidosis (DKA) during the COVID-19 pandemic. Objective To study whether the number of children admitted to the paediatric intensive care unit (PICU) for DKA due to new-onset T1D increased during the COVID-19 pandemic, and whether SARS-CoV-2 infection plays a role. Methods This retrospective cohort study comprises two datasets: (1) children admitted to PICU due to new-onset T1D and (2) children diagnosed with new-onset T1D and registered to the Finnish Pediatric Diabetes Registry in the Helsinki University Hospital from 1 April to 31 October in 2016–2020. We compared the incidence, number and characteristics of children with newly diagnosed T1D between the prepandemic and pandemic periods. Results The number of children admitted to PICU due to new-onset T1D increased from an average of 6.25 admissions in 2016–2019 to 20 admissions in 2020 (incidence rate ratio [IRR] 3.24 [95% CI 1.80 to 5.83]; p=0.0001). On average, 57.75 children were registered to the FPDR in 2016–2019, as compared with 84 in 2020 (IRR 1.45; 95% CI 1.13 to 1.86; p=0.004). 33 of the children diagnosed in 2020 were analysed for SARS-CoV-2 antibodies, and all were negative. Conclusions More children with T1D had severe DKA at diagnosis during the pandemic. This was not a consequence of SARS-CoV-2 infection. Instead, it probably stems from delays in diagnosis following changes in parental behaviour and healthcare accessibility., A Finnish retrospective cohort study of two datasets: children with Type 1 diabetes (T1D) admitted to PICU and children with T1D registered to the Finnish Pediatric Diabetes Registry. They found that more children with T1D had severe DKA at diagnosis during the pandemic. This stems from delay in presentation and diagnosis rather than a consequence of SARS-CoV-2 infection.

Background: The purpose of acuity assessment, triage, in the emergency department is to recognize critically ill patients and to allocate resources. The Emergency Severity Index (ESI) is used widely around the world and has been shown to be at least as good as other 5-level assessment instruments. In this study, we assess validity of the ESI triage system in a Finnish Emergency department for predicting 30-day mortality as primary outcome and hospital admissions, high dependency unit or intensive care unit admissions as secondary outcomes, and efficiency for predicting emergency department length-of-stay and utilized resources as secondary outcomes. Methods: We collected data of all adult patient visits to the emergency department during a one-month period. The data was analyzed for the primary and secondary outcomes stratified by age: younger adults (18-64 years), older adults (65-79 years) and oldest old (>80 years). Results: Of the 5909 visits, 5511 were eligible for analysis, 2725 of them men. Median age was 59 years; 30-day mortality was 150 (2.7%). In all age groups, 30-day mortality was consecutively higher with statistical significance between each step from between categories 1 to 3. There were 2274 admissions, 190 of the to HDU or ICU. Hospital admission rates were significantly higher between each step between categories 2 to 4 for all adults. HDU/ICU admissions were higher in category 2 than in category 3 in all age groups. Resource utilization was higher in category 3 than in category 4; categories 4 and 5 differed only in the younger adult group. Most patients in categories 4 and 5 required ≥2 and 0 resource, respectively. Median length of stay at the emergency department was 3h 47min. For all patients ED-LOS varied without linearity; LOS was longest in category 3 in all age groups. Conclusions: ESI seems to be a valid tool for acuity assessment in all age groups in our population: it recognized severely ill patients by predicting mortality and hospital admissions in the higher triage categories in all age groups. Having failed to predict both resource consumption and ED-LOS, ESI was not associated with efficiency in our population.

Simple Summary Most ovarian cancer patients initially show a response to primary treatments, but the development of refractory disease is a major problem. Currently, there are no blood-based prognostic biomarkers, and the prognosis of a patient is determined by the International Federation of Gynecology and Obstetrics (FIGO) stage and residual disease after cytoreductive surgery. In this study, we developed and validated a novel test based on the ratio of two circulatory lipids that enables the prognostic stratification of ovarian cancer patients at the time of diagnosis, prior to any oncological treatments. The translational relevance of this test is to find those patients with poor prognosis early on, and to identify patients that are at high risk of recurrence despite complete cytoreduction. Thus, the test enables the early direction of novel targeted therapies to those ovarian cancer patients at greatest risk of recurrence and death. Epithelial ovarian cancer (EOC) generally responds well to oncological treatments, but the eventual development of a refractory disease is a major clinical problem. Presently, there are no prognostic blood-based biomarkers for the stratification of EOC patients at the time of diagnosis. We set out to assess and validate the prognostic utility of a novel two-lipid signature, as the lipidome is known to be markedly aberrant in EOC patients. The study consisted of 499 women with histologically confirmed EOC that were prospectively recruited at the university hospitals in Turku (Finland) and Charite (Berlin, Germany). Lipidomic screening by tandem liquid chromatography-mass spectrometry (LC-MS/MS) was performed for all baseline serum samples of these patients, and additionally for 20 patients of the Turku cohort at various timepoints. A two-lipid signature, based on the ratio of the ceramide Cer(d18:1/18:0) and phosphatidylcholine PC(O-38:4), showed consistent prognostic performance in all investigated study cohorts. In the Turku cohort, the unadjusted hazard ratios (HRs) per standard deviation (SD) (95% confidence interval) were 1.79 (1.40, 2.29) for overall and 1.40 (1.14, 1.71) for progression-free survival. In a Charite cohort incorporating only stage III completely resected patients, the corresponding HRs were 1.59 (1.08, 2.35) and 1.53 (1.02, 2.30). In linear-mixed models predicting progression of the disease, the two-lipid signature showed higher performance (beta per SD increase 1.99 (1.38, 2.97)) than cancer antigen 125 (CA-125, 1.78 (1.13, 2.87)). The two-lipid signature was able to identify EOC patients with an especially poor prognosis at the time of diagnosis, and also showed promise for the detection of disease relapse.

Background The challenges encountered in emergency medical services (EMS) contacts with children are likely most pronounced in infants, but little is known about their out-of-hospital care. Our primary aim was to describe the characteristics of EMS contacts with infants. The secondary aims were to examine the symptom-based dispatch system for nonverbal infants, and to observe the association of unfavorable patient outcomes with patient and EMS mission characteristics. Methods In a population-based 5-year retrospective cohort of all 1712 EMS responses for infants (age Results 1712 infants with a median age of 6.7 months were encountered, comprising 0.4% of all EMS missions. The most common complaints were dyspnea, low-energy falls, and choking. Two infants died on-scene. The EMS transported 683 (39.9%) infants. One (0.1%) infant died during the 12-month follow-up period. Ninety-one infants had abnormal clinical examination upon arrival at the ED. PICU admissions (n = 28) were associated with young age (P P = 0.01), and previous EMS contacts within 72 h (P = 0.04). The adult-derived dispatch codes did not associate with the final diagnoses of the infants. Conclusions Infants form a small but distinct group in pediatric EMS care, with specific characteristics differing from the overall pediatric population. Many EMS contacts with infants were nonurgent or medically unjustified, possibly reflecting an unmet need for other family services. The use of adult-derived symptom codes for dispatching is not optimal for infants. Unfavorable patient outcomes were rare. Risk factors for such outcomes include quickly renewed contacts, young age and health problems in the neonatal period.

Recognizing stroke and other intracranial pathologies in prehospital phase facilitates prompt recanalization and other specific care. Recognizing these can be difficult in patients with decreased level of consciousness. We previously derived a scoring system combining systolic blood pressure, age and heart rate to recognize patients with intracranial pathology. In this study we aimed to validate the score in a larger, separate population.We conducted a register based retrospective study on patients ≥16 years old and Glasgow Coma Score15 encountered by helicopter emergency medical services. Diagnoses at the end of hospitalization were used to identify if patients had intracranial lesion or not. The performance of score was evaluated by area under the receiver operating characteristics curve (AUROC).Of 9,309 patients included, 1,925 (20.7%) had an intracranial lesion including 1,211 cases of stroke. Older age, higher blood pressure and lower heart rate were predictors for an intracranial lesion (P0.001 for all). The score distinguished patients with intracranial lesion with AUROC of 0.749 (95% CI 0.737 to 0.761). The performance slightly improved if only patients intubated in prehospital phase were included AUROC 0.780 (95% CI 0.770 to 0.806) or convulsion related diagnosis excluded AUROC of 0.788 (95% CI 0.768 to 0.792).A scoring of systolic blood pressure, heart rate and age help differentiate intracranial lesions in patients with decreased level of consciousness in prehospital care. This may facilitate direct transportation to stroke center and application of neuroprotective measures in prehospital critical care.

Introduction: The Coronary Event Risk Test (CERT) is a validated cardiovascular risk predictor that uses circulating ceramide concentrations to allocate patients into one of four risk categories. This test has recently been updated (CERT-2), now additionally including phosphatidylcholine concentrations. Hypothesis: We hypothesize that CERT and CERT-2 have the power to predict cardiovascular mortality in patients with cardiovascular disease (CVD). Methods: We investigated a patient cohort of 999 patients with established CVD. Results: Overall, comparing survival curves (figure) for over 12 years of follow up and the predictive power of survival models using net reclassification improvement (NRI), CERT-2 was the best predictor of cardiovascular mortality, surpassing CERT (NRI=0.456; p=0.01) and also the 2019 ESC-SCORE (NRI=0.163; p=0.04). Patients in the highest risk category of CERT as compared to the lowest category had a HR of 3.63 [2.09-6.30] for cardiovascular death; for CERT-2 the corresponding HR was 6.02 [2.47-14.64]. Among patients with T2DM (n=322), the HR for cardiovascular death was 3.00 [1.44-6.23] using CERT and 7.06 [1.64-30.50] using CERT-2; the corresponding HRs among non-diabetic subjects were 2.99 [1.20-7.46] and 3.43 [1.03-11.43], respectively. Conclusions: We conclude that both, CERT and CERT-2 scores are powerful predictors of cardiovascular mortality in CVD patients, especially in those patients with T2D, performance is even higher with CERT-2.

The Coronary Event Risk Test (CERT) is a validated cardiovascular risk predictor that uses circulating ceramide concentrations to allocate patients into one of four risk categories. This test has recently been updated (CERT-2), now additionally including phosphatidylcholine concentrations. The purpose of this study was to investigate the power of CERT and CERT-2 to predict cardiovascular mortality in patients with cardiovascular disease (CVD). We investigated a cohort of 999 patients with established CVD. Overall, comparing survival curves (figure) for over 12 years of follow up and the predictive power of survival models using net reclassification improvement (NRI), CERT-2 was the best predictor of cardiovascular mortality, surpassing CERT (NRI=0.456; p=0.01) and also the 2019 ESC-SCORE (NRI=0.163; p=0.04). Patients in the highest risk category of CERT as compared to the lowest category had a HR of 3.63 [2.09–6.30] for cardiovascular death; for CERT-2 the corresponding HR was 6.02 [2.47–14.64]. Among patients with T2DM (n=322), the HR for cardiovascular death was 3.00 [1.44–6.23] using CERT and 7.06 [1.64–30.50] using CERT-2; the corresponding HRs among non-diabetic subjects were 2.99 [1.20–7.46] and 3.43 [1.03–11.43], respectively. We conclude that both, CERT and CERT-2 scores are powerful predictors of cardiovascular mortality in CVD patients, especially in those patients with T2D. Performance is even higher with CERT-2. Funding Acknowledgement Type of funding source: None

BackgroundChildren are less vulnerable to serious forms of the COVID-19 disease. However, concerns have been raised about children being the second victims of the pandemic and its control measures. Therefore, we wanted to study if the pandemic, the infection control measures and their consequences to the society projected to paediatric prehospital emergency medical services (EMS) contacts.MethodsWe conducted a population-based cohort study concerning all children aged 0–15 years with EMS contacts in the Helsinki University Hospital area during 1 March 2020–31 May 2020 (study period) and equivalent periods in 2017–2019 (control periods). We analysed the demographic characteristics, time of EMS contact, reason for EMS contact, priority of the dispatch, reason for transportation, priority of transportation, if any consultations were made or additional units required, any medication or oxygen or fluids given, if intubation was performed, and whether paramedics took precautions when COVID-19 infection was suspected.ResultsThe number of paediatric EMS contacts decreased by 30.4% from mean of 1794 contacts to 1369 (p=0.003). The EMS contacts were more often due to trauma (+23.7%, pConclusionsThe number of EMS contacts decreased during the pandemic. Nevertheless, the children encountered by the EMS were more seriously ill than during the control periods.

Background Emergency care clinicians are expected to use the latest research evidence in practice. However, emergency nurses do not always consistently implement evidence-based practice (EBP). An educational intervention on EBP was implemented to promote emergency nurses' use of EBP, and the effectiveness of it was evaluated. Aims This study aimed to evaluate the effectiveness of an EBP educational intervention on emergency nurses' EBP attitudes, knowledge, self-efficacy, skills, and behavior. The study also examined learners' satisfaction with the EBP educational intervention. Methods A randomized controlled trial with parallel groups with evaluations before the education, immediately after it, and 6 and 12 months after the education was conducted at four emergency departments in two university hospitals. The experimental group (N = 40) received EBP education while the control group (N = 40) completed self-directed EBP education. The primary outcomes were emergency nurses' EBP attitudes, knowledge, self-efficacy, skills, and behavior, while the secondary outcome was satisfaction with the EBP education. Results Thirty-five participants of an experimental and 29 participants of a control group completed the study. There were no statistically significant (p

The Coronary Event Risk Test (CERT) is a validated cardiovascular risk predictor that uses circulating ceramide concentrations to allocate patients into one of four risk categories. This test has recently been updated (CERT-2), now additionally including phosphatidylcholine concentrations. We investigated the power of CERT and CERT-2 to predict cardiovascular mortality in 999 patients with cardiovascular disease (CVD). Overall, comparing survival curves (Figure) for over 12 years of follow up and the predictive power of survival models using net reclassification improvement (NRI), CERT-2 was the best predictor of cardiovascular mortality, surpassing CERT (NRI=0.456; p=0.01) and also the 2019 ESC-SCORE (NRI=0.163; p=0.04). Patients in the highest risk category of CERT as compared to the lowest category had a HR of 3.63[2.09-6.30] for cardiovascular death; for CERT-2 the corresponding HR was 6.02[2.47-14.64]. Among patients with T2DM (n=322), the HR for cardiovascular death was 3.00[1.44-6.23] using CERT and 7.06[1.64-30.50] using CERT-2; the corresponding HRs among nondiabetic subjects were 2.99[1.20-7.46] and 3.43[1.03-11.43], respectively. We conclude that both, CERT and CERT-2 scores are powerful predictors of cardiovascular mortality in CVD patients, especially in those patients with T2D. Performance is even higher with CERT-2. Disclosure A. Leiherer: None. A. Muendlein: None. C.H. Saely: None. R. Laaksonen: None. M. Laaperi: None. A. Vonbank: None. P. Fraunberger: None. H. Drexel: None.

Background: Identifying pediatric populations at risk for traumas would enable development of emergency medical services and emergency departments for children. Elucidation of the nature of socioeconomic differences in the incidence of pediatric out-of-hospital emergencies is needed to overcome inequities in child health. Methods: We retrieved all ambulance contacts during 17.12.2014-16.12.2018 involving children (0-15 years) in Helsinki, Finland and separated traumatic and nontraumatic emergencies. We compared the incidences of these emergencies in the pediatric population with socioeconomic markers of the scene of the emergency and of the residential area of the child. Results: Of 11,742 ambulance contacts involving children 4113 (35.0%) were traumatic. Traumatic emergencies occurred more often in neighborhoods with lower median income/household (P= 0.043) and were more common in children living in areas with lower median income/inhabitant (P = 0.001), higher unemployment (P < 0.001), and lower education (P < 0.001). The associations were weaker for traumatic than nontraumatic emergencies. Higher proportion of a pediatric population in a residential area (P= 0.005) had a protective effect. Exclusion of clinically unnecessary ambulance responses did not change the results. Conclusion: Traumatic emergencies in children are more common in areas with lower socioeconomic status. The possible protective effect of urban planning merits further studies. Type of study: Prognostic. Level of evidence: II. (c) 2020 Elsevier Inc. All rights reserved.

Aims Distinct ceramide lipids have been shown to predict the risk for cardiovascular disease (CVD) events, especially cardiovascular death. As phospholipids have also been linked with CVD risk, we investigated whether the combination of ceramides with phosphatidylcholines (PCs) would be synergistic in the prediction of CVD events in patients with atherosclerotic coronary heart disease in three independent cohort studies. Methods and results Ceramides and PCs were analysed using liquid chromatography–mass spectrometry (LC-MS) in three studies: WECAC (The Western Norway Coronary Angiography Cohort) (N = 3789), LIPID (Long-Term Intervention with Pravastatin in Ischaemic Disease) trial (N = 5991), and KAROLA (Langzeiterfolge der KARdiOLogischen Anschlussheilbehandlung) (N = 1023). A simple risk score, based on the ceramides and PCs showing the best prognostic features, was developed in the WECAC study and validated in the two other cohorts. This score was highly significant in predicting CVD mortality [multiadjusted hazard ratios (HRs; 95% confidence interval) per standard deviation were 1.44 (1.28–1.63) in WECAC, 1.47 (1.34–1.61) in the LIPID trial, and 1.69 (1.31–2.17) in KAROLA]. In addition, a combination of the risk score with high-sensitivity troponin T increased the HRs to 1.63 (1.44–1.85) and 2.04 (1.57–2.64) in WECAC and KAROLA cohorts, respectively. The C-statistics in WECAC for the risk score combined with sex and age was 0.76 for CVD death. The ceramide-phospholipid risk score showed comparable and synergistic predictive performance with previously published CVD risk models for secondary prevention. Conclusion A simple ceramide- and phospholipid-based risk score can efficiently predict residual CVD event risk in patients with coronary artery disease.

Background Nonspecific complaint (NSC) is a common presenting complaint in the emergency setting, especially in the elderly population. Individual studies have shown that it is associated with significant morbidity and mortality. This prognostic systematic review draws a synthesis of reported outcomes for patients presenting with NSC and compares them with outcomes for patients presenting with a specific complaint. Methods We conducted a literature search for publications, abstracts and conference presentations from Ovid, Scopus and Web of Science for the past 20 years. Studies were included which treated adult patients presenting to the Emergency Medical Services or Emergency Department with NSC. 2599 studies were screened for eligibility and quality was assessed using the SIGN assessment for bias tool. We excluded any low-quality studies, resulting in nine studies for quantitative analysis. We analysed the included studies for in-hospital mortality, triage category, emergency department length of stay, admission rate, hospital length of stay, intensive care admissions and re-visitation rate and compared outcomes to patients presenting with specific complaints (SC), where data were available. We grouped discharge diagnoses by ICD-10 category. Results We found that patients presenting with NSC were mostly older adults. Mortality for patients with NSC was significantly increased compared to patients presenting with SC [OR 2.50 (95% CI 1.40–4.47)]. They were triaged as urgent less often than SC patients [OR 2.12 (95% CI 1.08–4.16)]. Emergency department length of stay was increased in two out of three studies. Hospital length of stay was increased by 1–3 days. Admission rates were high in most studies, 55 to 84%, and increased in comparison to patients with SC [OR 3.86 (95% CI 1.76–8.47)]. These patients seemed to require more resources than patients with SC. The number for intensive care admissions did not seem to be increased. Data were insufficient to make conclusions regarding re-visitation rates. Discharge diagnoses were spread throughout the ICD-10 main chapters, infections being the most prevalent. Conclusions Patients with NSC have a high risk of mortality and their care in the Emergency Department requires more time and resources than for patients with SC. We suggest that NSC should be considered a major emergency presentation.

AimsLow-density lipoprotein cholesterol (LDL-C) is an established causal driver of atherosclerotic cardiovascular disease (ASCVD), but its performance and age-dependency as a biomarker for incident events and mortality arising from ASCVD is less clear. The aim was to determine the value of LDL-C as a susceptibility/risk biomarker for incident coronary heart disease (CHD), ASCVD, and stroke events and deaths, for the age groups Methods and resultsThe performance of LDL-C was evaluated in three cohorts, FINRISK 2002 (n = 7709), HUSK (n = 5431), and ESTHER (n = 4559), by Cox proportional hazards models, C-statistics, and net reclassification index calculations. Additionally, the hazard ratios (HRs) for the three cohorts were pooled by meta-analysis. The most consistent association was observed for CHD [95% confidence interval (CI) for HRs per standard deviation ranging from 0.99 to 1.37], whereas the results were more modest for ASCVD (0.96–1.18) due to lack of association with stroke (0.77–1.24). The association and discriminatory value of LDL-C with all endpoints in FINRISK 2002 and HUSK were attenuated in subjects 50 years and older [HRs (95% CI) obtained from meta-analysis 1.11 (1.04–1.18) for CHD, 1.15 (1.02–1.29) for CHD death, 1.02 (0.98–1.06) for ASCVD, 1.12 (1.02–1.23) for ASCVD death, and 0.97 (0.89–1.05) for stroke].ConclusionIn middle-aged and older adults, associations between LDL-C and all the studied cardiovascular endpoints were relatively weak, while LDL-C showed stronger association with rare events of pre-mature CHD or ASCVD death among middle-aged adults. The predictive performance of LDL-C also depends on the studied cardiovascular endpoint.

BackgroundNational Early Warning Score (NEWS) does not include age as a parameter despite age is a significant independent risk factor of death. The aim of this study was to examine whether age has an effect on predictive performance of short-term mortality of NEWS in a prehospital setting. We also evaluated whether adding age as an additional parameter to NEWS improved its short-term mortality prediction.MethodsWe calculated NEWS scores from retrospective prehospital electronic patient record data for patients 18 years or older with sufficient prehospital data to calculate NEWS. We used area under receiver operating characteristic (AUROC) to analyse the predictive performance of NEWS for 1 and 7 day mortalities with increasing age in three different age groups: ResultsWe analysed data from 35 800 ambulance calls. Predictive performance for 7-day mortality of NEWS decreased with increasing age: AUROC (95% CI) for 1-day mortality was 0.876 (0.848 to 0.904), 0.824 (0.794 to 0.854) and 0.820 (0.788 to 0.852) for first, second and third age groups, respectively. AUROC for 7-day mortality had a similar trend. Addition of age as an additional parameter to NEWS improved its ability to predict short-term mortality when assessed with continuous Net Reclassification Improvement.ConclusionsAge should be considered as an additional parameter to NEWS, as it improved its performance in predicting short-term mortality in this prehospital cohort.

Background The recently introduced Coronary Event Risk Test (CERT) is a validated cardiovascular risk predictor that uses circulating ceramide concentrations to allocate patients into one of four risk categories. Purpose The purpose of this study was to investigate the power of CERT to predict cardiovascular mortality in patients with established cardiovascular disease (CVD) including patients with type 2 diabetes (T2DM). Methods We investigated a total of 1087 patients with established CVD, including 360 patients with T2DM. At baseline, the prevalence of T2DM increased through CERT categories (29.1, 31.1, 37.4, and 53.4%, respectively, ptrend Results A total of 130 cardiovascular deaths occurred. Overall, cardiovascular mortality increased with increasing CERT categories (figure) and was higher in T2DM patients than in those who did not have diabetes (17.7 vs. 9.4%; p Cardiovascular survival of CVD patients Conclusion We conclude that CERT predicts cardiovascular mortality in CVD patients with T2DM as well as in those without diabetes.

Background Ceramides are enriched in atherosclerotic plaques, and a set of circulating ceramides including Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:1), and Cer(d18:1/24:0) has recently emerged as predictors of cardiovascular outcomes in coronary artery disease patients. Purpose The purpose of this study was to investigate their power to predict cardiovascular events in patients with peripheral artery disease (PAD). Methods We measured the serum concentrations of the above mentioned ceramides in a cohort of 380 patients with sonographically proven PAD, of whom 107 had type 2 diabetes (T2DM). Prospectively, we recorded 221 cardiovascular events over a mean follow-up time of 6.3±2.3 years. Results Cardiovascular event risk was higher in T2DM patients than in those who did not have diabetes (69 vs. 52%, p=0.001). The ceramides Cer(18:1/16:0) and Cer(18:1/24:1) and the respective ratios Cer(18:1/16:0) / Cer(18:1/24:0) and Cer(18:1/24:1) / Cer(18:1/24:0) were significant predictors of cardiovascular events both univariately and after multivariate adjustment including the presence of T2DM (figure). Conversely, T2DM predicted cardiovascular events independently from the investigated ceramides (adjusted HR 1.76 [1.31–2.35], p Conclusion We conclude that the investigated ceramides and T2DM are mutually independent predictors of cardiovascular events in PAD patients.

Introduction Intramuscular or intravenous oxytocin is used in out-of-hospital emergency care in Finland to prevent postpartum hemorrhage after unplanned out-of-hospital deliveries. However, the use of oxytocin by emergency medical services is based on in-hospital studies. The aim of this study was to determine whether the use of oxytocin is associated with diminished postpartum hemorrhage after unplanned out-of-hospital deliveries. Material and methods We studied patient records covering all unplanned out-of-hospital deliveries in the Helsinki University Hospital area between 1 January 2013 and 31 December 2017 inclusive. Oxytocin was available in ambulances responsible for half of the population of the study area and was not available in ambulances responsible for the other half. The study area corresponded to 25% of all deliveries in Finland. The primary outcome was the estimated total bleeding (mL). Secondary outcomes were (1) the first blood hemoglobin value measured in hospital (g/L), (2) whether blood hemoglobin was measured during the first 24 hours after delivery, (3) the need for red blood cell concentrate, (4) the need for uterotonic or prothrombotic medication in-hospital during the first 24 hours, (5) the need for any postpartum operation during the first 24 hours and (6) composite outcome combining the secondary outcomes 2-5. Results Of all ambulance responses in the study area, .04% concerned out-of-hospital deliveries. There were 216 analyzed out-of-hospital deliveries. Altogether, 111 of these occurred in the area with oxytocin available in ambulances and 105 in the area without. Oxytocin was administered in 57 of the 111 deliveries (51%) where it was available. No differences in the primary outcome (P = .548 for oxytocin available vs not available and P = .381 for oxytocin used vs not used) or secondary outcomes were detected between those deliveries where oxytocin was available vs not available or between those where it was used vs not used. Conclusions Out-of-hospital oxytocin was not associated with diminished postpartum hemorrhage in this study setting. Oxytocin does not seem to be an essential drug for all ambulance units. The in-hospital use of oxytocin was not evaluated and thus is not disputed by this study.

The ceramide ratios Cer(d18:1/16:0)/Cer(d18:1/24:0), Cer(d18:1/18:0)/Cer(d18:1/24:0) and Cer(d18:1/24:1)/Cer(d18:1/24:0) have recently been reported to be associated with cardiovascular risk. Data on their power to predict cardiovascular events in patients with type 2 diabetes (T2DM) are sparse, and it is unknown whether they prospectively predict cardiovascular events independently from the presence of coronary artery disease (CAD) at baseline. These issues are addressed in the present study. We measured the above-mentioned serum ceramide ratios in a cohort of 894 patients in whom the presence of CAD was determined angiographically. Prospectively, we recorded cardiovascular events over a mean follow-up time of 9.2±3.2 years. At baseline, the ratios Cer(d18:1/16:0)/Cer(d18:1/24:0), Cer(d18:1/18:0)/Cer(d18:1/24:0) and Cer(d18:1/24:1)/Cer(d18:1/24:0) were significantly higher in T2DM patients (n=239) than in patients without T2DM (0.11 vs. 0.10, p=0.011; 0.46 vs. 0.39, p Disclosure A. Leiherer: None. A. Muendlein: None. C.H. Saely: None. R. Laaksonen: None. M. Laaperi: None. A. Vonbank: None. B. Larcher: None. A. Mader: None. P. Fraunberger: None. H. Drexel: None.

The recently introduced Coronary Event Risk Test (CERT) is a validated cardiovascular risk predictor that uses circulating ceramide concentrations to allocate patients into one of four risk categories. We here aimed at investigating the power of CERT to predict cardiovascular mortality in 1087 patients with established cardiovascular disease (CVD) including 360 patients with type 2 diabetes (T2DM). At baseline, the prevalence of T2DM increased through CERT categories (29.1, 31.1, 37.4, and 53.4%, respectively, ptrend Disclosure A. Leiherer: None. A. Muendlein: None. C.H. Saely: None. R. Laaksonen: None. M. Laaperi: None. A. Vonbank: None. B. Larcher: None. A. Mader: None. I. Baumgartner: None. P. Fraunberger: None. H. Drexel: None.