Neurofilament light compared to neuron-specific enolase as a predictor of unfavourable outcome after out-of-hospital cardiac arrest.

AIM: We compared the prognostic abilities of neurofilament light (NfL) and neuron-specific enolase (NSE) in patients resuscitated from out-of-hospital cardiac arrest (OHCA) of various aetiologies. METHODS: We analysed frozen blood samples obtained at 24 and 48 hours from OHCA patients treated in 21 Finnish intensive care units in 2010 and 2011. We defined unfavourable outcome as Cerebral Performance Category (CPC) 3-5 at 12 months after OHCA. We evaluated the prognostic ability of the biomarkers by calculating the area under the receiver operating characteristic curves (AUROCs [95% confidence intervals]) and compared these with a bootstrap method. RESULTS: Out of 248 adult patients, 12-month outcome was unfavourable in 120 (48.4%). The median (interquartile range) NfL concentrations for patients with unfavourable and those with favourable outcome, respectively, were 689 (146-1804) pg/mL vs. 31 (17-61) pg/mL at 24 h and 1162 (147-4360) pg/mL vs. 36 (21-87) pg/mL at 48 h, p < 0.001 for both. The corresponding NSE concentrations were 13.3 (7.2-27.3) µg/L vs. 8.5 (5.8-13.2) µg/L at 24 h and 20.4 (8.1-56.6) µg/L vs. 8.2 (5.9-12.1) µg/L at 48 h, p < 0.001 for both. The AUROCs to predict an unfavourable outcome were 0.90 (0.86-0.94) for NfL vs. 0.65 (0.58-0.72) for NSE at 24 h, p < 0.001 and 0.88 (0.83-0.93) for NfL and 0.73 (0.66-0.81) for NSE at 48 h, p < 0.001. CONCLUSION: Compared to NSE, NfL demonstrated superior accuracy in predicting long-term unfavourable outcome after OHCA.

Costs, outcome and cost-effectiveness of neurocritical care: a multi-center observational study.

BACKGROUND: Neurocritical illness is a growing healthcare problem with profound socioeconomic effects. We assessed differences in healthcare costs and long-term outcome for different forms of neurocritical illnesses treated in the intensive care unit (ICU). METHODS: We used the prospective Finnish Intensive Care Consortium database to identify all adult patients treated for traumatic brain injury (TBI), intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH) and acute ischemic stroke (AIS) at university hospital ICUs in Finland during 2003-2013. Outcome variables were one-year mortality and permanent disability. Total healthcare costs included the index university hospital costs, rehabilitation hospital costs and social security costs up to one year. All costs were converted to euros based on the 2013 currency rate. RESULTS: In total 7044 patients were included (44% with TBI, 13% with ICH, 27% with SAH, 16% with AIS). In comparison to TBI, ICH was associated with the highest risk of death and permanent disability (OR 2.6, 95% CI 2.1-3.2 and OR 1.7, 95% CI 1.4-2.1), followed by AIS (OR 1.9, 95% CI 1.5-2.3 and OR 1.5, 95% CI 1.3-1.8) and SAH (OR 1.8, 95% CI 1.5-2.1 and OR 0.8, 95% CI 0.6-0.9), after adjusting for severity of illness. SAH was associated with the highest mean total costs (€51,906) followed by ICH (€47,661), TBI (€43,916) and AIS (€39,222). Cost per independent survivor was lower for TBI (€58,497) and SAH (€96,369) compared to AIS (€104,374) and ICH (€178,071). CONCLUSION: Neurocritical illnesses are costly and resource-demanding diseases associated with poor outcomes. Intensive care of patients with TBI or SAH more commonly result in independent survivors and is associated with lower total treatments costs compared to ICH and AIS.

Timing of onset of gastrointestinal bleeding in the ICU: Protocol for a preplanned observational study.

BACKGROUND: Critically ill patients are at risk of gastrointestinal bleeding, but clinically important gastrointestinal bleeding is rare. The majority of intensive care unit (ICU) patients receive stress ulcer prophylaxis (SUP), despite uncertainty concerning the balance between benefit and harm. For approximately half of ICU patients with gastrointestinal bleeding, onset is early, ie within the first two days of the ICU stay. The aetiology of gastrointestinal bleeding and consequently the balance between benefit and harm of SUP may differ between patients with early vs late gastrointestinal bleeding. METHODS: This is a protocol and statistical analysis plan for a preplanned exploratory substudy of the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) randomized clinical trial, comparing intravenous pantoprazole (40 mg once daily) with placebo in 3350 acutely ill adult ICU patients. We will describe baseline characteristics and assess the time to onset of the first clinically important episode of GI bleeding accounting for survival status and allocation to SUP or placebo. In addition, we will describe differences in therapeutic and diagnostic procedures used in patients with clinically important gastrointestinal bleeding according to early vs late bleeding and 90-day vital status. CONCLUSIONS: The study outlined in this protocol will provide detailed information on patient characteristics and the timing of onset of gastrointestinal bleeding in the patients enrolled in the SUP-ICU trial. This may provide additional knowledge and incentives for future studies on which patients benefit from SUP.

A pilot study of hyperoxemia on neurological injury, inflammation and oxidative stress.

BACKGROUND: Normobaric hyperoxia is used to alleviate secondary brain ischaemia in patients with traumatic brain injury (TBI), but clinical evidence is limited and hyperoxia may cause adverse events. METHODS: An open label, randomised controlled pilot study comparing blood concentrations of reactive oxygen species (ROS), interleukin 6 (IL-6) and neuron-specific enolase (NSE) between two different fractions of inspired oxygen in severe TBI patients on mechanical ventilation. RESULTS: We enrolled 27 patients in the Fi O2 0.40 group and 38 in the Fi O2 0.70 group; 19 and 23 patients, respectively, completed biochemical analyses. In baseline, there were no differences between Fi O2 0.40 and Fi O2 0.70 groups, respectively, in ROS (64.8 nM [22.6-102.1] vs. 64.9 nM [26.8-96.3], P = 0.80), IL-6 (group 92.4 pg/ml [52.9-171.6] vs. 94.3 pg/ml [54.8-133.1], P = 0.52) or NSE (21.04 ug/l [14.0-30.7] vs. 17.8 ug/l [14.1-23.9], P = 0.35). ROS levels did not differ at Day 1 (24.2 nM [20.6-33.5] vs. 29.2 nM [22.7-69.2], P = 0.10) or at Day 2 (25.4 nM [21.7-37.4] vs. 47.3 nM [34.4-126.1], P = 0.95). IL-6 concentrations did not differ at Day 1 (112.7 pg/ml [65.9-168.9) vs. 83.9 pg/ml [51.8-144.3], P = 0.41) or at Day 3 (55.0 pg/ml [34.2-115.6] vs. 49.3 pg/ml [34.4-126.1], P = 0.95). NSE levels did not differ at Day 1 (15.9 ug/l [9.0-24.3] vs. 15.3 ug/l [12.2-26.3], P = 0.62). There were no differences between groups in the incidence of pulmonary complications. CONCLUSION: Higher fraction of inspired oxygen did not increase blood concentrations of markers of oxidative stress, inflammation or neurological injury or the incidence of pulmonary complications in severe TBI patients on mechanical ventilation.

Stress ulcer prophylaxis in the intensive care unit trial: detailed statistical analysis plan.

BACKGROUND: In this statistical analysis plan, we aim to provide details of the pre-defined statistical analyses of the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) trial. The aim of the SUP-ICU trial is to assess benefits and harms of stress ulcer prophylaxis with a proton pump inhibitor in adult patients in the intensive care unit (ICU). METHODS: The SUP-ICU trial is an investigator-initiated, international, multicentre, randomised, blinded, parallel-group trial of intravenously pantoprazole 40 mg once daily vs. placebo in 3350 acutely ill adult ICU patients at risk of gastrointestinal bleeding. The primary outcome measure is 90-day mortality. Secondary outcomes include the proportion of patients with clinically important gastrointestinal bleeding, pneumonia, Clostridium difficile infection or myocardial ischaemia, days alive without life support, serious adverse reactions, 1-year mortality, and a health economic analysis. Two formal interim analyses will be performed. The statistical analyses will be conducted according to the outlined pre-defined statistical analysis plan. The primary analysis will be a logistic regression analysis adjusted for stratification variables comparing the two intervention groups in the intention-to-treat population. In a secondary analysis, we will additionally adjust the primary outcome for potential random differences in baseline characteristics. The conclusion will be based on the intention-to-treat population. CONCLUSION: Stress ulcer prophylaxis is standard of care in ICUs worldwide, but has never been tested in large high-quality randomised placebo-controlled trials. The SUP-ICU trial will provide important high-quality data on the balance between the benefits and harms of stress ulcer prophylaxis in adult critically ill patients.

Stress ulcer prophylaxis in the intensive care unit: an international survey of 97 units in 11 countries.

BACKGROUND: Stress ulcer prophylaxis (SUP) may decrease the incidence of gastrointestinal bleeding in patients in the intensive care unit (ICU), but the risk of infection may be increased. In this study, we aimed to describe SUP practices in adult ICUs. We hypothesised that patient selection for SUP varies both within and between countries. METHODS: Adult ICUs were invited to participate in the survey. We registered country, type of hospital, type and size of ICU, preferred SUP agent, presence of local guideline, reported indications for SUP, criteria for discontinuing SUP, and concerns about adverse effects. Fisher's exact test was used to assess differences between groups. RESULTS: Ninety-seven adult ICUs in 11 countries participated (eight European). All but one ICU used SUP, and 64% (62/97) reported having a guideline for the use of SUP. Proton pump inhibitors were the most common SUP agent, used in 66% of ICUs (64/97), and H2-receptor antagonists were used 31% (30/97) of the units. Twenty-three different indications for SUP were reported, the most frequent being mechanical ventilation. All patients were prescribed SUP in 26% (25/97) of the ICUs. Adequate enteral feeding was the most frequent reason for discontinuing SUP, but 19% (18/97) continued SUP upon ICU discharge. The majority expressed concern about nosocomial pneumonia and Clostridium difficile infection with the use of SUP. CONCLUSIONS: In this international survey, most participating ICUs reported using SUP, primarily proton pump inhibitors, but many did not have a guideline; indications varied considerably and concern existed about infectious complications.

Propofol causes more hypotension than etomidate in patients with severe aortic stenosis: a double-blind, randomized study comparing propofol and etomidate.

BACKGROUND: Vasodilatation and hypotension are thought to be harmful in patients with severe aortic stenosis. Etomidate is preferred to propofol for anaesthesia induction in haemodynamically unstable patients, but may disturb cortisol synthesis. We assessed the haemodynamic effects of etomidate vs. propofol as anaesthesia induction agents, and the effects of these drugs on cortisol concentrations, in patients with severe aortic stenosis. The main end-point of the study was the incidence of hypotension. METHODS: Sixty-six patients with severe aortic stenosis scheduled for elective aortic valve replacement were enrolled in the study. The patients were randomized to receive either propofol or etomidate for induction of anaesthesia. Haemodynamic parameters, i.e. mean arterial pressure (MAP), pulmonary capillary wedge pressure (PCWP) and cardiac index (CI), were measured. If MAP decreased below 70 mmHg for more than 30 s, phenylephedrine was administered. Serum cortisol concentrations were also measured. RESULTS: MAP decreased in all patients (P < 0.001). MAP decreased to a greater extent in patients receiving propofol than in those receiving etomidate (P = 0.006). Patients receiving propofol needed phenylephedrine more often than those receiving etomidate (20/30 vs. 8/30, P = 0.002). CI and PCWP decreased in both groups (P < 0.001), with no difference between the groups. Patients receiving etomidate had a lower serum cortisol concentration immediately after the operation than those receiving propofol (P < 0.001), but no differences between the groups were observed on the first post-operative morning. CONCLUSION: Propofol is twice as likely as etomidate to evoke hypotension in anaesthesia induction of patients with severe aortic stenosis; however, etomidate transiently decreases post-operative serum cortisol concentrations.

Similar effect of revascularization on technetium-99m( )sestamibi and 15-(p-iodophenyl)pentadecanoic acid uptake in myocardial infarction patients.

To study its usefulness as a tracer for assessment of the perfusion and viability of myocardium, 15-(p-iodophenyl)pentadecanoic acid (IPPA) was compared with technetium-99m sestamibi (MIBI). Dual-tracer single-photon emission tomography rest imaging was performed no more than 2 months before and 3 months after coronary artery bypass grafting in 28 patients with previous anterior (n=13) or inferior (n=15) infarction. The size of MIBI and IPPA defects decreased from 14%+/-12% and 13%+/-9% to 10%+/-11% and 9%+/-7%, respectively (P<0.001 for both). The MIBI uptake increased in the infarct zones from 35%+/-11% to 43%+/-8% (P<0.001), and in the peri-infarct zones from 50%+/-11% to 55%+/-10% (P<0.05). The IPPA uptake increased in the infarct zones from 37%+/-11% to 44%+/-13% (P<0.001), and in the peri-infarct zones from 51%+/-11% to 57%+/-12% (P<0.05). In nine patients with improved regional echocardiographic wall motion score after bypass surgery, the pre-operative uptake values of both MIBI and IPPA in the infarct and peri-infarct zones were on average slightly but not significantly higher than in 19 patients with no observed improvement in regional wall motion score. In patients with improved regional wall motion, the MIBI scans and the IPPA scans showed (non-significant) decreases in defect size and increases in infarct and peri-infarct zone uptake after bypass surgery. Similar (in some cases significant) changes were observed in the patients without improvement in wall motion. Thus IPPA and MIBI provided similar information about perfusion and viability in pre- and postoperative evaluation of patients with clinically evident myocardial infarction and with normal global ejection fraction. Regardless of the tracer used, the resolution capability of the dual-tracer method with a rest imaging protocol was not sufficient to differentiate viable from non-viable infarction defects in unselected individual patients with a normal ejection fraction.

["Implant"--software for the documentation of statement and course in the special dentist hour consultation of implantology]. / "Implant"--ein Programmpaket zur rechnergestützten Befund- und Verlaufsdokumentation in der Spezialsprechstunde "Implantatprothetik".

A programsystem is presented which supports the attending physician on entering symptoms of clinical and paraclinical parameters. The system runs on personal computer with Z-80 CPU under dBASE II. The program consists of six parts: 1. simple patient data, 2. oral documentation, 3. diagnostical base program, 4. sketch of therapeutics, 5. dispensaire documentation. It aims on the reduction on routine work (e. g. data in- and output) and simple statistical analysis (view of success of several implantationsystems).