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.

Increased need for interventions predicts mortality in the critically ill.

INTRODUCTION: The aim of this study was to determine the association of early treatment intensity with hospital mortality of intensive care unit (ICU) patients. METHODS: We performed an observational study based on a national ICU registry. We included adult patients treated in Finnish ICUs between 2003 and 2013 with the length of ICU stay of more than 3 days. We measured treatment intensity with the Therapeutic Intervention Scoring System (TISS-76). We assessed mean and daily TISS scores. To define the change in treatment intensity during the first days in the ICU, we calculated the difference between the TISS score on day 3 and the score on day 1 (ΔTISS). We used multivariate logistic regression to adjust for baseline differences and continuous net reclassification improvement (NRI) to determine the impact of adding TISS data to the baseline prediction model on its prognostic performance. RESULTS: We identified 42,493 patients eligible for the study. For 71% of the patients, ΔTISS was ≤ 0 and crude hospital mortality was 18%. ΔTISS > 0 was observed for 29% of the patients, with a hospital mortality of 23%. When compared to the group ΔTISS ≤ 0, the category ΔTISS > 0 was independently associated with substantially increased mortality. Adding TISS data to the prediction model resulted in the improvement of prognostic performance particularly in the patients with the lowest initial baseline risk. CONCLUSIONS: Early increase in TISS scores was associated with increased risk of death, especially in patients with a lower initial severity of illness.

Continuous wound infiltration with ropivacaine for analgesia after caesarean section: a randomised, placebo-controlled trial.

BACKGROUND: We evaluated the analgesic effect of ropivacaine infiltration into the surgical wound after caesarean section. METHODS: In a double-blind trial, 67 patients who were scheduled for caesarean section under spinal anaesthesia were randomly assigned to receive either 0.75% ropivacaine or placebo (NaCl 0.9%) through a multi-orifice catheter that was placed into the surgical wound, between the muscle fascia and the subcutaneous tissue. The study drug was administered as a bolus of 10 ml at the end of the operation, followed by an infusion at 2 ml/h for 48 h. All patients were also given paracetamol and ibuprofen. The primary outcome was the total amount of rescue oxycodone needed during the first 48 h post-operatively. Secondary outcomes included pain and patient satisfaction scores. Analyses were according to intention to treat. RESULTS: The mean (± standard deviation) amount of oxycodone administered during the first 48 h was 47.5 ± 20.9 mg in the ropivacaine group and 57.8 ± 29.4 mg in the placebo group (95% confidence interval for the difference between means, -22.8-2.2 mg; P = 0.10). There were no differences between the groups in pain scores or in patient satisfaction scores. CONCLUSION: Continuous wound infiltration with ropivacaine did not decrease the need for opioids and had no impact on pain scores or patient satisfaction after caesarean section.

Acute kidney injury in patients with severe sepsis in Finnish Intensive Care Units.

BACKGROUND: Severe sepsis is one of the leading causes of acute kidney injury (AKI). Patients with sepsis-associated AKI demonstrate high-hospital mortality. We evaluated the incidence of severe sepsis-associated AKI and its association with outcome in intensive care units (ICUs) in Finland. METHODS: This was a predetermined sub-study of the prospective, observational, multicentre FINNAKI study conducted in 17 ICUs during 1 September 2011 and 1 February 2012. All emergency ICU admissions and elective admissions exceeding 24 hours in the ICU were screened for presence of severe sepsis and AKI up to 5 days in ICU. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria and severe sepsis according to the American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) criteria. RESULTS: Of the 2901 included patients, severe sepsis was diagnosed in 918 (31.6%, 95% confidence interval [CI] 29.9-33.4%) patients. Of these 918 patients, 488 (53.2% [95% CI 49.9-56.5%]) had AKI. The 90-day mortality rate was 38.1% (95% CI 33.7-42.5%) for severe sepsis patients with AKI and 24.7% (95% CI 20.5-28.8%) for those without AKI. After adjusting for covariates, KDIGO stage 3 AKI was associated with an increased risk for 90-day mortality with an adjusted odds ratio (OR) of 1.94 (95% CI 1.28-2.94), but stages 1 and 2 were not. CONCLUSIONS: More than half of the patients with severe sepsis had AKI according to the KDIGO classification, and AKI stage 3 was independently associated with 90-day mortality.

Association of ICU size and annual case volume of renal replacement therapy patients with mortality.

BACKGROUND: We aimed to reveal whether the size of an intensive care unit (ICU) or its annual case volume of patients treated with renal replacement therapy (RRT) for acute kidney injury (AKI) is associated with hospital mortality. METHODS: This was a retrospective cohort study in the Finnish Intensive Care Consortium (FICC) database in 2007-2008. We divided the 23 FICC-member ICUs first into small or large according to ICU size, and second into low, medium, or high-volume tertiles according to annual case volume of patients with RRT. We compared crude hospital mortality, Simplified Acute Physiology Score (SAPS) II-, and case-mix-adjusted hospital mortality in small vs. large ICUs and in low- or medium-volume vs. high-volume ICUs. RESULTS: The median (interquartile range) annual case volume of patients with RRT for AKI per one ICU was 25 (19-45). Patients in small or low-volume ICUs were older and less severely ill. Crude and SAPS II -adjusted hospital mortality rates were significantly higher in small ICUs but not significantly different in case volume tertiles. After adjusting for age, severity of illness, intensity of care, propensity to receive RRT, and day of RRT initiation, treatment in low or medium volume ICUs was associated with an increased risk for hospital mortality. CONCLUSIONS: Crude and adjusted hospital mortality rates of patients treated with RRT for AKI were higher in small ICUs. Patients treated in high-volume ICUs had a decreased adjusted risk for hospital mortality compared to those in low-or medium volume ICUs.

Association of automated data collection and data completeness with outcomes of intensive care. A new customised model for outcome prediction.

BACKGROUND: The Finnish Intensive Care Consortium coordinates a national intensive care benchmarking programme. Clinical information systems (CISs) that collect data automatically are widely used. The aim of this study was to explore whether the severity of illness-adjusted hospital mortality of Finnish intensive care unit (ICU) patients has changed in recent years and whether the changes reflect genuine improvements in the quality of care or are explained by changes in measuring severity of illness. METHODS: We retrospectively analysed data collected prospectively to the database of the Consortium. During the years 2001-2008, there were 116,065 admissions to the participating ICUs. We excluded readmissions, cardiac surgery patients, patients under 18 years of age and those discharged from an ICU to another hospital's ICU. The study population comprised 85,547 patients. The Simplified Acute Physiology Score II (SAPS II) was used to measure severity of illness and to calculate standardised mortality ratios (SMRs, the number of observed deaths divided by the number of expected deaths). RESULTS: The overall hospital mortality rate was 18.4%. The SAPS II-based SMRs were 0.74 in 2001-2004 and 0.64 in 2005-2008. The severity of illness-adjusted odds of death were 24% lower in 2005-2008 than in 2001-2004. One fifth of this computational difference could be explained by differences in data completeness and the automation of data collection with a CIS. CONCLUSION: The use of a CIS and improving data completeness do decrease severity-adjusted mortality rates. However, this explains only one fifth of the improvement in measured outcomes of intensive care in Finland.

Mortality in out-of-hospital cardiac arrest patients has decreased in the era of therapeutic hypothermia.

BACKGROUND: Mild therapeutic hypothermia (TH) improves survival after out-of-hospital cardiac arrest (OHCA). This treatment was implemented in most Finnish intensive care units (ICUs) in 2003. The aim of this study was to find out whether hospital mortality of ICU-treated OHCA patients has changed in the era of TH. METHODS: This was a retrospective study of data collected prospectively into the database of the Finnish Intensive Care Consortium during the years 2000-2008. The study population consisted of 3958 patients for whom cardiac arrest was registered as the reason for ICU admission and who were transferred to the ICU from the emergency department. We divided the patients into those treated in the pre-hypothermia era (2000-2002) and those treated in the hypothermia era (2003-2008). We investigated whether the treatment period had any impact on hospital mortality. RESULTS: There were no differences between the periods regarding the age or initial Glasgow Coma Scores of the patients. Mean severity of illness was higher in the latter period. Despite this, mortality decreased: the hospital mortality rate was 57.9% in 2000-2002 and 51.1% in 2003-2008, P < 0.001. In a multivariate logistic regression analysis, treatment in 2003-2008 was associated with a reduced risk of in-hospital death (adjusted odds ratio 0.54, 95% confidence interval 0.45-0.64 and P < 0.001). Survival improved markedly between the years 2002 and 2003. This improvement has persisted, but there has been no further improvement. CONCLUSION: Concurrently with the implementation of TH, hospital mortality of OHCA patients treated in Finnish ICUs decreased.

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.

Corticosteroid therapy in intensive care unit patients with PCR-confirmed influenza A(H1N1) infection in Finland.

OBJECTIVE: To evaluate the incidence, treatment, and outcome of influenza A(H1N1) in Finnish intensive care units (ICUs) with special reference to corticosteroid treatment. METHODS: During the H1N1 outbreak in Finland between 11 October and 31 December 2009, we prospectively evaluated all consecutive ICU patients with high suspicion of or confirmed pandemic influenza A(H1N1) infection. We assessed severity of acute disease and daily organ dysfunction. Ventilatory support and other concomitant treatments were evaluated and recorded daily throughout the ICU stay. The primary outcome was hospital mortality. RESULTS: During the 3-month period altogether 132 ICU patients were tested polymerase chain reaction-positive for influenza A(H1N1). Of these patients, 78% needed non-invasive or invasive ventilatory support. The median (interquartile) length of ICU stay was 4 [2-12] days. Hospital mortality was 10 of 132 [8%, 95% confidence interval (CI) 3-12%]. Corticosteroids were administered to 72 (55%) patients, but rescue therapies except prone positioning were infrequently used. Simplified Acute Physiology Score II and Sequential Organ Failure Assessment scores in patients with and without corticosteroid treatment were 31 [24-36] and 6 [2-8] vs. 22 [5-30] and 3 [2-6], respectively. The crude hospital mortality was not different in patients with corticosteroid treatment compared to those without: 8 of 72 (11%, 95% CI 4-19%) vs. 2 of 60 (3%, 95% CI 0-8%) (P = 0.11). CONCLUSIONS: The majority of H1N1 patients in ICUs received ventilatory support. Corticosteroids were administered to more than half of the patients. Despite being more severely ill, patients given corticosteroids had comparable hospital outcome with patients not given corticosteroids.

Hydrogen release from liquid organic hydrogen carriers catalysed by platinum on rutile-anatase structured titania.

A liquid organic hydrogen carrier (LOHC) is an interesting concept for hydrogen storage. We describe herein a new, active catalyst system for dehydrogenation of perhydrogenated dibenzyl toluene (H18-DBT), which is a promising LOHC candidate. Pt supported on a rutile-anatase form of titania was found to be more active than Pt supported on anatase-only titania, or on alumina, and almost equally active as Pt supported on carbon. Robust and durable metal oxide supports are preferred for catalysing reactions at high temperatures.

Vector quantization as a method for integer EMG signal compression.

Vector quantization (VQ) is a well-known lossy compression method, which has not often been applied to biosignals. In this paper, VQ and its mean residual variant for encoding and decoding electromyography (EMG) signals have been tested. The methods are selected in such a way that they can be later applied in a low-resource embedded system. A neural network approach is used for codebook generation. The preservation of medical parameters is a prominent sign of quality in medical compression systems. Both signal level fidelity factors and preserving medical parameters are tested. The results show that mean residual vector quantization with short segments is a workable approach for EMG signal compression.

Association between lung cancer and microsomal epoxide hydrolase genotypes.

Microsomal epoxide hydrolase (mEH) is involved in the metabolism of tobacco-derived carcinogens. Polymorphisms in exons 3 and 4 of the EPHX gene have been reported to be associated with variations in mEH activity. We examined whether the predicted mEH activity modified the lung cancer risk among 150 cases and 172 controls, all French Caucasian smokers. A significant association was found between predicted mEH activity and lung cancer (P < 0.02), with a dose-effect relationship (P < 0.005). The risks associated with intermediate and high activities, compared to low activity, were 1.65 (95% CI, 0.95-2.86) and 2.66 (95% CI, 1.33-5.33), respectively. The effect of mEH activity on lung cancer risk was not significantly modified by smoking exposure, CYP1A1 genotype, or GSTM1 genotype. mEH may thus be an important genetic determinant of smoking-induced lung cancer.

Larynx cancer risk in relation to glutathione S-transferase M1 and T1 genotypes and tobacco smoking.

Glutathione S-transferase (GST) isoenzymes are involved in the detoxification of several tobacco smoke-derived carcinogens. It is thus conceivable that deficiency in GST activity due to homozygous deletion of the GSTM1 and GSTT1 genes (the null genotypes) may modulate susceptibility to smoking-induced cancers. The effects of the GSTM1 and GSTT1 null genotypes on laryngeal cancer risk were evaluated using peripheral blood DNA from 129 larynx cancer patients and 172 noncancer controls, all of whom were regular smokers. Increased larynx cancer risk was related to the GSTM1 null genotype [odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.0-2.8]. The OR associated with the GSTT1 null genotype was increased, although not significantly (OR = 1.4, 95% CI = 0.7-2.9). Individuals with concurrent lack of GSTM1 and GSTT1 genes had a doubled, although not significant, risk for larynx cancer when compared with those having at least one of these genes (OR = 2.0, 95% CI = 0.8-5.2) and had almost a 3-fold risk (OR = 2.7, 95% CI = 1.0-7.4) when compared with those with both genes. Moreover, a significant interaction between the GSTM1 genotype and levels of tobacco consumption (P < 0.05) was found; the GSTM1 null genotype was associated with an increased risk of larynx cancer among smokers of 20 g/day or less (OR = 2.9, 95% CI = 1.3-6.3) but not among heavier smokers (OR = 1.0; 95% CI = 0.5-2.0). In contrast, the GSTT1 null genotype posed an increased, although not significant, risk among long-term smokers (OR = 2.3, 95% CI = 0.9-5.4).

Temporal trends in cardiac arrest incidence and outcome in Finnish intensive care units from 2003 to 2013.

PURPOSE: To estimate temporal trends in incidence and hospital mortality after cardiac arrest in Finnish intensive care units. METHODS: Using a large nationwide intensive care unit (ICU) database we identified patients suffering from cardiac arrest following ICU admission (ICU-CA) during the study period (2003-2013). ICU-CA was defined as need for cardiopulmonary resuscitation and/or defibrillation (non-arrest cardioversions were excluded) according to the Therapeutic Intervention Scoring System-76. Patients admitted with an admission diagnosis of cardiac arrest were excluded. We determined crude incidence and risk-adjusted hospital mortality (based on a customized severity of illness model) for all ICU-CA patients, and for predefined admission diagnosis subgroups. Temporal trends for the observed period were calculated for crude incidence and risk-adjusted hospital mortality. RESULTS: Crude incidence for all ICU-CA patients was 29/1,000 ICU admissions, with the highest incidence 118/1,000 in the non-operative cardiovascular subgroup. Overall hospital mortality for ICU-CA patients was 55.5% [95% confidence interval (CI) 54-57%]. Hospital mortality was 53.1% (95% CI 50.4-55.8%) for non-operative cardiovascular ICU-CA patients, 32.9% (95% CI 26.9-38.9%) for post cardiac surgery ICU-CA patients, and 56.3% (95% CI 51.2-61.3%) for neurological/neurosurgical ICU-CA patients. There was a significant reduction in the overall ICU-CA incidence and in the risk-adjusted hospital mortality of ICU-CA and non-cardiac arrest cases (non-CA) over the observed study period (p < 0.001). CONCLUSION: Our data suggest that the incidence of ICU-CA has decreased in Finnish ICUs between 2003 and 2013. Similar reduction in hospital mortality over time was observed for both ICU-CA and non-CA populations.