Does the prehospital National Early Warning Score predict the short-term mortality of unselected emergency patients?

Objectives: The prehospital research field has focused on studying patient survival in cardiac arrest, as well as acute coronary syndrome, stroke, and trauma. There is little known about the overall short-term mortality and its predictability in unselected prehospital patients. This study examines whether a prehospital National Early Warning Score (NEWS) predicts 1-day and 30-day mortalities. Methods: Data from all emergency medical service (EMS) situations were coupled to the mortality data obtained from the Causes of Death Registry during a six-month period in Northern Finland. NEWS values were calculated from first clinical parameters obtained on the scene and patients were categorized to the low, medium and high-risk groups accordingly. Sensitivities, specificities, positive predictive values (PPVs), negative predictive values (NPVs), and likelihood ratios (PLRs and NLRs) were calculated for 1-day and 30-day mortalities at the cut-off risks. Results: A total of 12,426 EMS calls were included in the study. The overall 1-day and 30-day mortalities were 1.5 and 4.3%, respectively. The 1-day mortality rate for NEWS values = 13 higher than 20%. The high-risk NEWS group had sensitivities for 1-day and 30-day mortalities 0.801 (CI 0.74-0.86) and 0.42 (CI 0.38-0.47), respectively. Conclusion: In prehospital environment, the high risk NEWS category was associated with 1-day mortality well above that of the medium and low risk NEWS categories. This effect was not as noticeable for 30-day mortality. The prehospital NEWS may be useful tool for recognising patients at early risk of death, allowing earlier interventions and responds to these patients.Peer reviewe

Evaluating the relationship between circulating lipoprotein lipids and apolipoproteins with risk of coronary heart disease: A multivariable Mendelian randomisation analysis.

BACKGROUND: Circulating lipoprotein lipids cause coronary heart disease (CHD). However, the precise way in which one or more lipoprotein lipid-related entities account for this relationship remains unclear. Using genetic instruments for lipoprotein lipid traits implemented through multivariable Mendelian randomisation (MR), we sought to compare their causal roles in the aetiology of CHD. METHODS AND FINDINGS: We conducted a genome-wide association study (GWAS) of circulating non-fasted lipoprotein lipid traits in the UK Biobank (UKBB) for low-density lipoprotein (LDL) cholesterol, triglycerides, and apolipoprotein B to identify lipid-associated single nucleotide polymorphisms (SNPs). Using data from CARDIoGRAMplusC4D for CHD (consisting of 60,801 cases and 123,504 controls), we performed univariable and multivariable MR analyses. Similar GWAS and MR analyses were conducted for high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I. The GWAS of lipids and apolipoproteins in the UKBB included between 393,193 and 441,016 individuals in whom the mean age was 56.9 y (range 39-73 y) and of whom 54.2% were women. The mean (standard deviation) lipid concentrations were LDL cholesterol 3.57 (0.87) mmol/L and HDL cholesterol 1.45 (0.38) mmol/L, and the median triglycerides was 1.50 (IQR = 1.11) mmol/L. The mean (standard deviation) values for apolipoproteins B and A-I were 1.03 (0.24) g/L and 1.54 (0.27) g/L, respectively. The GWAS identified multiple independent SNPs associated at P < 5 × 10-8 for LDL cholesterol (220), apolipoprotein B (n = 255), triglycerides (440), HDL cholesterol (534), and apolipoprotein A-I (440). Between 56%-93% of SNPs identified for each lipid trait had not been previously reported in large-scale GWASs. Almost half (46%) of these SNPs were associated at P < 5 × 10-8 with more than one lipid-related trait. Assessed individually using MR, LDL cholesterol (odds ratio [OR] 1.66 per 1-standard-deviation-higher trait; 95% CI: 1.49-1.86; P < 0.001), triglycerides (OR 1.34; 95% CI: 1.25-1.44; P < 0.001) and apolipoprotein B (OR 1.73; 95% CI: 1.56-1.91; P < 0.001) had effect estimates consistent with a higher risk of CHD. In multivariable MR, only apolipoprotein B (OR 1.92; 95% CI: 1.31-2.81; P < 0.001) retained a robust effect, with the estimate for LDL cholesterol (OR 0.85; 95% CI: 0.57-1.27; P = 0.44) reversing and that of triglycerides (OR 1.12; 95% CI: 1.02-1.23; P = 0.01) becoming weaker. Individual MR analyses showed a 1-standard-deviation-higher HDL cholesterol (OR 0.80; 95% CI: 0.75-0.86; P < 0.001) and apolipoprotein A-I (OR 0.83; 95% CI: 0.77-0.89; P < 0.001) to lower the risk of CHD, but these effect estimates attenuated substantially to the null on accounting for apolipoprotein B. A limitation is that, owing to the nature of lipoprotein metabolism, measures related to the composition of lipoprotein particles are highly correlated, creating a challenge in making exclusive interpretations on causation of individual components. CONCLUSIONS: These findings suggest that apolipoprotein B is the predominant trait that accounts for the aetiological relationship of lipoprotein lipids with risk of CHD

Predictors of hospital and one-year mortality in intensive care patients with refractory status epilepticus : a populationbased study

Background: The aim was to determine predictors of hospital and 1-year mortality in patients with intensive care unit (ICU)-treated refractory status epilepticus (RSE) in a population-based study. Methods: This was a retrospective study of the Finnish Intensive Care Consortium (FICC) database of adult patients (16 years of age or older) with ICU-treated RSE in Finland during a 3-year period (2010-2012). The database consists of admissions to all 20 Finnish hospitals treating RSE in the ICU. All five university hospitals and 11 out of 15 central hospitals participated in the present study. The total adult referral population in the study hospitals was 3.92 million, representing 91% of the adult population of Finland. Patients whose condition had a post-anoxic aetiological basis were excluded. Results: We identified 395 patients with ICU-treated RSE, corresponding to an annual incidence of 3.4/100,000 (95% confidence interval (CI) 3.04-3.71). Hospital mortality was 7.4% (95% CI 0-16.9%), and 1-year mortality was 25. 4% (95% CI 21.2-29.8%). Mortality at hospital discharge was associated with severity of organ dysfunction. Mortality at 1 year was associated with older age (adjusted odds ratio (aOR) 1.033, 95% CI 1.104-1.051, p = 0.001), sequential organ failure assessment (SOFA) score (aOR 1.156, CI 1.051-1.271, p = 0.003), super-refractory status epilepticus (SRSE) (aOR 2.215, 95% CI 1.20-3.84, p = 0.010) and dependence in activities of daily living (ADL) (aOR 2.553, 95% CI 1.537-4.243, p <0.0001). Conclusions: Despite low hospital mortality, 25% of ICU-treated RSE patients die within a year. Super-refractoriness, dependence in ADL functions, severity of organ dysfunction at ICU admission and older age predict long-term mortality.Peer reviewe

Medical priority dispatch codes-comparison with National Early Warning Score

Background: In Finland, calls for emergency medical services are prioritized by educated non-medical personnel into four categories-from A (highest risk) to D (lowest risk)-following a criteria-based national dispatch protocol. Discrepancies in triage may result in risk overestimation, leading to inappropriate use of emergency medical services units and to risk underestimation that can negatively impact patient outcome. To evaluate dispatch protocol accuracy, we assessed association between priority assigned at dispatch and the patient's condition assessed by emergency medical services on the scene using an early warning risk assessment tool. Methods: Using medical charts, clinical variables were prospectively recorded and evaluated for all emergency medical services missions in two hospital districts in Northern Finland during 1.1.2014-30.6.2014. Risk assessment was then re-categorized as low, medium, or high by calculating the National Early Warning Score (NEWS) based on the patients' clinical variables measured at the scene. Results: A total of 12,729 emergency medical services missions were evaluated, of which 616 (4.8%) were prioritized as A, 3193 (25.1%) as B, 5637 (44.3%) as C, and 3283 (25.8%) as D. Overall, 67.5% of the dispatch missions were correctly estimated according to NEWS. Of the highest dispatch priority missions A and B, 76.9 and 78.3%, respectively, were overestimated. Of the low urgency missions (C and D), 10.7% were underestimated; 32.0% of the patients who were assigned NEWS indicating high risk had initially been classified as low urgency C or D priorities at the dispatch. Discussion and conclusion: The present results show that the current Finnish medical dispatch protocol is suboptimal and needs to be further developed. A substantial proportion of EMS missions assessed as highest priority were categorized as lower risk according to the NEWS determined at the scene, indicating over-triage with the protocol. On the other hand, only a quarter of the high risk NEWS patients were classified as the highest priority at dispatch, indicating considerable under-triage with the protocol.Peer reviewe

Raloxifene for women with Alzheimer disease: A randomized controlled pilot trial

OBJECTIVE: To determine whether raloxifene, a selective estrogen receptor modulator, improves cognitive function compared with placebo in women with Alzheimer disease (AD) and to provide an estimate of cognitive effect. METHODS: This pilot study was conducted as a randomized, double-blind, placebo-controlled trial, with a planned treatment of 12 months. Women with late-onset AD of mild to moderate severity were randomly allocated to high-dose (120 mg) oral raloxifene or identical placebo provided once daily. The primary outcome compared between treatment groups at 12 months was change in the Alzheimer's Disease Assessment Scale, cognitive subscale (ADAS-cog). RESULTS: Forty-two women randomized to raloxifene or placebo were included in intent-to-treat analyses (mean age 76 years, range 68-84), and 39 women contributed 12-month outcomes. ADAS-cog change scores at 12 months did not differ significantly between treatment groups (standardized difference 0.03, 95% confidence interval -0.39 to 0.44, 2-tailed p = 0.89). Raloxifene and placebo groups did not differ significantly on secondary analyses of dementia rating, activities of daily living, behavior, or a global cognition composite score. Caregiver burden and caregiver distress were similar in both groups. CONCLUSIONS: Results on the primary outcome showed no cognitive benefits in the raloxifene-treated group. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for women with AD, raloxifene does not have a significant cognitive effect. The study lacked the precision to exclude a small effect

Evaluating the direct effects of childhood adiposity on adult systemic metabolism:A multivariable Mendelian randomization analysis

Background: Individuals who are obese in childhood have an elevated risk of disease in adulthood. However, whether childhood adiposity directly impacts intermediate markers of this risk, independently of adult adiposity, is unclear. In this study, we have simultaneously evaluated the effects of childhood and adulthood body size on 123 systemic molecular biomarkers representing multiple metabolic pathways. Methods: Two-sample Mendelian randomization (MR) was conducted to estimate the causal effect of childhood body size on a total of 123 nuclear magnetic resonance-based metabolic markers using summary genome-wide association study (GWAS) data from up to 24 925 adults. Multivariable MR was then applied to evaluate the direct effects of childhood body size on these metabolic markers whilst accounting for adult body size. Further MR analyses were undertaken to estimate the potential mediating effects of these circulating metabolites on the risk of coronary artery disease (CAD) in adulthood using a sample of 60 801 cases and 123 504 controls. Results: Univariable analyses provided evidence that childhood body size has an effect on 42 of the 123 metabolic markers assessed (based on P < 4.07 × 10-4). However, the majority of these effects (35/42) substantially attenuated when accounting for adult body size using multivariable MR. We found little evidence that the biomarkers that were potentially influenced directly by childhood body size (leucine, isoleucine and tyrosine) mediate this effect onto adult disease risk. Very-low-density lipoprotein markers provided the strongest evidence of mediating the long-term effect of adiposity on CAD risk. Conclusions: Our findings suggest that childhood adiposity predominantly exerts its detrimental effect on adult systemic metabolism along a pathway that involves adulthood body size.publishedVersionPeer reviewe

Early exposure to social disadvantages and later life body mass index beyond genetic predisposition in three generations of Finnish birth cohorts

BackgroundThe study aimed to explore the association between early life and life-course exposure to social disadvantage and later life body mass index (BMI) accounting for genetic predisposition and maternal BMI.MethodsWe studied participants of Helsinki Birth Cohort Study born in 1934-1944 (HBCS1934-1944, n=1277) and Northern Finland Birth Cohorts born in 1966 and 1986 (NFBC1966, n=5807, NFBC1986, n=6717). Factor analysis produced scores of social disadvantage based on social and economic elements in early life and adulthood/over the life course, and was categorized as high, intermediate and low. BMI was measured at 62years in HBCS1934-1944, at 46years in NFBC1966 and at 16years in NFBC1986. Multivariable linear regression analysis was used to explore associations between social disadvantages and BMI after adjustments for polygenic risk score for BMI (PRS BMI), maternal BMI and sex.ResultsThe association between exposure to high early social disadvantage and increased later life BMI persisted after adjustments (beta =0.79, 95% CI, 0.33, 1.25, p 0.22, 95% CI -0.91,1.35, p=0.700). In HBCS1934-1944 and NFBC1966, participants who had reduced their exposure to social disadvantage during the life-course had lower later life BMI than those who had increased their exposure (beta -1.34, [-2.37,-0.31], p=0.011; beta -0.46, [-0.89,-0.03], p=0.038, respectively).ConclusionsHigh social disadvantage in early life appears to be associated with higher BMI in later life. Reducing exposure to social disadvantage during the life-course may be a potential pathway for obesity reduction.Peer reviewe

Web-based cardiac REhabilitatioN alternative for those declining or dropping out of conventional rehabilitation : results of the WREN feasibility randomised controlled trial

Introduction Cardiac rehabilitation (CR) is typically delivered in hospital-based classes and is recommended to help people reduce their risk of further cardiac events. However, many eligible people are not completing the programme. This study aimed to assess the feasibility of delivering a web-based CR intervention for those who decline/drop out from usual CR. Intervention A web-based CR programme for 6 months, facilitated with remote support. Methods Two-centre, randomised controlled feasibility trial. Patients were randomly allocated to web-based CR/usual care for 6 months. Data were collected to inform the design of a larger study: recruitment rates, quality of life (MacNew), exercise capacity (incremental shuttle walk test) and mood (Hospital Anxiety and Depression Scale). Feasibility of health utility collection was also evaluated. Results 60 patients were randomised (90% male, mean age 62±9 years, 26% of those eligible). 82% completed all three assessment visits. 78% of the web group completed the programme. Quality of life improved in the web group by a clinically meaningful amount (0.5±1.1 units vs 0.2±0.7 units: control). Exercise capacity improved in both groups but mood did not change in either group. It was feasible to collect health utility data. Conclusions It was feasible to recruit and retention to the end of the study was good. The web group reported important improvements in quality of life. This intervention has the opportunity to increase access to CR for patients who would otherwise not attend. Promising outcomes and recruitment suggest feasibility for a full-scale trial. Trial registration number 1072679