Red cell distribution width and mortality in older patients with frailty in the emergency department.

BACKGROUND: The red cell distribution width (RDW) reflects the degree of heterogeneity of red blood cells. Elevated RDW is associated both with frailty and with increased mortality in hospital-admitted patients. In this study we evaluate whether high RDW values are associated with mortality in older emergency department (ED) patients with frailty, and if the association is independent of the degree of frailty. METHODS: We included ED patients with the following criteria: ≥ 75 years of age, Clinical Frailty Scale (CFS) score of 4 to 8, and RDW % measured within 48 h of ED admission. Patients were allocated to six classes by their RDW value: ≤ 13%, 14%, 15%, 16%, 17%, and ≥ 18%. The outcome was death within 30 days of ED admission. Crude and adjusted odds ratios (OR) with 95% confidence intervals (CI) for a one-class increase in RDW for 30-day mortality were calculated via binary logistic regression analysis. Age, gender and CFS score were considered as potential confounders. RESULTS: A total of 1407 patients (61.2% female), were included. The median age was 85 with an inter-quartile range (IQR) of 80-89, median CFS score 6 (IQR: 5-7), and median RDW 14 (IQR: 13-16). Of the included patients, 71.9% were admitted to hospital wards. A total of 85 patients (6.0%) died during the 30-day follow-up. Mortality rate was associated with RDW increase (p for trend < .001). Crude OR for a one-class increase in RDW for 30-day mortality was 1.32 (95% CI: 1.17-1.50, p < .001). When adjusted for age, gender and CFS-score, OR of mortality for one-class RDW increase was still 1.32 (95% CI: 1.16-1.50, p < .001). CONCLUSION: Higher RDW values had a significant association with increased 30-day mortality risk in frail older adults in the ED, and this risk was independent of degree of frailty. RDW is a readily available biomarker for most ED patients. It might be beneficial to include it in risk stratification of older frail ED patients to identify those who could benefit from further diagnostic assessment, targeted interventions, and care planning.

Low body temperature and mortality in older patients with frailty in the emergency department.

PURPOSE: The aim of this study was to assess the association between low body temperature and mortality in frail older adults in the emergency department (ED). METHODS: Inclusion criteria were: ≥ 75 years of age, Clinical Frailty Scale (CFS) score of 4-8, and temperature documented at ED admission. Patients were allocated to three groups by body temperature: low ≤ 36.0 °C, normal 36.1-38.0 and high ≥ 38.1. Odds ratios (OR) for 30-day and 90-day mortality were analysed. RESULTS: 1577 patients, 61.2% female, were included. Overall mortalities were 85/1577 (5.4%) and 144/1557 (9.2%) in the 30-day and 90-day follow-ups, respectively. The ORs for low body temperature were 3.03 (1.72-5.35; P < 0.001) and 2.71 (1.68-4.38; P < 0.001) for 30-day and 90-day mortality, respectively. This association remained when adjusted for age, CFS score and gender. Mortality of the high-temperature group did not differ significantly when compared to the normal-temperature group. CONCLUSIONS: Low body temperature in frail older ED patients was associated with significantly higher 30- and 90-day mortality.

The emergency department arrival mode and its relations to ED management and 30-day mortality in acute heart failure: an ancillary analysis from the EURODEM study.

BACKGROUND: Acute heart failure patients are often encountered in emergency departments (ED) from 11% to 57% using emergency medical services (EMS). Our aim was to evaluate the association of EMS use with acute heart failure patients' ED management and short-term outcomes. METHODS: This was a sub-analysis of a European EURODEM study. Data on patients presenting with dyspnoea were collected prospectively from European EDs. Patients with ED diagnosis of acute heart failure were categorized into two groups: those using EMS and those self-presenting (non- EMS). The independent association between EMS use and 30-day mortality was evaluated with logistic regression. RESULTS: Of the 500 acute heart failure patients, with information about the arrival mode to the ED, 309 (61.8%) arrived by EMS. These patients were older (median age 80 vs. 75 years, p < 0.001), more often female (56.4% vs. 42.1%, p = 0.002) and had more dementia (18.7% vs. 7.2%, p < 0.001). On admission, EMS patients had more often confusion (14.2% vs. 2.1%, p < 0.001) and higher respiratory rate (24/min vs. 21/min, p = 0.014; respiratory rate > 30/min in 17.1% patients vs. 7.5%, p = 0.005). The only difference in ED management appeared in the use of ventilatory support: 78.3% of EMS patients vs. 67.5% of non- EMS patients received supplementary oxygen (p = 0.007), and non-invasive ventilation was administered to 12.5% of EMS patients vs. 4.2% non- EMS patients (p = 0.002). EMS patients were more often hospitalized (82.4% vs. 65.9%, p < 0.001), had higher in-hospital mortality (8.7% vs. 3.1%, p = 0.014) and 30-day mortality (14.3% vs. 4.9%, p < 0.001). The use of EMS was an independent predictor of 30-day mortality (OR = 2.54, 95% CI 1.11-5.81, p = 0.027). CONCLUSION: Most acute heart failure patients arrive at ED by EMS. These patients suffer from more severe respiratory distress and receive more often ventilatory support. EMS use is an independent predictor of 30-day mortality.

Systematic geriatric assessment for older patients with frailty in the emergency department: a randomised controlled trial.

BACKGROUND: Comprehensive geriatric assessment provided in hospital wards in frail patients admitted to hospital has been shown to reduce mortality and increase the likelihood of living at home later. Systematic geriatric assessment provided in emergency departments (ED) may be effective for reducing days in hospital and unnecessary hospital admissions, but this has not yet been proven in randomised trials. METHODS: We conducted a single-centre, randomised controlled trial with a parallel-group, superiority design in an academic hospital ED. ED patients aged ≥ 75 years who were frail, or at risk of frailty, as defined by the Clinical Frailty Scale, were included in the trial. Patients were recruited during the period between December 11, 2018 and June 7, 2019, and followed up for 365 days. For the intervention group, systematic geriatric assessment was added to their standard care in the ED, whereas the control group received standard care only. The primary outcome was cumulative hospital stay during 365-day follow-up. The secondary outcomes included: admission rate from the index visit, total hospital admissions, ED-readmissions, proportion of patients living at home at 365 days, 365-day mortality, and fall-related ED-visits. RESULTS: A total of 432 patients, 63 % female, with median age of 85 years, formed the analytic sample of 213 patients in the intervention group and 219 patients in the control group. Cumulative hospital stay during one-year follow-up as rate per 100 person-years for the intervention and control groups were: 3470 and 3149 days, respectively, with rate ratio of 1.10 (95 % confidence interval, 0.55-2.19, P = .78). Admission rates to hospital wards from the index ED visit for the intervention and control groups were: 62 and 70 %, respectively (P = .10). No significant differences were observed between the groups for any outcomes. CONCLUSION: Systematic geriatric assessment for older adults with frailty in the ED did not reduce hospital stay during one-year follow-up. No statistically significant difference was observed for any secondary outcomes. More coordinated, continuous interventions should be tested for potential benefits in long-term outcomes. TRIAL REGISTRATION: The trial was registered in the ClinicalTrials.gov (registration number and date NCT03751319 23/11/2018).

National Early Warning Score 2 (NEWS2) and 3-level triage scale as risk predictors in frail older adults in the emergency department.

BACKGROUND: The aim of the emergency department (ED) triage is to recognize critically ill patients and to allocate resources. No strong evidence for accuracy of the current triage instruments, especially for the older adults, exists. We evaluated the National Early Warning Score 2 (NEWS2) and a 3-level triage assessment as risk predictors for frail older adults visiting the ED. METHODS: This prospective, observational study was performed in a Finnish ED. The data were collected in a six-month period and included were ≥ 75-year-old residents with Clinical Frailty Scale score of at least four. We analyzed the predictive values of NEWS2 and the three-level triage scale for 30-day mortality, hospital admission, high dependency unit (HDU) and intensive care unit (ICU) admissions, a count of 72-h and 30-day revisits, and ED length-of-stay (LOS). RESULTS: A total of 1711 ED visits were included. Median for age, CFS, LOS and NEWS2 were 85 years, 6 points, 6.2 h and 1 point, respectively. 30-day mortality was 96/1711. At triage, 69, 356 and 1278 of patients were assessed as red, yellow and green, respectively. There were 1103 admissions, of them 31 to an HDU facility, none to ICU. With NEWS2 and triage score, AUCs for 30-day mortality prediction were 0.70 (0.64-0.76) and 0.62 (0.56-0.68); for hospital admission prediction 0.62 (0.60-0.65) and 0.55 (0.52-0.56), and for HDU admission 0.72 (0.61-0.83) and 0.80 (0.70-0.90), respectively. The NEWS2 divided into risk groups of low, medium and high did not predict the ED LOS (p = 0.095). There was a difference in ED LOS between the red/yellow and as red/green patient groups (p < 0.001) but not between the yellow/green groups (p = 0.59). There were 48 and 351 revisits within 72 h and 30 days, respectively. With NEWS2 AUCs for 72-h and 30-day revisit prediction were 0.48 (95% CI 0.40-0.56) and 0.47 (0.44-0.51), respectively; with triage score 0.48 (0.40-0.56) and 0.49 (0.46-0.52), respectively. CONCLUSIONS: The NEWS2 and a local 3-level triage scale are statistically significant, but poor in accuracy, in predicting 30-day mortality, and HDU admission but not ED LOS or revisit rates for frail older adults. NEWS2 also seems to predict hospital admission.

Acute heart failure with and without concomitant acute coronary syndromes: patient characteristics, management, and survival.

BACKGROUND: Acute coronary syndromes (ACS) may precipitate up to a third of acute heart failure (AHF) cases. We assessed the characteristics, initial management, and survival of AHF patients with (ACS-AHF) and without (nACS-AHF) concomitant ACS. METHODS AND RESULTS: Data from 620 AHF patients were analyzed in a prospective multicenter study. The ACS-AHF patients (32%) more often presented with de novo AHF (61% vs. 43%; P < .001). Although no differences existed between the 2 groups in mean blood pressure, heart rate, or routine biochemistry on admission, cardiogenic shock and pulmonary edema were more common manifestations in ACS-AHF (P < .01 for both). Use of intravenous nitrates, furosemide, opioids, inotropes, and vasopressors, as well as noninvasive ventilation and invasive coronary procedures (angiography, percutaneous coronary intervention, coronary artery bypass graft surgery), were more frequent in ACS-AHF (P < .001 for all). Although 30-day mortality was significantly higher for ACS-AHF (13% vs. 8%; P = .03), survival in the 2 groups at 5 years was similar. Overall, ACS was an independent predictor of 30-day mortality (adjusted odds ratio 2.0, 95% confidence interval 1.07-3.79; P = .03). CONCLUSIONS: Whereas medical history and the manifestation and initial treatment of AHF between ACS-AHF and nACS-AHF patients differ, long-term survival is similar. ACS is, however, independently associated with increased short-term mortality.

Frequency and Prognostic Significance of Abnormal Liver Function Tests in Patients With Cardiogenic Shock.

Cardiogenic shock (CS) is a cardiac emergency often leading to multiple organ failure and death. Assessing organ dysfunction and appropriate risk stratification are central for the optimal management of these patients. The purpose of this study was to assess the prevalence of abnormal liver function tests (LFTs), as well as early changes of LFTs and their impact on outcome in CS. We measured LFTs in 178 patients in CS from serial blood samples taken at 0 hours, 12 hours, and 24 hours. The associations of LFT abnormalities and their early changes with all-cause 90-day mortality were estimated using Fisher's exact test and Cox proportional hazards regression analysis. Baseline alanine aminotransferase (ALT) was abnormal in 58% of the patients, more frequently in nonsurvivors. Abnormalities in other LFTs analyzed (alkaline phosphatase, gamma-glutamyl transferase, and total bilirubin) were not associated with short-term mortality. An increase in ALT of >20% within 24 hours (ΔALT>+20%) was observed in 24% of patients. ΔALT>+20% was associated with a more than 2-fold increase in mortality compared with those with stable or decreasing ALT (70% and 28%, p <0.001). Multivariable regression analysis showed that ΔALT>+20% was associated with increased 90-day mortality independent of other known risk factors. In conclusion, an increase in ALT in the initial phase was seen in 1/4 of patients in CS and was independently associated with 90-day mortality. This finding suggests that serial ALT measurements should be incorporated in the clinical assessment of patients in CS.

Ventricular conduction abnormalities as predictors of long-term survival in acute de novo and decompensated chronic heart failure.

AIMS: Data on the prognostic role of left and right bundle branch blocks (LBBB and RBBB), and nonspecific intraventricular conduction delay (IVCD; QRS ≥ 110 ms, no BBB) in acute heart failure (AHF) are controversial. Our aim was to investigate electrocardiographic predictors of long-term survival in patients with de novo AHF and acutely decompensated chronic heart failure (ADCHF). METHODS AND RESULTS: We analysed the admission electrocardiogram of 982 patients from a multicenter European cohort of AHF with 3.9 years' mean follow-up. Half (51.5%, n = 506) of the patients had de novo AHF. LBBB, and IVCD were more common in ADCHF than in de novo AHF: 17.2% vs. 8.7% (P < 0.001) and 20.6% vs. 13.2% (P = 0.001), respectively, and RBBB was almost equally common (6.9% and 8.1%; P = 0.5), respectively. Mortality during the follow-up was higher in patients with RBBB (85.4%) and IVCD (73.7%) compared with patients with normal ventricular conduction (57.0%); P < 0.001 for both. The impact of RBBB on prognosis was prominent in de novo AHF (adjusted HR 1.93, 1.03-3.60; P = 0.04), and IVCD independently predicted death in ADCHF (adjusted HR 1.79, 1.28-2.52; P = 0.001). Both findings were pronounced in patients with reduced ejection fraction. LBBB showed no association with increased mortality in either of the subgroups. The main results were confirmed in a validation cohort of 1511 AHF patients with 5.9 years' mean follow-up. CONCLUSIONS: Conduction abnormalities predict long-term survival differently in de novo AHF and ADCHF. RBBB predicts mortality in de novo AHF, and IVCD in ADCHF. LBBB has no additive predictive value in AHF requiring hospitalization.

Dexmedetomidine in addition to benzodiazepine-based sedation in patients with alcohol withdrawal delirium.

Alcohol withdrawal delirium (AWD) is often refractory to conventional medication. We report a prospective series of patients treated with α2-agonist dexmedetomidine added to conventional sedation. Eighteen patients with AWD were diagnosed by Confusion assessment method for ICU score. Treatment, complications, length of stay (LOS) in ICU and hospital were recorded. In addition, hospital and 1-year mortality were assessed. Dexmedetomidine was given for 23.9 (18.4) h [mean (SD)]. All the patients also received benzodiazepines but three patients were given haloperidole. No patient was intubated. The maximum infusion rate of dexmedetomidine was 1.5 (1.2) µg/kg/h. Time to resolution of AWD was 3.8 (1.3) days. The ICU LOS was 7.1 (2.7) days and in-hospital LOS 12.1 (4.5) days. No adverse events were observed although one patient died from acute pancreatitis. The use of dexmedetomidine in AWD seems safe but warrants further studies.

Management of acute heart failure and the effect of systolic blood pressure on the use of intravenous therapies.

AIMS: To examine the use of the treatments for acute heart failure (AHF) recommended by ESC guidelines in different clinical presentations and blood pressure groups. METHODS: The use of intravenous diuretics, nitrates, opioids, inotropes, and vasopressors as well as non-invasive ventilation (NIV) was analysed in 620 patients hospitalized due to AHF. The relation between AHF therapies and clinical presentation, especially systolic blood pressure (SBP) on admission, was also assessed. RESULTS: Overall, 76% of patients received i.v. furosemide, 42% nitrates, 29% opioids, 5% inotropes and 7% vasopressors, and 24% of patients were treated with NIV. Furosemide was the most common treatment in all clinical classes and irrespective of SBP on admission. Nitrates were given most often in pulmonary oedema and hypertensive AHF. Overall, only SBP differed significantly between patients with and without the studied treatments. SBP was higher in patients treated with nitrates than in those who were not (156 vs. 141 mmHg, p<0.001). Still, only one-third of patients presenting acute decompensated heart failure and SBP over 120 mmHg were given nitrates. Inotropes and vasopressors were given most frequently in cardiogenic shock and pulmonary oedema, and their use was inversely related to initial SBP (p<0.001). NIV was used only in half of the cardiogenic shock and pulmonary oedema patients. CONCLUSIONS: The management of AHF differs between ESC clinical classes and the use of i.v. vasoactive therapies is related to the initial SBP. However, there seems to be room for improvement in administration of vasodilators and NIV.

Long-term survival after hospitalization for acute heart failure--differences in prognosis of acutely decompensated chronic and new-onset acute heart failure.

AIMS: To analyze the five-year mortality after hospitalization for acute heart failure (AHF) and compare predictors of prognosis in patients with and without a previous history of heart failure. METHODS: Patients with AHF (n=620) from the prospective multicenter FINN-AKVA study were classified as acutely decompensated chronic heart failure (ADCHF) or de-novo AHF if no previous history of heart failure was present. Both all-cause mortality during five years of follow-up and prognostic factors were determined. RESULTS: The overall mortality was 60.3% (n=374) at five years. ADCHF was associated with significantly poorer outcome compared to de-novo AHF; five-year mortality rate 75.6% vs. 44.4% (p<0.001). Initially, mortality was high (33.5% in ADCHF and 21.7% in de-novo AHF after 12 months), but in de-novo AHF the annual mortality declined markedly already after the first year. Compared to de-novo AHF, patients with ADCHF had an increased risk of death for several years after the index hospitalization. A previous history of heart failure was an independent predictor of five-year mortality (adjusted hazard ratio 1.8 (95% CI 1.4-2.2; p<0.001). Older age and impaired renal function were associated with adverse long-term prognosis in both ADCHF and de-novo AHF, while higher systolic blood pressure on admission predicted better outcome. CONCLUSION: The long-term prognosis after hospitalization for AHF is poor, with a significantly different survival observed in patients with de-novo AHF compared to ADCHF. A previous history of heart failure is an independent predictor of five-year mortality. Distinction between ADCHF and de-novo AHF may improve our understanding of patients with AHF.

Growth factor expression in degenerated intervertebral disc tissue. An immunohistochemical analysis of transforming growth factor beta, fibroblast growth factor and platelet-derived growth factor.

Degenerated intervertebral disc has lost its normal architecture, and there are changes both in the nuclear and annular parts of the disc. Changes in cell shape, especially in the annulus fibrosus, have been reported. During degeneration the cells become more rounded, chondrocyte-like, whereas in the normal condition annular cells are more spindle shaped. These chondrocyte-like cells, often forming clusters, affect extracellular matrix turnover. In previous studies transforming growth factor beta (TGFbeta) -1 and -2, basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) have been highlighted in herniated intervertebral disc tissue. In the present study the same growth factors are analysed immunohistochemically in degenerated intervertebral disc tissue. Disc material was obtained from 16 discs operated for painful degenerative disc disease. Discs were classified according to the Dallas Discogram Description. Different disc regions were analysed in parallel. As normal control disc tissue material from eight organ donors was used. Polyclonal antibodies against different growth factors and TGFbeta receptor type II were used, and the immunoreaction was detected by the avidin biotin complex method. All studied degenerated discs showed immunoreactivity for TGFbeta receptor type II and bFGF. Fifteen of 16 discs were immunopositive for TGFbeta-1 and -2, respectively, and none showed immunoreaction for PDGF. Immunopositivity was located in blood vessels and in disc cells. In the nucleus pulposus the immunoreaction was located almost exclusively in chondrocyte-like disc cells, whereas in the annular region this reaction was either in chondrocyte-like disc cells, often forming clusters, or in fibroblast-like disc cells. Chondrocyte-like disc cells were especially prevalent in the posterior disrupted area. In the anterior area of the annulus fibrosus the distribution was more even between these two cell types. bFGF was expressed in the anterior annulus fibrosus more often in chondrocyte-like disc cells than in fibroblast-like disc cells. Control discs showed cellular immunopositivity for only TGFbeta-1 and -2 and TGFbeta receptor type II . We suggest that growth factors create a cascade in intervertebral disc tissue, where they act and participate in cellular remodelling from the normal resting stage via disc degeneration to disc herniation.

Oncoprotein c-Fos and c-Jun immunopositive cells and cell clusters in herniated intervertebral disc tissue.

The oncoproteins c-Fos and c-Jun create a transcriptional site early response activating protein (AP-1) mediating the regulation of gene expression in response to extracellular signalling by, for example, cytokines. These proteins are important in the signalling pathway from the cell membrane to the nucleus. Previously, oncoproteins have been located in articular synovium and in chondrocytes, participating in transcription. There is, however, no such study of intervertebral disc tissue. In disc degeneration and after herniation, cell proliferation markers have been demonstrated. In the present study we visualize the AP-1 transcriptional site factors c-Fos and c-Jun in 38 human herniated intervertebral disc tissue samples by immunohistochemical staining with monoclonal antibodies. No immunoreactivity could be observed in control disc tissue, indicating that after herniation, disc cells are entering from the resting stage to the cell cycle. Furthermore, c-Jun immunoreactivity was also observed in disc cell clusters, thus demonstrating them to be active transcriptional sites in disc tissue. c-Fos immunoreactivity was seen in 15/38 and c-Jun in 28/38 herniated discs (39% and 74% respectively). Immunopositive groups of disc cells were noted in 7/28 (25%) of the oncoprotein-immunopositive samples. We did not see any difference in immunoreactivity between female and male patients. Furthermore, we did not notice any statistical difference regarding the immunoreaction for proto-oncogenes c-Fos and c-Jun in extrusions, sequesters and protrusions. Nor did immunostaining show any significant relationship with preoperative pain duration. We concluded that, in herniated disc tissue, the oncoproteins c-Fos and c-Jun are activated in disc cells and cell clusters. In the future, learning more about this transcriptional signal pathway may result in new specific treatments for intervertebral disc pathology.