Determinant Of Mortality In Patients Research Articles

Impact of Aortic Wall Thrombus on Long-term Changes in Renal Function Among Patients Treated by Fenestrated-Branched Endografts for Complex Aortic Aneurysms

Renal function deterioration (RFD) is an important determinant of mortality in patients treated for complex aortic aneurysms. Catheter and guidewire manipulations in diseased aortas during fenestrated-branched endovascular aneurysm repair (F-BEVAR) have been associated with risk of emboli leading to loss of renal function. The aim of this study was to describe the impact of atherosclerotic wall thrombus (AWT) on long-term RFD in patients treated by F-BEVAR for pararenal and extent IV thoracoabdominal aortic aneurysms. Clinical data of 212 patients treated for complex aortic aneurysms with F-BEVAR were entered into a prospectively maintained database (2007-2015). AWT was evaluated by computed tomography angiography using volumetric measurements in nonaneurysmal aortic segments. AWT was classified as mild, moderate, or severe using a score system based on thrombus extent, type, thickness, area, and circumference. Patient survival and renal outcomes were assessed at dismissal, at 6 to 8 weeks, at 6 months, and annually, including serum creatinine concentration, estimated glomerular filtration rate (eGFR), chronic kidney stage, RIFLE (risk, injury, failure, loss of kidney function, end-stage renal disease) criteria, need for renal replacement therapy, and presence of kidney infarction. There were 169 male (80%) and 43 female (20%) patients with mean age of 75 ± 7 years. Aneurysm extent was pararenal in 157 patients and extent IV thoracoabdominal aortic aneurysm in 55. A total of 700 renal-mesenteric arteries were incorporated (3.1 ± 1 vessels/patient). AWT was classified as mild in 98 patients (46%), moderate in 75 patients (35%), and severe in 39 patients (19%). At 30 days, 45 patients (21%) developed RFD (>30% decline in eGFR). Decline in eGFR and kidney infarction were associated with higher AWT volume index and severe AWT classification (P < .05). There was no association of AWT with 30-day mortality, which was 0.5% for the entire cohort. Mean follow-up was 29 ± 23 months. Freedom from RFD was 73% ± 6% for mild, 81% ± 6% for moderate, and 66% ± 8% for severe AWT patients at 3 years (P = .012). Patient survival was 73% ± 5% for mild, 72% ± 6% for moderate, and 69% ± 10% for severe AWT patients at 3 years (P = .67). Severe AWT is a significant predictor of kidney infarction and early and late decline in renal function among patients treated by F-BEVAR. Severe AWT had no impact on early and late patient survival. Preoperative planning and decision-making should include careful assessment of AWT in patients with complex aortic aneurysms considered for F-BEVAR.

PH-Responsive nanoparticles based on ibuprofen prodrug as drug carriers for inhibition of primary tumor growth and metastasis.

Cancer metastases represent a major determinant of mortality in patients with cancer. Cyclooxygenase-2 (COX-2) and its metabolites play important roles in tumor growth and metastasis. Overexpression of COX-2 have been found in various types of cancers including melanoma. Nonsteroidal anti-inflammatory drugs (NSAIDs) have been widely used to inhibit COX-2 and can be a promising additive for the management of aggressive cancers. A novel pH-sensitive drug delivery carrier based on PEG-derivatized ibuprofen, MPEG-PHEI, was synthesized for dual delivery of anticancer agents and NSAIDs. This amphiphilic and biodegradable copolymer could self-assemble into core-shell nanoparticles (NPs) and the hydrophobic doxorubicin (DOX) could be loaded into the core of the nanoparticles. DOX-loaded MPEG-PHEI nanoparticles (DOX/NPs) could release DOX in endosome microclimate via micelle collapse and ibuprofen via ester bond hydrolysis. In vitro DOX/NPs showed comparable cytotoxicity to DOX·HCl and comparable inhibition of COX-2 to ibuprofen. More importantly, DOX/NPs revealed a significant in vivo therapeutic efficacy in both experimental subcutaneous tumors and lung metastasis model while decreasing the toxicity of DOX. This study demonstrated the advantages of combining NSAIDs with chemotherapy agents and provided a novel nanoparticle system for both primary and metastatic tumor treatment.

Time is the enemy: Mortality in trauma patients with hemorrhage from torso injury occurs long before the “golden hour”

IntroductionThe concept of the “Golden Hour” has been a time-honored tenet of prehospital trauma care, despite a paucity of data to substantiate its validity. Non-compressible torso hemorrhage has been demonstrated to be a significant cause of mortality in both military and civilian settings. We sought to characterize the impact of prehospital time and torso injury severity on survival. Furthermore, we hypothesized that time would be a significant determinant of mortality in patients with higher Abbreviated Injury Scale (AIS) grades of torso injury (AIS ≥ 4) and field hypotension (prehospital SBP ≤ 110 mmHg) as these injuries are commonly associated with hemorrhage. MethodsData for this analysis was generated from a registry of 2,523,394 injured patients entered into the National Trauma Data Bank Research Data Set from 2012 to 2014. Patients with torso injury were identified utilizing Abbreviated Injury Scale (AIS) for body regions 4 (Thorax) and 5 (Abdomen). Specific inclusion criteria for this study included pre-hospital time, prehospital SBP ≤110 mmHg, torso injury qualified by AIS and mortality. Patients with non-survivable torso injury (AIS = 6), severe head injuries (AIS ≥ 3), no signs of life in the field (SBP = 0), interfacility transfers, or those with any missing data elements were excluded. This classification methodology identified a composite cohort of 42,135 adult patients for analysis. ResultsThe overall mortality rate of the study population was 7.9% (3326/42,135); Torso AIS and prehospital time were noted to be strong independent predictors of patient mortality in all population strata of the analysis (P < 0.05). The data demonstrated a profound incremental increase in mortality in the early time course after injury associated with torso AIS ≥4. ConclusionIn patients with high-grade torso injury, AIS grades ≥4, the degree anatomic disruption is associated with significant hemorrhage. In our study, a precipitous rise in patient mortality was exhibited in this high-grade injury group at prehospital times <30 min. Our data highlight the critical nature of prehospital time in patients with non-compressible torso hemorrhage. However, realizing that evacuation times ≤30 min may not be realistic, particularly in rural or austere environments, future efforts should be directed toward the development of therapies to increase the window of survival in the prehospital environment.

Implantable cardioverter-defibrillators in end-stage heart failure patients listed for heart transplantation: Results from a large retrospective registry

Implantable cardioverter-defibrillators (ICDs) are recommended in patients with low ejection fraction. However, the survival benefit of ICDs in patients with end-stage heart failure listed for heart transplantation is unclear. To evaluate the ICD benefit on mortality in this population. Three hundred and eighty consecutive patients listed for heart transplantation between 2005 and 2009 in one tertiary heart transplant centre were enrolled in a retrospective registry; 122 patients received an ICD before or within 3 months after being listed for heart transplantation (ICD group). Predictors of death on the waiting list were assessed by Cox regression. Overall, 15.6% of patients died while awaiting heart transplantation. Non-ICD patients presented more often haemodynamic compromise requiring mechanical circulatory support (29.1% vs. 9.8%; P<0.001), and were more likely to die while on the waiting list (19.0% vs. 8.3%; log-rank P=0.001). However, in the multivariable model, ICD did not remain an independent predictor of death. Need for mechanical circulatory support (P<0.001), low ejection fraction (P=0.001) and registration on the regular list (P=0.008) were the only independent predictors of death. Death was mainly caused by haemodynamic compromise (76.3% of deaths), which occurred more frequently in the non-ICD group (14.7% vs. 5.8%; log-rank P=0.002). Unknown/arrhythmic deaths did not differ significantly between the two groups (3.9% vs. 1.7%; log-rank P=0.21). ICD-related complications occurred in 21.4% of patients, mainly as a result of postoperative worsening of heart failure (11.9%). Haemodynamic failure appears as the main determinant of mortality in patients with end-stage heart failure awaiting heart transplantation. ICD seems to have little benefit on survival in this population.

Discovery of Genetic Variation on Chromosome 5q22 Associated with Mortality in Heart Failure.

Failure of the human heart to maintain sufficient output of blood for the demands of the body, heart failure, is a common condition with high mortality even with modern therapeutic alternatives. To identify molecular determinants of mortality in patients with new-onset heart failure, we performed a meta-analysis of genome-wide association studies and follow-up genotyping in independent populations. We identified and replicated an association for a genetic variant on chromosome 5q22 with 36% increased risk of death in subjects with heart failure (rs9885413, P = 2.7x10-9). We provide evidence from reporter gene assays, computational predictions and epigenomic marks that this polymorphism increases activity of an enhancer region active in multiple human tissues. The polymorphism was further reproducibly associated with a DNA methylation signature in whole blood (P = 4.5x10-40) that also associated with allergic sensitization and expression in blood of the cytokine TSLP (P = 1.1x10-4). Knockdown of the transcription factor predicted to bind the enhancer region (NHLH1) in a human cell line (HEK293) expressing NHLH1 resulted in lower TSLP expression. In addition, we observed evidence of recent positive selection acting on the risk allele in populations of African descent. Our findings provide novel genetic leads to factors that influence mortality in patients with heart failure.

Determinants of mortality in patients with type 2 diabetes: a review.

We aimed to review and summarize the evidence from accomplished trials analyzing factors influencing mortality in patients with T2DM and to provide some recommendations for targets and treatment in the European region. The following databases were searched for relevant trials: PubMed and the Cochrane Library. Of 3.806 citations, 134 trials met our inclusion criteria. The reduction in lifetime for 65+-years-old patients having less than 10years T2DM amounts to 1.8years. Having T2DM for more than 10years lifetime will be reduced by 2.7years. However, the lifetime shortening factor of T2DM will even be stronger for 40+-years-old patients at onset. Males will lose 11.6years of life and 18.6 QUALYs. T2DM among females will reduce life by 14 QUALYs by 22years. From a statistical point of view, the highest mortality rate will occur in an over 55-years-old European smoking and non-compliant diabetic woman with alcohol abuse living in a rural area with a low level of education and a low socio-economic status. Furthermore, other co-morbidities such as cardiovascular diseases, gout, and depression affect mortality. Additionally, mortality will increase with a BMI over 35 and also with a BMI under 20-25. This refers to the obesity paradox indicating a higher mortality rate among normal weight patients with T2DM compared to overweight patients with T2DM. HbA1c-levels between 6.5% and 7% are associated with the lowest impact on mortality.

Determinants of Mortality in Patients with Chronic Kidney Disease Undergoing Percutaneous Coronary Intervention

Background: Renal impairment is a known predictor of mortality in both the general population and in patients with cardiac disease. The aim of this study was to evaluate factors that determine mortality in patients with chronic kidney disease (CKD) who have undergone percutaneous coronary intervention (PCI). Methods: In this study we included 293 consecutive patients with CKD who underwent PCI between 1st January 2007 and 30th September 2012. The primary outcome that we studied was all-cause mortality in a follow-up period of 12-69 months (mean 38.8 ± 21.7). Results: Age (p < 0.001), PCI indication (p = 0.035), CKD stage (p < 0.001) and left ventricular ejection fraction (p < 0.001) were significantly related to mortality. CKD stage 5 [hazard ratio (HR) = 6.39, 95% CI: 1.51-27.12) and severely impaired left ventricular function (HR = 4.04, 95% CI: 2.15-7.59) were the strongest predictors of mortality. Other factors tested (gender, hypertension, diabetes, hyperlipidaemia, established peripheral vascular disease/stroke, coronary arteries intervened, number of vessels treated, number of stents implanted and length of lesion treated) did not show any correlation with mortality. Conclusions: The mortality of patients with CKD undergoing PCI increases with age, worsening CKD stage and deteriorating left ventricular systolic function, and it is also higher in patients with acute coronary syndromes compared to those with stable coronary artery disease.

0494: Do implantable cardioverter defibrillators really improve survival of patients listed for heart transplantation?

Implantable cardioverter defibrillators (ICD) are recommended in patients with low ejection fraction. However the survival benefit of ICD in patients with end-stage heart failure listed for heart transplantation is unclear. The objective was to evaluate the ICD benefit on mortality in this population. 380 consecutive patients listed for heart transplantation between 2005 and 2009 in one tertiary heart transplant center were enrolled in a retrospective registry. 122 patients received an ICD before or within 3 months after registry (ICD-group). Predictors of death in the waiting list were assessed by Cox regression. 15.6% of patients died while awaiting heart transplantation. NonICD patients presented more often haemodynamic compromise requiring mechanical circulatory support (MCS, 34.2% vs 14.9%, p<0.0001) and were more likely to die while in the waiting list (19.0% vs 8.3%, p=0.006). However, in the multivariate model, ICD did not remain an independent predictor of death. The need for a MCS and LVEF were the only independent predictors of death (p<0.0001 and p=0.001). Death was mainly due to haemodynamic compromise (76.6% of deaths), which occurred more frequently in the non-ICD group (14.7% vs 5.8%, p=0.019). Unknown/arrhythmic deaths did not significantly differ between the two groups (3.9% vs 1.7%, p=0.19). ICD-related complications occurred in 21.4% of patients, mainly due post-operative worsening of heart failure (11.9%). Haemodynamic failure appears as the main determinant of mortality in patients awaiting heart transplantation. ICD seems to have little benefit on survival in this population.

Inadequate Source Control and Inappropriate Antibiotics are Key Determinants of Mortality in Patients with Intra-Abdominal Sepsis and Associated Bacteremia.

Patients with intra-abdominal sepsis and associated bacteremia have a high mortality rate. However, outcomes studies in this population are limited, in part because of the small numbers of such patients. The objective of this study was to describe characteristics of critically ill patients with secondary blood stream infection (BSI) of intra-abdominal origin and identify predictors of mortality. This retrospective, single-center study evaluated patients admitted between January 2005 and January 2011 with bacteremia because of an intra-abdominal source. Patients were included if they met criteria for severe sepsis based on International Classification of Diseases, 9th Revision (ICD 9) codes for acute organ dysfunction, had a positive blood culture, had at least one ICD 9 code indicative of an intra-abdominal process, and had a confirmed or clinically suspected intra-abdominal infection (IAI) within 72 h of the blood culture. Chart review was performed to confirm the presence of these criteria and also the absence of any other potential source of bacteremia. Data were collected on patient demographics, BSI source, source control procedure details, microorganisms isolated, and antibiotics administered. Multivariable logistic regression analysis was performed to identify independent predictors of mortality. Three hundred six patients with BSI were identified, of which 108 episodes were deemed to be of intra-abdominal origin. Gram-negative organisms comprised 43% of blood isolates, followed by gram-positives (33%), anaerobes (14%), and yeast (9%). Appropriate antimicrobial therapy was administered in 71% of patients. The overall mortality rate was 27.8%. As compared with survivors, non-survivors were older, more likely to have underlying COPD or asthma, and have renal or metabolic failure (p<0.05 for all). Among non-survivors, adequate source control was obtained less frequently (64% vs. 91%, p=0.002) and median time to appropriate antibiotics was longer (23 h vs. 4 h, p=0.004). Logistic regression analysis revealed inadequate source control (p=0.002) and inappropriate antibiotics (p=0.016) to be independently associated with mortality. Critically ill patients with a BSI of abdominal origin are at high risk for mortality. Failure to achieve adequate source control and administration of inappropriate antibiotics were independent predictors of mortality. Thus, these represent potential opportunities to impact outcomes in patients with complicated IAI.

Linking autophagy with inflammation through IRF1 signaling in ER+ breast cancer

Resistance to antiestrogen therapy remains a critical determinant of mortality in patients affected by ER+ breast cancer. Our previous work identified autophagy and interferon regulatory factor 1 (IRF1) signaling as key regulators of this process. We have recently demonstrated a novel reciprocal interaction between IRF1 and ATG7, linking inflammation and autophagy.

Modeling of the relationship between the environmental air pollution, clinical risk factors, and hospital mortality due to myocardial infarction in Isfahan, Iran.

Background:This study aimed to determine the relationship between the environmental factor, clinical risk factors, and individual variables with mortality due to acute myocardial infarction (MI) in Isfahan.Materials and Methods:This cross-sectional study was performed between April 2012 and March 2013. The data on the patients’ mortality due to MI in Isfahan were obtained from the MI National Registry. The international classification system (ICD10: I21-I22) was used to diagnose MI. The air quality indicators and environmental variables were used to measure the air pollution. Multilevel logistic regression in the Stata software was used to determine the factors associated with mortality in patients and odds ratios (ORs) were calculated.Results:Six hundred eleven patients with MI were studied during 1-year. 444 (72.2%) patients were male and the rest were female. 4.7% of the patients died due to MI. The mean age at MI incidence was 62.2 ± 13 years. Of the air pollution parameters, PM10 had the maximum mean concentration (49.113 ppm), followed by NOX, NO, NO2, CO, SO2, and O3. The adjusted OR of mortality was derived 2.07 (95% CI: 1.5-2.85) for right bundle branch block, 1.5 (95% CI: 1.3-1.7) for ST-segment elevation MI, 1.84 (95% CI: 1.13-3) for age, 1.06 (95% CI: 1.01-1.20) for CO, 1.1 (95% CI: 1.03-1.30) for O3, and 1.04 (95% CI: 1.01-1.4) for SO2, all of which were considered as the risk factors of mortality. However, OR of mortality was 0.79 for precipitation (95% CI: 0.74-0.84) and 0.52 for angioplasty (95% CI: 0.4-0.68) were considered as protective factors of mortality. The individual characteristics including age, history of MI in the immediate family, hypertension, and diabetes were significantly associated with mortality from MI. The indices of air pollution including SO2, CO, O3, and environmental factors such as the precipitation and temperature were the determinants of mortality in patients with MI.Conclusion:With regards to the factors associated with mortality from MI reported in this study, air pollution and environmental factors, in addition to the risk factors and predictive factors, should be particularly addressed to control the mortality from MI.

Longitudinal Assessment of Right Ventricular Myocardial Strain in Relation to Transplant-Free Survival in Children with Idiopathic Pulmonary Hypertension

Right ventricular (RV) function is an important determinant of mortality in patients with idiopathic pulmonary arterial hypertension (iPAH). The aim of this study was to serially evaluate global and regional RV two-dimensional strain and their relation to transplantation-free survival in children with iPAH. RV regional and global longitudinal strain was retrospectively assessed in children with iPAH. Serial echocardiograms at 3 to 6months from presentation and then at yearly intervals were analyzed. Results were compared with those from controls and between iPAH survivors (group 1) and those who died or needed transplantation (group 2). Survival stratified by RV global longitudinal strain at presentation was analyzed. Seventeen patients with iPAH (mean age, 8.4±4.8years; seven male patients), of whom 11 were alive (group 1) and six had died or undergone transplantation (group 2), and 17 age-matched controls were studied. The median follow-up period was 1.5years (range, 0.04-7.8years). RV global longitudinal strain was significantly reduced in patients with iPAH compared with controls (-13.5 ± 5.9% vs -24.4 ± 3.9%, P<.001) and in group 2 compared with group 1 at presentation (-9 ± 2.8% vs -16 ± 5.7%, P<.05) and throughout follow-up. During follow-up, RV global and regional longitudinal strain worsened in group 2, especially in RV apical segments (-6.3 ± 5% vs -1.9 ± 1.6% at presentation compared with the last echocardiographic assessment in group 2, P<.05), but was unchanged in group 1. RV global longitudinal strain > -14% predicted transplantation-free survival with 100% sensitivity and 54.5% specificity. RV strain imaging may be useful for serial follow-up and prognostication in children with iPAH.

Clinical and Histologic Determinants of Mortality for Patients With Barrett’s Esophagus–Related T1 Esophageal Adenocarcinoma

Superficial (T1) esophageal adenocarcinoma (EAC) commonly is treated by endoscopic resection, yet little is known about factors that predict outcomes of this approach. We assessed clinical and histologic variables associated with the overall survival times of patients with T1 EAC who received therapy. In a retrospective analysis, we collected data from patients who underwent endoscopic mucosal resection (EMR) for T1 EAC (194 patients with T1a and 75 patients with T1b) at the Mayo Clinic, from 1995 through 2011. EMR specimens were reviewed systematically for depth of invasion, presence of lymphovascular invasion, grade of differentiation, and status of resection margins. Kaplan-Meier curves and proportional hazards regression models were used in statistical analyses. Demographic characteristics were similar between patients with T1a and T1b EAC. Overall survival at 5 years after EMR was 74.4% for patients with T1a (95% confidence interval [CI], 67.6%-81.8%) and 53.2% for patients with T1b EAC (95% CI, 40.3%-70.1%). Of surviving patients with T1a EAC, 94.1% remained free of cancer (95% CI, 89.8%-98.5%), and 94.7% of surviving patients with T1b EAC remained free of cancer (95% CI, 85.2%-100%). A multivariable model associated older age (per 10-year increment), evidence of lymphovascular invasion, and deep margin involvement with reduced overall survival in patients with T1 EAC. Systematic assessment of EMR specimens can help predict mortality and potentially guide treatment options for patients with T1 EAC.

Diabetic nephropathy: diagnosis and treatment

Nephropathy remains a major cause of morbidity and a key determinant of mortality in patients with type 1 or type 2 diabetes mellitus. Research is ongoing to identify biomarkers that in addition to albuminuria and glomerular filtration rate assist in the prediction and monitoring of renal disease in diabetes mellitus. Current strategies to treat this condition focus on intensification of glycaemic control and excellent control of blood pressure using regimens based on blockade of the renin-angiotensin system. Other approaches to control blood pressure and afford renoprotection are under active clinical investigation, including renal denervation and endothelin receptor antagonism. With increasing understanding of the underlying pathophysiological processes implicated in diabetic nephropathy, new specific renoprotective treatment strategies are anticipated to become available over the next few years.

Individual patient data meta-analysis of organ failure in acute pancreatitis: protocol of the PANCREA II study.

Organ failure is a major determinant of mortality in patients with acute pancreatitis. These patients usually require admission to high dependency or intensive care units and consume considerable health care resources. Given a low incidence rate of organ failure and a lack of large non-interventional studies in the field of acute pancreatitis, the characteristics of organ failure that influence outcomes of patients with acute pancreatitis remain largely unknown. Therefore, the Pancreatitis Across Nations Clinical Research and Education Alliance (PANCREA) aims to conduct a meta-analysis of individual patient data from prospective non-interventional studies to determine the influence of timing, duration, sequence, and combination of different organ failures on mortality in patients with acute pancreatitis.Pancreatologists currently active with acute pancreatitis clinical research will be invited to contribute. To be eligible for inclusion patients will have to meet the criteria of acute pancreatitis, develop at least one organ failure during the first week of hospitalization, and not be enrolled into an intervention study. Raw data will then be collated and checked. Individual patient data analysis based on a logistic regression model with adjustment for confounding variables will be done. For all analyses, corresponding 95% confidence intervals and P values will be reported.This collaborative individual patient data meta-analysis will answer important clinical questions regarding patients with acute pancreatitis that develop organ failure. Information derived from this study will be used to optimize routine clinical management and improve care strategies. It can also help validate outcome definitions, allow comparability of results and form a more accurate basis for patient allocation in further clinical studies.

Impact of chronic kidney disease in CRT effectiveness and long-term outcomes

Purpose: Chronic kidney disease (CKD) is an important determinant of mortality in patients with congestive heart failure, therefore we sought to determine the impact of CKD on cardiac resynchronization therapy (CRT) benefit and long-term outcomes. Methods: We evaluated 155 patients submitted to CRT between 2006 and 2012, in a single centre. Clinical features, laboratory and echocardiographic findings were analysed at baseline and 6 months after CRT. CKD was defined as a glomerular filtration rate (eGFR) < 60 mL/min/1.73m2, estimated by the Modification of Diet in Renal Disease equation. Six months after CRT, patients were classified as responders to CRT if they showed a decrease in left ventricular end-systolic volume >15%. The mean follow-up time was 41±26 months. The prognostic effect of CKD on long-term outcomes was assessed by Kaplan-Meier survival analysis, rehospitalisation rate due to heart failure and the combined endpoint of all-cause mortality and heart failure readmissions. Results: Patients with CKD (n=55, 35.5%) at the time of device implantation were older (69.0±7.9 vs. 58.4±9.9 years, p<0.01) than patients without CKD, but had no significant differences regarding preimplantation NYHA functional class, ejection fraction or other echocardiographic parameters. During long-term follow-up, CKD patients presented a higher mortality (18.2% vs. 7.0%, p<0.05) and a higher rate of the combined endpoint (49.1% vs. 31%, p<0.05). However, the proportion of echocardiographic responders between patients with and without CKD was similar (53.7% vs. 52.6%). Conclusions: CKD is common in patients undergoing CRT and it is associated with a higher mortality, even though they have similar echocardiographic response. Consequently, CKD should certainly be considered in the decision of implanting a CRT-P or a CRT-D.

Contribution of host, bacterial factors and antibiotic treatment to mortality in adult patients with bacteraemic pneumococcal pneumonia

RationaleHost and bacterial factors as well as different treatment regimens are likely to influence the outcome in patients with bacteraemic pneumococcal pneumonia.ObjectivesTo estimate the relative contribution of host factors as...

Relationship of serum sodium concentration to mortality in a wide spectrum of heart failure patients with preserved and with reduced ejection fraction: an individual patient data meta‐analysis†

Hyponatraemia has been associated with reduced survival in patients with heart failure and reduced ejection fraction (HF-REF). The relationship between serum sodium and outcome is unclear in heart failure with preserved (≥ 50%) ejection fraction (HF-PEF). Therefore, we used a large individual patient data meta-analysis to study the risk of death associated with hyponatraemia in HF-REF and in HF-PEF. This analysis included 14 766 patients from 22 studies that recruited patients without ejection fraction inclusion criterion at baseline and reported death from any cause. Cox proportional analysis was undertaken for hyponatraemia (sodium <135 mmol/L), adjusted for variables of clinical relevance, and stratified by study. The endpoint was death from any cause at 3 years. Patients with hyponatraemia (n = 1618) and patients with normal serum sodium had similar characteristics as regards to age, gender, and ischaemic aetiology. However, patients with hyponatraemia had higher New York Heart Association class and lower blood pressure. At follow-up, there were 335 deaths among 1618 patients with hyponatraemia (21%) and 2128 deaths among 13 148 patients with normal serum sodium (16%). The risk of death appeared to increase linearly with serum sodium levels <140 mmol/L. Hyponatraemia was identified in 1199 HF-REF patients (11%) and 419 HF-PEF patients (11%). Hyponatraemia was independently predictive of death in both HF-REF [adjusted hazard ratio (HR) 1.69, 95% confidence interval (CI) 1.50-1.91] and HF-PEF (adjusted HR 1.40, 95% CI 1.10-1.79, P for interaction 0.20). Hyponatraemia is a powerful determinant of mortality in patients with HF regardless of ejection fraction. Further work is needed to determine if correction of hyponatraemia translates into clinical benefit.

Prevalence and outcome of cirrhosis patients admitted to UK intensive care: a comparison against dialysis-dependent chronic renal failure patients: Reply to comments by Mason and Yeoman

Dear Editor, We thank Drs Mason and Yeoman for their comments on our paper [1] as these raise a number of very interesting points. However, we would challenge the statement that these points mitigate against our conclusions. As mentioned in the previous reply to Drs Berry and Thompson [2], we do not wish to be seen as champions of nihilism for patients with cirrhosis; rather, our pessimistic conclusions simply reflect the data presented. Indeed, despite improvements in many aspects of critical care over the last 20 years, ICU mortality rates associated with cirrhosis remain very high. We felt that it was time for a change in the message from ‘‘we must try harder’’ to something bolder. It is very hard to advocate continuing ICU care when mortality rates exceed 85–90 %, especially as the vast majority of patients will not be eligible for transplantation. We perhaps should have added a section about optimising pre-ICU care and feel the authors’ critical care bundle suggestion has considerable merit, although whether this would have a benefit on mortality rates remains of course uncertain. However, the suggestion that cirrhosis patients be admitted earlier to the ICU is simplistic and naive given that using Hospital Episode Statistic data we identified [100,000 patients admitted to UK hospitals 2010–2011 with complications of cirrhosis (http://www. hesonline.nhs.uk). As an alternative, we would suggest borrowing another approach from sepsis studies—that of early ‘‘goal-directed therapy’’ [3], either in the emergency room or on the acute admissions ward. Indeed, a recent study has demonstrated that delayed appropriate initial empiric antimicrobial therapy is associated with increased mortality in cirrhosis [4]. As we acknowledge in our paper, the comparison with renal replacement therapy is imperfect, and we again refer to this in our reply to Drs Berry and Thompson [2], However, this hardly mitigates against our conclusion that cirrhosis patients with organ failure have an extremely poor prognosis. Rather than labour this point, we would refer these authors to the very similar overall mortality (59.2 %) seen in patients with haematological malignancies admitted to ICU [5], as mentioned in our discussion; this is a group we hope that all will agree can be regarded as having a poor prognosis. We cannot agree that using the Intensive Care National Audit & Research Centre (ICNARC) database to examine the largest cohort of ICU admissions with liver cirrhosis reported to date can be regarded as a study weakness. We acknowledge in our discussion that neither the Acute Physiology and Chronic Health Evaluation II (APACHE II) nor ICNARC score contains information directly relating to liver failure and conclude that neither score can guide decision-making; however, the area under the receiver operating characteristic curve (AUROC) of 0.8 that is seen with the ICNARC score is comparable to that obtained using Sequential Organ Failure Assessment (SOFA) and Organ System Failure (OSF) models in other studies. Equally, the fact that these scores under-predicted mortality had not been reported before, and we thought it worthy of mention. Again, we do acknowledge in the paper that mortality associated with variceal bleeding has improved over time; as such, a breakdown of mortality associated with differing reasons for admission may have proved interesting. However, the key determinants of ICU mortality in patients with cirrhosis are sepsis and organ failure [6] and, therefore, the aim of the study was to examine these in detail.

Determinants of mortality in patients with traumatic brain injury.

We aimed to determine factors associated with mortality rates in patients with traumatic brain injury (TBI). Registered data of a national trauma project conducted in eight major cities in Iran during a five-year period were used. Patients with a TBI were identified and both univariate and multivariate analyses were performed. 2274 brain-injured patients including 1794 males (78.9%) were identified. The mean age of the patients was 30.1 ± 19.11 years. The age of 345 patients was less than 12, while 137 patients were older than 65. 383 patients (16.9%) died as a result of their injury. Univariate analysis showed a significant association between mortality and the following factors: age, sex, Glasgow Coma Scale (GCS), Injury Severity Score (ISS), systolic, diastolic and mean arterial blood pressure (BP), and respiratory rate (RR) (p<0.05).The logistic regression analysis revealed a statistically significant association between death and age (odds ratio [OR]=1.04), GCS (OR=0.59), ISS (OR=1.03), mean arterial BP (OR=0.71), and RR (OR=0.82) one-half hour after hospital arrival. Our results demonstrated that age, GCS, ISS, BP, and RR as prognostic factors in patients with TBI indicate those that need special care during the initial management in the emergency department.