Plasminogen activator inhibitor 1: a new prognostic marker in septic shock

The prognostic value of plasminogen activator inhibitor type 1 (PAI-1) in septic shock was investigated in 52 patients with septic shock. The patients had significantly elevated serum PAI-1 levels with respect to the control group (p = 0.002). In patients not having a rapidly fatal underlying disease, PAI-1 was significantly higher in patients dying within a week after onset of shock than in survivors (median PAI-1: 900 and 307 ng/ml, respectively; p = 0.001). The analysis of the distribution of PAI-1 levels permitted retrospectively to determine a threshold level of PAI-1 which had prognostic significance. Mortality was 71% in patients with serum PAI-1 above 550 ng/ml, whereas only two patients (6%) having a PAI-1 below 550 ng/ml died within a week. Thus, in patients with septic shock, PAI-1 appears to have a strong predictive value as to mortality. This early marker may help the clinician in identifying a subgroup of patients particularly at risk.     

Symptomatic unruptured capillary telangiectasia of the brain stem: report of three cases and review of the literature

OBJECTIVES: With increasing evidence that permanent tissue damage occurs early in the course of multiple sclerosis, it is important that treatment trials include patients in the earliest stages of the disease. For many patients with multiple sclerosis the first presentation is a clinically isolated syndrome. Not all patients with a clinically isolated syndrome develop multiple sclerosis, however, and treatment of all such patients would be unwarranted. A single abnormal brain MRI identifies patients at a higher risk for the early development of multiple sclerosis, but current criteria are limited by either poor specificity (T2 lesions) or sensitivity (contrast enhancing lesions). The aim of the study was to assess the positive predictive value, sensitivity, and specificity of MRI indices for the development of multiple sclerosis after 1 year from two MRI examinations obtained 3 months apart. METHODS: MRI examinations were performed in 68 patients with a clinically isolated syndrome, with a clinical assessment after 1 year. RESULTS: Contrast enhancing lesions at both time points were the most predictive indices for developing multiple sclerosis (positive predictive value 70%) but had low sensitivity (39%). The combination of T2 lesions at baseline with new T2 lesions at follow up had the best overall positive predictive value (53%), sensitivity (83%), and specificity (76%). In patients with T2 lesions at baseline, the presence or absence of new T2 lesions at follow up significantly altered the risk of multiple sclerosis within 1 year (55% and 5% respectively, p<0.001). Multiple sclerosis also developed in 10% of patients with a normal baseline MRI. CONCLUSIONS: Serial imaging in patients with clinically isolated syndromes improved the positive predictive value, sensitivity, and specificity of MRI for the development of early multiple sclerosis and also identified patients at a lower risk of early multiple sclerosis than would have been expected from their abnormal baseline MRI. Selection of patients with clinically isolated syndromes for therapeutic intervention or clinical trials may benefit from serial MRI, to target those at greatest risk of early development of multiple sclerosis.     

Use of soluble fibrin antigen instead of D-dimer as fibrin-related marker may enhance the prognostic power of the ISTH overt DIC score

The overt DIC score of the DIC subcommittee of the ISTH includes a fibrin-related marker (FRM) as indicator of intravascular fibrin formation. The type of marker to be used has not been specified, but D-dimer antigen, or fibrin degradation products are used by most investigators. Soluble fibrin complexes have been suggested as more specific indicators of acute intravascular fibrin formation. The aim of the present study was to compare the predictive value of the overt DIC score concerning clinical outcome in a surgical intensive care cohort, using either D-dimer antigen, or soluble fibrin antigen as FRM. The cutoff values for 2 and 3 score points for the FRM were assigned on the basis of the 25% and 75% quartiles of 1870 plasma samples obtained from 359 ICU patients during a period of 6 months. For 331 patients with complete diagnostic workup and day 1 blood samples, the Iatro SF as FRM component of the overt DIC score displayed the highest prognostic power concerning clinical outcome. The 28-day mortality of patients with overt DIC at day 1, using Iatro SF as FRM assay was 50.0%, whereas 28-day mortality of patients without overt DIC was 14.0% (p <0.0001). Using MDA D-dimer, and TINAquant D-dimer, 28-day mortality was between 35.5% and 39.3% in patients with overt DIC, and 15.5% to 15.6% in patients without overt DIC. Selection of the FRM as component of the DIC score has a small, but relevant impact on the prognostic performance of the overt DIC score. The present data on the distribution of values may provide a basis for the selection of appropriate cutoff points for assigning 2, and 3 points in the score.     

Predictive clinical factors of very early in-hospital mortality in subarachnoid hemorrhage.

This study was conducted to determine clinical predictors of very early in-hospital mortality (within the first 72 h) in patients with non-traumatic subarachnoid hemorrhage. Data of 184 patients with subarachnoid hemorrhage were obtained from consecutive stroke patients included in the prospective Barcelona Stroke Registry. Demographic, anamnestic, clinical, neurological and neuroimaging variables in the subgroup of patients who died within 72 h after the onset of symptoms were compared with those in the subgroup of patients that had survived this initial period. The independent predictive value of each variable on the development of very early death was assessed with a logistic regression analysis. Very early in-hospital death was observed in 18 patients (9.8%). These patients were significantly more likely to have progressive deficit, seizures, altered consciousness, limb weakness, sensory involvement and basal ganglia hematoma than patients without very early death. After multivariate analysis, only progressive deficit (odds ratio (OR) 6.90; 95% confidence interval (95% CI) 2-23.80) and limb weakness (OR 5.46; 95% CI 1.78-16.77) were independent clinical predictors of very early mortality. Progressive neurological deficit and limb weakness at the onset of stroke was independent predictive factors of very early death in patients with non-traumatic subarachnoid hemorrhage. These results further emphasize the need to establish an early etiological diagnosis and to manage these patients aggressively including early surgery in selected cases.     

Early inhibition of activated fibrinolysis predicts microbial infection, shock and mortality in febrile medical patients

To evaluate the contribution of an imbalance between coagulation activation and fibinolysis activation and inhibition to morbidity and mortality in sepsis, we determined in medical hospitalized patients at inclusion (day 0) for fever (temperature above 38.0 degrees C axillary or 38.3 degrees C rectally), and daily thereafter for two days, circulating thrombin-antithrombin III (TAT) complexes, plasmin-alpha2-antiplasmin (PAP) complexes (day 0 only), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and interleukin (IL)-6, the latter as a marker of the inflammatory host response. Study variables were 1) positive microbiological results for specimens from local sites associated with a clinical infection, positive blood cultures (including parasitemia) or both, within 7 days after inclusion, 2) development of shock, i.e. systolic blood pressure <90 mmHg or a reduction of 40 mmHg from baseline within 7 days after inclusion, and 3) death related to febrile illness within 28 days after inclusion. The peak plasma levels of TAT complexes were elevated in 44% and the PAP complexes in all patients. The t-PA and PAI-1 levels were elevated in 74 and 94% of patients, respectively. Values for TAT and PAP did not differ among subgroups, while peak t-PA and IL-6 levels were higher in patients with positive microbiological results, developing shock or ultimately dying than in those without the complications (p<0.005). Peak PAI-1 levels were elevated in patients developing shock and ultimate death versus those with an uncomplicated course (p <0.05). Peak IL-6 related to PAI-1 and t-PA levels, which interrelated. Patients with elevated TAT levels had increased plasma levels of IL-6, PAP, PAI-1 and t-PA versus those with normal TAT (p <0.05). Our data indicate that inhibition of activated fibrinolysis, which may partly depend on both cytokinemia and activation of coagulation, predicts microbial infection, septic shock and mortality of febrile medical patients. This suggests an early pathogenic role of inhibition of activated fibrinolysis in the downhill course of serious microbial infection.     

Risk factors for psychosis in an ultra high-risk group: psychopathology and clinical features

The identification of individuals at high risk of developing a psychotic disorder has long been a goal of clinicians because it is thought that early treatment of this group may prevent onset of the disorder. However, little is known of predictive factors of psychosis, even within a high-risk group. This study followed up 104 young people thought to be at 'ultra high risk' for schizophrenia and other psychotic disorders by virtue of having a family history of psychotic disorder combined with some functional decline or the presence of subthreshold or self-limiting psychotic symptoms. All subjects were therefore symptomatic, but not psychotic, at intake. Thirty-six subjects (34.6%) developed frank psychotic symptoms within 12 months. Measures of symptom duration, functioning, disability and psychopathology were made at intake, 6 and 12 months. Poor functioning, long duration of symptoms, high levels of depression and reduced attention were all predictors of psychosis. A combination of family history of psychosis, a recent significant decrease in functioning and recent experience of subthreshold psychotic symptoms was also predictive of psychosis. Combining highly predictive variables yielded a method of psychosis prediction at 12 months with good positive predictive value (80.8%), negative predictive value (81.8%) and specificity (92.6%) and moderate sensitivity (60.0%). Within our symptomatic high-risk group, therefore, it appears possible to identify those individuals who are at particularly high risk of developing a psychotic disorder such as schizophrenia. Given the very high PPV and low false positive rate with this two-step process, it may be justifiable to target these individuals for intensive monitoring of mental state and even low-dose neuroleptic medication or other biological and psychosocial treatments depending on clinical condition. This indicated prevention approach could be further developed and preventive strategies in the psychoses refined.     

Prognostic factors of early outcome and discharge status in patients undergoing surgical intervention following traumatic intracranial hemorrhage

Over the past several decades, the rate of traumatic brain injury (TBI)-related emergency room visits in the United States has steadily increased, yet mortality in these patients has decreased. This improvement in outcome is largely due to advances in prehospital care, intensive care unit management, and the effectiveness of neurosurgical procedures, such as decompressive craniectomies. It is imperative to identify clinical factors predictive of patients who benefit from early mobilization of resources and operative treatment. Equally important is the identification of patients with good prognostic signs among patients receiving surgical intervention for TBI. We conducted a retrospective chart review of 181 patients requiring craniectomies and craniotomies for decompression or evacuation of an intracranial hemorrhage following TBI at a single level I trauma center between 2008-2010. Demographic features and perioperative clinical characteristics of these patients were examined in relation to favorable outcomes, defined as discharge to home or a rehabilitation facility, and unfavorable outcomes, defined as in-hospital mortality or discharge to step-down medical facilities. Younger age, greater Glasgow Coma Scale (GCS) score on admission, absence of preoperative coagulopathies, absence of hypernatremia, and absence of fever were all independent predictors of favorable outcome. Additionally, increased operative duration and increased length of hospital stay were identified as independent predictors of negative outcomes after surgery. This work supports some of the current prognostic models in the literature and identifies additional clinical variables with predictive value of early outcome and discharge status in patients undergoing surgical evacuation of traumatic intracranial hemorrhages.     

Serum C-reactive protein and lipid hydroperoxides in predicting short-term clinical outcome after spontaneous intracerebral hemorrhage

There is no effective treatment for spontaneous intracerebral hemorrhage (sICH). We examined 46 patients with sICH within 48 hours after onset of symptoms, aiming to assess the predictive value of C-reactive protein (CRP) and lipid hydroperoxides (ROOH) on “first-week mortality” and “clinical outcome at discharge” by binary logistic regression. We found that serum CRP and hematoma volume were predictors of short-term mortality. Although serum ROOH level was positively correlated with mortality, it did not predict early lethal outcome. Serum ROOH concentration, however, was a predictor of poor clinical outcome in sICH survivors. After confirmation of the results obtained through observing a larger group of patients, an oxidative stress marker could be used as an additional criterion for patient stratification, especially when severe disability is expected and supplementary therapeutic approaches are urgent.     

Benefit/risk profile of high-dose antithrombin in patients with severe sepsis treated with and without concomitant heparin

A randomised, prospective, placebo-controlled phase III multicentre clinical trial (KyberSept) has been performed to test the efficacy of high-dose antithrombin therapy in patients with severe sepsis. Concomitant low-dose heparin has been routinely given in two thirds of patients for deep vein thrombosis prophylaxis. This study analyses heparin - antithrombin interactions in terms of long-term mortality, adverse events, and thromboembolic events. From a total of 2,314 patients with severe sepsis (placebo: n = 1,157; antithrombin: n = 1,157) 1,616 patients (placebo: 811, antithrombin: 805) received heparin concomitantly with study drug (antithrombin 30,000 IU) over four days, whereas 698 patients (346 and 352, respectively) did not. In patients with no concomitant heparin, 28-day mortality was lower with antithrombin than with placebo (37.8% vs. 43.6%; absolute reduction: 5.8%; risk ratio: 0.860 [0.725-1.019]), which increased until day-90 (44.9% vs. 52.5%; absolute reduction: 7.6%; risk ratio: 0.851 [0.735-0.987]). In patients with concomitant heparin, no effect of antithrombin on mortality was seen (28-day mortality: 39.4% vs. 36.6%; absolute increase: 2.8%; risk ratio: 1.08 [0.96-1.22]). Frequency of use of concomitant heparin increased during conduct of the study. Increased bleeding incidences were reported with antithrombin plus concomitant heparin as compared to antithrombin alone. Rates of thromboembolic events were similar when antithrombin was given with or without concomitant heparin. In the treatment of severe sepsis, high-dose antithrombin may sufficiently protect against development of venous thromboembolism when no concomitant heparin is given. Combined administration of the two increases bleeding risk and probably abolishes efficacy of antithrombin.     

Rate of stroke recurrence in patients with primary intracerebral hemorrhage

BACKGROUND AND PURPOSE: Primary intracerebral hemorrhage (PICH) is a devastating illness with high early mortality. Hypertension is a major risk factor both for ischemic cerebrovascular disease and for intracranial hemorrhage. Survivors of PICH are at risk for both recurrent hemorrhage and ischemic cerebrovascular disease. We sought to determine the rate of recurrence of ICH or cerebral ischemia in a cohort of PICH patients at the Toronto Hospital, Toronto, Canada. METHODS: A retrospective search of computerized hospital records from 1986 to 1996 for patients with a discharge diagnosis of intracerebral hemorrhage (International Classification of Diseases, Ninth Revision-Clinical Modification [ICD-9-CM] code 431) was conducted to identify the index cases. Charts were abstracted for demographic and clinical characteristics. CT scans, MR scans, or radiologist reports were reviewed. To determine recurrence, the database was linked to the Ontario Provincial Government Vital Statistics Registry and to the Canadian Institute for Health Information database of hospital discharge abstracts. Logistic regression analysis was used to identify predictive factors for mortality after PICH. A Cox proportional hazards model was fitted to identify predictive factors for recurrent ICH or stroke. RESULTS: A total of 746 charts were identified by computer search. After abstraction, 423 index patients with PICH were identified. Of these, 27.4% died in the first 30 days of their admission. Predictors of death were age, intraventricular rupture of hemorrhage, and trilobar hemorrhage. The recurrence rate for PICH was 2.4% (95% CI 1.4% to 3. 9%) per year, whereas the recurrence rate for ischemic cerebrovascular disease was 3.0% (95% CI 1.8% to 4.7%) per year. The only significant predictor of readmission for ICH was lobar location of the index hemorrhage, with a hazard ratio of 3.8 (95% CI 1.2 to 12.0). CONCLUSIONS: PICH has a high 30-day mortality rate. Survival from the initial insult portends a moderate risk of recurrence of 2. 4% per year for PICH and 3.0% per year for ischemic cerebrovascular disease. Patients with PICH are at risk for both ischemic stroke or TIA and recurrent hemorrhage; thus, PICH may be a marker for ischemic stroke. Patients with lobar hemorrhage have a 3.8-fold increased risk of recurrent ICH.     

Progressive Lacunar Strokes: A Predictive Score

Background and PurposeProgressive lacunar syndromes (PLS) occur in up to 20-30% of patients with lacunar strokes, increasing the risk of long term dependency. Our aim is to develop a predictive score to identify patients at high risk of presenting PLS.MethodsWe derived a risk score for PLS in a cohort of consecutive patients (n=187) presenting with one of the five classic lacunar syndromes (LS) and absence of vascular occlusion, perfusion deficit or symptomatic stenosis. A risk score was developed using the coefficients from the logistic regression model, and receiver operating characteristic (ROC) analysis was conducted to assess the prognostic value of the risk score. Sensitivity, specificity and accuracy were estimated for each total point score.ResultsOut of 187 patients included in our sample, 52 (27.8%) presented PLS. Previous history of diabetes mellitus (1 point), diastolic blood pressure at admission (2 points), clinical deficits consistent with a pure motor syndrome (1 point) and asymptomatic intracranial atheromatosis or stenosis in non-symptomatic territory (1 point) were independent predictors for PLS. The estimated area under the ROC curve for this model was 0.77 (95% CI,0.68 - 0.84).ConclusionThis score could be a useful tool in routine clinical practice to predict the occurrence of PLS, allowing the identification of those patients with LS who are at high risk of long term dependency due to early neurological worsening, and who would benefit the most from an intensive treatment.     

基本临床及实验室资料在成人结核性脑膜炎中的诊断价值

目的 以基本的临床及实验室资料为基础寻找成人结核性脑膜炎和新型隐球菌性脑膜炎的鉴别点,并建立相应诊断规则.方法 实验对象为中山大学附属第三医院2000年～2008连续住院的成人患者,包括100例结核性脑膜炎患者及119例新型隐球菌性脑膜炎患者,并分析其基本的临床及实验室资料.运用logistic回归分析寻找可独立预测结核性脑膜炎的危险因素,并建立相应的诊断规则.结果 Logistic回归分析得出六项可独立预测结核性脑膜炎的危险因素:性别、神志改变、视听损害、脑脊液蛋白、脑脊液白细胞数及合并颅外结核.利用上述因素建立的诊断规则其诊断结核性脑膜炎的灵敏度为78.0%,特异度为95.2%,阳性预测价值92.9%,阴性预测价值84.4%.结论 基本的临床及实验室资料有助于帮助鉴别结核性脑膜炎和新型隐球菌性脑膜炎,可在实验室条件不够完善的广大基层医院应用.     

Evaluating the performance of machine learning methods for risk estimation of delirium in patients hospitalized from the emergency department

Introduction

Delirium is a cerebral dysfunction seen commonly in the acute care setting. It is associated with increased mortality and morbidity and is frequently missed in the emergency department (ED) and inpatient care by clinical gestalt alone. Identifying those at risk of delirium may help prioritize screening and interventions in the hospital setting.

Objective

Our objective was to leverage electronic health records to identify a clinically valuable risk estimation model for prevalent delirium in patients being transferred from the ED to inpatient units.

Methods

This was a retrospective cohort study to develop and validate a risk model to detect delirium using patient data available from prior visits and ED encounter. Electronic health records were extracted for patients hospitalized from the ED between January 1, 2014, and December 31, 2020. Eligible patients were aged 65 or older, admitted to an inpatient unit from the emergency department, and had at least one DOSS assessment or CAM-ICU recorded within 72 h of hospitalization. Six machine learning models were developed to estimate the risk of delirium using clinical variables including demographic features, physiological measurements, medications administered, lab results, and diagnoses.

Results

A total of 28,531 patients met the inclusion criteria with 8057 (28.4%) having a positive delirium screening within the outcome observation period. Machine learning models were compared using the area under the receiver operating curve (AUC). The gradient boosted machine achieved the best performance with an AUC of 0.839 (95% CI, 0.837–0.841). At a 90% sensitivity threshold, this model achieved a specificity of 53.5% (95% CI 53.0%–54.0%) a positive predictive value of 43.5% (95% CI 43.2%–43.9%), and a negative predictive value of 93.1% (95% CI 93.1%–93.2%). A random forest model and L1-penalized logistic regression also demonstrated notable performance with AUCs of 0.837 (95% CI, 0.835–0.838) and 0.831 (95% CI, 0.830–0.833) respectively.

Conclusion

This study demonstrated the use of machine learning algorithms to identify a combination of variables that enables an estimation of risk of positive delirium screens early in hospitalization to develop prevention or management protocols.     

入院血清乳酸水平在重型颅脑损伤早期死亡风险评估中的价值

目的 探讨入院血清乳酸水平在重型颅脑损伤（sTBI）早期死亡风险评估中的价值。方法 回顾性分析2017年6月至2021年5月收治的287例sTBI的临床资料。早期死亡指伤后1周内死亡,1周内放弃治疗自动出院也视为早期死亡。结果 287例sTBI中,早期死亡103例,早期病死率为35.89%;存活184例。早期死亡病人入院血清乳酸水平[6.5(4.7～9.0)mmol/L]明显高于存活病人[4.0(2.63～5.5)mmol/L;P<0.05]。多因素logistic回归分析显示,入院血清乳酸水平增高是sTBI早期死亡的独立危险因子（P<0.001）。ROC曲线分析显示,入院血清乳酸水平预测早期死亡的曲线下面积为0.765(95%CI 0.711～0.820),最佳截断值为5.25 mmol/L,灵敏度及特异度分别为70.9%、71.7%。结论 入院血清乳酸水平增高,sTBI早期死亡风险明显增加。这提示入院血清乳酸水平可作为sTBI早期死亡风险的评估指标。     

Validation of a risk score identifying patients with acute pulmonary embolism, who are at low risk of clinical adverse outcome

A clinical predictive model that accurately identifies patients with pulmonary embolism who are at low risk of adverse medical outcomes may be useful for management decisions, such as outpatient treatment. We aimed to externally validate a previously derived prognostic score identifying emergency ward patients with acute pulmonary embolism at low risk of 3-month complications. One hundred and ninety-nine consecutive patients with proven pulmonary embolism were included from the emergency centres of three teaching and general hospitals. Adverse outcomes, such as death, major bleed, or recurrent venous thromboembolism, were recorded during a 3-month follow-up. We retrospectively computed the prognostic score for each patient and determined its predictive accuracy at different threshold values. The overall 3-month risk of adverse event after the diagnosis of pulmonary embolism was 9.5%. At a threshold of 2 points, eight patients with scores at or below the cut-off (5%; 95% CI 2.6-9.6) and 11 patients with scores above this cut-off (27.5%; 95% CI 16.1-42.8) presented a complication. The negative predictive value for an adverse out-come was 95.0% (95% CI 90.4-97.4). The receiver operating characteristic curve derived from the score distribution had an area of 0.77 (95% CI 0.65-0.89). This compared favourably with the characteristics of the derivation study. We conclude that the Geneva risk score has an acceptable predictive accuracy to identify patients with pulmonary embolism at low risk for 3-month adverse outcomes. Whether this score remains accurate and useful in clinical practice should be determined in a prospective multicentre validation study.     

Prospective validation of the Pulmonary Embolism Severity Index. A clinical prognostic model for pulmonary embolism

Practice guidelines recommend outpatient care for selected patients with non-massive pulmonary embolism (PE), but fail to specify how these low-risk patients should be identified. Using data from U.S. patients, we previously derived the Pulmonary Embolism Severity Index (PESI), a prediction rule that risk stratifies patients with PE. We sought to validate the PESI in a European patient cohort. We prospectively validated the PESI in patients with PE diagnosed at six emergency departments in three European countries. We used baseline data for the rule's 11 prognostic variables to stratify patients into five risk classes (I-V) of increasing probability of mortality. The outcome was overall mortality at 90 days after presentation. To assess the accuracy of the PESI to predict mortality, we estimated the sensitivity, specificity, and predictive values for low- (risk classes I/II) versus higher-risk patients (risk classes III-V), and the discriminatory power using the area under the receiver operating characteristic (ROC) curve. Among 357 patients with PE, overall mortality was 5.9%, ranging from 0% in class I to 17.9% in class V. The 186 (52%) low-risk patients had an overall mortality of 1.1% (95% confidence interval [CI]: 0.1-3.8%) compared to 11.1% (95% CI: 6.8-16.8%) in the 171 (48%) higher-risk patients. The PESI had a high sensitivity (91%, 95% CI: 71-97%) and a negative predictive value (99%, 95% CI: 96-100%) for predicting mortality. The area under the ROC curve was 0.78 (95% CI: 0.70-0.86). The PESI reliably identifies patients with PE who are at low risk of death and who are potential candidates for outpatient care. The PESI may help physicians make more rational decisions about hospitalization for patients with PE.     

Verbal fluency predicts mortality in Alzheimer disease.

OBJECTIVES: To assess the predictive value of neuropsychologic profiles, at diagnosis, for mortality in incident Alzheimer disease (AD). BACKGROUND: Rate of AD progression varies significantly across individuals for reasons that are not well understood. Several studies have linked rapid decline with disproportionately impaired executive functioning, presumably reflecting greater impairment of frontal networks. To the extent that differential neuropsychologic profiles reflect various neuropathologic presentations of AD, such profiles may inform survival estimates early in the disease. METHODS: Five neuropsychologic indices were used to characterize performance in 161 individuals at diagnosis of AD during a 15-year, longitudinal, primarily community-based study. RESULTS: Fifty-two percent of participants reached the mortality end point with a median survival of 5.52 years (95% confidence interval, 4.41-6.63). Cox proportional hazards analyses indicated that older age at diagnosis was associated with higher risk of mortality (risk ratios, 1.08; 95% confidence interval, 1.04-1.12) whereas Hispanic ethnicity predicted lower mortality [0.22 (0.09-0.55)]. Controlling for these 2 demographic variables, higher verbal fluency scores at diagnosis predicted lower mortality [0.69 (0.49-0.96)]. CONCLUSIONS: Disproportionate impairment of both category and letter fluency at the earliest stages of AD predicts mortality. The prognostic value of these tests may derive from their general psychometric properties, or may reflect the measures' sensitivity to an early or critical level of compromise to frontal networks.     

Use of antiplatelet agents in sepsis: A glimpse into the future

As mechanisms of sepsis pathophysiology have been elucidated with time, sepsis may be considered nowadays, as an uncontrolled inflammatory and pro-coagulant response to a pathogen. In this cascade of events, platelets play a key role, via interaction with endothelial cells and modulation of both innate and adaptive immune system. In that manner, inhibition of platelet function could represent a useful tool for attenuating inflammatory response and improving outcomes. Data on current antiplatelet agents, including acetylsalicylic acid, P2Y12 inhibitors and GPIIb/IIIa antagonists, in animal models are promising. Clinical data in patients hospitalized for pneumonia, at risk for acute lung injury, and/or critically ill revealed an association between antiplatelet therapy and reduction in both short-term mortality and prevalence of acute lung injury, as well as, the need for intensive care unit admission, without a concomitant increased bleeding risk. In need of innovative approach in the treatment of sepsis, further prospective, interventional, randomized trials are pivotal to establish potential use of antiplatelet agents in this context.     

Predictors of survival and functional outcome in acute stroke patients admitted to the stroke intensive care unit

Multivariate models have not been widely used to predict the outcome of acute stroke patients admitted to the intensive care unit (ICU). The purpose of this study was to determine potential measures observed in the first 12 h post-stroke that predict early mortality and functional outcomes in ICU-admitted stroke patients. Eight hundred and fifty acute stroke patients (ischemic stroke, 508; intracerebral hemorrhage, 342) were included in this analysis between November 2002 and December 2006. Measures of interest were obtained in the first 12 h after onset of stroke were analyzed for three types of outcome: 3-month mortality, 3-month mortality or institutional care, and poor functional outcomes at discharge. Poor functional outcomes were defined as a Barthel index <80 or a Rankin scale >2. Multivariate regression models were used to determine the predictive value of the observed measures. After 3 months, 17% of patients had died; 21% were alive but being cared for in institutional settings; and 62% were alive and living at home. Functional status at discharge indicated 16% of patients had died, poor function in 50%, and good function in 34% of patients. Initial stroke severity, measured by National Institute of Health Stroke Scale, and dependence on a ventilator predicts 3-month mortality and poor outcome in all stroke patients. In addition, old age, previous stroke, and total anterior circulatory infarct were associated with poor outcome in ischemic stroke patients; old age, low body mass index and the presence of intraventricular hemorrhage were associated with poor outcomes in intracerebral hemorrhage patients. In conclusion, early stroke mortality and outcome at discharge can be predicted in the first few hours following an acute stroke for moderate to severe ICU-admitted stroke patients.     

Adverse events during medical and surgical hospitalizations for persons with schizophrenia

CONTEXT: Persons with schizophrenia have a high risk of premature mortality. It is not clear if greater risk for adverse events during hospitalization is a contributing factor. OBJECTIVES: To estimate the prevalence of adverse events in medical and surgical hospitalizations for persons with schizophrenia compared with those for persons without schizophrenia and to examine the relation between adverse events and intensive care unit admission, in-hospital death, length of stay, and total charges for hospitalizations for persons with schizophrenia. DESIGN: Cross-sectional study. SETTING: We studied discharges from all Maryland acute care hospitals' medical and surgical services in 2001 and 2002.Patients There were 1746 medical and surgical hospitalizations for adults with a secondary diagnosis of schizophrenia and 732 158 for adults without schizophrenia. MAIN OUTCOME MEASURES: For primary outcomes, we applied the Agency for Healthcare Research and Quality's Patient Safety Indicators (PSIs), which were developed to detect adverse events in administrative data. We compared PSIs for hospitalizations for patients with a secondary diagnosis of schizophrenia with those for patients without and determined the association between schizophrenia and each PSI adjusting for patient and hospital characteristics. For hospitalizations for patients with schizophrenia, for secondary outcomes we examined the association between each PSI and intensive care unit admission, in-hospital death, length of stay, and total charges. RESULTS: Hospitalizations for patients with schizophrenia had the following higher adjusted relative odds of having PSIs compared with those for patients without schizophrenia: infections due to medical care (odds ratio [OR], 2.49 [95% confidence interval (CI), 1.28 to 4.88]); postoperative respiratory failure (OR, 2.08 [95% CI, 1.41 to 3.06]); postoperative deep venous thrombosis (OR, 1.96 [95% CI, 1.18 to 3.26]); and postoperative sepsis (OR, 2.29 [95% CI, 1.49 to 3.51]). For hospitalizations for patients with schizophrenia, having respiratory failure or sepsis resulted in at least twice the adjusted odds for intensive care unit admission and death. The median adjusted increase in length of stay was at least 10 days, and median hospital charges were elevated by at least $20 000 for infections due to medical care, respiratory failure, deep venous thrombosis, and sepsis. CONCLUSIONS: Medical and surgical hospitalizations for persons with schizophrenia had at least twice the odds of several types of adverse events than those for persons without schizophrenia. These adverse events were associated with poor clinical and economic outcomes during the hospital admission. Efforts to reduce these adverse events should become a research priority.