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Fatal Events (fatal + event)

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Medical Sciences	90%

Selected Abstracts

Safety update on the use of recombinant factor VIIa and the treatment of congenital and acquired deficiency of factor VIII or IX with inhibitors

HAEMOPHILIA, Issue 5 2008
T. ABSHIRE
Summary., Recombinant factor VIIa (rFVIIa, NovoSeven®) has been licensed for treatment of haemophilia with inhibitors in Europe since 1996 and in North America since 1999. Overall, approximately 1.5 million doses have since been administered. Safety data from licensure to April 2003 revealed 25 thromboembolic (TE) adverse events (AE) from over 700 000 doses given, a remarkably low incidence of TE events. Recent reports have cited a higher prevalence of TE events with rFVIIa use, especially when used off-label. This report reviews the TE and fatal events with use of rFVIIa for congenital and acquired haemophilia A or B from May 2003 to December 2006. Approximately 800 000 standard doses of rFVIIa have been administered during this time frame. All clinical trials, spontaneous and solicited reports, as well as a detailed literature review, were included in the data analysis. There were a total of 30 TE events and 6 TE-associated fatal events. Spontaneous reports captured 14/71 (20%) TE/AE and 2/34 TE-associated/total fatal events. From solicited reports, 5/40 (12.5%) were associated with a TE and 1/32 TE-associated fatal events. Literature review revealed 11/19 (58%) TE events and 3/6 TE-associated fatal events. Despite the use of high-dose rFVIIa (270 ,g kg,1) in some clinical trials and registries, rFVIIa appears safe, when used for congenital and acquired haemophilia. The prevalence of TE associated with rFVIIa use is less than 4/100 000 and a TE-associated fatal event is also extremely rare. However, use of rFVIIa for off-label indications should continue to be monitored closely via clinical trials and carefully designed registries. [source]

Gene therapy for haemophilia,yes, but,with non-viral vectors?

HAEMOPHILIA, Issue 3 2009
A. LIRAS
Summary., High-purity plasma-derived and recombinant factors are currently safe and efficient treatment for haemophilia. The mid-term future of haemophilia treatment will involve the use of modified recombinant factors to achieve advantages such as decreased immunogenicity in inhibitor formation and enhanced efficacy as a result of their longer half-life. In the long-term, gene therapy and cell therapy strategies will have to be considered. Achievements in cell therapy to date have been using embryonic stem cells and hepatic sinusoidal endothelial cells. Current gene therapy strategies for haemophilia are based on gene transfer using adeno-associated viruses and non-viral vectors. Gene therapy for haemophilia is justified because it is a chronic disease and because a very regular factor infusion is required that may involve fatal risks and because it is very expensive. Haemophilia is a very good candidate for use of gene therapy protocols because it is a monogenic disease, and even low expression is able to achieve reversion from a severe to a moderate phenotype. The current trends in haemophilia using adeno-associated viral vectors are safe but also involve immunogenicity problems. The other alternatives are non-viral vectors. There have been in recent years relevant advances in non-viral transfection that raise hope for considering this possibility. Several research groups are opting for this experimental alternative. An expression over 5%, representing a moderate phenotype, for a few months with a high safety, regarding vector, transfected cells, and implantation procedure, would already be a great success. This may represent an intermediate protocol in which the expression levels and times obtained are lower and shorter respectively as compared to viral vectors, but which provide a potential greater patient safety. This may more readily win acceptance among both patients and haematologists because fatal events in the past due to HIV/HCV infection may constrain the implementation of viruses as vectors. [source]

Safety update on the use of recombinant factor VIIa and the treatment of congenital and acquired deficiency of factor VIII or IX with inhibitors

Patterns of Transnational Terrorism, 1970,1999: Alternative Time-Series Estimates

INTERNATIONAL STUDIES QUARTERLY, Issue 2 2002
Walter Enders
Using alternative time-series methods, this paper investigates the patterns of transnational terrorist incidents that involve one or more deaths. Initially, an updated analysis of these fatal events for 1970,1999 is presented using a standard linear model with prespecified interventions that represent significant policy and political impacts. Next, a (regime-switching) threshold autoregressive (TAR) model is applied to this fatality time series. TAR estimates indicate that increases above the mean are not sustainable during high-activity eras, but are sustainable during low-activity eras. The TAR model provides a better fit than previously tried methods for the fatality time series. By applying a Fourier approximation to the nonlinear estimates, we get improved results. The findings in this study and those in our earlier studies are then applied to suggest some policy implications in light of the tragic attacks on the World Trade Center and the Pentagon on September 11, 2001. [source]

Agreement Between Nosologist and Cardiovascular Health Study Review of Deaths: Implications of Coding Differences

JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 1 2009
Diane G. Ives MPH
OBJECTIVES: To compare nosologist coding of underlying cause of death according to the death certificate with adjudicated cause of death for subjects aged 65 and older in the Cardiovascular Health Study (CHS). DESIGN: Observational. SETTING: Four communities: Forsyth County, North Carolina (Wake Forest University); Sacramento County, California (University of California at Davis); Washington County, Maryland (Johns Hopkins University); and Pittsburgh, Pennsylvania (University of Pittsburgh). PARTICIPANTS: Men and women aged 65 and older participating in CHS, a longitudinal study of coronary heart disease and stroke, who died through June 2004. MEASUREMENTS: The CHS centrally adjudicated underlying cause of death for 3,194 fatal events from June 1989 to June 2004 using medical records, death certificates, proxy interviews, and autopsies, and results were compared with underlying cause of death assigned by a trained nosologist based on death certificate only. RESULTS: Comparison of 3,194 CHS versus nosologist underlying cause of death revealed moderate agreement except for cancer (kappa=0.91, 95% confidence interval (CI)=0.89,0.93). kappas varied according to category (coronary heart disease, kappa=0.61, 95% CI=0.58,0.64; stroke, kappa=0.59, 95% CI=0.54,0.64; chronic obstructive pulmonary disease, kappa=0.58, 95% CI=0.51,0.65; dementia, kappa=0.40, 95% CI=0.34,0.45; and pneumonia, kappa=0.35, 95% CI=0.29,0.42). Differences between CHS and nosologist coding of dementia were found especially in older ages in the sex and race categories. CHS attributed 340 (10.6%) deaths due to dementia, whereas nosologist coding attributed only 113 (3.5%) to dementia as the underlying cause. CONCLUSION: Studies that use only death certificates to determine cause of death may result in misclassification and potential bias. Changing trends in cause-specific mortality in older individuals may be a function of classification process rather than incidence and case fatality. [source]

Cause of Death in Older Patients with Anatomo-Pathological Evidence of Chronic Bronchitis or Emphysema: A Case-Control Study Based on Autopsy Findings

JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 5 2001
Jean Paul Janssens MD
OBJECTIVES: To determine the most frequent causes of death of hospitalized older patients based on anatomo-pathological evidence and to compare the relative frequency of fatal events between patients with and without evidence of either chronic bronchitis (CB) or emphysema (E). DESIGN: Retrospective, case-control study based on a computerized database including anatomo-pathological data of patients deceased and autopsied over a 25-year period. SETTING: Two geriatric hospitals in Geneva. PARTICIPANTS: Not applicable. MEASUREMENTS: Autopsy records for cause(s) of death in patients with CB or E. RESULTS: 3,685 patients deceased in our institution (1,540 men; 2,145 women) were autopsied between 1972 and 1996; mean age at death was 81.5 ± 8.0 years. Anatomo-pathological evidence of CB or E was found in 983 patients (26.6% of total); 262 (7.2%) had predominantly CB, and 456 (12.3%) predominantly E. Pneumonia was the most frequent cause of death in all patients (21.8%). Myocardial infarction (MI) (17.6% vs 14%), and respiratory failure (5.1% vs 1.5%) occurred more frequently in subjects with CB and/or E than in controls. Fatal pulmonary embolism (PE) was more frequent in patients with E (18.4%) than in patients with CB (10.7%; odds ratio (OR) = 1.89, P = .008), or in controls (12.7%; OR = 1.56, P = .0008). CONCLUSION: Anatomo-pathological evidence of CB or E is highly prevalent in older patients, suggesting that CB and E are clinically underdiagnosed in this age group. Fatal MI occurred significantly more frequently in older patients with E or CB than in controls. Furthermore, patients with E were at significantly higher risk of fatal PE than patients with CB or controls. [source]

Clinical Course and Risk Stratification of Patients Affected with the Jervell and Lange-Nielsen Syndrome

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 11 2006
ILAN GOLDENBERG M.D.
Introduction: Data regarding risk factors and clinical course of patients affected with Jervell and Lange-Nielsen syndrome (JLNS), an autosomal recesssive form of the congenital long-QT syndrome (LQTS), are limited to several reported cases and a retrospective analysis. Methods and Results: We prospectively followed-up 44 JLNS patients from the U.S. portion of the International LQTS Registry and compared their clinical course with 2,174 patients with the phenotypically determined dominant form of LQTS (Romano-Ward syndrome [RWS]) and a subgroup of 285 patients with type 1 LQTS (LQT1). Mean (±SD) corrected QT interval (QTc) in the JLNS, RWS, and LQT1 groups were 548 ± 73, 500 ± 48, and 502 ± 46 msec, respectively (P < 0.001). The cumulative rates of cardiac events from birth through age 40 among JLNS and RWS patients were 93% (mean [±SD] age: 5.0 ± 7.0 years) and 54% (mean [±SD] age: 14.2 ± 9.3 years), respectively (P < 0.001). The JLNS:RWS and JLNS:LQT1 adjusted hazard ratios (HR) for cardiac events were highest among patients with a baseline QTc ,550 msec (HR = 15.83 [P < 0.001] and 13.80 [P < 0.001], respectively). Among JLNS patients treated with beta-blockers, the cumulative probability of LQTS-related death was 35%; defibrillator therapy was associated with a 0% mortality rate during a mean (±SD) follow-up period of 4.9 ± 3.4 years. Conclusions: Patients with JLNS experience a high rate of cardiac and fatal events from early childhood despite medical therapy. Defibrillator therapy appears to improve outcome in this high-risk population, although longer follow-up is needed to establish its long-term efficacy. [source]

Reduced lung function predicts increased fatality in future cardiac events.

JOURNAL OF INTERNAL MEDICINE, Issue 6 2006
A population-based study
Abstract. Objective., Moderately reduced lung function in apparently healthy subjects has been associated with incidence of coronary events. However, whether lung function is related to the fatality of the future events is unknown. This study explored whether reduced forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) in initially healthy men is related to the fatality of the future coronary events. Design., Prospective cohort study. Setting., Population-based study from Malmö, Sweden. Subjects., A total of 5452 healthy men, 28,61 years of age. Main outcome measures., Incidence of first coronary events was monitored over a mean follow-up of 19 years. The fatality of the future events was studied in relation to FEV and FVC. Results., A total of 589 men suffered a coronary event during follow-up, 165 of them were fatal during the first day. After risk factors adjustment, low FEV or FVC were associated with incidence of coronary events (fatal or nonfatal) and this relationship was most pronounced for the fatal events. Amongst men who subsequently had a coronary event, the case-fatality rates were higher in men with low FEV or FVC. Adjusted for risk factors, the odds ratio for death during the first day was 1.00 (reference), 1.63 (95% CI: 0.9,3.1), 1.86 (1.0,3.5) and 2.06 (1.1,3.9), respectively, for men with FVC in the 4th, 3rd, 2nd, and lowest quartiles (trend: P < 0.05). FEV showed similar relationships with the fatality rates. Conclusion., Apparently healthy men with moderately reduced lung function have higher fatality in future coronary events, with a higher proportion of coronary heart disease deaths and less nonfatal myocardial infarction. [source]

Is there a prognostic role for C-reactive protein in ischemic stroke?

ACTA NEUROLOGICA SCANDINAVICA, Issue 3 2010
G. Corso
Corso G, Bottacchi E, Brusa A, Di Benedetto M, Giardini G, Lia C, Reggiani M, Veronese Morosini M. Is there a prognostic role for C-reactive protein in ischemic stroke? Acta Neurol Scand: 122: 209,216. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives,,, We investigated the relationship between C-reactive protein (CRP)-values in the acute phase of stroke and the risk of further fatal and non-fatal ischemic events. Materials and methods,,, We analysed 462 consecutive incident ischemic strokes. Patients were divided into two subgroups on the basis of a CRP cut-off level of 9 mg/l. Primary end points were any new vascular fatal and non-fatal event recorded during the follow-up period. Results,,, During a follow-up of 2.27 years, in 132 patients occurred a primary end point. Patients with CRP values ,9 mg/l had more frequently primary end point. The hazard ratio (HR) for cardiovascular events was 3.59; 1.93 for cerebrovascular events; 7.43 for vascular deaths and 5.78 for death from any cause. Cox proportional hazard multivariate analysis identified CRP values ,9 (HR = 4.19, 95% CI: 1.85,9.50, P = 0.001), the lack of secondary prevention therapy at discharge (HR = 4.35, 95% CI: 1.87,10.1, P = 0.001), age >70 years (HR = 3.09, 95% CI: 1.04,9.24, P = 0.04) as independent predictors of fatal events. Conclusions,,, CRP levels ,9 mg/l, evaluated in incident ischemic stroke within 24 h, predict a higher risk of further ischemic events and mortality. [source]

HUVECs from newborns with a strong family history of myocardial infarction overexpress adhesion molecules and react abnormally to stimulating agents

CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2005
A. Paez
Summary Atherosclerosis is a complex disease involved in major fatal events such as myocardial infarction and stroke. It is the result of interactions between metabolic, dietetic and environmental risk factors acting on a genetic background that could result in endothelial susceptibility. Our aim was to determine the patterns of expression of adhesion molecules and whether phosphatidylserine is translocated to the cell surface of human umbilical vein endothelial cells (HUVECs) isolated from healthy newborns born to parents with a strong family history of myocardial infarction under TNF-, or oxLDL stimulated conditions. Compared to control HUVECs, experimental cords showed: (a) a four-fold increase in VCAM-1 expression under basal conditions, which showed no change after stimulation with the pro-atherogenic factors; (b) a two-fold increase in basal P-selectin expression that reached a 10-fold increase with any of the pro-atherogenic factors; (c) a basal ICAM-1 expression similar to P-selectin that was not modified by the pro-atherogenic molecules; (d) a similar PECAM-1 expression. Unexpectedly, phospathidylserine expression in experimental cord HUVECs was significantly increased (211 817 versus 3354 TFU) but was not associated to apoptotic death as the percentage of dead cells induced by TNF-, treatment was very low (0·55 versus 9·87% in control HUVECs). The latter result was corroborated by TUNEL staining. T cell adherence to HUVECs was highly up-regulated in the genetically predisposed samples. The analysis of nonpooled HUVECs, from newborns to family predisposed myocardial-infarction individuals, might represent a useful strategy to identify phenotypical and functional alterations, and hopefully, to take early preventive actions. [source]