首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到10条相似文献,搜索用时 156 毫秒
1.
Mortality in antiepileptic drug development programs   总被引:3,自引:0,他引:3  
BACKGROUND: Pooled data from New Drug Applications (NDAs) submitted to the U.S. Food and Drug Administration (FDA) provide an opportunity to study the incidence of and risk factors for rare events. OBJECTIVE: To examine the incidence and causes of mortality in patients with epilepsy participating in clinical trials of antiepileptic drugs (AEDs); and to examine the incidence of and risk factors for sudden unexplained death in such patients. METHODS: Exposure data and death narratives were obtained from the NDAs of five recently reviewed AEDs. Deaths were classified as sudden unexplained, accidental, or other cause using the 1993 Burroughs-Wellcome expert panel criteria, and mortality rates were calculated for each category. Add-on trials were analyzed separately from monotherapy initiation trials. RESULTS: Among 9,144 patients in the add-on trial database, the all-cause and sudden unexplained mortality rates were 9.1 and 3.8 deaths per 1,000 person-years (124 and 52 deaths in 13,617.1 person-years of drug exposure). Sixty-five percent of all deaths were related to the underlying epilepsy. Of the examined risk factors, only age was associated with the incidence of sudden unexplained death. Among 1,293 patients in the monotherapy initiation trials, the all-cause and sudden unexplained mortality rates were 7.1 and 0 deaths per 1,000 person-years (7 and 0 deaths in 982.5 person-years of drug exposure). CONCLUSIONS: A large proportion of the deaths in the add-on cohort was attributable to epilepsy-related causes. Mortality due to sudden death in the add-on cohort falls into the high end of the reported range for patients with epilepsy. The difference in mortality due to sudden death between the add-on and monotherapy initiation cohorts suggests that disease severity is the primary determining factor for risk of sudden unexplained death.  相似文献   

2.
Aim To describe the frequency and causes of death in children with epilepsy, ascertain the contribution of seizure disorder to cause of death, and compare with rates of sudden unexplained death in children without epilepsy. Method This study was a retrospective review of clinical and death certificate records. It examined two UK population‐based samples of deaths in children with epilepsy from 1 month to 18 years, together comprising the largest reported series of deaths in children with epilepsy (n=265). Results In approximately two‐thirds, the death was not due to the seizure disorder. Rates of unexplained death were similar in the two samples at 7.3% and 9.7%: all were in children with symptomatic or presumed symptomatic epilepsy. There were no unexplained deaths in the children with idiopathic epilepsy. Four per cent of the deaths were of children experiencing acute symptomatic seizures as part of their final illness. The risk of unexpected, unexplained death in children with idiopathic epilepsy is not more than 65 per 100 000 child‐years. Interpretation Epilepsy is associated with an increased risk of death in childhood but this risk is almost entirely confined to those with an associated neurodevelopmental disorder. The risk of unexpected, unexplained death in children with idiopathic epilepsy is extremely small.  相似文献   

3.
Epilepsy and mortality: a record linkage study in a U.K. population   总被引:2,自引:0,他引:2  
Morgan CL  Kerr MP 《Epilepsia》2002,43(10):1251-1255
PURPOSE: To examine patterns of mortality for a population with epilepsy compared with the nonepilepsy population. METHODS: The study used cross-sectional record linkage, combining an electronic death register with an epilepsy patient register constructed from a variety of routine health data sources collected from 1991 to 1997. The study was conducted in Cardiff and the Vale of Glamorgan, Wales, U.K., and included all deaths recorded between 1993 and 1996. RESULTS: There were 352 deaths for patients with epilepsy, 2.0% of all deaths. The crude mortality rates for patients with and without epilepsy were 36.2 and 9.9 per 1,000. The Standardised Mortality Ratio was 2.14 (95% CI, 1.74-2.55) for 1996 deaths. The single most common disease group was cancer, accounting for 66 (18.8%) of deaths for people with epilepsy (SMR, 1.47; 95% CI, 1.11-1.82). Significant excesses were demonstrated for cerebrovascular disease, diseases of the digestive system, respiratory diseases, and other causes of death. CONCLUSIONS: People with epilepsy have an increased mortality over the population as a whole. The main causes of death are those most common in the population as a whole and those that underlie the epilepsy itself.  相似文献   

4.
Summary: Purpose : A cohort consisting of all persons with known mental retardation (MR) and living in a Swedish province on December 31, 1985, was followed for 7 years (1987–1992) to study the mortality pattern.
Methods : A file of the cohort was linked to the cause-of-death pattern of the general population in the study area.
Results : One hundred twenty-four deaths (8.4%) occurred among the 1,478 persons with MR. Thirty deaths (10.1%) occurred among the 296 persons with epilepsy and MR. The standardized mortality ratio (SMR) in those with only MR was significantly increased as compared with that of the general population: 1.6 [95% confidence interval (CI) 1.3–2.01; MR and epilepsy, 5.0 (CI 3.3–7.5); and MR, epilepsy, and cerebral palsy (CP), 5.8 (CI 3.4–9.7). Mortality was increased both in patients with partial seizures without seizures secondarily generalized (SMR 3.7, CI 1.0–13.6) and in patients with seizures secondarily generalized (5.0, CI 2.3–11.0). The highest mortality occurred in patients who had seizures that were always generalized from the onset: 8.1 (CI 5.7–11.5). Mortality increased with increasing seizure frequency during the year preceding the prevalence date. In patients with epilepsy and MR, pneumonia was the most common cause of death and a seizure was the probable cause of death in 6.7%.
Conclusions : Epilepsy is associated with a significantly increased mortality in persons with MR. The increase is related to seizure type and seizure frequency. Death in persons with epilepsy and MR is seldom directly due to seizures. Other impairments associated with epilepsy and MR are important causes of death.  相似文献   

5.
To determine the magnitude of risk factors and causes of premature mortality associated with epilepsy in low‐ and middle‐income countries (LMICs). We conducted a systematic search of the literature reporting mortality and epilepsy in the World Bank‐defined LMICs. We assessed the quality of the studies based on representativeness; ascertainment of cases, diagnosis, and mortality; and extracted data on standardized mortality ratios (SMRs) and mortality rates in people with epilepsy. We examined risk factors and causes of death. The annual mortality rate was estimated at 19.8 (range 9.7–45.1) deaths per 1,000 people with epilepsy with a weighted median SMR of 2.6 (range 1.3–7.2) among higher‐quality population‐based studies. Clinical cohort studies yielded 7.1 (range 1.6–25.1) deaths per 1,000 people. The weighted median SMRs were 5.0 in male and 4.5 in female patients; relatively higher SMRs within studies were measured in children and adolescents, those with symptomatic epilepsies, and those reporting less adherence to treatment. The main causes of death in people with epilepsy living in LMICs include those directly attributable to epilepsy, which yield a mean proportional mortality ratio (PMR) of 27.3% (range 5–75.5%) derived from population‐based studies. These direct causes comprise status epilepticus, with reported PMRs ranging from 5 to 56.6%, and sudden unexpected death in epilepsy (SUDEP), with reported PMRs ranging from 1 to 18.9%. Important causes of mortality indirectly related to epilepsy include drowning, head injury, and burns. Epilepsy in LMICs has a significantly greater premature mortality, as in high‐income countries, but in LMICs the excess mortality is more likely to be associated with causes attributable to lack of access to medical facilities such as status epilepticus, and preventable causes such as drowning, head injuries, and burns. This excess premature mortality could be substantially reduced with education about the risk of death and improved access to treatments, including AEDs.  相似文献   

6.
The United Kingdom National General Practice Study of Epilepsy is a prospective, population-based study of newly diagnosed epilepsy. A cohort of 792 patients has now been followed for up to 14 years (median follow-up [25th, 75th percentiles] 11.8 years, range 10.6-11.7 years), a total of 11,400 person-years. These data are sufficient for a detailed analysis of mortality in this early phase of epilepsy. Over 70% of patients in this cohort have developed lasting remission from seizures, although the mortality rate in the long term was still twice that of the general population. The standardized mortality ratio (SMR), the number of observed deaths per number of expected deaths, was 2.1 (95% confidence interval [CI] = 1.8, 2.4). Patients with acute symptomatic epilepsy (SMR 3.0; 95% CI = 2.0, 4.3), remote symptomatic epilepsy (SMR 3.7; 95% CI = 2.9, 4.6), and epilepsy due to congenital neurological deficits (SMR 25; 95% CI = 5.1, 73.1) had significantly increased long-term mortality rates, whereas patients with idiopathic epilepsy did not (SMR 1.3; 95% CI = 0.9, 1.9). This increase in mortality rate was noted particularly in the first few years after diagnosis. Multivariate Cox regression and time-dependent co-variate analyses were utilized for the first time in a prospective study of mortality in epilepsy. The former showed that patients with generalized tonic-clonic seizures had an increased risk of mortality. The hazard ratio (HR), or risk of mortality in a particular group with a particular risk factor compared to another group without that particular risk factor, was 6.2 (95% CI = 1.4, 27.7; p = 0.049). Cerebrovascular disease (HR 2.4; 95% CI = 1.7, 3.4; p < 0.0001), central nervous system tumor (HR 12.0; 95% CI = 7.9, 18.2; p < 0.0001), alcohol (HR 2.9; 95% CI = 1.5, 5.7; p = 0.004), and congenital neurological deficits (HR 10.9; 95% CI = 3.2, 36.1; p = 0.003) as causes for epilepsy and older age at index seizure (HR 1.9; 95% CI = 1.7,2.0; p < 0.0001) were also associated with significantly increased mortality rates. These hazard ratios suggest that epilepsy due to congenital neurological deficits may carry almost the same risk of mortality as epilepsy due to central nervous system tumors and that epileptic seizures subsequent to alcohol abuse may carry almost the same risk of mortality as epilepsy due to cerebrovascular disease. The occurrence of one or more seizures before the index seizure (the seizure that led to the diagnosis of epilepsy and enrolment in the study) was associated with a significantly reduced mortality rate (HR 0.57; 95% CI = 0.42, 0.76; p = 0.00001). Time-dependent co-variate analysis was used to examine the influence of ongoing factors, such as seizure recurrence, remission, and antiepileptic drug use, on mortality rates in the cohort. Seizure recurrence (HR 1.30; 95% CI = 0.84, 2.01) and antiepileptic drug treatment (HR 0.97; 95% CI = 0.67, 1.38) did not influence mortality rate. There were only 5 epilepsy-related deaths (1 each of sudden unexpected death in epilepsy, status epilepticus, burns, drowning, and cervical fracture), suggesting that death directly due to epileptic seizures is uncommon in a population-based cohort with epilepsy.  相似文献   

7.
Chang YH  Ho WC  Tsai JJ  Li CY  Lu TH 《Seizure》2012,21(4):254-259
ObjectivePrevious studies suggested a higher risk of all-cause mortality in patients with epilepsy than in the general population. However, information on the age- and sex-specific risk of mortality, as well as on the cause-specific risk of mortality has been sparse. This study aims to determine sex-, age-, and cause-specific risk of mortality among patients with epilepsy from southern Taiwan.MethodsA total of 2180 patients treated in a tertiary hospital in southern Taiwan between 1989 and 2008 were compared to the general population of Taiwan for age-, sex- and cause-specific mortalities. The age-, sex-, and calendar year-standardized mortality ratios (SMRs) were calculated to estimate the relative risks of mortality associated with the epilepsy.ResultsThere are 266 (12.2%) deaths noted in the study period. The patients with epilepsy experienced a significantly increased SMR of all-cause mortality (SMR, 2.5; 95% confidence interval (CI), 2.2–2.8). The most significantly elevated age-specific SMR was 51.8 (95% CI, 6.2–187.2) and 8.6 (95% CI, 4.4–14.9) for male patients aged 0–9 years and female patients aged 20–29 years, respectively. Additionally, the most increased cause-specific SMR was noted for brain tumor (SMR, 21.4; 95% CI, 9.23–23.1), followed by accidental drowning (SMR, 8.8; 95% CI, 3.5–9.6) and falls (SMR, 5.7; 95% CI, 2.2–6.1).ConclusionYounger epilepsy should be the object of aggressive treatments. Advancement in treating brain tumors and prevention of accidental injuries may help improve the survival of patients with epilepsy.  相似文献   

8.
Summary: Purpose: To determine rates of all-cause mortality and of sudden, unexpected, unexplained deaths in epilepsy (SUDEP) in a cohort of individuals treated with the Neuro Cybernetic Prosthesis (NCP) System for intractable epilepsy, and; to contrast the NCP experience with other epilepsy cohorts.
Methods: A cohort of 791 individuals were followed for 1, 335 person-years from implantation. Of the total cohort, 120 individuals had their NCP System devices deactivated. The 15 deaths which occurred during NCP System activation were reviewed for SUDEP by a panel. There were three additional deaths and 242.5 person-years of monitoring after deactivation.
Results: The standardized mortality ratios for NCP System were 5.3, 95% confidence interval (CI) 3.0–8.7; and for the time period after device deactivation, 4.4, 95% CI 0.9–12.8. Six of the deaths during stimulation were considered definite or probable SUDEP and two as possible SUDEP. Seven were not considered to be SUDEP. The incidence of definite/probable SUDEP was 4.5 per 1,000 person-years and 6.0 per 1,000 person-years for definite/probable/possible SUDEP.
Conclusions: The mortality rates and standardized mortality ratios are comparable with studies of young adults with intractable epilepsy who were not treated with NCP System. These SUDEP rates are not significantly different from those reported in the recent studies of lamotrigine (LTG), gabapentin (GBP), and tiagabine (TGB). The higher rates of SUDEP in the NCP System cohort, as compared with recent drug trials, presumably is explained by the selection of relatively higher-risk patients for the NCP System device.  相似文献   

9.
Purpose: Death rates of patients with epilepsy are two to three times higher than expected. The aim of our study was to further delineate the causes and the patterns of premature death in patients with epilepsy. Methods: We included all patients who were prospectively enrolled between 1970 and 1999 in our epilepsy outpatient clinical database. Patients were followed until death or December 31, 2003. Standardized mortality ratios (SMRs) were calculated using reference rates from the same region. Key Findings: After 48,595 person years of follow‐up, 648 of 3,334 patients had died, resulting in an overall SMR of 2.2 (95% confidence interval [CI] 2.0–2.4). The highest SMRs were for patients aged 26–45 years (6.8, 95% CI 3.8–11.2) and with symptomatic epilepsies (3.1, 95% CI 2.3–4.9); those for cryptogenic causes (2.2, 95% CI 1.6–3.1) were also elevated, whereas those for idiopathic causes were not increased (2.7, 95% CI 0.7–7.0) after 2 years of follow‐up. SMRs for patients with persistent seizures (3.3, 95% CI 2.6–4.4) were higher than those for seizure‐free patients (1.4, 95% CI 0.8–2.3). The highest cause‐specific SMRs were for epilepsy (91.6, 95% CI 66.3–123.4), brain tumors (22.7, 95% CI 15.7–31.8), and external causes (2.4, 95% CI 1.8–3.3) at end of study period. Significance: Epilepsy patients have a higher‐than‐expected risk of death throughout life and especially during the first 2 years following diagnosis. Standardized mortality rates were especially high in younger patients and in patients with symptomatic epilepsies. Persistent seizures are strongly related to excess mortality.  相似文献   

10.
OBJECTIVE: The objective of this study was to compare the effect of depression on the risk of death in adults with and without cancer and by specific cancer site among those with cancer. RESEARCH DESIGN AND METHODS: We analyzed data on 10,025 participants in the population-based National Health and Nutrition Examination Survey (NHANES) 1 Epidemiologic Follow-up Study. Four groups were created based on cancer and depression status in 1982: (a) no cancer, no depression (reference group; no CA, no DEP); (b) depression but no cancer (DEP, no CA); (c) cancer but no depression (CA, no DEP); and (d) cancer and depression (CA+DEP). Six CA sites were defined: lung, breast, gastrointestinal (GI), genitourinary (GU), skin and other. Cox proportional models were used to calculate adjusted hazard for death for each group compared with the reference group and by cancer site. RESULTS: Over 8 years (78,433 person-years of follow-up), 1925 deaths were documented. The mortality rate per 1000 person-years of follow-up was highest in the CA+DEP group. Compared to the reference group, the hazard ratios (HRs) for all-cause mortality were as follows: CA, no DEP: 1.43 [95% confidence interval (95% CI)=1.23-1.67]; DEP, no CA: 1.44 (95% CI=1.28-1.63); CA+DEP: 1.87 (95% CI=1.49-2.34). HRs for depression by site were as follows: lung: 1.30 (95% CI=0.49-3.99); breast: 1.27 (95% CI=0.58-2.79); GI: 1.47 (95% CI=0.58-3.75); GU: 0.93 (95% CI=0.50-1.74); skin: 1.07 (95% CI=0.67-1.69); other: 2.13 (95% CI=0.55-8.25). CONCLUSION: The coexistence of cancer and depression is associated with a significantly increased risk of death, and the effect of depression on the risk of death differs by cancer site.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号