Estimation of the burden of active and life-time epilepsy: A meta-analytic approach
TL;DR: To estimate the burden of lifetime epilepsy (LTE) and active epilepsy (AE) and examine the influence of study characteristics on prevalence estimates.
Abstract: SUMMARY Purpose: To estimate the burden of lifetime epilepsy (LTE) and active epilepsy (AE) and examine the influence of study characteristics on prevalence estimates. Methods: We searched online databases and identified articles using prespecified criteria. Random-effects metaanalyses were used to estimate the median prevalence in developed countries and in urban and rural settings in developing countries. The impact of study characteristics on prevalence estimates was determined using metaregression models. Results: The median LTE prevalence for developed countries was 5.8 per 1,000 (5th–95th percentile range 2.7– 12.4) compared to 15.4 per 1,000 (4.8–49.6) for rural and 10.3 (2.8–37.7) for urban studies in developing countries. The median prevalence of AE was 4.9 per 1,000 (2.3–10.3) for developed countries and 12.7 per 1,000 (3.5–45.5) and 5.9 (3.4–10.2) in rural and urban studies in developing countries. The estimates of burden for LTE and AE in developed countries were 6.8 million (5th–95th percentile range 3.2–14.7) and 5.7 million (2.7–12.2), respectively. In developing countries these were 45 (14–145) million LTE and 17 (10–133) million AE in rural areas and 17 (5–61) million LTE and 10 (5–17) million AE in urban areas. Studies involving all ages or only adults showed higher estimates than pediatric studies. Higher prevalence estimates were also associated with rural location and small study size. Conclusions: This study estimates the global burden of epilepsy and the proportions with AE, which may benefit from treatment. There are systematic differences in reported prevalence estimates, which are only partially
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Valery L. Feigin1, Amanuel Alemu Abajobir2, Kalkidan Hassen Abate3, Foad Abd-Allah4 +267 more•Institutions (138)
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors (GBD) study provides such information but does not routinely aggregate results that are of interest to clinicians specialising in neurological conditions as discussed by the authors.
Abstract: Summary Background Comparable data on the global and country-specific burden of neurological disorders and their trends are crucial for health-care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study provides such information but does not routinely aggregate results that are of interest to clinicians specialising in neurological conditions. In this systematic analysis, we quantified the global disease burden due to neurological disorders in 2015 and its relationship with country development level. Methods We estimated global and country-specific prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) for various neurological disorders that in the GBD classification have been previously spread across multiple disease groupings. The more inclusive grouping of neurological disorders included stroke, meningitis, encephalitis, tetanus, Alzheimer's disease and other dementias, Parkinson's disease, epilepsy, multiple sclerosis, motor neuron disease, migraine, tension-type headache, medication overuse headache, brain and nervous system cancers, and a residual category of other neurological disorders. We also analysed results based on the Socio-demographic Index (SDI), a compound measure of income per capita, education, and fertility, to identify patterns associated with development and how countries fare against expected outcomes relative to their level of development. Findings Neurological disorders ranked as the leading cause group of DALYs in 2015 (250·7 [95% uncertainty interval (UI) 229·1 to 274·7] million, comprising 10·2% of global DALYs) and the second-leading cause group of deaths (9·4 [9·1 to 9·7] million], comprising 16·8% of global deaths). The most prevalent neurological disorders were tension-type headache (1505·9 [UI 1337·3 to 1681·6 million cases]), migraine (958·8 [872·1 to 1055·6] million), medication overuse headache (58·5 [50·8 to 67·4 million]), and Alzheimer's disease and other dementias (46·0 [40·2 to 52·7 million]). Between 1990 and 2015, the number of deaths from neurological disorders increased by 36·7%, and the number of DALYs by 7·4%. These increases occurred despite decreases in age-standardised rates of death and DALYs of 26·1% and 29·7%, respectively; stroke and communicable neurological disorders were responsible for most of these decreases. Communicable neurological disorders were the largest cause of DALYs in countries with low SDI. Stroke rates were highest at middle levels of SDI and lowest at the highest SDI. Most of the changes in DALY rates of neurological disorders with development were driven by changes in YLLs. Interpretation Neurological disorders are an important cause of disability and death worldwide. Globally, the burden of neurological disorders has increased substantially over the past 25 years because of expanding population numbers and ageing, despite substantial decreases in mortality rates from stroke and communicable neurological disorders. The number of patients who will need care by clinicians with expertise in neurological conditions will continue to grow in coming decades. Policy makers and health-care providers should be aware of these trends to provide adequate services. Funding Bill & Melinda Gates Foundation.
2,995 citations
01 Nov 2017
1,173 citations
Centers for Disease Control and Prevention1, Mario Negri Institute for Pharmacological Research2, University of Texas Health Science Center at Houston3, Northern Illinois University4, Children's Memorial Hospital5, Mayo Clinic6, Fudan University7, Columbia University8, Boston University9, RTI International10, University of Arizona11, University of Hawaii at Manoa12, University of Bari13, University College London14, Wellcome Trust15, University of California, San Francisco16, Mississippi University for Women17, University of Limoges18, UCL Institute of Neurology19, Medical University of South Carolina20, National Institutes of Health21, Karolinska Institutet22, University of Calgary23
TL;DR: The purpose of this document is to promote consistency in definitions and methods in an effort to enhance future population‐based epidemiologic studies, facilitate comparison between populations, and encourage the collection of data useful for the promotion of public health.
Abstract: Worldwide, about 65 million people are estimated to have epilepsy. Epidemiologic studies are necessary to define the full public health burden of epilepsy; to set public health and health care priorities; to provide information needed for prevention, early detection, and treatment; to identify education and service needs; and to promote effective health care and support programs for people with epilepsy. However, different definitions and epidemiologic methods complicate the tasks of these studies and their interpretations and comparisons. The purpose of this document is to promote consistency in definitions and methods in an effort to enhance future population-based epidemiologic studies, facilitate comparison between populations, and encourage the collection of data useful for the promotion of public health. We discuss: (1) conceptual and operational definitions of epilepsy, (2) data resources and recommended data elements, and (3) methods and analyses appropriate for epidemiologic studies or the surveillance of epilepsy. Variations in these are considered, taking into account differing resource availability and needs among countries and differing purposes among studies.
844 citations
Cites background from "Estimation of the burden of active ..."
...In low and middle income countries, estimates of the corresponding rates are generally higher (Hauser, 1995; Kotsopoulos et al., 2002; Sander, 2003; Burneo et al., 2005b; Preux & Druet-Cabanac, 2005; Ngugi et al., 2010)....
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...Worldwide, there are an estimated at least 65 million people living with epilepsy (Ngugi et al., 2010)....
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TL;DR: Overall outcomes in newly diagnosed epilepsy have not improved and most patients who attain control do so with the first or second AED, although the probability of achieving seizure freedom diminishes substantially with each subsequent AED regimen tried.
Abstract: Importance A study published in 2000 showed that more than one-third of adults with epilepsy have inadequate control of seizures with antiepileptic drugs (AEDs). This study evaluates overall treatment outcomes in light of the introduction of more than 1 dozen new AEDs in the past 2 decades. Objective To assess long-term treatment outcome in patients with newly diagnosed and treated epilepsy. Design, Setting, and Participants This longitudinal observational cohort study was conducted at the Epilepsy Unit of the Western Infirmary in Glasgow, Scotland. A total of 1795 individuals who were newly treated for epilepsy with AEDs between July 1, 1982, and October 31, 2012, were included in this analysis. All patients were followed up for a minimum of 2 years (until October 31, 2014) or until death, whichever came sooner. Data analysis was completed between March 2015 and May 2016. Exposures Treatment with antiepileptic drugs for patients newly diagnosed with epilepsy. Main Outcomes and Measures Seizure control was assessed at the end of the study period. Probability of achieving 1-year seizure freedom was estimated for each AED regimen prescribed. Multivariable models assessed the associations between risk factors and AED treatment outcome after adjustments were made for demographic and clinical characteristics. Results Of the 1795 included patients, 964 (53.7%) were male; the median age was 33 years (range, 9-93 years). At the end of the study period, 1144 patients (63.7%) had been seizure free for the previous year or longer. Among those achieving 1-year seizure freedom, 993 (86.8%) were taking monotherapy and 1028 (89.9%) had achieved seizure control with the first or second AED regimens. Of the total patient pool, 906 (50.5%) remained seizure free for 1 year or longer with the initial AED. If this AED failed, the second and third regimens provided an additional 11.6% and 4.4% likelihoods of seizure freedom, respectively. Only 2.12% of patients attained optimal seizure control with subsequent AEDs. Epilepsy that was not successfully controlled with the first AED had 1.73 times greater odds of not responding to treatment for each subsequent medication regimen (odds ratio, 1.73; 95% CI, 1.56-1.91;P Conclusions and Relevance Despite the availability of many new AEDs with differing mechanisms of action, overall outcomes in newly diagnosed epilepsy have not improved. Most patients who attain control do so with the first or second AED. The probability of achieving seizure freedom diminishes substantially with each subsequent AED regimen tried. More than one-third of patients experience epilepsy that remains uncontrolled.
768 citations
TL;DR: The lives of most people with epilepsy continue to be adversely affected by gaps in knowledge, diagnosis, treatment, advocacy, education, legislation, and research and Concerted actions to address these challenges are urgently needed.
674 citations
References
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TL;DR: A new quantity is developed, I 2, which the authors believe gives a better measure of the consistency between trials in a meta-analysis, which is susceptible to the number of trials included in the meta- analysis.
Abstract: Cochrane Reviews have recently started including the quantity I 2 to help readers assess the consistency of the results of studies in meta-analyses. What does this new quantity mean, and why is assessment of heterogeneity so important to clinical practice?
Systematic reviews and meta-analyses can provide convincing and reliable evidence relevant to many aspects of medicine and health care.1 Their value is especially clear when the results of the studies they include show clinically important effects of similar magnitude. However, the conclusions are less clear when the included studies have differing results. In an attempt to establish whether studies are consistent, reports of meta-analyses commonly present a statistical test of heterogeneity. The test seeks to determine whether there are genuine differences underlying the results of the studies (heterogeneity), or whether the variation in findings is compatible with chance alone (homogeneity). However, the test is susceptible to the number of trials included in the meta-analysis. We have developed a new quantity, I 2, which we believe gives a better measure of the consistency between trials in a meta-analysis.
Assessment of the consistency of effects across studies is an essential part of meta-analysis. Unless we know how consistent the results of studies are, we cannot determine the generalisability of the findings of the meta-analysis. Indeed, several hierarchical systems for grading evidence state that the results of studies must be consistent or homogeneous to obtain the highest grading.2–4
Tests for heterogeneity are commonly used to decide on methods for combining studies and for concluding consistency or inconsistency of findings.5 6 But what does the test achieve in practice, and how should the resulting P values be interpreted?
A test for heterogeneity examines the null hypothesis that all studies are evaluating the same effect. The usual test statistic …
45,105 citations
"Estimation of the burden of active ..." refers methods in this paper
...Because heterogeneity was expected a priori due to clinical and methodologic diversity in the studies, we also quantified the degree of heterogeneity across studies using the statistic I(2) = ((Q)df)/Q) x 100%, where Q is the Cochran chi-square statistic and df is its degrees of freedom (Higgins & Thompson, 2002; Higgins et al., 2003)....
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...The studies included in these analyses, however, showed considerable heterogeneity, which we quantified using robust meta-analysis (Egger et al., 1997a,b; Higgins & Thompson, 2002; Higgins et al., 2003)....
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...…priori due to clinical and methodologic diversity in the studies, we also quantified the degree of heterogeneity across studies using the statistic I2 = ((Q)df)/Q) x 100%, where Q is the Cochran chi-square statistic and df is its degrees of freedom (Higgins & Thompson, 2002; Higgins et al., 2003)....
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TL;DR: Funnel plots, plots of the trials' effect estimates against sample size, are skewed and asymmetrical in the presence of publication bias and other biases Funnel plot asymmetry, measured by regression analysis, predicts discordance of results when meta-analyses are compared with single large trials.
Abstract: Objective: Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. Design: Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30% of the trial); analysis of funnel plots from 37 meta-analyses identified from a hand search of four leading general medicine journals 1993-6 and 38 meta-analyses from the second 1996 issue of the Cochrane Database of Systematic Reviews . Main outcome measure: Degree of funnel plot asymmetry as measured by the intercept from regression of standard normal deviates against precision. Results: In the eight pairs of meta-analysis and large trial that were identified (five from cardiovascular medicine, one from diabetic medicine, one from geriatric medicine, one from perinatal medicine) there were four concordant and four discordant pairs. In all cases discordance was due to meta-analyses showing larger effects. Funnel plot asymmetry was present in three out of four discordant pairs but in none of concordant pairs. In 14 (38%) journal meta-analyses and 5 (13%) Cochrane reviews, funnel plot asymmetry indicated that there was bias. Conclusions: A simple analysis of funnel plots provides a useful test for the likely presence of bias in meta-analyses, but as the capacity to detect bias will be limited when meta-analyses are based on a limited number of small trials the results from such analyses should be treated with considerable caution. Key messages Systematic reviews of randomised trials are the best strategy for appraising evidence; however, the findings of some meta-analyses were later contradicted by large trials Funnel plots, plots of the trials9 effect estimates against sample size, are skewed and asymmetrical in the presence of publication bias and other biases Funnel plot asymmetry, measured by regression analysis, predicts discordance of results when meta-analyses are compared with single large trials Funnel plot asymmetry was found in 38% of meta-analyses published in leading general medicine journals and in 13% of reviews from the Cochrane Database of Systematic Reviews Critical examination of systematic reviews for publication and related biases should be considered a routine procedure
37,989 citations
TL;DR: It is concluded that H and I2, which can usually be calculated for published meta-analyses, are particularly useful summaries of the impact of heterogeneity, and one or both should be presented in publishedMeta-an analyses in preference to the test for heterogeneity.
Abstract: The extent of heterogeneity in a meta-analysis partly determines the difficulty in drawing overall conclusions. This extent may be measured by estimating a between-study variance, but interpretation is then specific to a particular treatment effect metric. A test for the existence of heterogeneity exists, but depends on the number of studies in the meta-analysis. We develop measures of the impact of heterogeneity on a meta-analysis, from mathematical criteria, that are independent of the number of studies and the treatment effect metric. We derive and propose three suitable statistics: H is the square root of the chi2 heterogeneity statistic divided by its degrees of freedom; R is the ratio of the standard error of the underlying mean from a random effects meta-analysis to the standard error of a fixed effect meta-analytic estimate, and I2 is a transformation of (H) that describes the proportion of total variation in study estimates that is due to heterogeneity. We discuss interpretation, interval estimates and other properties of these measures and examine them in five example data sets showing different amounts of heterogeneity. We conclude that H and I2, which can usually be calculated for published meta-analyses, are particularly useful summaries of the impact of heterogeneity. One or both should be presented in published meta-analyses in preference to the test for heterogeneity.
25,460 citations
"Estimation of the burden of active ..." refers methods in this paper
...The studies included in these analyses, however, showed considerable heterogeneity, which we quantified using robust meta-analysis (Egger et al., 1997a,b; Higgins & Thompson, 2002; Higgins et al., 2003)....
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...The standard test for heterogeneity, the Cochran chi-square (v2) test, was used to examine the null hypothesis that the observed heterogeneity was due sampling error (Higgins & Thompson, 2002)....
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...…priori due to clinical and methodologic diversity in the studies, we also quantified the degree of heterogeneity across studies using the statistic I2 = ((Q)df)/Q) x 100%, where Q is the Cochran chi-square statistic and df is its degrees of freedom (Higgins & Thompson, 2002; Higgins et al., 2003)....
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TL;DR: These principles are discussed, along with the practical steps in performing meta-analysis, which allow a more objective appraisal of the evidence than traditional narrative reviews, provide a more precise estimate of a treatment effect, and may explain heterogeneity between the results of individual studies.
Abstract: Meta-analysis is a statistical procedure that integrates the results of several independent studies considered to be “combinable.”1 Well conducted meta-analyses allow a more objective appraisal of the evidence than traditional narrative reviews, provide a more precise estimate of a treatment effect, and may explain heterogeneity between the results of individual studies.2 Ill conducted meta-analyses, on the other hand, may be biased owing to exclusion of relevant studies or inclusion of inadequate studies.3 Misleading analyses can generally be avoided if a few basic principles are observed. In this article we discuss these principles, along with the practical steps in performing meta-analysis.
Meta-analysis should be viewed as an observational study of the evidence. The steps involved are similar to any other research undertaking: formulation of the problem to be addressed, collection and analysis of the data, and reporting of the results. Researchers should write in advance a detailed research protocol that clearly states the objectives, the hypotheses to be tested, the subgroups of interest, and the proposed methods and criteria for identifying and selecting relevant studies and extracting and analysing information.
As with criteria for including and excluding patients in clinical studies, eligibility criteria have to be defined for the data to be included. Criteria relate to the quality of trials and to the combinability of treatments, patients, outcomes, and lengths of follow up. Quality and design features of a study can influence the results.4 5 Ideally, researchers should consider including only controlled trials with proper randomisation of patients that report on all initially included patients according to the intention to treat principle and with an objective, preferably blinded, outcome assessment.6 Assessing the quality of a study …
2,040 citations
"Estimation of the burden of active ..." refers methods in this paper
...The studies included in these analyses, however, showed considerable heterogeneity, which we quantified using robust meta-analysis (Egger et al., 1997a,b; Higgins & Thompson, 2002; Higgins et al., 2003)....
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TL;DR: Age‐and gender‐specific incidence trends were similar to those of epilepsy, but a higher proportion of cases was of unknown etiology and was characterized by generalized onset seizures.
Abstract: The incidence of epilepsy and of all unprovoked seizures was determined for residents of Rochester, Minnesota U.S.A. from 1935 through 1984. Age-adjusted incidence of epilepsy was 44 per 100,000 person-years. Incidence in males was significantly higher than in females and was high in the first year of life but highest in persons aged > or = 75 years. Sixty percent of new cases had epilepsy manifested by partial seizures, and two thirds had no clearly identified antecedent. Cerebrovascular disease was the most commonly identified antecedent, accounting for 11% of cases. Neurologic deficits from birth, mental retardation and/or cerebral palsy, observed in 8% of cases, was the next most frequently identified preexisting condition. The cumulative incidence of epilepsy through age 74 years was 3.1%. The age-adjusted incidence of all unprovoked seizures was 61 per 100,000 person-years. Age- and gender-specific incidence trends were similar to those of epilepsy, but a higher proportion of cases was of unknown etiology and was characterized by generalized onset seizures. The cumulative incidence of all unprovoked seizures was 4.1% through age 74 years. With time, the incidence of epilepsy and of unprovoked seizures decreased in children and increased in the elderly.
1,866 citations
"Estimation of the burden of active ..." refers background or methods in this paper
...(Hauser et al., 1993; Da Mota et al., 2002; Racoosin, 2003; Tidman et al., 2003) or the use of the Health Maintenance Organizations’ records (Annegers et al....
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...All meta-analyses were carried out in STATA 10 (StataCorp, College Station, TX, U.S.A.)....
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...Others include use of the diagnostic record system in Rochester, an area of New York, NY, U.S.A. (Hauser et al., 1993; Da Mota et al., 2002; Racoosin, 2003; Tidman et al., 2003) or the use of the Health Maintenance Organizations’ records (Annegers et al., 1999; Holden et al., 2005)....
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