Familial aggregation of seizure outcomes in four familial epilepsy cohorts.

OBJECTIVE: To assess the possible effects of genetics on seizure outcome by estimating the familial aggregation of three outcome measures: seizure remission, history of ≥4 tonic-clonic seizures, and seizure control for individuals taking antiseizure medication. METHODS: We analyzed families containing multiple persons with epilepsy in four previously collected retrospective cohorts. Seizure remission was defined as being 5 and 10 years seizure-free at last observation. Total number of tonic-clonic seizures was dichotomized at <4 and ≥4 seizures. Seizure control in patients taking antiseizure medication was defined as no seizures for 1, 2, and 3 years. We used Bayesian generalized linear mixed-effects model (GLMM) to estimate the intraclass correlation coefficient (ICC) of the family-specific random effect, controlling for epilepsy type, age at epilepsy onset, and age at last data collection as fixed effects. We analyzed each cohort separately and performed meta-analysis using GLMMs. RESULTS: The combined cohorts included 3644 individuals with epilepsy from 1463 families. A history of ≥4 tonic-clonic seizures showed strong familial aggregation in three separate cohorts and meta-analysis (ICC .28, 95% confidence interval [CI] .21-.35, Bayes factor 8 × 1016). Meta-analyses did not reveal significant familial aggregation of seizure remission (ICC .08, 95% CI .01-.17, Bayes factor 1.46) or seizure control for individuals taking antiseizure medication (ICC .13, 95% CI 0-.35, Bayes factor 0.94), with heterogeneity among cohorts. SIGNIFICANCE: A history of ≥4 tonic-clonic seizures aggregated strongly in families, suggesting a genetic influence, whereas seizure remission and seizure control for individuals taking antiseizure medications did not aggregate consistently in families. Different seizure outcomes may have different underlying biology and risk factors. These findings should inform the future molecular genetic studies of seizure outcomes.

Attachment styles and healthcare utilization: exploring the role of the patient-doctor relationship.

BACKGROUND: With the purpose of improving healthcare, past research has examined the link between healthcare utilization and attachment. It is suggested that an individual's attachment style influences both the quality of their patient-physician relationship and healthcare utilization patterns. Nevertheless, most studies concentrate on the individual aspect, overlooking the dyadic dimension; specifically, the investigation of how insecure attachment relates to health behavior within patient-physician relationships. This gap leaves the role of the patient-doctor relationship in this process unclear. Therefore, to elucidate this complex interplay, we hypothesized that the correlation between attachment and healthcare utilization is mediated by the quality of the patient-physician-relationship. METHOD: Participant selection was based on electoral districts, a random-route procedure, and the Kish selection grid. The participants were visited by a trained interviewer who collected psychometric and sociodemographic information. Participants answered the Experiences in Close Relationships-Revised questionnaire (ECR-RD8) and the Patient-Doctor Relationship Questionnaire (PDRQ-9). Additionally, participants were asked about their healthcare utilization. The final sample consisted of N = 2.275 participants. RESULTS: In average the participants reported consulting their primary health care practitioner M(SD) = 4.44 (4.76) times in the past 12 months. Generally, the participants rated the quality of the relationship with their primary health care practitioner close to "totally appropriate" (M = 4.12 ± .69). The degree of insecure attachment manifested towards the lower extremity of the scale. The total effect of the mediation analyses was significant. Regardless, the indirect effect indicated a trend result with minimal effect sizes. CONCLUSION: The findings of the current study bridged the gap between attachment styles and healthcare utilization. Nonetheless, our results suggested insufficient support for the mediating role of the primary care physician in the relationship between attachment style and healthcare utilization. Considering the characteristics of the sample, this outcome may not apply in a clinical context. However, further research is needed to shed light in the revealed trends and indicate implications.

Incidence of mental health conditions by seizure control among adults with epilepsy in the United States.

BACKGROUND: Mental health conditions (MHCs) are frequent comorbidities among people with epilepsy; however, the influence of seizure control on the incidence of MHCs is not well reported. This retrospective observational cohort study based on claims data evaluated the effects of indicators of poor seizure control on the incidence of MHCs among MHC-naïve people with epilepsy. We hypothesized that poor seizure control is associated with new-onset MHC diagnoses and/or new prescription drugs for MHCs. METHODS: This study utilized a sample of patients from HealthVerity Marketplace, which includes more than 150 US commercial, Medicare, and Medicaid payers, to identify a cohort of adults (age ≥18 years) with prevalent epilepsy. Follow-up started on day 1 (January 1) after a 1-year eligibility assessment period occurring in calendar year 2017 or 2018. Patients were followed up until the occurrence of an incident MHC event (primary outcome), defined as a mental health diagnosis or psychotropic drug prescription. Time from follow-up to incident MHC diagnosis or to a drug prescription specific to depression or anxiety disorder was analyzed as a secondary outcome. Multivariate Cox proportional hazards regressions were estimated with time-varying covariates, measured in 6-month intervals during follow-up. Time-varying covariates were based on the occurrence of 4 variables used as indicators of poor seizure control in the prior period: epilepsy-related emergent care admissions, epilepsy-related inpatient admissions, epilepsy electroencephalography referrals, and exposure to one or more new antiseizure medications (ASMs). RESULTS: From a random sample of 40,000 people with epilepsy, 2563 (mean age 46.1 years; 50.6% male) were included in the analysis. Incident MHC events were observed in 27.7% (incidence rate 24.4 events per 100 person-years over 2,915.7 total person-years of follow-up). Mean (standard deviation [SD]) time to event was 232.7 (186.3) days. Among the 4 variables, epilepsy-related emergent care admissions were associated with an increased risk of incident MHC events in the following 6-month period (hazard ratio [HR] = 1.676, 95% confidence interval [CI]: 1.386, 2.026, p < 0.001) as were prescriptions for new ASMs in the previous period (HR = 1.702, 95% CI: 1.359, 2.132, p < 0.001). Previous epilepsy-related emergent care admissions (HR = 1.650, 95% CI: 1.347, 2.021, p < 0.001) and new ASMs (HR = 1.632, 95% CI: 1.280, 2.081, p < 0.001) also predicted an increased risk of incident depression or anxiety in the following 6-month period. CONCLUSIONS: Previous indicators of poor seizure control, including epilepsy-related emergent care admissions and new ASMs, predicted increased risk of new MHC events, including depression and anxiety, during the following 6-month interval in MHC-naïve patients with prevalent epilepsy. These data suggest that poor seizure control can increase the subsequent risk of new mental health diagnoses and treatment among people with epilepsy.

[Critical discussion of new data regarding prevalence of opioid use disorder in patients with chronic pain in Germany]. / Kritische Auseinandersetzung mit neuen Daten zur Prävalenz von Opioidgebrauchsstörungen bei Patienten mit chronischen Schmerzen in Deutschland.

BACKGROUND: There is no opioid crisis in Germany. However, new studies involving patients with chronic noncancer pain (CNCP) in Germany show an unexpectedly high prevalence of opioid use disorder according to DSM­5 (Diagnostic and Statistical Manual for Psychiatric Diseases). OBJECTIVES: Critical discussion of new study results on the prevalence of opioid use disorder in CNCP patients in Germany. MATERIALS AND METHODS: Selective literature search and multiprofessional classification of results by an expert panel (pain therapy, neurology, psychiatry, palliative medicine, general medicine and addiction therapy). RESULTS: The DSM­5 criteria for the diagnosis of "opioid use disorder" have limited applicability to patients with CNCP, but may raise awareness of problematic behavior. The diagnosis of opioid use disorder is not the same as the diagnosis of substance dependence according to ICD-10, as the DSM­5 diagnosis covers a much broader spectrum (mild, moderate, severe). Risk factors for opioid use disorder include younger age, depressive disorders, somatoform disorders, and high daily opioid doses. The interdisciplinary guideline on long-term opioid use for CNCP (LONTS) includes recommendations intended to reduce the risk for opioid use disorder. CONCLUSION: An adaptation of the DSM­5 diagnostic criteria of opioid use disorder to the specific situation of CNCP patients and a validation of these criteria could help to collect more accurate data on opioid use disorders of patients with chronic pain in Germany in the future. Prescribers should be sensitized to this problem without pathologizing or even stigmatizing patients. Further research is needed to classify this previously underestimated phenomenon.

[German S1 Guideline Long-/Post-COVID]. / S1-Leitlinie Long-/Post-COVID.

The German Society of Pneumology initiated 2021 the AWMF S1 guideline Long COVID/Post-COVID. In a broad interdisciplinary approach, this S1 guideline was designed based on the current state of knowledge.The clinical recommendations describe current Long COVID/Post-COVID symptoms, diagnostic approaches, and therapies.In addition to the general and consensus introduction, a subject-specific approach was taken to summarize the current state of knowledge.The guideline has an explicit practical claim and will be developed and adapted by the author team based on the current increase in knowledge.

Interictal dysphoric disorder in people with and without epilepsy.

OBJECTIVE: Interictal dysphoric disorder (IDD) has been regarded as an affective disorder occurring only in people with epilepsy (PWE). Data showing similar characteristics and similar prevalence of IDD in patients with migraine and with psychogenic nonepileptic seizures question the epilepsy-specific nature of IDD. The aim of the study was to investigate the nature of IDD in people with prevalent epilepsy with mood disorders and people with mood disorders who are free of neurological disease. METHODS: This is a case-control study, with 142 patients with a confirmed diagnosis of epilepsy and major depressive disorder (MDD; cases) and 222 patients with MDD only (controls). MDD diagnosis was confirmed by a structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition (SCID-I-RV). We used the Beck Depression Inventory and the Beck Anxiety Inventory to estimate anxiety and depression levels and the Interictal Dysphoric Disorder Inventory (IDDI) to confirm the presence of IDD. Mann-Whitney U test, Pearson chi-squared, Spearman correlation, and logistic regression were used. RESULTS: No differences were found in the prevalence of IDD between PWE with MDD and people with MDD alone (88.73% vs. 85.13%, χ2 = .96, p = .32). There were no differences between the groups overall or for any IDDI subscales (all p > .05). In both groups, IDD symptoms were grouped with the same incidence and had the same duration and periodicity. IDD was not associated with epilepsy (odds ratio = .84, 95% confidence interval = .40-1.98, p = .72). No significant correlation was found between epilepsy, demographic characteristics, and all IDDI subscales (all p > .05). Notably, patients with IDD suffered from affective disorders longer (6.68 ± 6.82 years vs. 3.7 ± 3.97 years, p = .001) and also received higher scores on all psychometric scales (all p < .05). SIGNIFICANCE: This study does not confirm the specificity of IDD for epilepsy. The presence of IDD symptoms may be associated with a more severe course of MDD and significant anxiety distress.

A multistate joint model for interval-censored event-history data subject to within-unit clustering and informative missingness, with application to neurocysticercosis research.

We propose a multistate joint model to analyze interval-censored event-history data subject to within-unit clustering and nonignorable missing data. The model is motivated by a study of the neurocysticercosis (NC) cyst evolution at the cyst-level, taking into account the multiple cysts phases with intermittent missing data and loss to follow-up, as well as the intra-brain clustering of observations made on a predefined data collection schedule. Of particular interest in this study is the description of the process leading to cyst resolution, and whether this process varies by antiparasitic treatment. The model uses shared random effects to account for within-brain correlation and to explain the hidden heterogeneity governing the missing data mechanism. We developed a likelihood-based method using a Monte Carlo EM algorithm for the inference. The practical utility of the methods is illustrated using data from a randomized controlled trial on the effect of antiparasitic treatment with albendazole on NC cysts among patients from six hospitals in Ecuador. Simulation results demonstrate that the proposed methods perform well in the finite sample and misspecified models that ignore the data complexities could lead to substantial biases.

Long-term opioid therapy of non-cancer pain : Prevalence and predictors of hospitalization in the event of possible misuse.

BACKGROUND: One major concern of long-term opioid therapy (LTOT) for chronic noncancer pain (CNCP) is the risk of abuse of prescribed opioids. OBJECTIVE: To examine the prevalence and predictors of opioid use-related hospitalizations and potential abuse of prescribed opioids by persons with LTOT for CNCP in a sample representative of the German statutory health insurance companies. METHODS: Retrospective cross-sectional study in 2014. Anonymized German health claims database, including 4,028,618 insured individuals of 69 German statutory health insurances. Univariate logistic regression models to evaluate demographic and medical characteristics associated with hospital stays and a diagnosis of mental and behavioral disorders due to alcohol, opioids, tranquilizers, multiple substances and intoxications by narcotic agents in insured individuals with CNCP receiving LTOT. RESULTS: The prevalence of LTOT for CNCP was 0.8%; 9.9% of these insured individuals received high-dose LTOT (≥120 morphine equivalent mg/day). The 1­year prevalence of hospital stays with a diagnosis of mental and behavioral disorders due to alcohol, opioids, tranquilizers, multiple substances and intoxications by narcotic agents was 1.75% of persons with LTOT. These diagnoses were strongly associated with prescriptions of tranquilizers (odds ratio [OR] 3.63; 95% confidence interval [CI] 3.03; 4.36) and moderately associated with diagnosis of depression (OR 2.52; 95% CI 2.12; 3.00) and slightly associated with diagnosis of somatoform pain disorder (OR 1.89; 95% CI 1.56; 2.28) and high-dose LTOT (OR 1.81; 95% CI 1.44; 2.27). DISCUSSION: The study is in line with the recommendations of the German national guidelines on long-term opioid therapy of chronic non-cancer pain (LONTS) to avoid concomitant prescription of tranquilizers for CNCP and to carefully select and monitor patients with depression and somatoform pain disorder.

Exploring the complex associations over time among albendazole treatment, cyst evolution, and seizure outcomes in neurocysticercosis.

OBJECTIVE: To develop a causal model for the occurrence of neurocysticercosis (NC)-related seizures and test hypotheses generated from the model. METHODS: We used data from a randomized controlled trial comparing albendazole with placebo among patients newly diagnosed with NC. Based on our causal model, we explored the associations among albendazole treatment, NC cyst evolution, and seizure outcomes over 24 months of follow-up using generalized linear mixed effect models. RESULTS: We included 153 participants, of whom 51% received albendazole. The association between seizure outcomes and treatment over time demonstrated lack of linearity and heterogeneity, requiring the inclusion of time-treatment interaction terms for valid modeling. Participants in the albendazole group had fewer seizures overall and of partial onset at all time points compared with the placebo group, but the difference increased over the first few months following treatment, then decreased over time. Generalized seizures exhibited a more complex association; those in the albendazole group had fewer seizures compared with those in the placebo group for the first few months after treatment, and then the association reversed and those in the placebo arm had fewer seizures. Adjusting for the number of NC cysts in each phase resulted in an attenuation of the strength of association between albendazole and seizure outcomes, consistent with mediation. Among participants in whom all cysts had disappeared (n = 21), none continued to have seizures. SIGNIFICANCE: Albendazole treatment is associated with a possible reduction in focal seizures in the short term (3-6 months), perhaps by hastening the resolution of the cysts. However, the effect is not discernible over the long term, because most cysts either calcify or resolve completely, regardless of whether treated with albendazole. The stage of evolution of the cysticercus is an important consideration in the evaluation of albendazole effect on seizure outcome.

Fetal growth and premature delivery in pregnant women on antiepileptic drugs.

OBJECTIVE: To evaluate the effects of epilepsy and antiepileptic drugs (AEDs) used during pregnancy on fetal growth and preterm delivery. METHODS: This study included singleton liveborn infants born to women enrolled in the North American Antiepileptic Drug Pregnancy Registry between 1997 and 2016. Data were collected prospectively through telephone interviews. The prevalence of preterm birth (<37 weeks) and small for gestational age status (SGA) among infants exposed prenatally to AEDs when used by women with epilepsy (WWE) or women without epilepsy (WWOE) was compared with that among infants unexposed to AEDs and born to WWOE. Multivariate log-binomial regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: The study population included infants born to 6,777 AED-WWE, 696 AED-WWOE, and 486 no-AED-WWOE. The risk of prematurity was 6.2% for no-AED-WWOE, 9.3% for AED-WWE (RR = 1.5, 95% CI = 1.0-2.1), and 10.5% for AED-WWOE (RR = 1.5, 95% CI = 1.0-2.4). Prenatal exposure to AEDs in WWE and WWOE was associated with a mean lower birth weight of 110 and 136g, respectively, as compared to no-AED-WWOE. The prevalence of SGA was 5.0% for no-AED-WWOE, 10.9% for AED-WWE (RR = 2.0, 95% CI = 1.3-3.0), and 11.0% for AED-WWOE (RR = 1.9, 95% CI = 1.2-2.9). Within users of AEDs in monotherapy, the prevalence of SGA ranged from 7.3% for lamotrigine to 18.5% for topiramate. INTERPRETATION: Women on AEDs during pregnancy, whether for epilepsy or for other neuropsychiatric indications, are at a higher risk of delivering prematurely and giving birth to SGA newborns. The risk may vary by drug. Ann Neurol 2017;82:457-465.

[Long-term opioid therapy of non-cancer pain : Prevalence and predictors of hospitalization in the event of possible misuse]. / Langzeitopioidtherapie von nichttumorbedingten Schmerzen : Prävalenz und Prädiktoren von Krankenhausaufenthalten bei möglicher missbräuchlicher Verwendung.

BACKGROUND: One major concern of long-term opioid therapy (LTOT) for chronic noncancer pain (CNCP) is the risk of abuse of prescribed opioids. OBJECTIVE: To examine the prevalence and predictors of opioid use-related hospitalizations and potential abuse of prescribed opioids by persons with LTOT for CNCP in a sample representative of the German statutory health insurance companies. METHODS: Retrospective cross-sectional study in 2014. Anonymized German health claims database, including 4,028,618 insured individuals of 69 German statutory health insurances. Univariate logistic regression models to evaluate demographic and medical characteristics associated with hospital stays and a diagnosis of mental and behavioral disorders due to alcohol, opioids, tranquilizers, multiple substances and intoxications by narcotic agents in insured individuals with CNCP receiving LTOT. RESULTS: The prevalence of LTOT for CNCP was 0.8%; 9.9% of these insured individuals received high-dose LTOT (≥120 morphine equivalent mg/day). The 1­year prevalence of hospital stays with a diagnosis of mental and behavioral disorders due to alcohol, opioids, tranquilizers, multiple substances and intoxications by narcotic agents was 1.75% of persons with LTOT. These diagnoses were strongly associated with prescriptions of tranquilizers (odds ratio [OR] 3.63; 95% confidence interval [CI] 3.03; 4.36) and moderately associated with diagnosis of depression (OR 2.52; 95% CI 2.12; 3.00) and slightly associated with diagnosis of somatoform pain disorder (OR 1.89; 95% CI 1.56; 2.28) and high-dose LTOT (OR 1.81; 95% CI 1.44; 2.27). DISCUSSION: The study is in line with the recommendations of the German national guidelines on long-term opioid therapy of chronic non-cancer pain (LONTS) to avoid concomitant prescription of tranquilizers for CNCP and to carefully select and monitor patients with depression and somatoform pain disorder.

EULAR revised recommendations for the management of fibromyalgia.

OBJECTIVE: The original European League Against Rheumatism recommendations for managing fibromyalgia assessed evidence up to 2005. The paucity of studies meant that most recommendations were 'expert opinion'. METHODS: A multidisciplinary group from 12 countries assessed evidence with a focus on systematic reviews and meta-analyses concerned with pharmacological/non-pharmacological management for fibromyalgia. A review, in May 2015, identified eligible publications and key outcomes assessed were pain, fatigue, sleep and daily functioning. The Grading of Recommendations Assessment, Development and Evaluation system was used for making recommendations. RESULTS: 2979 titles were identified: from these 275 full papers were selected for review and 107 reviews (and/or meta-analyses) evaluated as eligible. Based on meta-analyses, the only 'strong for' therapy-based recommendation in the guidelines was exercise. Based on expert opinion, a graduated approach, the following four main stages are suggested underpinned by shared decision-making with patients. Initial management should involve patient education and focus on non-pharmacological therapies. In case of non-response, further therapies (all of which were evaluated as 'weak for' based on meta-analyses) should be tailored to the specific needs of the individual and may involve psychological therapies (for mood disorders and unhelpful coping strategies), pharmacotherapy (for severe pain or sleep disturbance) and/or a multimodal rehabilitation programme (for severe disability). CONCLUSIONS: These recommendations are underpinned by high-quality reviews and meta-analyses. The size of effect for most treatments is relatively modest. We propose research priorities clarifying who will benefit from specific interventions, their effect in combination and organisation of healthcare systems to optimise outcome.

Stress is associated with an increased risk of recurrent seizures in adults.

OBJECTIVE: The literature is sparse on the complex interrelationships between stressors, depression, anxiety disorders, and epilepsy. We hypothesized that a relationship exists between stress and epilepsy. We evaluated whether markers of stress are associated with seizure recurrence in a low income community-based cohort of adults with single unprovoked seizure or newly diagnosed epilepsy. METHODS: We ascertained adult residents of Northern Manhattan and Harlem, New York City, with a first unprovoked seizure or newly diagnosed epilepsy, between December 2010 and January 2013. At enrollment, we collected information about seizure phenomenology, demographics, clinical information, and measures of stress (environmental stress, stressful life events, facets of allostatic load-i.e., the cumulative effect of adaptation to stress, psychiatric disorders, and low collective efficacy). Collective efficacy assesses neighborhood characteristics and incorporates social cohesion and informal social control. All subjects were followed for 2 years for further seizures. Cox proportional hazard regression models were used to estimate the hazard ratios of seizure recurrence during the 2 years of follow-up. RESULTS: We identified 52 subjects (64.2%) with a single unprovoked seizure and 29 (35.9%) with newly diagnosed epilepsy. Seizure recurrence was recorded in 38.5% (N = 20) of subjects with a single unprovoked seizure and in 69% of those with epilepsy (N = 20) (p = 0.01). In the overall sample, the hazard of seizure recurrence was increased by lifetime generalized anxiety disorder (3.0-fold) and by low collective efficacy (2.7-fold). In a second model, the hazard was increased by lifetime mood disorder (2.1-fold) and low collective efficacy (2.5-fold). SIGNIFICANCE: Markers of stress (i.e., low collective efficacy, lifetime mood disorder, and lifetime generalized anxiety disorder) were associated with an increased risk for seizure recurrence in adults with a single unprovoked seizure or newly diagnosed epilepsy. Stress-reducing interventions, such as mindfulness, may be a useful, safe, and inexpensive adjunctive treatment for epilepsy.

Reasons for discontinuation of reversible contraceptive methods by women with epilepsy.

OBJECTIVE: To report the reasons for discontinuation of contraceptive methods by women with epilepsy (WWE). METHODS: These retrospective data come from a web-based survey regarding the contraceptive practices of 1,144 WWE in the community, ages 18-47 years. We determined the frequencies of contraceptive discontinuations and the reasons for discontinuation. We compared risk ratios for rates of discontinuation among contraceptive methods and categories. We used chi-square analysis to test the independence of discontinuation reasons among the various contraceptive methods and categories and when stratified by antiepileptic drug (AED) categories. RESULTS: Nine hundred fifty-nine of 2,393 (40.6%) individual, reversible contraceptive methods were discontinued. One-half (51.8%) of the WWE who discontinued a method discontinued at least two methods. Hormonal contraception was discontinued most often (553/1,091, 50.7%) with a risk ratio of 1.94 (1.54-2.45, p < 0.0001) compared to intrauterine devices (IUDs), the category that was discontinued the least (57/227, 25.1%). Among all individual methods, the contraceptive patch was stopped most often (79.7%) and the progestin-IUD was stopped the least (20.1%). The top three reasons for discontinuation among all methods were reliability concerns (13.9%), menstrual problems (13.5%), and increased seizures (8.6%). There were significant differences among discontinuation rates and reasons when stratified by AED category for hormonal contraception but not for any other contraceptive category. SIGNIFICANCE: Contraception counseling for WWE should consider the special experience profiles that are unique to this special population on systemic hormonal contraception.

Premature mortality of epilepsy in low- and middle-income countries: A systematic review from the Mortality Task Force of the International League Against Epilepsy.

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.

The burden of premature mortality of epilepsy in high-income countries: A systematic review from the Mortality Task Force of the International League Against Epilepsy.

Since previous reviews of epidemiologic studies of premature mortality among people with epilepsy were completed several years ago, a large body of new evidence about this subject has been published. We aim to update prior reviews of mortality in epilepsy and to reevaluate and quantify the risks, potential risk factors, and causes of these deaths. We systematically searched the Medline and Embase databases to identify published reports describing mortality risks in cohorts and populations of people with epilepsy. We reviewed relevant reports and applied criteria to identify those studies likely to accurately quantify these risks in representative populations. From these we extracted and summarized the reported data. All population-based studies reported an increased risk of premature mortality among people with epilepsy compared to general populations. Standard mortality ratios are especially high among people with epilepsy aged <50 years, among those whose epilepsy is categorized as structural/metabolic, those whose seizures do not fully remit under treatment, and those with convulsive seizures. Among deaths directly attributable to epilepsy or seizures, important immediate causes include sudden unexpected death in epilepsy (SUDEP), status epilepticus, unintentional injuries, and suicide. Epilepsy-associated premature mortality imposes a significant public health burden, and many of the specific causes of death are potentially preventable. These require increased attention from healthcare providers, researchers, and public health professionals.

Epilepsy and treatment gap in urban and rural areas of the Southern Kazakhstan in adults.

PURPOSE: There are no data in the English literature about the epidemiology of epilepsy in the large countries in the Asian region of the former Soviet Union. This paper presents the results of epidemiological studies of active epilepsy in the population 14years of age and older in the Province of South Kazakhstan. METHODS: The study population consisted of 306.44 thousand persons: 139.42 in the urban Enbekshinskiy district of the city of Shymkent and 167.02 in the rural Sairam district. To collect patient's data, multiple medical sources were used. For each person with epilepsy (PWE), a questionnaire was completed by members of the research team. Clinical profiles, seizure type, clinical syndrome, etiology, seizure frequency, therapy, educational level, and social status were abstracted. RESULTS: Overall, 1351 PWE were identified: 459 in the urban district and 892 in the rural district. The age-adjusted prevalence of epilepsy was 3.14/1000 (CI95%: 2.86-3.45) in the urban district and 4.95/1000 (CI95%: 4.62-5.30) in the rural district. Prevalence for men was higher than for women. Focal seizures predominated in both regions. Traumatic brain injury was the most frequently identified cause of epilepsy. The other important antecedents were pre/perinatal disorders, CNS infection, and cerebrovascular disease. Half of PWE experienced more than 12seizures per year. Substantial social impacts of epilepsy were observed: 44% of PWE received disability pensions from the government; only 15.5% were employed. About a quarter of all PWE were not taking AEDs at the time of the record review. For those on treatment, regimens were frequently suboptimal. CONCLUSION: In the first study performed according to the guidelines for epidemiologic studies on epilepsy of ILAE in the Asian part of the former Soviet Union, poor seizure control and a substantial treatment gap were identified. The need for improvement of epilepsy care was highlighted, especially in the rural regions.

Folic acid use by women with epilepsy: Findings of the Epilepsy Birth Control Registry.

PURPOSE: To determine the prevalence and predictors of folic acid (FA) use by women with epilepsy (WWE) at risk of unintended pregnancy. METHODS: These retrospective data come from the Epilepsy Birth Control Registry (EBCR) web-based survey of 1144 WWE in the community, 18-47years, who provided demographic, epilepsy, AED, contraception, pregnancy, healthcare visits and FA data. We report prevalence and predictors of FA use in relation to risk of pregnancy (not at risk, at risk, seeking pregnancy, pregnant), demographics, seizure types and AED and contraception categories. RESULTS: 368 (47.6%) of the 773 WWE at risk of unintended pregnancy in the EBCR took FA supplement. Being at risk was a significant predictor in comparison to WWE not at risk (OR=1.464 [1.103-1.944], p=0.008). In comparison to WWE at risk, FA use trended greater for WWE actively seeking pregnancy (29/47, 61.7% v 368/773, 47.6%; p=0.0605) and was greater for pregnant WWE (17/19, 89.5% v 368/773, 47.6%; p=0.0007). Demographic predictors for WWE at risk were race (p=0.003), education (p=0.012) and income (0.043) with significantly greater FA use by Caucasians than minorities and direct correlations between FA use and levels of education and household income. Seizure type, AED use, category and dosage, polytherapy and contraceptive category were not predictors. A healthcare provider visit during the year prior to the survey was not a predictor. Prevalence of FA use was similar following visits with gynecologists - 51.7%, neurologists - 48.7% and primary care - 48.6%. FA supplementation by prescription was greater for WWE at risk on AED versus no AED (190/355, 53.5% v 3/13, 23.1%; p=0.045). CONCLUSION: Low prevalence of preconception FA use may reflect a need for more education. In addition, further research is needed to provide definitive evidence that FA reduces congenital malformations in the offspring of WWE.

[Methodology report of the 2017 guidelines on fibromyalgia syndrome]. / Methodenreport der Leitlinie 2017 zum Fibromyalgiesyndrom.

BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF number 145/004, was planned for April 2017. METHODS: The guidelines were developed by 13 scientific societies and 2 patient self-help organizations coordinated by the German Pain Society. Working groups (n = 8) with a total of 42 members were formed balanced with respect to gender, medical expertise, position in the medical or scientific hierarchy and potential conflicts of interest. RESULTS: A systematic search of the literature from December 2010 to May 2016 was performed in the Cochrane library, MEDLINE, PsycINFO and Scopus databases. Levels of evidence were assigned according to the classification system of the Oxford Centre for Evidence-Based Medicine version 2009. The strength of recommendations was achieved by multiple step formalized procedures to reach a consensus. Efficacy, risks, patient preferences and applicability of therapies available were weighed up against each other. The guidelines were reviewed and approved by the board of directors of the societies engaged in the development of the guidelines. CONCLUSION: The guidelines are published in several forms, i.e. complete and short scientific versions and clinical practice and patient versions.