bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and pharmacokinetics of intravenous levetiracetam infusion as add‐on in status epilepticus
Authors: Uges Joris W.F. , Van Huizen Marc D. , Engelsman Jeroen , Wilms Erik B. , Touw Daniel J. , Peeters Els , Vecht Charles J. 
Published: November 2008

SummaryPurpose: To evaluate the feasibility and safety of intravenous (iv) levetiracetam (LEV) added to the standard therapeutic regimen in adults with status epilepticus (SE), and as secondary objective to assess a population pharmacokinetic (PK) model for ivLEV in patients with SE.Methods: In 12 adults presenting with SE, 2,500 mg ivLEV was added as soon as possible to standardized protocol, consisting of iv clonazepam and/or rectal diazepam, as needed followed by phenytoin or valproic acid. ivLEV was administered over approximately 5 min, in general after administration of clonazepam, regardless the need for further treatment. During 24‐h follow‐up, patients were observed for any clinically relevant side‐effects. Blood samples for PK analysis were available in 10 patients. A population PK model was developed by iterative two‐stage Bayesian analysis and compared to PK data of healthy volunteers.Results: Eleven patients with a median age of 60 years were included in the per protocol analysis. Five were diagnosed as generalized‐convulsive SE, five as partial‐convulsive SE, and one as a nonconvulsive SE. The median time from hospital admission to ivLEV was 36 min. No serious side effects could be related directly to the administration of ivLEV. During PK analysis, four patients showed a clear distribution phase, lacking in the others. The PK of the population was best described by a two‐compartment population model. Mean (standard deviation, SD) population parameters included volume of distribution of central compartment: 0.45 (0.084) L/kg; total body clearance: 0.0476 (0.0147) L/h/kg; distribution rate constants, central to peripheral compartment (k12): 0.24 (0.12)/h, and peripheral to central (k21): 0.70 (0.22)/h. Mean maximal plasma concentration was 85 (19) mg/L.Discussion: The addition of ivLEV to the standard regimen for controlling SE seems feasible and safe. PK data of ivLEV in patients with SE correspond to earlier values derived from healthy volunteers, confirming a two‐compartment population model.
Clinical spectrum and medical treatment of children with electrical status epilepticus in sleep (ESES)
Authors: Kramer Uri , Sagi Liora , Goldberg‐Stern Hadassa , Zelnik Nathanel , Nissenkorn Andreea , Ben‐Zeev Bruria 
Published: November 2008

SummaryPurposes: To describe the clinical spectrum and to evaluate the efficacy of different therapeutic agents in children with electrical status epilepticus in sleep (ESES).Methods: Clinical data of all patients with ESES (not including patients with Landau‐Kleffner syndrome) in four pediatric neurology outpatient clinics were analyzed. Thirty patients with ESES had been treated between 1994 and 2007.Results: Eleven (37%) children had benign partial epilepsies of childhood, five (17%) had cerebral palsy, five (17%) had hydrocephalus, one (3%) had schizencephaly, one (3%) had prenatal parenchymal bleeding, and the etiology was unclear in seven (23%). The duration of ESES ranged between 2 and 60 months. The antiepileptic drugs that were found to be efficacious were: levetiracetam (41%), clobazam (31%), and sulthiame (17%). Valproic acid, lamotrigine, topiramate, and ethosuximide showed no efficacy. Steroids were efficacious in 65%; immunoglobulins were efficacious in 33%. High‐dose diazepam was efficacious in 37%, but all the children had temporary response. Seventeen patients (57%) had cognitive deterioration, whereas the rest presented with regression in attention, speech, communication, and behavior. Fourteen children had permanent cognitive deficit. There was a significant correlation (p = 0.029) between the duration of ESES and residual intellectual deficit at follow‐up.Conclusions: ESES reflects an evolution of benign partial epilepsy of childhood in more than one‐third of the patients, whereas there is an underlying structural brain anomaly in another one‐third. The most efficacious antiepileptic drugs (AEDs) are levetiracetam and clobazam. The duration of ESES correlated significantly with residual intellectual deficit at follow‐up.
Cognitive complaints after a first seizure in adulthood: Influence of psychological adjustment
Authors: Velissaris Sarah L. , Wilson Sarah J. , Newton Mark R. , Berkovic Samuel F. , Saling Michael M. 
Published: November 2008

SummaryPurpose:  To examine the nature and determinants (biologic and psychological) of cognitive complaints in first‐seizure patients. We analyzed this in the context of our previous findings that a sense of loss of control after a newly diagnosed seizure (limited or pervasive) predicts subsequent psychological adjustment trajectories.Methods:  Eighty‐five consecutive First Seizure Clinic patients were assessed at 1 and 3 months. Cognitive complaints were evaluated qualitatively, with a semistructured interview, and quantitatively, with the A‐B Neuropsychological Assessment Schedule (ABNAS). Objective attentional processing was assessed with reaction time tasks and the Wechsler Adult Intelligence Scale‐3rd edition (WAIS‐III) Processing Speed Index. Mood was assessed with the Hospital Anxiety and Depression Scale (HADS). Psychological adjustment trajectories were represented by previous classification of patients into limited and pervasive groups, as derived from semistructured interview.Results:  Cognitive complaints at 1 and 3 months were strongly associated with mood, and unrelated to objective attentional processing. Psychological adjustment trajectories influenced the longitudinal course of cognitive complaints, and these effects were partially mediated by mood differences between the limited and pervasive groups. The course of cognitive complaints was also altered by commencing antiepileptic drugs. Patients experiencing seizure recurrence reported greater cognitive complaints, even before their seizure recurred. Mediation analyses showed this effect was likely attributable to increased mood disturbance in the seizure recurrence group, and was unrelated to objective attentional processing.Discussion:  Understanding cognitive complaints in first‐seizure patients requires a longitudinal perspective that takes into account the patients’ changing psychological and medical contexts. Patients presenting with extensive cognitive complaints may warrant assessment for mood and adjustment issues.
Magnetic resonance imaging abnormalities associated with vigabatrin in patients with epilepsy
Authors: Wheless James W. , Carmant Lionel , Bebin Martina , Conry Joan A. , Chiron Catherine , Elterman Roy D. , Frost Michael , Paolicchi Juliann M. , Donald Shields W. , Thiele Elizabeth A. , Zupanc Mary L. , Collins Stephen D. 
Published: November 2008

SummaryPurpose:  Vigabatrin used to treat infantile spasms (IS) has been associated with transient magnetic resonance imaging (MRI) abnormalities. We carried out a retrospective review to better characterize the frequency of those abnormalities in IS and in children and adults treated with vigabatrin for refractory complex partial seizures (CPS).Methods:  Medical records and 332 cranial MRIs from 205 infants (aged ≤24 months) with IS treated at 10 sites in the United States and Canada were collected. Similarly, 2,074 images from 668 children (aged 2–16 years) and adults (aged >16 years) with CPS were re‐reviewed. Prespecified MRI abnormalities were defined as any hyperintensity on T2‐weighted or fluid‐attenuated inversion‐recovery (FLAIR) sequences with or without diffusion restriction not readily explained by a radiographically well‐characterized pathology. MRIs were read by two neuroradiologists blinded to treatment group. The incidence and prevalence of MRI abnormalities associated with vigabatrin were estimated.Results:  Among infants with IS, the prevalence of prespecified MRI abnormalities was significantly higher among vigabatrin‐treated versus vigabatrin‐naive subjects (22% vs. 4%; p < 0.001). Of nine subjects in the prevalence population with at least one subsequent determinate MRI, resolution of MRI abnormalities occurred in six (66.7%)—vigabatrin was discontinued in four. Among adults and children treated with vigabatrin for CPS, there was no statistically significant difference in the incidence or prevalence of prespecified MRI abnormalities between vigabatrin‐exposed and vigabatrin‐naive subjects.Discussion:  Vigabatrin is associated with transient, asymptomatic MRI abnormalities in infants treated for IS. The majority of these MRI abnormalities resolved, even in subjects who remained on vigabatrin therapy.
Sociodemographic disparities in epilepsy care: Results from the Houston/New York City health care use and outcomes study
Authors: Begley Charles E. , Basu Rituparna , Reynolds Thomas , Lairson David R. , Dubinsky Stephanie , Newmark Michael , Barnwell Forbes , Hauser Allen , Hesdorffer Dale , Hernandez Nora , Karceski Steven C. , Shih Tina 
Published: November 2008

SummaryPurpose:  The purpose of this study was to identify sociodemographic disparities in health care use among epilepsy patients receiving care at different sites and the extent to which the disparities persisted after adjusting for patient characteristics and site of care.Methods:  Three months of health care use data were obtained from baseline interviews of approximately 560 patients at four sites. One‐half of the patients were from a Houston site and two NYC sites that serve predominantly low‐income, minority, publicly insured, or uninsured patients. The other half were at the remaining site in Houston that serves a more balanced racial/ethnic and higher sociodemographic population. Differences in general and specialist visits, hospital emergency room (ER) care, and hospitalizations were associated with race/ethnicity, income, and coverage. Logistic regression was used to assess the extent to which the differences persisted when adjusting for individual patient characteristics and site of care.Results:  Compared to whites, blacks and Hispanics had higher rates of generalist visits [odds ratio (OR) = 5.3 and 4.9, p < 0.05), ER care (OR = 3.1 and 2.9, p < 0.05) and hospitalizations (OR = 5.4 and 6.2, p < 0.05), and lower rates of specialist visits (OR = 0.3 and 0.4, p < 0.05). A similar pattern was found related to patient income and coverage. The magnitude and significance of the disparities persisted when adjusting for individual characteristics but decreased substantially or were eliminated when site of care was added to the model.Discussion:  There are sociodemographic disparities in health care for people with epilepsy that are largely explained by differences in where patients receive care.
Stress, the hippocampus, and epilepsy
Authors: Joëls Marian 
Published: November 2008

SummaryStress is among the most frequently self‐reported precipitants of seizures in patients with epilepsy. This review considers how important stress mediators like corticotropin‐releasing hormone, corticosteroids, and neurosteroids could contribute to this phenomenon. Cellular effects of stress mediators in the rodent hippocampus are highlighted. Overall, corticosterone—with other stress hormones—rapidly enhances CA1/CA3 hippocampal activity shortly after stress. At the same time, corticosterone starts gene‐mediated events, which enhance calcium influx several hours later. This later effect serves to normalize activity but also imposes a risk for neuronal injury if and when neurons are concurrently strongly depolarized, for example, during epileptic activity. In the dentate gyrus, stress‐induced elevations in corticosteroid level are less effective in changing membrane properties such as calcium influx; here, enhanced inhibitory tone mediated through neurosteroid effects on γ‐aminobutyric acid (GABA) receptors might dominate. Under conditions of repetitive stress (e.g., caused from experiencing repetitive and unpredictable seizures) and/or early life stress, hormonal influences on the inhibitory tone, however, are diminished; instead, enhanced calcium influx and increased excitation become more important. In agreement, perinatal stress and elevated steroid levels accelerate epileptogenesis and lower seizure threshold in various animal models for epilepsy. It will be interesting to examine how curtailing the effects of stress in adults, for example, by brief treatment with antiglucocorticoids, may be beneficial to the treatment of epilepsy.
Cumulative Anticholinergic Exposure Is Associated with Poor Memory and Executive Function in Older Men
Authors: Han Ling , Agostini Joseph V. , Allore Heather G. 
Published: November 2008

OBJECTIVES: To examine the longitudinal relationship between cumulative exposure to anticholinergic medications and memory and executive function in older men.DESIGN: Prospective cohort study.SETTING: A Department of Veterans Affairs primary care clinic.PARTICIPANTS: Five hundred forty‐four community‐dwelling men aged 65 and older with diagnosed hypertension.MEASUREMENTS: The outcomes were measured using the Hopkins Verbal Recall Test (HVRT) for short‐term memory and the instrumental activity of daily living (IADL) scale for executive function at baseline and during follow‐up. Anticholinergic medication use was ascertained using participants' primary care visit records and quantified as total anticholinergic burden using a clinician‐rated anticholinergic score.RESULTS: Cumulative exposure to anticholinergic medications over the preceding 12 months was associated with poorer performance on the HVRT and IADLs. On average, a 1‐unit increase in the total anticholinergic burden per 3 months was associated with a 0.32‐point (95% confidence interval (CI)= 0.05–0.58) and 0.10‐point (95% CI=0.04–0.17) decrease in the HVRT and IADLs, respectively, independent of other potential risk factors for cognitive impairment, including age, education, cognitive and physical function, comorbidities, and severity of hypertension. The association was attenuated but remained statistically significant with memory (0.29, 95% CI=0.01–0.56) and executive function (0.08, 95% CI=0.02–0.15) after further adjustment for concomitant non‐anticholinergic medications.CONCLUSION: Cumulative anticholinergic exposure across multiple medications over 1 year may negatively affect verbal memory and executive function in older men. Prescription of drugs with anticholinergic effects in older persons deserves continued attention to avoid deleterious adverse effects.
The Influence of Educational Level on Polypharmacy and Inappropriate Drug Use: A Register‐Based Study of More Than 600,000 Older People
Authors: Haider Syed Imran , Johnell Kristina , Weitoft Gunilla Ringbäck , Thorslund Mats , Fastbom Johan 
Published: November 2008

OBJECTIVES:To investigate whether low educational attainment is associated with polypharmacy and potential inappropriate drug use (IDU) in older people.DESIGN:Cross‐sectional register‐based study.SETTING:Sweden.PARTICIPANTS:Older people aged 75 to 89 who, filled at least one drug prescription between August and October 2005 and, consequently, were listed in the Swedish Prescribed Drug Register (SPDR) (N=626,258). Data were obtained from the SPDR, the inpatient register, and the education register.MEASUREMENTS:The main outcome measures were polypharmacy (concurrent use of ≥5 drugs), excessive polypharmacy (concurrent use of ≥10 drugs), and potential IDU. Four quality indicators developed by the Swedish National Board of Health and Welfare were used for the assessment of potential IDU: concurrent use of three or more psychotropic drugs, prescription of long‐acting benzodiazepines, prescription of anticholinergics, and at least one clinically relevant potential drug–drug interaction (DDI). Comorbidity was measured using the Charlson Comorbidity Index.RESULTS:Subjects with low education had a higher probability of polypharmacy (odds ratio (OR)=1.11, 95% confidence interval (CI)=1.10–1.12), excessive polypharmacy (OR=1.15, 95% CI=1.13–1.17), and potential IDU (OR=1.09, 95% CI=1.07–1.17), after adjustment for age, sex, comorbidity, and type of residential area (urban or rural). Decreasing educational attainment was associated with a higher probability of using three or more psychotropic drugs and potential DDIs, whereas the opposite association was observed for anticholinergic drugs. Long‐acting benzodiazepines showed no association. Elderly women with low education were slightly more likely to have polypharmacy, excessive polypharmacy, and potential IDU than men with low education. Overall, the ORs were modest and statistically significant because of the large sample size.CONCLUSION:Low educational attainment was associated with a greater likelihood of poypharmacy, excessive polypharmacy, and potential IDU in elderly Swedish persons, even after controlling for age, sex, place of residence, and comorbidity. Women with low education had slightly higher likelihood of receiving polypharmacy and potential IDU than men with low education. The recently established SPDR may be useful for continuous monitoring and for designing interventions to improve drug quality in low‐educated elderly people.
Lack of Effect of Tai Chi Chuan in Preventing Falls in Elderly People Living at Home: A Randomized Clinical Trial
Authors: Logghe Inge H. J. , Zeeuwe Petra E. M. , Verhagen Arianne P. , Wijnen‐Sponselee Ria M. T. , Willemsen Sten P. , Bierma‐Zeinstra Sita M. A. , Van Rossum Erik , Faber Marjan J. , Koes Bart W. 
Published: November 2008

OBJECTIVES: To evaluate the effectiveness of Tai Chi Chuan in fall prevention in elderly people living at home with a high risk of falling.DESIGN: Randomized controlled trial.SETTING: Two industrial towns in the western part of the Netherlands.PARTICIPANTS: Two hundred sixty‐nine elderly people (average age 77) living at home with a high risk of falling.INTERVENTIONS: The intervention group received Tai Chi Chuan training for 1 hour twice a week for 13 weeks; the control group received usual care. Both groups received a brochure containing general information on how to prevent fall incidents.MEASUREMENTS: Primary outcome was the number of falls over 12 months. Secondary outcomes were balance, fear of falling, blood pressure, heart rate at rest, forced expiratory volume during the first second, peak expiratory flow, physical activity, and functional status.RESULTS: After 12 months, no lower fall risk in the Tai Chi Chuan group was observed than in the control group (adjusted hazard ratio=1.16; 95% confidence interval=0.84–1.60), and there were no significant intervention effects on the secondary outcome measures.CONCLUSION: These results suggest that Tai Chi Chuan may not be effective in elderly people at a high risk of falling who live at home.
Albumin, Apolipoprotein E‐ɛ4 and Cognitive Decline in Community‐Dwelling Chinese Older Adults
Authors: Ng Tze‐Pin , Niti Mathew , Feng Lei , Kua Ee‐Heok , Yap Keng‐Bee 
Published: November 2008

OBJECTIVES: To examine the association between serum albumin and cognitive impairment and decline in community‐living older adults.DESIGNS: Population‐based cohort study, followed up to 2 years; serum albumin, apolipoprotein E (APOE)‐ɛ4, and cognitive impairment measured at baseline and cognitive decline (≥2‐point drop in Mini‐Mental State Examination (MMSE) score). Odds ratios were controlled for age, sex, education, medical comorbidity, hypertension, diabetes mellitus, cardiac disease, stroke, smoking, alcohol drinking, depression, APOE‐ɛ4, nutritional status, body mass index, anemia, glomerular filtration rate, and baseline MMSE.SETTINGS: Local area whole population.PARTICIPANTS: One thousand six hundred sixty‐four Chinese older adults aged 55 and older.RESULTS: The mean age of the cohort was 66.0±7.3, 65% were women, mean serum albumin was 42.3±3.1 g/L, and mean MMSE score was 27.2±3.2. Lower albumin tertile was associated with greater risk of cognitive impairment in cross‐sectional analysis (low, odds ratio (OR)=2.30, 95% confidence interval (CI)=1.31–4.03); medium, OR=1.59, 95% CI=0.88–2.88) versus high (P for trend=.002); and with cognitive decline in longitudinal analyses: low, OR=1.73, 95% CI=1.18–2.55; medium, OR=1.32, 95% CI=0.89–1.95, vs high (P for trend=.004). In cognitively unimpaired respondents at baseline (MMSE≥24), similar associations with cognitive decline were observed (P for trends <.002). APOE‐ɛ4 appeared to modify the association, due mainly to low rates of cognitive decline in subjects with the APOE‐ɛ4 allele and high albumin.CONCLUSION: Low albumin was an independent risk marker for cognitive decline in community‐living older adults.
Cause of Death in Older Men After the Diagnosis of Prostate Cancer
Authors: Ketchandji Melanie , Kuo Yong‐Fang , Shahinian Vahakn B. , Goodwin James S. 
Published: November 2008

OBJECTIVES: To compare survival and cause of death in men aged 65 and older diagnosed with prostate cancer and with survival and cause of death in a noncancer control population.DESIGN: Retrospective cohort from a population‐based tumor registry linked to Medicare claims data.SETTING: Eleven regions of the Surveillance, Epidemiology and End Results (SEER) Tumor Registry.PARTICIPANTS: Men aged 65 to 84 (N=208,601) diagnosed with prostate cancer from 1988 through 2002 formed the basis for different analytical cohorts.MEASUREMENTS: Survival as a function of stage and tumor grade (low, Gleason grade<7; moderate, grade=7; and high, grade=8–10) was compared with survival in men without any cancer using Cox proportional hazards regression. Cause of death according to stage and tumor grade were compared using chi‐square statistics.RESULTS: Men with early‐stage prostate cancer and with low‐ to moderate‐grade tumors (59.1% of the entire sample) experienced a survival not substantially worse than men without prostate cancer. In those men, cardiovascular disease and other cancers were the leading causes of death.CONCLUSION: The excellent survival of older men with early‐stage, low‐ to moderate‐grade prostate cancer, along with the patterns of causes of death, implies that this population would be well served by an ongoing focus on screening and prevention of cardiovascular disease and other cancers.