Hippocampal sclerosis and temporal lobe epilepsy following febrile status epilepticus: The FEBSTAT study.

OBJECTIVE: This study was undertaken to determine whether hippocampal T2 hyperintensity predicts sequelae of febrile status epilepticus, including hippocampal atrophy, sclerosis, and mesial temporal lobe epilepsy. METHODS: Acute magnetic resonance imaging (MRI) was obtained within a mean of 4.4 (SD = 5.5, median = 2.0) days after febrile status on >200 infants with follow-up MRI at approximately 1, 5, and 10 years. Hippocampal size, morphology, and T2 signal intensity were scored visually by neuroradiologists blinded to clinical details. Hippocampal volumetry provided quantitative measurement. Upon the occurrence of two or more unprovoked seizures, subjects were reassessed for epilepsy. Hippocampal volumes were normalized using total brain volumes. RESULTS: Fourteen of 22 subjects with acute hippocampal T2 hyperintensity returned for follow-up MRI, and 10 developed definite hippocampal sclerosis, which persisted through the 10-year follow-up. Hippocampi appearing normal initially remained normal on visual inspection. However, in subjects with normal-appearing hippocampi, volumetrics indicated that male, but not female, hippocampi were smaller than controls, but increasing hippocampal asymmetry was not seen following febrile status. Forty-four subjects developed epilepsy; six developed mesial temporal lobe epilepsy and, of the six, two had definite, two had equivocal, and two had no hippocampal sclerosis. Only one subject developed mesial temporal epilepsy without initial hyperintensity, and that subject had hippocampal malrotation. Ten-year cumulative incidence of all types of epilepsy, including mesial temporal epilepsy, was highest in subjects with initial T2 hyperintensity and lowest in those with normal signal and no other brain abnormalities. SIGNIFICANCE: Hippocampal T2 hyperintensity following febrile status epilepticus predicted hippocampal sclerosis and significant likelihood of mesial temporal lobe epilepsy. Normal hippocampal appearance in the acute postictal MRI was followed by maintained normal appearance, symmetric growth, and lower risk of epilepsy. Volumetric measurement detected mildly decreased hippocampal volume in males with febrile status.

Spontaneous Appearance of Triiodide Covering the Topmost Layer of the Iodide Solution Interface Without Photo-Oxidation.

Ions containing iodine atoms at the vapor-aqueous solution interfaces critically affect aerosol growth and atmospheric chemistry due to their complex chemical nature and multivalency. While the surface propensity of iodide ions has been intensely discussed in the context of the Hofmeister series, the stability of various ions containing iodine atoms at the vapor-water interface has been debated. Here, we combine surface-specific sum-frequency generation (SFG) vibrational spectroscopy with ab initio molecular dynamics simulations to examine the extent to which iodide ions cover the aqueous surface. The SFG probe of the free O-D stretch mode of heavy water indicates that the free O-D group density decreases drastically at the interface when the bulk NaI concentration exceeds ∼2 M. The decrease in the free O-D group density is attributed to the spontaneous appearance of triiodide that covers the topmost interface rather than to the surface adsorption of iodide. This finding demonstrates that iodide is not surface-active, yet the highly surface-active triiodide is generated spontaneously at the water-air interface, even under dark and oxygen-free conditions. Our study provides an important first step toward clarifying iodine chemistry and pathways for aerosol formation.

Ultrafast Surface-Specific Spectroscopy of Water at a Photoexcited TiO2 Model Water-Splitting Photocatalyst.

A critical step in photocatalytic water dissociation is the hole-mediated oxidation reaction. Molecular-level insights into the mechanism of this complex reaction under realistic conditions with high temporal resolution are highly desirable. Here, we use femtosecond time-resolved, surface-specific vibrational sum frequency generation spectroscopy to study the photo-induced reaction directly at the interface of the photocatalyst TiO2 in contact with liquid water at room temperature. Thanks to the inherent surface specificity of the spectroscopic method, we can follow the reaction of solely the interfacial water molecules directly at the interface at timescales on which the reaction takes place. Following the generation of holes at the surface immediately after photoexcitation of the catalyst with UV light, water dissociation occurs on a sub-20 ps timescale. The reaction mechanism is similar at pH 3 and 11. In both cases, we observe the conversion of H2 O into Ti-OH groups and the deprotonation of pre-existing Ti-OH groups. This study provides unique experimental insights into the early steps of the photo-induced dissociation processes at the photocatalyst-water interface, relevant to the design of improved photocatalysts.

Bulklike Vibrational Coupling of Surface Water Revealed by Sum-Frequency Generation Spectroscopy.

Vibrational coupling between interfacial water molecules is important for energy dissipation after on-water chemistry, yet intensely debated. Here, we quantify the interfacial vibrational coupling strength through the linewidth of surface-specific vibrational spectra of the water's O─H (O─D) stretch region for neat H_{2}O/D_{2}O and their isotopic mixtures. The local-field-effect-corrected experimental SFG spectra reveal that the vibrational coupling between hydrogen-bonded interfacial water O─H groups is comparable to that in bulk water, despite the effective density reduction at the interface.

A review of whole-process control of industrial volatile organic compounds in China.

Volatile organic compounds (VOCs) play an important role in the formation of ground-level ozone and secondary organic aerosol (SOA), and they have been key issues in current air pollution prevention and control in China. Considerable attention has been paid to industrial activities due to their large and relatively complex VOCs emissions. The present research aims to provide a comprehensive review on whole-process control of industrial VOCs, which mainly includes source reduction, collection enhancement and end-pipe treatments. Lower VOCs materials including water-borne ones are the keys to source substitution in industries related to coating and solvent usage, leak detection and repair (LDAR) should be regarded as an efficient means of source reduction in refining, petrochemical and other chemical industries. Several types of VOCs collection methods such as gas-collecting hoods, airtight partitions and others are discussed, and airtight collection at negative pressure yields the best collection efficiency. Current end-pipe treatments like UV oxidation, low-temperature plasma, activated carbon adsorption, combustion, biodegradation, and adsorption-combustion are discussed in detail. Finally, several recommendations are made for future advanced treatment and policy development in industrial VOCs emission control.

Molecular Structure and Modeling of Water-Air and Ice-Air Interfaces Monitored by Sum-Frequency Generation.

From a glass of water to glaciers in Antarctica, water-air and ice-air interfaces are abundant on Earth. Molecular-level structure and dynamics at these interfaces are key for understanding many chemical/physical/atmospheric processes including the slipperiness of ice surfaces, the surface tension of water, and evaporation/sublimation of water. Sum-frequency generation (SFG) spectroscopy is a powerful tool to probe the molecular-level structure of these interfaces because SFG can specifically probe the topmost interfacial water molecules separately from the bulk and is sensitive to molecular conformation. Nevertheless, experimental SFG has several limitations. For example, SFG cannot provide information on the depth of the interface and how the orientation of the molecules varies with distance from the surface. By combining the SFG spectroscopy with simulation techniques, one can directly compare the experimental data with the simulated SFG spectra, allowing us to unveil the molecular-level structure of water-air and ice-air interfaces. Here, we present an overview of the different simulation protocols available for SFG spectra calculations. We systematically compare the SFG spectra computed with different approaches, revealing the advantages and disadvantages of the different methods. Furthermore, we account for the findings through combined SFG experiments and simulations and provide future challenges for SFG experiments and simulations at different aqueous interfaces.

Effect of Electronic Nicotine Delivery Systems on Cigarette Abstinence in Smokers With No Plans to Quit: Exploratory Analysis of a Randomized Placebo-Controlled Trial.

INTRODUCTION: The extent to which use of electronic nicotine delivery systems (ENDS) for smoking reduction leads to cigarette abstinence in smokers with no plans to quit smoking is unclear. This exploratory analysis examined the effects of ENDS delivering different amounts of nicotine on cigarette abstinence up to 24-week follow-up, in comparison to placebo or a behavioral substitute. METHODS: This four-arm parallel-group, randomized, placebo-controlled trial took place at two academic medical centers in the United States (Penn State Hershey and Virginia Commonwealth University). Participants were current adult smokers (N = 520) interested in reducing but not planning to quit. They received brief advice and were randomized to one of four 24-week conditions, receiving either an eGo-style ENDS paired with 0, 8, or 36 mg/ml nicotine liquid (double-blind) or a cigarette-shaped tube, as a cigarette substitute (CS). Self-reported daily cigarette consumption and exhaled carbon monoxide (CO) were measured at all study visits. Outcomes included intent-to-treat, self-reported 7-day cigarette abstinence, biochemically confirmed by exhaled CO at 24 weeks after randomization. RESULTS: At 24 weeks, significantly more participants in the 36 mg/ml condition (14/130, 10.8%) than in the 0 mg/ml condition (1/130, 0.8%) and the CS condition (4/130, 3.1%) were abstinent (relative risk = 14 [95% CI = 1.9-104.9] and 3.5 [95% CI = 1.2-10.4], respectively). The abstinence rate in the 8 mg/ml condition was 4.6% (6/130). CONCLUSIONS: When smokers seeking to reduce smoking tried ENDS, few quit smoking in the short term. However, if smokers continued to use an ENDS with cigarette-like nicotine delivery, a greater proportion completely switched to ENDS, as compared with placebo or a cigarette substitute. IMPLICATIONS: The extent to which use of electronic nicotine delivery systems (ENDS) for smoking reduction leads to cigarette abstinence in smokers with no plans to quit smoking was unclear. This randomized trial found that ENDS with nicotine delivery approaching that of a cigarette are more effective in helping ambivalent smokers to quit cigarette smoking.

Accurate molecular orientation at interfaces determined by multimode polarization-dependent heterodyne-detected sum-frequency generation spectroscopy via multidimensional orientational distribution function.

Many essential processes occur at soft interfaces, from chemical reactions on aqueous aerosols in the atmosphere to biochemical recognition and binding at the surface of cell membranes. The spatial arrangement of molecules specifically at these interfaces is crucial for many of such processes. The accurate determination of the interfacial molecular orientation has been challenging due to the low number of molecules at interfaces and the ambiguity of their orientational distribution. Here, we combine phase- and polarization-resolved sum-frequency generation (SFG) spectroscopy to obtain the molecular orientation at the interface. We extend an exponentially decaying orientational distribution to multiple dimensions, which, in conjunction with multiple SFG datasets obtained from the different vibrational modes, allows us to determine the molecular orientation. We apply this new approach to formic acid molecules at the air-water interface. The inferred orientation of formic acid agrees very well with ab initio molecular dynamics data. The phase-resolved SFG multimode analysis scheme using the multidimensional orientational distribution thus provides a universal approach for obtaining the interfacial molecular orientation.

Nucleation and dissociation of methane clathrate embryo at the gas-water interface.

Among natural energy resources, methane clathrate has attracted tremendous attention because of its strong relevance to current energy and environment issues. Yet little is known about how the clathrate starts to nucleate and disintegrate at the molecular level, because such microscopic processes are difficult to probe experimentally. Using surface-specific sum-frequency vibrational spectroscopy, we have studied in situ the nucleation and disintegration of methane clathrate embryos at the methane-gas-water interface under high pressure and different temperatures. Before appearance of macroscopic methane clathrate, the interfacial structure undergoes 3 stages as temperature varies, namely, dissolution of methane molecules into water interface, formation of cage-like methane-water complexes, and appearance of microscopic methane clathrate, while the bulk water structure remains unchanged. We find spectral features associated with methane-water complexes emerging in the induction time. The complexes are present over a wide temperature window and act as nuclei for clathrate growth. Their existence in the melt of clathrates explains why melted clathrates can be more readily recrystallized at higher temperature, the so-called "memory effect." Our findings here on the nucleation mechanism of clathrates could provide guidance for rational control of formation and disintegration of clathrates.

Nature of Excess Hydrated Proton at the Water-Air Interface.

Understanding the interfacial molecular structure of acidic aqueous solutions is important in the context of, e.g., atmospheric chemistry, biophysics, and electrochemistry. The hydration of the interfacial proton is necessarily different from that in the bulk, given the lower effective density of water at the interface, but has not yet been elucidated. Here, using surface-specific vibrational spectroscopy, we probe the response of interfacial protons at the water-air interface and reveal the interfacial proton continuum. Combined with spectral calculations based on ab initio molecular dynamics simulations, the proton at the water-air interface is shown to be well-hydrated, despite the limited availability of hydration water, with both Eigen and Zundel structures coexisting at the interface. Notwithstanding the interfacial hydrated proton exhibiting bulk-like structures, a substantial interfacial stabilization by -1.3 ± 0.2 kcal/mol is observed experimentally, in good agreement with our free energy calculations. The surface propensity of the proton can be attributed to the interaction between the hydrated proton and its counterion.

Decoding the molecular water structure at complex interfaces through surface-specific spectroscopy of the water bending mode.

The structure of interfacial water determines atmospheric chemistry, wetting properties of materials, and protein folding. The challenge of investigating the properties of specific interfacial water molecules has frequently been confronted using surface-specific sum-frequency generation (SFG) vibrational spectroscopy using the O-H stretch mode. While perfectly suited for the water-air interface, for complex interfaces, a potential complication arises from the contribution of hydroxyl or amine groups of non-water species present at the surface, such as surface hydroxyls on minerals, or O-H and N-H groups contained in proteins. Here, we present a protocol to extract the hydrogen bond strength selectively of interfacial water, through the water bending mode. The bending mode vibrational frequency distribution provides a new avenue for unveiling the hydrogen bonding structure of interfacial water at complex aqueous interfaces. We demonstrate this method for the water-CaF2 and water-protein interfaces. For the former, we show that this method can indeed single out water O-H groups from surface hydroxyls, and that with increasing pH, the hydrogen-bonded network of interfacial water strengthens. Furthermore, we unveil enhanced hydrogen bonding of water, compared to bulk water, at the interface with human serum albumin proteins, a prototypical bio-interface.

Impact of adolescent obesity on middle-age health of women given data MAR.

We analyze adolescent BMI and middle-age systolic blood pressure (SBP) repeatedly measured on women enrolled in the Fels Longitudinal Study (FLS) between 1929 and 2010 to address three questions: Do adolescent-specific growth rates in body mass index (BMI) and menarche affect middle-age SBP? Do they moderate the aging effect on middle-age SBP? Have the effects changed over historical time? To address the questions, we propose analyzing a growth curve model (GCM) that controls for age, birth-year cohort, and historical time. However, several complications in the data make the GCM analysis nonstandard. First, the person-specific adolescent BMI and middle-age SBP trajectories are unobservable. Second, missing data are substantial on BMI, SBP, and menarche. Finally, modeling the latent trajectories for BMI and SBP, repeatedly measured on two distinct sets of unbalanced time points, are computationally intensive. We adopt a bivariate GCM for BMI and SBP with correlated random coefficients. To efficiently handle missing values of BMI, SBP, and menarche assumed missing at random, we estimate their joint distribution by maximum likelihood via the EM algorithm where the correlated random coefficients and menarche are multivariate normal. The estimated distribution will be transformed to the desired GCM for SBP that includes the random coefficients of BMI and menarche as covariates. We demonstrate unbiased estimation by simulation. We find that adolescent growth rates in BMI and menarche are positively associated with, and moderate, the aging effect on SBP in middle age, controlling for age, cohort, and historical time, but the effect sizes are at most modest. The aging effect is significant on SBP, controlling for cohort and historical time, but not vice versa.

How surface-specific is 2nd-order non-linear spectroscopy?

Surfaces and interfaces play important roles in many processes and reactions and are therefore intensively studied, often with the aim of obtaining molecular-level information from just the interfacial layer. Generally, only the first few molecular layers next to the interface are relevant for the surface processes. In the past decades, 2nd-order nonlinear spectroscopies including sum-frequency generation and second harmonic generation have developed into powerful tools for obtaining molecularly specific insights into the interfacial region. These approaches have contributed substantially to our understanding of a wide range of physical phenomena. However, along with their wide-ranging applications, it has been realized that the implied surface-specificity of these approaches may not always be warranted. Specifically, the bulk quadrupole contribution beyond the electric dipole-approximation for a system with a weak nonlinear interface signal, as well as the diffuse layer contribution at charged interfaces, could mask the surface information. In this perspective paper, we discuss the surface-specificity of 2nd-order nonlinear spectroscopy, especially considering these two contributions.

Orientational Distribution of Free O-H Groups of Interfacial Water is Exponential.

The orientational distribution of free O-H (O-D) groups at the H_{2}O- (D_{2}O-)air interface is investigated using combined molecular dynamics (MD) simulations and sum-frequency generation (SFG) experiments. The average angle of the free O-H groups, relative to the surface normal, is found to be ∼63°, substantially larger than previous estimates of 30°-40°. This discrepancy can be traced to erroneously assumed Gaussian or stepwise orientational distributions of free O-H groups. Instead, the MD simulation and SFG measurement reveal a broad and exponentially decaying orientational distribution. The broad orientational distribution indicates the presence of the free O-H group pointing down to the bulk. We ascribe the origin of such free O-H groups to the presence of capillary waves on the water surface.

Surface sum-frequency vibrational spectroscopy of nonpolar media.

Sum-frequency generation spectroscopy is surface specific only if the bulk contribution to the signal is negligible. Negligible bulk contribution is, however, not necessarily true, even for media with inversion symmetry. The inevitable challenge is to find the surface spectrum in the presence of bulk contribution, part of which has been believed to be inseparable from the surface contribution. Here, we show that, for nonpolar media, it is possible to separately deduce surface and bulk spectra from combined phase-sensitive sum-frequency vibrational spectroscopic measurements in reflection and transmission. The study of benzene interfaces is presented as an example.

[Risk Factors of Retained Central Venous Catheter Associated Bloodstream Infections in Hospitalized Patients].

BACKGROUND: Despite recent efforts in Taiwan to reduce the risk and incidence of central venous catheter associated bloodstream infections (CABSI), the results as reported by the Taiwan Centers for Disease Control, when compared with the results achieved in the USA, indicate that Taiwan must promote the central venous catheter bundle approach more effectively. Furthermore, the risk factors for CABSI should be explored further in order to facilitate the development and implementation of effective related improvement strategies. PURPOSE: To explore the risk factors for CABSI after adjusting for confounding factors and to analyze the appropriate protocol for applying retained central venous catheters in hospitalized patients and the impact of CABSI. METHODS: The ethics committee approved this retrospective case-control study. Hospitalized patients who were older than 20 years of age and were currently experiencing their first instance of CABSI were recruited between March 1, 2014 to October 31, 2014 as the case group. In addition, a control group was recruited in a 1:2 ratio from a random sample of patients listed in the medical order system who had received a central venous catheter but did not experience CABSI. Anyone who did not meet the above criteria was excluded. Data collected included basic demographic characteristics, basic catheter information, and the main reason for the catheter being in situ during the 48 hours prior to contracting CABSI or catheter removal. RESULTS: A total of 65 patients with CABSI comprised the case group and 130 patients without CABSI comprised the control group. After controlling for potentially confounding factors using logistic regression analysis, the independent risk factors of CABSI (p < .05) were identified as: staying in the intensive care unit, having a high APACHE II (acute physiology and chronic health evaluation II) score, and having diabetes mellitus. Moreover, while having inappropriate central venous catheter in situ was found to not significantly influence CABSI (OR, 2.41; 95% CI [0.65-8.91]), we identified that about 10.8% of retained central venous catheter applications were unnecessary due to the lack of sufficient indications for use. CONCLUSIONS: We recommend that nursing staffs should remind physicians to evaluate carefully the need to use central venous catheters and should fully implement sterile protocols to protect the health of high-risk patients. In addition, nursing staffs should assess the central venous catheter daily and should remind physicians to remove the catheter as soon as possible in the absence of indications for use.

Plasma cytokines associated with febrile status epilepticus in children: A potential biomarker for acute hippocampal injury.

OBJECTIVE: Our aim was to explore the association between plasma cytokines and febrile status epilepticus (FSE) in children, as well as their potential as biomarkers of acute hippocampal injury. METHODS: Analysis was performed on residual samples of children with FSE (n = 33) as part of the Consequences of Prolonged Febrile Seizures in Childhood study (FEBSTAT) and compared to children with fever (n = 17). Magnetic resonance imaging (MRI) was obtained as part of FEBSTAT within 72 h of FSE. Cytokine levels and ratios of antiinflammatory versus proinflammatory cytokines in children with and without hippocampal T2 hyperintensity were assessed as biomarkers of acute hippocampal injury after FSE. RESULTS: Levels of interleukin (IL)-8 and epidermal growth factor (EGF) were significantly elevated after FSE in comparison to controls. IL-1ß levels trended higher and IL-1RA trended lower following FSE, but did not reach statistical significance. Children with FSE were found to have significantly lower ratios of IL-1RA/IL-1ß and IL-1RA/IL-8. Specific levels of any one individual cytokine were not associated with FSE. However, lower ratios of IL-1RA/IL-1ß, IL-1RA/1L-6, and IL-1RA/ IL-8 were all associated with FSE. IL-6 and IL-8 levels were significantly higher and ratios of IL-1RA/IL-6 and IL-1RA/IL-8 were significantly lower in children with T2 hippocampal hyperintensity on MRI after FSE in comparison to those without hippocampal signal abnormalities. Neither individual cytokine levels nor ratios of IL-1RA/IL-1ß or IL-1RA/IL-8 were predictive of MRI changes. However, a lower ratio of IL-1RA/IL-6 was strongly predictive (odds ratio [OR] 21.5, 95% confidence interval [CI] 1.17-393) of hippocampal T2 hyperintensity after FSE. SIGNIFICANCE: Our data support involvement of the IL-1 cytokine system, IL-6, and IL-8 in FSE in children. The identification of the IL-1RA/IL-6 ratio as a potential biomarker of acute hippocampal injury following FSE is the most significant finding. If replicated in another study, the IL-1RA/IL-6 ratio could represent a serologic biomarker that offers rapid identification of patients at risk for ultimately developing mesial temporal lobe epilepsy (MTLE).

Parental stress, pediatric quality of life, and behavior at baseline and one-year follow-up: Results from the FEBSTAT study.

Febrile status epilepticus is a serious and frightening event in the life of the child and parent. It is regarded as a medical emergency with potential long lasting consequences. The purpose of this study was to look at the immediate and long term effects of such an event on parental stress and parents' perception of their child's physical and psychosocial wellbeing. METHODS: From 2003 to 2010, 199 subjects, age 1 month to 5 years, were recruited as part of a prospective, multicenter study (FEBSTAT) of consequences of febrile status epilepticus (FSE). At one month and one year after the episode of FSE, parents were asked to complete the Parenting Stress Index, short form (PSI/SF), the Pediatric Quality of Life Inventory (PedsQL) and the Child Behavior Checklist (CBCL). In addition to PedsQL and CBCL in the FEBSTAT subjects only, a comparison was made between Columbia Study of First Febrile Seizures subjects with a first simple febrile seizure (SFS) and the FEBSTAT group, including 15 subjects with FSE from the Columbia group, in the area of parental stress which was administered at the same time intervals in both studies. RESULTS: At baseline, the PSI/SF was statistically significantly higher for SFS versus FSE on the parent-child dysfunctional score and the total raw score, however at one year this difference resolved. In the FSE group, significantly higher parental stress over one year was reported in children with abnormal versus normal prior development (p= 0.02). Prior abnormal development was a risk factor at 1 year for lower total PEDSQL (p=0.01) versus prior normal development. Mean scores on the CBCL at baseline and 1 year were within the normal range for both empirically based scales and major risk factors. CONCLUSIONS: Parents of children experiencing a SFS experienced more stress at baseline than those with FSE. Families of children in the FEBSTAT cohort with identified development problems at baseline that continued, or progressed over the one year period, reported decreasing QOL.

Nonlinear response surface in the study of interaction analysis of three combination drugs.

Few articles have been written on analyzing three-way interactions between drugs. It may seem to be quite straightforward to extend a statistical method from two-drugs to three-drugs. However, there may exist more complex nonlinear response surface of the interaction index (II) with more complex local synergy and/or local antagonism interspersed in different regions of drug combinations in a three-drug study, compared in a two-drug study. In addition, it is not possible to obtain a four-dimensional (4D) response surface plot for a three-drug study. We propose an analysis procedure to construct the dose combination regions of interest (say, the synergistic areas with II≤0.9). First, use the model robust regression method (MRR), a semiparametric method, to fit the entire response surface of the II, which allows to fit a complex response surface with local synergy/antagonism. Second, we run a modified genetic algorithm (MGA), a stochastic optimization method, many times with different random seeds, to allow to collect as many feasible points as possible that satisfy the estimated values of II≤0.9. Last, all these feasible points are used to construct the approximate dose regions of interest in a 3D. A case study with three anti-cancer drugs in an in vitro experiment is employed to illustrate how to find the dose regions of interest.

Risk factors for subsequent febrile seizures in the FEBSTAT study.

OBJECTIVES: To identify risk and risk factors for developing a subsequent febrile seizure (FS) in children with a first febrile status epilepticus (FSE) compared to a first simple febrile seizure (SFS). To identify home use of rescue medications for subsequent FS. METHODS: Cases included a first FS that was FSE drawn from FEBSTAT and Columbia cohorts. Controls were a first SFS. Cases and controls were classified according to established FEBSTAT protocols. Cumulative risk for subsequent FS over a 5-year period was compared in FSE versus SFS, and Cox proportional hazards regression was conducted. Separate analysis examined subsequent FS within FSE. The use of rescue medications at home was assessed for subsequent FS. RESULTS: Risk for a subsequent FSE was significantly increased in FSE versus SFS. Any magnetic resonance imaging (MRI) abnormality increased the risk 3.4-fold (p < 0.05), adjusting for age at first FS and FSE and in analyses restricted to children whose first FS was FSE (any MRI abnormality hazard ratio [HR] 2.9, p < 0.05). The risk for a second FS of any type or of subsequent FS lasting >10 min over the 5-year follow-up did not differ in FSE versus SFS. Rectal diazepam was administered at home to 5 (23.8%) of 21 children with subsequent FS lasting ≥10 min. SIGNIFICANCE: Compared to controls, FSE was associated with an increased risk for subsequent FSE, suggesting the propensity of children with an initial prolonged seizure to experience a prolonged recurrence. Any baseline MRI abnormality increased the recurrence risk when FSE was compared to SFS and when FSE was studied alone. A minority of children with a subsequent FS lasting 10 min or longer were treated with rectal diazepam at home, despite receiving prescriptions after the first FSE. This indicates the need to further improve the education of clinicians and parents in order to prevent subsequent FSE.