Periodic and rhythmic patterns in critically ill children: Incidence, interrater agreement, and seizures.

OBJECTIVES: We aimed to determine the incidence of periodic and rhythmic patterns (PRP), assess the interrater agreement between electroencephalographers scoring PRP using standardized terminology, and analyze associations between PRP and electrographic seizures (ES) in critically ill children. METHODS: This was a prospective observational study of consecutive critically ill children undergoing continuous electroencephalographic monitoring (CEEG). PRP were identified by one electroencephalographer, and then two pediatric electroencephalographers independently scored the first 1-h epoch that contained PRP using standardized terminology. We determined the incidence of PRPs, evaluated interrater agreement between electroencephalographers scoring PRP, and evaluated associations between PRP and ES. RESULTS: One thousand three hundred ninety-nine patients underwent CEEG. ES occurred in 345 (25%) subjects. PRP, ES + PRP, and ictal-interictal continuum (IIC) patterns occurred in 142 (10%), 81 (6%), and 93 (7%) subjects, respectively. The most common PRP were generalized periodic discharges (GPD; 43, 30%), lateralized periodic discharges (LPD; 34, 24%), generalized rhythmic delta activity (GRDA; 34, 24%), bilateral independent periodic discharges (BIPD; 14, 10%), and lateralized rhythmic delta activity (LRDA; 11, 8%). ES risk varied by PRP type (p < .01). ES occurrence was associated with GPD (odds ratio [OR] = 6.35, p < .01), LPD (OR = 10.45, p < .01), BIPD (OR = 6.77, p < .01), and LRDA (OR = 6.58, p < .01). Some modifying features increased the risk of ES for each of those PRP. GRDA was not significantly associated with ES (OR = 1.34, p = .44). Each of the IIC patterns was associated with ES (OR = 6.83-8.81, p < .01). ES and PRP occurred within 6 h (before or after) in 45 (56%) subjects. SIGNIFICANCE: PRP occurred in 10% of critically ill children who underwent CEEG. The most common patterns were GPD, LPD, GRDA, BIPD, and LRDA. The GPD, LPD, BIPD, LRDA, and IIC patterns were associated with ES. GRDA was not associated with ES.

Validation of a model to predict electroencephalographic seizures in critically ill children.

OBJECTIVE: Electroencephalographic seizures (ESs) are common in encephalopathic critically ill children, but identification requires extensive resources for continuous electroencephalographic monitoring (CEEG). In a previous study, we developed a clinical prediction rule using three clinical variables (age, acute encephalopathy category, clinically evident seizure[s] prior to CEEG initiation) and two electroencephalographic (EEG) variables (EEG background category and interictal discharges within the first 30 minutes of EEG) to identify patients at high risk for ESs for whom CEEG might be essential. In the current study, we aimed to validate the ES prediction model using an independent cohort. METHODS: The prospectively acquired validation cohort consisted of 314 consecutive critically ill children treated in the Pediatric Intensive Care Unit of a quaternary care referral hospital with acute encephalopathy undergoing clinically indicated CEEG. We calculated test characteristics using the previously developed prediction model in the validation cohort. As in the generation cohort study, we selected a 0.10 cutpoint to emphasize sensitivity. RESULTS: The incidence of ESs in the validation cohort was 22%. The generation and validation cohorts were alike in most clinical and EEG characteristics. The ES prediction model was well calibrated and well discriminating in the validation cohort. The model had a sensitivity of 90%, specificity of 37%, positive predictive value of 28%, and negative predictive value of 93%. If applied, the model would limit 31% of patients from undergoing CEEG while failing to identify 10% of patients with ESs. The model had similar performance characteristics in the generation and validation cohorts. SIGNIFICANCE: A model employing five readily available clinical and EEG variables performed well when validated in a new consecutive cohort. Implementation would substantially reduce CEEG utilization, although some patients with ESs would not be identified. This model may serve a critical role in targeting limited CEEG resources to critically ill children at highest risk for ESs.

Development of a model to predict electroencephalographic seizures in critically ill children.

OBJECTIVE: Electroencephalographic seizures (ESs) are common in encephalopathic critically ill children, but ES identification with continuous electroencephalography (EEG) monitoring (CEEG) is resource-intense. We aimed to develop an ES prediction model that would enable clinicians to stratify patients by ES risk and optimally target limited CEEG resources. We aimed to determine whether incorporating data from a screening EEG yielded better performance characteristics than models using clinical variables alone. METHODS: We performed a prospective observational study of 719 consecutive critically ill children with acute encephalopathy undergoing CEEG in the pediatric intensive care unit of a quaternary care institution between April 2017 and February 2019. We identified clinical and EEG risk factors for ES. We evaluated model performance with area under the receiver-operating characteristic (ROC) curve (AUC), validated the optimal model with the highest AUC using a fivefold cross-validation, and calculated test characteristics emphasizing high sensitivity. We applied the optimal operating slope strategy to identify the optimal cutoff to define whether a patient should undergo CEEG. RESULTS: The incidence of ES was 26%. Variables associated with increased ES risk included age, acute encephalopathy category, clinical seizures prior to CEEG initiation, EEG background, and epileptiform discharges. Combining clinical and EEG variables yielded better model performance (AUC 0.80) than clinical variables alone (AUC 0.69; P < .01). At a 0.10 cutoff selected to emphasize sensitivity, the optimal model had a sensitivity of 92%, specificity of 37%, positive predictive value of 34%, and negative predictive value of 93%. If applied, the model would limit 29% of patients from undergoing CEEG while failing to identify 8% of patients with ES. SIGNIFICANCE: A model employing readily available clinical and EEG variables could target limited CEEG resources to critically ill children at highest risk for ES, making CEEG-guided management a more viable neuroprotective strategy.

Standardized ethograms and a device for assessing amphibian thermal responses in a warming world.

Most predictions of how populations and species of ectotherms will respond to global warming are based on estimates of the temperature at which organisms lose motor control (i.e., CTmax - the Critical Thermal Maximum). Here, we describe a non-lethal protocol and ethograms to estimate the relative tolerance of amphibians to increasing temperatures. These methods-suitable for field or laboratory conditions-are replicable, inexpensive and applicable to both post-metamorphic stages and organisms with direct development. We illustrate the use of this standardized protocol for four amphibians from a tropical cloud forest in Veracruz, Mexico with contrasting life histories: a lungless salamander (Aquiloeurycea cafetalera: Plethodontidae), a leaf-litter frog (Craugastor rhodopis: Craugastoridae), a semiaquatic frog (Lithobates berlandieri: Ranidae), and a tree frog (Rheohyla miotympanum: Hylidae). We identified four behavioral responses preceding CTmax for all amphibians included in this study: 1) Optimal Activity Range, 2) Supra-optimal Activity Range, 3) Heat Stress Range, and 4) Involuntary Movements Range. Additionally, we identified a fifth parameter associated with resilience to heat shock: 5) Recovery Stage after reaching CTmax. We conclude that the behavioral responses preceding the Critical Thermal Maximum are as informative as CTmax. Using behavioral responses to estimate thermal tolerance has the additional advantage of reducing the risk of injury or death of amphibians during physiological experiments.

Electroencephalographic seizures in critically ill children: Management and adverse events.

OBJECTIVE: Guidelines recommend that encephalopathic critically ill children undergo continuous electroencephalographic (CEEG) monitoring for electrographic seizure (ES) identification and management. However, limited data exist on antiseizure medication (ASM) safety for ES treatment in critically ill children. METHODS: We performed a single-center prospective observational study of encephalopathic critically ill children undergoing CEEG. Clinical and EEG features and ASM utilization patterns were evaluated. We determined the incidence, types, and risk factors for adverse events associated with ASM administration. RESULTS: A total of 472 consecutive critically ill children undergoing CEEG were enrolled. ES occurred in 131 children (28%). Clinicians administered ASM to 108 children with ES (82%). ES terminated after the initial ASM in 38% of patients who received one ASM, after the second ASM in 35% of patients who received two ASMs, after the third ASM in 50% of patients who received three ASMs, and after the fourth ASM in 53% of patients who received four ASMs. Thirty patients (28%) received anesthetic infusions for ES management. Adverse events occurred in 18 patients (17%). Adverse effects were expected and resolved in all patients, and they were generally serious (in 15 patients) and definitely related (in 12 patients). Adverse events were rare in patients with acute symptomatic seizures requiring only one to two ASMs for treatment, but were more common in children with epilepsy, ictal-interictal continuum EEG patterns, or patients requiring more extensive ASM management. SIGNIFICANCE: ES ceased after one ASM in only 38% of critically ill children but ceased after two ASMs in 73% of critically ill children. Thus, ES management was often accomplished with readily available medications, but optimization of multistep ES management strategies might be beneficial. Adverse events were rare and manageable in children with acute symptomatic seizures requiring only one to two ASMs for treatment. Future studies are needed to determine whether management of acute symptomatic ES improves neurobehavioral outcomes.

Thermal biology mediates responses of amphibians and reptiles to habitat modification.

Human activities often replace native forests with warmer, modified habitats that represent novel thermal environments for biodiversity. Reducing biodiversity loss hinges upon identifying which species are most sensitive to the environmental conditions that result from habitat modification. Drawing on case studies and a meta-analysis, we examined whether observed and modelled thermal traits, including heat tolerances, variation in body temperatures, and evaporative water loss, explained variation in sensitivity of ectotherms to habitat modification. Low heat tolerances of lizards and amphibians and high evaporative water loss of amphibians were associated with increased sensitivity to habitat modification, often explaining more variation than non-thermal traits. Heat tolerances alone explained 24-66% (mean = 38%) of the variation in species responses, and these trends were largely consistent across geographic locations and spatial scales. As habitat modification alters local microclimates, the thermal biology of species will likely play a key role in the reassembly of terrestrial communities.

Averting biodiversity collapse in tropical forest protected areas.

The rapid disruption of tropical forests probably imperils global biodiversity more than any other contemporary phenomenon. With deforestation advancing quickly, protected areas are increasingly becoming final refuges for threatened species and natural ecosystem processes. However, many protected areas in the tropics are themselves vulnerable to human encroachment and other environmental stresses. As pressures mount, it is vital to know whether existing reserves can sustain their biodiversity. A critical constraint in addressing this question has been that data describing a broad array of biodiversity groups have been unavailable for a sufficiently large and representative sample of reserves. Here we present a uniquely comprehensive data set on changes over the past 20 to 30 years in 31 functional groups of species and 21 potential drivers of environmental change, for 60 protected areas stratified across the world's major tropical regions. Our analysis reveals great variation in reserve 'health': about half of all reserves have been effective or performed passably, but the rest are experiencing an erosion of biodiversity that is often alarmingly widespread taxonomically and functionally. Habitat disruption, hunting and forest-product exploitation were the strongest predictors of declining reserve health. Crucially, environmental changes immediately outside reserves seemed nearly as important as those inside in determining their ecological fate, with changes inside reserves strongly mirroring those occurring around them. These findings suggest that tropical protected areas are often intimately linked ecologically to their surrounding habitats, and that a failure to stem broad-scale loss and degradation of such habitats could sharply increase the likelihood of serious biodiversity declines.

Thermal quality influences habitat use of two anole species.

Regeneration of secondary forests on previously deforested or degraded land is one of the most dominant forms of land-use change in the tropics. However, the response of animal communities to forest regeneration is poorly understood. To evaluate support for thermal quality as a mechanism driving reptile species distributions during secondary forest succession, we measured operative temperatures and occupancy in three successional forest stages (pasture, secondary forest, and old growth forest) for two anole species common in the landscape (Norops humilis and Norops limifrons). We then measured thermal preference in laboratory experiments and used operative temperature and temperature preference measurements to determine how thermal quality of habitat changes over the course of secondary forest succession, and if occupancy varies as a function of thermal quality. We found that thermal quality was lowest in pasture habitat because of a large frequency of temperatures above the thermal preference range. However, in low thermal quality pasture sites, riparian habitats and remnant trees provided a thermal refuge for both lizard species. Our results support thermal quality as a mechanism for reptile species distributions in altered landscapes and highlight the importance of the maintenance of riparian corridors.

Tropical amphibians in shifting thermal landscapes under land-use and climate change.

Land-cover and climate change are both expected to alter species distributions and contribute to future biodiversity loss. However, the combined effects of land-cover and climate change on assemblages, especially at the landscape scale, remain understudied. Lowland tropical amphibians may be particularly susceptible to changes in land cover and climate warming because many species have narrow thermal safety margins resulting from air and body temperatures that are close to their critical thermal maxima (CTmax ). We examined how changing thermal landscapes may alter the area of thermally suitable habitat (TSH) for tropical amphibians. We measured microclimates in 6 land-cover types and CTmax of 16 frog species in lowland northeastern Costa Rica. We used a biophysical model to estimate core body temperatures of frogs exposed to habitat-specific microclimates while accounting for evaporative cooling and behavior. Thermally suitable habitat area was estimated as the portion of the landscape where species CTmax exceeded their habitat-specific maximum body temperatures. We projected changes in TSH area 80 years into the future as a function of land-cover change only, climate change only, and combinations of land-cover and climate-change scenarios representing low and moderate rates of change. Projected decreases in TSH area ranged from 16% under low emissions and reduced forest loss to 30% under moderate emissions and business-as-usual land-cover change. Under a moderate emissions scenario (A1B), climate change alone contributed to 1.7- to 4.5-fold greater losses in TSH area than land-cover change only, suggesting that future decreases in TSH from climate change may outpace structural habitat loss. Forest-restricted species had lower mean CTmax than species that occurred in altered habitats, indicating that thermal tolerances will likely shape assemblages in changing thermal landscapes. In the face of ongoing land-cover and climate change, it will be critical to consider changing thermal landscapes in strategies to conserve ectotherm species.

Infection risk decreases with increasing mismatch in host and pathogen environmental tolerances.

The fungal pathogen Batrachochytrium dendrobatidis (Bd) has caused the greatest known wildlife pandemic, infecting over 500 amphibian species. It remains unclear why some host species decline from disease-related mortality whereas others persist. We introduce a conceptual model that predicts that infection risk in ectotherms will decrease as the difference between host and pathogen environmental tolerances (i.e. tolerance mismatch) increases. We test this prediction using both local-scale data from Costa Rica and global analyses of over 11 000 Bd infection assays. We find that infection prevalence decreases with increasing thermal tolerance mismatch and with increasing host tolerance of habitat modification. The relationship between environmental tolerance mismatches and Bd infection prevalence is generalisable across multiple amphibian families and spatial scales, and the magnitude of the tolerance mismatch effect depends on environmental context. These findings may help explain patterns of amphibian declines driven by a global wildlife pandemic.

Impact of an ICU EEG monitoring pathway on timeliness of therapeutic intervention and electrographic seizure termination.

OBJECTIVES: We aimed to determine whether implementation of a structured multidisciplinary electroencephalography (EEG) monitoring pathway improved the timeliness of administration of antiseizure medication in response to electrographic seizures in encephalopathic critically ill children. METHODS: A multidisciplinary team developed a pathway to standardize EEG monitoring and seizure management in encephalopathic critically ill children, aiming to decrease the time from electrographic seizure onset to antiseizure medication administration. Data were collected to inform the team of improvement opportunities, which were then provided by an institutional pathway, staff education, and streamlined communication. Measurements were obtained before and after pathway implementation to assess for improvement. RESULTS: We collected data on 41 patients before and 21 after pathway implementation. There were no differences between the baseline and pathway groups in demographic characteristics, acute encephalopathy etiologies, or antiseizure medications utilized. The median duration [interquartile range, IQR] from seizure onset to antiseizure medication administration was shorter for patients treated with the pathway (64 min [50, 101]) compared to patients treated prior to pathway implementation (139 min [71, 189]; p = 0.0006). The median [IQR] interval from seizure onset to antiseizure medication order was shorter for the pathway group (31 min [20, 49]) than the baseline group (71 min [33, 131]; p = 0.003). The median [IQR] interval from antiseizure medication order to administration was shorter for the pathway group (30 min [19, 40]) than the baseline group (40 min [17, 68]) (p = 0.047). Seizure termination was more likely to occur following initial antiseizure medication administration in the pathway than baseline group (67% vs. 27%, p = 0.002). SIGNIFICANCE: Implementation of the pathway resulted in a significant reduction in the duration between electrographic seizure onset and antiseizure medication administration, and a significant increase in the rate of electrographic seizure termination following an initial antiseizure medication. Further study is needed to determine whether these changes are associated with improved outcomes.

The importance of defining focal assemblages when evaluating amphibian and reptile responses to land use.

Habitat loss and degradation are primary threats to amphibians and reptiles, but the relative effects of common land uses on assemblages and the mechanisms that underlie faunal responses are poorly studied. We reviewed the effects of four prevalent types of habitat alteration (urbanization, agriculture, livestock grazing, and silviculture) on amphibian and reptile species richness and abundance by summarizing reported responses in the literature and by estimating effect sizes across studies for species richness in each land-use type. We then used a multinomial model to classify species as natural habitat specialists, generalists, and disturbed habitat specialists and examined variation in effect sizes for each land-use type according to habitat specialization categories. There were mixed conclusions from individual studies, some reporting negative, neutral, or positive effects of land use on species richness and total abundance. A large proportion of studies reported species-specific effects of individual species abundance. However, in our analysis of effect sizes, we found a general trend of negative effects of land use on species richness. We also demonstrate that habitat associations of common species and species turnover can explain variation in the effect of land use on herpetofauna. Our review highlights the pervasive negative effects of common land uses on amphibians and reptiles, the importance of identifying groups vulnerable to land-use change (e.g., forest-associated species) in conservation studies, and the potential influence of disturbance-associated species on whole assemblage analyses.

Mechanistic insights into landscape genetic structure of two tropical amphibians using field-derived resistance surfaces.

Conversion of forests to agriculture often fragments distributions of forest species and can disrupt gene flow. We examined effects of prevalent land uses on genetic connectivity of two amphibian species in northeastern Costa Rica. We incorporated data from field surveys and experiments to develop resistance surfaces that represent local mechanisms hypothesized to modify dispersal success of amphibians, such as habitat-specific predation and desiccation risk. Because time lags can exist between forest conversion and genetic responses, we evaluated landscape effects using land-cover data from different time periods. Populations of both species were structured at similar spatial scales but exhibited differing responses to landscape features. Litter frog population differentiation was significantly related to landscape resistances estimated from abundance and experiment data. Model support was highest for experiment-derived surfaces that represented responses to microclimate variation. Litter frog genetic variation was best explained by contemporary landscape configuration, indicating rapid population response to land-use change. Poison frog genetic structure was strongly associated with geographic isolation, which explained up to 45% of genetic variation, and long-standing barriers, such as rivers and mountains. However, there was also partial support for abundance- and microclimate response-derived resistances. Differences in species responses to landscape features may be explained by overriding effects of population size on patterns of differentiation for poison frogs, but not litter frogs. In addition, pastures are likely semi-permeable to poison frog gene flow because the species is known to use pastures when remnant vegetation is present, but litter frogs do not. Ongoing reforestation efforts will probably increase connectivity in the region by increasing tree cover and reducing area of pastures.

JC virus reactivation during prolonged natalizumab monotherapy for multiple sclerosis.

OBJECTIVE: To determine the prevalence of JC virus (JCV) reactivation and JCV-specific cellular immune response during prolonged natalizumab treatment for multiple sclerosis (MS). METHODS: We enrolled 43 JCV-seropositive MS patients, including 32 on natalizumab monotherapy >18 months, 6 on interferon ß-1a monotherapy >36 months, and 5 untreated controls. We performed quantitative real-time polymerase chain reaction in cerebrospinal fluid (CSF), blood, and urine for JCV DNA, and we determined JCV-specific T-cell responses using enzyme-linked immunosorbent spot (ELISpot) and intracellular cytokine staining (ICS) assays, ex vivo and after in vitro stimulation with JCV peptides. RESULTS: JCV DNA was detected in the CSF of 2 of 27 (7.4%) natalizumab-treated MS patients who had no symptoms or magnetic resonance imaging-detected lesions consistent with progressive multifocal leukoencephalopathy. JCV DNA was detected in blood of 12 of 43 (27.9%) and in urine of 11 of 43 (25.6%) subjects without a difference between natalizumab-treated patients and controls. JC viral load was higher in CD34(+) cells and in monocytes compared to other subpopulations. ICS was more sensitive than ELISpot. JCV-specific T-cell responses, mediated by both CD4(+) and CD8(+) T lymphocytes, were detected more frequently after in vitro stimulation. JCV-specific CD4(+) T cells were detected ex vivo more frequently in MS patients with JCV DNA in CD34(+) (p = 0.05) and B cells (p = 0.03). INTERPRETATION: Asymptomatic JCV reactivation may occur in CSF of natalizumab-treated MS patients. JCV DNA load is higher in circulating CD34(+) cells and monocytes compared to other mononuclear cells, and JCV in blood might trigger a JCV-specific CD4(+) T-cell response. JCV-specific cellular immune response is highly prevalent in all JCV-seropositive MS patients, regardless of treatment.

Evaluating connectivity for tropical amphibians using empirically derived resistance surfaces.

Agricultural expansion continues to drive forest loss in species-rich tropical systems and often disrupts movement and distributions of organisms. The ability of species to occupy and move through altered habitats likely depends on the level of contrast between natural forest and surrounding land uses. Connectivity models, such as circuit theory models, are widely used in conservation biology, and their primary input consists of resistance surfaces representing movement costs associated with landscape features. Cost values are most frequently determined by expert opinion, which may not capture relevant levels of contrast among features. We developed resistance surfaces using experiments that represent different local mechanisms hypothesized to affect connectivity for two Neotropical amphibian species. Response ratios were calculated to translate experimental results to cost values used in connectivity modeling. We used relative abundance data in three land-cover types to generate resistance surfaces for evaluating independent support of models derived from experiments. Finally, we analyzed agreement among movement pathways predicted for each species and among three commonly used connectivity measures: Euclidean, least cost, and resistance distances. Experiments showed that extreme microclimates associated with altered habitats significantly increased desiccation and mortality risk for both species. Resistances estimated from microclimate experiments were concordant with those from survey data for both species. For one focal species, resistance estimates derived from predator encounter rates were also highly correlated with abundance-derived resistances. There was generally low agreement among the three alternative distance measures, which underscores the importance of choosing connectivity models that are most appropriate for the study objectives. Overall, similarity among linkages modeled for each species was high, but decreased with declining forest cover. Our results highlight the value of experiments for drawing inferences about processes in resistance modeling, as well as the need to consider model differences and species-specific responses when developing strategies to maintain connectivity.

Electrographic Seizure Characteristics and Electrographic Status Epilepticus Prediction.

PURPOSE: We aimed to characterize electrographic seizures (ES) and electrographic status epilepticus (ESE) and determine whether a model predicting ESE exclusively could effectively guide continuous EEG monitoring (CEEG) utilization in critically ill children. METHODS: This was a prospective observational study of consecutive critically ill children with encephalopathy who underwent CEEG. We used descriptive statistics to characterize ES and ESE, and we developed a model for ESE prediction. RESULTS: ES occurred in 25% of 1,399 subjects. Among subjects with ES, 23% had ESE, including 37% with continuous seizures lasting >30 minutes and 63% with recurrent seizures totaling 30 minutes within a 1-hour epoch. The median onset of ES and ESE occurred 1.8 and 0.18 hours after CEEG initiation, respectively. The optimal model for ESE prediction yielded an area under the receiver operating characteristic curves of 0.81. A cutoff selected to emphasize sensitivity (91%) yielded specificity of 56%. Given the 6% ESE incidence, positive predictive value was 11% and negative predictive value was 99%. If the model were applied to our cohort, then 53% of patients would not undergo CEEG and 8% of patients experiencing ESE would not be identified. CONCLUSIONS: ESE was common, but most patients with ESE had recurrent brief seizures rather than long individual seizures. A model predicting ESE might only slightly improve CEEG utilization over models aiming to identify patients at risk for ES but would fail to identify some patients with ESE. Models identifying ES might be more advantageous for preventing ES from evolving into ESE.

Infection and co-infection by the amphibian chytrid fungus and ranavirus in wild Costa Rican frogs.

Amphibian populations are globally threatened by emerging infectious diseases, and 2 pathogens in particular are recognized as major threats: the amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd) and ranaviruses. Here, we evaluated the prevalence of infection by Bd and ranavirus in an assemblage of frogs from a lowland wet forest in Costa Rica. We found an overall prevalence of 21.3% for Bd and 16.6% for ranavirus, and detected both pathogens widely among our 20 sampled species. We found a positive association between ranavirus and Bd infection in one of our 4 most commonly sampled species. We also found a positive but non-significant association between infection by ranavirus and infection by Bd among species overall. Our study is among the first detailed evaluations of ranavirus prevalence in the American tropics, and to our knowledge is the first to detect a positive association between Bd and ranavirus in any species. Considerable research attention has focused on the ecology of Bd in tropical regions, yet we argue that greater research focus is necessary to understand the ecology and conservation impact of ranaviruses on amphibian populations already decimated by the emergence of Bd.

Validation of a Model for Targeted EEG Monitoring Duration in Critically Ill Children.

PURPOSE: Continuous EEG monitoring (CEEG) to identify electrographic seizures (ES) in critically ill children is resource intense. Targeted strategies could enhance implementation feasibility. We aimed to validate previously published findings regarding the optimal CEEG duration to identify ES in critically ill children. METHODS: This was a prospective observational study of 1,399 consecutive critically ill children with encephalopathy. We validated the findings of a multistate survival model generated in a published cohort ( N = 719) in a new validation cohort ( N = 680). The model aimed to determine the CEEG duration at which there was <15%, <10%, <5%, or <2% risk of experiencing ES if CEEG were continued longer. The model included baseline clinical risk factors and emergent EEG risk factors. RESULTS: A model aiming to determine the CEEG duration at which a patient had <10% risk of ES if CEEG were continued longer showed similar performance in the generation and validation cohorts. Patients without emergent EEG risk factors would undergo 7 hours of CEEG in both cohorts, whereas patients with emergent EEG risk factors would undergo 44 and 36 hours of CEEG in the generation and validation cohorts, respectively. The <10% risk of ES model would yield a 28% or 64% reduction in CEEG hours compared with guidelines recommending CEEG for 24 or 48 hours, respectively. CONCLUSIONS: This model enables implementation of a data-driven strategy that targets CEEG duration based on readily available clinical and EEG variables. This approach could identify most critically ill children experiencing ES while optimizing CEEG use.

EEG Monitoring in Critically Ill Children: Establishing High-Yield Subgroups.

PURPOSE: Continuous EEG monitoring (CEEG) is increasingly used to identify electrographic seizures (ES) in critically ill children, but it is resource intense. We aimed to assess how patient stratification by known ES risk factors would impact CEEG utilization. METHODS: This was a prospective observational study of critically ill children with encephalopathy who underwent CEEG. We calculated the average CEEG duration required to identify a patient with ES for the full cohort and subgroups stratified by known ES risk factors. RESULTS: ES occurred in 345 of 1,399 patients (25%). For the full cohort, an average of 90 hours of CEEG would be required to identify 90% of patients with ES. If subgroups of patients were stratified by age, clinically evident seizures before CEEG initiation, and early EEG risk factors, then 20 to 1,046 hours of CEEG would be required to identify a patient with ES. Patients with clinically evident seizures before CEEG initiation and EEG risk factors present in the initial hour of CEEG required only 20 (<1 year) or 22 (≥1 year) hours of CEEG to identify a patient with ES. Conversely, patients with no clinically evident seizures before CEEG initiation and no EEG risk factors in the initial hour of CEEG required 405 (<1 year) or 1,046 (≥1 year) hours of CEEG to identify a patient with ES. Patients with clinically evident seizures before CEEG initiation or EEG risk factors in the initial hour of CEEG required 29 to 120 hours of CEEG to identify a patient with ES. CONCLUSIONS: Stratifying patients by clinical and EEG risk factors could identify high- and low-yield subgroups for CEEG by considering ES incidence, the duration of CEEG required to identify ES, and subgroup size. This approach may be critical for optimizing CEEG resource allocation.

Periodic Discharges in Critically Ill Children: Predictors and Outcome.

OBJECTIVES: We aimed to identify clinical and EEG monitoring characteristics associated with generalized, lateralized, and bilateral-independent periodic discharges (GPDs, LPDs, and BIPDs) and to determine which patterns were associated with outcomes in critically ill children. METHODS: We performed a prospective observational study of consecutive critically ill children undergoing continuous EEG monitoring, including standardized scoring of GPDs, LPDs, and BIPDs. We identified variables associated with GPDs, LPDs, and BIPDs and assessed whether each pattern was associated with hospital discharge outcomes including the Glasgow Outcome Scale-Extended Pediatric version (GOS-E-Peds), Pediatric Cerebral Performance Category (PCPC), and mortality. RESULTS: PDs occurred in 7% (91/1,399) of subjects. Multivariable logistic regression indicated that patients with coma (odds ratio [OR], 3.45; 95% confidence interval [CI]: 1.55, 7.68) and abnormal EEG background category (OR, 6.85; 95% CI: 3.37, 13.94) were at increased risk for GPDs. GPDs were associated with mortality (OR, 3.34; 95% CI: 1.24, 9.02) but not unfavorable GOS-E-Peds (OR, 1.93; 95% CI: 0.88, 4.23) or PCPC (OR, 1.64; 95% CI: 0.75, 3.58). Patients with acute nonstructural encephalopathy did not experience LPDs, and LPDs were not associated with mortality or unfavorable outcomes. BIPDs were associated with mortality (OR, 3.68; 95% CI: 1.14, 11.92), unfavorable GOS-E-Peds (OR, 5.00; 95% CI: 1.39, 18.00), and unfavorable PCPC (OR, 5.96; 95% CI: 1.65, 21.46). SIGNIFICANCE: Patients with coma or more abnormal EEG background category had an increased risk for GPDs and BIPDs, and no patients with an acute nonstructural encephalopathy experienced LPDs. GPDs were associated with mortality and BIPDs were associated with mortality and unfavorable outcomes, but LPDs were not associated with unfavorable outcomes.