Chronopharmacology of Anti-Convulsive Therapy

Approximately one-third of patients with epilepsy continue to have seizures despite antiepileptic therapy. Many seizures occur in diurnal, sleep/wake, circadian, or even monthly patterns. The relationship between biomarkers and state changes is still being investigated, but early results suggest that some of these patterns may be related to endogenous circadian patterns whereas others may be related to wakefulness and sleep or both. Chronotherapy, the application of treatment at times of greatest seizure susceptibility, is a technique that may optimize seizure control in selected patients. It may be used in the form of differential dosing, as preparations designed to deliver sustained or pulsatile drug delivery or in the form of ‘zeitgebers’ that shift endogenous rhythms. Early trials in epilepsy suggest that chronopharmacology may provide improved seizure control compared with conventional treatment in some patients. The present article reviews chronopharmacology in the treatment of epilepsy as well as future treatment avenues

Risk Factors Associated with Death in In-Hospital Pediatric Convulsive Status Epilepticus

Objective: To evaluate in-patient mortality and predictors of death associated with convulsive status epilepticus (SE) in a large, multi-center, pediatric cohort. Patients and Methods: We identified our cohort from the KID Inpatient Database for the years 1997, 2000, 2003 and 2006. We queried the database for convulsive SE, associated diagnoses, and for inpatient death. Univariate logistic testing was used to screen for potential risk factors. These risk factors were then entered into a stepwise backwards conditional multivariable logistic regression procedure. P-values less than 0.05 were taken as significant. Results: We identified 12,365 (5,541 female) patients with convulsive SE aged 0–20 years (mean age 6.2 years, standard deviation 5.5 years, median 5 years) among 14,965,571 pediatric inpatients (0.08%). Of these, 117 died while in the hospital (0.9%). The most frequent additional admission ICD-9 code diagnoses in addition to SE were cerebral palsy, pneumonia, and respiratory failure. Independent risk factors for death in patients with SE, assessed by multivariate calculation, included near drowning (Odds ratio [OR] 43.2; Confidence Interval [CI] 4.4–426.8), hemorrhagic shock (OR 17.83; CI 6.5–49.1), sepsis (OR 10.14; CI 4.0–25.6), massive aspiration (OR 9.1; CI 1.8–47), mechanical ventilation >96 hours (OR9; 5.6–14.6), transfusion (OR 8.25; CI 4.3–15.8), structural brain lesion (OR7.0; CI 3.1–16), hypoglycemia (OR5.8; CI 1.75–19.2), sepsis with liver failure (OR 14.4; CI 5–41.9), and admission in December (OR3.4; CI 1.6–4.1). African American ethnicity (OR 0.4; CI 0.2–0.8) was associated with a decreased risk of death in SE. Conclusion: Pediatric convulsive SE occurs in up to 0.08% of pediatric inpatient admissions with a mortality of up to 1%. There appear to be several risk factors that can predict mortality. These may warrant additional monitoring and aggressive management

Predicting Hemolytic Uremic Syndrome and Renal Replacement Therapy in Shiga Toxin-producing Escherichia coli-infected Children.

BACKGROUND: Shiga toxin-producing Escherichia coli (STEC) infections are leading causes of pediatric acute renal failure. Identifying hemolytic uremic syndrome (HUS) risk factors is needed to guide care. METHODS: We conducted a multicenter, historical cohort study to identify features associated with development of HUS (primary outcome) and need for renal replacement therapy (RRT) (secondary outcome) in STEC-infected children without HUS at initial presentation. Children agedeligible. RESULTS: Of 927 STEC-infected children, 41 (4.4%) had HUS at presentation; of the remaining 886, 126 (14.2%) developed HUS. Predictors (all shown as odds ratio [OR] with 95% confidence interval [CI]) of HUS included younger age (0.77 [.69-.85] per year), leukocyte count ≥13.0 × 103/μL (2.54 [1.42-4.54]), higher hematocrit (1.83 [1.21-2.77] per 5% increase) and serum creatinine (10.82 [1.49-78.69] per 1 mg/dL increase), platelet count \u3c250 \u3e× 103/μL (1.92 [1.02-3.60]), lower serum sodium (1.12 [1.02-1.23 per 1 mmol/L decrease), and intravenous fluid administration initiated ≥4 days following diarrhea onset (2.50 [1.14-5.46]). A longer interval from diarrhea onset to index visit was associated with reduced HUS risk (OR, 0.70 [95% CI, .54-.90]). RRT predictors (all shown as OR [95% CI]) included female sex (2.27 [1.14-4.50]), younger age (0.83 [.74-.92] per year), lower serum sodium (1.15 [1.04-1.27] per mmol/L decrease), higher leukocyte count ≥13.0 × 103/μL (2.35 [1.17-4.72]) and creatinine (7.75 [1.20-50.16] per 1 mg/dL increase) concentrations, and initial intravenous fluid administration ≥4 days following diarrhea onset (2.71 [1.18-6.21]). CONCLUSIONS: The complex nature of STEC infection renders predicting its course a challenge. Risk factors we identified highlight the importance of avoiding dehydration and performing close clinical and laboratory monitoring

Comparing two definitions of pediatric complexity among children cared for in general and pediatric emergency departments in a statewide sample

Abstract Objective The number of children cared for in emergency departments (EDs) with medical complexity continues to rise. We sought to identify the concordance between 2 commonly used criteria of medical complexity among children presenting to a statewide sample of EDs. Methods We conducted a retrospective cross‐sectional study of children presenting to a statewide sample of Illinois EDs between 2016 and 2021. We classified patients as having medical complexity when using 2 definitions (≥1 pediatric Complex Chronic Condition [CCC] or complex chronic disease using the Pediatric Medical Complexity Algorithm [PMCA]) and compared their overlap and clinical outcomes. Results Of 6,550,296 pediatric ED encounters, CCC criteria and PMCA criteria were met in 217,609 (3.3%) and 175,708 (2.7%) encounters, respectively. Among patients with complexity, 100,015 (34.1%) met both criteria, with moderate agreement (κ = 0.49). Children with complexity by CCC had similar rates of presentation to a pediatric hospital (16.3% vs 14.8%), admission (28.5% vs 33.7%), ICU stay (10.0% vs 10.1%), and in‐hospital mortality (0.5% vs 0.5%) compared to children with complexity by PMCA. The most common visit diagnoses for children with CCCs were related to sickle cell disease with crisis (3.9%), abdominal pain (3.6%), and non‐specific chest pain (2.7%). The most common diagnoses by PMCA were related to depressive disorders (4.9%), sickle cell disease with crisis (4.8%), and seizures (3.2%). Conclusions and Relevance The CCC and PMCA criteria of multisystem complexity identified different populations, with moderate agreement. Careful selection of operational definitions is required for proper application and interpretation in clinical and health services research

United States’ Emergency Department Visits for Fever by Young Children 2007-2017

Introduction: Our goal in this study was to estimate rates of emergency department (ED) visits for fever by children <2 years of age, and evaluate frequencies of testing and treatment during these visits.Methods: We performed a cross-sectional study of ED encounters from 2007-2017 using the National Hospital Ambulatory Medical Care Survey, a cross-sectional, multi-stage probability sample survey of visits to nonfederal United States EDs. We included encounters with a visit reason of “fever” or recorded fever in the ED. We report demographics and management strategies in two groups: infants ≤90 days in age; and children 91 days to <2 years old. For patients 91 days to <2 years, we compared testing and treatment strategies between general and pediatric EDs using chi-squared tests.Results: Of 1.5 billion encounters over 11 years, 2.1% (95% confidence interval [CI], 1.9-2.2%) were by children <2 years old with fever. Two million encounters (95% CI, 1.7-2.4 million) were by infants ≤90 days, and 28.4 million (95% CI, 25.5-31.4 million) were by children 91 days to <2 years. Among infants ≤90 days, 27.6% (95% CI, 21.1-34.1%) had blood and 21.3% (95% CI, 13.6-29.1%) had urine cultures; 26.8% (95% CI, 20.9-32.7%) were given antibiotics, and 21.1% (95% CI, 15.3-26.9%) were admitted or transferred. Among patients 91 days to <2 years in age, 6.8% (95% CI, 5.8-7.8%) had blood and 7.7% (95% CI 6.1-9.4%) had urine cultures; 40.5% (95% CI, 40.5-40.5%) were given antibiotics, and 4.4% (95% CI, 3.5-5.3%) were admitted or transferred. Patients 91 days to <2 years who were evaluated in general EDs had higher rates of radiography (27.1% vs 15.2%; P<0.01) and antibiotic utilization (42.3% vs 34.2%; P<0.01), but lower rates of urine culture testing (6.4% vs 11.6%, p = 0.03), compared with patients evaluated in pediatric EDs.Conclusion: Approximately 180,000 patients ≤90 days old and 2.6 million patients 91 days to <2 years in age with fever present to US EDs annually. Given existing guidelines, blood and urine culture performance was low for infants ≤90 days old. For children 91 days to <2 years, rates of radiography and antibiotic use were higher in general EDs compared to pediatric EDs. These findings suggest opportunities to improve care among febrile young children in the ED

United States’ Emergency Department Visits for Fever by Young Children 2007-2017

Introduction: Our goal in this study was to estimate rates of emergency department (ED) visits for fever by children <2 years of age, and evaluate frequencies of testing and treatment during these visits.Methods: We performed a cross-sectional study of ED encounters from 2007-2017 using the National Hospital Ambulatory Medical Care Survey, a cross-sectional, multi-stage probability sample survey of visits to nonfederal United States EDs. We included encounters with a visit reason of “fever” or recorded fever in the ED. We report demographics and management strategies in two groups: infants ≤90 days in age; and children 91 days to <2 years old. For patients 91 days to <2 years, we compared testing and treatment strategies between general and pediatric EDs using chi-squared tests.Results: Of 1.5 billion encounters over 11 years, 2.1% (95% confidence interval [CI], 1.9-2.2%) were by children <2 years old with fever. Two million encounters (95% CI, 1.7-2.4 million) were by infants ≤90 days, and 28.4 million (95% CI, 25.5-31.4 million) were by children 91 days to <2 years. Among infants ≤90 days, 27.6% (95% CI, 21.1-34.1%) had blood and 21.3% (95% CI, 13.6-29.1%) had urine cultures; 26.8% (95% CI, 20.9-32.7%) were given antibiotics, and 21.1% (95% CI, 15.3-26.9%) were admitted or transferred. Among patients 91 days to <2 years in age, 6.8% (95% CI, 5.8-7.8%) had blood and 7.7% (95% CI 6.1-9.4%) had urine cultures; 40.5% (95% CI, 40.5-40.5%) were given antibiotics, and 4.4% (95% CI, 3.5-5.3%) were admitted or transferred. Patients 91 days to <2 years who were evaluated in general EDs had higher rates of radiography (27.1% vs 15.2%; P<0.01) and antibiotic utilization (42.3% vs 34.2%; P<0.01), but lower rates of urine culture testing (6.4% vs 11.6%, p = 0.03), compared with patients evaluated in pediatric EDs.Conclusion: Approximately 180,000 patients ≤90 days old and 2.6 million patients 91 days to <2 years in age with fever present to US EDs annually. Given existing guidelines, blood and urine culture performance was low for infants ≤90 days old. For children 91 days to <2 years, rates of radiography and antibiotic use were higher in general EDs compared to pediatric EDs. These findings suggest opportunities to improve care among febrile young children in the ED

Age‐based centiles for diastolic blood pressure among children in the out‐of‐hospital emergency setting

Abstract Objective To compare Pediatric Advanced Life Support (PALS) diastolic blood pressure (DBP) criteria to empirically derived DBP criteria for the prediction of out‐of‐hospital interventions in children. Methods We performed a retrospective study of pediatric (90th centile). The accuracy of low DBP for out‐of‐hospital interventions between the two criteria was similar. Conclusion PALS criteria for DBP classified a high proportion of children as having abnormal vital signs, particularly with diastolic hypertension. Empirically derived DBP thresholds more accurately predict the delivery of key out‐of‐hospital interventions. If externally validated, correlated to in‐hospital outcomes, and combined with thresholds for other vital signs, these may better predict the need for out‐of‐hospital interventions