Diabetic kidney disease is among the most important causes of end-stage kidney disease worldwide. Risk factors for diabetic kidney disease remain incompletely defined. Recent studies document a high ...frequency of acute kidney injury (AKI) during diabetic ketoacidosis (DKA) in children, raising the question of whether these AKI episodes might contribute to future risk of diabetic kidney disease.
To determine whether episodes of AKI occurring during DKA in children are associated with increased risk of development of microalbuminuria.
This retrospective review of medical records included children with type 1 diabetes with 1 or more urine albumin levels measured during routine diabetes care from 2 university-affiliated urban tertiary children's hospitals in the United States from January 2006 to December 2019. Age at diagnosis of diabetes, hemoglobin A1c levels, episodes of DKA, pH and creatinine levels during DKA, and urine albumin and creatinine measurements were analyzed. Cox proportional hazards regression models were used to identify variables affecting the hazard rate for microalbuminuria development. Analyses began January 2021 and ended May 2021.
Episodes of DKA and episodes of AKI occurring during DKA.
AKI occurrence and AKI stage were determined from serum creatinine measurements during DKA using Kidney Disease: Improving Global Outcomes criteria. Microalbuminuria was defined as urine albumin-to-creatinine ratio of 30 mg/g or more or excretion of 30 mg or more of albumin in 24 hours.
Of 2345 children, the mean (SD) age at diagnosis was 9.4 (4.4) years. One or more episodes of DKA occurred in 963 children (41%), and AKI occurred during DKA in 560 episodes (47%). In multivariable models adjusting for the associations of age at diagnosis and mean hemoglobin A1c level since diagnosis, each episode of AKI during DKA was associated with a hazard ratio of 1.56 (95% CI, 1.3-1.87) for development of microalbuminuria. Four or more episodes increased the hazard rate by more than 5-fold. DKA episodes without AKI did not significantly increase the hazard rate for microalbuminuria development after adjusting for other covariates.
These data demonstrate that episodes of AKI occurring during DKA in children with type 1 diabetes are significantly associated with risk of developing microalbuminuria. Greater efforts are necessary to reduce the frequency of DKA.
In young febrile infants, serious bacterial infections (SBIs), including urinary tract infections, bacteremia, and meningitis, may lead to dangerous complications. However, lumbar punctures and ...hospitalizations involve risks and costs. Clinical prediction rules using biomarkers beyond the white blood cell count (WBC) may accurately identify febrile infants at low risk for SBIs.
To derive and validate a prediction rule to identify febrile infants 60 days and younger at low risk for SBIs.
Prospective, observational study between March 2011 and May 2013 at 26 emergency departments. Convenience sample of previously healthy febrile infants 60 days and younger who were evaluated for SBIs. Data were analyzed between April 2014 and April 2018.
Clinical and laboratory data (blood and urine) including patient demographics, fever height and duration, clinical appearance, WBC, absolute neutrophil count (ANC), serum procalcitonin, and urinalysis. We derived and validated a prediction rule based on these variables using binary recursive partitioning analysis.
Serious bacterial infection, defined as urinary tract infection, bacteremia, or bacterial meningitis.
We derived the prediction rule on a random sample of 908 infants and validated it on 913 infants (mean age was 36 days, 765 were girls 42%, 781 were white and non-Hispanic 43%, 366 were black 20%, and 535 were Hispanic 29%). Serious bacterial infections were present in 170 of 1821 infants (9.3%), including 26 (1.4%) with bacteremia, 151 (8.3%) with urinary tract infections, and 10 (0.5%) with bacterial meningitis; 16 (0.9%) had concurrent SBIs. The prediction rule identified infants at low risk of SBI using a negative urinalysis result, an ANC of 4090/µL or less (to convert to ×109 per liter, multiply by 0.001), and serum procalcitonin of 1.71 ng/mL or less. In the validation cohort, the rule sensitivity was 97.7% (95% CI, 91.3-99.6), specificity was 60.0% (95% CI, 56.6-63.3), negative predictive value was 99.6% (95% CI, 98.4-99.9), and negative likelihood ratio was 0.04 (95% CI, 0.01-0.15). One infant with bacteremia and 2 infants with urinary tract infections were misclassified. No patients with bacterial meningitis were missed by the rule. The rule performance was nearly identical when the outcome was restricted to bacteremia and/or bacterial meningitis, missing the same infant with bacteremia.
We derived and validated an accurate prediction rule to identify febrile infants 60 days and younger at low risk for SBIs using the urinalysis, ANC, and procalcitonin levels. Once further validated on an independent cohort, clinical application of the rule has the potential to decrease unnecessary lumbar punctures, antibiotic administration, and hospitalizations.
Benzodiazepine-refractory, or established, status epilepticus is thought to be of similar pathophysiology in children and adults, but differences in underlying aetiology and pharmacodynamics might ...differentially affect response to therapy. In the Established Status Epilepticus Treatment Trial (ESETT) we compared the efficacy and safety of levetiracetam, fosphenytoin, and valproate in established status epilepticus, and here we describe our results after extending enrolment in children to compare outcomes in three age groups.
In this multicentre, double-blind, response-adaptive, randomised controlled trial, we recruited patients from 58 hospital emergency departments across the USA. Patients were eligible for inclusion if they were aged 2 years or older, had been treated for a generalised convulsive seizure of longer than 5 min duration with adequate doses of benzodiazepines, and continued to have persistent or recurrent convulsions in the emergency department for at least 5 min and no more than 30 min after the last dose of benzodiazepine. Patients were randomly assigned in a response-adaptive manner, using Bayesian methods and stratified by age group (<18 years, 18–65 years, and >65 years), to levetiracetam, fosphenytoin, or valproate. All patients, investigators, study staff, and pharmacists were masked to treatment allocation. The primary outcome was absence of clinically apparent seizures with improved consciousness and without additional antiseizure medication at 1 h from start of drug infusion. The primary safety outcome was life-threatening hypotension or cardiac arrhythmia. The efficacy and safety outcomes were analysed by intention to treat. This study is registered in ClinicalTrials.gov, NCT01960075.
Between Nov 3, 2015, and Dec 29, 2018, we enrolled 478 patients and 462 unique patients were included: 225 children (aged <18 years), 186 adults (18–65 years), and 51 older adults (>65 years). 175 (38%) patients were randomly assigned to levetiracetam, 142 (31%) to fosphenyltoin, and 145 (31%) were to valproate. Baseline characteristics were balanced across treatments within age groups. The primary efficacy outcome was met in those treated with levetiracetam for 52% (95% credible interval 41–62) of children, 44% (33–55) of adults, and 37% (19–59) of older adults; with fosphenytoin in 49% (38–61) of children, 46% (34–59) of adults, and 35% (17–59) of older adults; and with valproate in 52% (41–63) of children, 46% (34–58) of adults, and 47% (25–70) of older adults. No differences were detected in efficacy or primary safety outcome by drug within each age group. With the exception of endotracheal intubation in children, secondary safety outcomes did not significantly differ by drug within each age group.
Children, adults, and older adults with established status epilepticus respond similarly to levetiracetam, fosphenytoin, and valproate, with treatment success in approximately half of patients. Any of the three drugs can be considered as a potential first-choice, second-line drug for benzodiazepine-refractory status epilepticus.
National Institute of Neurological Disorders and Stroke, National Institutes of Health.
This study aimed to compare prehospital spinal immobilization techniques applied to age-based cohorts of children with and without cervical spine injury (CSI) after blunt trauma.
We compared ...prehospital spinal immobilization in 3 age-based cohorts of children with blunt trauma-related CSI transported to 1 of 17 participating hospitals. We also compared children younger than 2 years with CSI with those at risk for but without CSI after blunt trauma. We identified patients through query of billing and radiology databases. We compared immobilization methods using Fisher's exact test for homogeneity.
We identified 16 children younger than 2 years, 78 children 2 to 7 years old, and 221 children 8 to 15 years old with CSI, and 66 children younger than 2 years without CSI. There were no significant differences in spinal immobilization techniques applied to children younger than 2 years old with and without CSI (P = 0.34). Of the 82 children younger than 2 years, 34 (41%) were fully immobilized in a cervical collar and rigid long board. There was a significant difference between spinal immobilization techniques applied to children with CSI younger than 2 years and 8 to 15 years old (P < 0.01). Six (38%) children with CSI younger than 2 years were fully immobilized versus 49 (63%) children 2 to 7 years old and 175 (79%) children 8 to 15 years old.
In this retrospective, observational study involving several emergency departments and Emergency Medical Services systems, we found that full spinal immobilization is inconsistently applied to children younger than 2 years after blunt trauma regardless of the presence of CSI. Full spinal immobilization is applied more consistently to older children with CSI.
Diabetic ketoacidosis in children may cause brain injuries ranging from mild to severe. Whether intravenous fluids contribute to these injuries has been debated for decades.
We conducted a 13-center, ...randomized, controlled trial that examined the effects of the rate of administration and the sodium chloride content of intravenous fluids on neurologic outcomes in children with diabetic ketoacidosis. Children were randomly assigned to one of four treatment groups in a 2-by-2 factorial design (0.9% or 0.45% sodium chloride content and rapid or slow rate of administration). The primary outcome was a decline in mental status (two consecutive Glasgow Coma Scale scores of <14, on a scale ranging from 3 to 15, with lower scores indicating worse mental status) during treatment for diabetic ketoacidosis. Secondary outcomes included clinically apparent brain injury during treatment for diabetic ketoacidosis, short-term memory during treatment for diabetic ketoacidosis, and memory and IQ 2 to 6 months after recovery from diabetic ketoacidosis.
A total of 1389 episodes of diabetic ketoacidosis were reported in 1255 children. The Glasgow Coma Scale score declined to less than 14 in 48 episodes (3.5%), and clinically apparent brain injury occurred in 12 episodes (0.9%). No significant differences among the treatment groups were observed with respect to the percentage of episodes in which the Glasgow Coma Scale score declined to below 14, the magnitude of decline in the Glasgow Coma Scale score, or the duration of time in which the Glasgow Coma Scale score was less than 14; with respect to the results of the tests of short-term memory; or with respect to the incidence of clinically apparent brain injury during treatment for diabetic ketoacidosis. Memory and IQ scores obtained after the children's recovery from diabetic ketoacidosis also did not differ significantly among the groups. Serious adverse events other than altered mental status were rare and occurred with similar frequency in all treatment groups.
Neither the rate of administration nor the sodium chloride content of intravenous fluids significantly influenced neurologic outcomes in children with diabetic ketoacidosis. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Health Resources and Services Administration; PECARN DKA FLUID ClinicalTrials.gov number, NCT00629707 .).
The Bacterial Meningitis Score, a derived and validated clinical decision rule, identifies children with cerebrospinal fluid (CSF) pleocytosis who are at very low risk of bacterial meningitis. ...Low-risk features include the following: negative CSF Gram stain, CSF absolute neutrophil count (ANC) <1000 cells/μl, CSF protein <80 mg/dl, peripheral blood ANC <10 000 cells/μl and no seizure at or prior to initial presentation. The study objective of the present work was to calculate the performance of the Bacterial Meningitis Score by performing a meta-analysis of all published validation studies.
A meta-analysis of all studies published between 2002 and 2012 was performed, evaluating the performance of the Bacterial Meningitis Score in children with CSF pleocytosis. Study quality was assessed using the assessment of diagnostic accuracy studies instrument and then the test performance of the prediction rule was calculated.
From 8 studies, 5312 patients were identified, of whom 4896 (92%) had sufficient clinical data to calculate the Bacterial Meningitis Score. Bacterial meningitis was diagnosed in 1242 children (23% of study patients). The combined sensitivity of the Bacterial Meningitis Score for bacterial meningitis was 99.3% (1224/1233; 95% CI 98.7% to 99.7%), specificity 62.1% (2274/3663; 95% CI 60.5% to 63.7%) negative predictive value 99.7% (2274/2283, 95% CI 99.3% to 99.9%), positive likelihood ratio 2.6 (95% CI 2.5 to 2.7) and negative likelihood ratio 0.01 (95% CI 0.01 to 0.02).
The Bacterial Meningitis Score is a highly accurate clinical scoring system that could be used to assist clinical decision making for the management of children with CSF pleocytosis.
INTRODUCTION:
Electronic clinical decision support (CDS) may improve the safe, evidence-based management of children with mild traumatic brain injuries (mTBI) and intracranial injuries.
METHODS:
...Emergency medicine and neurosurgery physicians were recruited to participate in study sessions to test the usability and acceptability of a novel CDS prototype in a simulated electronic health record environment. Testing sessions included interacting with the tool using three simulated clinical cases (https://head-injury-risk-predictor.web.app/case-1.htmlt), a think-aloud protocol, an acceptability and usability survey, and a semi-structured interview. The prototype was updated twice during testing (phases 1-3) to reflect user feedback. Usability problems were categorized and quantified using content analysis and reported with a descriptive summary. The semi-structured interviews were analyzed using thematic analysis.
RESULTS:
Twenty physicians (10 each from neurosurgery and emergency medicine) were recruited from nine separate hospitals. Most participants worked at teaching hospitals (80%) and level 1 trauma centers (75%). During the prototype updates, problems with clarity of terminology and wording were identified and corrected, along with problems navigating through and using the CDS interface. Corresponding to these changes, the number of usability problems dropped from 35 in phase 1 to 8 in phase 3, and the number of mistakes made went from 18 in phase 1 to 2 in phase 3. Through the survey, most participants found the tool easy to use (90%), useful for determining a patient’s level of care (95%), and likely to improve resource use (90%) and patient safety (79%). Major interview themes related to the CDS’s ability to support evidence-based decision-making and improve clinical workflow, proposed implementation strategies, and potential pitfalls to avoid.
CONCLUSION:
After the iterative evaluation and refinement, the elctronic CDS tool was found to be highly usable and useful for aiding the management of children with mTBI and intracranial injuries.
INTRODUCTION:
The management of children with mild traumatic brain injuries (mTBI) and intracranial injuries is not evidence-based and may place some children at risk of harm. Evidence-based ...electronic clinical decision support (CDS) may improve patient safety and decrease resource use.
METHODS:
We conducted semi-structured qualitative focus group interviews to identify sociotechnical influences on CDS implementation. Physicians from neurosurgery, emergency medicine, critical care, and pediatric general surgery were included, along with information technology specialists. Participants were recruited from nine hospitals in the United States. Focus group transcripts were coded and analyzed using thematic analysis. The final themes were cross-referenced with previously defined sociotechnical dimensions.
RESULTS:
We included 28 physicians and four information technology specialists in seven focus groups. Ten participants had administrative leadership positions, and the largest group (34%) was from neurosurgery. Through inductive thematic analysis, we identified five primary themes: 1) clinical impact; 2) stakeholders and users; 3) tool content; 4) clinical practice integration; and 5) post-implementation evaluation measures. Participants generally supported using CDS to determine an appropriate level-of-care for these children, and also noted potential secondary uses (e.g., informing family discussions). However, some also identified potential harm that could result from misuse (e.g., conflict across specialties). Feedback from the interviews helped refine the tool content, highlight potential implementation barriers, and identify appropriate measures to evaluate after implementation.
CONCLUSION:
We identified key factors impacting the implementation of electronic CDS for children with mTBI and intracranial injuries, providing a strong foundation for prospective implementation efforts.
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