Evaluating Gabapentin Dosing, Efficacy and Safety in Infants.

OBJECTIVE: Gabapentin for management of neuropathic pain, irritability, neonatal abstinence syndrome, rescue sedation, feeding intolerance and visceral hyperalgesia in infants has grown over the past decade. There remains little guidance for indications, initiation, titration and maintenance dosing trends and assessment of outcomes. The primary objective was to describe gabapentin dosing, and the secondary objectives were to identify outcomes to assess efficacy and describe weaning practices. METHODS: A retrospective single-center study was performed in infants younger than 1 year who received gabapentin at Boston Children's Hospital between 2015 and 2021. The primary outcome was indication, initiation and maximum gabapentin dose. Secondary outcomes included mortality, adverse reactions and impact on feeding volumes, weight-for-age Z-scores and face, legs, activity, cry, consolability (FLACC) scores. Descriptive statistics were utilized. RESULTS: Sixty-six infants received gabapentin at a mean ± SD age of 5.5 ± 2.7 months (range of 0-11 months). The mean ± SD initiation dose of gabapentin was 8.6 ± 5.4 mg/kg/day with a median interval of 24 hours (8-24 hours). The maximum mean dose was 23.2 ± 14.4 mg/kg/day at a median interval of every 8 hours (8 hours). The most common indications for initiation were irritability, rescue sedation, and visceral hyperalgesia. There was a statistical improvement in weight-for-age Z scores from 24 hours prior to gabapentin initiation to 2 weeks after the maximum dose of gabapentin (-2.23 ± 1.78 to -1.66 ± 1.91, p < 0.001) and a reduction in FLACC scores (2.29 ± 1.64 to 1.52 ± 1.76, p = 0.007) from 24 hours prior to gabapentin initiation to 3 days after the maximum dose of gabapentin. Three patients experienced minor adverse events. CONCLUSIONS: Gabapentin was well tolerated in infants. Initial gabapentin dosing of 5 mg/kg/dose every 24 hours appears safe and consistent with other published studies in infants. The improvement in outcomes with few adverse events suggests a beneficial role for gabapentin.

Impact of a Documented Penicillin Allergy on Antibiotic Selection in Pediatric Patients With Osteomyelitis.

Penicillin allergy labels are common in hospitalized patients, and there is a frequent misconception that these patients cannot receive cephalosporins. Through retrospective review, we found that patients with reported penicillin allergies were significantly less likely to receive first-line therapy for acute hematogenous osteomyelitis.

Quality Improvement Incorporating a Feedback Loop for Accurate Medication Reconciliation.

OBJECTIVES: Medication reconciliation errors on hospital admission can lead to significant patient harm. A pediatric intermediate care unit initiated a quality improvement project and aimed to reduce errors in admission medication reconciliation by 50% in 12 months. METHODS: From August 2017 to December 2018, a multidisciplinary team conducted a quality improvement project with plan-do-study-act methodology. Continuous data collection was achieved by reviewing medications with home caregivers within 18 hours of admission to identify errors. Cycle 1 consisted of nursing training in accurate and thorough medication history documentation. Cycle 2 was aimed at improving data collection. Cycle 3 was aimed at improving pediatric housestaff processes for medication reconciliation. In cycle 4 intervention, the reconciliation process was redesigned to incorporate the bedside nurse reviewing final medication orders with the patient's home caregivers once the medication reconciliation process was complete. Intermittent maintenance data collection continued for 12 months thereafter. RESULTS: Cycle 1 and 2 interventions resulted in improvement in the medication reconciliation error rate from 9.8% to 4.7%. In cycle 2, the data collection rate improved from 61% to 80% of admissions sustained. Cycle 3 resulted in a further reduction in the medication error rate to 2.9%, which was sustained in cycle 4 and over the 12-month maintenance period. A patient's number of home medications did not correlate with the error rate. CONCLUSIONS: Reductions in admission medication reconciliation errors can be achieved with staff education on medication history and process for medication reconciliation and with process redesign that incorporates active medication order review as a closed-loop communication with home caregivers.

Evaluation of a modified South African Triage Score as a predictor of patient disposition at a tertiary hospital in Rwanda.

BACKGROUND: Triage is essential for efficient and effective delivery of care in emergency centers (ECs) where numerous patients present simultaneously with varying acuity of conditions. Implementing EC triage systems provides a method of recognizing which patients may require admission and are at higher risks for poor health outcomes. Rwanda is experiencing increased demand for emergency care; however, triage has not been well-studied. The University Teaching Hospital of Kigali (UTH-K) is an urban tertiary care health center utilizing a locally modified South African Triage Score (mSATS) that classifies patients into five color categories. Our study evaluated the utility of the mSATS tool at UTH-K. METHODS: UTH-K implemented mSATS in April 2013. All patients aged 15 years or older from August 2015 to July 2016 were eligible for inclusion in the database. Variables of interest included demographic information, mSATS category, patient case type (trauma or medical), disposition from the ED and mortality. RESULTS: 1438 cases were randomly sampled; the majority were male (61.9%) and median age was 35 years. Injuries accounted for 56.7% of the cases while medical conditions affected 43.3%. Admission likelihood significantly increased with higher triage color category for medical patients (OR: Yellow = 3.61, p < .001 to Red (with alarm) = 7.80, p < .01). Likelihood for trauma patients, however, was not significantly increased (OR: Yellow = .84, p = .75 to Red (with alarm) = 1.50, p = .65). Mortality rates increased with increasing triage category with the red with alarm category having the highest mortality (7.7%, OR 18.91). CONCLUSION: The mSATS tool accurately predicted patient disposition and mortality for the overall ED population. The mSATS tool provided useful clinical guidance on the need for hospital admission for medical patients but did not accurately predict patient disposition for injured patients. Further trauma-specific triage studies are needed to improve emergency care in Rwanda.

Platelet Inhibition With IV Glycoprotein IIb/IIIa Inhibitor to Prevent Thrombosis in Pediatric Patients Undergoing Aortopulmonary Shunting.

OBJECTIVES: Shunt thrombosis, a potential complication of aortopulmonary shunting, is associated with high mortality. Commonly used oral antiplatelet drugs such as aspirin demonstrate variable absorption and inconsistent antiplatelet effect in critically ill patients early after surgery. IV glycoprotein IIb/IIIa inhibitors are antiplatelet agents with rapid and reproducible effect that may be beneficial as a bridge to oral therapy. DESIGN: Retrospective review of pediatric patients undergoing treatment with IV tirofiban. Discarded blood samples were used to determine pharmacokinetic parameters. SETTING: Pediatric cardiac ICU at a single institution. PATIENTS: Fifty-two pediatric patients (< 18 yr) undergoing surgical aortopulmonary shunt procedure who received tirofiban infusion as a bridge to oral aspirin. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome measures were shunt thrombosis and bleeding events, whereas secondary outcomes included measurement of platelet inhibition by thromboelastography with platelet mapping and pharmacokinetic analysis (performed in a subset of 15 patients). Shunt thrombosis occurred in two of 52 patients (3.9%) after prophylaxis treatment with tirofiban; both thrombosis events occurred after discontinuation of the drug. One patient (1.9%) experienced bleeding complication during the infusion. A tirofiban bolus of 10 µg/kg and infusion of 0.15 µg/kg/min resulted in significantly increased platelet inhibition via adenosine diphosphate pathway (median 66% [43-96] pre-tirofiban compared with 97% [92-99%] at 2 hr; p < 0.05). Half-life of tirofiban in plasma was 142 ± 1.5 minutes, and the average steady-state concentration was 112 ± 62 ng/mL. Age and serum creatinine were significant covariates associated with systemic clearance. Dosing simulations were generated based upon one compartment model. CONCLUSIONS: IV glycoprotein IIb/IIIa inhibitor as a bridge to oral antiplatelet therapy is safe in pediatric patients after aortopulmonary shunting. Dosing considerations should include both age and renal function. Randomized trials are warranted to establish efficacy compared with current anticoagulation practices.

Adverse event rate during inpatient sotalol initiation for the management of supraventricular and ventricular tachycardia in the pediatric and young adult population.

BACKGROUND: Sotalol is an important antiarrhythmic drug in the pediatric population. Given the risk of proarrhythmia, sotalol is initiated in inpatient settings, with adult studies as recent as 2015 supporting this practice. OBJECTIVE: The purpose of this study was to determine the frequency of adverse events (AEs) during sotalol initiation for the management of atrial, supraventricular, or ventricular arrhythmias in pediatric patients. METHODS: A retrospective cohort analysis of pediatric patients 21 years or younger initiated on oral sotalol for supraventricular tachycardia or ventricular tachycardia (VT) at Boston Children's Hospital from January 1, 2007, through July 1, 2016, was performed. The primary end point was an AE defined as significant bradycardia, new or increased ventricular arrhythmias, conduction block, or corrected QT interval (QTc) prolongation, resulting in dose reduction or cessation. RESULTS: There were 190 patients who met inclusion criteria, with 110 patients (58%) 6 months or younger. A total of 115 patients (60%) had congenital heart disease. Arrhythmias for which sotalol was initiated included atrioventricular reciprocating tachycardia/atrioventricular nodal reciprocating tachycardia (n = 105 [55%]), atrial flutter (n = 31 [16%]), ectopic atrial tachycardia (n = 26 [14%]), VT (n = 21 [11%]), and atrial fibrillation (n = 7 [4%]). The median pre-sotalol QTc was 438 ms (interquartile range 348-530 ms). Five patients (3%) (aged 0.1-18 years) had AEs including bradycardia <40 beats/min (n = 2) and <100 beats/min (n = 1) and QTc prolongation (n = 2). All 5 patients with AEs had repaired congenital heart disease. CONCLUSION: The incidence of AEs in pediatric patients initiating sotalol for atrial tachycardia, supraventricular tachycardia, or VT is low (3%), with no deaths or malignant rhythms reported in this series.

Evaluation of a modified South African Triage Score as a predictor of patient disposition at a tertiary hospital in Rwanda

Background: Triage is essential for efficient and effective delivery of care in emergency centers (ECs) where numerous patients present simultaneously with varying acuity of conditions. Implementing EC triage systems provides a method of recognizing which patients may require admission and are at higher risks for poor health outcomes. Rwanda is experiencing increased demand for emergency care; however, triage has not been well studied. The University Teaching Hospital of Kigali (UTH-K) is an urban tertiary care health center utilizing a locally modified South African Triage Score (mSATS) that classifies patients into five color categories. Our study evaluated the utility of the mSATS tool at UTH-K. Methods: UTH-K implemented mSATS in April 2013. All patients aged 15 years or older from August 2015 to July 2016 were eligible for inclusion in the database. Variables of interest included demographic information, mSATS category, patient case type (trauma or medical), disposition from the ED and mortality. Results: 1438 cases were randomly sampled; the majority were male (61.9%) and median age was 35 years. Injuries accounted for 56.7% of the cases while medical conditions affected 43.3%. Admission likelihood significantly increased with higher triage color category for medical patients (OR: Yellow=3.61, p<.001 to Red (with alarm)=7.80, p<.01). Likelihood for trauma patients, however, was not significantly increased (OR:Yellow=.84, p=.75 to Red (with alarm)=1.50, p=.65). Mortality rates increased with increasing triage category with the red with alarm category having the highest mortality (7.7%, OR 18.91). Conclusion: The mSATS tool accurately predicted patient disposition and mortality for the overall ED population. The mSATS tool provided useful clinical guidance on the need for hospital admission for medical patients but did not accurately predict patient disposition for injured patients. Further trauma-specific triage studies are needed to improve emergency care in Rwanda

Cosmic radiation exposure and persistent cognitive dysfunction.

The Mars mission will result in an inevitable exposure to cosmic radiation that has been shown to cause cognitive impairments in rodent models, and possibly in astronauts engaged in deep space travel. Of particular concern is the potential for cosmic radiation exposure to compromise critical decision making during normal operations or under emergency conditions in deep space. Rodents exposed to cosmic radiation exhibit persistent hippocampal and cortical based performance decrements using six independent behavioral tasks administered between separate cohorts 12 and 24 weeks after irradiation. Radiation-induced impairments in spatial, episodic and recognition memory were temporally coincident with deficits in executive function and reduced rates of fear extinction and elevated anxiety. Irradiation caused significant reductions in dendritic complexity, spine density and altered spine morphology along medial prefrontal cortical neurons known to mediate neurotransmission interrogated by our behavioral tasks. Cosmic radiation also disrupted synaptic integrity and increased neuroinflammation that persisted more than 6 months after exposure. Behavioral deficits for individual animals correlated significantly with reduced spine density and increased synaptic puncta, providing quantitative measures of risk for developing cognitive impairment. Our data provide additional evidence that deep space travel poses a real and unique threat to the integrity of neural circuits in the brain.

What happens to your brain on the way to Mars.

As NASA prepares for the first manned spaceflight to Mars, questions have surfaced concerning the potential for increased risks associated with exposure to the spectrum of highly energetic nuclei that comprise galactic cosmic rays. Animal models have revealed an unexpected sensitivity of mature neurons in the brain to charged particles found in space. Astronaut autonomy during long-term space travel is particularly critical as is the need to properly manage planned and unanticipated events, activities that could be compromised by accumulating particle traversals through the brain. Using mice subjected to space-relevant fluences of charged particles, we show significant cortical- and hippocampal-based performance decrements 6 weeks after acute exposure. Animals manifesting cognitive decrements exhibited marked and persistent radiation-induced reductions in dendritic complexity and spine density along medial prefrontal cortical neurons known to mediate neurotransmission specifically interrogated by our behavioral tasks. Significant increases in postsynaptic density protein 95 (PSD-95) revealed major radiation-induced alterations in synaptic integrity. Impaired behavioral performance of individual animals correlated significantly with reduced spine density and trended with increased synaptic puncta, thereby providing quantitative measures of risk for developing cognitive decrements. Our data indicate an unexpected and unique susceptibility of the central nervous system to space radiation exposure, and argue that the underlying radiation sensitivity of delicate neuronal structure may well predispose astronauts to unintended mission-critical performance decrements and/or longer-term neurocognitive sequelae.

Lambda and alpha interferons inhibit hepatitis B virus replication through a common molecular mechanism but with different in vivo activities.

The type III interferons (IFN-lambda1, 2, and 3) induce an antiviral response similar to IFN-alpha/beta, but mediate their activity through a unique receptor. We found that like IFN-alpha/beta, IFN-lambda prevents the assembly of HBV capsids, demonstrating convergence of the two signaling pathways through a single antiviral mechanism. In contrast to IFN-lambda, the structurally related cytokine interleukin (IL)-22 only minimally reduced HBV replication. The transcriptional program activated by IL-22 displayed little similarity to that induced by IFN-lambda, but instead resembled the response elicited by IL-6. We also found that murine IFN-lambda2 had only weak antiviral activity against HBV in the liver of transgenic mice, and that human IFN-lambda2 activity in serum correlated with the sensitivity of the cytokine to proteases. These results demonstrate that the IFN-alpha/beta and IFN-lambda anti-HBV responses operate through a single molecular mechanism, and support the notion that IFN-lambda plays a local, rather than systemic, role in antiviral immunity.