Faculty Bibliography

INTRODUCTION/BACKGROUND:Aripiprazole is an atypical antipsychotic with unique receptor-binding properties that has a favorable safety profile in therapeutic doses compared to other antipsychotics. Massive aripiprazole overdose in children, however, presents with profound lethargy and may have neurologic, hemodynamic, and cardiac effects, often requiring admission to a high level of care. CASE REPORT/METHODS:We describe a case of a 21-month-old male with a reported 52-milligram aripiprazole ingestion. Initial vital signs were remarkable for tachycardia and hypertension, which rapidly resolved. The patient did not develop hypotension throughout hospitalization. He experienced 60 hours of lethargy. Irritability associated with upper extremity spasms and tremors occurred from 36-72 hours post ingestion, which resolved without intervention. The initial electrocardiogram demonstrated ST-segment depressions in the anteroseptal leads; further cardiac workup was normal. Concurrent medical workup was unrevealing. Aripiprazole and dehydro-aripiprazole serum concentrations sent 46 hours after reported exposure were 266.5 nanograms per milliliter (ng/mL) and 138.6 ng/mL, respectively. He returned to neurologic baseline and was discharged 72 hours after ingestion. CONCLUSION/CONCLUSIONS:Antipsychotics, including aripiprazole, should be considered as a potential toxicological cause of persistent central nervous system depression; ingestion of a single dose has the potential to cause significant toxicity.

INTRODUCTION/BACKGROUND:Sepsis is a common cause of emergency department (ED) presentation and hospital admission, accounting for a disproportionate number of deaths each year relative to its incidence. Sepsis outcomes have improved with increased recognition and treatment standards promoted by the Surviving Sepsis Campaign. Due to delay in recognition and other barriers, sepsis bundle compliance remains low nationally. We hypothesised that a targeted education intervention regarding use of an electronic health record (EHR) tool for identification and management of sepsis would lead to increased EHR tool utilisation and increased sepsis bundle compliance. METHODS:We created a multidisciplinary quality improvement team to provide training and feedback on EHR tool utilisation within our ED. A prospective evaluation of the rate of EHR tool utilisation was monitored from June through December 2020. Simultaneously, we conducted two retrospective cohort studies comparing overall sepsis bundle compliance for patients when EHR tool was used versus not used. The first cohort was all patients with intention-to-treat for any sepsis severity. The second cohort of patients included adult patients with time of recognition of sepsis in the ED admitted with a diagnosis of severe sepsis or septic shock. RESULTS:EHR tool utilisation increased from 23.3% baseline prior to intervention to 87.2% during the study. In the intention-to-treat cohort, there was a statistically significant difference in compliance between EHR tool utilisation versus no utilisation in overall bundle compliance (p<0.001) and for several individual components: initial lactate (p=0.009), repeat lactate (p=0.001), timely antibiotics (p=0.031), blood cultures before antibiotics (p=0.001), initial fluid bolus (p<0.001) and fluid reassessment (p<0.001). In the severe sepsis and septic shock cohort, EHR tool use increased from 71.2% pre-intervention to 85.0% post-intervention (p=0.008). CONCLUSION/CONCLUSIONS:With training, feedback and EHR optimisation, an EHR tool can be successfully integrated into current workflows and appears to increase sepsis bundle compliance.

BACKGROUND:Pediatric burns account for 120,000 emergency department visits and 10,000 hospitalizations annually. The American Burn Association has guidelines regarding referrals to burn centers; however there is variation in burn center distribution. We hypothesized that disparity in access would be related to burn center access. METHODS:Using weighted discharge data from the Nationwide Inpatient Sample 2001-2011, we identified pediatric patients with International Classification of Diseases-9th Revision codes for burns that also met American Burn Association criteria. Key characteristics were compared between pediatric patients treated at burn centers and those that were not. RESULTS:Of 54,529 patients meeting criteria, 82.0% (n = 44,632) were treated at burn centers. Patients treated at burn centers were younger (5.6 versus 6.7 years old; p < 0.0001) and more likely to have burn injuries on multiple body regions (88% versus 12%; p < 0.0001). In urban areas, 84% of care was provided at burn centers versus 0% in rural areas (p < 0.0001), a difference attributable to the lack of burn centers in rural areas. Both length of stay and number of procedures were significantly higher for patients treated at burn centers (7.3 versus 4.4 days, p < 0.0001 and 2.3 versus 1.1 procedures, p < 0.0001; respectively). There were no significant differences in mortality (0.7% versus 0.8%, p = 0.692). CONCLUSION:The majority of children who met criteria were treated at burn centers. There was no significant difference between geographical regions. Of those who were treated at burn centers, more severe injury patterns were noted, but there was no significant mortality difference. Further study of optimal referral of pediatric burn patients is needed.

In total, 80% of clubfoot cases occur in low- and middle-income countries, where lack of clinical knowledge of the Ponseti method of treatment presents as a major barrier to treatment. This study aims to determine the effectiveness of an electronic learning course to teach clinicians in Tanzania Ponseti method theory. A total of 30 clinicians were recruited from clinics with high referral rates for clubfoot patients and invited to 1 of 3 training sites: Mbeya (n = 15), Zanzibar (n = 10), and Mwanza (n = 5). Baseline knowledge, measured through a pretest, was compared to performance on a posttest after e-learning course completion. Scores for Mbeya and Zanzibar participants improved from 44 ± 12.5 to 69.8 ± 16.5 (P < .0001) and 44.3 ± 14.0 to 67.9 ± 21.4 (P = .01), respectively. Our results suggest that an e-learning course may be an effective method of disseminating Ponseti method theory in Tanzania. Successful implementation requires an understanding of the device availability and technology literacy of the users.

Rates of diabetes and its associated comorbidities have been increasing in the United States, with diabetic foot ulcer treatment representing a large cost to the patient and healthcare system. These ulcers often result in multiple hospital admissions. This study examined readmissions following inpatient care for a diabetic foot ulcer and identified modifiable factors associated with all-cause 30-day readmissions to the inpatient or emergency department (ED) setting. We hypothesized that patients undergoing aggressive treatment would have lower 30-day readmission rates. We identified patient discharge records containing International Classification of Disease ninth revision codes for both diabetes mellitus and distal foot ulcer in the State Inpatient and Emergency Department databases from the Agency for Healthcare Research and Quality, Healthcare Cost and Utilization Project in Florida and New York, 2011-2012. All-cause 30-day return to care visits (ED or inpatient) were analyzed. Patient demographics and treatment characteristics were evaluated using univariate and multivariable regression models. The cohort included 25,911 discharges, having a mean age of 63 and an average of 3.8 comorbidities. The overall rate of return to care was 30%, and 21% of subjects underwent a toe or midfoot amputation during their index stay. The most common diagnosis codes upon readmission were diabetes mellitus (19%) and infection (13%). Patients with a toe or midfoot amputation procedure were less likely to be readmitted within 30 days (odds ratio: 0.78; 95% confidence interval: 0.73, 0.84). Presence of comorbidities, black and Hispanic ethnicities, and Medicare and Medicaid payer status were also associated with higher odds of readmission following initial hospitalization (p < 0.05). The study suggests that there are many factors that affect readmission rates for diabetic foot ulcer patients. Understanding patients at high-risk for readmission can improve counseling and treatment strategies for this fragile patient population.

Obesity is a crucial public health issue in developed countries, with implications for cardiovascular and brain health as we age. A number of commonly-carried genetic variants are associated with obesity. Here we aim to see whether variants in obesity-associated genes--NEGR1, FTO, MTCH2, MC4R, LRRN6C, MAP2K5, FAIM2, SEC16B, ETV5, BDNF-AS, ATXN2L, ATP2A1, KCTD15, and TNN13K--are associated with white matter microstructural properties, assessed by high angular resolution diffusion imaging (HARDI) in young healthy adults between 20 and 30 years of age from the Queensland Twin Imaging study (QTIM). We began with a multi-locus approach testing how a number of common genetic risk factors for obesity at the single nucleotide polymorphism (SNP) level may jointly influence white matter integrity throughout the brain and found a wide spread genetic effect. Risk allele rs2815752 in NEGR1 was most associated with lower white matter integrity across a substantial portion of the brain. Across the area of significance in the bilateral posterior corona radiata, each additional copy of the risk allele was associated with a 2.2% lower average FA. This is the first study to find an association between an obesity risk gene and differences in white matter integrity. As our subjects were young and healthy, our results suggest that NEGR1 has effects on brain structure independent of its effect on obesity.

Several common genetic variants influence cholesterol levels, which play a key role in overall health. Myelin synthesis and maintenance are highly sensitive to cholesterol concentrations, and abnormal cholesterol levels increase the risk for various brain diseases, including Alzheimer's disease. We report significant associations between higher serum cholesterol (CHOL) and high-density lipoprotein levels and higher fractional anisotropy in 403 young adults (23.8 ± 2.4 years) scanned with diffusion imaging and anatomic magnetic resonance imaging at 4 Tesla. By fitting a multi-locus genetic model within white matter areas associated with CHOL, we found that a set of 18 cholesterol-related, single-nucleotide polymorphisms implicated in Alzheimer's disease risk predicted fractional anisotropy. We focused on the single-nucleotide polymorphism with the largest individual effects, CETP (rs5882), and found that increased G-allele dosage was associated with higher fractional anisotropy and lower radial and mean diffusivities in voxel-wise analyses of the whole brain. A follow-up analysis detected white matter associations with rs5882 in the opposite direction in 78 older individuals (74.3 ± 7.3 years). Cholesterol levels may influence white matter integrity, and cholesterol-related genes may exert age-dependent effects on the brain.