Resistin Pathway as Novel Mechanism of Post-lung Transplantation Bronchial Stenosis.

BACKGROUND: Bronchial stenosis remains a significant source of morbidity among lung transplant recipients. Though infection and anastomotic ischemia have been proposed etiologies of the development of bronchial stenosis, the pathophysiologic mechanism has not been well elucidated. METHODS: In this single-centered prospective study, from January 2013 through September 2015, we prospectively collected bronchoalveolar lavage (BAL) and endobronchial epithelial brushings from the direct anastomotic site of bronchial stenosis of bilateral lung transplant recipients who developed unilateral post-transplant bronchial stenosis. Endobronchial epithelial brushings from the contralateral anastomotic site without bronchial stenosis and BAL from bilateral lung transplant recipients who did not develop post-transplant bronchial stenosis were used as controls. Total RNA was isolated from the endobronchial brushings and real-time polymerase chain reaction reactions were performed. Electrochemiluminescence biomarker assay was used to measure 10 cytokines from the BAL. RESULTS: Out of 60 bilateral lung transplant recipients, 9 were found to have developed bronchial stenosis with 17 samples adequate for analysis. We observed a 1.56 to 70.8 mean-fold increase in human resistin gene expression in the anastomotic bronchial stenosis epithelial cells compared with nonstenotic airways. Furthermore, IL-1ß (21.76±10.96 pg/mL; control 0.86±0.44 pg/mL; P <0.01) and IL-8 levels (990.56±326.60 pg/mL; control 20.33±1.17 pg/mL; P <0.01) were significantly elevated in the BAL of the lung transplant patients who developed anastomotic bronchial stenosis. CONCLUSION: Our data suggest that the development of postlung transplantation bronchial stenosis may be in part mediated through the human resistin pathway by IL-1ß induced transcription factor nuclear factor-κß activation and downstream upregulation of IL-8 in alveolar macrophages. Further study is needed in the larger patient cohorts and to determine its potential therapeutic role in the management of post-transplant bronchial stenosis.

Comparison of Taboo Search Methods for Atomic Cluster Global Optimization with a Basin-Hopping Algorithm.

The basin-hopping algorithm (BHA) allows for the efficient exploration of atomic cluster potential energy surfaces by random perturbations in configuration space, followed by energy minimizations. Here, the taboo search method is incorporated to prevent the search from revisiting recently visited regions of the search space. Two taboo search modes are implemented, one mode resets the search to random coordinates upon encountering the taboo region, while the other simply rejects any proposed move into the taboo region. These two modes are tested and compared on a variety of potential energy surfaces─several clusters where atomic interactions are described by the Lennard-Jones potential, and Au55 where a semi-empirical tight binding potential is used to describe atomic interactions. Some differences in performance between the two taboo search modes were noted for LJ38 and Au55, with the mode that rejects all hops into the taboo region performing better, offering a means to improve the efficiency of the BHA for multifunnel systems. However, both taboo search modes failed to significantly improve performance on multifunnel systems where more than two funnels were present in the system.

Comparing modalities for risk assessment in patients with pulmonary lesions and nondiagnostic bronchoscopy for suspected lung cancer.

BACKGROUND: Bronchoscopy is commonly utilized for non-surgical sampling of indeterminant pulmonary lesions, but nondiagnostic procedures are common. Accurate assessment of the risk of malignancy is essential for decision making in these patients, yet we lack tools that perform well across this heterogeneous group of patients. We sought to evaluate the accuracy of three previously validated risk models and physician-assessed risk (PAR) in patients with a newly identified lung lesion undergoing bronchoscopy for suspected lung cancer where the result is nondiagnostic. METHODS: We performed an analysis of prospective data collected for the Percepta Bronchial Genomic Classifier Multicenter Registry. PAR and three previously validated risk models (Mayo Clinic, Veteran's Affairs, and Brock) were used to determine the probability of lung cancer (low, intermediate, or high) in 375 patients with pulmonary lesions who underwent bronchoscopy for possible lung cancer with nondiagnostic pathology. Results were compared to the actual adjudicated prevalence of malignancy in each pre-test risk group, determined with a minimum of 12 months follow up after bronchoscopy. RESULTS: PAR and the risk models performed poorly overall in the assessment of risk in this patient population. PAR most closely matched the observed prevalence of malignancy in patients at 12 months after bronchoscopy, but all modalities had a low area under the curve, and in all clinical models more than half of all the lesions labeled as high risk were truly or likely benign. The studied risk model calculators overestimate the risk of malignancy compared to PAR, particularly in the subset in older patients, irregularly bordered nodules, and masses > 3 cm. Overall, the risk models perform only slightly better when confined to lung nodules < 3 cm in this population. CONCLUSION: The currently available tools for the assessment of risk of malignancy perform suboptimally in patients with nondiagnostic findings following a bronchoscopic evaluation for lung cancer. More accurate and objective tools for risk assessment are needed. TRIAL REGISTRATION: not applicable.

Shedding Light on Amoxicillin, Amoxicillin-clavulanate, and Cephalexin Dosing in Children from a Pharmacist's Perspective.

Selection of an antibiotic and dosing regimen requires consideration of multiple factors including microbiological data, site of infection, pharmacokinetics, and how it relates to the pharmacodynamic target. Given the multiple dosage regimens of amoxicillin with/without clavulanate and cephalexin, we review the principles of dose selection from a pharmacist's perspective.

Bleeding Risk With Combination Intrapleural Fibrinolytic and Enzyme Therapy in Pleural Infection: An International, Multicenter, Retrospective Cohort Study.

BACKGROUND: Combination intrapleural fibrinolytic and enzyme therapy (IET) has been established as a therapeutic option in pleural infection. Despite demonstrated efficacy, studies specifically designed and adequately powered to address complications are sparse. The safety profile, the effects of concurrent therapeutic anticoagulation, and the nature and extent of nonbleeding complications remain poorly defined. RESEARCH QUESTION: What is the bleeding complication risk associated with IET use in pleural infection? STUDY DESIGN AND METHODS: This was a multicenter, retrospective observational study conducted in 24 centers across the United States and the United Kingdom. Protocolized data collection for 1,851 patients treated with at least one dose of combination IET for pleural infection between January 2012 and May 2019 was undertaken. The primary outcome was the overall incidence of pleural bleeding defined using pre hoc criteria. RESULTS: Overall, pleural bleeding occurred in 76 of 1,833 patients (4.1%; 95% CI, 3.0%-5.0%). Using a half-dose regimen (tissue plasminogen activator, 5 mg) did not change this risk significantly (6/172 [3.5%]; P = .68). Therapeutic anticoagulation alongside IET was associated with increased bleeding rates (19/197 [9.6%]) compared with temporarily withholding anticoagulation before administration of IET (3/118 [2.6%]; P = .017). As well as systemic anticoagulation, increasing RAPID score, elevated serum urea, and platelets of < 100 × 109/L were associated with a significant increase in bleeding risk. However, only RAPID score and use of systemic anticoagulation were independently predictive. Apart from pain, non-bleeding complications were rare. INTERPRETATION: IET use in pleural infection confers a low overall bleeding risk. Increased rates of pleural bleeding are associated with concurrent use of anticoagulation but can be mitigated by withholding anticoagulation before IET. Concomitant administration of IET and therapeutic anticoagulation should be avoided. Parameters related to higher IET-related bleeding have been identified that may lead to altered risk thresholds for treatment.

A Direct Comparative Study of Bronchoscopic Navigation Planning Platforms for Peripheral Lung Navigation: The ATLAS Study.

BACKGROUND: The use of mapping to guide peripheral lung navigation (PLN) represents an advance in the management of peripheral pulmonary lesions (PPL). Software has been developed to virtually reconstruct computed tomography images into 3-dimensional airway maps and generate navigation pathways to target PPL. Despite this there remain significant gaps in understanding the factors associated with navigation success and failure including the cartographic performance characteristics of these software algorithms. This study was designed to determine whether differences exist when comparing PLN mapping platforms. METHODS: An observational direct comparison was performed to evaluate navigation planning software packages for the lung. The primary endpoint was distance from the terminal end of the virtual navigation pathway to the target PPL. Secondary endpoints included distal virtual and segmental airway generations built to the target and/or in each lung. RESULTS: Twenty-five patient chest computed tomography scans with 41 PPL were evaluated. Virtual airway and navigation pathway maps were generated for each scan/nodule across all platforms. Virtual navigation pathway comparison revealed differences in the distance from the terminal end of the navigation pathway to the target PPL (robotic bronchoscopy 9.4 mm vs. tip-tracked electromagnetic navigation 14.2 mm vs. catheter based electromagnetic navigation 17.2 mm, P=0.0005) and in the generation of complete distal airway maps. CONCLUSION: Comparing PLN planning software revealed significant differences in the generation of virtual airway and navigation maps. These differences may play an unrecognized role in the accurate PLN and biopsy of PPL. Further prospective trials are needed to quantify the effect of the differences reported.

Quantifying the Quality of Web-Based Health Information on Student Health Center Websites Using a Software Tool: Design and Development Study.

BACKGROUND: The internet has become a major source of health information, especially for adolescents and young adults. Unfortunately, inaccurate, incomplete, or outdated health information is widespread on the web. Often adolescents and young adults turn to authoritative websites such as the student health center (SHC) website of the university they attend to obtain reliable health information. Although most on-campus SHC clinics comply with the American College Health Association standards, their websites are not subject to any standards or code of conduct. In the absence of quality standards or guidelines, monitoring and compliance processes do not exist for SHC websites. Thus, there is no oversight of the health information published on SHC websites by any central governing body. OBJECTIVE: The aim of this study is to develop, describe, and validate an open-source software that can effectively and efficiently assess the quality of health information on SHC websites in the United States. METHODS: Our cross-functional team designed and developed an open-source software, QMOHI (Quantitative Measures of Online Health Information), that assesses information quality for a specified health topic from all SHC websites belonging to a predetermined list of universities. The tool was designed to compute 8 different quality metrics that quantify various aspects of information quality based on the retrieved text. We conducted and reported results from 3 experiments that assessed the QMOHI tool in terms of its scalability, generalizability in health topics, and robustness to changes in universities' website structure. RESULTS: Empirical evaluation has shown the QMOHI tool to be highly scalable and substantially more efficient than manually assessing web-based information quality. The tool's runtime was dominated by network-related tasks (98%), whereas the metric computations take <2 seconds. QMOHI demonstrated topical versatility, evaluating SHC website information quality for four disparate and broad health topics (COVID, cancer, long-acting reversible contraceptives, and condoms) and two narrowly focused topics (hormonal intrauterine device and copper intrauterine device). The tool exhibited robustness, correctly measuring information quality despite changes in SHC website structure. QMOHI can support longitudinal studies by being robust to such website changes. CONCLUSIONS: QMOHI allows public health researchers and practitioners to conduct large-scale studies of SHC websites that were previously too time- and cost-intensive. The capability to generalize broadly or focus narrowly allows a wide range of applications of QMOHI, allowing researchers to study both mainstream and underexplored health topics. QMOHI's ability to robustly analyze SHC websites periodically promotes longitudinal investigations and allows QMOHI to be used as a monitoring tool. QMOHI serves as a launching pad for our future work that aims to develop a broadly applicable public health tool for web-based health information studies with potential applications far beyond SHC websites.

Predicting Lymph Node Metastasis in Non-small Cell Lung Cancer: Prospective External and Temporal Validation of the HAL and HOMER Models.

BACKGROUND: Two models, the Help with the Assessment of Adenopathy in Lung cancer (HAL) and Help with Oncologic Mediastinal Evaluation for Radiation (HOMER), were recently developed to estimate the probability of nodal disease in patients with non-small cell lung cancer (NSCLC) as determined by endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA). The objective of this study was to prospectively externally validate both models at multiple centers. RESEARCH QUESTION: Are the HAL and HOMER models valid across multiple centers? STUDY DESIGN AND METHODS: This multicenter prospective observational cohort study enrolled consecutive patients with PET-CT clinical-radiographic stages T1-3, N0-3, M0 NSCLC undergoing EBUS-TBNA staging. HOMER was used to predict the probability of N0 vs N1 vs N2 or N3 (N2|3) disease, and HAL was used to predict the probability of N2|3 (vs N0 or N1) disease. Model discrimination was assessed using the area under the receiver operating characteristics curve (ROC-AUC), and calibration was assessed using the Brier score, calibration plots, and the Hosmer-Lemeshow test. RESULTS: Thirteen centers enrolled 1,799 patients. HAL and HOMER demonstrated good discrimination: HAL ROC-AUC = 0.873 (95%CI, 0.856-0.891) and HOMER ROC-AUC = 0.837 (95%CI, 0.814-0.859) for predicting N1 disease or higher (N1|2|3) and 0.876 (95%CI, 0.855-0.897) for predicting N2|3 disease. Brier scores were 0.117 and 0.349, respectively. Calibration plots demonstrated good calibration for both models. For HAL, the difference between forecast and observed probability of N2|3 disease was +0.012; for HOMER, the difference for N1|2|3 was -0.018 and for N2|3 was +0.002. The Hosmer-Lemeshow test was significant for both models (P = .034 and .002), indicating a small but statistically significant calibration error. INTERPRETATION: HAL and HOMER demonstrated good discrimination and calibration in multiple centers. Although calibration error was present, the magnitude of the error is small, such that the models are informative.

Safety and efficacy of direct two-step penicillin challenges with an inpatient pharmacist-driven allergy evaluation.

Background: Penicillin allergy is commonly reported and has clinical and financial consequences for patients and hospitals. A penicillin evaluation program can safely delabel patients and optimize antibiotic therapy. Pharmacists who perform this task have focused on a detailed interview or penicillin skin testing (PST). Antibiotic graded challenge after PST requires more resources and is more costly than going directly to a two-step challenge. Objective: To determine whether a pharmacist-driven penicillin allergy evaluation and a testing protocol that primarily uses direct oral challenges can safely delabel patients. Methods: Adult patients (ages >18 years) with a penicillin allergy in their electronic medical record (EMR) who were admitted between September 2019 and June 2020 were eligible. Although all patients with penicillin allergy were eligible, priority was given to patients who required antibiotics. Patients were interviewed, and, if indicated, based on an institutional protocol, were tested by using PST and/or two-step oral challenge. If the patient passed the challenge, then the penicillin allergy label was removed in the EMR and the patient counseled. Demographic information, allergy questionnaire results, testing results, and changes in antimicrobial therapy were collected. Results: Fifty patients were evaluated from September 2019 to June 2020. Ninety-six percent of the patients were delabeled, and antibiotic therapy changed for 54%. Twenty patients were delabeled with an interview alone, and 30 patients underwent oral two-step challenge. Only one patient required PST. Conclusion: A pharmacist-driven penicillin allergy evaluation program focused on direct oral graded challenges and bypassing PST can effectively delabel admitted patients. However, more safety data are needed before implementation of similar programs to optimize antibiotic treatment.

Characterization of Therapeutic Drug Monitoring Practices of Voriconazole and Posaconazole at a Pediatric Hospital.

OBJECTIVES: To characterize the voriconazole and posaconazole serum trough ordering practices in patients receiving prophylactic and treatment antifungal therapy. METHODS: A retrospective chart review over a 6-year period of pediatric patients who received voriconazole and/or posaconazole for >24 hours. RESULTS: A total of 113 patients were included in this study and of these patients, 105 received voriconazole and 16 received posaconazole during the study period. Additionally, 167 trough levels were assessed in this study. Only 50% and 54% of levels were considered within goal recommendations for voriconazole and posaconazole, respectively. The median dose required to achieve goal trough concentration was dependent on drug, indication, and dosage form. Lastly, the most common adverse drug reactions (ADRs) were hepatoxicity, QTc prolongation, and CNS changes, which were in concordance with ADRs documented in the clinical trials for voriconazole and posaconazole. Approximately 20% of patients receiving either voriconazole or posaconazole died during the study period and the median trough in both groups was subtherapeutic. CONCLUSIONS: Increased monitoring of trough concentrations may be warranted to prevent death or breakthrough invasive fungal infections. Further studies are warranted for assessing the relationship between trough concentrations and treatment outcomes as well as relationship between dosing and achieving goal trough concentrations.

Sex differences in M2 polarization, chemokine and IL-4 receptors in monocytes and macrophages from asthmatics.

Allergic asthma affects more women than men. It is mediated partially by IL-4/IL-13-driven polarization of monocyte-derived macrophages in the lung. We tested whether sex differences in asthma are due to differential IL-4 responsiveness and/or chemokine receptor expression in monocytes and monocyte-derived macrophages from healthy and allergic asthmatic men and women. We found female cells expressed M2 genes more robustly following IL-4 stimulation than male cells, as did cells from asthmatics than those from healthy controls. This likely resulted from increased expression ofγC, part of the type I IL-4 receptor, and reduced IL-4-induced SOCS1, a negative regulator of IL-4 signaling, in asthmatic compared to healthy macrophages. Monocytes from asthmatic women expressed more CX3CR1, which enhances macrophage survival. Our findings highlight how sex differences in IL-4 responsiveness and chemokine receptor expression may affect monocyte recruitment and macrophage polarization in asthma, potentially leading to new sex-specific therapies to manage the disease.

Impact of Video Game Cross-Training on Learning Bronchoscopy. A Pilot Randomized Controlled Trial.

Background: Video game playing requires many of the same skill sets as medical procedures such as bronchoscopy. These include visual-spatial awareness, rapid decision making, and psychomotor skills. The role of video game cross-training on learning bronchoscopy is unknown. Objective: We studied the association of baseline video gaming experience with, and the impact of short-term video game playing on, visual-spatial awareness and acquisition of basic bronchoscopic skills among medical trainees. Methods: Bronchoscopy-naive medical trainees underwent formal didactic and hands-on instruction on basic bronchoscopy, along with a baseline assessment measuring bronchoscopic and visual-spatial skills. Half of the subjects were subsequently randomized to playing a videogame (Rocket League) for 8 weeks. All participants returned at 4 weeks for a refresher course and at 8 weeks for a final assessment. Results: Thirty subjects completed the study, 16 of them in the intervention arm who all met the minimum video game playing time requirement. At baseline, video game players had significantly lower airway collision rates (6.82 collisions/min vs. 11.64 collisions/min; P = 0.02) and higher scores on the Purdue Visual Spatial Test: Visualization of Rotations test (27.5 vs. 23.54; P = 0.04). At completion, the intervention group had no significant differences in airway collisions, bronchoscopy time, or Bronchoscopy Skills and Tasks Assessment Tool scores. There was moderate correlation between airway collision rate and mean Purdue Visual Spatial Test: Visualization of Rotations score (Spearman's rho, -0.59; P < 0.001). Conclusion: At baseline, learners with former video game-playing experience have higher visual-spatial awareness and fewer airway collisions. The impact of video game playing as an aid to simulation-based bronchoscopic education is uncertain.

Cognitive Load in Electromagnetic Navigational and Robotic Bronchoscopy for Pulmonary Nodules.

Background: Electromagnetic navigational bronchoscopy (ENB) and robotic-assisted bronchoscopy (RB) require a high degree of decision-making and psychomotor skill. Cognitive load theory is the overall effort expended by individuals in response to a task and is closely related to the usability of devices for medical procedures. High cognitive workload leads to poor surgical outcomes and represents a bottleneck for learning that affects performance.Objective: To analyze the cognitive load associated with ENB and RB in experienced ENB practitioners learning RB.Methods: Six experienced ENB bronchoscopists performed ENB and RB on a human cadaver model of peripheral pulmonary nodules. To assess cognitive load, we used the Surgery Task Load Index (SURG-TLX) and biometric changes. The SURG-TLX questionnaire was given to the provider after every peripheral pulmonary nodule biopsy with ENB and RB. Pupillary dilation and screen changes were continuously measured throughout the procedure for each biopsy attempt to collect biometric measures of cognitive load. Procedural time and biopsy outcome were also recorded.Results: Forty procedures (ENB and RB) were analyzed. Task complexity (23%) and mental demand (21.4%) were the highest contributors to cognitive load in ENB and RB. The cumulative SURG-TLX was significantly lower for the RB (69.25 vs. 101.25; P < 0.01). Total procedure time was greater for ENB (6.7 min; SD 1.5) compared with RB (4.4 min; SD 1.5; P = 0.01). Pupillary diameter was similar across the modalities (RB vs. ENB), but the diameter was higher during the biopsy portion (4.25 mm) than the navigation portion (4.01 mm).Conclusion: The intrinsic cognitive load of RB was highly manageable by existing ENB practitioners, and in this study, RB appeared to be less mentally demanding. Future development and training should focus on task complexity and mental demand for RB. The biopsy portion, regardless of bronchoscopic modality, should be a focus for education and training.

Assessment of Ergonomic Strain and Positioning During Bronchoscopic Procedures: A Feasibility Study.

BACKGROUND: Poor ergonomics place health care workers at risk for work-related overuse injuries. Repetitive and prolonged hand maneuvers, such as those performed during endoscopic procedures, may lead to musculoskeletal complaints and work-related injuries. However, the prevalence of health care-related work injuries among physicians is thought to be underreported and there is a paucity of literature investigating the impact of ergonomic strain on bronchoscopy. We designed a feasibility study to explore the differences in ergonomic strain and muscle activity of bronchoscopists. MATERIALS AND METHODS: A prospective study of bronchoscopic procedures was performed in a simulated environment. Preselected target areas were identified and airway sampling was performed with real-time ergonomic assessment utilizing electromyogram (EMG), grip strength, and musculoskeletal use and motion analysis. RESULTS: Procedural data was obtained for all procedures (78 bronchoscopies by 13 subjects) for both ergonomic and EMG scores. Experienced bronchoscopists demonstrated less EMG burden (P=0.007) and improved ergonomic positioning (P=0.007) during bronchoscopy when compared with less experienced bronchoscopists. Procedures performed with rotational-head bronchoscopes trended toward improved ergonomics (P=0.15) and lower EMG scores (P=0.88). A significant improvement in ergonomic scores was seen with the rotational-head bronchoscope when targeting the left upper lobe (P=0.036). CONCLUSION: Poor ergonomic positioning and excessive muscle strain appear present within bronchoscopy procedures but may be improved in those with more bronchoscopy experience. Technological advances in bronchoscope design may also have the potential to improve procedural ergonomics. Additional prospective studies are warranted to define the long-term impact on bronchoscopic ergonomics.

A Prospective Randomized Comparative Study of Three Guided Bronchoscopic Approaches for Investigating Pulmonary Nodules: The PRECISION-1 Study.

BACKGROUND: The capability of bronchoscopy in the diagnosis of peripheral pulmonary nodules (PPNs) remains limited. Despite decades of effort, evidence suggests that the diagnostic accuracy for electromagnetic navigational bronchoscopy (EMN) and radial endobronchial ultrasound (EBUS) approach only 50%. New developments in robotic bronchoscopy (RB) may offer improvements in the assessment of PPNs. METHODS: A prospective single-blinded randomized controlled comparative study to assess success in localization and puncture of PPNs, using an ultrathin bronchoscope with radial EBUS (UTB-rEBUS) vs EMN vs RB in a human cadaver model of PPNs < 2 cm, was performed. The primary end point was the ability to successfully localize and puncture the target nodule, verified by cone-beam CT comparing RB and EMN. Secondary end points included needle to target position "miss" distance, and UTB-rEBUS comparisons. RESULTS: Sixty procedures were performed to target 20 PPNs over the study period. Implanted PPNs were distributed across all lobes, with 80% located within the lung periphery. The target PPN mean diameter was 16.5 ± 1.5 mm, with 50% noted to have a CT bronchus sign. The rate of successful PPN localization and puncture was superior when using RB, compared with EMN (80% vs 45%; P = .02). Among unsuccessful needle passes, the median needle to target "miss" distance was significantly different when comparing UTB-rEBUS, EMN, and RB (P = .0014). CONCLUSIONS: In a cadaver model, use of RB significantly increased the ability to localize and successfully puncture small PPNs when compared with existing technologies. This study demonstrates the potential of RB to precisely reach, localize, and puncture small nodules in the periphery of the lung.

Clinical impact of an antimicrobial stewardship program on high-risk pediatric patients.

OBJECTIVE: To evaluate the clinical impact of an antimicrobial stewardship program (ASP) on high-risk pediatric patients. DESIGN: Retrospective cohort study. SETTING: Free-standing pediatric hospital. PATIENTS: This study included patients who received an ASP review between March 3, 2008, and March 2, 2017, and were considered high-risk, including patients receiving care by the neonatal intensive care (NICU), hematology/oncology (H/O), or pediatric intensive care (PICU) medical teams. METHODS: The ASP recommendations included stopping antibiotics; modifying antibiotic type, dose, or duration; or obtaining an infectious diseases consultation. The outcomes evaluated in all high-risk patients with ASP recommendations were (1) hospital-acquired Clostridium difficile infection, (2) mortality, and (3) 30-day readmission. Subanalyses were conducted to evaluate hospital length of stay (LOS) and tracheitis treatment failure. Multivariable generalized linear models were performed to examine the relationship between ASP recommendations and each outcome after adjusting for clinical service and indication for treatment. RESULTS: The ASP made 2,088 recommendations, and 50% of these recommendations were to stop antibiotics. Recommendation agreement occurred in 70% of these cases. Agreement with an ASP recommendation was not associated with higher odds of mortality or hospital readmission. Patients with a single ASP review and agreed upon recommendation had a shorter median LOS (10.2 days vs 13.2 days; P < .05). The ASP recommendations were not associated with high rates of tracheitis treatment failure. CONCLUSIONS: ASP recommendations do not result in worse clinical outcomes among high-risk pediatric patients. Most ASP recommendations are to stop or to narrow antimicrobial therapy. Further work is needed to enhance stewardship efforts in high-risk pediatric patients.

Characterization of Severe Adverse Drug Reactions at a Free-Standing Children's Hospital.

We performed a retrospective chart review on severe adverse drug reactions (ADRs) detected by a pharmacovigilance program at a free-standing pediatric hospital from January 2011 through September 2014. The pharmacist-led program identifies ADRs using electronic medical record triggers. A systematic approach was used to classify ADR type and severity and assure accurate documentation. Data collection included demographics, implicated medication, type of ADR, Naranjo probability scale, ADR-associated International Classification of Diseases, 9th Revision E codes, 30-day mortality, and health care visit cost. One hundred sixty-six severe pediatric ADRs were included, occurring in 163 unique patients. Severe ADRs were commonly associated with antimicrobials (48%), antineoplastics (10%), and antiepileptics (10%). The majority of ADRs were classified by the Naranjo probability scale as probable (59%). One hundred fifty-four patients were admitted to the hospital, with a median length of stay of 3 days; 22 of these patients required admission to the pediatric intensive care unit for a median of 3 days. The median estimated health care cost associated with severe ADRs was $4055.52. No deaths occurred. Nearly 40% of severe ADRs would have gone unidentified using ADR-associated International Classification of Diseases, 9th Revision E codes alone. The impact of pediatric ADRs on the health care system is underestimated. Strategies such as active pharmacovigilance programs enhance the identification, characterization, and documentation of these otherwise unrecognized ADRs.