Duke Raleigh Hospital

Undoped, high-quality diamond is, under almost all circumstances, one of the best insulators known. However, diamond covered with chemically bound hydrogen shows a pronounced conductivity when exposed to air. This conductivity arises from positive-charge carriers (holes) and is confined to a narrow near-surface region. Although several explanations have been proposed, none has received wide acceptance, and the mechanism remains controversial. Here, we report the interactions of hydrogen-terminated, macroscopic diamonds and diamond powders with aqueous solutions of controlled pH and oxygen concentration. We show that electrons transfer between the diamond and an electrochemical reduction/oxidation couple involving oxygen. This charge transfer is responsible for the surface conductivity and also influences contact angles and zeta potentials. The effect is not confined to diamond and may play a previously unrecognized role in other disparate systems.

BACKGROUND AND METHODS: Persons of low socioeconomic status are known to have reduced life expectancy. In a study of the relation of socioeconomic status to disability-free or active life expectancy among older persons, we analyzed prospectively gathered data on 2219 blacks and 1838 whites who were 65 years of age or older in the Piedmont region of North Carolina. We defined disability as the inability to perform independently one or more basic functional activities such as walking, bathing, dressing, eating, and using the toilet. For subgroups defined by sex, race, and education, statistical models were used to estimate, for persons at each year of age, the probability of transition from not being disabled or being disabled at base line to not being disabled, being disabled, or having died one year later. These transition probabilities were then entered into increment-decrement life tables to generate estimates of total, active, and disabled life expectancy (with total life expectancy equal to active life expectancy plus disabled life expectancy). RESULTS: Sixty-five-year-old black men had a lower total life expectancy (11.4 years) and active life expectancy (10 years) than white men (total life expectancy, 12.6 years; active life expectancy, 11.2 years), although the differences were reduced after we controlled for education. The estimates for 65-year-old black women (total life expectancy, 18.7 years; active life expectancy, 15.9 years) were similar to those for white women. Black men and women 75 years old and older had higher values for total life expectancy and active life expectancy than whites, and the differences were larger after stratification for education. Education had a substantially stronger relation to total life expectancy and active life expectancy than did race. At the age of 65, those with 12 or more years of education had an active life expectancy that was 2.4 to 3.9 years longer than the values for those with less education in all the four subgroups defined by sex and race. Overall, the subgroups with longer total life expectancy and active life expectancy also lived more years with a disability. CONCLUSIONS: Among older blacks and whites, the level of education, a measure of socioeconomic status, has a greater effect than race on total life expectancy and active life expectancy.

BACKGROUND: Financial burden for patients, providers, and payers can reduce access to physical therapy (PT) after total knee arthroplasty (TKA). The purpose of the present study was to examine the effect of a virtual PT program on health-care costs and clinical outcomes as compared with traditional care after TKA. METHODS: At least 10 days before unilateral TKA, patients from 4 clinical sites were enrolled and randomized 1:1 to the virtual PT program (involving an avatar [digitally simulated] coach, in-home 3-dimensional biometrics, and telerehabilitation with remote clinician oversight by a physical therapist) or to traditional PT care in the home or outpatient clinic. The primary outcome was total health-care costs for the 12-week post-hospital period. Secondary (noninferiority) outcomes included 6 and 12-week Knee injury and Osteoarthritis Outcome Score (KOOS); 6-week knee extension, knee flexion, and gait speed; and 12-week safety measures (patient-reported falls, pain, and hospital readmissions). All outcomes were analyzed on a modified intent-to-treat basis. RESULTS: Of 306 patients (mean age, 65 years; 62.5% women) who were randomized from November 2016 to November 2017, 290 had TKA and 287 (including 143 in the virtual PT group and 144 in the usual care group) completed the trial. Virtual PT had lower costs at 12 weeks after discharge than usual care (median, $1,050 compared with $2,805; p < 0.001). Mean costs were $2,745 lower for virtual PT patients. Virtual PT patients had fewer rehospitalizations than the usual care group (12 compared with 30; p = 0.007). Virtual PT was noninferior to usual PT in terms of the KOOS at 6 weeks (difference, 0.77; 90% confidence interval [CI], -1.68 to 3.23) and 12 weeks (difference, -2.33; 90% CI, -4.98 to 0.31). Virtual PT was also noninferior to usual care at 6 weeks in terms of knee extension, knee flexion, and gait speed and at 12 weeks in terms of pain and hospital readmissions. Falls were reported by 19.4% of virtual PT patients and 14.6% of usual care patients (difference, 4.83%; 90% CI, -2.60 to 12.25). CONCLUSIONS: Relative to traditional home or clinic PT, virtual PT with telerehabilitation for skilled clinical oversight significantly lowered 3-month health-care costs after TKA while providing similar effectiveness. These findings have important implications for patients, health systems, and payers. Virtual PT with clinical oversight should be considered for patients managed with TKA. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Early, systemic, wide-spectrum antibiotic therapy is necessary for the treatment of open fractures. The bead pouch technique delivers antibiotics locally and prevents secondary wound contamination. The open fracture wound should be thoroughly débrided. To avoid the complication of gas gangrene, the wound should not be closed. Extensive soft-tissue damage may necessitate the use of local or free flaps. Techniques of fracture stabilization depend on the anatomic location of the fracture and the characteristics of the injury. Early bone grafting and supplemental procedures may be needed to achieve healing. Management of the infected open fracture is based on radical débridement, skeletal stabilization, microbial-specific antibiotics, soft-tissue coverage, and reconstruction of bone defects.

BACKGROUND: We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19. METHODS: In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov, NCT04501978. FINDINGS: Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50-72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74-1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67-1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74-1·58]; BRII-196 plus BRII-198 1·00 [0·68-1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91-1·37]) and 155 (88%) in the BRII-196 plus BRII-198 group (1·08 [0·88-1·32]). The composite safety outcome up to day 90 was met by 48 (27%) patients in the placebo group, 42 (23%) in the sotrovimab group, and 45 (26%) in the BRII-196 plus BRII-198 group. 13 (7%) patients in the placebo group, 14 (8%) in the sotrovimab group, and 15 (9%) in the BRII-196 plus BRII-198 group died up to day 90. INTERPRETATION: Neither sotrovimab nor BRII-196 plus BRII-198 showed efficacy for improving clinical outcomes among adults hospitalised with COVID-19. FUNDING: US National Institutes of Health and Operation Warp Speed.

OBJECTIVE: This study examined (1) the relationship of fear of falling to depression, anxiety, activity level, and activity restriction and (2) whether depression or anxiety predicted fear of falling, activity level, activity restriction, or changes in activity level. METHOD: We administered the Survey of Activities and Fear of Falling in the Elderly; the Geriatric Depression Scale-30; and the Hamilton Anxiety Scale, IVR Version, during a one-time visit to 99 community-dwelling adults ≥55 yr old. RESULTS: We found significant relationships between (1) fear of falling and depression, anxiety, and activity level; (2) depression and anxiety; and (3) activity restriction and depression. Activity level was negatively correlated with activity restriction, fear of falling, depression, and anxiety. Anxiety predicted both fear of falling and activity level. Both anxiety and depression predicted activity restriction because of fear of falling and for other reasons. CONCLUSION: Occupational therapy practitioners should consider screening their older adult clientele for fear of falling, anxiety, and depression because these states may lead to fall risk and activity restriction.

BACKGROUND: Schizophrenia (SZ) is a severe neuropsychiatric disorder associated with disrupted connectivity within the thalamic-cortico-cerebellar network. Resting-state functional connectivity studies have reported thalamic hypoconnectivity with the cerebellum and prefrontal cortex as well as thalamic hyperconnectivity with sensory cortical regions in SZ patients compared with healthy comparison participants (HCs). However, fundamental questions remain regarding the clinical significance of these connectivity abnormalities. METHOD: Resting state seed-based functional connectivity was used to investigate thalamus to whole brain connectivity using multi-site data including 183 SZ patients and 178 matched HCs. Statistical significance was based on a voxel-level FWE-corrected height threshold of p < 0.001. The relationships between positive and negative symptoms of SZ and regions of the brain demonstrating group differences in thalamic connectivity were examined. RESULTS: HC and SZ participants both demonstrated widespread positive connectivity between the thalamus and cortical regions. Compared with HCs, SZ patients had reduced thalamic connectivity with bilateral cerebellum and anterior cingulate cortex. In contrast, SZ patients had greater thalamic connectivity with multiple sensory-motor regions, including bilateral pre- and post-central gyrus, middle/inferior occipital gyrus, and middle/superior temporal gyrus. Thalamus to middle temporal gyrus connectivity was positively correlated with hallucinations and delusions, while thalamus to cerebellar connectivity was negatively correlated with delusions and bizarre behavior. CONCLUSIONS: Thalamic hyperconnectivity with sensory regions and hypoconnectivity with cerebellar regions in combination with their relationship to clinical features of SZ suggest that thalamic dysconnectivity may be a core neurobiological feature of SZ that underpins positive symptoms.

Uveitis is one of the most common ocular diseases and one of the most common causes of blindness in dogs. The purpose of this retrospective study was to correlate the signalment, history, clinical signs and ophthalmic findings of dogs with uveitis with the underlying etiology. We conducted a retrospective study of 102 dogs presented to the NCSU-VTH from 1989 to 2000 with clinical signs of uveitis. Medical records of dogs presented for uveitis were reviewed. Dogs were included in the study only if a complete diagnostic work-up database was collected, if sufficient follow-up was documented, and if the uveitis was not secondary to trauma or a hypermature cataract. The mean age +/- SD of all dogs in this study was 6.2 +/- 3.6 years. There were 33 intact and 16 castrated males, and 14 intact and 27 neutered females. Fourteen breeds were represented, with the Golden Retriever (n = 14) most common. Fifty-nine dogs (58%) were diagnosed with idiopathic/immune-mediated uveitis, neoplasia was diagnosed in 25 dogs (24.5%) and 18 dogs (17.6%) were diagnosed with infectious causes of uveitis. Aqueous flare was the most common clinical sign, occurring in 88 dogs (86%). The most common infectious organisms associated with uveitis in the dogs of this study were Ehrlichia canis (n = 7). Lymphosarcoma (n = 17) was the most common neoplasm. In approximately 60% of dogs presenting for uveitis an underlying cause was not found, and a diagnosis of immune-mediated or idiopathic uveitis was made. However, approximately 25% of dogs had ocular and/or systemic neoplasia (with 17% of cases having lymphosarcoma) and 18% with an underlying infectious cause for uveitis. Because of the high percentage of systemic disease associated with uveitis in dogs, extensive diagnostic testing is recommended before instituting symptomatic anti-inflammatory therapy.

BACKGROUND: Alloimmunization remains a significant complication of transfusion and has been associated with multiple factors, including inflammation, an important pathophysiologic mechanism in sickle cell disease (SCD). We explored whether alloimmunization is associated with disease severity in SCD. STUDY DESIGN AND METHODS: Adult SCD patients were enrolled in a study of outcome-modifying genes in SCD. Historical records of patients with SCD at two participating institutions were reviewed for data on antigen phenotype and alloimmunization. Differences in demographic, clinical, and laboratory findings; end-organ damage; and overall disease severity were then compared between alloimmunized and nonalloimmunized patients. RESULTS: Of 319 patients, 87 (27%) were alloimmunized. Alloantibody specificities differed from those previously described, especially due to the significantly higher frequency of anti-S. Although alloimmunization was not associated with frequency of vasoocclusive episodes, a higher percentage of alloimmunized patients had chronic pain, as defined by daily use of short-acting narcotics (p = 0.006), long-acting narcotics (p = 0.013), or both (p = 0.03). Additionally, alloimmunized patients had poorer survival (hazard ratio, 1.92; p = 0.01) and were more likely to have avascular necrosis (p = 0.024), end-organ damage (p = 0.049), and red blood cell autoantibodies (p < 0.001), even after controlling for the effects of age, sex, and hemoglobin diagnosis. Alloimmunization was not associated with other SCD-related complications, such as acute chest syndrome or stroke. CONCLUSION: Alloimmunization in SCD may be associated with chronic pain, risk of end-organ damage, and shorter survival. These novel findings suggest new directions for the investigation of immune response-mediated pathways common to alloimmunization and chronic pain.

BACKGROUND AND PURPOSE: Although neurofibromatosis type 1 (NF1) may be associated with an incompletely understood vasculopathy, relative odds of stroke in this population is not known. METHODS: Using the 1998 to 2009 US Nationwide Inpatient Sample, we performed a case-control study matching cases of NF1 to controls without such a diagnosis. We then compared the odds of stroke between the 2 groups. We used multivariable logistic regression to adjust for known or suspected confounders. RESULTS: NF1 was associated with younger mean age at the time of stroke (41 versus 48) and a lower prevalence of stroke risk factors among adult patients. Pediatric patients with NF1, however, were more likely to have hypertension. Patients with NF1 were significantly more likely to be diagnosed with any stroke (odds ratio, 1.2; P<0.0001) than the general population. The odds of intracerebral hemorrhage were greatest among hemorrhagic stroke types analyzed (odds ratio, 1.9; P<0.0001). In the pediatric NF1 population, the odds of intracerebral hemorrhage were more dramatically elevated (odds ratio, 8.1; P<0.0001). The odds of ischemic stroke were also increased with NF1 in the pediatric (odds ratio, 3.4; P<0.0001) but not in the adult population. CONCLUSIONS: When compared with the general population, the odds of any type of stroke are significantly increased for patients with NF1, both adult and pediatric. This risk is most notable for hemorrhagic strokes although it is also increased for ischemic strokes in children. Physicians should be aware of the increased risk of stroke in this population, and consider stroke as a potential cause of new neurological symptoms.

Preparing future nursing leaders to be successful is important because many current leaders will retire in large numbers in the future. A structured nursing leadership development program utilizing the Essentials of Nurse Manager Orientation online program provided future nursing leaders with content aligned with nursing leadership competencies. Paired with assigned mentors and monthly leadership sessions, the participants increased their perception of leadership competence.

Previous studies of von Willebrand disease indicate that a deficiency of blood clotting Factor VIII/von Willebrand factor (FVIII/vWF) activity is responsible for the failure of platelets to participate fully in the initial stages of hemostasis. We have recently identified specific FVIII/vWF binding sites on platelets, suggesting that the interaction of these sites with FVIII/vWF may be functionally important in the development of platelet clumps. We have now studied how different ristocetin concentrations, various known platelet aggregation inhibitors, and the exposure of platelets to proteases affect the ability of platelets to bind FVIII/vWF and to form aggregates. Our results demonstrate a highly significant linear correlation between the degree of FVIII/vWF receptor binding and the extent of ristocetin-induced platelet aggregation. Because neither FVIII/vWF binding nor platelet aggregation occurs after platelets are exposed to low concentrations of proteases, the FVIII/vWF receptors must be in the platelet membrane. We conclude that the interaction between FVIII/vWF protein and its receptors on the platelet membrane is an important mechanism by which platelet aggregation occurs during primary phase hemostasis.

BACKGROUND: Hospitalization for low-risk pulmonary embolism (PE) is common, expensive, and of questionable benefit. OBJECTIVE: The objective was to determine if low-risk PE patients discharged from the emergency department (ED) on rivaroxaban require fewer hospital days compared to standard of care (SOC). METHODS: Multicenter, open-label randomized trial in low-risk PE defined by Hestia criteria. Adult subjects were randomized to early ED discharge on rivaroxaban or SOC. Primary outcome was total number of initial hospital hours, plus hours of hospitalization for bleeding or venous thromboembolism (VTE), 30 days after randomization. A 90-day composite safety endpoint was defined as major bleeding, clinically relevant nonmajor bleeding, and mortality. RESULTS: Of 114 randomized subjects, 51 were early discharge and 63 were SOC. Of 112 (98.2%) receiving at least one dose of study drug, 99 (86.8%) completed the study. Initial hospital LOS was 4.8 hours versus 33.6 hours, with a mean difference of -28.8 hours (95% confidence interval [CI] = -42.55 to -15.12 hours) for early discharge versus SOC, respectively. At 90 days, mean total hospital days (for any reason) were less for early discharge than SOC, 19.2 hours versus 43.2 hours, with a mean difference of 26.4 hours (95% CI = -46.97 to -3.34 hours). At 90 days, there were no bleeding events, recurrent VTE, or deaths. The composite safety endpoint was similar in both groups, with a difference in proportions of 0.005 (95% CI = -0.18 to 0.19). Total costs were $1,496 for early discharge and $4,234 for SOC, with a median difference of $2,496 (95% CI = -$2,999 to -$2,151). CONCLUSIONS: Low-risk ED PE patients receiving early discharge on rivaroxaban have similar outcomes to SOC, but fewer total hospital days and lower costs over 30 days.

BACKGROUND: Initiation of treatment for substance use disorders is low among young women from disadvantaged communities in Cape Town, South Africa. Yet little is known about the factors that influence perceived need for treatment (a determinant of treatment entry) within this population. METHODS: Baseline data on 720 young, drug-using women, collected as part of a randomized field experiment were analyzed to identify predisposing, enabling and health need factors associated with perceived need for treatment. RESULTS: Overall, 46.0% of our sample perceived a need for treatment. Of these participants, 92.4% wanted treatment for their substance use problems but only 50.1% knew where to access services. In multivariable logistic regression analyses, we found significant main effects for ethnicity (AOR = 1.54, 95% CI = 1.05-1.65), income (AOR = 0.96, 95% CI = 0.93-0.99), anxiety (AOR = 1.22, 95% CI = 1.05-1.45), and not having family members with drug problems (AOR = 1.45, 95% CI = 1.05-2.04) on perceived need for treatment. When the sample was stratified by methamphetamine use, income (AOR = 0.87, 95% CI = 0.79-0.96), awareness of treatment services (AOR =1.84, 95% CI = 1.03-3.27), anxiety (AOR =1.41, 95% CI = 1.06-1.87) and physical health status (AOR = 6.29, 95% CI = 1.56-25.64) were significantly associated with perceived need for treatment among those who were methamphetamine-negative. No variables were significantly associated with perceived need for treatment among participants who were methamphetamine-positive. CONCLUSIONS: A sizeable proportion of young women who could benefit from substance use treatment do not believe they need treatment, highlighting the need for interventions that enhance perceived need for treatment in this population. Findings also show that interventions that link women who perceive a need for treatment to service providers are needed. Such interventions should address barriers that limit young women's use of services for substance use disorders.

Lesions of the ventrolateral brainstem, clivus, and cerebellopontine angle pose significant challenges for surgeons, and the rate of morbidity and mortality from classic neurosurgical approaches has proven to be unacceptably high. Early attempts to expose this region consisted primarily of an extended suboccipital craniectomy, with opening of the tentorium and ligation of the sigmoid sinus for additional exposure. During the 1960s, technological innovations including the surgical microscope and the pneumatic drill allowed surgeons to gain additional exposure by removing more bone from the base of the skull. This let surgeons define combined infra- and supratentorial approaches, which rely less on brain retraction to resect these difficult tumors successfully. These approaches rely on a combined posterior mastoid approach with an anterior petrosectomy. The evolution of this approach is discussed in this paper.

Nerve capping techniques have been introduced as a promising treatment modality for the treatment of painful neuroma with varied outcomes; however, its exact mechanism is still unknown. RhoA is one of the members of the RAS superfamily of GTPases that operate as molecular switches and plays an important role in peripheral nerve regeneration. Our aim was to investigate the structural and morphologic mechanisms by which the nerve capping technique prevents the formation of painful neuromas after neuroectomy. We also hoped to provide a theoretical basis for this treatment approach. An aligned nanofiber conduit was used for the capping procedure and the sciatic nerve of Sprague-Dawley rats was selected as the animal model. Behavioral analysis, extent of neuroma formation, histological assessment, expressions of pain markers of substance P and c-fos, molecular biological changes as well as ultrastructural features were investigated and compared with the findings in a no-capping control group. The formation of traumatic neuromas was significantly inhibited in the capping group with relatively "normal" structural and morphological features and no occurrence of autotomy and significantly lower expression of pain markers compared to the no-capping group. The gene expression of RhoA was consistently in a higher level in the capping group within 8 weeks after surgery. This study shows that capping technique will alter the regeneration state of transected nerves and reduce painful neuroma formation, indicating a promising approach for the treatment of painful neuroma. The initiation of the "regenerative brake" induced by structural as well as morphological improvements in the severed nerve is theorized to be most likely a key mechanism for the capping technique in the prevention of painful neuroma formation.

The early history of the Laségue sign has been reviewed, and credit is given to Fajersztajn for the first demonstration of the crossed or well-leg-raising test. Numerous observers have shown that flexion of the thigh on the abdomen with the leg extended causes rostral movement of the contralateral extradural nerve roots at the fourth and fifth lumbar and first. sacral levels, with approximation of these nerve roots to the anterior spine wall; these findings have been confirmed. It has been shown that approximately one-third of all Patients with verified disc protrusions have a positive well-leg-raising test, and that almost all of these have large protrusions. In the cases which this relationship has been studied, the disc protrusion has been found on the medial aspect of the affected nerve root.

STUDY DESIGN: Economic modeling of data from a multicenter, prospective registry. OBJECTIVE: The aim of this study was to analyze the cost utility of recombinant human bone morphogenetic protein-2 (BMP) in adult spinal deformity (ASD) surgery. SUMMARY OF BACKGROUND DATA: ASD surgery is expensive and presents risk of major complications. BMP is frequently used off-label to reduce the risk of pseudarthrosis. METHODS: Of 522 ASD patients with fusion of five or more spinal levels, 367 (70%) had at least 2-year follow-up. Total direct cost was calculated by adding direct costs of the index surgery and any subsequent reoperations or readmissions. Cumulative quality-adjusted life years (QALYs) gained were calculated from the change in preoperative to final follow-up SF-6D health utility score. A decision-analysis model comparing BMP versus no-BMP was developed with pseudarthrosis as the primary outcome. Costs and benefits were discounted at 3%. Probabilistic sensitivity analysis was performed using mixed first-order and second-order Monte Carlo simulations. One-way sensitivity analyses were performed by varying cost, probability, and QALY estimates (Alpha = 0.05). RESULTS: BMP was used in the index surgery for 267 patients (73%). The mean (±standard deviation) direct cost of BMP for the index surgery was $14,000 ± $6400. Forty patients (11%) underwent revision surgery for symptomatic pseudarthrosis (BMP group, 8.6%; no-BMP group, 17%; P = 0.022). The mean 2-year direct cost was significantly higher for patients with pseudarthrosis ($138,000 ± $17,000) than for patients without pseudarthrosis ($61,000 ± $25,000) (P < 0.001). Simulation analysis revealed that BMP was associated with positive incremental utility in 67% of patients and considered favorable at a willingness-to-pay threshold of $150,000/QALY in >52% of patients. CONCLUSION: BMP use was associated with reduction in revisions for symptomatic pseudarthrosis in ASD surgery. Cost-utility analysis suggests that BMP use may be favored in ASD surgery; however, this determination requires further research. LEVEL OF EVIDENCE: 2.

BACKGROUND: Malignant central airway obstruction (CAO) occurs in approximately 20-30% of patients with lung cancer and is associated with debilitating symptoms and poor prognosis. Multimodality therapeutic bronchoscopy can relieve malignant CAO, though carries risk. Evidence to guide clinicians regarding which patients may benefit from such interventions is sparse. We aimed to assess the clinical and radiographic predictors associated with therapeutic bronchoscopy success in relieving malignant CAO. METHODS: We reviewed all cases of therapeutic bronchoscopy performed for malignant CAO at our institution from January 2010-February 2017. Therapeutic bronchoscopy success was defined as establishing airway patency of > 50%. Patient demographics and baseline characteristics, oncology history, degree of airway obstruction, procedural interventions, and complications were compared between successful and unsuccessful groups. Univariate and multivariate logistic regression identified the significant clinical and radiographic predictors for therapeutic success. The corresponding simple and conditional odds ratio were calculated. A time-to-event analysis with Kaplan-Meier plots was performed to estimate overall survival. RESULTS: During the study period, 301 therapeutic bronchoscopies were performed; 44 (14.6%) were considered unsuccessful. Factors associated with success included never vs current smoking status (OR 5.36, 95% CI:1.45-19.74, p = 0.010), patent distal airway on CT imaging (OR 15.11, 95% CI:2.98-45.83, p < 0.0001) and patent distal airway visualized during bronchoscopy (OR 10.77, 95% CI:3.63-31.95, p < 0.001) in univariate analysis. Along with patent distal airway on CT imaging, increased time from radiographic finding to therapeutic bronchoscopy was associated with lower odds of success in multivariate analysis (OR 0.96, 95% CI:0.92-1.00, p = 0.048). Median survival was longer in the successful group (10.2 months, 95% CI:4.8-20.2) compared to the unsuccessful group (6.1 months, 95% CI:2.1-10.8, log rank p = 0.015). CONCLUSIONS: Predictors associated with successful therapeutic bronchoscopy for malignant CAO include distal patent airway visualized on CT scan and during bronchoscopy. Odds of success are higher in non-smokers, and with decreased time from radiographic finding of CAO to intervention.

OBJECTIVES: The aim of this study was to provide an overview of the presenting features, etiologies, and outcomes of children enrolled in the Drug-induced Liver Injury Network (DILIN) prospective and retrospective studies. METHODS: Consecutive definite, highly likely, or probable cases in children enrolled into the ongoing DILIN prospective and retrospective studies between September 2004 and February 2017 were reviewed. RESULTS: Fifty-seven cases were adjudicated as definite (14), highly likely (30), or probable (13) DILI. Median age was 14.3 years (1.7-17.9), 67% female, and 82% Caucasian. At DILI onset, 82% had hepatocellular injury with a median alanine aminotransferase of 411 U/L (33-4185), alkaline phosphatase 203 U/L (62-1177), and total bilirubin 3.3 mg/dL (0.2-33.9). The median duration of suspect medication use was 55 days (1-2789) and the most frequently implicated individual agents were minocycline (n = 11) and valproate (n = 6). Sixty-three percent were hospitalized and 3 (5%) underwent liver transplant within 1 month of DILI onset. Among 46 children followed for at least 6 months, 8 (17%) met criteria for chronic DILI with 6 of them having persistent liver injury at 24 months of follow-up. A genome-wide association study in 39 Caucasian children focusing on regions associated with pediatric cholestatic liver disease failed to demonstrate any single nucleotide polymorphism associated with DILI susceptibility or outcome. CONCLUSIONS: Antimicrobials (51%) and antiepileptic drugs (21%) are the most frequently implicated agents in pediatric DILI patients. Although the majority of cases are self-limited, there is potential for serious morbidity including acute liver failure, chronic liver injury, and death.