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Background: Vital signs are an essential component of the emergency department (ED) assessment. Vital sign abnormalities are associated with adverse events in the ED setting and may indicate a risk of poor outcomes after ED discharge., Clinical Question: What is the risk of adverse events among adult patients with abnormal vital signs at the time of ED discharge?, Evidence Review: Studies retrieved included 6 retrospective studies with adult patients discharged from the ED. These studies evaluated adverse outcomes in adult patients discharged from the ED with abnormal vital signs. Hypotension at discharge was associated with the highest odds of adverse events after discharge. Tachycardia was also a key predictor of adverse events after discharge and may be easily missed by ED clinicians., Conclusion: Based on the available evidence, the specific vital sign abnormality and the number of total abnormalities influence the risk of adverse outcomes after discharge. Vital sign abnormalities at the time of discharge also increase the risk of ED revisit. The most common abnormal vital sign at the time of discharge is tachycardia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Children with vesicoureteral reflux (VUR), particularly high-grade VUR, are known to be at increased risk for urinary tract infection (UTI). Current guidelines highlight certain clinical factors in the management of children with VUR; however, the clinical utility of upper tract dilation in the setting of VUR remains unclear., Objective: The purpose of this study is to evaluate risk factors for febrile UTI (fUTI) in children with primary VUR in a modern cohort with emphasis on upper tract dilation parameters, including hydronephrosis and hydroureter., Methods: A prospectively maintained database of children with VUR at a single academic institution from July 2013 to February 2023 was reviewed. Demographic and clinical data were included. Ultrasounds closest to initial VCUG were reviewed for upper tract dilation, including the presence of hydronephrosis, Society of Fetal Urology (SFU) hydronephrosis grade, presence of hydroureter, and anterior-posterior renal pelvic diameter (APRPD). The primary outcome of interest was the development of a fUTI after VUR diagnosis. Patients were censored after their first fUTI or after VUR surgery., Results: A total of 235 children with primary VUR were evaluated, including 125 (53.2 %) females and 110 (46.8 %) males. The median age of VUR diagnosis was 10.8 months (IQR: 2.3-63.6 months). A total of 41 (17.4 %) children developed a fUTI after VUR diagnosis with a median follow up of 2.3 years (IQR: 0.9-4.6 years). On univariate analysis, variables found to be associated with fUTI included age <1 year at VUR diagnosis (p = 0.021), female sex (p = 0.013), high-grade VUR (p = 0.024), APRPD ≥7 mm (p = 0.007), high-grade hydronephrosis (p = 0.004), presence of hydronephrosis (p = 0.029), and hydroureter (p = 0.008). In children with VUR and high-grade hydronephrosis, a larger APRPD was associated with higher fUTI rates (p = 0.008). On multivariate analysis controlling for age, sex, and VUR grade, APRPD ≥7 mm (OR 2.8, p = 0.009), high-grade hydronephrosis (OR 2.5, p = 0.025), and presence of hydronephrosis (OR 2.3, p = 0.049) were independent risk factors for fUTI. On multivariate models controlling for other upper tract dilation parameters, APRPD ≥7 mm was the most significant parameter associated with increased fUTI risk in primary VUR., Conclusion: Upper tract dilation is a novel, independent risk factor for fUTI in children with primary VUR, with APRPD being the strongest predictor. Clinicians may consider upper tract dilation parameters in addition to age, sex, and VUR grade when individualizing care in children with primary VUR., Competing Interests: Conflict of interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Nirmatrelvir/ritonavir (NMV/r) is an orally administered antiviral indicated for the outpatient treatment of patients with mild-to-moderate COVID-19 at high risk for disease progression to severe illness. We estimated the cost-effectiveness of NMV/r versus best supportive care for patients with mild-to-moderate COVID-19 at high risk for progression to severe illness from a US health sector perspective., Methods: A cost-effectiveness model was developed using a short-term decision-tree (1 year) followed by a lifetime 2-state Markov model (alive and dead). The short-term decision-tree captured costs and outcomes associated with the primary infection and healthcare utilization; survivors of the short-term decision-tree were followed until death assuming US quality-adjusted life years (QALYs), adjusted in the short-term for survivors of mechanical ventilation. Baseline rate of hospitalization and NMV/r effectiveness were taken from an Omicron-era US real-world study. Remaining inputs were informed by previous COVID-19 studies and publicly available US sources. Sensitivity analyses were conducted for all model inputs to test the robustness of model results., Results: NMV/r was found to decrease COVID-19 related hospitalizations (-0.027 per infected case) increase QALYs (+0.030), decrease hospitalization costs (-$1110), and increase total treatment cost (+$271), resulting in an incremental cost-effectiveness ratio of $8931/QALY. Results were most sensitive to baseline risk of hospitalization and NMV/r treatment effectiveness parameters. The probabilistic analysis indicated that NMV/r has a >99% probability of being cost-effective at a $100 000 willingness-to-pay threshold., Conclusions: NMV/r is cost-effective vs best supportive care for patients at high risk for severe COVID-19 from a US health sector perspective., Competing Interests: Author Disclosures Links to the individual disclosure forms provided by the authors are available here., (Copyright © 2023 International Society for Pharmacoeconomics and Outcomes Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Examine the association between neighborhood segregation and 6-year incident metabolic syndrome (MetSyn) in the Hispanic Community Health Study/Study of Latinos., Methods: Prospective cohort of adults residing in Miami, Chicago, the Bronx, and San Diego. The analytic sample included 6,710 participants who did not have MetSyn at baseline. The evenness and exposure dimensions of neighborhood segregation, based on the Gini and Isolation indices, respectively, were categorized into quintiles (Q). Racialized economic concentration was measured with the Index of Concentration at the Extremes (continuously and Q)., Results: Exposure, but not evenness, was associated with higher disease odds (Q1 (lower segregation) vs. Q4, OR = 1.53, 95% CI = 1.082.17; Q5, OR = 2.29, 95% CI = 1.493.52). Economic concentrationprivilege (continuous OR = 0.87, 95% CI = 0.770.98), racial concentrationracialized privilege (Q1 (greater concentration) vs. Q2 OR = 0.75, 95% CI = 0.541.04; Q3 OR = 0.68, 95% CI = 0.441.05; Q4 OR = 0.68, 95% CI = 0.451.01; Q5 OR = 0.64, 95% CI = 0.420.98)(continuous OR = 0.93, 95% CI = 0.821.04), and racialized economic concentrationprivilege (i.e., higher SES non-Hispanic White, continuous OR = 0.86, 95% CI = 0.760.98) were associated with lower disease odds., Conclusion: Hispanics/Latino adults residing in neighborhoods with high segregation had higher risk of incident MetSyn compared to those residing in neighborhoods with low segregation. Research is needed to identify the mechanisms that link segregation to poor metabolic health., (Copyright © 2022. Published by Elsevier Inc.)

Study Objective: To examine whether objective bladder function after robot-assisted radical hysterectomy (RRH) for early-stage cervical cancer is correlated with subjective patient-reported outcomes and quality of life during the first year after RRH., Design: Prospective observational study., Setting: Karolinska University Hospital, Sweden., Patients: Women with early-stage cervical cancer (International Federation of Gynecology and Obstetrics stage IA2-IB1) between July 2017 and May 2019 were assessed for eligibility., Interventions: RRH., Measurements and Main Results: Subjective bladder function was evaluated with the Female Lower Urinary Tract Symptoms and Urinary Incontinence Quality of Life modules of the International Consultation on Incontinence Questionnaire. Objective urinary function was characterized with urodynamic tests, and the nerves ablated at RRH were quantified by using immunohistochemical staining of biopsies from the resected paracervix, vesicouterine, and sacrouterine ligaments. Twenty-seven women were included for analysis at baseline, 2 weeks, 3 months, and 12 months after surgery. RRH caused hypotonia of the urinary bladder (p <.05). Patient-reported outcomes of voiding and filling dysfunction were most significant 2 weeks after surgery (p <.05) but for most of the women, bladder function recovered within 3 months. No correlations were found with either subjective or objective urinary function and the number of ablated nerves., Conclusion: For most women, objective and subjective urinary bladder dysfunction recovered within 3 months after RRH. The absence of correlation between functional outcomes and ablated autonomous nerves suggests that other underlying causes play a significant role. Early detection of bladder overextension after RRH is paramount, and the role of postoperative bladder catheterization needs further investigation., (Copyright © 2022 AAGL. Published by Elsevier Inc. All rights reserved.)

The ideal timing of acetabular fractures fixation remains contentious. Early immediate fixation was thought to increase the surgery duration and blood loss while facilitating earlier mobilization and shorter hospital stay; and vice versa for the late fixation after 7 days. The purpose of this review was to compare the impact of early (defined as within 48 hours) versus later definitive fixation of acetabular fractures on postoperative outcomes. It was found that early surgical treatment has certain advantages with regards to blood loss, operative time, and LOS especially in patients with lower ISS. However, further studies are necessary to provide more evidence in terms of long-term outcomes., Competing Interests: Declaration of Competing Interest None for all authors, (Copyright © 2022. Published by Elsevier Ltd.)

The shift of middle-class jobs to home settings, which occurred as a result of COVID-19 health measures that also closed schools and daycares, introduced dynamic changes to everyday life. We investigate these changes drawing on data from our study in which participants in Nova Scotia, Canada, who were working at home due to the pandemic, wrote journal entries in response to weekly prompts. Participants not only documented changes to their routines and challenges of managing work and parenting simultaneously and in the same physical space, but also reflected on their conflicted emotions about life during the pandemic and their vision for life as things return to "normal." Their narratives prompt us to consider these experiences and emotions in relation to Arlie Hochschild's scholarship on feeling rules, emotion work, and gender and work more broadly. We find that from our participants' struggle to meet existing expectations on activities and emotion while simultaneously managing new sets of protocols and feeling rules what emerges is a resistance to norms of busyness, productivity, and exhaustion., (© 2021 Elsevier Ltd. All rights reserved.)

The Keap1-Nrf2 complex is a central regulator that mediates transcriptional responses to xenobiotic stimuli and is highly related with multiple human diseases. The molecular mechanisms and biological functions of Keap1 and Nrf2 are not fully understood. The Drosophila Keap1 homolog (dKeap1) is conserved with mammalian Keap1 except that dKeap1 contains a 156 aa C-terminal tail (CTD). A dKeap1 truncation with the CTD removed (dKeap1-ΔCTD) shows abolished nuclear localization and chromatin-binding. Expression of dKeap1-ΔCTD in the dKeap1 null background significantly rescues this mutant to the adult stage, but the files showed partial lethality, sterility and defects in adipose tissue. In the rescued flies, expression levels of ecdysone-response genes, ecdysone-synthetic genes and adipogenesis genes were down-regulated in specific tissues, indicating that the chromatin-binding of dKeap1 mediates the activation of these developmental genes. At the same time, dKeap1-ΔCTD can still suppress the basal expression of detoxifying genes and mediate the activation of these genes in response to xenobiotic stimuli, suggesting that the chromatin-binding of dKeap1 is not required for the regulation of detoxifying genes. These results support a model in which dKeap1 on one hand functions as an inhibitor for the Nrf2-mediated transcription in the xenobiotic response pathway and on the other hand functions as a chromatin-binding transcription activator in the developmental pathway. Our study reveals a novel mechanism whereby Keap1-Nrf2 xenobiotic response signaling regulates development using a mechanism independent of redox signaling., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2021. Published by Elsevier Inc.)

Introduction: The International Neuromodulation Society convened a multispecialty group of physicians based on expertise with international representation to establish evidence-based guidance on the use of neurostimulation in the cervical region to improve outcomes. This Neurostimulation Appropriateness Consensus Committee (NACC) project intends to provide evidence-based guidance for an often-overlooked area of neurostimulation practice., Materials and Methods: Authors were chosen based upon their clinical expertise, familiarity with the peer-reviewed literature, research productivity, and contributions to the neuromodulation literature. Section leaders supervised literature searches of MEDLINE, BioMed Central, Current Contents Connect, Embase, International Pharmaceutical Abstracts, Web of Science, Google Scholar, and PubMed from 2017 (when NACC last published guidelines) to the present. Identified studies were graded using the US Preventive Services Task Force criteria for evidence and certainty of net benefit. Recommendations are based on the strength of evidence or consensus when evidence was scant., Results: The NACC examined the published literature and established evidence- and consensus-based recommendations to guide best practices. Additional guidance will occur as new evidence is developed in future iterations of this process., Conclusions: The NACC recommends best practices regarding the use of cervical neuromodulation to improve safety and efficacy. The evidence- and consensus-based recommendations should be utilized as a guide to assist decision making when clinically appropriate., (Copyright © 2021 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Altered gut microbiomes may play a role in rapid evolution to anthropogenic change but remain poorly understood. Atlantic killifish (Fundulus heteroclitus) in the Elizabeth River, VA have evolved resistance to polycyclic aromatic hydrocarbons (PAHs) and provide a unique opportunity to examine the links between shifts in the commensal microbiome and organismal physiology associated with evolved resistance. Here, 16S rRNA sequence libraries derived from fish guts and sediments sampled from a highly PAH contaminated site revealed significant differences collected at similar samples from an uncontaminated site. Phylogenetic groups enriched in the libraries derived from PAH-resistant fish were dissimilar to their associated sediment libraries, suggesting the specific environment within the PAH-resistant fish intestine influence the gut microbiome composition. Gut metabolite analysis revealed shifts between PAH-resistant and non-resistant subpopulations. Notably, PAH-resistant fish exhibited reduced levels of tryptophan and increased levels of sphingolipids. Exposure to PAHs appears to impact several bacterial in the gut microbiome, particularly sphingolipid containing bacteria. Bacterial phylotypes known to include species containing sphingolipids were generally lower in the intestines of fish subpopulations exposed to high concentrations of PAHs, inferring a complex host-microbiome relationship. Overall, killifish microbial community shifts appear to be related to a suppression of overall metabolite level, indicating a potential role of the gut in organismal response to anthropogenic environmental change. These results on microbial and metabolomics shifts are potentially linked to altered bioenergetic phenotype observed in the same PAH-resistant killifish populations in other studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: To compare the atrial fibrillatory rate (AFR) derived from a local right atrial intracardiac recording (RA-FR) and from a single-lead surface electrocardiogram (ECG) during atrial fibrillation (AF) and to evaluate the correlation with transvenous electrical cardioversion (TVEC) threshold (in Joules), number of shocks and cardioversion success rate in horses., Animals: ECGs and clinical records of horses with AF treated by TVEC. Horses were included if a simultaneous recording of the right atrial intracardiac electrogram and a modified base-apex ECG were available., Materials and Methods: Clinical records of horses with AF treated by TVEC were reviewed. Three-minute long episodes of simultaneous electrograms and surface ECG during AF were selected for analysis and compared using Bland-Altman analysis. The mean RA-FR was measured from the deflections on the intracardiac electrogram, while the AFR was extracted from the surface ECG using spatiotemporal QRS and T-wave cancellation., Results: Seventy-three horses satisfied the inclusion criteria. The mean difference between RA-FR and AFR was -13 fibrillations per minute (fpm), the 95% limits of agreement were between -66 and 40 fpm, and there was a moderate (ρ = 0.65) correlation between RA-FR and AFR (p < 0.001). Neither RA-FR nor AFR appeared to influence the TVEC cardioversion threshold or the number of TVEC shocks applied., Conclusions: The AFR may allow non-invasive long-term monitoring of AF dynamics. Neither RA-FR nor AFR could be used to predict the minimal defibrillation threshold for TVEC., Competing Interests: Conflicts of interest None of the authors have any conflicts of interest or financial ties to disclose., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The adaptive and innate branches of the vertebrate immune system work in close collaboration to protect organisms from harmful pathogens. As an organism ages its immune system undergoes immunosenescence, characterized by declined performance or malfunction in either immune branch, which can lead to disease and death. In this study we develop a mathematical framework of coupled innate and adaptive immune responses, namely the integrated immune branch (IIB) model. This model describes dynamics of immune components in both branches, uses a shape-space representation to encode pathogen-specific immune memory, and exhibits three steady states - health, septic death, and chronic inflammation - qualitatively similar to clinically-observed immune outcomes. In this model, the immune system (initialized in the health state) is subjected to a sequence of pathogen encounters, and we use the number of prior pathogen encounters as a proxy for the "age" of the immune system. We find that repeated pathogen encounters may trigger a fragility in which any encounter with a novel pathogen will cause the system to irreversibly switch from health to chronic inflammation. This transition is consistent with the onset of "inflammaging", a condition observed in aged individuals who experience chronic low-grade inflammation even in the absence of pathogens. The IIB model predicts that the onset of chronic inflammation strongly depends on the history of encountered pathogens; the timing of onset differs drastically when the same set of infections occurs in a different order. Lastly, the coupling between the innate and adaptive immune branches generates a trade-off between rapid pathogen clearance and a delayed onset of immunosenescence. Overall, by considering the complex feedback between immune compartments, our work suggests potential mechanisms for immunosenescence and provides a theoretical framework at the system level and on the scale of an organism's lifetime to account for clinical observations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

There are many possible failure points in the transmission of genetic information that can produce heritable germline mutations. Once a mutation has been passed from parents to offspring for several generations, it can be difficult or impossible to identify its root cause; however, sometimes the nature of the ancestral and derived DNA sequences can provide mechanistic clues about a genetic change that happened hundreds or thousands of generations ago. Here, we review evidence that the sequence context 'spectrum' of germline mutagenesis has been evolving surprisingly rapidly over the history of humans and other species. We go on to discuss possible causal factors that might underlie rapid mutation spectrum evolution., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Generally considered benign, electrocardiographic (ECG) early repolarization (ER) pattern was claimed to be an indicator of increased susceptibility to ventricular arrhythmias during acute ischemia., Objective: The purpose of this study was to assess in a nonselected population whether ER pattern documented before ST-elevation myocardial infarction (STEMI) is associated with risk of hemodynamically unstable ventricular tachycardia (VT) or ventricular fibrillation (VF) during acute STEMI., Methods: For STEMI patients admitted for primary percutaneous coronary intervention from 2007-2010, the latest ECGs recorded before STEMI were exported in digital format. After excluding ECGs with paced rhythm and QRS duration ≥120 ms, the remaining ECGs were processed using the Glasgow algorithm allowing automatic ER detection. The association between ER pattern and VT/VF during the first 48 hours of STEMI was tested using logistic regression., Results: ECGs recorded before STEMI were available for 1584 patients. Of these patients, 124 did not meet inclusion criteria, leaving 1460 patients available for analysis (age 68 ± 12 years; 67% male). ER pattern was present in 272 patients (18.6%; ER+ group). ER+ and ER- groups did not differ with regard to clinical characteristics. VT/VF during the first 48 hours of STEMI occurred in 19 ER+ (7.0%) and 105 ER- patients (8.8%; P = .398). ER was not associated with any VT/VF (odds ratio [OR] 0.78; 95% confidence interval [CI] 0.47-1.29; P = .324); VT/VF before reperfusion (OR 0.48; 95% CI 0.23-1.001; P = .051); or reperfusion-related VT/VF (OR 1.28; 95% CI 0.55-3.01; P = .569)., Conclusion: In a nonselected population of STEMI patients, the ER pattern on ECG recorded before the acute coronary event was not associated with VT/VF during the first 48 hours of STEMI., (Copyright © 2019 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Deep brain stimulation (DBS) surgery is an option for patients experiencing medically resistant neurologic symptoms. DBS complications are rare; finding significant predictors requires a large number of surgeries. Machine learning algorithms may be used to effectively predict these outcomes. The aims of this study were to 1) investigate preoperative clinical risk factors and 2) build machine learning models to predict adverse outcomes., Methods: This multicenter registry collected clinical and demographic characteristics of patients undergoing DBS surgery (n = 501) and tabulated occurrence of complications. Logistic regression was used to evaluate risk factors. Supervised learning algorithms were trained and validated on 70% and 30%, respectively, of both oversampled and original registry data. Performance was evaluated using area under the receiver operating characteristics curve (AUC), sensitivity, specificity, and accuracy., Results: Logistic regression showed that the risk of complication was related to the operating institution in which the surgery was performed (odds ratio [OR] = 0.44, confidence interval [CI] = 0.25-0.78), body mass index (OR = 0.94, CI = 0.89-0.99), and diabetes (OR = 2.33, CI = 1.18-4.60). Patients with diabetes were almost 3× more likely to return to the operating room (OR = 2.78, CI = 1.31-5.88). Patients with a history of smoking were 4× more likely to experience postoperative infection (OR = 4.20, CI = 1.21-14.61). Supervised learning algorithms demonstrated high discrimination performance when predicting any complication (AUC = 0.86), a complication within 12 months (AUC = 0.91), return to the operating room (AUC = 0.88), and infection (AUC = 0.97). Age, body mass index, procedure side, gender, and a diagnosis of Parkinson disease were influential features., Conclusions: Multiple significant complication risk factors were identified, and supervised learning algorithms effectively predicted adverse outcomes in DBS surgery., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: To find an alternative for quality-adjusted life-year (QALY) and equal value of life (EVL) measures. Despite the importance of QALY in cost-effectiveness analysis (CEA)-because it captures the effects of both life expectancy and health-related quality of life (QOL) and enables comparisons across interventions and disease areas-its potential to be discriminatory towards patients with lower QOL presents a critical challenge that has resulted in the exclusion of its use in some public decision making (eg, US Medicare) on healthcare in the United States. Alternatives to QALY, such as EVL, have not gained traction because EVL fails to recognize the QOL gains during added years of life., Methods: We present a new metric for effectiveness for CEA, health years in total (HYT), which overcomes both the specific distributional issue raised by QALY and the efficiency challenges of EVL., Results: The HYT framework separates life expectancy changes and QOL changes on an additive scale. HYT have the same axiomatic foundations as QALY and perform better than both QALY, in terms of the discriminatory implications, and EVL, in terms of capturing QOL gains during added years of life. HYT are straightforward to calculate within a CEA model. We found that thresholds of $34 000/HYT and $89 000/HYT correspond to CEA thresholds of $50 000/QALY and $150 000/QALY, respectively., Conclusions: The HYT framework may provide a viable alternative to both the QALY and the EVL; its application to diverse healthcare technologies and stakeholder assessments are important next steps in its development and evaluation., (Copyright © 2019 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Background: Recent studies in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients have drawn attention to atrial fibrillation (AF) as an arrhythmic manifestation of ARVC and as an indicator of atrial involvement in the disease progression. We aimed to assess the prevalence of AF in the Scandinavian cohort of ARVC patients and to evaluate its association with disease clinical manifestations., Methods: Study sample comprised of 293 definite ARVC patients by 2010 Task Force criteria (TFC2010) and 141 genotype-positive family members (total n = 434, 43% females, median age at ARVC diagnosis 41 years [interquartile range (IQR) 28-52 years]). ARVC diagnostic score was calculated as the sum of major (2 points) and minor (1 point) criteria in all categories of the TFC2010., Results: AF was diagnosed in 42 patients (10%): in 41 patients with definite ARVC diagnosis (14%) vs in one genotype-positive family member (1%), p < 0.001. The median age at AF onset was 51 (IQR 38-58) years. The prevalence of AF was related to the ARVC diagnostic score: it significantly increased starting with the diagnostic score 4 (2% in those with score 3 vs 13% in those with score 4, p = 0.023) and increased further with increased diagnostic score (Somer's d value is 0.074, p < 0.001)., Conclusion: AF is seen in 14% of definite ARVC patients and is related to the severity of disease phenotype thus suggesting AF being an arrhythmic manifestation of this cardiomyopathy indicating atrial myocardial involvement in the disease progression., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Methylmalonic acidemia (MMA) and propionic acidemia (PA) are related disorders of mitochondrial propionate metabolism, caused by defects in methylmalonyl-CoA mutase (MUT) and propionyl-CoA carboxylase (PCC), respectively. These biochemical defects lead to a complex cascade of downstream metabolic abnormalities, and identification of these abnormal pathways has important implications for understanding disease pathophysiology. Using a multi-omics approach in cellular models of MMA and PA, we identified serine and thiol metabolism as important areas of metabolic dysregulation., Methods: We performed global proteomic analysis of fibroblasts and untargeted metabolomics analysis of plasma from individuals with MMA to identify novel pathways of dysfunction. We probed these novel pathways in CRISPR-edited, MUT and PCCA null HEK293 cell lines via targeted metabolomics, gene expression analysis, and flux metabolomics tracing utilization of 13 C-glucose., Results: Proteomic analysis of fibroblasts identified upregulation of multiple proteins involved in serine synthesis and thiol metabolism including: phosphoserine amino transferase (PSAT1), cystathionine beta synthase (CBS), and mercaptopyruvate sulfurtransferase (MPST). Metabolomics analysis of plasma revealed significantly increased levels of cystathionine and glutathione, central metabolites in thiol metabolism. CRISPR-edited MUT and PCCA HEK293 cells recapitulate primary defects of MMA and PA and have upregulation of transcripts associated with serine and thiol metabolism including PSAT1. 13 C-glucose flux metabolomics in MUT and PCCA null HEK293 cells identified increases in serine de novo biosynthesis, serine transport, and abnormal downstream TCA cycle utilization., Conclusion: We identified abnormal serine metabolism as a novel area of cellular dysfunction in MMA and PA, thus introducing a potential new target for therapeutic investigation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aim: Ventricular fibrillation (VF) during reperfusion in ST-elevation myocardial infarction (STEMI) is associated with increased in-hospital mortality. Dispersion of ventricular repolarization contributes to ventricular vulnerability during ischemia. T peak -T end interval was proposed as a ventricular repolarization dispersion marker, however its value for prediction of reperfusion VF remains uncertain. We aimed to assess whether T peak -T end before PCI in STEMI is associated with reperfusion VF., Methods: STEMI patients admitted for primary PCI were retrospectively assessed for VF during reperfusion. Pre-PCI ECGs recorded in 40 patients with reperfusion VF (rVF group; age 65 ± 13 years, 80% male) were compared with 374 consecutive patients without reperfusion arrhythmias (No-rVF group; age 67 ± 12 years; 68% male). Digital ECGs were automatically processed and T peak -T end interval computed on a per-lead basis. The global T peak -T end was calculated between the earliest T peak and the latest T end in any lead, and tested for association with reperfusion VF using logistic regression analysis., Results: The leftward shift of T peak toward QRS complex in ischemic leads resulted in T peak -T end prolongation. Global T peak -T end in rVF group was higher than in No-rVF group (142 ± 24 vs 130 ± 27 ms; p = 0.007). Global T peak -T end  ≥ 131 ms predicted reperfusion VF (OR = 3.41; 95% CI 1.66-7.04; p = 0.001) and remained a significant predictor of reperfusion VF in multivariable analysis., Conclusion: T peak -T end interval before PCI in STEMI was an independent predictor of reperfusion VF. Our findings warrants further research aimed at prospective validation of T peak -T end as a marker of periprocedural arrhythmic risk., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A 4-year-old intact male mini lop rabbit (Oryctolagus cuniculus) was presented with a 2-week history of severe progressive lethargy. A right parasternal continuous heart murmur and an irregular rhythm were detected on physical examination. Echocardiography identified vegetative aortic and tricuspid valve (TV) endocarditis. There was an aortocavitary fistula between the right sinus of Valsalva into the right ventricle, creating a left-to-right intracardiac shunt. Based on the echocardiographic findings, it was suspected that the infection originated in the aortic valve, eroded through the periannular tissue, and secondarily infected the TV. Pleural and peritoneal effusion secondary to right-sided congestive heart failure was also found during the echocardiogram. Atrial fibrillation, conducted with a left bundle branch block morphology, was identified using electrocardiography. Necropsy findings directly correlated with the echocardiographic diagnosis; marked periodontal disease was also identified. Aerobic culture of the aortic and tricuspid vegetations resulted in significant growth of Haemophilus parainfluenzae. Haemophilus spp. belong to a group of similar gram-negative coccobacillus bacteria (HACEK group), which can act as an uncommon cause of endocarditis in humans. HACEK endocarditis is most commonly associated with oral infection and/or dental procedures in people. This is the first case report of a rabbit with periannular complications of infective endocarditis. It remains unknown whether dental disease resulted in endocarditis in this patient., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: The gene therapy voretigene neparvovec (VN) is the first Food and Drug Administration-approved treatment for vision loss owing to the ultra-rare RPE65-mediated inherited retinal disorders. We modeled the cost-utility of VN compared with standard of care (SoC)., Study Design: A 2-state Markov model, alive and dead, with a lifetime horizon., Methods: Visual acuity (VA) and visual field (VF) were tracked to model quality-adjusted life-years (QALYs). VN led to an improvement in VA and VF that we assumed was maintained for 10 years followed by a 10-year waning period. The cost of VN was $850 000, and other direct medical costs for depression and trauma were included for a US healthcare system perspective. A modified societal perspective also included direct nonmedical costs and indirect costs., Results: VN provided an additional 1.3 QALYs over the remaining lifetime of an individual. The average total lifetime direct medical cost for individuals treated with VN was $1 039 000 compared with $213 400 for SoC, leading to an incremental cost-effectiveness ratio (ICER) of $643 800/QALY from the US healthcare system perspective. Direct nonmedical costs totalled $1 070 900 for VN and $1 203 300 for SoC, and indirect costs totalled $405 400 for VN and $482 900 for SoC, leading to an ICER of $480 100/QALY from the modified societal perspective., Conclusions: At the current price, VN was unlikely to reach traditional cost-effectiveness standards compared with SoC. VN has important implications for both development and pricing of future gene therapies; therefore clinical and economic analyses must be carefully considered., (Copyright © 2019 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Introduction: Dorsal root ganglion stimulation (DRGS) is a powerful tool in the treatment of chronic, neuropathic pain. The premise of DRGS is similar to that of conventional spinal cord stimulation (cSCS), however, there is more variability in how it can be utilized. While it is this variability that likely gives it its versatility, DRGS is not as straightforward to implement as cSCS. The purpose of this study was to assess the efficacy of DRGS on a broad number of diagnoses, determine which dorsal root ganglia were associated with better outcomes for particular body parts/diagnoses, and evaluate what factors/parameters were associated with higher rates of trial success., Methods: This is a physician initiated, multicenter retrospective registry of 217 patients trialed with DRGS. Data were collected via an online questionnaire that assessed specifics regarding the patient's pain, distribution, size, and response to treatment. The data were analyzed to see if there were certain diagnoses and/or parameters that were more or less associated with trial success., Results: DRGS was found to be an effective treatment in all diagnoses evaluated within this study, most of which had statistically significant improvements in pain. The most important predictor of trial success was the amount of painful area covered by paresthesias during the programing phase. The number of leads utilized had a direct and indirect impact on trial success. Pain in the distribution of a specific peripheral nerve responded best and there was no statistical difference based on what body part was being treated., Conclusion: DRGS can be an effective treatment for a variety of neuropathic pain syndromes, in addition to CRPS. It is recommended that a minimum of 2 leads should be utilized per area being treated. In addition, this therapy was shown to be equally efficacious in any body part/region so long as the area being treated is focal and not widespread., (© 2018 International Neuromodulation Society.)

Purpose: The purpose of this study was to compare healing time for diaphyseal tibia fractures (OTA/AO 42 A, B, C) treated with intramedullary nailing (IMN) in one geographic cohort using nonsteroidal anti-inflammatory drugs (NSAIDs) for post-operative pain control to that of another geographic cohort using opioid medications. The groups represent differing cultural approaches to post-operative pain control. We hypothesized there would be no difference in healing time., Methods: Tibia fractures presenting at two level I trauma centers located in different countries between January 1, 2010 and December 31, 2017 were retrospectively screened for enrollment. Fractures classified as OTA/AO 42 A, B, or C that were treated with IMN and had radiographic follow up to union were included. At hospital discharge, one cohort (n = 190) was prescribed NSAIDs and the other (n = 182) was prescribed opioids for pain control. Each analgesic method represented the standard of care for that location. Fracture union was defined as cortical bridging in at least 3 out of 4 cortices on AP and lateral radiographs. The primary outcome was healing time on radiographic evaluation., Results: There was no statistically significant difference in healing time between the opioid and NSAID groups: 185 vs 180.5 days respectively (p = 0.64). Both groups had similar mean age. Student t-tests were run to compare rates of tobacco use, diabetes mellitus (DM), open fractures, and polytrauma between the two groups. The opioid cohort had statistically significant higher rates of tobacco use, DM, and polytrauma. The NSAID cohort, however, had a larger number of open fractures., Conclusion: The difference in healing time between the NSAID and opioid groups was not statistically significant. The deleterious effect of NSAID use on fracture healing has been debated for decades. Numerous animal studies have supported this theory; however, high quality clinical studies in humans have not provided convincing evidence to substantiate this negative effect. Our study suggests that NSAIDs may be used safely and effectively in the acute phase of fracture healing without significantly increasing the risk of delayed union or nonunion. Prospective randomized studies are necessary to rule out the negative effect of NSAIDS on bone healing., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: Spinal cord stimulation (SCS) is an accepted, cost-effective treatment option for a variety of chronic pain syndromes, including failed back surgery syndrome (FBSS). The application of SCS in the cervical spine, particularly for pain after cervical spine surgery, has been drawn into question in recent years by payers due to a purported lack of clinical evidence. To challenge this claim, we analyzed data from a prospective registry to support the use of SCS in the cervical spine for pain after spine surgery., Materials and Methods: Data from the EMPOWER and PAIN registries were analyzed on patients diagnosed with pain after neck surgery (C-FBSS) for the following outcomes: patient reported percent pain relief (PRPR), pain disability index (PDI), quality of life (QoL), and satisfaction at 3-, 6-, and 12-month post-implantation. Statistical analysis was provided for all measures., Results: Fifteen patients with C-FBSS were successfully implanted with SCS leads in the cervical spine. PRPR was 65.2%, 62.4%, and 71.9% at 3-, 6-, and 12-month post-implantation, respectively. PDI scores were significantly reduced from baseline (51.21-23.70 at 12 months, p = 0.001). At one-year post-implantation, the average overall QoL was reported to be improved/greatly improved and patient satisfaction was rated satisfied/greatly satisfied., Conclusions: For many, the application of SCS in the neck for pain after surgery is based on the obvious similarities to FBSS or anecdotal experience rather than published data. The data contained herein suggest SCS for C-FBSS is an effective therapy that improves QoL and patient satisfaction, as well as decreasing pain and PDI. The use of successful application of neurostimulation as a therapy has largely been predicated on the principles of patient selection, implantation technique, and stimulation parameters. As such, SCS would appear to be an appropriate and valid treatment for C-FBSS that requires further study and investigation to make additional recommendations., (© 2018 International Neuromodulation Society.)

Background: Over 60% of Latinas report not meeting moderate to vigorous physical activity (MVPA) guidelines of 150 minutes/week. Ecological models of health posit that intrapersonal and environmental factors interact with one another to influence physical activity. Understanding their interactions in relation to transportation behaviors may inform interventions to increase Latinas' physical activity., Purpose: To 1) objectively estimate walking and vehicle time in Latinas, 2) examine the association of, and interactions between, intrapersonal (socio-demographics and weight status) and neighborhood environmental correlates with objective daily walking and vehicle time., Methods: A subsample of Latinas (n=87) participating in a health intervention wore an accelerometer and GPS device for at least two valid wear days at baseline. The Personal Activity Location and Measurement System (PALMS) software estimated daily walking and vehicle time. Participants' anthropometrics were measured, and they completed a survey assessing socio-demographic characteristics and perceived neighborhood environment. Generalized linear mixed models examined main effects and interactions of four intrapersonal and five environmental factors on daily walking and vehicle time., Results: On average, participants walked 16 min/day and spent 69 min/day in a vehicle. Overweight/obesity was negatively associated with walking time (p=.04) and positively associated with vehicle time (p=0.01). Household income was positively associated with vehicle time (p=0.02). For daily walking time, two interactions were significant: perceived access to destinations X household income (p=0.01), and perceived sidewalk maintenance X acculturation (p= 0.01). For daily vehicle time, two interactions were significant: perceived access to destinations X weight status (p<0.001), and perceived safety from crime X education (p=0.01)., Conclusion: Latinas participated in relatively low walking time and high amounts of vehicle time. Findings suggest intrapersonal sub-group differences in the association of the neighborhood environment with walking and vehicle time. Improving neighborhood environments to promote walking and reduce vehicle time may help improve Latinas' overall physical activity.

Introduction: Spinal cord stimulation (SCS) devices are cost effective and improve function as well as quality of life. Despite the demonstrated benefits of SCS, some patients have the device explanted. We are interested in exploring the patient characteristics of those explanted., Methods: This is a retrospective chart review of neurostimulation patients who underwent explantation at 18 centers across the United States within the previous five years., Results: Data from 352 patients were collected and compiled. Failed Back Surgery syndrome was the most common diagnosis (38.9%; n = 136/350) and over half of the patients reported numerical rating scale (NRS) scores ≥8 prior to implant (64.3%; n = 207/322). All patients reported changes in NRS scores across time, with an initial decrease after implant followed by a pre-explant increase (F (2, 961) = 121.7, p < 0.001). The most common reason for device explant was lack or loss of efficacy (43.9%; 152/346) followed by complications (20.2%; 70/346). Eighteen percent (18%; 62/343) of patients were explanted by a different physician than the implanting one. Rechargeable devices were explanted at a median of 15 months, whereas primary cell device explants occurred at a median of 36 months (CI 01.434, 2.373; median endpoint time ratio = 2.40)., Discussion: Loss or lack of efficacy and complications with therapy represent the most frequent reasons for neurostimulation explantation. Of the devices that were explanted, therapy was terminated earlier when devices were rechargeable, when complications occurred, or when pain relief was not achieved or maintained. Furthermore, in nearly 20% of the cases, a different provider than the implanting physician performed device removal., Conclusions: SCS is largely a safe and efficacious strategy for treating select chronic refractory pain syndromes. Further prospective data and innovation are needed to improve patient selection, maintain SCS therapeutic efficacy and reduce the reasons that lead to device explant., (© 2017 International Neuromodulation Society.)

Background: Atrial fibrillation (AF) detection in ischemic stroke patients triggers initiation of oral anticoagulant therapy (OAC). However, little is known regarding whether the persistency of AF affects long-term prognosis after ischemic stroke. We aimed to assess the impact of AF types and OAC on the outcome during a 10-year follow-up (FU) after first-ever ischemic stroke., Material and Methods: The study sample comprised 336 first-ever ischemic stroke patients (median age 76, interquartile range 25-75% (IQR) 67-82years, 136 female) included in the Lund Stroke Register (LSR) in 2001-2002. At baseline, 109 patients had either permanent (n=44) or recurrent (n=65) AF. OAC was assessed using the Lund University Hospital anticoagulation database. All-cause mortality was assessed via linkage with the Swedish Causes of Death Register., Results: During FU, 200 patients died. AF independently predicted all-cause mortality (hazard ratio (HR) 1.52 95% CI 1.14-2.04, p=0.005); the worst prognosis was observed for permanent AF (HR 1.86 95% CI 1.29-2.69, p=0.001). Patients with recurrent AF receiving OAC had similar survival rates to patients without AF (HR 0.73 95% CI 0.38-1.39, p=0.333), while prognosis was worst for patients with permanent AF without OAC (HR 2.28 95% CI 1.38-3.77, p=0.001) and intermediate for patients with permanent AF on OAC (HR 1.57 95% CI 0.92-2.67, p=0.099)., Conclusion: All-cause mortality was independently associated with AF and was the greatest in stroke patients with permanent AF. Patients with recurrent AF receiving OAC have the most favorable outcome, similar to those without AF and significantly better than OAC-treated patients with permanent AF., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Tools for assessing the severity and risk of near-miss events in radiation oncology are few and needed. Recent work has described guidelines for the use of a 5-tier near-miss risk index (NMRI) for the classification of near-miss events. The purpose of this study was to assess the reliability of the NMRI among users in a radiation oncology department., Methods and Materials: Reliability of the NMRI was assessed using an online survey distributed to members of a radiation oncology department. The survey contained 70 events extracted from the department's incident learning system (ILS). Survey participants rated each event using the NMRI guidelines, reported their attendance to weekly ILS meetings (used as a surrogate for familiarity with the ILS), and indicated their familiarity with the radiation oncology workflow. Interrater reliability was determined using Krippendorff's alpha. Use of the NMRI to rate actual events during 5 weekly ILS meetings was also assessed and interrater reliability determined., Results: Twenty-eight survey respondents represented a wide variety of care providers. Krippendorff's alpha was calculated for the whole respondent cohort to be 0.376, indicating fair agreement among raters. Respondents who had the most participation at ILS meetings (n = 4) had moderate agreement with an alpha of 0.501. Interestingly, there were significant differences in reliability and median NMRI scores between professions. NMRI use during weekly NMRI meetings (80 events rated), participants showed moderate reliability (alpha = 0.607)., Conclusions: Using the NMRI guidelines, raters from a wide variety of professions were able to assess the severity of near-miss incidents with fair agreement. Those experienced with the ILS showed better agreement, and higher agreement was seen during multidisciplinary ILS meetings. These data support the use the indices such as the NMRI for near-miss risk assessment in patient safety and prioritization of process improvements in radiation oncology., (Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: Radiation treatment planning is a complex process with potential for error. We hypothesized that shorter time from simulation to treatment would result in rushed work and higher incidence of errors. We examined treatment planning factors predictive for near-miss events., Methods and Materials: Treatments delivered from March 2012 through October 2014 were analyzed. Near-miss events were prospectively recorded and coded for severity on a 0 to 4 scale; only grade 3-4 (potentially severe/critical) events were studied in this report. For 4 treatment types (3-dimensional conformal, intensity modulated radiation therapy, stereotactic body radiation therapy [SBRT], neutron), logistic regression was performed to test influence of treatment planning time and clinical variables on near-miss events., Results: There were 2257 treatment courses during the study period, with 322 grade 3-4 near-miss events. SBRT treatments had more frequent events than the other 3 treatment types (18% vs 11%, P = .04). For the 3-dimensional conformal group (1354 treatments), univariate analysis showed several factors predictive of near-miss events: longer time from simulation to first treatment (P = .01), treatment of primary site versus metastasis (P < .001), longer treatment course (P < .001), and pediatric versus adult patient (P = .002). However, on multivariate regression only pediatric versus adult patient remained predictive of events (P = 0.02). For the intensity modulated radiation therapy, SBRT, and neutron groups, time between simulation and first treatment was not found to be predictive of near-miss events on univariate or multivariate regression., Conclusions: When controlling for treatment technique and other clinical factors, there was no relationship between time spent in radiation treatment planning and near-miss events. SBRT and pediatric treatments were more error-prone, indicating that clinical and technical complexity of treatments should be taken into account when targeting safety interventions., (Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: Paroxysmal atrial fibrillation (AF) may be underdiagnosed in ischemic stroke patients but may be pivotal for initiation of oral anticoagulation therapy. We assessed clinical and ECG predictors of new-onset AF during 10-year follow-up (FU) in ischemic stroke patients., Methods: The study sample comprised of 227 first-ever ischemic stroke patients without AF (median age 73, interquartile range 25%-75% 63-80years, 92 female) and 1:1 age- and gender-matched controls without stroke and AF enrolled in the Lund Stroke Register from March 2001 to February 2002. New-onset AF during FU was assessed by screening through regional ECG database and by record linkage with Swedish National Patient Register. The standard 12-lead sinus rhythm ECGs at stroke admission were retrieved from electronic database and digitally processed. Clinical baseline characteristics were studied using medical records., Results: During FU, AF was found in 39 stroke patients and 30 controls, p=0.296. In stroke patients in multivariate Cox regression analysis AF was associated with hypertension (HR 3.45 CI 95% 1.40-3.49, p=0.007) and QRS duration (HR 1.02 CI 95% 1.00-1.03, p=0.049). High cardiovascular risk was predictive for AF development: for CHADS2≥4 HR 2.46 CI 95% 1.45-4.18, p=0.001 and for CHA2DS2-VASc≥5 HR 2.29 CI 95% 1.43-3.68, p=0.001. New onset AF was not associated with baseline ischemic stroke: HR 1.46 95% CI 0.90-2.35, p=0.121., Conclusion: High CHADS2 and CHA2DS2-VASc scores, but not baseline ischemic stroke, predict new onset AF in FU. QRS duration might be considered a potential risk marker for prediction of AF after ischemic stroke., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Emergent radiation treatments may be subject to more errors because of the compressed time frame. Few data exist on the magnitude of this problem or how to guide safety improvement interventions. The purpose of this study is to examine patterns of near-miss events in emergent treatments using a large institutional incident reporting system., Methods and Materials: Events in the incident reporting database from February 2012 to October 2013 were reviewed prospectively by a multidisciplinary team to identify emergent treatments. Reports were scored for potential near-miss risk index (NMRI) on a 0 to 4 scale. Workflow steps of where events originated and were detected were analyzed. Events were categorized by use of the causal factor system from the Radiation Oncology Incident Learning System. Mann-Whitney U tests were used to compare mean NMRI score, and Fisher exact tests were performed to compare the proportion of high-risk events between emergent and nonemergent treatments and between emergent treatments on weekdays and weekends or holidays., Results: Over the study period, approximately 1600 patients were treated, 190 of them emergently. Seventy-one incident reports were submitted for 55 unique patients. Fewer events were reported for emergent treatments than for nonemergent treatments (0.37 events per new treatment vs 0.86; P < .01). Mean risk index for emergent reports was 1.90 versus 1.48 for nonemergent reports (P < .01). Rate of NMRI 4 was 10% for emergent treatments versus 4% for nonemergent treatments (P < .01). Emergent treatments started on a weekend or holiday had a higher proportion of critical near-miss events than emergent treatments started during the week (37% vs 7.9%, P = .034)., Conclusions: In this study, fewer near-miss incidents were reported per treatment course for emergent treatments. This may be attributable to reporting bias. More importantly, when emergent near misses occur, they are of greater severity., (Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Allergic asthma is a chronic inflammatory disease of the airways characterized by excessive eosinophilic and lymphocytic inflammation with associated changes in the extracellular matrix (ECM) resulting in airway wall remodeling. Hyaluronan (HA) is a nonsulfated glycosaminoglycan ECM component that functions as a structural cushion in its high molecular mass (HMM) but has been implicated in metastasis and other disease processes when it is degraded to smaller fragments. However, relatively little is known about the role HA in mediating inflammatory responses in allergy and asthma. In the present study, we used a murine Aspergillus fumigatus inhalational model to mimic human disease. After observing in vivo that a robust B cell recruitment followed a massive eosinophilic egress to the lumen of the allergic lung and corresponded with the detection of low molecular mass HA (LMM HA), we examined the effect of HA on B cell chemotaxis and cytokine production in the ex vivo studies. We found that LMM HA functioned through a CD44-mediated mechanism to elicit chemotaxis of B lymphocytes, while high molecular mass HA (HMM HA) had little effect. LMM HA, but not HMM HA, also elicited the production of IL-10 and TGF-β1 in these cells. Taken together, these findings demonstrate a critical role for ECM components in mediating leukocyte migration and function which are critical to the maintenance of allergic inflammatory responses., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

Purpose: Rigorous use of departmental incident learning is integral to improving patient safety and quality of care. The goal of this study was to quantify the impact of a high-volume, departmental incident learning system on patient safety culture., Methods and Materials: A prospective, voluntary, electronic incident learning system was implemented in February 2012 with the intent of tracking near-miss/no-harm incidents. All incident reports were reviewed weekly by a multiprofessional team with regular department-wide feedback. Patient safety culture was measured at baseline with validated patient safety culture survey questions. A repeat survey was conducted after 1 and 2 years of departmental incident learning. Proportional changes were compared by χ(2) or Fisher exact test, where appropriate., Results: Between 2012 and 2014, a total of 1897 error/near-miss incidents were reported, representing an average of 1 near-miss report per patient treated. Reports were filed by a cross section of staff, with the majority of incidents reported by therapists, dosimetrists, and physicists. Survey response rates at baseline and 1 and 2 years were 78%, 80%, and 80%, respectively. Statistically significant and sustained improvements were noted in several safety metrics, including belief that the department was openly discussing ways to improve safety, the sense that reports were being used for safety improvement, and the sense that changes were being evaluated for effectiveness. None of the surveyed dimensions of patient safety culture worsened. Fewer punitive concerns were noted, with statistically significant decreases in the worry of embarrassment in front of colleagues and fear of getting colleagues in trouble., Conclusions: A comprehensive incident learning system can identify many areas for improvement and is associated with significant and sustained improvements in patient safety culture. These data provide valuable guidance as incident learning systems become more widely used in radiation oncology., (Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: Understanding factors which may promote walking in mid-life and older adults with mobility impairments is key given the association between physical activity and positive health outcomes., Objective: To examine the relationship between active trips and objective measures of the home neighborhood built environment., Methods: Global positioning systems (GPS) data collected on 28 adults age 50+ with mobility disabilities were analyzed for active trips from home. Objective and geographic information systems (GIS) derived measures included Walk Score, population density, street connectivity, crime rates, and slope within the home neighborhood. For this cross-sectional observational study, we conducted mean comparisons between participants who took active trips from home and those who did not for the objective measures. Effect sizes were calculated to assess the magnitude of group differences., Results: Nine participants (32%) took active trips from home. Walking in the home neighborhood was significantly associated with GIS derived measures (Walk Score, population density, and street density; effect sizes 0.9-1.2). Participants who used the home neighborhood for active trips had less slope within 1 km of home but the difference was not significant (73.5 m ± 22 vs. 100.8 m ± 38.1, p = 0.06, d = 0.8). There were no statistically significant differences in mean scores for crime rates between those with active trips from home and those without., Conclusions: The findings provide preliminary evidence that more walkable environments promote active mobility among mid-life and older adults with mobility disabilities. The data suggest that this population can and does use active transportation modes when the built environment is supportive., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Schizophrenia is associated with very high rates of tobacco smoking. The latter may be related to an attempt to self-medicate symptoms and/or to alterations in function of high-affinity β2-subunit-containing nicotinic acetylcholine receptors (β2*-nAChRs)., Methods: Smoking and nonsmoking subjects with schizophrenia (n=31) and age-, smoking-, and sex-matched comparison subjects (n=31) participated in one [123I]5-IA-85380 single photon emission computed tomography scan to quantify β2*-nAChR availability. Psychiatric, cognitive, nicotine craving, and mood assessments were obtained during active smoking, as well as smoking abstinence., Results: There were no differences in smoking characteristics between smokers with and without schizophrenia. Subjects with schizophrenia had lower β2*-nAChR availability relative to comparison group, and nonsmokers had lower β2*-nAChR availability relative to smokers. However, there was no smoking by diagnosis interaction. Relative to nonsmokers with schizophrenia, smokers with schizophrenia had higher β2*-nAChR availability in limited brain regions. In smokers with schizophrenia, higher β2*-nAChR availability was associated with lower negative symptoms of schizophrenia and better performance on tests of executive control. Chronic exposure to antipsychotic drugs was not associated with changes in β2*-nAChR availability in schizophrenia., Conclusions: Although subjects with schizophrenia have lower β2*-nAChR availability relative to comparison group, smokers with schizophrenia appear to upregulate in the cortical regions. Lower receptor availability in smokers with schizophrenia in the cortical regions is associated with a greater number of negative symptoms and worse performance on tests of executive function, suggesting smoking subjects with schizophrenia who upregulate to a lesser degree may be at risk for poorer outcomes., (© 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.)