Sex and Age Differences in Atypical Chief Complaints for Acute Decompensated Heart Failure in Emergency Department Visits.

Objectives: Around one million United States emergency department (ED) visits annually are due to acute decompensated heart failure (ADHF) symptoms. Characterizing ED symptom presentation of ADHF patients may improve clinical care, yet sex and age differences in ED chief complaints have not been thoroughly investigated. This paper aims to describe differences in chief complaints and comorbid conditions for ED patients with a ADHF diagnosis, stratified by sex and age. Methods: Retrospective analysis of adults presenting to North Carolina EDs in NC DETECT, a statewide syndromic surveillance system, between 2010 and 2016 with a diagnosis of ADHF. Frequencies of chief complaint categories for ED visits and comorbid conditions, stratified by sex and age, were evaluated and standardized differences computed. Results: Top chief complaints were dyspnea (19.1%), chest pain (13.5%), and other respiratory complaints (13.4%). In the 18-44 age group, females when compared to males reported more nausea/vomiting (6.7% versus 4.1%) and headache (4.2% versus 2.0%). In those 45-64 and 65+ years old, complaints were similar by sex. When stratified by age group alone, the 18-44 and 45-64 age groups had more complaints of chest pain, whereas balance issues, weakness, and confusion were more common in the 65+ age group. Conclusion: Sex and age differences in atypical ADHF symptoms were seen in in ED patients with ADHF. Characterizing variation of ADHF symptoms in ED patients can inform the identification of ED patients with ADHF and the management of ADHF-related symptoms.

Initiative to deprescribe high-risk drugs for older adults presenting to the emergency department after falls.

BACKGROUND: Over 35 million falls occur in older adults annually and are associated with increased emergency department (ED) revisits and 1-year mortality. Despite associations between medications and falls, the prevalence of fall risk-increasing drugs remains high. Our objective was to implement an ED-based medication reconciliation for patients presenting after falls and determine whether an intervention targeting high-risk medications was related to decreased future falls. METHODS: This was an observational prospective cohort study at a single site in the United States. Adults 65 years and older presenting to the ED after falls had a pharmacist review their medicines. Pharmacists made recommendations to taper, stop, or discuss medications with the primary clinician. At 3, 6, and 12 months, we recorded the number of fall-related return ED visits and determined if recommended medication changes had been implemented. We compared the rate of return visits of patients who had followed the medication change recommendations and those who received recommendations but had no change in their medications using chi-square tests. RESULTS: A total of 577 patients (mean age 81 years, 63.6% female) were enrolled of 1509 potentially eligible patients. High-risk medications were identified in 310 patients (53.7%) who received medication recommendations. High-risk medications were associated with repeat fall-related visits at 12 months (risk difference 8.1% [95% confidence interval 0.97-15.0]). A total of 134 (43%) patients on high-risk medications had evidence of medication modification. At 12 months, there was no statistically significant difference in return fall visits between patients who had modifications to medications compared with those who had not implemented changes (p = 0.551). CONCLUSIONS: Our findings identified opportunities for medication optimization in over half of emergency visits for falls and demonstrated that medication counseling in the ED is feasible. However, evaluation of the effect on future falls was limited.

Accuracy of the electronic health record's problem list in describing multimorbidity in patients with heart failure in the emergency department.

Patients with heart failure (HF) often suffer from multimorbidity. Rapid assessment of multimorbidity is important for minimizing the risk of harmful drug-disease and drug-drug interactions. We assessed the accuracy of using the electronic health record (EHR) problem list to identify comorbid conditions among patients with chronic HF in the emergency department (ED). A retrospective chart review study was performed on a random sample of 200 patients age ≥65 years with a diagnosis of HF presenting to an academic ED in 2019. We assessed participant chronic conditions using: (1) structured chart review (gold standard) and (2) an EHR-based algorithm using the problem list. Chronic conditions were classified into 37 disease domains using the Agency for Healthcare Research Quality's Elixhauser Comorbidity Software. For each disease domain, we report the sensitivity, specificity, positive predictive value, and negative predictive of using an EHR-based algorithm. We calculated the intra-class correlation coefficient (ICC) to assess overall agreement on Elixhauser domain count between chart review and problem list. Patients with HF had a mean of 5.4 chronic conditions (SD 2.1) in the chart review and a mean of 4.1 chronic conditions (SD 2.1) in the EHR-based problem list. The five most prevalent domains were uncomplicated hypertension (90%), obesity (42%), chronic pulmonary disease (38%), deficiency anemias (33%), and diabetes with chronic complications (30.5%). The positive predictive value and negative predictive value of using the EHR-based problem list was greater than 90% for 24/37 and 32/37 disease domains, respectively. The EHR-based problem list correctly identified 3.7 domains per patient and misclassified 2.0 domains per patient. Overall, the ICC in comparing Elixhauser domain count was 0.77 (95% CI: 0.71-0.82). The EHR-based problem list captures multimorbidity with moderate-to-good accuracy in patient with HF in the ED.

Cost variation and revisit rate for adult patients with asthma presenting to the emergency department.

BACKGROUND: Asthma is common, resulting in 53 million emergency department (ED) visits annually. Little is known about variation in cost and quality of ED asthma care. STUDY OBJECTIVE: We sought to describe variation in costs and 7-day ED revisit rates for asthma care across EDs. Our primary objective was to test for an association between ED costs and the likelihood of a 7-day revisit for another asthma exacerbation. METHODS: We used the 2014 Florida State Emergency Department Database to perform an observational study of ED visits by patients ≥18 years old with a primary diagnosis of asthma that were discharged home. We compared patient and hospital characteristics of index ED discharges with and without 7-day revisits, then tested the association between ED revisits and index ED costs. Multilevel regression was performed to account for hospital-level clustering. RESULTS: In 2014, there were 54,060 adult ED visits for asthma resulting in discharge, and 1667 (3%) were associated with an asthma-related ED revisit within 7 days. Median cost for an episode of ED asthma care was $597 with an interquartile range of $371-980. After adjusting for both patient and hospital characteristics, lack of insurance was associated with higher odds of revisit (OR 1.42, 95% CI 1.18-1.71), while private insurance, female gender, and older age were associated with lower odds of revisit. Hospital costs were not associated with ED revisits (OR = 1.00; 95% CI 1.00-1.00). CONCLUSION: Hospital costs associated with ED asthma visits vary but are not associated with odds of ED revisit.

User centered clinical decision support to implement initiation of buprenorphine for opioid use disorder in the emergency department: EMBED pragmatic cluster randomized controlled trial.

OBJECTIVE: To determine the effect of a user centered clinical decision support tool versus usual care on rates of initiation of buprenorphine in the routine emergency care of individuals with opioid use disorder. DESIGN: Pragmatic cluster randomized controlled trial (EMBED). SETTING: 18 emergency department clusters across five healthcare systems in five states representing the north east, south east, and western regions of the US, ranging from community hospitals to tertiary care centers, using either the Epic or Cerner electronic health record platform. PARTICIPANTS: 599 attending emergency physicians caring for 5047 adult patients presenting with opioid use disorder. INTERVENTION: A user centered, physician facing clinical decision support system seamlessly integrated into user workflows in the electronic health record to support initiating buprenorphine in the emergency department by helping clinicians to diagnose opioid use disorder, assess the severity of withdrawal, motivate patients to accept treatment, and complete electronic health record tasks by automating clinical and after visit documentation, order entry, prescribing, and referral. MAIN OUTCOME MEASURES: Rate of initiation of buprenorphine (administration or prescription of buprenorphine) in the emergency department among patients with opioid use disorder. Secondary implementation outcomes were measured with the RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) framework. RESULTS: 1 413 693 visits to the emergency department (775 873 in the intervention arm and 637 820 in the usual care arm) from November 2019 to May 2021 were assessed for eligibility, resulting in 5047 patients with opioid use disorder (2787 intervention arm, 2260 usual care arm) under the care of 599 attending physicians (340 intervention arm, 259 usual care arm) for analysis. Buprenorphine was initiated in 347 (12.5%) patients in the intervention arm and in 271 (12.0%) patients in the usual care arm (adjusted generalized estimating equations odds ratio 1.22, 95% confidence interval 0.61 to 2.43, P=0.58). Buprenorphine was initiated at least once by 151 (44.4%) physicians in the intervention arm and by 88 (34.0%) in the usual care arm (1.83, 1.16 to 2.89, P=0.01). CONCLUSIONS: User centered clinical decision support did not increase patient level rates of initiating buprenorphine in the emergency department. Although streamlining and automating electronic health record workflows can potentially increase adoption of complex, unfamiliar evidence based practices, more interventions are needed to look at other barriers to the treatment of addiction and increase the rate of initiating buprenorphine in the emergency department in patients with opioid use disorder. TRIAL REGISTRATION: ClinicalTrials.gov NCT03658642.

Advance Care Planning for Emergency Department Patients With COVID-19 Infection: An Assessment of a Physician Training Program.

OBJECTIVE: Coronavirus Disease 2019 (COVID-19) has heightened the importance of advance care planning (ACP), particularly in the emergency department (ED). The objective of this study was to determine the effect of an educational program for emergency physicians on ACP conversations in the ED during the COVID-19 pandemic. DESIGN: This was an observational pre-/post-interventional study. SETTING: This study was conducted at a Southeastern U.S. academic ED. PARTICIPANTS: 143 patients with confirmed COVID-19 infection in the 2 weeks up to and including the ED encounter of interest (between March 26 and May 25, 2020) were included. INTERVENTIONS: The primary intervention was an ACP training toolkit with three components: (1) an evidence-based guide to COVID-19 risk stratification, (2) education on language to initiate ACP conversations, and (3) modification of the electronic health record (EHR) to facilitate ACP documentation. Palliative care physicians also delivered a 60-minute ACP educational session for emergency medicine physicians. OUTCOME MEASURES: The primary outcome was a composite of ACP activities including: (1) identification of a healthcare decision-maker (HCDM), (2) an order for a code status, or (3) a documented goals of care conversation. RESULTS: There was a 25.4% (95% CI: 7.0-43.9) increase in the composite outcome of ED-based ACP. After adjustment for patient demographics and triage score, there was a non-statistically significant increase in ACP activity (OR = 2.71, 95% CI: 0.93-8.64; P = .08). CONCLUSION: A rapid and simple physician-facing educational intervention demonstrated a trend, though lacking in statistical significance, towards increased ED-based ACP activities for patients with COVID-19.

Emergency Department Visits for Nonfatal Opioid Overdose During the COVID-19 Pandemic Across Six US Health Care Systems.

STUDY OBJECTIVE: People with opioid use disorder are vulnerable to disruptions in access to addiction treatment and social support during the COVID-19 pandemic. Our study objective was to understand changes in emergency department (ED) utilization following a nonfatal opioid overdose during COVID-19 compared to historical controls in 6 healthcare systems across the United States. METHODS: Opioid overdoses were retrospectively identified among adult visits to 25 EDs in Alabama, Colorado, Connecticut, North Carolina, Massachusetts, and Rhode Island from January 2018 to December 2020. Overdose visit counts and rates per 100 all-cause ED visits during the COVID-19 pandemic were compared with the levels predicted based on 2018 and 2019 visits using graphical analysis and an epidemiologic outbreak detection cumulative sum algorithm. RESULTS: Overdose visit counts increased by 10.5% (n=3486; 95% confidence interval [CI] 4.18% to 17.0%) in 2020 compared with the counts in 2018 and 2019 (n=3020 and n=3285, respectively), despite a 14% decline in all-cause ED visits. Opioid overdose rates increased by 28.5% (95% CI 23.3% to 34.0%) from 0.25 per 100 ED visits in 2018 to 2019 to 0.32 per 100 ED visits in 2020. Although all 6 studied health care systems experienced overdose ED visit rates more than the 95th percentile prediction in 6 or more weeks of 2020 (compared with 2.6 weeks as expected by chance), 2 health care systems experienced sustained outbreaks during the COVID-19 pandemic. CONCLUSION: Despite decreases in ED visits for other medical emergencies, the numbers and rates of opioid overdose-related ED visits in 6 health care systems increased during 2020, suggesting a widespread increase in opioid-related complications during the COVID-19 pandemic. Expanded community- and hospital-based interventions are needed to support people with opioid use disorder and save lives during the COVID-19 pandemic.

Association of Convalescent Plasma Treatment with Reduced Mortality and Improved Clinical Trajectory in Patients Hospitalized with COVID-19 in the Community Setting

BackgroundConvalescent plasma (CP) quickly emerged as one of the first investigational treatment options for COVID-19. Evidence supporting CP for treating patients hospitalized with COVID-19 has been inconclusive, leading to conflicting recommendations regarding its use. The primary objective was to perform a comparative effectiveness study of CP for all-cause, in-hospital mortality in patients with COVID-19. MethodsThe matched, multicenter, electronic health records-based, retrospective cohort study included 44,770 patients hospitalized with COVID-19 in one of 176 HCA Healthcare-affiliated community hospitals across the United States from March 2 to October 7, 2020. Coarsened exact matching (1:k) was employed resulting in a sample of 3,774 CP and 10,687 comparison patients. ResultsExamining mortality using a shared frailty model and controlling for concomitant medications, calendar date of admission, and days from admission to transfusion demonstrated a significant association of CP with lower risk of mortality compared to the comparison group (aHR = 0.71, 95% CI 0.59-0.86, p<0.001). Examination of patient risk trajectories, represented by 400 clinico-demographic features from our Real-Time Risk Model (RTRM), indicated that patients who received CP recovered more quickly. The time from admission to CP transfusion was significantly associated with risk of mortality and stratification revealed that CP within 3 days after admission, but not 4-7 days, was associated with a significant reduction in mortality risk (aHR = 0.53, 95% CI 0.47-0.60, p<0.001). CP serology level was inversely associated with mortality when controlling for interaction with days to transfusion (HR = 0.998, 95% CI 0.997-0.999, p = 0.013) but was not significant in a univariable analysis. ConclusionUtilizing this large, diverse, multicenter cohort, we demonstrate that CP is significantly associated with reduced risk of in-hospital mortality. These observations demonstrate the utility of real-world evidence and suggest the need for further evaluation prior to abandoning CP as a viable therapy for COVID-19. FundingThis research was supported, in whole, by HCA Healthcare and/or an HCA Healthcare affiliated entity including Sarah Cannon and Genospace. Research in Context Evidence before this studyDiscrepant reports of the efficacy of various treatments for COVID-19, including convalescent plasma (CP), emerged from a rapidly evolving political and interventional landscape of the pandemic. Furthermore, clinical interpretations of this discordant data led to underuse, overuse and misuse of certain interventions, often ignoring mechanistic context altogether. CP has been utilized in prior pandemics/epidemics to introduce antibodies to elicit an immune response during the viral phase of infection. Thus, CP received early priority for emergency use and randomized trial engagement. Initially, the United States had issued individual emergency investigational new drug (eIND) use for CP and initiated its expanded access protocol (EAP) to monitor its safety profile and to allow broader access. This effectively restricted access to those with severe disease, which is not mechanistically aligned with targeting the viral phase. Many randomized control trials (RCTs) were being setup for testing efficacy of CP in the inpatient setting and, to a lesser extent, the outpatient setting. Some trial designs focused on severe disease and others on less severe. United States RCTs had additional enrollment challenges due to competing patient access to EAP. All studies were limited by supply and demand due to regional outbreaks and to the shear operational effort of coordinating donations, sampling, serology testing, ordering, and distribution. To date, most matched studies and RCTs around the globe have shown a trend of CP providing survival benefit, but all had relatively small cohorts except the RECOVERY trial, which failed to show a benefit with CP. Results ranged from no significant effect to 56% reduction in mortality with the latter coming out of a multisite RCT based in New York and Rio De Janeiro. There has been a minimum of nine matched control studies and seven randomized control trials evaluating convalescent plasma. We frequently assessed World Health Organization (WHO), United Stated Food and Drug Administration (FDA), BARDA/Mayo Clinic led EAP, and the United States Center for Disease Control and Prevention (CDC) resources as well as queried both preprint archives (MedRXIV & SSRN) and PubMed with the search terms "retrospective", "convalescent plasma", "randomized", "trial", "comparative effect", "COVID", "hospital", "in-hospital", "hospitalized" and "mortality" to ensure we were considering the most recent methodology and results generated for CP. The last search was performed on May 14, 2021. No date restrictions or language filters were applied. Added value of this studyTo our knowledge, this study is the largest and most geographically diverse of its kind to comprehensively evaluate and confirm the beneficial association of CP with all-cause mortality in patients hospitalized with COVID-19. Our data provides context to optimal delivery and validates recent trends in the literature showing CP benefit. There is a dose-response effect with CP antibody levels and we demonstrate that sooner really is better in accordance with the mechanisms of viral clearance and immune regulation. Finally, this is all done in the context of a diverse community setting in one of the largest hospital systems in the United States. Implications of all the available evidenceAs novel, more virulent and transmissible SARS-CoV-2 variants emerge around the globe and as reports of post-vaccine "breakthrough" infections and vaccine hesitancy increase, there is a renewed motivation to identify effective treatments for hospitalized patients. The data presented here, along with a growing body of evidence from matched-control studies and RCTs, demonstrate that further evaluation is required prior to abandoning CP as an effective intervention in the treatment of hospitalized COVID-19 patients.

Development of a Real-Time Risk Model (RTRM) for Predicting In-Hospital COVID-19 Mortality

BackgroundWith over 83 million cases and 1.8 million deaths reported worldwide by the end of 2020 for SARS-CoV-2 (COVID-19), there is an urgent need to enhance identification of high-risk populations to properly evaluate therapy effectiveness with real-world evidence and improve outcomes. MethodsBaseline and daily indicators were evaluated using electronic health records for 46,971 patients hospitalized with COVID-19 from 176 HCA Healthcare-affiliated hospitals, presenting from March to September 2020, to develop a real-time risk model (RTRM) of all-cause, hospitalized mortality. Patient facility, dates-of-care, clinico-demographics, comorbidities, vitals, laboratory markers, and respiratory support findings were aggregated in a logistic regression model. FindingsThe RTRM predicted overall mortality as well as mortality 1, 3, and 7 days in advance with an area under the receiver operating characteristic curve (AUCROC) of 0.905, 0.911, 0.905, and 0.901 respectively, significantly outperforming a combined model of age and daily modified WHO progression scale (all p<0.0001; AUCROC, 0.846, 0.848, 0.850, and 0.852). The RTRM delineated risk at presentation from ongoing risk associated with medical care and showed that mortality rates decreased over time due to both decreased severity and changes in care. InterpretationTo our knowledge, this study is the largest of its kind to comprehensively evaluate predictors and incorporate daily risk measures of COVID-19 mortality. The RTRM validates current literature trends in mortality across time and allows direct translation for research and clinical applications. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSDue to the rapidly evolving nature of the COVID-19 pandemic, the body of evidence and published literature was considered prior to study initiation and throughout the course of the study. Although at study initiation there was a growing consensus that age and disease severity at presentation were the greatest contributors to predicting in-hospital mortality, there was less of a consensus on the key demographics, comorbidities, vitals and laboratory values. In addition, early on, most potential predictors of in-hospital mortality had been assessed by univariable analysis. In April of 2020, a systematic review of prediction studies for COVID-19 revealed that there were only 8 publications for prognosis of hospital mortality. All were deemed to have high potential for bias due to low sample size, model overfitting, vague reporting and/or insufficient follow-up. Over the duration of the study, in-hospital prediction models were published ranging from simplified scores to machine learning. There were at least 8 prediction studies that were published during the course of our own that had comparable sample size or extensive multivariable analysis with the greatest accuracy of prediction reported as 74%. Moreover, a report in December of 2020 independently validated 4 simple prediction models, with none achieving greater than an AUCROC of 0.72%. Lastly, an eight-variable score developed by a UK consortium on a comparable sample size demonstrated an AUCROC of 0.77. To our knowledge, however, none to-date have modeled daily risk beyond baseline. We frequently assessed World Health Organization (WHO) resources as well as queried both MedRXIV and PubMed with the search terms "COVID", "prediction", "hospital" and "mortality" to ensure we were assessing all potential predictors of hospitalized mortality. The last search was performed on January 5, 2021 with the addition of "multi", "daily", "real time" or "longitudinal" terms to confirm the novelty of our study. No date restrictions or language filters were applied. Added value of this studyTo our knowledge, this study is the largest and most geographically diverse of its kind to comprehensively evaluate predictors of in-hospital COVID-19 mortality that are available retrospectively in electronic health records and to incorporate longitudinal, daily risk measures to create risk trajectories over the entire hospital stay. Not only does our Real-Time Risk Model (RTRM) validate current literature, demonstrating reduced mortality over the course of the COVID-19 pandemic and identifying age and WHO severity as major drivers of mortality in regards to baseline characteristics, but it also outperforms a model of age and daily WHO score combined, achieving an AUCROC of 0.91 on the test set. Furthermore, the fact that the RTRM delineates risk at baseline from risk over the course of care allows more granular interpretation of the impact of various parameters on mortality risk, as demonstrated in the current study using both sex disparity and calendar epochs that were based on evolving treatment recommendations as proofs-of-principle. Implications of all the available evidenceThe goal of the RTRM was to create a flexible tool that could be used to assess intervention and treatment efficacy in real-world, evidence-based studies as well as provide real-time risk assessment to aid clinical decisions and resourcing with further development. Implications of this work are broad. The depth of the multi-facility, harmonized electronic health record (EHR) dataset coupled with the transparency we provide in the RTRM results provides a resource for others to interpret impact of markers of interest and utilize data that is relevant to their own studies. The RTRM will allow optimal matching in retrospective cohort studies and provide a more granular endpoint for evaluation of interventions beyond general effectiveness, such as optimal delivery, including dosing and timing, and identification of the population/s benefiting from an intervention or combination of interventions. In addition, beyond the scope of the current study, the RTRM and its resultant daily risk scores allow for flexibility in developing prediction models for other clinical outcomes, such as progression of pulmonary disease, need for invasive mechanical ventilation, and development of sepsis and/or multiorgan failure, all of which could provide a framework for real-time personalized care.

Hospital Centralization Impacts High-Risk Lung and Bladder Cancer Surgical Patients.

We investigated the effects of hospital centralization on the distribution of the individual surgical patient risk in higher versus lower volume hospitals. Lung (n = 28,471) and bladder (n = 8,160) cancer surgical patients were selected from the New York Statewide Planning and Research Cooperative System database, 1997-2011. Estimated patient risk was consistently lower in the highest compared to the lowest hospital volume-quartiles for lung and bladder cancer mortality, complications, and long length of stay. Although centralization has improved outcomes, lower volume hospitals continue to perform surgery on higher surgical risk patients compared to higher volume hospitals.

Venous thromboembolism in metastatic urothelial carcinoma or variant histologies: incidence, associative factors, and effect on survival.

Venous thromboembolism (VTE) is common in cancer patients. However, little is known about VTE risk in metastatic urothelial carcinoma or variant histologies (UC/VH). We sought to characterize the incidence, associative factors, including whether various chemotherapy regimens portend different risk, and impact of VTE on survival in metastatic UC/VH patients. Patients diagnosed with metastatic UC/VH from 2000 to 2013 were included in this multicenter retrospective, international study from 29 academic institutions. Cumulative and 6-month VTE incidence rates were determined. The association of first-line chemotherapy (divided into six groups) and other baseline characteristics on VTE were analyzed. Each chemotherapy treatment group and statistically significant baseline clinical characteristics were assessed in a multivariate, competing-risk regression model. VTE patients were matched to non-VTE patients to determine the impact of VTE on overall survival. In all, 1762 patients were eligible for analysis. There were 144 (8.2%) and 90 (5.1%) events cumulative and within the first 6 months, respectively. VTE rates based on chemotherapy group demonstrated no statistical difference when gemcitabine/cisplatin was used as the comparator. Non-urotheilal histology (SHR: 2.67; 95% CI: 1.72-4.16, P < 0.001), moderate to severe renal dysfunction (SHR: 2.12; 95% CI: 1.26-3.59, P = 0.005), and cardiovascular disease (CVD) or CVD risk factors (SHR: 2.27; 95% CI: 1.49-3.45, P = 0.001) were associated with increased VTE rates. Overall survival was worse in patients with VTE (median 6.0 m vs. 10.2 m, P < 0.001). Thus, in metastatic UC/VH patients, VTE is common and has a negative impact on survival. We identified multiple associated potential risk factors, although different chemotherapy regimens did not alter risk.

The Khorana Score in Predicting Venous Thromboembolism for Patients With Metastatic Urothelial Carcinoma and Variant Histology Treated With Chemotherapy.

BACKGROUND: The Khorana score is a predictive risk model for venous thromboembolism (VTE) in patients with cancer planning to receive chemotherapy. Urothelial carcinoma and variant histologies (UC/VH) were underrepresented in the model. We sought to evaluate whether the Khorana score predicts for VTE in a retrospective multinational data set of patients with metastatic UC/VH. METHODS: Patients diagnosed with metastatic UC/VH who received chemotherapy were eligible. Those with incomplete or miscoded data were excluded. Khorana scores were calculated based on the pretreatment data and categorized into high (≥3) or intermediate (1-2) VTE risk. Other patient-, tumor-, and therapy-related factors were also analyzed. The χ2 and logistic regression analyses were used to assess differences in VTE rates based on the clinical characteristics. Subgroup analyses were performed to evaluate the Khorana score and associated variables for early (<3 months) and late (>3 months) VTE. RESULTS: A total of 943 patients were eligible for analysis. The cumulative VTE rate was 9.9%. There was no statistical difference in overall VTE rate between Khorana high- and intermediate-risk groups ( P = .16). In the multivariate analysis, nonurothelial histology (odds ratio [OR] = 2.56; P = .002) and the presence of cardiovascular disease (CVD) or CVD risk factors (OR = 2.14; P = .002) were associated with increased VTE risk. In the first 3 months from initiation of chemotherapy, Khorana high risk (OR = 2.08; P = .04) was associated with higher VTE rates. White blood cell (WBC) count (OR = 1.05; P = .04) was the only significant Khorana variable for early VTE. CONCLUSIONS: The Khorana score stratifies early but not overall VTE risk in patients with metastatic UC/VH. The WBC count drives the increased early VTE risk seen with the Khorana score.

Competitive Disinhibition Mediates Behavioral Choice and Sequences in Drosophila.

Even a simple sensory stimulus can elicit distinct innate behaviors and sequences. During sensorimotor decisions, competitive interactions among neurons that promote distinct behaviors must ensure the selection and maintenance of one behavior, while suppressing others. The circuit implementation of these competitive interactions is still an open question. By combining comprehensive electron microscopy reconstruction of inhibitory interneuron networks, modeling, electrophysiology, and behavioral studies, we determined the circuit mechanisms that contribute to the Drosophila larval sensorimotor decision to startle, explore, or perform a sequence of the two in response to a mechanosensory stimulus. Together, these studies reveal that, early in sensory processing, (1) reciprocally connected feedforward inhibitory interneurons implement behavioral choice, (2) local feedback disinhibition provides positive feedback that consolidates and maintains the chosen behavior, and (3) lateral disinhibition promotes sequence transitions. The combination of these interconnected circuit motifs can implement both behavior selection and the serial organization of behaviors into a sequence.

The Relationship between Centralization of Care and Geographic Barriers to Cystectomy for Bladder Cancer.

Background: Centralization of cystectomy treatment for bladder cancer, while associated with improved outcomes, may impose geographic barriers to care. However, whether this effect may be counterbalanced by an increased number of high volume centers has not previously been explored. Objective: To characterize changes in geographic disparities to high volume cystectomy centers over time. Methods: Data on all inpatient admissions for cystectomy in New York State (NYS) from 1997-2011 was obtained from the Department of Health. Using these data, we classified hospitals according to cystectomy volume and measured patient distance traveled to a cystectomy center. Population weights, from the US Census, were used to describe changes in minimum travel distance to high- or very high-volume (HV/VHV) facilities across the NYS population. Results: Bladder cancer patients underwent cystectomies at 195 hospitals during the study period. In 1997-2001, eleven HV/VHV facilities accounted for 37.5% of all cystectomies, while sixteen HV/VHV hospitals accounted for 71.5% of all procedures during 2007-2011. Median distance traveled by cystectomy patients to all hospitals increased from 9.6 to 14.4 miles in 1997-2001 to 2007-2011, respectively. In the same time span, the median travel distance for the NYS population to a HV/VHV center decreased by 1.9 and 9.4 miles at the median and 75th percentile, respectively. Conclusions: Our findings demonstrate a complicated relationship between centralization and geographic access. While centralization has led to a decrease in overall access to cystectomy facilities, the process simultaneously improved access to high volume centers.

Alkyne Metathesis with Silica-Supported and Molecular Catalysts at Parts-per-Million Loadings.

Improvement of the activity, stability, and chemoselectivity of alkyne-metathesis catalysts is necessary before this promising methodology can become a routine method to construct C≡C triple bonds. Herein, we show that grafting of the known molecular catalyst [MesC≡Mo(OtBuF6 )3 ] (1, Mes=2,4,6-trimethylphenyl, OtBuF6 =hexafluoro-tert-butoxy) onto partially dehydroxylated silica gave a well-defined silica-supported active alkyne-metathesis catalyst [(≡SiO)Mo(≡CMes)(OtBuF6 )2 ] (1/SiO2-700 ). Both 1 and 1/SiO2-700 showed very high activity, selectivity, and stability in the self-metathesis of a variety of carefully purified alkynes, even at parts-per-million catalyst loadings. Remarkably, the lower turnover frequencies observed for 1/SiO2-700 by comparison to 1 do not prevent the achievement of high turnover numbers. We attribute the lower reactivity of 1/SiO2-700 to the rigidity of the surface Mo species owing to the strong interaction of the metal site with the silica surface.

INTRAVENOUS PAMIDRONATE IS ASSOCIATED WITH REDUCED MORTALITY IN PATIENTS WITH CHRONIC CRITICAL ILLNESS.

OBJECTIVE: Chronic critical illness (CCI), characterized by prolonged mechanical ventilation and tracheostomy, commonly manifests with elevated bone resorption, which has previously been shown to abate after treatment with intravenous (IV) bisphosphonates. Our study assessed the impact of pamidronate administration on clinical outcomes in a CCI cohort. METHODS: A retrospective case series was performed on 148 patients admitted to The Mount Sinai Hospital Respiratory Care Unit (RCU) from 2009-2010. We identified patients with CCI who did (n = 30) or did not (n = 118) receive IV pamidronate (30 to 90 mg). Both groups included patients with normal and abnormal renal function. Pamidronate was administered for elevated urine or serum N-telopeptide, hypercalciuria, or hypercalcemia. RESULTS: RCU and 1-year mortality were significantly lower in the pamidronate group (0 and 20%, respectively) compared to nonreceivers (19 and 56%, respectively) (P = .0077 and P = .0004, respectively). After adjusting for differences in baseline creatinine, estimated glomerular filtration rate, and serum calcium, the association with reduced mortality remained significant at 1 year (P = .0132) and with borderline significance for RCU mortality (P = .0911). Creatinine was significantly lower 7 days following pamidronate administration (P = .0025), with no significant difference at 14 days compared to baseline. Pamidronate receivers showed a greater increase in albumin during the RCU stay (2.49 to 3.23 g/dL), compared to nonreceivers (2.43 to 2.64 g/dL) (P = .0007). Pamidronate administration was associated with a significantly reduced rate of hypoglycemia compared to RCU patients not receiving pamidronate (0.09 versus 0.12; P = .0071). CONCLUSION: Pamidronate use in a CCI population is associated with reduced mortality, lower hypoglycemia rates, improved albumin, and stable renal function. ABBREVIATIONS: BMI = body mass index CCI = chronic critical illness CI = confidence interval CKD = chronic kidney disease CTx = C-telopeptide eGFR = estimated glomerular filtration rate ICU = intensive care unit IV = intravenous NTx = N-telopeptide PMV = prolonged mechanical ventilation RCU = respiratory care unit.

Effectiveness of Adjuvant Chemotherapy for Locally Advanced Bladder Cancer.

PURPOSE: Given that randomized trials exploring adjuvant chemotherapy for bladder cancer have been underpowered and/or terminated prematurely, yielding inconsistent results and creating an evidence gap, we sought to compare the effectiveness of cystectomy versus cystectomy plus adjuvant chemotherapy in real-world patients. PATIENTS AND METHODS: We conducted an observational study to compare the effectiveness of adjuvant chemotherapy versus observation postcystectomy in patients with pathologic T3-4 and/or pathologic node-positive bladder cancer using the National Cancer Data Base. We compared overall survival using propensity score (-adjusted, -stratified, -weighted, and -matched) analyses based on patient-, facility-, and tumor-level characteristics. A sensitivity analysis was performed to examine the impact of performance status. RESULTS: A total of 5,653 patients met study inclusion criteria; 23% received adjuvant chemotherapy postcystectomy. Chemotherapy-treated patients were younger and more likely to have private insurance, live in areas with a higher median income and higher percentage of high school-educated residents, and have lymph node involvement and positive surgical margins (P < .05 for all comparisons). Stratified analyses adjusted for propensity score demonstrated an improvement in overall survival with adjuvant chemotherapy (hazard ratio, 0.70; 95% CI, 0.64 to 0.76), and similar results were achieved with propensity score matching and weighting. The association between adjuvant chemotherapy and improved survival was consistent in subset analyses and was robust to the effects of poor performance status. CONCLUSION: In this observational study, adjuvant chemotherapy was associated with improved survival in patients with locally advanced bladder cancer. Although neoadjuvant chemotherapy remains the preferred approach based on level I evidence, these data lend further support for the use of adjuvant chemotherapy in patients with locally advanced bladder cancer postcystectomy who did not receive chemotherapy preoperatively.

The Impact of Regionalization of Cystectomy on Racial Disparities in Bladder Cancer Care.

PURPOSE: Regionalization of surgical care has improved the quality of care for patients with bladder cancer. We explored whether regionalization has benefited white and black patients equally. MATERIALS AND METHODS: We used a New York State inpatient database to identify all patients who underwent cystectomy for bladder cancer from 1997 to 2011. Hospital volume was classified in quintiles based on the number of cystectomies performed in the first 5 years of the study. Logistic regression was done to assess the association between race and low volume/very low volume hospitals. Racial disparities were further characterized using stratification by time and by the racial composition of the patient community. RESULTS: A total of 8,168 patients treated with cystectomy for bladder cancer were included in analysis. Compared with white race, black race was associated with a higher likelihood of low volume/very low volume hospital use (OR 1.59, 95% CI 1.26-2.02). The disparity was most prominent in 2002 to 2006 (OR 2.51, 95% CI 1.64-3.85) but it did not persist in 2007 to 2011 (OR 1.46, 95% CI 0.92-2.32). Black patients living in a black community had the highest likelihood of low volume/very low volume hospitalization during all periods of increased regionalization (2002 to 2006 OR 4.14, 95% CI 1.84-9.34 and 2007 to 2011 OR 2.40, 95% CI 1.07-5.39). CONCLUSIONS: Regionalization of cystectomy transiently worsened the racial disparity in bladder cancer care, although the disparity did not persist with time. Specific efforts may be needed to address the consequences of regionalization in particularly vulnerable subpopulations, such as black patients who live in a black community where disparities have persisted.