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Objective The objective of this study is to examine patent ductus arteriosus (PDA) response by treatment course and investigate associations with postmenstrual age (PMA), chronological age (CA), gestational age (GA), antenatal steroid exposure (ANS), birthweight (BW), weight at treatment initiation (WT), and PDA/left pulmonary artery (LPA) ratio. Study Design This is a single-center retrospective cohort study of preterm infants less than 37 weeks' GA born January 1, 2016 to December 31, 2018 who received acetaminophen and/or indomethacin for PDA treatment. Cox proportional hazards regression models were used to determine whether factors of interest were associated with PDA response to medical treatment. Results In total, 289 treatment courses were administered to 132 infants. Thirty-one (23%) infants experienced treatment-associated PDA closure. Ninety-four (71%) infants had evidence of PDA constriction following any treatment course. Ultimately, 84 (64%) infants experienced definitive PDA closure. For each 7-day increase in CA at the time of treatment initiation, the PDA was 59% less likely to close (p = 0.04) and 42% less likely to respond (i.e., constrict or close) to treatment (p Conclusion In this cohort, PDA closure is independent of PMA, GA, ANS, BW, and WT; however, CA at treatment initiation predicted both treatment-associated PDA closure and PDA response (i.e., constriction or closure), and PDA/LPA ratio was associated with treatment-associated closure. Most infants experienced PDA constriction rather than closure, despite receiving up to four treatment courses. Key Points

Background Therapeutic options for patients with advanced soft-tissue sarcoma (STS) are limited. The goal of the current phase 2 study was to examine the clinical activity and safety of the combination of gemcitabine plus pazopanib, a multityrosine kinase inhibitor with activity in STS. Methods The current randomized, phase 2 trial enrolled patients with advanced nonadipocytic STS who had received prior anthracycline-based therapy. Patients were assigned 1:1 to receive gemcitabine at a dose of 1000 mg/m2 on days 1 and 8 with pazopanib at a dose of 800 mg daily (G+P) or gemcitabine at a dose of 900 mg/m2 on days 1 and 8 and docetaxel at a dose of 100 mg/m2 on day 8 (G+T) every 3 weeks. Crossover was allowed at the time of disease progression. The study used a noncomparative statistical design based on the precision of 95% confidence intervals for reporting the primary endpoints of median progression-free survival (PFS) and rate of grade ≥3 adverse events (AEs) for these 2 regimens based on the intent-to-treat patient population (AEs were graded using version 4.0 of the National Cancer Institute Common Terminology Criteria for Adverse Events). Results A total of 90 patients were enrolled: 45 patients on each treatment arm. The median PFS was 4.1 months for each arm (P = .3, log-rank test). The best overall response of stable disease or better (complete response + partial response + stable disease) was the same for both treatment arms (64% for both the G+T and G+P arms). The rate of related grade ≥3 AEs was 82% for the G+T arm and 78% for the G+P arm. Related grade ≥3 AEs occurring in ≥10% of patients in the G+T and G+P arms were anemia (36% and 20%, respectively), fatigue (29% and 13%, respectively), thrombocytopenia (53% and 49%, respectively), neutropenia (20% and 49%, respectively), lymphopenia (13% and 11%, respectively), and hypertension (2% and 20%, respectively). Conclusions The data from the current study have demonstrated the safety and efficacy of G+P as an alternative to G+T for patients with nonadipocytic STS.

Background and aims Within the context of busy clinical settings, health-care providers need practical, evidence-based options to engage smokers in quitting. Sampling of nicotine replacement therapy [i.e. provision of nicotine replacement therapy (NRT starter kits)] is a brief, pragmatic strategy to address this need. We aimed to compare the effects of NRT sampling plus standard care (SC), relative to SC alone, provided by primary care providers during routine clinic visits. Design Cluster-randomized clinical trial. Setting Twenty-two primary care clinics in South Carolina, USA. Participants Adult smokers [n = 1245; 61% female, mean age = 50.7, standard deviation (SD) = 13.5] both motivated and unmotivated to quit, seen during routine clinical visit. Interventions were provider-delivered SC (n = 652, 12 clinics) cessation advice or SC + a 2-week supply of both nicotine patch and lozenge, with minimal instructions on use (n = 593; 10 clinics). Measurements The primary outcome was 7-day point prevalence smoking abstinence at 6-month follow-up, using intent-to-treat. Additional outcomes included NRT use and quit attempts, assessed at 1, 3 and 6 months following baseline. Findings Seven-day point prevalence abstinence rates were significantly higher in the NRT sampling group throughout follow-up, including at 6 months [12 versus 8%, odds ratio (OR) = 1.5, 95% confidence interval (CI) = 1.0-2.4]. NRT sampling increased prevalence of any use of NRT (65 versus 25%, OR = 5.8, 95% CI = 4.3-7.7), with higher prevalence of use at 6 months (25 versus 14%, OR = 2.0, 95% CI = 1.5-2.7). NRT sampling increased the rate of quit attempts in the initial month (24 versus 18%, OR = 1.5, 95% CI = 1.0-2.3) but had no significant effect on overall rate of quit attempts (48 versus 45%, OR = 1.2, 95% CI = 0.8-1.7). Conclusion Providing smokers with a free 2-week starter kit of nicotine replacement therapy increased quit attempts, use of stop smoking medications and smoking abstinence compared with standard care in a primary care setting.

Older adults are a high priority population for smoking cessation. This study observed the influence of older age on the relationship between quitting predictors and cessation. Secondary analysis was conducted of a primary care trial of adults who smoke cigarettes randomized to standard advice to quit or advice plus 2 week supply of nicotine replacement therapy. Logistic regressions assessed interactions of age (

Adequate bone marrow recovery is a discharge requirement after admission for febrile neutropenia in oncology patients, without specific threshold in consensus guidelines. In January 2016, our institution implemented count recovery criteria of absolute neutrophil count ≥100 cells/μL and absolute phagocyte count ≥300 cells/μL compared with prior criteria of absolute neutrophil count ≥500 cells/μL. Retrospective analysis comparing pre (July 2013 to December 2015, N=68) and post (January 2016 to June 2018, N=30) groups showed no difference in readmissions (P>0.9), no patient deaths, and decreased average length of stay in the post group (P

Background There is robust preclinical literature and preliminary clinical findings supporting the use of N-Acetylcysteine (NAC) to treat substance use disorders, including tobacco use disorder (TUD). However, randomized controlled trials have yielded mixed results and NAC’s efficacy for TUD has not been established. The goals of this study were to assess the efficacy of NAC in promoting early and end-of-treatment abstinence and preventing relapse among adult smokers. Methods This randomized, double-blinded clinical trial enrolled adult, daily smokers (N = 114; ages 23–64; 51 % female; 65 % White; 29 % Black/African American; 7% Hispanic/Latinx), who were randomized 1:1 to receive NAC (n = 59) or placebo (n = 55) (1200 mg b.i.d.) for eight weeks. Participants received brief cessation counseling and incentives for abstinence during the first three days of the quit attempt. Primary outcomes: (i) carbon monoxide (CO)-confirmed abstinence during the first three days of the quit attempt. Secondary outcomes: (ii) time to relapse; (iii) biologically confirmed abstinence at Week 8. Results No differences were found between NAC and placebo groups on measures of early abstinence (3-day quit attempt; 11 % for NAC vs. 15 % for placebo; all p > 0.11), time to relapse (p = 0.19), and end-of-treatment abstinence (7% for NAC vs. 11 % for placebo; all p > 0.40]. Conclusions Results indicate that NAC is a well-tolerated pharmacotherapy but is unlikely to be efficacious as a monotherapy for TUD in adults. Considered in the collective context of other research, NAC may potentially be more useful in a younger population, as a combination pharmacotherapy, or in the presence of more intensive psychosocial treatment.

Background: The safety of higher dose vitamin D (vitD) supplementation in women who change from exclusive or full breastfeeding to combination feeding or who continue supplementation after cessation of breastfeeding is unknown. Objective: Compare vitD supplementation safety of 6,400 to 400 IU/day and 2,400 IU/day using specific laboratory parameters in postpartum women and their infants through 7 months postpartum by feeding type. Design: In this randomized controlled trial, mothers (exclusively breastfeeding or formula-feeding) were randomized at 4–6 weeks' postpartum to 400, 2,400, or 6,400 IU vitD(3) (cholecalciferol)/day for 6 months. Breastfeeding infants in 400 IU group received oral 400 IU vitD(3)/day; infants in 2,400 and 6,400 IU groups received placebo. Maternal safety parameters (serum vitD, 25-hydroxy-vitamin D [25(OH)D; calcidiol], calcium, phosphorus, intact PTH; urinary calcium/creatinine ratios; and feeding type/changes) were measured monthly; infant parameters were measured at months 1, 4, and 7. Sufficiency was defined as 25(OH)D >50 nmol/L. Feeding type was defined as exclusive/full, combination, or formula-feeding. Data were analyzed using SAS 9.4. Results: Four hundred nineteen mother-infant pairs were randomized into the three treatment groups and followed: 346 breastfeeding and 73 formula-feeding pairs. A dose of 6400 IU/day safely and significantly increased maternal vitD and 25(OH)D from baseline in all mothers regardless of feeding type (p

Introduction Medication sampling is a clinically useful tool to engage smokers in the quitting process. Whether varenicline is suitable for sampling purposes is unclear. The purpose of this study was to examine the feasibility, uptake, and preliminary outcomes of varenicline sampling. Methods Smokers (N = 99), both motivated to quit and not, were recruited and randomized to varenicline sampling versus not, with 12 week follow-up. The intervention consisted of mailing one-time samples of varenicline (lasting 2–4 wks), with minimally suggestive guidance on use. Results Uptake of varenicline was strong, at 2 weeks (54% any use, 66% daily use) and 4 weeks (38%, 46%), with 58% of medication users seeking additional medication. Most users followed conventional titration patterns, self-titrating from 0.5 mg to 2 mg. Relative to control, varenicline sampling increased motivation (p = 0.006) and confidence to quit (p = 0.02), and decreased cigarette smoking (p = 0.02). Smokers receiving varenicline samples were significantly more likely to achieve 50% reduction in cigarettes per day (CPD), both immediately following the sampling exercise (Adjusted Odds Ratio [AOR] = 4.12; 95% CI: 1.39 to 12.17) and at final follow-up (AOR = 4.50; 95% CI: 1.56 to 13.01). Though cessation outcomes were not statistically significant, there was a 1.5 to 3-fold increase in quit attempts and abstinence from varenicline sampling throughout follow-up. These outcomes were comparable among smokers motivated to quit and not. Conclusions Unguided, user-driven sampling of varenicline sampling is a concrete behavioral exercise that is feasible to do and seems to suggest clinical utility. Sampling is a pragmatic clinical approach to engage more smokers in quitting. Implications Use of evidence-based pharmacotherapies for smoking cessation is low. Medication sampling is a pragmatic behavioral exercise that allows smokers to experience the benefits of using them, while promoting positive downstream effects towards quitting. While previous studies have shown that nicotine replacement therapy (NRT) sampling is viable and effective, whether this extends to varenicline is unclear. Results from this trial demonstrate that varenicline sampling is feasible, safe, and suggestive of clinically important steps toward quitting, deserving of a larger trial. Clinical Trial Registration NCT #03742154.

Background: Primary management of advanced head/neck cancers involves concurrent chemoradiotherapy . Subsequently, regional and local failures are managed with resection but there have been few reports that describe the morbidity and disease control outcomes of surgical salvage in this setting. Methods: Retrospective analysis describes complications, survival, and patterns of failure after salvage resection of isolated local and/or regional failures of head/neck cancer following definitive concurrent chemoradiotherapy. Results: Sixteen patients were identified for inclusion: laryngectomy in 11 patients, oral cavity/oropharynx resection in 2 patients, and neck dissection alone in 4 patients. Ten patients required graft tissue reconstruction (6 pedicle and 4 free flap). Median post-operative hospitalization was 7 days (range 3-19), and 4 patients required hospital re-admission. At a median survivor follow-up of 15.8 months (range 4.3-34.9), 10 patients were alive (6 without evidence of disease). Seven patients experienced disease recurrence at a median 6.7 months (range 0-12.6) following salvage resection (2 with isolated distant failures). Estimated 2-year local/regional control, freedom from failure, and overall survival were 58%, 39%, and 58%, respectively. Conclusions: Surgical salvage after primary definitive concurrent chemoradiotherapy is feasible with toxicity and outcomes similar to prior radiotherapy alone or sequential chemotherapy and radiation. Local andregional recurrence remains the predominant pattern of failure.

The purpose of the present study was (1) to examine demographic differences between smokers who successfully quit (n = 1809), who relapsed (n = 6548), and who did not attempt to quit (n = 11 102) within the last year, and (2) to examine state-level tobacco policies/programs as predictors of quit success. Data were utilized from the 2014-2015 Tobacco Use Supplement to the Current Population Survey, which were paired with 2014 data on taxation, appropriations, and smoke-free air laws. As compared with smokers who relapsed, those who successfully quit were more likely to be white, married, more highly educated, of higher income, and heavier smokers. Compared with those who did not attempt to quit, those who attempted to quit, regardless of success, were younger and more likely to be Hispanic. State comprehensive smoke-free air laws and tobacco excise taxation significantly predicted quit success. Thus, expansions of these policies should be considered to promote successful quitting.

Background Preclinical and clinical research suggests that the oxytocin system is implicated in the development and maintenance of stress and anxiety-related psychiatric conditions, such as posttraumatic stress disorder (PTSD). Recent research also suggests that intranasal oxytocin holds promise as a treatment for PTSD. However, little is known about the relationship between levels of peripheral oxytocin and PTSD symptom severity, PTSD treatment response, and repeated intranasal oxytocin administration. Methods In the current study, we examined associations between PTSD symptom severity and peripheral oxytocin levels measured in plasma before and after a course of prolonged exposure (PE) for PTSD (n = 13); participants were randomized to adjunctive intranasal oxytocin (n = 6) or placebo (n = 7). Results Baseline peripheral oxytocin levels were not associated with baseline PTSD symptom severity. Change in peripheral oxytocin levels did not differ by treatment condition and did not correspond to change in PTSD symptoms. Conclusions This proof-of-concept study illustrates the acceptability and feasibility of measuring peripheral oxytocin among individuals engaged in psychotherapy for PTSD and informs the utilization of these procedures in future adequately powered studies.

OBJECTIVES: Bioequivalence of vitamins (vit) E, B12 and folate in a single oral dose multivitamin (MVI) gummies vs. tablets METHODS: This crossover clinical trial involved healthy adults randomized to either gummy or tablet MVI containing vitE, B12 and folate as a single dose in Phase 1 with serial blood samples obtained to measure vitE, B12 and folate at baseline 0, 0.5-, 1-, 2-, 4-, 6-, 8-, 9-, 10-, 24-, and 48-hrs followed by a 2-wk washout period. In Phase 2, participants then crossed over to receive MVI in the form not previously given, with blood sampling at same timepoints. Time course of absorption of gummy vs. tablet form was compared: Cmax and Area Under the Curve (AUC) calculated for each subject for vitamins at specific time intervals based on known t½. Data analyzed using SAS 9.4 (Cary, NC). RESULTS: Six healthy subjects completed the study. For vitE, there were no differences in AUC geometric mean ratios (GMR), log AUC GMR, or Cmax compared as GMR, log GMR or for Tmax GMR for gummy vs. tablet. For vitB12, no statistical differences on any of metrics with Cmax and Tmax GMR similar between gummy vs. tablet. For folate, there were significant differences in time course of absorption: folate absorption peaked earlier in gummy group (Tmax 1.59 hrs) vs. tablet group (Tmax 4.08 hrs), shifting mean values in the gummy group to earlier timepoints, with higher mean values at mid timepoints in tablet group. Shorter Tmax in gummy group suggested a difference in bioavailability in that preparation when compared to tablet. For folate, geometric and log AUC GMR, incremental AUC ratios, and Cmax measures showed no statistically significant differences in the gummy vs. tablet groups. CONCLUSIONS: Overall, under the conditions of this pilot study, both gummy and tablet showed similar absorption of vitamins E and B12. The time course of absorption of folate differed significantly between gummy vs. tablet formulation, with more rapid absorption with the gummy form. Cmax for gummy vs. tablet were similar for the 3 vitamins. A definitive study is planned with a larger sample size powered to verify these preliminary results. FUNDING SOURCES: Church & Dwight Co., Inc.

Cigarette smoking is increasingly concentrated among marginalized populations with limited access to evidence-based cessation treatment. This includes racial/ethnic minorities, lower income individuals, those with lower educational attainment, and residents of rural areas. To reach Healthy People 2020 objectives, successful cessation interventions must narrow these disparities. Nicotine replacement therapy (NRT) sampling is an easily translatable and scalable intervention that could enhance treatment access and thus narrow disparities. The present study examined individual-level demographic moderators of the impact of NRT sampling on cessation-related behaviors including: 1) use of a cessation medication, 2) making a 24-hour quit attempt, 3) floating abstinence, and 4) 7-day point prevalence abstinence at 6-months. Study participants included N = 1245 adult smokers enrolled in the Tobacco Intervention in Primary Care Treatment Opportunities for Providers (TIP TOP) study, a recently concluded large-scale clinical trial of NRT sampling relative to standard care within 22 primary care clinics across South Carolina. Generalized linear models examined individual-level demographic moderators of treatment effect. Results suggest that NRT sampling may be more effective among some of the most disadvantaged groups of smokers, including smokers with lower income and education, as well those who live in more rural areas. The effects of NRT sampling did not differ by race. In sum, NRT sampling is a low-cost, low-burden intervention that could be disseminated broadly to reach large numbers of smokers and potentially narrow cessation disparities.

Posttraumatic stress disorder (PTSD) is a chronic, debilitating condition for which Prolonged Exposure (PE) therapy is highly efficacious. However, for some individuals, premature dropout and residual PTSD symptoms remain obstacles. The neuropeptide oxytocin is a promising candidate to enhance PE due to its ability to enhance 1) prosocial cognition and behavior, which are theorized to promote positive working alliance, and 2) extinction learning, which is the central mechanism of action underlying successful PE treatment. Despite a robust theoretical rationale, no studies to date have combined evidence-based psychotherapy for PTSD with oxytocin. This randomized, placebo-controlled, double-blind pilot trial examined the feasibility, safety, and preliminary efficacy of augmenting PE with oxytocin. Participants were 17 individuals with diverse index traumas. Participants self-administered intranasal oxytocin (40 IU) or matching placebo 45 min prior to each weekly PE therapy session. One adverse event occurred in the placebo group and three individuals dropped out (17.6%; 2 oxytocin group and 1 placebo group). The oxytocin group demonstrated lower PTSD and depression symptoms during PE, and had higher working alliance scores, although these differences did not reach statistical significance. Although preliminary, the findings support the feasibility of oxytocin combined with PE. Adequately powered studies are necessary to determine whether oxytocin enhances PE treatment outcomes and to examine potential mechanisms, such as accelerating extinction learning, enhancing early response, and preventing premature dropout. NCT03238924.

Objective The goal of this study is to determine the effect of primary surgery vs radiotherapy (RT) on overall survival (OS) in patients with early stage oral cavity squamous cell carcinoma (OCSCC). In addition, this study attempts to identify factors associated with receiving primary RT. Study Design Retrospective cohort study. Setting National Cancer Database (NCDB, 2004-2013). Subjects and Methods Reviewing the NCDB from 2004 to 2013, patients with early stage I to II OCSCC were identified. Kaplan-Meier estimates of survival, Cox regression analysis, and propensity score matching were used to examine differences in OS between primary surgery and primary RT. Multivariable logistic regression analysis was performed to identify factors associated with primary RT. Results Of the 20,779 patients included in the study, 95.4% (19,823 patients) underwent primary surgery and 4.6% (956 patients) underwent primary RT. After adjusting for covariates, primary RT was associated with an increased risk of mortality (adjusted hazard ratio [aHR], 1.97; 99% confidence interval [CI], 1.74-2.22). On multivariable analysis, factors associated with primary RT included age ≥70 years, black race, Medicaid or Medicare insurance, no insurance, oral cavity subsite other than tongue, clinical stage II disease, low-volume treatment facilities, and earlier treatment year. Conclusion Primary RT for early stage OCSCC is associated with increased mortality. Approximately 5% of patients receive primary RT; however, this percentage is decreasing. Patients at highest risk for receiving primary RT include those who are elderly, black, with public insurance, and treated at low-volume facilities.

BACKGROUND The objective of this study was to determine the effects of National Comprehensive Cancer Network (NCCN) guideline–adherent initiation of postoperative radiation therapy (PORT) and different time-to-PORT intervals on the overall survival (OS) of patients with head and neck squamous cell carcinoma (HNSCC). METHODS The National Cancer Data Base was reviewed for the period of 2006-2014, and patients with HNSCC undergoing surgery and PORT were identified. Kaplan-Meier survival estimates, Cox regression analysis, and propensity score matching were used to determine the effects of initiating PORT within 6 weeks of surgery and different time-to-PORT intervals on survival. RESULTS This study included 41,291 patients. After adjustments for covariates, starting PORT >6 weeks postoperatively was associated with decreased OS (adjusted hazard ratio [aHR], 1.13; 99% confidence interval [CI], 1.08-1.19). This finding remained in the propensity score–matched subset (hazard ratio, 1.21; 99% CI, 1.15-1.28). In comparison with starting PORT 5 to 6 weeks postoperatively, initiating PORT earlier was not associated with improved survival (aHR for ≤ 4 weeks, 0.93; 99% CI, 0.85-1.02; aHR for 4-5 weeks, 0.92; 99% CI, 0.84-1.01). Increasing durations of delay beyond 7 weeks were associated with small, progressive survival decrements (aHR, 1.09, 1.10, and 1.12 for 7-8, 8-10, and >10 weeks, respectively). CONCLUSIONS Nonadherence to NCCN guidelines for initiating PORT within 6 weeks of surgery was associated with decreased survival. There was no survival benefit to initiating PORT earlier within the recommended 6-week timeframe. Increasing durations of delay beyond 7 weeks were associated with small, progressive survival decrements. Cancer 2017;123:4841-50. © 2017 American Cancer Society.

To refine public health policy amidst a changing landscape of tobacco products in the United States, it is first necessary to describe fully the nature of smokers’ alternative product use. Little research addresses smokers’ snus use, and most studies are limited by small samples, cross-sectional designs, and crude outcome measurement. This study sample includes 626 adult US smokers who denied intention to quit in the next month and were randomized to receive free snus during a 6-week sampling period, after which no snus was provided. Participants were then followed for one year. Outcome data were collected via phone. Participants (mean age: 48.7 years) were predominately female, White non-Hispanic. Eighty-four percent reported trial of snus. Eleven percent reported purchase (i.e., adoption). Current use declined from 47.1% at the end of the sampling period to 6.5% at the end of follow-up. Frequency and quantity of snus use among current users was low. Among snus users, 79.3% said it functioned as an alternative to smoking and 58.4% said it provided a means of coping with smoking restrictions; options not mutually exclusive. In logistic regressions, men were more likely to report trial (odds ratio [OR]=2.33, p < .01) and adoption (OR=1.84, p < .05) than women. Baseline expectations about the nature of snus use also predicted snus outcomes (OR=1.28–1.78, p < .05). Smokers showed willingness to try snus, but product interest waned over time. Snus as currently marketed is unlikely to play a prominent role in US tobacco control efforts.

Introduction: A significant proportion of acute ischemic stroke (AIS) patients who are evaluated through telestroke consultation are transferred to thrombectomy-capable stroke centers (TSCs) for concern of large vessel occlusion (LVO). Patient triage selection is commonly based on the clinical suspicion of LVO, which lacks specificity and could result in unnecessary transfers. In this study, we aimed to assess the accuracy of the most commonly used LVO recognition scales in telestroke setting. Methods: AIS patients transferred to TSCs for suspicion of an LVO were included in this retrospective study. Patients were evaluated by a stroke neurologist through a telestroke consult before transfer. The National Institute of Health Stroke Scale (NIHSS) score documented by the stroke neurologist was retrieved from medical records and used to calculate five other LVO recognition scales (Rapid Arterial Occlusion Evaluation Scale [RACE], Field Assessment Stroke Triage for Emergency Destination [FAST-ED], Cincinnati Prehospital Stroke Severity Scale [CPSSS], 3-item stroke scale [3I-SS], and Prehospital Acute Stroke Severity Scale [PASS]). We calculated the sensitivity, specificity, accuracy, positive and negative predictive values, false positive rate (FPR), and false negative rate (FNR) of each score using published cutoffs and then examined all possible cutoff values for each of these scales in addition to the NIHSS. Results: A total of 439 patients were included in the final analysis. A total of 48.5% of patients had an LVO confirmed on computed tomography angiogram. RACE score had the highest accuracy (78%). Overall, the five derived LVO recognition scores have at least 10% FNR. When examining all possible cutoff values, the NIHSS (cutoff of 6) had a 3% FNR but 73% FPR (false transfer). Conclusion: The use of the NIHSS and other LVO recognition scores over telestroke may result in unnecessary transfers. Better diagnostic tools that could maximize sensitivity with acceptable specificity are urgently needed.

Introduction Electronic nicotine delivery systems (ENDS) vary on a wide range of characteristics that may affect reinforcement value and use. One characteristic is the ratio of two solvents commonly used in most e-liquids: propylene glycol (PG) and vegetable glycerin (VG). The goal of this study was to understand how PG/VG ratio affects subjective effects, reinforcement value, and tobacco use patterns among current smokers who try using ENDS. Aims and Methods Current smokers with minimal ENDS use history (n = 30) sampled, in a double-blind fashion, three different e-liquids that varied in PG/VG ratio (70/30, 50/50, 0/100) while holding constant other aspects of the e-liquid and ENDS. Participants tried each e-liquid before rating the subjective effects on a modified version of the Cigarette Evaluation Questionnaire. Reinforcement value was assessed using a preference task where participants chose between the three e-liquids. The impact of each e-liquid on cigarette reinforcement was assessed using a modified version of the Cigarette Purchase Task. Participants were randomly assigned to receive one e-liquid to take home for 1 week. Results PG/VG ratio had minimal impact on most of the tested outcomes. Participants rated the highest PG concentration as having a stronger “throat hit” than the other two. There was no significant difference between the number of participants who preferred each of the PG/VG ratios in the preference assessment. PG/VG ratio did not affect cigarette or ENDS use during the sampling week. Conclusions These data suggest that PG/VG ratio has minimal impact on subjective effects and reinforcement value in ENDS naive current smokers. Implications These data suggest that PG/VG ratio, within the range that is commonly used, has minimal impact on subjective effects, reinforcement value, or uptake in current smokers with minimal ENDS experience.

Background and objectives Metabolic syndrome (MetS) is a constellation of cardiovascular risk factors shown to increase the risk of developing various malignancies, as well as diminish tumor response to conventional therapies. The effects of MetS and its individual components on therapeutic response and treatment-related outcomes were examined in patients with locally advanced rectal cancer (LARC). Methods Data was retrospectively collected on LARC patients treated with neoadjuvant chemoradiation (nCRT) and surgery. Medical records were reviewed for patient characteristics, staging, treatment plan, and outcomes. Results One hundred two patients were included in the study. Patients with HTN had a significantly decreased nCRT response and were four times more likely to experience a poor response to treatment compared to patients without HTN. Additionally, HTN was found to significantly increase the rate of surgical complications. Neither DM nor obesity exhibited any significant effect on therapeutic response or complication rates, either individually or in combination with another risk factor. Conclusion This study demonstrates the importance of considering underlying MetS risk factors, especially HTN, when predicting tumor response in LARC patients undergoing nCRT followed by radical surgery. The results provide support for an increased focus on pre-treatment risk factor control to optimize cancer therapy outcomes.

BackgroundObservational studies and a few clinical trials suggest that use of low nitrosamine smokeless tobacco (snus) can facilitate smoking cessation. To better understand the real-world impact of snus on smoking behaviour, a large-scale, long-term clinical trial of naturalistic snus use among smokers is needed.Study designA nationwide clinical trial compared abstinence outcomes among smokers who were randomised to receive free samples of snus versus not. Participants (N=1236) were recruited throughout the US and assessed for 1 year following a 6-week naturalistic sampling period, with high retention throughout. Primary outcomes included self-reported quit attempts, floating abstinence (any 7-day period of non-smoking) and 7-day point-prevalence abstinence at 6 months and 12 months. Secondary outcomes were changes in smoking, motivation and confidence to quit and adverse events. No tobacco industry support was provided.ResultsWithin snus group, 82% used at least once, and 16% were using regularly at end of sampling period. Compared to control participants, smokers in the snus group were less likely to make any quit attempt (RR=0.83; 95% CI 0.70 to 1.00), and any 24 h quit attempt (RR=0.77; 95% CI 0.63 to 0.95). There were no group differences on any measure of abstinence.ConclusionsProvision of snus in a naturalistic context resulted in minimal uptake, and as a whole, undermined quit attempts and did not increase smoking abstinence. Results do not support the unguided, free provision of snus among smokers not motivated to quit as a means to facilitate quit attempts.Trial registration numberNCT01509586, Results.

Objective Maternal stress in humans influences behavior of children and can be assessed using biological markers. Mothers and their one-month-old infants were recruited from an existing study to examine baseline maternal serum oxytocin and hypothalamic-pituitary-adrenal axis response to infant blood heel stick stress as measured by salivary cortisol in the dyads. Objectives were to explore (1) relationships between mother and infant cortisol levels, (2) gender differences in infant biologic cortisol response, and (3) the association of cortisol levels in the dyads and maternal oxytocin levels Methods Forty-two mother–infant dyads provided biologic samples and self-report data. Maternal oxytocin samples were obtained. Initial salivary cortisol was assessed in both the mother and infant, followed by a heel stick blood draw. Twenty minutes later, salivary cortisol was collected again from dyads. Results Self-report measures were negative for depression and risk for childhood neglect. Although oxytocin and baseline cortisol in the infants was higher in mothers that did some breast-feeding, there was no statistically significant difference ( p = 0.2 and p = 0.1, respectively). Analyses showed (a) higher baseline cortisol in mothers was related to higher baseline cortisol in infants ( p ≤ 0.0001), (b) following the stressor, female infants had a larger positive change in cortisol, after adjusting for baseline cortisol ( p = 0.045), and (c) there was no relationship between dyad cortisol levels and maternal oxytocin. Conclusions Maternal and infant biologic stress measures are related. Female infants have a larger hypothalamic-pituitary-adrenal response to a blood draw stressor as measured by salivary cortisol than male infants.

Introduction Adenovirus (AdV) infections can cause high morbidity and mortality. Reports that early PCR detection in stool preceded viremia led to a change in institutional screening practices. Objectives To describe the impact of AdV stool PCR screening. Methods We conducted a retrospective chart review of pediatric allo-HSCT at our institution from July 2007 – July 2018. Weekly AdV blood PCR screening was done throughout with addition of weekly stool AdV PCR screening from July 2010. Incidence rates were compared by Fisher's exact tests. Kappa statistic was used to measure agreement. Results We identified 117 transplants with 113 patients. Eight transplants were removed from analysis due to incomplete screening. Pre-stool screening AdV incidence was 6.7% (1 pneumonia,1 urine) with no deaths due to AdV. Post-stool screening AdV incidence was 31.6% (10 stool, 5 stool/blood, 5 blood, 2 respiratory, 2 stool/respiratory,1 stool/blood/respiratory) with 1 death due to AdV pneumonia despite cidofovir treatment with initial stool only detection. AdV detection was significantly increased in patients with stool testing versus blood testing alone (p=0.007) with poor agreement between the blood and stool testing (κ=0.25). Stool detection had limited value related to respiratory disease. No difference was seen in AdV incidence based on respiratory testing alone between patients with and without stool testing (p>0.9). The 2 patients with stool/respiratory AdV received cidofovir with initial stool only detection yet developed respiratory AdV. For the entire cohort, 27 patients tested positive for AdV with 68% of positive AdV patients receiving serotherapy or in vivo/ex vivo T-cell depletion (TCD). Of the patients with blood and stool testing (N=79), only 5% were stool only positive and did not have serotherapy or TCD. Stool AdV testing is $799/sample. Blood AdV testing is $383/sample. Conclusion AdV incidence was higher with the addition of stool testing. The addition of AdV stool screening however had limited impact on respiratory AdV, the cause of the one AdV-related death in our cohort. Given the high association of positive AdV in patients receiving serotherapy or TCD, a risk-targeted screening strategy may be considered for a cost-effective approach.

Introduction E-cigarettes have risen in prevalence in recent years, and most public health experts agree they deliver fewer toxicants than combustible tobacco products such as cigarettes. Thus, it is important to understand how use of e-cigarettes by current smokers impacts dependence on combustible cigarettes. Methods The present study is a secondary analysis of a randomized pilot trial of e-cigarette sampling. Nontreatment seeking current smokers were randomized in a 2:1 ratio to either receive or not receive a weekly supply of e-cigarettes for 3 weeks. Participants completed the Brief Wisconsin Inventory of Smoking Dependence Motives (WISDM) scale and the cigarette purchase task before and after the sampling period and at monthly follow-up visits for 3 months. Results Individuals assigned to receive an e-cigarette had significantly lower mean WISDM scores at the end of sampling and the end of the follow-up period compared with those in the control group. Both frequency of e-cigarette use as well as nicotine concentration of the e-cigarette given to smokers were significant predictors of changes in the mean WISDM score. E-cigarette sampling significantly reduced the demand parameter Omax, which measures the maximum amount of money participants estimate they would spend on cigarettes in a single day. Conclusions These data suggest that current smokers who try using an e-cigarette may experience reductions in dependence on combustible cigarettes. Implications The present analysis suggests that providing an e-cigarette to current cigarette smokers is likely to reduce cigarette dependence, especially if the e-cigarette delivers sufficient nicotine and is used frequently.

PurposeClinical disaster medicine requires providers working collaboratively to care for multiple patients, yet many clinicians lack competency-based training. A 5-hour emergency preparedness training (EPT) curriculum was created using didactics, small group discussion, and scenario-based learning. The goal was to evaluate the effect of a short course on improving clinical-provider knowledge, confidence and skill.MethodsParticipants were enrolled in a medical university between 2011 and 2014. The course consisted of didactic lectures, small group exercises, and live mass-casualty training scenarios. Core competencies and performance objectives were developed by a task force and assessed via facilitator observation, pre- and posttesting, and a course evaluation.ResultsA total of 708 participants were trained, including 49.9% physicians, 31.9% medical students, 7.2% nurses, and 11% allied health personnel. The average percentage of correct answers increased from 39% to 60% (PConclusionA brief, intensive EPT course can improve the disaster knowledge and comfort level of a diverse group of clinical providers as well as foster disaster-performance skills. (Disaster Med Public Health Preparedness. 2018;12:121–126)

BACKGROUND: The use of ambulatory assessment to study behavior and physiology in daily life is becoming more common, yet barriers to implementation remain. Limitations in budget, time, and expertise may inhibit development or purchase of dedicated ambulatory assessment software. Research Electronic Data Capture (REDCap) is widely used worldwide, offering a cost-effective and accessible option for implementing research studies. OBJECTIVES: To present a step-by-step guideline on how to implement ambulatory assessment using REDCap and provide preliminary evidence of feasibility. METHODS: Feasibility and acceptability data are presented for randomized participants (N ranged from 19 to 36, depending on analysis) from an ongoing 8-week smoking cessation pharmacological clinical trial (ClinicalTrials.gov Identifier: NCT02737358). Participants (N = 36; 50% female) completed up to three ambulatory assessment surveys per day, depending on the phase of the study. These included self-report and video confirmation of smoking biomarkers and medication adherence. RESULTS: Participants completed 74.8% of morning reports (86.6% for study completers), 73.8% of videos confirming smoking biomarkers, and 70.4% of videos confirming medication adherence. Study completers reported that the REDCap assessments were easy to use, and 78.9% of participants preferred the REDCap assessments to traditional, paper measures. CONCLUSIONS: These data from a pharmacological trial suggest feasibility of remote data collection using REDCap. As REDCap functionality is continually evolving, it is likely that options for collecting ambulatory assessment data via this platform will progressively improve allowing for greater individualization of assessment scheduling for enhancing data collection in clinical trials.

Background As statisticians develop new methodological approaches, there are many factors that influence whether others will utilize their work. This paper is a bibliometric study that identifies and quantifies associations between characteristics of new biostatistics methods and their citation counts. Of primary interest was the association between numbers of citations and whether software code was available to the reader. Methods Statistics journal articles published in 2010 from 35 statistical journals were reviewed by two biostatisticians. Generalized linear mixed models were used to determine which characteristics (author, article, and journal) were independently associated with citation counts (as of April 1, 2017) in other peer-reviewed articles. Results Of 722 articles reviewed, 428 were classified as new biostatistics methods. In a multivariable model, for articles that were not freely accessible on the journal’s website, having code available appeared to offer no boost to the number of citations (adjusted rate ratio = 0.96, 95% CI = 0.74 to 1.24, p = 0.74); however, for articles that were freely accessible on the journal’s website, having code available was associated with a 2-fold increase in the number of citations (adjusted rate ratio = 2.01, 95% CI = 1.30 to 3.10, p = 0.002). Higher citation rates were also associated with higher numbers of references, longer articles, SCImago Journal Rank indicator (SJR), and total numbers of publications among authors, with the strongest impact on citation rates coming from SJR (rate ratio = 1.21 for a 1-unit increase in SJR; 95% CI = 1.11 to 1.32). Conclusion These analyses shed new insight into factors associated with citation rates of articles on new biostatistical methods. Making computer code available to readers is a goal worth striving for that may enhance biostatistics knowledge translation.

Pseudohyperphosphatemia due to an interaction between liposomal amphotericin B and the Beckman Coulter PHOSm assay occurs sporadically and remains underrecognized in clinical practice. This retrospective case-control study compares the incidences of hyperphosphatemia in adult inpatients exposed to liposomal amphotericin B or a triazole. A case series of patients with confirmed pseudohyperphosphatemia is described. A total of 80 exposures to liposomal amphotericin B and 726 exposures to triazoles were identified. Among subjects without chronic kidney disease and no concomitant acute kidney injury, hyperphosphatemia occurred more often during liposomal amphotericin B therapy than during triazole therapy (40% [14/35 cases] versus 10% [47/475 cases] of cases; P < 0.01; adjusted odds ratio, 5.2 [95% confidence interval {CI}, 2.3 to 11.9]). Among individuals with chronic kidney disease and no concomitant acute kidney injury, hyperphosphatemia also occurred more often during liposomal amphotericin B exposure (59% [10/17 cases] versus 20% [34/172 cases] of cases; P < 0.01; adjusted odds ratio, 6.0 [95% CI, 2.0 to 18.0]). When acute kidney injury occurred during antifungal exposure, the frequencies of hyperphosphatemia were not different between treatments. Seven episodes of unexpected hyperphosphatemia during liposomal amphotericin B exposure prompted a confirmatory test using an endpoint-based assay that found lower serum phosphorus levels (median difference of 2.5 mg/dl [range, 0.6 to 3.6 mg/dl]). Liposomal amphotericin B exposure confers a higher likelihood of developing hyperphosphatemia than that with exposure to a triazole antifungal, which is likely attributable to pseudohyperphosphatemia. Elevated phosphorus levels in patients receiving liposomal amphotericin B at institutions using the Beckman Coulter PHOSm assay should be interpreted cautiously.

The Consortium for Oral Health Research and Informatics (COHRI) is leading the way in use of the Dental Diagnostic System (DDS) terminology in the axiUm electronic health record (EHR). This collaborative pilot study had two aims: 1) to investigate whether use of the DDS terms positively impacted predoctoral dental students' critical thinking skills measured by the Health Sciences Reasoning Test (HSRT), and 2) to refine study protocols. The study design was a natural experiment with cross-sectional data collection using the HSRT for 15 classes (2013-17) of students at three dental schools. Characteristics of students who had been exposed to the DDS terms were compared with students who had not, and the differences were tested by t-tests or chi-square tests. Generalized linear models were used to evaluate the relationship between exposure and outcome on the overall critical thinking score. The results showed that exposure was significantly related to overall score (p=0.01), with not-exposed students having lower mean overall scores. This study thus demonstrated a positive impact of using the DDS terminology in an EHR on the critical thinking skills of predoctoral dental students in three COHRI schools as measured by their overall score on the HSRT. These preliminary findings support future research to further evaluate a proposed model of critical thinking in clinical dentistry.

Up-front fecal diversion can palliate emergent symptoms related to locally advanced rectal cancer (LARC) allowing patients to receive neoadjuvant chemoradiation therapy (nCRT). We analyzed outcomes of pretreatment-diverted LARC patients relative to nondiverted patients to define the impact of this management strategy. We retrospectively collected data on 103 LARC patients treated with nCRTand surgery. Medical records were reviewed for patient characteristics, staging, treatment plan, and outcomes. Thirteen LARC patients underwent pretreatment diversion for urgent symptoms and 90 LARC patients proceeded directly to nCRT. In all, 50 per cent of diverted patients presented with T4 tumor compared with 14 per cent in the nondiverted patients ( P = 0.003). Diverted patients experienced a delay in time-to-treatment initiation of 12 days, although this difference was not statistically significant. Similar rates of chemoradiation and surgical toxicities were observed. Even though diverted patients demonstrated less pathologic response to nCRT compared with nondiverted patients ( P = 0.04), there was no significant difference in overall survival. In conclusion, our study demonstrates the effectiveness of up-front fecal diversion at managing emergent obstructive symptoms related to advanced rectal cancer without additional complications, allowing patients to proceed with nCRT followed by radical surgery.

Asthma affects 5% to 10% of the population and its severity is assessed using 4 parameters: lung function, symptom frequency, rescue inhaler use, and number of asthma exacerbations. Asthma is increasingly recognized as a clinical syndrome rather than a single disease. However, the current classification system fails to reflect the heterogeneous characteristics of the disease.A retrospective chart review of 139 patients with mild, moderate, and severe persistent asthma was performed. Variables including baseline and maximal forced expiratory volume over first second (percent predicted), and age of asthma onset were used to classify patients.This yielded 5 clusters similar to Severe Asthma Research Program (SARP). Subjects in cluster 1 (n = 32) and cluster 2 (n = 47) had early-onset atopic asthma and reduced lung function but differed in medication requirement and health care utilization. Cluster 3 (n = 32) consisted of older obese women with late-onset asthma, less atopy, and mildly reduced forced expiratory volume over first second. Members of cluster 4 (n = 20) and cluster 5 (n = 8) had atopic asthma with severe obstruction but differed in bronchodilator response, age of onset, and oral corticosteroid use. Compared with SARP, our subjects were older, had a higher percentage of African Americans and obesity, and less severe asthma (P0.05). The observed clusters differed from SARP clusters in the following: (1) more frequent asthma exacerbations and medication use among cluster 1 and cluster 2; (2) lower medication use in cluster 3 and cluster 4; (3) although total health care utilization was similar, there were fewer emergency department visits in cluster 3 (P0.05).The SARP algorithm may be used to classify diverse asthmatic populations into a clinically reproducible phenotypic cluster.

Objectives To characterize antibiotic regimens utilized for bacteremic Enterobacteriaceae urinary tract infections and assess treatment failure associated with intravenous-only compared to intravenous transitioned to oral antibiotic treatment. Design Retrospective cohort. Settings Tertiary care academic medical center. Patients 241 adult patients hospitalized between July 1, 2010, and June 30, 2015, with positive blood and urine cultures with the same Enterobacteriaceae pathogen. Main Results Hospital days on antibiotics as well as length of stay were less in the group treated with any oral antibiotics (intravenous/oral, median 5 [IQR 3–7] days vs intravenous-only antibiotics 6 [4–10] days, p

With the previous norepinephrine shortage, alternative agents were required to treat patients with septic shock. This retrospective study evaluated whether the shortage of norepinephrine had an adverse effect on patients admitted to the intensive care unit with a diagnosis of severe sepsis or septic shock.This was a retrospective chart review, which compared patients who received norepinephrine versus those who did not. Eligible patients were those ≥ 18 years old who were admitted to an intensive care unit with a diagnosis of sepsis and were initiated on a vasopressor to maintain hemodynamic stability. The specific primary endpoint was whether using norepinephrine versus other vasopressors had an effect on ICU length of stay. Secondary outcomes included mortality, blood pressure, mean arterial pressure, development of renal insufficiency, and vasopressor requirements.There were 288 patients screened and 214 patients who met the inclusion criteria (norepinephrine group=106 and nonnorepinephrine group=108). After accounting for potential differences in disease severity (APACHE II score), age, weight and gender, there was no difference in ICU length of stay (p=0.4); however, the odds of survival were 5.9 (95% CI: 3.1 to 11.1) times higher for those in the non-norepinephrine group (p0.0001).Based on this retrospective analysis, patients that did not receive norepinephrine had a similar ICU LOS but had a higher rate of survival. The norepinephrine shortage did not have an adverse effect on patient outcomes.

OBJECTIVE: To identify the vitamin D status to optimize calcium and bone health in preterm infants. STUDY DESIGN: Very low birth weight infants had measurement of 25-hydroxyvitamin D status and markers of calcium and bone health from birth to term age. Piecewise linear regression modeling was performed to identify a 25-hydroxyvitamin D threshold associated with stable parathyroid hormone concentration and bone mineralization. RESULTS: In a cohort of 89 infants at term age, femur BMC and density increased linearly with 25-hydroxyvitamin D status until reaching a threshold of 48 ng/mL and 46 ng/mL, respectively. Parathyroid hormone status decreased as vitamin D status increased until reaching a plateau at 25-hydroxyvitamin D of 42 ng/mL. CONCLUSION: Preterm infant vitamin D status was significantly associated with PTH status and femur mineralization with suggestion that achieving a specific 25-hydroxyvitamin concentration is associated with optimal calcium homeostasis and femur bone mineralization.

Introduction: Approximately 70% of lung adenocarcinomas express TTF-1. EGFR mutations are present in 13-15% of Western adenocarcinoma patients. This paper investigates TTF1 as a negative predictor of mutant EGFR in lung adenocarcinomas. Results: In the pilot cohort (N = 301) two of 224 specimens positive for EGFR mutations had negative TTF-1 expression (sensitivity 99.1%, 95% confidence interval (CI) 96.8-99.9%). Estimated negative predictive values (NPV) for EGFR mutation prevalence rates of 13% and 15% are 99.5% (95% credible interval (CRI) 98.6%99.9%) and 99.4% (CRI – 98.4%-99.9%). For EGFR mutation rates of 13% and 15%, using validation cohort data (211 patients), the estimated NPVs were 97% (95% CRI 92%-99%) and 96% (95% CRI 91%-99%). Methods: Formalin-fixed paraffin-embedded tumors from lung adenocarcinoma patients were analyzed for EGFR mutations by allele-specific PCR in the ‘pilot cohort’. TTF-1 status was documented as positive or negative. Negative predictive value (NPV) for a range of true prevalence of EGFR mutation (1%-50%) was estimated using Bayesian modeling. The hypothesis was validated in a separate ‘validation’ cohort using the same modeling. Conclusion: An overwhelming majority of TTF-1 negative adenocarcinomas will be negative for EGFR mutations. This finding allows for earlier initiation of chemotherapy in newly diagnosed TTF-1 negative adenocarcinomas of the lung with stage IV disease.

Background As most smokers initiate smoking during adolescence, assessment of smoking motives that underlie trajectories of dependence is critical for both prevention and cessation efforts. In the current study, we expected participants with higher nicotine dependence would smoke (a) less for positive reinforcement (PR) and (b) more for negative reinforcement (NR) motives. We secondarily assessed the relative contribution of PR to NR motives across levels of dependence. Methods Data were drawn from a study on cue-elicited craving among occasional versus daily adolescent smokers aged 16-20 years (N = 111). Smoking motives were assessed in relation to 3 commonly used measures of nicotine dependence: (a) Fagerstrom Test for Nicotine Dependence (FTND), (b) Autonomy over Smoking Scale (AUTOS), and (c) Nicotine Dependence Syndrome Scale (NDSS). Results Compared to occasional smokers, daily smokers had significantly higher scores on each dependence measure and endorsed more prominent NR smoking motives. Each measure of nicotine dependence was strongly associated with NR motives for smoking, although measures differed in their association with PR motives. As expected, the FTND, AUTOS, and NDSS each significantly predicted smoking motive difference score (PR - NR), such that higher dependence was associated with more prominent NR motives for smoking. Conclusions Results are consistent with our understanding of dependence and provide further support for 3 common measures of nicotine dependence among early stage smokers.

This study explores the relationship of lymph node ratio (LNR) and radiotherapy (RT) to overall survival (OS) for patients with resected pancreatic cancer. The impact of adjuvant RT, number of lymph nodes (LN) resected, positive LN resected, and disease extension was also evaluated.The SEER database from 1998 to 2006 was reviewed, and 3314 patients with nonmetastatic carcinoma of the pancreas, surgical resection, examination of the regional LN, and a survival of2 months were identified. Of these, 1597 patients received RT. Cox proportional hazards regression models and the logrank test were used to determine whether specific variables were related to OS.Median OS for patients having surgery alone was 14 months (1-y survival 58.1%, 2-y survival 33.6%) and for patients having adjuvant RT was 19 months (1-y survival 73.5%, 2-y survival 41.4%), P0.001. For patients with LNR of 0%, OS was better compared with patients with any LN involvement, regardless of treatment group. Multivariable analysis found OS significantly related to LNR, total LN resected, positive resected LN, year of diagnosis, and regional extent of disease in patients without adjuvant RT. In patients who received adjuvant RT, OS significance was only persistent for LNR, the total LN resected, and positive resected LN.A higher LNR was indicative of worse OS in all patients. A strong association with improvement in OS was seen in patients having received adjuvant RT.

INTRODUCTION Although the majority of smokers are ambivalent about quitting, few treatments specifically target smokers lacking motivation to quit in the near future. Most existing interventions are instead predicated on the belief that active treatments should only be distributed to smokers interested in quitting, a largely untested assumption. METHODS In the current clinical trial (N = 157), motivated smokers wanting to quit in the next 30 days were given a 2-week nicotine replacement therapy (NRT) sample and a referral to a quitline (Group MNQ), while unmotivated smokers were randomized to receive the same treatment (Group UNQ) or a quitline referral only (Group UQ). Participants were tracked via telephone for 3 months to assess quitting behaviors and smoking reduction. RESULTS Groups significantly differed across all comparisons with regard to incidence of any quit attempt (MNQ: 77%, UNQ: 40%, UQ: 18%, p < .05) and any 24-hr quit attempts (62%, 32%, 16%, p < .05). Clinically meaningful differences emerged in the rates of floating (19%, 17%, 6%) and point prevalence abstinence (17%, 15%, 5%). Compared to participants in Group UQ (11%), a greater proportion of participants in Group MNQ (48%, p = .01) and Group UNQ (31%, p = .01) reduced their daily cigarette consumption by at least half. Proxy measures of cessation readiness (e.g., motivation) favored participants receiving active forms of treatment. CONCLUSIONS Providing NRT samples engaged both motivated and unmotivated smokers into the quitting process and produced positive changes in smoking outcomes. This suggests that motivation should not be considered a necessary precondition to receiving treatment.

Introduction Snus uptake is nominal among US smokers. This longitudinal study examines (1) perceptions of snus among US smokers given free snus for 6 weeks and (2) a method for assessment of an alternative tobacco product at the population level. Methods Adult smokers (n = 543; 69.2% female; Mage = 49.3 years), uninterested in quitting, received free snus for ad libitum use. Based on their snus use during a 6-week sampling period, participants included: (1) never users (18.4%, n = 100); (2) experimenters; that is, used ≥ once, but not during the last week of sampling (33.1%; n = 180); and (3) persistent users; that is, used ≥ once during the final week, and ≥ once during any other week of the sampling period. (48.4%; n = 263). Results Following the sampling period, those who became persistent users were more likely than experimenters to report that switching to alternative tobacco products would lower their risk for health problems (66.5% vs. 50.0%; p = .006). Persistent users also reported greater negative affect relief and craving reduction (ps < .001) than experimenters. Finally, persistent users were more likely than experimenters to describe snus in favorable terms with respect to ease of use, satisfaction, and liking (ps < .05). Conclusions Subjective experiences with snus, rather than nicotine dependence, explained experimentation versus persistent use. Even among smokers who became persistent snus users, snus was perceived as a poor substitute for cigarettes. This study design (randomized, yet naturalistic) could be extended to other novel tobacco products, including e-cigarettes, to help understand the role new products may have in the tobacco landscape. Implications This is the first large scale, US-based naturalistic assessment of smokers' reactions to snus during an extended sampling period. This study is directly in line with FDA goals to better understand predictors of initiation, uptake, and use of other tobacco products such as snus, and serves as model for assessment methods of alternative tobacco products at the population level. Most smokers tried the provided sample of snus (approximately 82%). Subjective experiences with snus, rather than nicotine dependence, explained experimentation versus persistent use. Even among smokers who became persistent snus users, snus was perceived as a poor substitute for cigarettes.

11008 Background: P is a multi-tyrosine kinase inhibitor with efficacy in many sarcoma subtypes. We designed a trial to assess the benefit of adding P to G as an alternative regimen to the commonly used combination of G+T in pts with STS (NCT01593748). Methods: We performed an open-label, randomized phase 2 trial enrolling pts with advanced non-adipocytic STS who had received prior anthracycline based therapy. Pts were assigned (1:1 stratified randomization based on leiomyosarcoma and prior pelvic radiation) to receive G 1000 mg/m2 on days 1 and 8 with P 800 mg daily or G 900 mg/m2 on days 1 and 8 and T 100 mg/m2 on day 8, repeated q 3 wks. The primary objectives were estimating median PFS and rate of grade ≥3 adverse events (AEs). Secondary objectives included estimating the hazard ratio (HR) and response rates. Cross-over was allowed for RECIST progression. Sample size of 90 was derived based on the precision of 95% confidence intervals (CI) for reporting toxicity and PFS in each arm. Results: A total of 90 pts enrolled; 45 on each arm. Pt characteristics and results are detailed in Table. Median PFS was 4.1 months for each arm (p= 0.3, based on stratified log-rank test). The clinical benefit rate (PR+SD) was 29% for each arm (p>0.99, based on Fisher’s exact test). The rate of related grade ≥3 AEs were 20.6% with G+T and 19.9% with G+P. Related grade ≥3 AEs (%) occurring in ≥10% of pts (G+T; G+P): anemia (36, 20), fatigue (29; 13), low platelets (56; 51), low neutrophils (20; 49), AST increase (2; 13) and hypertension (2; 20). Conclusions: This study demonstrates comparable efficacy between G+P and G+T, suggesting that G+P can be considered for second-line therapy in advanced non-adipocytic STS. Pt Characteristics and Results. Clinical trial information: NCT01593748. [Table: see text]

The objective of this investigation was to compare bioavailability between single oral dose Vitamin D3 (vitD3) gummies vs. tablets in healthy adults. An initial crossover, randomized clinical trial involving healthy adults (n = 9) was conducted followed by a larger, confirmatory study (n = 31). Healthy participants aged 18&ndash, 45 years with body mass index (BMI) 18&ndash, 30 without anemia or vitD deficiency were randomized to receive 20,000 international units (IU) vitD3 as single dose gummies or tablets with serial samples obtained to measure plasma vitD3 at baseline, 3, 6, 10, 24, and 48 h followed by a 2-week washout period. The same participants then crossed over to receive 20,000 IU vitD3 in the form not previously given, with sampling at the same time points. Deidentified blood samples were analyzed for vitD3 concentration by liquid chromatography (LC)-mass spectroscopy. In Study 1, results suggested bioavailability was greater with gummies compared with tablets, (effect size 1.08 at 24 h). In Study 2, the area under the concentration curve (AUC) was higher with gummies than tablets (gummy mean (95% CI): 1474 ng&middot, /mL (1393&ndash, 1555), tablet mean (95% CI): 774 ng&middot, h/mL (693&ndash, 855), p &lt, 0.0001). Average peak blood concentration (Cmax) values were significantly higher with gummies (gummy: 47.3 ng/mL, tablet: 23.4 ng/mL, p &lt, 0.0001). VitD3 gummies had greater bioavailability than tablets with higher vitD concentrations over time, which may have implications for achieving vitD sufficiency.