Wilcoxon Signed Rank Sum Test Research Articles

Comprehensive Analysis of Vascular Endothelial Growth Factor-C Related Factors in Stomach Cancer

Vascular endothelial growth factor-C (VEGF-C), which contributes to lymphatic metastasis (LM) in malignant disease, is one of the most important factors involved in physical and pathological lymphangiogenesis. Some VEGF-C related factors such as sine oculis homeobox homolog (SIX) 1, contactin (CNTN) 1 and dual specificity phosphatase (DUSP) 6 have been extensively studied in malignancies, but their expression levels and associations have still to be elucidated in stomach cancer. We detected their expression levels in 30 paired stomach cancer tissues using quantitative real-time reverse transcription-PCR (qRT-PCR). The expression and clinical significance of each factor was analyzed using Wilcoxon signed rank sum test. The correlation among all the factors was performed by Spearman rank correlation analysis. The results suggest that VEGF-C and CNTN1 are significantly correlated with tumor size, SIX1 with the age and CNTN1 also with the cTNM stage. There are significant correlations of expression levels among VEGF-C, SIX1, CNTN1 and DUSP6. There exists an important regulatory crosstalk involving SIX1, VEGF-C, CNTN1 and DUSP6 in stomach cancer.

Tracheal intubation with a flexible fibreoptic scope or the McGrath videolaryngoscope in simulated difficult airway scenarios

Flexible fibreoptic endoscopic (FFE) intubation is considered the 'gold-standard' when difficult airway management is anticipated. Several videolaryngoscopes have been developed to facilitate intubation by laryngoscopy. The aim of the study was to compare the performance of the McGrath series 5 videolaryngoscope (McGrath videolaryngoscope) and the FFE for tracheal intubation in manikins with a simulated difficult airway, hypothesizing that the McGrath videolaryngoscope intubation would prove faster than FFE intubation. A randomised controlled study. The Danish Institute for medical simulation between December 2009 and June 2010. Twenty-eight anaesthesia residents participating in the Danish mandatory 3-day airway management course. All participants received instructions and training in the use of the McGrath videolaryngoscope and FFE. The participants then performed tracheal intubation on a SimMan manikin once with the McGrath videolaryngoscope and once with the FFE in three difficult airway scenarios: (1) pharyngeal obstruction; (2) pharyngeal obstruction and cervical rigidity; (3) tongue oedema. We measured successful intubations, defined as intubation within 120 s, and time to tracheal intubation. The trachea was intubated within 120 s with the McGrath videolaryngoscope in 25 out of 27 (93%), 25 out of 28 (89%) and 18 out of 28 (64%) occasions compared with 11 out of 28 (40%), 11 out of 28 (40%) and 16 out of 28 (57%) with the FFE in scenarios (1), (2) and (3), respectively. Time to tracheal intubation was shorter with the McGrath videolaryngoscope in scenarios (1) and (2) than with the FFE (Wilcoxon signed rank sum test, P < 0.0001). The McGrath videolaryngoscope is a valuable device with higher success rate and a quicker performance in simulated difficult airways. In patients, videolaryngoscopy may have a role in difficult airway algorithms, but the optimal device has yet to be found.

Comparison of four cardiovascular risk prediction functions among Chinese patients with diabetes mellitus in the primary care setting.

To assess the feasibility, convergent validity and sensitivity of four cardiovascular risk prediction functions in Chinese diabetic patients in the primary care setting. A cross-sectional study of 1,140 diabetic patients was carried out to compare four cardiovascular risk functions, which were respectively developed from the Framingham heart study, the USA-People's Republic of China Collaborative Study of Cardiovascular and Cardiopulmonary Epidemiology cohort (PRC), the United Kingdom Prospective Diabetes Study (UKPDS) and the Joint Asia Diabetes Evaluation program (JADE). Feasibility was assessed by the percentage of patients with complete data for risk prediction. Convergent validity was measured by Spearman's rank correlation, paired Wilcoxon signed-rank sum test and Bland-Altman plots. Effect size differences between clinical risk groups were used to assess the sensitivity. Risk prediction was feasible by the Framingham, UKPDS and PRC risk functions in more than 98% patients, whereas just 74% of patients had complete data for the JADE function. The annual total coronary heart disease (CHD) risk predicted by the JADE and the UKPDS functions showed excellent agreement with no significant difference, and a correlation of 0.8048. The Framingham and the PRC functions predicted significantly lower CHD risk than those by the UKPDS and the JADE functions. The UKPDS and the Framingham functions were more sensitive in differentiating clinical risk groups. The UKPDS risk engine showed good feasibility, convergent validity and sensitivity in predicting CHD risk in Chinese diabetic patients. The JADE function showed excellent agreement with the UKPDS risk engine, but it was less feasible in the primary care setting.

Application of three kinds of non-invasive positive pressure ventilation as a primary mode of ventilation in premature infants with respiratory distress syndrome: a randomized controlled trial

Non-invasive positive pressure ventilation has increasingly been chosen as the primary ventilation mode in respiratory distress syndrome (RDS) in preterm infants. In order to further understand the application of various non-invasive positive pressure ventilation modes, we compared the advantages and disadvantages of three modes as a primary mode of ventilation in premature infants with RDS. From December 2011 to March 2013, 107 preterm infants with RDS who received intubation-pulmonary surfactant (PS) -extubation in our NICU were randomly divided (by means of random number table) into three groups based on the primary mode of ventilation: nasal continuous positive airway pressure [NCPAP, n = 39, male/female ratio was 27/12, mean gestational age (GA) was (32.0 ± 2.1)weeks, mean birth weight (BW) was (1752 ± 457)g], bi-level positive airway pressure [BiPAP, n = 35, male/female ratio was 25/10, GA was (31.4 ± 2.0) weeks, BW was (1530 ± 318) g], and synchronized bi-level positive airway pressure [SBiPAP, n = 33, male/female rate was 25/8, GA was (31.5 ± 2.2) weeks, BW was (1622 ± 447) g]. Ventilation settings including FiO(2) were adjusted according to transcutaneous SPO(2) monitoring or blood gas analysis. Various settings and adverse events were recorded as well. The main parameter was the FiO(2) at 24 h post-positive-pressure ventilation. Statistical analyses were performed using χ(2) test, rank sum test, one-way analysis of variance for least-significant difference value, paired-sample t-test, two related sample Wilcoxon signed rank sum test and Logistic regression. The PaCO(2) (mmHg, 1 mmHg = 0.133 kPa), oxygen index (OI) at 12-24 h, and FiO(2) at 24 h post-ventilation in BiPAP and SBiPAP groups were lower than that in NCPAP groups with significant difference (44 ± 9 and 45 ± 9 vs. 50 ± 9, 2.76 ± 0.96 and 2.79 ± 0.60 vs. 3.24 ± 0.72, 0.34 ± 0.10 and 0.35 ± 0.07 vs. 0.39 ± 0.07; F = 4.456, 5.146 and 4.123; P = 0.014, 0.007 and 0.019, respectively). There was no significant difference between BiPAP and SBiPAP groups. There was no significant difference among three groups (all P > 0.05) in the following events: respiratory index (RI) at 12-24 h post-ventilation, abdominal distension, period of non-invasive ventilation, ratio of intubation for invasive ventilation if failed noninvasive ventilation, air-leak syndrome, neonatal necrotizing enterocolitis, periventricular-intraventricular haemorrhage, bronchopulmonary dysplasia, retinopathy of prematurity, mortality rate after 36 h of age or rate of abandon for discharge. The independent risk factors for failure of non-invasive positive pressure ventilation were gender, gestational age, antepartum steroid at 24 h before birth to 7 d, and birth weight, with the OR (95% confidence interval) being 14.120 (1.135, 175.662), 2.862 (1.479, 5.535), 61.084 (3.115, 1 198.031), and 8.306 (1.488, 46.383), respectively. As the primary mode of ventilation in premature infants with RDS, both BiPAP and SBiPAP are more beneficial than NCPAP in improving oxygenation and reducing CO(2) retention without increasing the incidence of adverse events.

Effect of time on electronic working length determination with a novel endodontic module in preclinical endodontic training

Aim: To evaluate electrical conductivity of the medium provided with ModuPRO endodontic modules, and compare it with those of alginate and vinyl polysiloxane impression materials over varying time intervals. Materials and Methods: A 24 Real Endo-t teeth were mounted in the ModuPRO Endo™ modules using three different mounting media [Groups A (Apex Putty), B (alginate), C (extra-light body vinyl polysiloxane)]. The working lengths were predetermined by microscopy, and the root canals were prepared with ProFile rotary instruments before mounting. Working lengths were checked with an electronic apex locator at 24 and 48 hours; 1, 4, and 6 weeks; and 6 months. Data were analyzed using one-way analysis of variance (ANOVA), the Tukey-Kramer multiple comparison tests, and the Wilcoxon Signed Rank Sum test, with significance set at P Results: Group C showed higher measurements and significant differences from groups A and B for up to 6 weeks (P 0.05). After 6 months, all groups showed significantly higher working lengths from those predetermined, but no statistically significant differences were observed among them (P > 0.05). For all groups, differences from predetermined working lengths were lowest at the 1-week interval. Conclusions: Both alginate and the Apex Putty can be used for determining the working lengths using an apex locator over a longer time period. Our study has shown that ModuPRO Endo™ modules, along with the Apex Putty, are effective tools for teaching working length determination with apex locators in preclinical endodontic training.

Do Privatisation Model, Contractual and Institutional Factors Play Any Role in Infrastructure Post-privatisation Efficiency? Exploring Port Concessions in Nigeria

Privatisation is often seen as the key to achieving efficiency in infrastructure service delivery. In most cases, however, the model of privatisation and the right institutional environment under which they perform best are ignored in addressing the privatisation-to-efficiency debate. Recognising this, we seek to underscore the contractual and institutional factors influencing infrastructure post-privatisation efficiency in Landlord port models as applied in Nigeria’s port reform. In so doing, the study explores the Landlord port privatisation model in Nigeria. The paired t-test and Wilcoxon signed rank sum test are employed to determine if there are significant improvements in port output (general cargo throughput, liquid bulk throughput, number of vessels, gross registered tonnage and container traffic) and efficiency (average waiting time, turnaround time, berth occupancy rate) proxies between the pre-concession, transition and post-concession periods in Nigeria. The result of these tests indicates that although there are significant improvements in the port output proxies, efficiency in the port did not improve significantly. The study identified lack of appropriate legal framework, weak regulatory capacity, absence of efficiency targets in concession contract and non-adherence to investment targets as the major constraints to efficiency gain in the Landlord port model.

Role Of Aggressive Chemotherapeutic Regimens In Double Hit Lymphoma- Can Alternate Aggressive Induction Regimens Overcome The Poor Prognosis Of Diffuse Large B Cell Lymphoma?

BackgroundDouble-hit (DH) diffuse large B cell lymphomas (DLBCL), characterized by concurrent translocations involving MYC and BCL2, or BCL6, portend to have an aggressive clinical course. Recent studies have highlighted the fact that DH lymphomas are resistant to standard R-CHOP or experience a short disease free interval. There is however limited data evaluating patient outcomes with alternative therapy that include aggressive regimens often used to treat high grade lymphoma. MethodsFive hundred sixty patients (pts) diagnosed with DLBCL at a single institution between January 2004 and December 2012 were included in our analysis after obtaining IRB approval. Descriptive statistics, Wilcoxon signed rank sum test and Kaplan-Meier analysis were performed using SPSS.19 software. ResultsOf the 560 pts, 34 were confirmed as DH based on FISH analysis. The median age at diagnosis was 63 yrs (range 36-87). Twenty pts (59%) were male. Thirty-one pts (91%) were Caucasian. Fourteen pts (53%) had an Eastern Cooperative Oncology Group performance status of 2-3. Thirty pts (89%) had advanced stage disease (stages III and IV). Thirteen pts (38%) had bone marrow involvement, and twenty-six pts (76%) had more than one extranodal site. The majority of pts (70%) had high intermediate or high risk based on the International Prognostic Index (IPI). Of the 34 pts, 15 (46%) received R-CHOP, 6 (18%) received R-Hyper CVAD/Ara-C/MTX, 8 (24%) received DA-R-EPOCH and 2 (6%) received other aggressive forms of chemotherapy. Two pts died before any therapy was initiated. Ten pts (29%) received central nervous system prophylaxis. Five pts (15%) underwent stem cell transplant, 2 of which in CR1. Twenty-eight pts (82%) were alive at the time of analysis. At a median follow up of one year, the median overall survival (OS) of all pts was 12.2 months. The median OS was 16.8 months for pts who received R-CHOP and 12.2 months for pts receiving other aggressive chemotherapy (P=0.07) (figure 1). The progression free survival for pts who received R-CHOP was 32.6 months as compared with 7.6 months in pts treated with R-hyper CVAD/Ara-C/MTX or DA-R-EPOCH. This was not statistically significant (P=0.44) (figure 2). In addition, there was no significant difference in disease free interval between the two groups of patients. [Display omitted] [Display omitted] ConclusionOur data suggests that prognosis of patients with DH-DLBCL remains poor independently of the chemotherapy administered, whether conventional R-CHOP or more aggressive regimens such as R-HyperCVAD or DA-R-EPOCH. Durable long term remission with R-CHOP is still possible in a minority of patients. There is a need to modify and incorporate novel agents in the initial treatment strategy for DH-DLBCL. Disclosures:No relevant conflicts of interest to declare.

Pilot study of proton therapy for treatment of regional lymphatics in patients with breast cancer.

100 Background: To determine the feasibility of proton therapy (PT) for regional nodal irradiation (RNI) in women with breast cancer and to compare target coverage and normal tissue avoidance between PT and conventional radiation. Methods: From May 2012 to May 2013, 14 women were prospectively enrolled in this pilot study; 5 had right-sided and 9 had left-sided. Median age at the time of PT was 53.7 years (range 37-73). The breast or chest wall and supraclavicular, axillary, and internal mammary (IM) lymph nodes were treated in all patients. Proton and conventional plans were developed for each patient; the superior plan, as defined by organ at risk sparing and target coverage, was treated. Targets and normal tissues were delineated on treatment CT scans. Wilcoxon signed rank sum test was used to compare dose-volume parameters. Results: For all 14 patients, the proton plan better met the dosimetric goals, and was used for treatment delivery. Median heart V5 measured 0.8% for the proton plans versus 23% for the conventional plans (p=0.0005). Median mean heart dose measured 0.55 Gy (range 0– 3.2Gy) for the proton plans versus 4.9 Gy (range 2-9.1 Gy) for the conventional plans (p=0.0005). Significant difference in median lung V5 and median V20 were found: 41% and 24% for the proton plans and 67% and 38% for conventional plans, respectively. PTV breast/chest wall coverage was adequate with both plans. Coverage of the level II axilla was higher in the proton plans (D95 48 Gy vs 44 Gy, p=0.01) as was coverage of the IM nodes (D95 50 Gy vs 46 Gy, p=0.01). Acute toxicity data is available for 12 patients. The most common acute toxicity was radiation dermatitis, with 9 patients experiencing grade 2 and 3 patients experiencing grade 3 toxicity. Other grade 2 toxicities included fatigue (n=3), pain (n=2), esophagitis (n=4), and skin infection (n=1). Radiation dermatitis was the only grade 3 toxicity. No grade 4 or 5 toxicities developed. Conclusions: Adjuvant PT is a well-tolerated, technically feasible modality for RNI, with a significant decrease in cardiac V5, V20, and mean heart dose as well as lung V5 and V20. Further investigation of PT for RNI in breast cancer is warranted to improve the therapeutic ratio by decreasing radiation exposure to the heart and lung. Clinical trial information: NCT01365845.

Lapatinib impact on pulmonary hypertension.

160 Background: Pulmonary Arterial Hypertension (PAH) and cancer share growth factor and protein kinase signaling pathways that result in smooth muscle cell proliferation and vasculopathy. A number of tyrosine kinase inhibitors (TKI) have been developed for the treatment of cancer, and some of these like Imatinib have been investigated in PAH. There is little known about the impact of other TKI on the pulmonary vasculature. After reporting a case of lapatinib-induced PAH that reversed after withdrawal of the drug, we investigated the association of lapatinib with the development of PAH in our institution. Methods: A retrospective chart review was conducted, in accordance with IRB protocol, of all patients treated with lapatinib over the past five years at our institution. Patients who had undergone 2-D echocardiogram both prior to and after treatment were included in the analysis. Systolic Pulmonary Artery Pressures (PASP), right-sided chamber dilation and function, TAPSE were each evaluated. Through chart review, patients were evaluated in terms of risk factors for non-Group 1 PAH. A Wilcoxon signed-rank sum test was used to compare the changes in PASP before and after the initiation of lapatinib. Results: A total of 27 patients were found to have 2-D echo done before and after starting treatment with lapatinib. All patients had normal PASP before starting treatment. Eight patients developed elevated PASP following treatment. Two patients had evidence of left-sided heart disease felt to contribute to their elevated pressures, while the remaining 6 patients had no evidence for Group 2 (associated with left heart disease), 3 (associated with lung disease or hypoxemia) or chronic thromboembolic PAH. Right heart catheterization was available in one patient, confirming the diagnosis of PAH. The median pre-treatment and post treatment PASP in those 6 patients was 29.5 mmHg and 65.5 mmHg respectively (N=6; p = 0.03). Conclusions: Lapatinib is a TKI with a selective inhibition to EGFR and HER2, approved by FDA in 2007 as a second line agent in advanced breast cancer. Given the potential of TKIs as anti-proliferative agents in PAH, a number are currently under study, but little is yet known. This is the first study in the literature to show that PAH is a potential side effect of lapatinib.

일 지역 노인의 인플루엔자와 폐구균 예방접종 실태 및 인지도 차이비교

Purpose: The purpose of this study was to investigate differences in vaccination status and awareness between influenza and pneumococcal vaccinations in the elderly. Methods: This cross-sectional study was used with a questionnaire. Data were collected from 107 older people over 65 years registered at one community center in December, 2012. The data were analysed with Chi-square, Fisher's exact-test, Wilcoxon Signed rank sum test, Mann-Whitney U test, and Kruskall-Wallis test. Results: There were significant differences in the experiences of vaccination and reason for unvaccination by vaccine types. The mean scores for awareness of vaccination were 1.81 (range 0~3) in influenza and 1.50 in pneumococcus (range 0~3). There was a significant difference in awareness by vaccine types (Z=6.12, p<.001). There was a positive association between influenza and pneumococcal vaccination awareness (rho=.236, p=.014). Conclusion: This study showed different vaccination status and awareness in vaccine types. It is necessary to consider vaccination status and awareness by vaccine types of the target population in the education program related to vaccination.

A Novel Website to Prepare Diverse Older Adults for Decision Making and Advance Care Planning: A Pilot Study

ContextWe have reconceptualized advance care planning (ACP) as a multistep process focused on preparing patients with skills needed for communication and in-the-moment decision making. ObjectivesTo operationalize this paradigm, we created an easy-to-use ACP website (prepareforyourcare.org) based on a theoretical framework of behavior change and pilot-tested its efficacy to engage older adults in ACP. MethodsAt baseline and 1 week after viewing the PREPARE website, we assessed behavior change in ACP by using a validated survey that includes Process Measures (knowledge, contemplation, self-efficacy, and readiness, 5-point Likert scales) and Action Measures (yes/no whether an ACP behavior was completed). We also assigned participants into behavior change stages (i.e., precontemplation, contemplation, preparation, action, maintenance) and determined the percentage of participants who moved from precontemplation at baseline to higher stages at 1 week. We also assessed PREPARE ease-of-use (10-point scale, 10 being the easiest). Changes were assessed with Wilcoxon signed rank sum tests and McNemar’s tests. ResultsMean age of the participants was 68.4 years (SD 6.6), and 65% were nonwhite. Behavior Change Process Measures average Likert scores increased from 3.1 (0.9) to 3.7 (0.7), P < 0.001. Action Measures did not change significantly. However, precontemplation significantly decreased for most actions (e.g., talking to doctor about desired medical care, 61% to 35%, P < 0.003), with a mean decrease of 21% (range, 16%-33%). PREPARE was rated a nine of ten (±1.9) for ease-of-use. ConclusionA new, patient-centered ACP website that focuses on preparing patients for communication and decision making significantly improves engagement in the process of ACP and behavior change. A clinical trial of PREPARE is currently underway.

Primed low‐frequency repetitive transcranial magnetic stimulation and constraint‐induced movement therapy in pediatric hemiparesis: a randomized controlled trial

The aim of this study was to determine the feasibility and efficacy of five treatments of 6 Hz primed, low-frequency, repetitive transcranial magnetic stimulation (rTMS) combined with constraint-induced movement therapy (CIMT) to promote recovery of the paretic hand in children with congenital hemiparesis. Nineteen children with congenital hemiparesis aged between 8 and 17 years (10 males, nine females; mean age 10 years 10 months, SD 2 years 10 months; Manual Ability Classification Scale levels I-III) underwent five sessions of either real rTMS (n=10) or sham rTMS (n=9) alternated daily with CIMT. CIMT consisted of 13 days of continuous long-arm casting with five skin-check sessions. Each child received a total of 10 hours of one-to-one therapy. The primary outcome measure was the Assisting Hand Assessment (AHA) and the secondary outcome variables were the Canadian Occupational Performance Measure (COPM) and stereognosis. A Wilcoxon signed-rank sum test was used to analyze differences between pre- and post-test scores within the groups. Analysis of covariance was used to compute mean differences between groups adjusting for baseline. Fisher's exact test was used to compare individual change in AHA raw scores with the smallest detectable difference (SDD) of 4 points. All participants receiving treatment finished the study. Improvement in AHA differed significantly between groups (p=0.007). No significant differences in the secondary outcome measures were found. Eight out of 10 participants in the rTMS/CIMT group showed improvement greater than the SDD, but only two out of nine in the sham rTMS/CIMT group showed such improvement (p=0.023). No serious adverse events occurred. Primed, low-frequency rTMS combined with CIMT appears to be safe, feasible, and efficacious in pediatric hemiparesis. Larger clinical trials are now indicated.

Reduced lung dose and improved inspiration level reproducibility in visually guided DIBH compared to audio coached EIG radiotherapy for breast cancer patients

Introduction. Patients with left-sided breast cancer with lymph node involvement have routinely been treated with enhanced inspiration gating (EIG) for a decade at our institution. In a transition from EIG to deep inspiration breath hold (DIBH) we compared the two techniques with focus on target coverage, dose to organs at risk and reproducibility of the inspiration level (IL). Material and methods. Twenty-four patients were computed tomography (CT) scanned with EIG and DIBH. For DIBH we used visual feedback and for EIG audio coaching, both during scan and treatment. Treatment plans for 50 Gy over 25 fractions were calculated. Seventeen of the patients were included in the analysis of reproducibility. They were audio coached for one minute before beam-on in DIBH at nine treatment sessions. These respiration curves were analysed with average maximum IL and standard deviation (SD) for the EIG part of the respiratory signal, and mean IL and SD for the DIBH. Comparison of dosimetric and respiration parameters were performed with the Wilcoxon signed rank-sum test. Results. In DIBH, the ipsilateral lung volume increased further compared to EIG (p < 0.0004, mean increase 11%). This lead to a 9% mean reduction (p = 0.002) of the ipsilateral lung volume receiving 20 Gy (V20 Gy). We found no other significant dosimetric differences between the two methods. The reproducibility of the IL was better with the DIBH method, observed as a significantly smaller SD in most patients (p < 0.04 for 16 of 17 patients). Conclusion. The DIBH method resulted in a significantly larger lung volume and lower ipsilateral lung V20 Gy compared to EIG. The IL for visually guided DIBH was more reproducible than audio-coached EIG. Based on these findings, the DIBH technique is our new breathing adaptation standard for radiotherapy of patients with left-sided breast cancer with lymph node involvement.

EPITOME-4, an open-label phase 3b study evaluating a new formulation of epoprostenol sodium in Japanese pulmonary arterial hypertension patients following switch from Flolan

Rationale: Intravenous epoprostenol sodium with glycine and mannitol excipients (Flolan®) is an agent used for the treatment of pulmonary arterial hypertension (PAH). A new epoprostenol sodium formulation with arginine and sucrose excipients (epoprostenol AS), improving stability at room temperature, has been developed to improve quality of life for patients. The primary objective was to evaluate safety and tolerability of switching from Flolan® to epoprostenol AS. Methods: This was a two-site, open label, single-arm phase 3b study. Eight adult Japanese PAH patients treated with Flolan® on a stable dose were switched to epoprostenol AS, and followed for 12 weeks. Changes from baseline to 12 weeks were evaluated for hemodynamic parameters, measured at baseline, immediately after switching and after 12 weeks. Patient treatment satisfaction was assessed by the Treatment Satisfaction Questionnaire for Medication (TSQM-9). Results: The mean (range) age was 48 (25–69) years and 7 patients were female. The mean (range) time since PAH diagnosis was 6.2 (0.6–13.9) years. There were no unexpected safety or tolerability concerns after switching from Flolan® to epoprostenol AS up to Week 12. The dosage of the study treatment was maintained after switching (Table). In terms of pulmonary hemodynamics, the Wilcoxon signed rank sum test did not reveal any significant differences in change from baseline to immediately after switching or to Week 12 at the 5% level (Table). Treatment satisfaction as assessed by TSQM-9 showed a significant improvement in terms of convenience (51.40±10.19 at baseline versus 58.33±12.96 at week 12, p < 0.05). Epoprostenol AS dose and hemodynamics at Conclusions: Switching from Flolan® to epoprostenol AS at the same dosage was well tolerated up to Week 12, and pulmonary hemodynamics were maintained. In addition, patient treatment satisfaction appeared to be improved with use of epoprostenol AS.

Neurological Outcome Scale for Traumatic Brain Injury: III. Criterion-Related Validity and Sensitivity to Change in the NABIS Hypothermia-II Clinical Trial

The neurological outcome scale for traumatic brain injury (NOS-TBI) is a measure assessing neurological functioning in patients with TBI. We hypothesized that the NOS-TBI would exhibit adequate concurrent and predictive validity and demonstrate more sensitivity to change, compared with other well-established outcome measures. We analyzed data from the National Acute Brain Injury Study: Hypothermia-II clinical trial. Participants were 16-45 years of age with severe TBI assessed at 1, 3, 6, and 12 months postinjury. For analysis of criterion-related validity (concurrent and predictive), Spearman's rank-order correlations were calculated between the NOS-TBI and the glasgow outcome scale (GOS), GOS-extended (GOS-E), disability rating scale (DRS), and neurobehavioral rating scale-revised (NRS-R). Concurrent validity was demonstrated through significant correlations between the NOS-TBI and GOS, GOS-E, DRS, and NRS-R measured contemporaneously at 3, 6, and 12 months postinjury (all p<0.0013). For prediction analyses, the multiplicity-adjusted p value using the false discovery rate was <0.015. The 1-month NOS-TBI score was a significant predictor of outcome in the GOS, GOS-E, and DRS at 3 and 6 months postinjury (all p<0.015). The 3-month NOS-TBI significantly predicted GOS, GOS-E, DRS, and NRS-R outcomes at 6 and 12 months postinjury (all p<0.0015). Sensitivity to change was analyzed using Wilcoxon's signed rank-sum test of subsamples demonstrating no change in the GOS or GOS-E between 3 and 6 months. The NOS-TBI demonstrated higher sensitivity to change, compared with the GOS (p<0.038) and GOS-E (p<0.016). In summary, the NOS-TBI demonstrated adequate concurrent and predictive validity as well as sensitivity to change, compared with gold-standard outcome measures. The NOS-TBI may enhance prediction of outcome in clinical practice and measurement of outcome in TBI research.

Evaluation of Treatment Tolerability, Satisfaction and Laboratory Parameters in HIV+ Patients Switching from Ritonavir Capsule to Tablet Formulation§

This study evaluated treatment satisfaction, gastrointestinal tolerability, depressive symptoms and alterations in laboratory parameters before and after switching from ritonavir capsule to tablet formulation. HIV+ adults switching from ritonavir capsules to tablets were eligible for the study. The HIV Treatment Satisfaction Questionnaire (HIVTSQ), Gastrointestinal Symptom Rating Scale (GSRS) and CES-D Depression inventory were self-administered before, and 3-4 months after switching. Results of laboratory tests within three months of each questionnaire were collected. A subset underwent plasma drug level sampling. Wilcoxon signed rank sum test was used for comparison of continuous variables and McNemar's test for dichotomised data. Most of the 71 participants were Caucasian men, median age 51 years. Participants were taking ritonavir in combination with either atazanavir (n=48 [67.6%]), darunavir (n=18 [25.4%]), fosamprenavir (n=3 [4.2%]) or saquinavir (n=2 [2.8%]). In general after the switch to tablets, participants reported improved treatment satisfaction (median [interquartile range] HIVTSQ score 53/60 [48, 58] after vs 49/60 [45, 54] before, p <0.001), fewer gastrointestinal symptoms (GSRS score 4/45 [1, 9] vs 5/45 [3,13], p < 0.001) and had higher HDL cholesterol (1.22 mmol/L [1.07, 1.45] vs 1.09 mmol/L [0.90,1.32], p = 0.003) and lower total cholesterol/HDL ratio (3.82 [3.05, 4.40] vs 4.23 [3.45, 4.84], p<0.001). There were no significant changes in plasma viral load, CD4 counts, depression scores, or atazanavir or ritonavir trough levels. Results of this study suggest that the newer tablet formulation of ritonavir is better tolerated and has fewer gastrointestinal side effects than the older capsule formulation.

Use of intravaginal 17-β estradiol to improve sexual function and menopausal symptoms in postmenopausal women with breast cancer on aromatase inhibitors.

9610 Background: The majority of women with early stage breast cancer (BC) will become long-term survivors, living with the sequelae of treatment. Attention to symptoms and quality of life (QoL) are therefore of increasing importance both during treatment and survivorship. Aromatase inhibitors (AIs) are used to treat postmenopausal women with hormone-receptor positive (HR+) BC and can lead to profound urogenital atrophy. Atrophic vaginitis in BC survivors is prevalent, its management is complex and it negatively impacts QoL. Methods: A prospective longitudinal IRB-approved study was performed at MSKCC in26 postmenopausal women with stage I-III HR+ BC on adjuvant letrozole or anastrozole for at least 3 months and had urogenital atrophy. All women were initiated on 10µg intravaginal 17-β estradiol. Patients completed the Female Sexual Function Index (FSFI) and Menopausal Symptom Checklist (MSCL) at baseline and wks 12 &amp; 24. Increase in FSFI score means better sexual function and a decrease in MSCL score means improved symptoms. We used the Wilcoxon Signed Rank Sum test to compare QoL measures at baseline to wks 12 and 24. The primary endpoint was change in systemic estradiol level from baseline to wk 12. Serial estradiol/FSH levels were measured at baseline and wks 2, 7, 12, 18 &amp; 24; we used a highly sensitive estradiol radioimmunoassay, ESTR-US-CT, from Cisbio US, Inc. Herein we report the results from the QoL secondary endpoints. Results: During treatment with intravaginal 17-β estradiol 10mcg, improvement in sexual function as measured by the FSFI was seen from a median of 12.4 at baseline to 21.2 at wk 12 (p=.0091) and 21.8 at wk 24 (p=.0271). Improvement was seen from baseline to wk 12 in lubrication (p=.0091), desire (p=.0303), satisfaction (p=.0331) and pain (p=.0005) and from baseline to wk 24 in lubrication (p=.0210), desire (p=.0309) and orgasm (p=.0369). A reduction in menopausal symptoms was also seen from 30.0 at baseline to 23.6 at wk 12 (p=.01) and 22.5 at wk 24 (p=.003). Conclusions: Intravaginal 10μg 17-β estradiol provided relief from menopausal symptoms and improvement in sexual dysfunction in the domains of lubrication, desire, satisfaction, orgasm, and pain.

Abstract 1783: Examination of the chemoresistant subpopulation in ovarian cancer identifies DNA repair genes contributing to survival after primary therapy.

Abstract Background: Although the majority of patients with advance stage epithelial ovarian cancer respond to platinum and taxane-based chemotherapy, most patients ultimately develop recurrent disease, demonstrating that a select subpopulation of cancer cells is capable of surviving this initial challenge. Tumor heterogeneity makes identification of genes most relevant to this process difficult. A comparison of matched primary tumors and tumors still present after initial chemotherapy could shed light onto which genes are contributing to survival after primary therapy. DNA repair pathways may be important in this process. Methods: After IRB approval, 45 patients were identified in whom both primary and secondary (recurrent) tumor samples were collected. For 12 of these, the recurrent tumor was collected immediately at the completion of primary therapy, therefore representing the population that survived chemotherapy and referred to as “persistent disease”. Tumor cells were extracted from FFPE slides by laser capture microdissection and subjected to a qPCR array consisting of 84 genes participating in DNA damage response and repair (SA Biosystems, Qiagen). Gene expression was compared between the two samples, and select genes identified as significantly different were validated with qPCR. Expression of genes of interest was also examined in 3 pairs of matched chemosensitive/chemoresistant ovarian cancer cell lines: A2780/A2780cp55, HeyA8/HeyA8MDR, and SKOV3ip1/SKOV3TRip2 both at baseline, and with 24-hour exposure to carboplatin. Levels of gene expression were compared with the Wilcoxon signed-rank sum test for non-parametric data, and the student's t-test for normally distributed data. Results: Of 84 genes evaluated in the DNA repair pathway array, 7 were significantly different (p&amp;lt;0.05) between the primary and persistent patient tumors: SUMO1, CDKN1A (p21), Microcephalin 1, DDB2, HUS1, RAD9A, and APEX1. Additionally, trends towards significance (p&amp;lt;0.10) were noted by overexpression in DDB1, RAD18, XRCC3, PARP1, and BARD1; and reduced expression of MSH2 and ATRX. Trends seen in BARD-1, APEX1 and ATRX were mirrored in the highly cisplatin-resistant cell lines. Decreased expression of MSH2 was mirrored in the taxane-resistant lines compared to the parental lines, suggesting a role for MSH2 in taxane resistance. Short-term treatment of parental A2780ip1 confirmed that BARD1 is induced by exposure to carboplatin. Conclusions: We have identified several genes participating in DNA repair pathways that may contribute to survival of primary therapy in epithelial ovarian cancer. Such genes might be targeted for downregulation in an attempt to overcome the ability of cancer cells to repair DNA damage induced by chemotherapy and reduce rates of relapsed disease. Citation Format: Britt K. Erickson, Adam D. Steg, Zach C. Dobbin, Ashwini A. Katre, Ronald D. Alvarez, Charles N. Landen. Examination of the chemoresistant subpopulation in ovarian cancer identifies DNA repair genes contributing to survival after primary therapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1783. doi:10.1158/1538-7445.AM2013-1783

Observer Variability of an Angiographic Grading Scale Used for the Assessment of Intracranial Aneurysms Treated with Flow-Diverting Stents

Novel angiographic grading scales for the assessment of intracranial aneurysms treated with flow-diverting stents have been recently developed because previous angiographic grading scales cannot be applied to these aneurysms. The purpose of this study was to evaluate the inter- and intraobserver variability of the novel O'Kelly Marotta grading scale, which was developed specifically for the angiographic assessment of aneurysms treated with flow-diverting stents. Multiple raters (n = 31) from the disciplines of neuroradiology and neurosurgery were presented with pre- and posttreatment angiographic images of 14 aneurysms treated with intraluminal flow diverters. Raters were asked to classify pre- and posttreatment angiograms by using the OKM grading scale. Statistical analyses were subsequently performed with calculation of a generalized multirater κ statistic for assessment of inter- and intraobserver variability and by performing a Wilcoxon signed rank sum test for assessment of group differences. Variability analysis of the OKM grading scale yielded substantial (κ = 0.74) and almost perfect (κ = 0.99) inter- and intraobserver agreement, respectively, with no statistically significant differences between raters with a background of neuroradiology versus neurosurgery or attending physician versus trainee. The OKM grading scale for the assessment of intracranial aneurysms treated with flow-diverting stents is a reliable grading scale that can be used equally well by users of varying backgrounds and levels of training. Comparison with interobserver variability of pre-existing angiographic grading scales shows equal or better performance.

Impact of school-based oral health education program on oral health of 12 and 15 years old school children

Background:Health education for the school age child is a specialized field within the broad discipline of education. Oral health education program are educational aspects of any curative, preventive and promotional health activity.Aim:The study has been undertaken to evaluate the impact of oral health education on the status of plaque, gingival health and dental caries among 12 and 15 years old children attending government school in Shimla city.Materials and Methods:Two hundred and seventy six school children participated in the study. The study was conducted over a period of 4 months from May 2010 to August 2010 in Government Senior Secondary School, Sanjauli. Plaque, gingival and caries status was assessed by using Silness and Loe plaque index, Loe and Silness gingival index and WHO modified DMFT index, respectively. Data was analyzed using the software SPSS version 15. Paired t-test and Wilcoxon signed rank sum test were used appropriately for statistical comparisons. P value ≤0.05 was considered statistically significant.Results:Overall mean plaque score and gingival score decreased significantly after oral health education irrespective of gender. However, decrease in plaque score among 15 years old female children and gingival scores among 12 and 15 years old female subjects was not significant. Difference in mean caries status was statistically insignificant among all the subjects.Conclusion:Short term oral health education program may be useful in improving oral hygiene and gingival health. Coordinating efforts should be enhanced between school personnel, parents and health professionals to ensure long-term benefits of such program.