Phase 2 Study of Concurrent Cetuximab Plus Definitive Thoracic Radiation Therapy Followed by Consolidation Docetaxel Plus Cetuximab in Poor Prognosis or Elderly Patients With Locally Advanced Non-Small Cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dilling, Thomas J.; Extermann, Martine; Kim, Jongphil

Background: Recursive partitioning analysis has shown that Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≥2, male sex, and age ≥70 years are prognostic of poor outcome in locally advanced non-small cell lung cancer (LA-NSCLC) patients. Concurrent chemoradiation therapy (CRT) improves survival, but toxicity is a concern in this frail patient cohort. We therefore opened this trial of concurrent definitive thoracic radiation therapy (XRT) and cetuximab, followed by consolidation docetaxel plus cetuximab. Methods and Materials: Eligible patients had pathologically proven, unresectable LA-NSCLC (stage IIA-“dry” IIIB). They had ECOG PS 2 or weight loss ≥5% in 3 months or were aged ≥70 years. Themore » primary objective was progression-free survival (PFS). Secondary objectives included overall survival (OS) and overall response rate (ORR). Results: From May 2008 to November 2010, a total of 32 patients were evaluated in our single-institution, institutional review board–approved prospective clinical trial. Three patients were screen failures and 2 more withdrew consent before treatment, leaving 27 evaluable patients. One was removed because of poor therapy compliance, and 2 were taken off trial because of grade 3 cetuximab-related toxicities but were followed up under intent-to-treat analysis. The median follow-up and OS were 10.5 months. The median PFS was 7.5 months. The ORR was 59.3%. Eight early/sudden deaths were reported. Upon review, 6 patients developed severe pulmonary complications. Conclusions: Patients enrolled in this trial had improved OS compared with poor-PS historical controls (10.5 vs 6.4 months) and comparable OS to good-PS historical controls (10.5 vs 11.9 months) treated with XRT alone. However, pulmonary toxicity is a concern. Consolidative cetuximab/docetaxel, in conjunction with high-dose radiation therapy, is a putative cause.« less

Preoperative chemoradiation with paclitaxel-carboplatin or with fluorouracil-oxaliplatin-folinic acid (FOLFOX) for resectable esophageal and junctional cancer: the PROTECT-1402, randomized phase 2 trial.

PubMed

Messager, Mathieu; Mirabel, Xavier; Tresch, Emmanuelle; Paumier, Amaury; Vendrely, Véronique; Dahan, Laetitia; Glehen, Olivier; Vasseur, Frederique; Lacornerie, Thomas; Piessen, Guillaume; El Hajbi, Farid; Robb, William B; Clisant, Stéphanie; Kramar, Andrew; Mariette, Christophe; Adenis, Antoine

2016-05-18

Often curative treatment for locally advanced resectable esophageal or gastro-esophageal junctional cancer consists of concurrent neoadjuvant radiotherapy and chemotherapy followed by surgery. Currently, one of the most commonly used chemotherapy regimens in this setting is a combination of a fluoropyrimidin and of a platinum analogue. Due to the promising results of the recent CROSS trial, another regimen combining paclitaxel and carboplatin is also widely used by European and American centers. No clinical study has shown the superiority of one treatment over the other. The objective of this Phase II study is to clarify clinical practice by comparing these two chemotherapy treatments. Our aim is to evaluate, in operable esophageal and gastro-esophageal junctional cancer, the complete resection rate and severe postoperative morbidity rate associated with these two neoadjuvant chemotherapeutic regimens (carboplatin-paclitaxel or fluorouracil-oxaliplatin-folinic acid) when each is combined with the radiation regime utilized in the CROSS trial. PROTECT is a prospective, randomized, multicenter, open arms, phase II trial. Eligible patients will have a histologically confirmed adenocarcinoma or squamous cell carcinoma and be treated with neoadjuvant radiochemotherapy followed by surgery for stage IIB or stage III resectable esophageal cancer. A total of 106 patients will be randomized to receive either 3 cycles of FOLFOX combined to concurrent radiotherapy (41.4 Grays) or carboplatin and paclitaxel with the same radiation regimen, using a 1:1 allocation ratio. This ongoing trial offers the unique opportunity to compare two standards of chemotherapy delivered with a common regimen of preoperative radiation, in the setting of operable locally advanced esophageal or gastro-esophageal junctional tumors. NCT02359968 (ClinicalTrials.gov) (registration date: 9 FEB 2015), EudraCT: 2014-000649-62 (registration date: 10 FEB 2014).

A novel approach to quality improvement in a safety-net practice: concurrent peer review visits.

PubMed

Fiscella, Kevin; Volpe, Ellen; Winters, Paul; Brown, Melissa; Idris, Amna; Harren, Tricia

2010-12-01

Concurrent peer review visits are structured office visits conducted by clinician peers of the primary care clinician that are specifically designed to reduce competing demands, clinical inertia, and bias. We assessed whether a single concurrent peer review visit reduced clinical inertia and improved control of hypertension, hyperlipidemia, and diabetes control among underserved patients. We conducted a randomized encouragement trial to evaluate concurrent peer review visits with a community health center. Seven hundred twenty-seven patients with hypertension, hyperlipidemia, and/or diabetes who were not at goal for systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), and/or glycated hemoglobin (A1c) were randomly assigned to an invitation to participate in a concurrent peer review visit or to usual care. We compared change in these measures using mixed models and rates of therapeutic intensification during concurrent peer review visits with control visits. One hundred seventy-one patients completed a concurrent peer review visit. SBP improved significantly (p < .01) more among those completing concurrent peer review visits than among those who failed to respond to a concurrent peer review invitation or those randomized to usual care. There were no differences seen for changes in LDL-C or A1c. Concurrent peer review visits were associated with statistically significant greater clinician intensification of blood pressure (p < .001), lipid (p < .001), and diabetes (p < .005) treatment than either for control visits for patients in either the nonresponse group or usual care group. Concurrent peer review visits represent a promising strategy for improving blood pressure control and improving therapeutic intensification in community health centers.

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

PubMed Central

Wilde, Elisabeth A.; Moretti, Paolo; MacLeod, Marianne C.; Pedroza, Claudia; Drever, Pamala; Fourwinds, Sierra; Frisby, Melisa L.; Beers, Sue R.; Scott, James N.; Hunter, Jill V.; Traipe, Elfrides; Valadka, Alex B.; Okonkwo, David O.; Zygun, David A.; Puccio, Ava M.; Clifton, Guy L.

2013-01-01

Abstract 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. PMID:23617608

Pooled Analysis of Individual Patient Data on Concurrent Chemoradiotherapy for Stage III Non-Small-Cell Lung Cancer in Elderly Patients Compared With Younger Patients Who Participated in US National Cancer Institute Cooperative Group Studies.

PubMed

Stinchcombe, Thomas E; Zhang, Ying; Vokes, Everett E; Schiller, Joan H; Bradley, Jeffrey D; Kelly, Karen; Curran, Walter J; Schild, Steven E; Movsas, Benjamin; Clamon, Gerald; Govindan, Ramaswamy; Blumenschein, George R; Socinski, Mark A; Ready, Neal E; Akerley, Wallace L; Cohen, Harvey J; Pang, Herbert H; Wang, Xiaofei

2017-09-01

Purpose Concurrent chemoradiotherapy is standard treatment for patients with stage III non-small-cell lung cancer. Elderly patients may experience increased rates of adverse events (AEs) or less benefit from concurrent chemoradiotherapy. Patients and Methods Individual patient data were collected from 16 phase II or III trials conducted by US National Cancer Institute-supported cooperative groups of concurrent chemoradiotherapy alone or with consolidation or induction chemotherapy for stage III non-small-cell lung cancer from 1990 to 2012. Overall survival (OS), progression-free survival, and AEs were compared between patients age ≥ 70 (elderly) and those younger than 70 years (younger). Unadjusted and adjusted hazard ratios (HRs) for survival time and CIs were estimated by single-predictor and multivariable frailty Cox models. Unadjusted and adjusted odds ratio (ORs) for AEs and CIs were obtained from single-predictor and multivariable generalized linear mixed-effect models. Results A total of 2,768 patients were classified as younger and 832 as elderly. In unadjusted and multivariable models, elderly patients had worse OS (HR, 1.20; 95% CI, 1.09 to 1.31 and HR, 1.17; 95% CI, 1.07 to 1.29, respectively). In unadjusted and multivariable models, elderly and younger patients had similar progression-free survival (HR, 1.01; 95% CI, 0.93 to 1.10 and HR, 1.00; 95% CI, 0.91 to 1.09, respectively). Elderly patients had a higher rate of grade ≥ 3 AEs in unadjusted and multivariable models (OR, 1.35; 95% CI, 1.07 to 1.70 and OR, 1.38; 95% CI, 1.10 to 1.74, respectively). Grade 5 AEs were significantly higher in elderly compared with younger patients (9% v 4%; P < .01). Fewer elderly compared with younger patients completed treatment (47% v 57%; P < .01), and more discontinued treatment because of AEs (20% v 13%; P < .01), died during treatment (7.8% v 2.9%; P < .01), and refused further treatment (5.8% v 3.9%; P = .02). Conclusion Elderly patients in concurrent chemoradiotherapy trials experienced worse OS, more toxicity, and had a higher rate of death during treatment than younger patients.

Modality and Task Switching Interactions using Bi-Modal and Bivalent Stimuli

ERIC Educational Resources Information Center

Sandhu, Rajwant; Dyson, Benjamin J.

2013-01-01

Investigations of concurrent task and modality switching effects have to date been studied under conditions of uni-modal stimulus presentation. As such, it is difficult to directly compare resultant task and modality switching effects, as the stimuli afford both tasks on each trial, but only one modality. The current study investigated task and…

Can Rational Prescribing Be Improved by an Outcome-Based Educational Approach? A Randomized Trial Completed in Iran

ERIC Educational Resources Information Center

Esmaily, Hamideh M.; Silver, Ivan; Shiva, Shadi; Gargani, Alireza; Maleki-Dizaji, Nasrin; Al-Maniri, Abdullah; Wahlstrom, Rolf

2010-01-01

Introduction: An outcome-based education approach has been proposed to develop more effective continuing medical education (CME) programs. We have used this approach in developing an outcome-based educational intervention for general physicians working in primary care (GPs) and evaluated its effectiveness compared with a concurrent CME program in…

Randomized Controlled Trial for Behavioral Smoking and Weight Control Treatment: Effect of Concurrent Versus Sequential Intervention.

ERIC Educational Resources Information Center

Spring, Bonnie; Pagoto, Sherry; Pingitore, Regina; Doran, Neal; Schneider, Kristin; Hedeker, Don

2004-01-01

The authors compared simultaneous versus sequential approaches to multiple health behavior change in diet, exercise, and cigarette smoking. Female regular smokers (N = 315) randomized to 3 conditions received 16 weeks of behavioral smoking treatment, quit smoking at Week 5, and were followed for 9 months after quit date. Weight management was…

Primary and key secondary results from the ROCKET AF trial, and their implications on clinical practice.

PubMed

Shah, Rohan; Patel, Manesh R

2017-03-01

The safety and efficacy of the oral anticoagulant rivaroxaban were studied in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF trial). A number of subanalyses of the ROCKET AF trial have subsequently analyzed the use of rivaroxaban in special patient populations. The outcomes of the ROCKET AF trial were reviewed. The use of rivaroxaban in higher risk populations, as determined by the presence of co-morbidities included in the CHADS2 criteria, was analyzed. Requirements for dose adjustment in patients with renal impairment and in East Asian patients were described. Finally, clinical management challenges, including interruptions in therapy, drug discontinuation, management of bleeding events, drug interactions, and management of patients requiring cardioversion/ablation were reviewed. Rivaroxaban is efficacious in high-risk populations, including elderly patients, patients with diabetes, heart failure, history of stroke, prior myocardial infarction, or peripheral arterial disease (PAD). Patients with PAD have a higher risk of bleeding with rivaroxaban compared with warfarin. East Asian populations do not require a dose adjustment for rivaroxaban, while a reduced dose of 15 mg daily is required for patients with moderate renal impairment. Rivaroxaban remains effective with temporary interruptions in therapy and in patients requiring cardioversion/ablation. Rates of major bleeding and subsequent outcomes were similar in patients on warfarin and rivaroxaban, although rates of gastrointestinal bleeding were higher with rivaroxaban. Concurrent use of antiarrhythmic therapy was not associated with adverse outcomes. Rivaroxaban represents an efficacious alternative to warfarin in high-risk patients with AF. Dose adjustment is required for patients with moderate renal impairment. Rivaroxaban can be used safely in a number of challenging clinical management scenarios although the concurrent use of amiodarone requires more study.

Concurrent cannabis use during treatment for comorbid ADHD and cocaine dependence: effects on outcome.

PubMed

Aharonovich, Efrat; Garawi, Fatima; Bisaga, Adam; Brooks, Daniel; Raby, Wilfrid N; Rubin, Eric; Nunes, Edward V; Levin, Frances R

2006-01-01

Cannabis is the most widely used illicit substance in the United States with especially high prevalence of use among those with psychiatric disorders. Few studies have examined the relationship between concurrent cannabis use and treatment outcome among patients receiving treatment for comorbid substance abuse and psychiatric disorders. This study investigated the effects of cannabis use on treatment retention and abstinence from cocaine among cocaine dependent patients with Attention Deficit Hyperactivity Disorder (ADHD). Cocaine dependent patients diagnosed with current ADHD (DSM-IV, N = 92) aged 25 to 51 participated in a randomized clinical trial of methylphenidate for treatment of ADHD and cocaine dependence in an outpatient setting. The majority of patients (69%) used cannabis during treatment. Results suggest that moderate/intermittent cannabis users had greater retention rates compared to abstainers and consistent users (p = .02). This study is the first to examine concurrent cannabis use in cocaine dependent patients diagnosed with ADHD.

Intensified High-Dose Chemoradiotherapy With Induction Chemotherapy in Patients With Locally Advanced Non-Small-Cell Lung Cancer-Safety and Toxicity Results Within a Prospective Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poettgen, Christoph, E-mail: christoph.poettgen@uk-essen.d; Eberhardt, Wilfried E.; Gauler, Thomas

2010-03-01

Purpose: To analyze the toxicity profile of an intensified definitive chemoradiotherapy (CRT) schedule in patients with locally advanced non-small-cell lung cancer (Stage IIIA N2/selected IIIB) treated within a prospective multicenter trial. Patients and Methods: After mediastinoscopy and routine staging procedures, three cycles of induction chemotherapy (cisplatin 50 mg/m{sup 2}, Days 1 and 8; paclitaxel 175 mg/m{sup 2} Day 1, every 21 days) were planned, followed by concurrent CRT (accelerated-hyperfractionated regimen, 45 Gy, 2 x 1.5 Gy/d, cisplatin 50 mg/m{sup 2}, Days 64 and 71, vinorelbine 20 mg/m{sup 2}, Days 64 and 71). At 45 Gy, a multidisciplinary panel decision wasmore » made regarding operability. Inoperable patients received definitive radiotherapy (total dose 65 or 71 Gy, depending on the mean lung dose) with additional concurrent chemotherapy (cisplatin 40 mg/m{sup 2}, Day 85; vinorelbine 15 mg/m{sup 2}, Days 85 and 92). Results: A total of 28 patients (23 men and 5 women; median age, 58 years; range 41-73; Stage IIIA in 3 and Stage IIIB in 25) were judged ineligible for surgery by the multidisciplinary panel and underwent definitive CRT (75% of the patients received 71 Gy). The maximum toxicity (Grade 3 or greater) during induction chemotherapy included leukopenia (11%) and anemia (4%). During concurrent CRT, leukopenia (Grade 3 or greater) was observed in 39% of the patients. The maximal nonhematologic toxicity during concurrent CRT included esophagitis (Grade 3 or greater) in 18% and pneumonitis (Grade 3 or greater) in 4% of the patients. At 3 years, the locoregional control rate was 52% (95% confidence interval, 29-75%) and the overall survival rate was 31% (95% confidence interval, 12-50%). Conclusion: This intensified treatment protocol with induction chemotherapy and concurrent CRT, including hyperfractionated-accelerated RT, showed only moderate toxicity and proved feasible. This treatment represents the definitive CRT arm of our ongoing multicenter randomized trial comparing definitive CRT and trimodality treatment.« less

Randomized Controlled Trial of Osmotic-Release Methylphenidate with Cognitive-Behavioral Therapy in Adolescents with Attention-Deficit/Hyperactivity Disorder and Substance Use Disorders

ERIC Educational Resources Information Center

Riggs, Paula D.; Winhusen, Theresa; Davies, Robert D.; Leimberger, Jeffrey D.; Mikulich-Gilbertson, Susan; Klein, Constance; Macdonald, Marilyn; Lohman, Michelle; Bailey, Genie L.; Haynes, Louise; Jaffee, William B.; Haminton, Nancy; Hodgkins, Candace; Whitmore, Elizabeth; Trello-Rishel, Kathlene; Tamm, Leanne; Acosta, Michelle C.; Royer-Malvestuto, Charlotte; Subramaniam, Geetha; Fishman, Marc; Holmes, Beverly W.; Kaye, Mary Elyse; Vargo, Mark A.; Woody, George E.; Nunes, Edward V.; Liu, David

2011-01-01

Objective: To evaluate the efficacy and safety of osmotic-release methylphenidate (OROS-MPH) compared with placebo for attention-deficit/hyperactivity disorder (ADHD), and the impact on substance treatment outcomes in adolescents concurrently receiving cognitive-behavioral therapy (CBT) for substance use disorders (SUD). Method: This was a…

EFFECTS OF BROILER REARING ENVIRONMENT ON TRANSMISSION OF F-STRAIN MYCOPLASMA GALLISEPTICUM FROM COMMERCIAL LAYER HENS TO BROILER CHICKENS: ROLE OF ACID-BASE BALANCE

USDA-ARS?s Scientific Manuscript database

Two trials were conducted concurrently to determine and compare, blood pH, blood gases, hematocrit, and hemoglobin in mycoplasma-free, F-strain Mycoplasma gallisepticum (FMG) inoculation layers, and FMG contact-infected broilers. FMG-inoculated layers had the highest partial pressure of O2 and the l...

Phase II randomized trial of radiation therapy, cetuximab, and pemetrexed with or without bevacizumab in patients with locally advanced head and neck cancer.

PubMed

Argiris, A; Bauman, J E; Ohr, J; Gooding, W E; Heron, D E; Duvvuri, U; Kubicek, G J; Posluszny, D M; Vassilakopoulou, M; Kim, S; Grandis, J R; Johnson, J T; Gibson, M K; Clump, D A; Flaherty, J T; Chiosea, S I; Branstetter, B; Ferris, R L

2016-08-01

We previously reported the safety of concurrent cetuximab, an antibody against epidermal growth factor receptor (EGFR), pemetrexed, and radiation therapy (RT) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). In this non-comparative phase II randomized trial, we evaluated this non-platinum combination with or without bevacizumab, an inhibitor of vascular endothelial growth factor (VEGF). Patients with previously untreated stage III-IVB SCCHN were randomized to receive: conventionally fractionated radiation (70 Gy), concurrent cetuximab, and concurrent pemetrexed (arm A); or the identical regimen plus concurrent bevacizumab followed by bevacizumab maintenance for 24 weeks (arm B). The primary end point was 2-year progression-free survival (PFS), with each arm compared with historical control. Exploratory analyses included the relationship of established prognostic factors to PFS and quality of life (QoL). Seventy-eight patients were randomized: 66 oropharynx (42 HPV-positive, 15 HPV-negative, 9 unknown) and 12 larynx; 38 (49%) had heavy tobacco exposure. Two-year PFS was 79% [90% confidence interval (CI) 0.69-0.92; P < 0.0001] for arm A and 75% (90% CI 0.64-0.88; P < 0.0001) for arm B, both higher than historical control. No differences in PFS were observed for stage, tobacco history, HPV status, or type of center (community versus academic). A significantly increased rate of hemorrhage occurred in arm B. SCCHN-specific QoL declined acutely, with marked improvement but residual symptom burden 1 year post-treatment. RT with a concurrent non-platinum regimen of cetuximab and pemetrexed is feasible in academic and community settings, demonstrating expected toxicities and promising efficacy. Adding bevacizumab increased toxicity without apparent improvement in efficacy, countering the hypothesis that dual EGFR-VEGF targeting would overcome radiation resistance, and enhance clinical benefit. Further development of cetuximab, pemetrexed, and RT will require additional prospective study in defined, high-risk populations where treatment intensification is justified. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Immunotherapeutic Strategies in Breast Cancer: Preclinical and Clinical Trials

DTIC Science & Technology

2011-09-01

infection; known to be HIV positive, have hepatitis, or an immunocompromising condition; concurrent anti-cancer standard or investigational therapies...supportive care, including antibiotics , transfusions, and treatment of other newly diagnosed or concurrent medical conditions. Statistical

Effects of Helicobacter pylori treatment on rosacea: A single-arm clinical trial study.

PubMed

Saleh, Parviz; Naghavi-Behzad, Mohammad; Herizchi, Hamdieh; Mokhtari, Fatemeh; Mirza-Aghazadeh-Attari, Mohammad; Piri, Reza

2017-09-01

Rosacea is a chronic dermatological disease. Helicobacter pylori has been discussed as one of its causative factors. In this clinical trial study, we attempted to evaluate the effect of H. pylori standard eradication protocol on the rosacea clinical course. In this single-arm clinical trial, patients ascertained to have H. pylori infection based on serological studies were assessed to examine existence of rosacea. Patients with concurrent rosacea and H. pylori infection were included in the study and underwent standard H. pylori eradication therapy. Rosacea was evaluated using the Duluth rosacea grading score at the beginning, 2 months later and at the end of the trial (day 180). Of 872 patients positive for H. pylori, 167 patients (19.15%) manifested the clinical features of rosacea. The patients with concurrent rosacea were younger (P < 0.001) and with a female sex predominance (P = 0.03) when compared with rosacea-free patients. Of 167 patients, 150 received H. pylori eradication therapy, demonstrating a 92% (138/150) cure rate. The rosacea Duluth score grading on day 0, 60 and 180 among 138 patients significantly decreased in most of the criteria except for telangiectasias (P = 0.712), phymatous changes (P = 0.535) and the existence of peripheral involvement (P = 0.431). The present study concluded that H. pylori eradication leads to improvement of rosacea. © 2017 Japanese Dermatological Association.

Compatibility of ASO3-adjuvanted H1N1pdm09 and seasonal trivalent influenza vaccines in adults: results of a randomized, controlled trial.

PubMed

Scheifele, David W; Ward, Brian J; Dionne, Marc; Vanderkooi, Otto G; Loeb, Mark; Coleman, Brenda L; Li, Yan

2012-07-06

When Canada chose a novel adjuvanted vaccine to combat the 2009 influenza pandemic, seasonal trivalent inactivated vaccine (TIV) was also available but compatibility of the two had not been assessed. To compare responses after concurrent or sequential administration of these vaccines, adults 20-59 years old were randomly assigned (1:1) to receive ASO3-adjuvanted H1N1pdm09 vaccine (Arepanrix, GSK, Quebec City, Quebec), with TIV (Vaxigrip, Sanofi Pasteur, Toronto) given concurrently or 21 days later. Blood was obtained at baseline and 21 days after each vaccination to measure hemagglutination inhibition (HAI) titers. Adverse effects were assessed using symptom diaries and personal interviews. 282 participants completed the study (concurrent vaccines 145, sequential vaccines 137). HAI titers to H1N1pdm09 were ≥ 40 at baseline in 15-18% of participants and following vaccination in 91-92%. Initially seropositive subjects (titer ≥ 10) had lower H1N1pdm09 geometric mean HAI titers (GMT) after concurrent than separate vaccinations (320.0 vs 476.5, p=0.039) but both exceeded GM responses of initially naïve participants, which were unaffected by concurrent TIV. Responses to TIV were not lower after concurrent than separate vaccination. Adverse event rates were not increased by concurrent vaccinations above those with H1N1pdm09 vaccine alone. This adjuvanted H1N1pdm09 vaccine was immunogenic and compatible with concurrently administered TIV. Copyright © 2012 Elsevier Ltd. All rights reserved.

Concurrent and sequential initiation of ovarian function suppression with chemotherapy in premenopausal women with endocrine-responsive early breast cancer: an exploratory analysis of TEXT and SOFT.

PubMed

Regan, M M; Walley, B A; Francis, P A; Fleming, G F; Láng, I; Gómez, H L; Colleoni, M; Tondini, C; Pinotti, G; Salim, M; Spazzapan, S; Parmar, V; Ruhstaller, T; Abdi, E A; Gelber, R D; Coates, A S; Goldhirsch, A; Pagani, O

2017-09-01

Recent breast cancer treatment guidelines recommend that higher-risk premenopausal patients should receive ovarian function suppression (OFS) as part of adjuvant endocrine therapy. If chemotherapy is also given, it is uncertain whether to select concurrent or sequential OFS initiation. We analyzed 1872 patients enrolled in the randomized phase III TEXT and SOFT trials who received adjuvant chemotherapy for hormone receptor-positive, HER2-negative breast cancer and upon randomization to an OFS-containing adjuvant endocrine therapy, initiated gonadotropin-releasing-hormone-agonist triptorelin. Breast cancer-free interval (BCFI) was compared between patients who received OFS concurrently with chemotherapy in TEXT (n = 1242) versus sequentially post-chemotherapy in SOFT (n = 630). Because timing of trial enrollment relative to adjuvant chemotherapy differed, we implemented landmark analysis re-defining BCFI beginning 1 year after final dose of chemotherapy (median, 15.5 and 8.1 months from enrollment to landmark in TEXT and SOFT, respectively). As a non-randomized treatment comparison, we implemented comparative-effectiveness propensity score methodology with weighted Cox modeling. Distributions of several clinico-pathologic characteristics differed between groups. Patients who were premenopausal post-chemotherapy in SOFT were younger on average. The median duration of adjuvant chemotherapy was 18 weeks in both groups. There were 231 (12%) BC events after post-landmark median follow-up of about 5 years. Concurrent use of triptorelin with chemotherapy was not associated with a significant difference in post-landmark BCFI compared with sequential triptorelin post-chemotherapy, either in the overall population (HR = 1.11, 95% CI 0.72-1.72; P = 0.72; 4-year BCFI 89% in both groups), or in the subgroup of 692 women <40 years at diagnosis (HR = 1.13, 95% CI 0.69-1.84) who are less likely to develop chemotherapy-induced amenorrhea. Based on comparative-effectiveness modeling of TEXT and SOFT after about 5 years median follow-up, with limited statistical power especially for the subgroup <40 years, neither detrimental nor beneficial effect of concurrent administration of OFS with chemotherapy on the efficacy of adjuvant therapy that includes chemotherapy was detected. NCT00066690 and NCT00066703. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Does Concurrent Radiochemotherapy Affect Cosmetic Results in the Adjuvant Setting After Breast-Conserving Surgery? Results of the ARCOSEIN Multicenter, Phase III Study: Patients' and Doctors' Views

DOE Office of Scientific and Technical Information (OSTI.GOV)

Toledano, Alain H.; Bollet, Marc A.; Fourquet, Alain

2007-05-01

Purpose: To evaluate the cosmetic results of sequential vs. concurrent adjuvant chemotherapy with radiotherapy after breast-conserving surgery for breast cancer, and to compare ratings by patients and physicians. Methods and Materials: From 1996 to 2000, 716 patients with Stage I-II breast cancers were included in a multicenter, Phase III trial (the ARCOSEIN study) comparing, after breast-conserving surgery with axillary dissection, sequential treatment with chemotherapy first followed by radiotherapy vs. chemotherapy administered concurrently with radiotherapy. Cosmetic results with regard to both the overall aspect of the breast and specific changes (color, scar) were evaluated in a total of 214 patients (107more » in each arm) by means of questionnaires to both the patient and a physician whose rating was blinded to treatment allocation. Results: Patients' overall satisfaction with cosmesis was not statistically different between the two arms, with approximately 92% with at least satisfactory results (p = 0.72), although differences between the treated and untreated breasts were greater after the concurrent regimen (29% vs. 14% with more than moderate differences; p 0.0015). Physician assessment of overall cosmesis was less favorable, with lower rates of at least satisfactory results in the concurrent arm (60% vs. 85%; p = 0.001). Consequently, the concordance for overall satisfaction with cosmesis between patients and doctors was only fair ({kappa} = 0.62). Conclusion: After breast-conserving surgery, the concurrent use of chemotherapy with radiotherapy is significantly associated with greater differences between the breasts. These differences do not translate into patients' lessened satisfaction with cosmesis.« less

A noninferiority clinical trial comparing fluconazole and ketoconazole in combination with cephalexin for the treatment of dogs with Malassezia dermatitis.

PubMed

Sickafoose, L; Hosgood, G; Snook, T; Westermeyer, R; Merchant, S

2010-01-01

This double-blinded noninferiority clinical trial evaluated the use of oral fluconazole for the treatment of Malassezia dermatitis in dogs by comparing it with use of an accepted therapeutic agent, ketoconazole. Dogs presenting with Malassezia dermatitis were treated with either fluconazole or ketoconazole in addition to cephalexin for concurrent bacterial dermatitis. Statistically significant improvements in cytologic yeast count, clinical signs associated with Malassezia dermatitis, and pruritus were seen with both antifungal treatments. There was no statistical difference between the treatments with regard to the magnitude of reduction in these parameters. These results suggest that fluconazole is at least as effective as ketoconazole for the treatment of dogs with Malassezia dermatitis.

On the role of verbalization during task set selection: switching or serial order control?

PubMed

Bryck, Richard L; Mayr, Ulrich

2005-06-01

Recent task-switching work in which paper-and-pencil administered single-task lists were compared with task-alternation lists has demonstrated large increases in task-switch costs with concurrent articulatory suppression (AS), implicating a crucial role for verbalization during switching (Baddeley, Chincotta, & Adlam, 2001; Emerson & Miyake, 2003). Experiment 1 replicated this result, using computerized assessment, albeit with much smaller effect sizes than in the original reports. In Experiment 2, AS interference was reduced when a sequential cue (spatial location) that indicated the current position in the sequence of task alternations was given. Finally, in Experiment 3, switch trials and no-switch trials were compared within a block of alternating runs of two tasks. Again, AS interference was obtained mainly when the endogenous sequencing demand was high, and it was comparable for no-switch and switch trials. These results suggest that verbalization may be critical for endogenous maintenance and updating of a sequential plan, rather than exclusively for the actual switching process.

Phase II clinical trial of whole-brain irradiation plus three-dimensional conformal boost with concurrent topotecan for brain metastases from lung cancer

PubMed Central

2013-01-01

Background Patients with brain metastases from lung cancer have poor prognoses and short survival time, and they are often excluded from clinical trials. Whole-cranial irradiation is considered to be the standard treatment, but its efficacy is not satisfactory. The purpose of this phase II clinical trial was to evaluate the preliminary efficacy and safety of the treatment of whole-brain irradiation plus three-dimensional conformal boost combined with concurrent topotecan for the patients with brain metastases from lung cancer. Methods Patients with brain metastasis from lung cancer received concurrent chemotherapy and radiotherapy: conventional fractionated whole-brain irradiation, 2 fields/time, 1 fraction/day, 2 Gy/fraction, 5 times/week, and DT 40 Gy/20 fractions; for the patients with ≤ 3 lesions with diameter ≥ 2 cm, a three-dimensional (3-D) conformal localised boost was given to increase the dosage to 56–60 Gy; and during radiotherapy, concurrent chemotherapy with topotecan was given (the chemoradiotherapy group, CRT). The patients with brain metastasis from lung cancer during the same period who received radiotherapy only were selected as the controls (the radiotherapy-alone group, RT). Results From March 2009 to March 2012, both 38 patients were enrolled into two groups. The median progression-free survival(PFS) time , the 1- and 2-year PFS rates of CRT group and RT group were 6 months, 42.8%, 21.6% and 3 months, 11.6%, 8.7% (χ2 = 6.02, p = 0.014), respectively. The 1- and 2-year intracranial lesion control rates of CRT and RT were 75.9% , 65.2% and 41.6% , 31.2% (χ2 = 3.892, p = 0.049), respectively. The 1- and 2-year overall survival rates (OS) of CRT and RT were 50.8% , 37.9% and 40.4% , 16.5% (χ2 = 1.811, p = 0.178), respectively. The major side effects were myelosuppression and digestive toxicities, but no differences were observed between the two groups. Conclusion Compared with radiotherapy alone, whole-brain irradiation plus 3-D conformal boost irradiation and concurrent topotecan chemotherapy significantly improved the PFS rate and the intracranial lesion control rate of patients with brain metastases from lung cancer, and no significant increases in side effects were observed. Based on these results, this treatment method is recommended for phase III clinical trial. PMID:24125485

Visualization Improves Supraclavicular Access to the Subclavian Vein in a Mixed Reality Simulator.

PubMed

Sappenfield, Joshua Warren; Smith, William Brit; Cooper, Lou Ann; Lizdas, David; Gonsalves, Drew B; Gravenstein, Nikolaus; Lampotang, Samsun; Robinson, Albert R

2018-07-01

We investigated whether visual augmentation (3D, real-time, color visualization) of a procedural simulator improved performance during training in the supraclavicular approach to the subclavian vein, not as widely known or used as its infraclavicular counterpart. To train anesthesiology residents to access a central vein, a mixed reality simulator with emulated ultrasound imaging was created using an anatomically authentic, 3D-printed, physical mannequin based on a computed tomographic scan of an actual human. The simulator has a corresponding 3D virtual model of the neck and upper chest anatomy. Hand-held instruments such as a needle, an ultrasound probe, and a virtual camera controller are directly manipulated by the trainee and tracked and recorded with submillimeter resolution via miniature, 6 degrees of freedom magnetic sensors. After Institutional Review Board approval, 69 anesthesiology residents and faculty were enrolled and received scripted instructions on how to perform subclavian venous access using the supraclavicular approach based on anatomic landmarks. The volunteers were randomized into 2 cohorts. The first used real-time 3D visualization concurrently with trial 1, but not during trial 2. The second did not use real-time 3D visualization concurrently with trial 1 or 2. However, after trial 2, they observed a 3D visualization playback of trial 2 before performing trial 3 without visualization. An automated scoring system based on time, success, and errors/complications generated objective performance scores. Nonparametric statistical methods were used to compare the scores between subsequent trials, differences between groups (real-time visualization versus no visualization versus delayed visualization), and improvement in scores between trials within groups. Although the real-time visualization group demonstrated significantly better performance than the delayed visualization group on trial 1 (P = .01), there was no difference in gain scores, between performance on the first trial and performance on the final trial, that were dependent on group (P = .13). In the delayed visualization group, the difference in performance between trial 1 and trial 2 was not significant (P = .09); reviewing performance on trial 2 before trial 3 resulted in improved performance when compared to trial 1 (P < .0001). There was no significant difference in median scores (P = .13) between the real-time visualization and delayed visualization groups for the last trial after both groups had received visualization. Participants reported a significant improvement in confidence in performing supraclavicular access to the subclavian vein. Standard deviations of scores, a measure of performance variability, decreased in the delayed visualization group after viewing the visualization. Real-time visual augmentation (3D visualization) in the mixed reality simulator improved performance during supraclavicular access to the subclavian vein. No difference was seen in the final trial of the group that received real-time visualization compared to the group that had delayed visualization playback of their prior attempt. Training with the mixed reality simulator improved participant confidence in performing an unfamiliar technique.

The influence of emotional interference on cognitive control: A meta-analysis of neuroimaging studies using the emotional Stroop task.

PubMed

Song, Sensen; Zilverstand, Anna; Song, Hongwen; d'Oleire Uquillas, Federico; Wang, Yongming; Xie, Chao; Cheng, Li; Zou, Zhiling

2017-05-18

The neural correlates underlying the influence of emotional interference on cognitive control remain a topic of discussion. Here, we assessed 16 neuroimaging studies that used an emotional Stroop task and that reported a significant interaction effect between emotion (stimulus type) and cognitive conflict. There were a total of 330 participants, equaling 132 foci for an activation likelihood estimation (ALE) analysis. Results revealed consistent brain activation patterns related to emotionally-salient stimuli (as compared to emotionally-neutral trials) during cognitive conflict trials [incongruent trials (with task-irrelevant information interfering), versus congruent/baseline trials (less disturbance from task-irrelevant information)], that span the lateral prefrontal cortex (dorsolateral prefrontal cortex and inferior frontal gyrus), the medial prefrontal cortex, and the dorsal anterior cingulate cortex. Comparing mild emotional interference trials (without semantic conflict) versus intense emotional interference trials (with semantic conflict), revealed that while concurrent activation in similar brain regions as mentioned above was found for intense emotional interference trials, activation for mild emotional interference trials was only found in the precentral/postcentral gyrus. These data provide evidence for the potential neural mechanisms underlying emotional interference on cognitive control, and further elucidate an important distinction in brain activation patterns for different levels of emotional conflict across emotional Stroop tasks.

Concurrent information affects response inhibition processes via the modulation of theta oscillations in cognitive control networks.

PubMed

Chmielewski, Witold X; Mückschel, Moritz; Dippel, Gabriel; Beste, Christian

2016-11-01

Inhibiting responses is a challenge, where the outcome (partly) depends on the situational context. In everyday situations, response inhibition performance might be altered when irrelevant input is presented simultaneously with the information relevant for response inhibition. More specifically, irrelevant concurrent information may either brace or interfere with response-relevant information, depending on whether these inputs are redundant or conflicting. The aim of this study is to investigate neurophysiological mechanisms and the network underlying such modulations using EEG beamforming as method. The results show that in comparison to a baseline condition without concurrent information, response inhibition performance can be aggravated or facilitated by manipulating the extent of conflict via concurrent input. This depends on whether the requirement for cognitive control is high, as in conflicting trials, or whether it is low, as in redundant trials. In line with this, the total theta frequency power decreases in a right hemispheric orbitofrontal response inhibition network including the SFG, MFG, and SMA, when concurrent redundant information facilitates response inhibition processes. Vice versa, theta activity in a left-hemispheric response inhibition network (i.e., SFG, MFG, and IFG) increases, when conflicting concurrent information compromises response inhibition processes. We conclude that concurrent information bi-directionally shifts response inhibition performance and modulates the network architecture underlying theta oscillations which are signaling different levels of the need for cognitive control.

Randomized control trial of benzydamine HCl versus sodium bicarbonate for prophylaxis of concurrent chemoradiation-induced oral mucositis.

PubMed

Chitapanarux, Imjai; Tungkasamit, Tharatorn; Petsuksiri, Janjira; Kannarunimit, Danita; Katanyoo, Kanyarat; Chakkabat, Chakkapong; Setakornnukul, Jiraporn; Wongsrita, Somying; Jirawatwarakul, Naruemon; Lertbusayanukul, Chawalit; Sripan, Patumrat; Traisathit, Patrinee

2018-03-01

The purpose of the study is to compare the efficacy of benzydamine HCl with sodium bicarbonate in the prevention of concurrent chemoradiation-induced oral mucositis in head and neck cancer patients. Sixty locally advanced head and neck cancer patients treated with high-dose radiotherapy concurrently with platinum-based chemotherapy were randomly assigned to receive either benzydamine HCl or sodium bicarbonate from the first day of treatment to 2 weeks after the completion of treatment. The total score for mucositis, based on the Oral Mucositis Assessment Scale (OMAS), was used for the assessment, conducted weekly during the treatment period and at the fourth week of the follow-up. Pain score, all prescribed medications, and tube feeding needs were also recorded and compared. The median of total OMAS score was statistically significant lower in patients who received benzydamine HCl during concurrent chemo-radiotherapy (CCRT) than in those who received sodium bicarbonate, (p value < 0.001). There was no difference in median pain score, (p value = 0.52). Nineteen percent of patients in sodium bicarbonate arm needed oral antifungal agents whereas none in the benzydamine HCl arm required such medications, (p value = 0.06). Tube feeding needs and the compliance of CCRT were not different between the two study arms. For patients undergoing high-dose radiotherapy concurrently with platinum-based chemotherapy, using benzydamine HCl mouthwash as a preventive approach was superior to basic oral care using sodium bicarbonate mouthwash in terms of reducing the severity of oral mucositis and encouraging trend for the less need of oral antifungal drugs.

Radiotherapy for Prostate Cancer: is it 'what you do' or 'the way that you do it'? A UK Perspective on Technique and Quality Assurance.

PubMed

Mason, M D; Moore, R; Jones, G; Lewis, G; Donovan, J L; Neal, D E; Hamdy, F C; Lane, J A; Staffurth, J N

2016-09-01

The treatment of prostate cancer has evolved markedly over the last 40 years, including radiotherapy, notably with escalated dose and targeting. However, the optimal treatment for localised disease has not been established in comparative randomised trials. The aim of this article is to describe the history of prostate radiotherapy trials, including their quality assurance processes, and to compare these with the ProtecT trial. The UK ProtecT randomised trial compares external beam conformal radiotherapy, surgery and active monitoring for clinically localised prostate cancer and will report on the primary outcome (disease-specific mortality) in 2016 following recruitment between 1999 and 2009. The embedded quality assurance programme consists of on-site machine dosimetry at the nine trial centres, a retrospective review of outlining and adherence to dose constraints based on the trial protocol in 54 participants (randomly selected, around 10% of the total randomised to radiotherapy, n = 545). These quality assurance processes and results were compared with prostate radiotherapy trials of a comparable era. There has been an increasingly sophisticated quality assurance programme in UK prostate radiotherapy trials over the last 15 years, reflecting dose escalation and treatment complexity. In ProtecT, machine dosimetry results were comparable between trial centres and with the UK RT01 trial. The outlining review showed that most deviations were clinically acceptable, although three (1.4%) may have been of clinical significance and were related to outlining of the prostate. Seminal vesicle outlining varied, possibly due to several prostate trials running concurrently with different protocols. Adherence to dose constraints in ProtecT was considered acceptable, with 80% of randomised participants having two or less deviations and planning target volume coverage was excellent. The ProtecT trial quality assurance results were satisfactory and comparable with trials of its era. Future trials should aim to standardise treatment protocols and quality assurance programmes where possible to reduce complexities for centres involved in multiple trials. Copyright © 2016. Published by Elsevier Ltd.

Antiangiogenesis and gene aberration-related therapy may improve overall survival in patients with concurrent KRAS and TP53 hotspot mutant cancer

PubMed Central

Wang, Zhijie; Piha-Paul, Sarina; Janku, Filip; Subbiah, Vivek; Shi, Naiyi; Gong, Jing; Wathoo, Chetna; Shaw, Kenna; Hess, Kenneth; Broaddus, Russell; Naing, Aung; Hong, David; Tsimberidou, Apostolia M.; Karp, Daniel; Yao, James; Meric-Bernstam, Funda; Fu, Siqing

2017-01-01

Purpose Genetic alterations such as activating KRAS and/or inactivating TP53 are thought to be the most common drivers to tumorigenesis. Therefore, we assessed phase I cancer patients with KRAS+/TP53+ mutations. Results Approximately 8% of patients referred to phase I clinical trials harbored concurrent KRAS and TP53 mutations. Patients who received a phase I trial therapy (n = 57) had a median OS of 12 months, compared with 4.6 months in those who were not treated (n = 106; p = 0.003). KRAS G13 and TP53 R273 mutations were associated with poor overall survival (OS), while antiangiogenesis and gene aberration-related therapies were associated with prolonged OS. A prognostic model using neutrophilia, thrombocytosis, hypoalbuminemia, body mass index <30 kg/m2, and the absence of lung metastasis was established and validated. Phase I cancer patients in the low-risk group had a median OS of 16.6 months compared with 5.4 months in the high-risk group (p < 0.001). Untreated patients in the low-risk group had a median OS of 6.7 months compared with 3.6 months in the high-risk group (p = 0.033). Experimental Design We analyzed 163 consecutive patients with advanced KRAS+/TP53+ mutant cancer who were referred to phase I clinical trials, to identify molecular aberrations, clinical characteristics, survivals, and potentially effective treatment regimens. Conclusions This study provided preliminary evidence that besides modulation of the proinflammatory state, antiangiogensis and concomitant gene aberration-related therapies may improve the treatment of KRAS+/TP53+ mutant cancer. PMID:28430579

Influence of moving visual environment on sit-to-stand kinematics in children and adults.

PubMed

Slaboda, Jill C; Barton, Joseph E; Keshner, Emily A

2009-08-01

The effect of visual field motion on the sit-to-stand kinematics of adults and children was investigated. Children (8 to12 years of age) and adults (21 to 49 years of age) were seated in a virtual environment that rotated in the pitch and roll directions. Participants stood up either (1) concurrent with onset of visual motion or (2) after an immersion period in the moving visual environment, and (3) without visual input. Angular velocities of the head with respect to the trunk, and trunk with respect to the environment, w ere calculated as was head andtrunk center of mass. Both adults and children reduced head and trunk angular velocity after immersion in the moving visual environment. Unlike adults, children demonstrated significant differences in displacement of the head center of mass during the immersion and concurrent trials when compared to trials without visual input. Results suggest a time-dependent effect of vision on sit-to-stand kinematics in adults, whereas children are influenced by the immediate presence or absence of vision.

Use of exocentric and egocentric representations in the concurrent planning of sequential saccades.

PubMed

Sharika, K M; Ramakrishnan, Arjun; Murthy, Aditya

2014-11-26

The concurrent planning of sequential saccades offers a simple model to study the nature of visuomotor transformations since the second saccade vector needs to be remapped to foveate the second target following the first saccade. Remapping is thought to occur through egocentric mechanisms involving an efference copy of the first saccade that is available around the time of its onset. In contrast, an exocentric representation of the second target relative to the first target, if available, can be used to directly code the second saccade vector. While human volunteers performed a modified double-step task, we examined the role of exocentric encoding in concurrent saccade planning by shifting the first target location well before the efference copy could be used by the oculomotor system. The impact of the first target shift on concurrent processing was tested by examining the end-points of second saccades following a shift of the second target during the first saccade. The frequency of second saccades to the old versus new location of the second target, as well as the propagation of first saccade localization errors, both indices of concurrent processing, were found to be significantly reduced in trials with the first target shift compared to those without it. A similar decrease in concurrent processing was obtained when we shifted the first target but kept constant the second saccade vector. Overall, these results suggest that the brain can use relatively stable visual landmarks, independent of efference copy-based egocentric mechanisms, for concurrent planning of sequential saccades. Copyright © 2014 the authors 0270-6474/14/3416009-13$15.00/0.

Primary and key secondary results from the ROCKET AF trial, and their implications on clinical practice

PubMed Central

Shah, Rohan; Patel, Manesh R.

2016-01-01

Background: The safety and efficacy of the oral anticoagulant rivaroxaban were studied in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF trial). A number of subanalyses of the ROCKET AF trial have subsequently analyzed the use of rivaroxaban in special patient populations. Methods: The outcomes of the ROCKET AF trial were reviewed. The use of rivaroxaban in higher risk populations, as determined by the presence of co-morbidities included in the CHADS2 criteria, was analyzed. Requirements for dose adjustment in patients with renal impairment and in East Asian patients were described. Finally, clinical management challenges, including interruptions in therapy, drug discontinuation, management of bleeding events, drug interactions, and management of patients requiring cardioversion/ablation were reviewed. Results: Rivaroxaban is efficacious in high-risk populations, including elderly patients, patients with diabetes, heart failure, history of stroke, prior myocardial infarction, or peripheral arterial disease (PAD). Patients with PAD have a higher risk of bleeding with rivaroxaban compared with warfarin. East Asian populations do not require a dose adjustment for rivaroxaban, while a reduced dose of 15 mg daily is required for patients with moderate renal impairment. Rivaroxaban remains effective with temporary interruptions in therapy and in patients requiring cardioversion/ablation. Rates of major bleeding and subsequent outcomes were similar in patients on warfarin and rivaroxaban, although rates of gastrointestinal bleeding were higher with rivaroxaban. Concurrent use of antiarrhythmic therapy was not associated with adverse outcomes. Conclusions: Rivaroxaban represents an efficacious alternative to warfarin in high-risk patients with AF. Dose adjustment is required for patients with moderate renal impairment. Rivaroxaban can be used safely in a number of challenging clinical management scenarios although the concurrent use of amiodarone requires more study. PMID:27555569

Accelerated hypofractionated three-dimensional conformal radiation therapy (3 Gy/fraction) combined with concurrent chemotherapy for patients with unresectable stage III non-small cell lung cancer: preliminary results of an early terminated phase II trial.

PubMed

Ren, Xiao-Cang; Wang, Quan-Yu; Zhang, Rui; Chen, Xue-Ji; Wang, Na; Liu, Yue-E; Zong, Jie; Guo, Zhi-Jun; Wang, Dong-Ying; Lin, Qiang

2016-04-23

Increasing the biological effective dose (BED) of radiotherapy for non-small cell lung cancer (NSCLC) can increase local control rates and improve overall survival. Compared with conventional fractionated radiotherapy, accelerated hypofractionated radiotherapy can yield higher BED, shorten the total treatment time, and theoretically obtain better efficacy. However, currently, there is no optimal hypofractionated radiotherapy regimen. Based on phase I trial results, we performed this phase II trial to further evaluate the safety and preliminary efficacy of accelerated hypofractionated three-dimensional conformal radiation therapy(3-DCRT) combined with concurrent chemotherapy for patients with unresectable stage III NSCLC. Patients with previously untreated unresectable stage III NSCLC received 3-DCRT with a total dose of 69 Gy, delivered at 3 Gy per fraction, once daily, five fractions per week, completed within 4.6 weeks. At the same time, platinum doublet chemotherapy was applied. After 12 patients were enrolled in the group, the trial was terminated early. There were five cases of grade III radiation esophagitis, of which four cases completed the radiation doses of 51 Gy, 51 Gy, 54 Gy, and 66 Gy, and one case had 16 days of radiation interruption. The incidence of grade III acute esophagitis in patients receiving an irradiation dose per fraction ≥2.7 Gy on the esophagus was 83.3% (5/6). The incidence of symptomatic grade III radiation pneumonitis among the seven patients who completed 69 Gy according to the plan was 28.6% (2/7). The median local control (LC) and overall survival (OS) were not achieved; the 1-year LC rate was 59.3%, and the 1-year OS rate was 78.6%. For unresectable stage III NSCLC, the accelerated hypofractionated radiotherapy with a total dose of 69 Gy (3 Gy/f) combined with concurrent chemotherapy might result in severe radiation esophagitis and pneumonitis to severely affect the completion of the radiotherapy. Therefore, we considered that this regimen was infeasible. During the hypofractionated radiotherapy with concurrent chemotherapy, the irradiation dose per fraction to esophagus should be lower than 2.7 Gy. Further studies should be performed using esophageal tolerance as a metric in dose escalation protocols. NCT02720614, the date of registration: March 23, 2016.

Randomized Clinical Trial of Weekly vs. Triweekly Cisplatin-Based Chemotherapy Concurrent With Radiotherapy in the Treatment of Locally Advanced Cervical Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ryu, Sang-Young, E-mail: ryu@kcch.re.kr; Lee, Won-Moo; Kim, Kidong

Purpose: To compare compliance, toxicity, and outcome of weekly and triweekly cisplatin administration concurrent with radiotherapy in locally advanced cervical cancer. Methods and Materials: In this open-label, randomized trial, 104 patients with histologically proven Stage IIB-IVA cervical cancer were randomly assigned by a computer-generated procedure to weekly (weekly cisplatin 40 mg/m{sup 2}, six cycles) and triweekly (cisplatin 75 mg/m{sup 2} every 3 weeks, three cycles) chemotherapy arms during concurrent radiotherapy. The difference of compliance and the toxicity profiles between the two arms were investigated, and the overall survival rate was analyzed after 5 years. Results: All patients tolerated both treatmentsmore » very well, with a high completion rate of scheduled chemotherapy cycles. There was no statistically significant difference in compliance between the two arms (86.3% in the weekly arm, 92.5% in the triweekly arm, p > 0.05). Grade 3-4 neutropenia was more frequent in the weekly arm (39.2%) than in the triweekly arm (22.6%) (p = 0.03). The overall 5-year survival rate was significantly higher in the triweekly arm (88.7%) than in the weekly arm (66.5%) (hazard ratio 0.375; 95% confidence interval 0.154-0.914; p = 0.03). Conclusions: Triweekly cisplatin 75-mg/m{sup 2} chemotherapy concurrent with radiotherapy is more effective and feasible than the conventional weekly cisplatin 40-mg/m{sup 2} regimen and may be a strong candidate for the optimal cisplatin dose and dosing schedule in the treatment of locally advanced cervical cancer.« less

Compelled attention: the effects of viewing trauma-related stimuli on concurrent task performance in posttraumatic stress disorder.

PubMed

Chemtob, C M; Roitblat, H L; Hamada, R S; Muraoka, M Y; Carlson, J G; Bauer, G B

1999-04-01

We examined the ability of Vietnam veterans with PTSD to focus attention on a primary digit detection task while concurrently viewing neutral or Vietnam-related picture and word distractors. Controlling for combat exposure, military service, and psychopathology, veterans with PTSD took longer to detect the target when Vietnam-related pictures were distractors. There were no reaction time differences when word stimuli were distractors. The latency effect was specific to trials with trauma-related pictures and did not spread to neutral trials interleaved within a mixed block of trauma and neutral pictures. Individuals with PTSD recalled proportionally more Vietnam-related words than other groups, implying differential attention to Vietnam-related words. Attending to trauma-related pictures interferes with performance of a concurrent task by individuals with PTSD.

Reliability and concurrent validity of the Microsoft Xbox One Kinect for assessment of standing balance and postural control.

PubMed

Clark, Ross A; Pua, Yong-Hao; Oliveira, Cristino C; Bower, Kelly J; Thilarajah, Shamala; McGaw, Rebekah; Hasanki, Ksaniel; Mentiplay, Benjamin F

2015-07-01

The Microsoft Kinect V2 for Windows, also known as the Xbox One Kinect, includes new and potentially far improved depth and image sensors which may increase its accuracy for assessing postural control and balance. The aim of this study was to assess the concurrent validity and reliability of kinematic data recorded using a marker-based three dimensional motion analysis (3DMA) system and the Kinect V2 during a variety of static and dynamic balance assessments. Thirty healthy adults performed two sessions, separated by one week, consisting of static standing balance tests under different visual (eyes open vs. closed) and supportive (single limb vs. double limb) conditions, and dynamic balance tests consisting of forward and lateral reach and an assessment of limits of stability. Marker coordinate and joint angle data were concurrently recorded using the Kinect V2 skeletal tracking algorithm and the 3DMA system. Task-specific outcome measures from each system on Day 1 and 2 were compared. Concurrent validity of trunk angle data during the dynamic tasks and anterior-posterior range and path length in the static balance tasks was excellent (Pearson's r>0.75). In contrast, concurrent validity for medial-lateral range and path length was poor to modest for all trials except single leg eyes closed balance. Within device test-retest reliability was variable; however, the results were generally comparable between devices. In conclusion, the Kinect V2 has the potential to be used as a reliable and valid tool for the assessment of some aspects of balance performance. Copyright © 2015 Elsevier B.V. All rights reserved.

Management of Locally Advanced Cancer Cervix an Indian Perspective.

PubMed

Singh, J K; Chauhan, Richa

2015-01-01

Cervical cancer has a major impact on the lives of Indian women with an estimated 122, 844 new cases of cervical cancer in the year 2012. About 80% of these cases present in a locally advanced stage leading to high morbidity and mortality. Because of lack of public awareness and infrastructure for screening and early detection in developing countries, this late presentation is likely to continue in the coming years. Radiation therapy has been the treatment of choice for patients with locally advanced cancer cervix. Many clinical trials and meta-analyses have shown a significant improvement in overall and progression-free survival with decreased local and distant recurrences with the use of concurrent chemotherapy with radiation. Most of these trials have been done in women from developed countries where the patient and disease profile are entirely different from ours. Recently, few trials from India have also shown promising results in locally advanced cancer cervix with concurrent chemoradiotherapy but toxicities remain a major concern. Further exploration is required for the use of concurrent chemo radiation prior to incorporating it into routine clinical practice.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gomez, Daniel R., E-mail: dgomez@mdanderson.org; Gillin, Michael; Liao, Zhongxing

Background: Many patients with locally advanced non-small cell lung cancer (NSCLC) cannot undergo concurrent chemotherapy because of comorbidities or poor performance status. Hypofractionated radiation regimens, if tolerable, may provide an option to these patients for effective local control. Methods and Materials: Twenty-five patients were enrolled in a phase 1 dose-escalation trial of proton beam therapy (PBT) from September 2010 through July 2012. Eligible patients had histologically documented lung cancer, thymic tumors, carcinoid tumors, or metastatic thyroid tumors. Concurrent chemotherapy was not allowed, but concurrent treatment with biologic agents was. The dose-escalation schema comprised 15 fractions of 3 Gy(relative biological effectivenessmore » [RBE])/fraction, 3.5 Gy(RBE)/fraction, or 4 Gy(RBE)/fraction. Dose constraints were derived from biologically equivalent doses of standard fractionated treatment. Results: The median follow-up time for patients alive at the time of analysis was 13 months (range, 8-28 months). Fifteen patients received treatment to hilar or mediastinal lymph nodes. Two patients experienced dose-limiting toxicity possibly related to treatment; 1 received 3.5-Gy(RBE) fractions and experienced an in-field tracheoesophageal fistula 9 months after PBT and 1 month after bevacizumab. The other patient received 4-Gy(RBE) fractions and was hospitalized for bacterial pneumonia/radiation pneumonitis 4 months after PBT. Conclusion: Hypofractionated PBT to the thorax delivered over 3 weeks was well tolerated even with significant doses to the lungs and mediastinal structures. Phase 2/3 trials are needed to compare the efficacy of this technique with standard treatment for locally advanced NSCLC.« less

Validity and reliability of a novel measure of activity performance and participation.

PubMed

Murgatroyd, Phil; Karimi, Leila

2016-01-01

To develop and evaluate an innovative clinician-rated measure, which produces global numerical ratings of activity performance and participation. Repeated measures study with 48 community-dwelling participants investigating clinical sensibility, comprehensiveness, practicality, inter-rater reliability, responsiveness, sensitivity and concurrent validity with Barthel Index. Important clinimetric characteristics including comprehensiveness and ease of use were rated >8/10 by clinicians. Inter-rater reliability was excellent on the summary scores (intraclass correlation of 0.95-0.98). There was good evidence that the new outcome measure distinguished between known high and low functional scoring groups, including both responsiveness to change and sensitivity at the same time point in numerous tests. Concurrent validity with the Barthel Index was fair to high (Spearman Rank Order Correlation 0.32-0.85, p > 0.05). The new measure's summary scores were nearly twice as responsive to change compared with the Barthel Index. Other more detailed data could also be generated by the new measure. The Activity Performance Measure is an innovative outcome instrument that showed good clinimetric qualities in this initial study. Some of the results were strong, given the sample size, and further trial and evaluation is appropriate. Implications for Rehabilitation The Activity Performance Measure is an innovative outcome measure covering activity performance and participation. In an initial evaluation, it showed good clinimetric qualities including responsiveness to change, sensitivity, practicality, clinical sensibility, item coverage, inter-rater reliability and concurrent validity with the Barthel Index. Further trial and evaluation is appropriate.

Preliminary evidence of improved cognitive performance following vestibular rehabilitation in children with combined ADHD (cADHD) and concurrent vestibular impairment.

PubMed

Lotfi, Younes; Rezazadeh, Nima; Moossavi, Abdollah; Haghgoo, Hojjat Allah; Rostami, Reza; Bakhshi, Enayatollah; Badfar, Faride; Moghadam, Sedigheh Farokhi; Sadeghi-Firoozabadi, Vahid; Khodabandelou, Yousef

2017-12-01

Balance function has been reported to be worse in ADHD children than in their normal peers. The present study hypothesized that an improvement in balance could result in better cognitive performance in children with ADHD and concurrent vestibular impairment. This study was designed to evaluate the effects of comprehensive vestibular rehabilitation therapy on the cognitive performance of children with combined ADHD and concurrent vestibular impairment. Subject were 54 children with combined ADHD. Those with severe vestibular impairment (n=33) were randomly assigned to two groups that were matched for age. A rehabilitation program comprising overall balance and gate, postural stability, and eye movement exercises was assigned to the intervention group. Subjects in the control group received no intervention for the same time period. Intervention was administered twice weekly for 12 weeks. Choice reaction time (CRT) and spatial working memory (SWM) subtypes of the Cambridge Neuropsychological Test Automated Battery (CANTAB) were completed pre- and post-intervention to determine the effects of vestibular rehabilitation on the cognitive performance of the subjects with ADHD and concurrent vestibular impairment. ANCOVA was used to compare the test results of the intervention and control group post-test. The percentage of correct trial scores for the CRT achieved by the intervention group post-test increased significantly compared to those of the control group (p=0.029). The CRT mean latency scores were significantly prolonged in the intervention group following intervention (p=0.007) compared to the control group. No significant change was found in spatial functioning of the subjects with ADHD following 12 weeks of intervention (p>0.05). The study highlights the effect of vestibular rehabilitation on the cognitive performance of children with combined ADHD and concurrent vestibular disorder. The findings indicate that attention can be affected by early vestibular rehabilitation, which is a basic program for improving memory function in such children. Appropriate vestibular rehabilitation programs based on the type of vestibular impairment of children can improve their cognitive ability to some extent in children with ADHD and concurrent vestibular impairment (p>0.05). Copyright © 2017 Elsevier B.V. All rights reserved.

Induction Chemotherapy plus Concurrent Chemoradiotherapy in Endemic Nasopharyngeal Carcinoma: Individual Patient Data Pooled Analysis of Four Randomized Trials.

PubMed

Chen, Yu-Pei; Tang, Ling-Long; Yang, Qi; Poh, Sharon-Shuxian; Hui, Edwin P; Chan, Anthony T C; Ong, Whee-Sze; Tan, Terence; Wee, Joseph; Li, Wen-Fei; Chen, Lei; Ma, Brigette B Y; Tong, Macy; Tan, Sze-Huey; Cheah, Shie-Lee; Fong, Kam-Weng; Sommat, Kiattisa; Soong, Yoke Lim; Guo, Ying; Lin, Ai-Hua; Sun, Ying; Hong, Ming-Huang; Cao, Su-Mei; Chen, Ming-Yuan; Ma, Jun

2018-04-15

Purpose: Because of the uneven geographic distribution and small number of randomized trials available, the value of additional induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC) remains controversial. This study performed an individual patient data (IPD) pooled analysis to better assess the precise role of IC + CCRT in locoregionally advanced NPC. Experimental Design: Four randomized trials in endemic areas were identified, representing 1,193 patients; updated IPD were obtained. Progression-free survival (PFS) and overall survival (OS) were the primary and secondary endpoints, respectively. Results: Median follow-up was 5.0 years. The HR for PFS was 0.70 [95% confidence interval (CI), 0.56-0.86; P = 0.0009; 9.3% absolute benefit at 5 years] in favor of IC + CCRT versus CCRT alone. IC + CCRT also improved OS (HR = 0.75; 95% CI, 0.57-0.99; P = 0.04) and reduced distant failure (HR = 0.68; 95% CI, 0.51-0.90; P = 0.008). IC + CCRT had a tendency to improve locoregional control compared with CCRT alone (HR = 0.70; 95% CI, 0.48-1.01; P = 0.06). There was no heterogeneity between trials in any analysis. No interactions between patient characteristics and treatment effects on PFS or OS were found. After adding two supplementary trials to provide a more comprehensive overview, the conclusions remained valid and were strengthened. In a supplementary Bayesian network analysis, no statistically significant differences in survival between different IC regimens were detected. Conclusions: This IPD pooled analysis demonstrates the superiority of additional IC over CCRT alone in locoregionally advanced NPC, with the survival benefit mainly associated with improved distant control. Clin Cancer Res; 24(8); 1824-33. ©2018 AACR . ©2018 American Association for Cancer Research.

Signaled and Unsignaled Terminal Links in Concurrent Chains I: Effects of Reinforcer Probability and Immediacy

ERIC Educational Resources Information Center

Mattson, Karla M.; Hucks, Andrew; Grace, Randolph C.; McLean, Anthony P.

2010-01-01

Eight pigeons responded in a three-component concurrent-chains procedure, with either independent or dependent initial links. Relative probability and immediacy of reinforcement in the terminal links were both varied, and outcomes on individual trials (reinforcement or nonreinforcement) were either signaled or unsignaled. Terminal-link fixed-time…

Randomized Controlled Trial for Behavioral Smoking and Weight Control Treatment: Effect of Concurrent versus Sequential Intervention

PubMed Central

Spring, Bonnie; Doran, Neal; Pagoto, Sherry; Schneider, Kristin; Pingitore, Regina; Hedeker, Don

2014-01-01

Prospects for changing multiple health behaviors conjointly remain controversial. We compared effects on tobacco abstinence and weight gain of adding diet and exercise concurrently or after smoking treatment. Female regular smokers (n=315) randomized to 3 conditions received 16 weeks of behavioral smoking treatment, quit at week 5, and were followed for 9 months after the quit date. Weight management was added to the first 8 weeks for Early Diet (ED), the final 8 weeks for Late Diet (LD), and omitted for Control. Both Diet groups tended to show greater bio-verified abstinence than Control although differences were nonsignificant. Compared to Control, ED initially suppressed weight gain but lost that effect over time, whereas LD initially lacked but gradually acquired a weight suppression effect that stabilized [p = .004]. Behavioral weight control did not undermine smoking cessation and slowed the rate of weight gain when initiated after the smoking quit date, supporting a sequential approach to multiple behavior change. PMID:15482037

Rowing performance, body composition, and bone mineral density outcomes in college-level rowers after a season of concurrent training.

PubMed

Young, Kaelin C; Kendall, Kristina L; Patterson, Kaitlyn M; Pandya, Priyanka D; Fairman, Ciaran M; Smith, Samuel W

2014-11-01

To assess changes in body composition, lumbar-spine bone mineral density (BMD), and rowing performance in college-level rowers over a competition season. Eleven Division I college rowers (mean ± SD 21.4 ± 3.7 y) completed 6 testing sessions throughout the course of their competition season. Testing included measurements of fat mass, bone-free lean mass (BFLM), body fat (%BF), lumbar-spine BMD, and 2000-m time-trial performance. After preseason testing, rowers participated in a periodized training program, with the addition of resistance training to the traditional aerobic-training program. Significant (P < .05) improvements in %BF, total mass, and BFLM were observed at midseason and postseason compared with preseason. Neither lumbar-spine BMD nor BMC significantly changed over the competitive season (P > .05). Finally, rowing performance (as measured by 2000-m time and average watts achieved) significantly improved at midseason and postseason compared with preseason. Our results highlight the efficacy of a seasonal concurrent training program serving to improve body composition and rowing performance, as measured by 2000-m times and average watts, among college-level rowers. Our findings offer practical applications for coaches and athletes looking to design a concurrent strength and aerobic training program to improve rowing performance across a season.

Demographic and clinical characteristics of treatment seeking women with full and subthreshold PTSD and concurrent cannabis and cocaine use disorders.

PubMed

Ruglass, Lesia M; Shevorykin, Alina; Brezing, Christina; Hu, Mei-Chen; Hien, Denise A

2017-09-01

While the detrimental effects of concurrent substance use disorders (SUDs) are now being well documented, very few studies have examined this comorbidity among women with posttraumatic stress disorder (PTSD). Data for these analyses were derived from the "Women and Trauma" study conducted within the National Drug Abuse Treatment Clinical Trials Network. Women with full or subthreshold PTSD and co-occurring cannabis use disorder (CUD) and cocaine use disorder (COD; N=99) were compared to their counterparts with co-occurring CUD only (N=26) and co-occurring COD only (N=161) on rates of trauma exposure, psychiatric disorders, psychosocial problems, and other substance use utilizing a set of multivariate logistic regressions. In models adjusted for age and race/ethnicity, women with PTSD and COD only were significantly older than their counterparts with CUD only and concurrent CUD+COD. Relative to those with CUD only, women with concurrent CUD+COD had higher odds of adult sexual assault. Relative to those with COD only, women with concurrent CUD+COD had higher odds of alcohol use disorder in the past 12months. Finally, relative to those with CUD only, women with COD only had higher odds of ever being arrested/convicted and adult sexual assault. The higher rates of adult sexual assault and alcohol use disorder among those with concurrent CUD+COD suggest the need for trauma-informed approaches that can respond to the needs of this dually-diagnosed population. Moreover, the causal link between repeated traumatic stress exposure and polysubstance use requires further examination. Copyright © 2017 Elsevier Inc. All rights reserved.

The Efficacy of an 8-Week Concurrent Strength and Endurance Training Programme on Hand Cycling Performance.

PubMed

Nevin, Jonpaul; Waldron, Mark; Patterson, Stephen; Smith, Paul; Price, Mike; Hunt, Alex

2018-03-20

The aim of the present study was to investigate the effects of an 8-week concurrent strength and endurance training programme in comparison to endurance training only on several key determinants of hand cycling performance. Five H4 and five H3 classified hand cyclists with at least one year's hand cycling training history consented to participate in the study. Subjects underwent a battery of tests to establish body mass, body composition, VO2peak, maximum aerobic power, gross mechanical efficiency, maximal upper body strength, and 30 km time trial performance. Subjects were matched into pairs based upon 30 km time trial performance and randomly allocated to either a concurrent strength and endurance or endurance training only, intervention group. Following an 8-week training programme based upon a conjugated block periodisation model, subjects completed a second battery of tests. A mixed model, 2-way analysis of variance (ANOVA) revealed no significant changes between groups. However, the calculation of effect sizes (ES) revealed that both groups demonstrated a positive improvement in most physiological and performance measures with subjects in the concurrent group demonstrating a greater magnitude of improvement in body composition (ES -0.80 vs. -0.22) maximal aerobic power (ES 0.97 vs. 0.28), gross mechanical efficiency (ES 0.87 vs. 0.63), bench press 1 repetition maximum (ES 0.53 vs. 0.33), seated row 1 repetition maximum (ES 1.42 vs. 0.43), and 30 km time trial performance (ES -0.66 vs. -0.30). In comparison to endurance training only, an 8-week concurrent training intervention based upon a conjugated block periodisation model appears to be a more effective training regime for improving the performance capabilities of hand cyclists.

Concurrent Stereotactic Radiosurgery and Bevacizumab in Recurrent Malignant Gliomas: A Prospective Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cabrera, Alvin R.; Cuneo, Kyle C.; Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan

2013-08-01

Purpose: Virtually all patients with malignant glioma (MG) eventually recur. This study evaluates the safety of concurrent stereotactic radiosurgery (SRS) and bevacizumab (BVZ), an antiangiogenic agent, in treatment of recurrent MG. Methods and Materials: Fifteen patients with recurrent MG, treated at initial diagnosis with surgery and adjuvant radiation therapy/temozolomide and then at least 1 salvage chemotherapy regimen, were enrolled in this prospective trial. Lesions <3 cm in diameter were treated in a single fraction, whereas those 3 to 5 cm in diameter received 5 5-Gy fractions. BVZ was administered immediately before SRS and 2 weeks later. Neurocognitive testing (Mini-Mental Statusmore » Exam, Trail Making Test A/B), Functional Assessment of Cancer Therapy-Brain (FACT-Br) quality-of-life assessment, physical exam, and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) were performed immediately before SRS and 1 week and 2 months following completion of SRS. The primary endpoint was central nervous system (CNS) toxicity. Secondary endpoints included survival, quality of life, microvascular properties as measured by DCE-MRI, steroid usage, and performance status. Results: One grade 3 (severe headache) and 2 grade 2 CNS toxicities were observed. No patients experienced grade 4 to 5 toxicity or intracranial hemorrhage. Neurocognition, quality of life, and Karnofsky performance status did not change significantly with treatment. DCE-MRI results suggest a significant decline in tumor perfusion and permeability 1 week after SRS and further decline by 2 months. Conclusions: Treatment of recurrent MG with concurrent SRS and BVZ was not associated with excessive toxicity in this prospective trial. A randomized trial of concurrent SRS/BVZ versus conventional salvage therapy is needed to establish the efficacy of this approach.« less

Conducting qualitative research within Clinical Trials Units: avoiding potential pitfalls.

PubMed

Cooper, Cindy; O'Cathain, Alicia; Hind, Danny; Adamson, Joy; Lawton, Julia; Baird, Wendy

2014-07-01

The value of using qualitative research within or alongside randomised controlled trials (RCTs) is becoming more widely accepted. Qualitative research may be conducted concurrently with pilot or full RCTs to understand the feasibility and acceptability of the interventions being tested, or to improve trial conduct. Clinical Trials Units (CTUs) in the United Kingdom (UK) manage large numbers of RCTs and, increasingly, manage the qualitative research or collaborate with qualitative researchers external to the CTU. CTUs are beginning to explicitly manage the process, for example, through the use of standard operating procedures for designing and implementing qualitative research with trials. We reviewed the experiences of two UK Clinical Research Collaboration (UKCRC) registered CTUs of conducting qualitative research concurrently with RCTs. Drawing on experiences gained from 15 studies, we identify the potential for the qualitative research to undermine the successful completion or scientific integrity of RCTs. We show that potential problems can arise from feedback of interim or final qualitative findings to members of the trial team or beyond, in particular reporting qualitative findings whilst the trial is on-going. The problems include: We make recommendations for improving the management of qualitative research within CTUs. Copyright © 2014. Published by Elsevier Inc.

Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn's disease: a randomized controlled trial.

PubMed

Farrell, Richard J; Alsahli, Mazen; Jeen, Yoon-Tae; Falchuk, Kenneth R; Peppercorn, Mark A; Michetti, Pierre

2003-04-01

We assessed the relationship between antibodies to infliximab (ATI) and the loss of response postinfliximab, infusion reactions and, in a randomized trial, investigated whether intravenous hydrocortisone premedication can reduce ATI. Initially, we prospectively evaluated clinical response, adverse events, and ATI levels in 53 consecutive patients with Crohn's disease who received 199 infliximab (5 mg/kg) infusions. Subsequently, 80 patients with Crohn's disease were randomized to intravenous hydrocortisone 200 mg or placebo immediately before their first and subsequent infliximab infusions. The primary endpoint was reduction in median ATI levels at week 16. Analysis was by intention to treat. Nineteen of our initial 53 patients (36%) developed ATI, including all 7 patients with serious infusion reactions (median ATI level, 19.6 microg/mL). Eleven of 15 patients (73%) who lost their initial response were ATI positive compared with none of 21 continuous responders, (8.9 vs. 0.7 microg/mL, P < 0.0001). Administering a second infusion within 8 weeks of the first (OR, 0.13; 95% CI, 0.03-0.5; P = 0.0007) or concurrent immunosuppressants (OR, 0.19; 95% CI, 0.04-1.03; P = 0.007) significantly reduced ATI formation. In the placebo-controlled trial, ATI levels were lower at week 16 among hydrocortisone-treated patients (1.6 vs. 3.4 microg/mL, P = 0.02), and 26% of hydrocortisone-treated patients developed ATI compared with 42% of placebo-treated patients, P = 0.06. Loss of initial response and infusion reactions post-infliximab is strongly related to ATI formation and level. Administering a second infusion within 8 weeks of the first and concurrent immunosuppressant therapy significantly reduce ATI formation. Intravenous hydrocortisone premedication significantly reduces ATI levels but does not eliminate ATI formation or infusion reactions.

Phase III Trial of Trimodality Therapy With Cisplatin, Fluorouracil, Radiotherapy, and Surgery Compared With Surgery Alone for Esophageal Cancer: CALGB 9781

PubMed Central

Tepper, Joel; Krasna, Mark J.; Niedzwiecki, Donna; Hollis, Donna; Reed, Carolyn E.; Goldberg, Richard; Kiel, Krystyna; Willett, Christopher; Sugarbaker, David; Mayer, Robert

2016-01-01

Purpose The primary treatment modality for patients with carcinoma of the esophagus or gastroesophageal junction has been surgery, although primary radiation therapy with concurrent chemotherapy produces similar results. As both have curative potential, there has been great interest in the use of trimodality therapy. To this end, we compared survival, response, and patterns of failure of trimodality therapy to esophagectomy alone in patients with nonmetastatic esophageal cancer. Patients and Methods Four hundred seventy-five eligible patients were planned for enrollment. Patients were randomly assigned to either esophagectomy with node dissection alone or cisplatin 100 mg/m2 and fluorouracil 1,000 mg/m2/d for 4 days on weeks 1 and 5 concurrent with radiation therapy (50.4 Gy total: 1.8 Gy/fraction over 5.6 weeks) followed by esophagectomy with node dissection. Results Fifty-six patients were enrolled between October 1997 and March 2000, when the trial was closed due to poor accrual. Thirty patients were randomly assigned to trimodality therapy and 26 were assigned to surgery alone. Patient and tumor characteristics were similar between groups. Treatment was generally well tolerated. Median follow-up was 6 years. An intent-to-treat analysis showed a median survival of 4.48 v 1.79 years in favor of trimodality therapy (exact stratified log-rank, P = .002). Five-year survival was 39% (95% CI, 21% to 57%) v 16% (95% CI, 5% to 33%) in favor of trimodality therapy. Conclusion The results from this trial reflect a long-term survival advantage with the use of chemoradiotherapy followed by surgery in the treatment of esophageal cancer, and support trimodality therapy as a standard of care for patients with this disease. PMID:18309943

Proposed variations of the stepped-wedge design can be used to accommodate multiple interventions.

PubMed

Lyons, Vivian H; Li, Lingyu; Hughes, James P; Rowhani-Rahbar, Ali

2017-06-01

Stepped-wedge design (SWD) cluster-randomized trials have traditionally been used for evaluating a single intervention. We aimed to explore design variants suitable for evaluating multiple interventions in an SWD trial. We identified four specific variants of the traditional SWD that would allow two interventions to be conducted within a single cluster-randomized trial: concurrent, replacement, supplementation, and factorial SWDs. These variants were chosen to flexibly accommodate study characteristics that limit a one-size-fits-all approach for multiple interventions. In the concurrent SWD, each cluster receives only one intervention, unlike the other variants. The replacement SWD supports two interventions that will not or cannot be used at the same time. The supplementation SWD is appropriate when the second intervention requires the presence of the first intervention, and the factorial SWD supports the evaluation of intervention interactions. The precision for estimating intervention effects varies across the four variants. Selection of the appropriate design variant should be driven by the research question while considering the trade-off between the number of steps, number of clusters, restrictions for concurrent implementation of the interventions, lingering effects of each intervention, and precision of the intervention effect estimates. Copyright © 2017 Elsevier Inc. All rights reserved.

Pharmacological evidence that both cognitive memory and habit formation contribute to within-session learning of concurrent visual discriminations

PubMed Central

Turchi, Janita; Devan, Bryan; Yin, Pingbo; Sigrist, Emmalynn; Mishkin, Mortimer

2010-01-01

The monkey's ability to learn a set of visual discriminations presented concurrently just once a day on successive days (24-hr ITI task) is based on habit formation, which is known to rely on a visuo-striatal circuit and to be independent of visuo-rhinal circuits that support one-trial memory. Consistent with this dissociation, we recently reported that performance on the 24-hr ITI task is impaired by a striatal-function blocking agent, the dopaminergic antagonist haloperidol, and not by a rhinal-function blocking agent, the muscarinic cholinergic antagonist scopolamine. In the present study, monkeys were trained on a short-ITI form of concurrent visual discrimination learning, one in which a set of stimulus pairs is repeated not only across daily sessions but also several times within each session (in this case, at about 4-min ITIs). Asymptotic discrimination learning rates in the non-drug condition were reduced by half, from ~11 trials/pair on the 24-hr ITI task to ~5 trials/pair on the 4-min ITI task, and this faster learning was impaired by systemic injections of either haloperidol or scopolamine. The results suggest that in the version of concurrent discrimination learning used here, the short ITIs within a session recruit both visuo-rhinal and visuo-striatal circuits, and that the final performance level is driven by both cognitive memory and habit formation working in concert. PMID:20144631

Pharmacological evidence that both cognitive memory and habit formation contribute to within-session learning of concurrent visual discriminations.

PubMed

Turchi, Janita; Devan, Bryan; Yin, Pingbo; Sigrist, Emmalynn; Mishkin, Mortimer

2010-07-01

The monkey's ability to learn a set of visual discriminations presented concurrently just once a day on successive days (24-h ITI task) is based on habit formation, which is known to rely on a visuo-striatal circuit and to be independent of visuo-rhinal circuits that support one-trial memory. Consistent with this dissociation, we recently reported that performance on the 24-h ITI task is impaired by a striatal-function blocking agent, the dopaminergic antagonist haloperidol, and not by a rhinal-function blocking agent, the muscarinic cholinergic antagonist scopolamine. In the present study, monkeys were trained on a short-ITI form of concurrent visual discrimination learning, one in which a set of stimulus pairs is repeated not only across daily sessions but also several times within each session (in this case, at about 4-min ITIs). Asymptotic discrimination learning rates in the non-drug condition were reduced by half, from approximately 11 trials/pair on the 24-h ITI task to approximately 5 trials/pair on the 4-min ITI task, and this faster learning was impaired by systemic injections of either haloperidol or scopolamine. The results suggest that in the version of concurrent discrimination learning used here, the short ITIs within a session recruit both visuo-rhinal and visuo-striatal circuits, and that the final performance level is driven by both cognitive memory and habit formation working in concert.

Patterns of prevalent HPV and STI co-infections and associated factors among HIV-negative young Western Cape, South African women: the EVRI trial.

PubMed

Menezes, Lynette J; Pokharel, Ubin; Sudenga, Staci L; Botha, Matthys H; Zeier, Michele; Abrahamsen, Martha E; Glashoff, Richard H; Engelbrecht, Susan; Schim van der Loeff, Maarten F; van der Laan, Louvina E; Kipping, Siegfried; Taylor, Douglas; Giuliano, Anna R

2018-02-01

To estimate the prevalence and describe the patterns of concurrent human papillomavirus (HPV) and STIs and associated factors among HIV-negative young Western Cape, South African women participating in the Efficacy of HPV Vaccine to Reduce HIV Infection (EVRI) trial. HIV-negative women aged 16-24 years old were enrolled in the EVRI trial (NCT01489527) and randomised to receive the licensed four-valent HPV vaccine or placebo. At study entry, participants were clinically evaluated for five STIs: herpes simplex virus type 2 (HSV-2), chlamydia, gonorrhoea, syphilis and disease-causing HPV genotypes (6/11/16/18/31/33/35/39/45/51/52/56/58/59/68). Demographic and sexual history characteristics were compared among women with STI co-infections, single infection and no infection using Pearson χ 2 and Mann-Whitney tests. ORs were calculated to evaluate factors associated with STI co-infection prevalence. Among 388 young women, STI co-infection prevalence was high: 47% had ≥2 concurrent STIs, 36% had a single STI and 17% had none of the five evaluated STIs. HPV/HSV-2 (26%) was the most prevalent co-infection detected followed by HPV/HSV-2/ Chlamydia trachomatis (CT) (17%) and HPV/CT (15%). Co-infection prevalence was independently associated with alcohol use (adjusted OR=2.01, 95% CI 1.00 to 4.06) and having a sexual partner with an STI (adjusted OR=6.96, 95% CI 1.53 to 30.08). Among high-risk young women from underserved communities such as in Southern Africa, a multicomponent prevention strategy that integrates medical and behavioural interventions targeting both men and women is essential to prevent acquisition of concurrent STI infections and consequent disease. NCT01489527; Post-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

CHARACTERISTICS OF MULTIPLE AND CONCURRENT PARTNERSHIPS AMONG WOMEN AT HIGH RISK FOR HIV INFECTION

PubMed Central

Adimora, Adaora A.; Hughes, James P.; Wang, Jing; Haley, Danielle F.; Golin, Carol E.; Magnus, Manya; Rompalo, Anne; Justman, Jessica; del Rio, Carlos; El-Sadr, Wafaa; Mannheimer, Sharon; Soto-Torres, Lydia; Hodder, Sally L.

2014-01-01

Objectives We examined parameters of sexual partnerships, including respondents’ participation in concurrency, belief that their partner had concurrent partnerships (partners’ concurrency), and partnership intervals, among the 2,099 women in HIV Prevention Trials Network 064, a study of women at high risk for HIV infection, in ten US communities. Methods We analyzed baseline survey responses about partnership dates to determine prevalence of participants’ and partners’ concurrency, intervals between partnerships, knowledge of whether recent partner(s) had undergone HIV testing, and intercourse frequency during the preceding 6 months. Results Prevalence of participants’ and partners’ concurrency was 40% and 36% respectively; 24% of respondents had both concurrent partnerships and non-monogamous partners. Among women with >1 partner and no concurrent partnerships themselves, the median gap between partners was one month. Multiple episodes of unprotected vaginal intercourse with >2 of their most recent partners was reported by 60% of women who had both concurrent partnerships and non-monogamous partners, 50% with only concurrent partners and no partners’ concurrency, and 33% with only partners’ concurrency versus 14% of women with neither type of concurrency (p<.0001). Women who had any involvement with concurrency were also more likely than women with no concurrency involvement to report lack of awareness of whether recent partners had undergone HIV testing (participants’ concurrency 41%, partners’ concurrency 40%, both participants’ and partners’ concurrency 48%, neither 17%; p<.0001). Conclusions These network patterns and short gaps between partnerships may create substantial opportunities for HIV transmission in this sample of women at high risk for HIV infection. PMID:24056163

Searching ClinicalTrials.gov did not change the conclusions of a systematic review.

PubMed

Wilson, Lisa M; Sharma, Ritu; Dy, Sydney M; Waldfogel, Julie M; Robinson, Karen A

2017-10-01

We assessed the effect of searching ClinicalTrials.gov on the conclusions of a systematic review. We conducted this case study concurrently with a systematic review. We searched ClinicalTrials.gov on March 9, 2016, to identify trial records eligible for inclusion in the review. Two independent reviewers screened ClinicalTrials.gov records. We compared conclusions and strength of evidence grade with and without ClinicalTrials.gov records for 31 comparisons and 2 outcomes. We identified 106 trials (53 in the peer-reviewed literature only, 23 in ClinicalTrials.gov only, and 30 in both sources). For one comparison, the addition of results identified through ClinicalTrials.gov reduced the pooled effect size. We found evidence of selective outcome reporting for two comparisons and suspected publication bias for another two comparisons. For all other comparisons, searching ClinicalTrials.gov did not change conclusions or the strength of evidence grading for the two outcomes. Our search of ClinicalTrials.gov bolstered suspicions of reporting biases but did not change either the conclusions or the strength of evidence grading. Further research is needed to determine the effect of searching ClinicalTrials.gov on the conclusions of systematic reviews in different topic areas and as the new rules for registration of trial results take effect. Copyright © 2017 Elsevier Inc. All rights reserved.

Recruitment of urban US women at risk for HIV infection and willingness to participate in future HIV vaccine trials

PubMed Central

Metch, Barbara; Frank, Ian; Novak, Richard; Swann, Edith; Metzger, David; Morgan, Cecilia; Lucy, Debbie; Dunbar, Debora; Graham, Parrie; Madenwald, Tamra; Escamilia, Gina; Koblin, Beryl

2012-01-01

Enrollment of US women with sufficient risk of HIV infection into HIV vaccine efficacy trials has proved challenging. A cohort of 799 HIV-negative women, aged 18-45, recruited from three US cities was enrolled to assess recruitment strategies based on geographic risk pockets, social and sexual networks and occurrence of sexual concurrency and to assess HIV seroincidence during follow-up (to be reported later). Among enrolled women, 90% lived or engaged in risk behaviors within a local risk pocket, 64% had a male partner who had concurrent partners and 50% had a male partner who had been recently incarcerated. Nearly half (46%) were recruited through peer referral. At enrollment, 86% of women said they were willing to participate in a vaccine efficacy trial. Results indicate that participant and partner risk behaviors combined with a peer referral recruitment strategy may best identify an at-risk cohort willing to participate in future trials. PMID:23090677

Final results of a multi-institutional phase II trial of reirradiation with concurrent weekly cisplatin and cetuximab for recurrent or second primary squamous cell carcinoma of the head and neck.

PubMed

Awan, M J; Nedzi, L; Wang, D; Tumati, V; Sumer, B; Xie, X-J; Smith, I; Truelson, J; Hughes, R; Myers, L L; Lavertu, P; Wong, S; Yao, M

2018-04-01

The optimal regimen of chemotherapy and reirradiation (re-XRT) for recurrent head and neck squamous cell carcinoma (HNSCC) is controversial. We report the final outcomes of a multicenter phase II trial evaluating cetuximab and cisplatin-based chemotherapy concurrent with re-XRT for patients with recurrent HNSCC. Patients with unresectable recurrent disease or positive margins after salvage surgery arising within a previously irradiated field with KPS ≥ 70 were eligible for this trial. Cetuximab 400 mg/m2 was delivered as a loading dose in week 1 followed by weekly cetuximab 250 mg/m2 and cisplatin 30 mg/m2 concurrent with 6 weeks of intensity-modulated radiotherapy to a dose of 60-66 Gy in 30 daily fractions. Patients who previously received both concurrent cetuximab and cisplatin with radiation or who received radiotherapy less than 6 months prior were ineligible. From 2009 to 2013, 48 patients enrolled on this trial, 2 did not receive any protocol treatment. Of the remaining 46 patients, 34 were male and 12 female, with a median age of 62 years (range 36-85). Treatment was feasible and only 1 patient did not complete the treatment course. Common grade 3 or higher acute toxicities were lymphopenia (46%), pain (22%), dysphagia (13%), radiation dermatitis (13%), mucositis (11%) and anorexia (11%). There were no grade 5 acute toxicities. Eight grade 3 late toxicities were observed, four of which were swallowing related. With a median follow-up of 1.38 years, the 1-year overall survival (OS) was 60.4% and 1-year recurrence-free survival was 34.1%. On univariate analysis, OS was significantly improved with young age (P = 0.01). OS was not associated with radiation dose, surgery before re-XRT or interval from prior XRT. Concurrent cisplatin and cetuximab with re-XRT is feasible and offers good treatment outcomes for patients with high-risk features. Younger patients had significantly improved OS. NCT00833261.

Randomised phase III trial of concurrent chemoradiotherapy with extended nodal irradiation and erlotinib in patients with inoperable oesophageal squamous cell cancer.

PubMed

Wu, Shi-Xiu; Wang, Lv-Hua; Luo, Hong-Lei; Xie, Cong-Ying; Zhang, Xue-Bang; Hu, Wei; Zheng, An-Ping; Li, Duo-Jie; Zhang, Hong-Yan; Xie, Cong-Hua; Lian, Xi-Long; Du, De-Xi; Chen, Ming; Bian, Xiu-Hua; Tan, Bang-Xian; Jiang, Hao; Zhang, Hong-Bo; Wang, Jian-Hua; Jing, Zhao; Xia, Bing; Zhang, Ni; Zhang, Ping; Li, Wen-Feng; Zhao, Fu-Jun; Tian, Zhi-Feng; Liu, Hui; Huang, Ke-Wei; Hu, Jin; Xie, Rui-Fei; Du, Lin; Li, Gang

2018-04-01

This randomised phase III study was conducted to investigate the efficacy of extended nodal irradiation (ENI) and/or erlotinib in inoperable oesophageal squamous cell cancer (ESCC). Patients with histologically confirmed locally advanced ESCC or medically inoperable disease were randomly assigned (ratio 1:1:1:1) to one of four treatment groups: group A, radiotherapy adoption of ENI with two cycles of concurrent TP chemotherapy (paclitaxel 135 mg/m 2  day 1 and cisplatin 20 mg/m 2 days 1-3, every 4 weeks) plus erlotinib (150 mg per day during chemoradiotherapy); group B, radiotherapy adoption of ENI with two cycles of concurrent TP; group C, radiotherapy adoption of conventional field irradiation (CFI) with two cycles of concurrent TP plus erlotinib; group D, radiotherapy adoption of CFI with two cycles of concurrent TP. A total of 352 patients (88 assigned to each treatment group) were enrolled. The 2-year overall survival rates of group A, B, C and D were 57.8%, 49.9%, 44.9% and 38.7%, respectively (P = 0.015). Group A significantly improved 2-year overall survival compared with group D. The ENI significantly improved overall survival in patients with inoperable ESCC (P = 0.014). The addition of erlotinib significantly decreased loco-regional recurrence (P = 0.042). Aside from rash and radiation oesophagitis, the incidence of grade 3 or greater toxicities did not differ among 4 groups. Chemoradiotherapy with ENI and erlotinib might represent a substantial improvement on the standard of care for inoperable ESCC. ENI alone should be adopted in concurrent chemoradiotherapy for ESCC patients. Copyright © 2018 Elsevier Ltd. All rights reserved.

Whole-pelvis, 'mini-pelvis,' or prostate-only external beam radiotherapy after neoadjuvant and concurrent hormonal therapy in patients treated in Radiation Therapy Oncology Group 9413 trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roach, Mack; De Silvio, Michelle; Valicenti, Richard

2006-11-01

Purpose: Radiation Therapy Oncology Group (RTOG) 9413 trial demonstrated a better progression-free survival (PFS) with whole-pelvis (WP) radiotherapy (RT) compared with prostate-only (PO) RT. This secondary analysis was undertaken to determine whether 'mini-pelvis' (MP; defined as {>=}10 x 11 cm but <11 x 11 cm) RT resulted in progression-free survival (PFS) comparable to that of WP RT. To avoid a timing bias, this analysis was limited to patients receiving neoadjuvant and concurrent hormonal therapy (N and CHT) in Arms 1 and 2 of the study. Methods and Materials: Eligible patients had a risk of lymph node (LN) involvement >15%. Neoadjuvantmore » and concurrent hormonal therapy (N and CHT) was administered 2 months before and during RT for 4 months. From April 1, 1995, to June 1, 1999, a group of 325 patients were randomized to WP RT + N and CHT and another group of 324 patients were randomized to receive PO RT + N and CHT. Patients randomized to PO RT were dichotomized by median field size (10 x 11 cm), with the larger field considered an 'MP' field and the smaller a PO field. Results: The median PFS was 5.2, 3.7, and 2.9 years for WP, MP, and PO fields, respectively (p = 0.02). The 7-year PFS was 40%, 35%, and 27% for patients treated to WP, MP, and PO fields, respectively. There was no association between field size and late Grade 3+ genitourinary toxicity but late Grade 3+ gastrointestinal RT complications correlated with increasing field size. Conclusions: This subset analysis demonstrates that RT field size has a major impact on PFS, and the findings support comprehensive nodal treatment in patients with a risk of LN involvement of >15%.« less

Short-course versus long-course chemoradiation in rectal cancer--time to change strategies?

PubMed

Palta, Manisha; Willett, Christopher G; Czito, Brian G

2014-09-01

There is significant debate regarding the optimal neoadjuvant regimen for resectable rectal cancer patients. Short-course radiotherapy, a standard approach throughout most of northern Europe, is generally defined as 25 Gy in 5 fractions over the course of 1 week without the concurrent administration of chemotherapy. Long-course radiotherapy is typically defined as 45 to 50.4 Gy in 25-28 fractions with the administration of concurrent 5-fluoropyrimidine-based chemotherapy and is the standard approach in other parts of Europe and the United States. At present, two randomized trials have compared outcomes for short course radiotherapy with long-course chemoradiation showing no difference in respective study endpoints. Late toxicity data are lacking given limited follow-up. Although the ideal neoadjuvant regimen is controversial, our current bias is long-course chemoradiation to treat patients with locally advanced, resectable rectal cancer.

Developing stepped care treatment for depression (STEPS): study protocol for a pilot randomised controlled trial.

PubMed

Hill, Jacqueline J; Kuyken, Willem; Richards, David A

2014-11-20

Stepped care is recommended and implemented as a means to organise depression treatment. Compared with alternative systems, it is assumed to achieve equivalent clinical effects and greater efficiency. However, no trials have examined these assumptions. A fully powered trial of stepped care compared with intensive psychological therapy is required but a number of methodological and procedural uncertainties associated with the conduct of a large trial need to be addressed first. STEPS (Developing stepped care treatment for depression) is a mixed methods study to address uncertainties associated with a large-scale evaluation of stepped care compared with high-intensity psychological therapy alone for the treatment of depression. We will conduct a pilot randomised controlled trial with an embedded process study. Quantitative trial data on recruitment, retention and the pathway of patients through treatment will be used to assess feasibility. Outcome data on the effects of stepped care compared with high-intensity therapy alone will inform a sample size calculation for a definitive trial. Qualitative interviews will be undertaken to explore what people think of our trial methods and procedures and the stepped care intervention. A minimum of 60 patients with Major Depressive Disorder will be recruited from an Improving Access to Psychological Therapies service and randomly allocated to receive stepped care or intensive psychological therapy alone. All treatments will be delivered at clinic facilities within the University of Exeter. Quantitative patient-related data on depressive symptoms, worry and anxiety and quality of life will be collected at baseline and 6 months. The pilot trial and interviews will be undertaken concurrently. Quantitative and qualitative data will be analysed separately and then integrated. The outcomes of this study will inform the design of a fully powered randomised controlled trial to evaluate the effectiveness and efficiency of stepped care. Qualitative data on stepped care will be of immediate interest to patients, clinicians, service managers, policy makers and guideline developers. A more informed understanding of the feasibility of a large trial will be obtained than would be possible from a purely quantitative (or qualitative) design. Current Controlled Trials ISRCTN66346646 registered on 2 July 2014.

28 CFR 52.01 - Civil proceedings: Special master, pretrial, trial, appeal.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Civil proceedings: Special master...) PROCEEDINGS BEFORE U.S. MAGISTRATE JUDGES § 52.01 Civil proceedings: Special master, pretrial, trial, appeal... as special master, if the attorney, with the concurrence of his or her supervisor, determines that...

28 CFR 52.01 - Civil proceedings: Special master, pretrial, trial, appeal.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Civil proceedings: Special master...) PROCEEDINGS BEFORE U.S. MAGISTRATE JUDGES § 52.01 Civil proceedings: Special master, pretrial, trial, appeal... as special master, if the attorney, with the concurrence of his or her supervisor, determines that...

28 CFR 52.01 - Civil proceedings: Special master, pretrial, trial, appeal.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Civil proceedings: Special master...) PROCEEDINGS BEFORE U.S. MAGISTRATE JUDGES § 52.01 Civil proceedings: Special master, pretrial, trial, appeal... as special master, if the attorney, with the concurrence of his or her supervisor, determines that...

28 CFR 52.01 - Civil proceedings: Special master, pretrial, trial, appeal.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Civil proceedings: Special master...) PROCEEDINGS BEFORE U.S. MAGISTRATE JUDGES § 52.01 Civil proceedings: Special master, pretrial, trial, appeal... as special master, if the attorney, with the concurrence of his or her supervisor, determines that...

Self-controlled concurrent feedback facilitates the learning of the final approach phase in a fixed-base flight simulator.

PubMed

Huet, Michaël; Jacobs, David M; Camachon, Cyril; Goulon, Cedric; Montagne, Gilles

2009-12-01

This study (a) compares the effectiveness of different types of feedback for novices who learn to land a virtual aircraft in a fixed-base flight simulator and (b) analyzes the informational variables that learners come to use after practice. An extensive body of research exists concerning the informational variables that allow successful landing. In contrast, few studies have examined how the attention of pilots can be directed toward these sources of information. In this study, 15 participants were asked to land a virtual Cessna 172 on 245 trials while trying to follow the glide-slope area as accurately as possible. Three groups of participants practiced under different feedback conditions: with self-controlled concurrent feedback (the self-controlled group), with imposed concurrent feedback (the yoked group), or without concurrent feedback (the control group). The self-controlled group outperformed the yoked group, which in turn outperformed the control group. Removing or manipulating specific sources of information during transfer tests had different effects for different individuals. However, removing the cockpit from the visual scene had a detrimental effect on the performance of the majority of the participants. Self-controlled concurrent feedback helps learners to more quickly attune to the informational variables that allow them to control the aircraft during the approach phase. Knowledge concerning feedback schedules can be used for the design of optimal practice methods for student pilots, and knowledge about the informational variables used by expert performers has implications for the design of cockpits and runways that facilitate the detection of these variables.

Biomechanical Analyses of Stair-climbing while Dual-tasking

PubMed Central

Vallabhajosula, Srikant; Tan, Chi Wei; Mukherjee, Mukul; Davidson, Austin J.; Stergiou, Nicholas

2015-01-01

Stair-climbing while doing a concurrent task like talking or holding an object is a common activity of daily living which poses high risk for falls. While biomechanical analyses of overground walking during dual-tasking have been studied extensively, little is known on the biomechanics of stair-climbing while dual-tasking. We sought to determine the impact of performing a concurrent cognitive or motor task during stair-climbing. We hypothesized that a concurrent cognitive task will have a greater impact on stair climbing performance compared to a concurrent motor task and that this impact will be greater on a higher-level step. Ten healthy young adults performed 10 trials of stair-climbing each under four conditions: stair ascending only, stair ascending and performing subtraction of serial sevens from a three-digit number, stair ascending and carrying an empty opaque box and stair ascending, performing subtraction of serial sevens from a random three-digit number and carrying an empty opaque box. Kinematics (lower extremity joint angles and minimum toe clearance) and kinetics (ground reaction forces and joint moments and powers) data were collected. We found that a concurrent cognitive task impacted kinetics but not kinematics of stair-climbing. The effect of dual-tasking during stair ascent also seemed to vary based on the different phases of stair ascent stance and seem to have greater impact as one climbs higher. Overall, the results of the current study suggest that the association between the executive functioning and motor task (like gait) becomes stronger as the level of complexity of the motor task increases. PMID:25773590

Risk of upper gastrointestinal bleeding with selective serotonin reuptake inhibitors with or without concurrent nonsteroidal anti-inflammatory use: a systematic review and meta-analysis.

PubMed

Anglin, Rebecca; Yuan, Yuhong; Moayyedi, Paul; Tse, Frances; Armstrong, David; Leontiadis, Grigorios I

2014-06-01

There is emerging concern that selective serotonin reuptake inhibitors (SSRIs) may be associated with an increased risk of upper gastrointestinal (GI) bleeding, and that this risk may be further increased by concurrent use of nonsteroidal anti-inflammatory (NSAID) medications. Previous reviews of a relatively small number of studies have reported a substantial risk of upper GI bleeding with SSRIs; however, more recent studies have produced variable results. The objective of this study was to obtain a more precise estimate of the risk of upper GI bleeding with SSRIs, with or without concurrent NSAID use. MEDLINE, EMBASE, PsycINFO, the Cochrane central register of controlled trials (through April 2013), and US and European conference proceedings were searched. Controlled trials, cohort, case-control, and cross-sectional studies that reported the incidence of upper GI bleeding in adults on SSRIs with or without concurrent NSAID use, compared with placebo or no treatment were included. Data were extracted independently by two authors. Dichotomous data were pooled to obtain odds ratio (OR) of the risk of upper GI bleeding with SSRIs +/- NSAID, with a 95% confidence interval (CI). The main outcome and measure of the study was the risk of upper GI bleeding with SSRIs compared with placebo or no treatment. Fifteen case-control studies (including 393,268 participants) and four cohort studies were included in the analysis. There was an increased risk of upper GI bleeding with SSRI medications in the case-control studies (OR=1.66, 95% CI=1.44,1.92) and cohort studies (OR=1.68, 95% CI=1.13,2.50). The number needed to harm for upper GI bleeding with SSRI treatment in a low-risk population was 3,177, and in a high-risk population it was 881. The risk of upper GI bleeding was further increased with the use of both SSRI and NSAID medications (OR=4.25, 95% CI=2.82,6.42). SSRI medications are associated with a modest increase in the risk of upper GI bleeding, which is lower than has previously been estimated. This risk is significantly elevated when SSRI medications are used in combination with NSAIDs, and physicians prescribing these medications together should exercise caution and discuss this risk with patients.

Validity of clinical outcome measures to evaluate ankle range of motion during the weight-bearing lunge test.

PubMed

Hall, Emily A; Docherty, Carrie L

2017-07-01

To determine the concurrent validity of standard clinical outcome measures compared to laboratory outcome measure while performing the weight-bearing lunge test (WBLT). Cross-sectional study. Fifty participants performed the WBLT to determine dorsiflexion ROM using four different measurement techniques: dorsiflexion angle with digital inclinometer at 15cm distal to the tibial tuberosity (°), dorsiflexion angle with inclinometer at tibial tuberosity (°), maximum lunge distance (cm), and dorsiflexion angle using a 2D motion capture system (°). Outcome measures were recorded concurrently during each trial. To establish concurrent validity, Pearson product-moment correlation coefficients (r) were conducted, comparing each dependent variable to the 2D motion capture analysis (identified as the reference standard). A higher correlation indicates strong concurrent validity. There was a high correlation between each measurement technique and the reference standard. Specifically the correlation between the inclinometer placement at 15cm below the tibial tuberosity (44.9°±5.5°) and the motion capture angle (27.0°±6.0°) was r=0.76 (p=0.001), between the inclinometer placement at the tibial tuberosity angle (39.0°±4.6°) and the motion capture angle was r=0.71 (p=0.001), and between the distance from the wall clinical measure (10.3±3.0cm) to the motion capture angle was r=0.74 (p=0.001). This study determined that the clinical measures used during the WBLT have a high correlation with the reference standard for assessing dorsiflexion range of motion. Therefore, obtaining maximum lunge distance and inclinometer angles are both valid assessments during the weight-bearing lunge test. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Improved survival and complete response rates in patients with advanced melanoma treated with concurrent ipilimumab and radiotherapy versus ipilimumab alone.

PubMed

Koller, Kristian M; Mackley, Heath B; Liu, Jason; Wagner, Henry; Talamo, Giampaolo; Schell, Todd D; Pameijer, Colette; Neves, Rogerio I; Anderson, Bryan; Kokolus, Kathleen M; Mallon, Carol A; Drabick, Joseph J

2017-01-02

There is a growing body of evidence supporting the synergistic roles of radiotherapy and immunotherapy in the treatment of malignancy. Published case studies of the abscopal effect have been reported with the use of ipilimumab and radiotherapy in metastatic melanoma, but evidence supporting the routine use of this combination of therapy is limited. We conducted a retrospective analysis to evaluate patients treated with ipilimumab for advanced melanoma at a single institution from May 2011 to June 2015. Patients were grouped into those who had received concurrent radiotherapy while on ipilimumab (Ipi-RT), and those who did not. We then evaluated the treatment response following completion of ipilimumab. A total of 101 patients received ipilimumab in the prespecified time frame. 70 received Ipi-RT and 31 received ipilimumab without concurrent radiotherapy. Median overall survival (OS) was significantly increased in the concurrent Ipi-RT arm at 19 months vs. 10 months for ipilimumab alone (p = 0.01). Median progression free survival (PFS) was marginally increased in the Ipi-RT group compare with the ipilimumab alone group (5 months vs. 3 months, p = 0.20). Rates of complete response (CR) were significantly increased in the Ipi-RT group vs. ipilimumab alone (25.7% vs. 6.5%; p = 0.04), and rates of overall response (OR) in the groups were 37.1% vs. 19.4% (p = 0.11). No increase in toxicities was observed in the Ipi-RT group compare with ipilimumab alone. Prospective trials are needed to further clarify the role of radiotherapy with ipilimumab, but these encouraging preliminary observations suggest that this combination can induce more durable responses to immunotherapy.

Improved survival and complete response rates in patients with advanced melanoma treated with concurrent ipilimumab and radiotherapy versus ipilimumab alone

PubMed Central

Koller, Kristian M.; Mackley, Heath B.; Liu, Jason; Wagner, Henry; Talamo, Giampaolo; Schell, Todd D.; Pameijer, Colette; Neves, Rogerio I.; Anderson, Bryan; Kokolus, Kathleen M.; Mallon, Carol A.; Drabick, Joseph J.

2017-01-01

ABSTRACT There is a growing body of evidence supporting the synergistic roles of radiotherapy and immunotherapy in the treatment of malignancy. Published case studies of the abscopal effect have been reported with the use of ipilimumab and radiotherapy in metastatic melanoma, but evidence supporting the routine use of this combination of therapy is limited. We conducted a retrospective analysis to evaluate patients treated with ipilimumab for advanced melanoma at a single institution from May 2011 to June 2015. Patients were grouped into those who had received concurrent radiotherapy while on ipilimumab (Ipi-RT), and those who did not. We then evaluated the treatment response following completion of ipilimumab. A total of 101 patients received ipilimumab in the prespecified time frame. 70 received Ipi-RT and 31 received ipilimumab without concurrent radiotherapy. Median overall survival (OS) was significantly increased in the concurrent Ipi-RT arm at 19 months vs. 10 months for ipilimumab alone (p = 0.01). Median progression free survival (PFS) was marginally increased in the Ipi-RT group compare with the ipilimumab alone group (5 months vs. 3 months, p = 0.20). Rates of complete response (CR) were significantly increased in the Ipi-RT group vs. ipilimumab alone (25.7% vs. 6.5%; p = 0.04), and rates of overall response (OR) in the groups were 37.1% vs. 19.4% (p = 0.11). No increase in toxicities was observed in the Ipi-RT group compare with ipilimumab alone. Prospective trials are needed to further clarify the role of radiotherapy with ipilimumab, but these encouraging preliminary observations suggest that this combination can induce more durable responses to immunotherapy. PMID:27905824

Proposed variations of the stepped-wedge design can be used to accommodate multiple interventions

PubMed Central

Lyons, Vivian H; Li, Lingyu; Hughes, James P; Rowhani-Rahbar, Ali

2018-01-01

Objective Stepped wedge design (SWD) cluster randomized trials have traditionally been used for evaluating a single intervention. We aimed to explore design variants suitable for evaluating multiple interventions in a SWD trial. Study Design and Setting We identified four specific variants of the traditional SWD that would allow two interventions to be conducted within a single cluster randomized trial: Concurrent, Replacement, Supplementation and Factorial SWDs. These variants were chosen to flexibly accommodate study characteristics that limit a one-size-fits-all approach for multiple interventions. Results In the Concurrent SWD, each cluster receives only one intervention, unlike the other variants. The Replacement SWD supports two interventions that will not or cannot be employed at the same time. The Supplementation SWD is appropriate when the second intervention requires the presence of the first intervention, and the Factorial SWD supports the evaluation of intervention interactions. The precision for estimating intervention effects varies across the four variants. Conclusion Selection of the appropriate design variant should be driven by the research question while considering the trade-off between the number of steps, number of clusters, restrictions for concurrent implementation of the interventions, lingering effects of each intervention, and precision of the intervention effect estimates. PMID:28412466

Comparison of the clinical efficacy between single-agent and dual-agent concurrent chemoradiotherapy in the treatment of unresectable esophageal squamous cell carcinoma: a multicenter retrospective analysis.

PubMed

Li, Jie; Gong, Youling; Diao, Peng; Huang, Qingmei; Wen, Yixue; Lin, Binwei; Cai, Hongwei; Tian, Honggang; He, Bing; Ji, Lanlan; Guo, Ping; Miao, Jidong; Du, Xiaobo

2018-01-22

Some Chinese patients with esophageal squamous cell carcinomaare often treated with single-agent concurrent chemoradiotherapy. However, no results have been reported from randomized controlled clinical trials comparing single-agent with double-agent concurrent chemoradiotherapy. It therefore remains unclear whether these regimens are equally clinically effective. In this study, we retrospectively analyzed and compared the therapeutic effects of single-agent and double-agent concurrent chemoradiotherapy in patients with unresectable esophageal squamous cell carcinoma. This study enrolled 168 patients who received definitive concurrent chemoradiotherapy for locally advanced unresectable esophageal squamous carcinoma at 10 hospitals between 2010 and 2015. We evaluated survival time and toxicity. The Kaplan-Meier method was used to estimate survival data. The log-rank test was used in univariate analysis A Cox proportional hazards regression model was used to conduct a multivariate analysis of the effects of prognostic factors on survival. In this study, 100 (59.5%) and 68 patients (40.5%) received single-agent and dual-agent combination chemoradiotherapy, respectively. The estimate 5-year progression-free survival (PFS) rate and overall survival (OS) rate of dual-agent therapy was higher than that of single-agent therapy (52.5% and 40.9%, 78.2% and 60.7%, respectively), but there were no significant differences (P = 0.367 and 0.161, respectively). Multivariate analysis showed that sex, age,and radiotherapy dose had no significant effects on OS or PFS. Only disease stage was associated with OS and PFS in the multivariable analysis (P = 0.006 and 0.003, respectively). In dual-agent group, the incidence of acute toxicity and the incidence of 3 and4 grade toxicity were higher than single-agent group. The 5-year PFS and OS rates of dual-agent therapy were higher than those of single-agent concurrent chemoradiotherapy for patients with unresectable esophageal squamous cell carcinoma; however, there were no significant differences in univariate analysis and multivariable analysis. Single-agent concurrent chemotherapy had less toxicity than a double-drug regimen. Therefore, we suggest that single therapis not inferior to dual therapy y. In the future, we aim to confirm our hypothesis through a prospective randomized study.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hoppe, Bradford S., E-mail: bhoppe@floridaproton.org; Henderson, Randal; Pham, Dat

Purpose: Proton therapy has been shown to reduce radiation dose to organs at risk (OAR) and could be used to safely escalate the radiation dose. We analyzed outcomes in a group of phase 2 study patients treated with dose-escalated proton therapy with concurrent chemotherapy for stage 3 non-small cell lung cancer (NSCLC). Methods and Materials: From 2009 through 2013, LU02, a phase 2 trial of proton therapy delivering 74 to 80 Gy at 2 Gy/fraction with concurrent chemotherapy for stage 3 NSCLC, was opened to accrual at our institution. Due to slow accrual and competing trials, the study was closed after justmore » 14 patients (stage IIIA, 9 patients; stage IIIB, 5 patients) were accrued over 4 years. During that same time period, 55 additional stage III patients were treated with high-dose proton therapy, including 7 in multi-institutional proton clinical trials, 4 not enrolled due to physician preference, and 44 who were ineligible based on strict entry criteria. An unknown number of patients were ineligible for enrollment due to insurance coverage issues and thus were treated with photon radiation. Median follow-up of surviving patients was 52 months. Results: Two-year overall survival and progression-free survival rates were 57% and 25%, respectively. Median lengths of overall survival and progression-free survival were 33 months and 14 months, respectively. There were no acute grade 3 toxicities related to proton therapy. Late grade 3 gastrointestinal toxicity and pulmonary toxicity each occurred in 1 patient. Conclusions: Dose-escalated proton therapy with concurrent chemotherapy was well tolerated with encouraging results among a small cohort of patients. Unfortunately, single-institution proton studies may be difficult to accrue and consideration for pragmatic and/or multicenter trial design should be considered when developing future proton clinical trials.« less

Reliability and Validity of Objective Measures of Physical Activity in Youth With Cerebral Palsy Who Are Ambulatory.

PubMed

O'Neil, Margaret E; Fragala-Pinkham, Maria; Lennon, Nancy; George, Ameeka; Forman, Jeffrey; Trost, Stewart G

2016-01-01

Physical therapy for youth with cerebral palsy (CP) who are ambulatory includes interventions to increase functional mobility and participation in physical activity (PA). Thus, reliable and valid measures are needed to document PA in youth with CP. The purpose of this study was to evaluate the inter-instrument reliability and concurrent validity of 3 accelerometer-based motion sensors with indirect calorimetry as the criterion for measuring PA intensity in youth with CP. Fifty-seven youth with CP (mean age=12.5 years, SD=3.3; 51% female; 49.1% with spastic hemiplegia) participated. Inclusion criteria were: aged 6 to 20 years, ambulatory, Gross Motor Function Classification System (GMFCS) levels I through III, able to follow directions, and able to complete the full PA protocol. Protocol activities included standardized activity trials with increasing PA intensity (resting, writing, household chores, active video games, and walking at 3 self-selected speeds), as measured by weight-relative oxygen uptake (in mL/kg/min). During each trial, participants wore bilateral accelerometers on the upper arms, waist/hip, and ankle and a portable indirect calorimeter. Intraclass coefficient correlations (ICCs) were calculated to evaluate inter-instrument reliability (left-to-right accelerometer placement). Spearman correlations were used to examine concurrent validity between accelerometer output (activity and step counts) and indirect calorimetry. Friedman analyses of variance with post hoc pair-wise analyses were conducted to examine the validity of accelerometers to discriminate PA intensity across activity trials. All accelerometers exhibited excellent inter-instrument reliability (ICC=.94-.99) and good concurrent validity (rho=.70-.85). All accelerometers discriminated PA intensity across most activity trials. This PA protocol consisted of controlled activity trials. Accelerometers provide valid and reliable measures of PA intensity among youth with CP. © 2016 American Physical Therapy Association.

A phase III concurrent chemoradiotherapy trial with cisplatin and paclitaxel or docetaxel or gemcitabine in unresectable non-small cell lung cancer: KASLC 0401.

PubMed

Oh, In-Jae; Kim, Kyu-Sik; Kim, Young-Chul; Ban, Hee-Jung; Kwon, Yong-Soo; Kim, Yu-Il; Lim, Sung-Chul; Chung, Woong-Ki; Nam, Taek-Keun; Song, Joo-Young; Yoon, Mee-Sun; Ahn, Sung-Ja

2013-12-01

Concurrent chemoradiotherapy (CCRT) is recommended for the management of patients with unresectable non-small cell lung cancer (NSCLC). This prospective study aimed to compare the efficacy of concurrently delivered cisplatin doublets with paclitaxel, or docetaxel, or gemcitabine. The main eligibility criteria consisted of previously untreated stage IIIB NSCLC. The subjects were randomized into three arms: paclitaxel 45 mg/m(2)/week (TP), docetaxel 20 mg/m(2)/week (DP), and gemcitabine 350 mg/m(2)/week (GP) in addition to cisplatin 20 mg/m(2)/week. Three-dimensional conformal radiotherapy was given once daily, weekly 5 fractions and the total prescription dose was 60-66 Gy. The primary endpoint was response rate, and the secondary endpoints were survival and toxicity. A total of 101 patients were recruited into this trial of whom 93 (TP: 33, DP: 29, GP: 31) patients were treated with CCRT from March 2005 to July 2007. Similar response rates were observed across arms: TP: 63.6 %, DP: 72.4 %, GP: 61.3 % (p = 0.679). There was no statistically significant difference of median survival (TP: 27.3, DP: 27.6, GP: 16.5 months, p = 0.771). In subgroup analysis, a survival benefit of consolidation chemotherapy was not seen, but leucopenia (63.2 %) and neutropenia (68.4 %) more than grade 3 were significantly high in DP arm. The grade ≥3 radiation esophagitis was more frequent in the GP arm (22.6 %, p = 0.163). Among the three arms, no statistically significant difference in response rate, survival, and toxicity was observed. However, clinically significant radiation toxicity was more frequent in the GP arm.

Mechanical and Pharmacologic Methods of Labor Induction: A Randomized Controlled Trial

PubMed Central

Levine, Lisa D.; Downes, Katheryne L.; Elovitz, Michal A.; Parry, Samuel; Sammel, Mary D.; Srinivas, Sindhu K

2016-01-01

Objective To evaluate the effectiveness of four commonly used induction methods. Methods This randomized trial compared four induction methods: Misoprostol alone, Foley alone, Misoprostol–cervical Foley concurrently, and Foley–oxytocin concurrently,. Women undergoing labor induction with full term (≥37 weeks), singleton, vertex presenting gestations, with no contraindication to vaginal delivery, intact membranes, Bishop score ≤6, and cervical dilation ≤2cm were included. Women were enrolled only once during the study period. Our primary outcome was time to delivery. Neither patients nor providers were blinded to assigned treatment group since examinations are required for placement of all methods; however, research personnel were blinded during data abstraction. A sample size of 123 per group (N=492) was planned to compare the four groups pairwise (P≤.008), with a 4-hour reduction in delivery time considered clinically meaningful. Results From May 2013 through June 2015, 997 women were screened and 491 were randomized and analyzed. Demographic and clinical characteristics were similar among the four treatment groups. When comparing all induction method groups, combination methods achieved a faster median time to delivery than single-agent methods, (misoprostol–Foley: 13.1 hours, Foley–oxytocin: 14.5 hours, misoprostol: 17.6 hours, Foley: 17.7 hours, p<0.001). When censored for cesarean and adjusting for parity, women who received misoprostol–Foley delivered almost twice as likely to deliver before women who received misoprostol alone (hazard ratio (HR, 95% CI) 1.92 [1.42–2.59]) or Foley alone (HR, 95%CI: 1.87 [1.39–2.52]), whereas Foley–oxytocin was not statistically different from single-agent methods. Conclusion After censoring for cesarean and adjusting for parity, misoprostol–cervical Foley resulted in twice the chance of delivering before either single-agent method. PMID:27824758

Pushing typists back on the learning curve: Memory chunking in the hierarchical control of skilled typewriting.

PubMed

Yamaguchi, Motonori; Logan, Gordon D

2016-12-01

Hierarchical control of skilled performance depends on the ability of higher level control to process several lower level units as a single chunk. The present study investigated the development of hierarchical control of skilled typewriting, focusing on the process of memory chunking. In the first 3 experiments, skilled typists typed words or nonwords under concurrent memory load. Memory chunks developed and consolidated into long-term memory when the same typing materials were repeated in 6 consecutive trials, but chunks did not develop when repetitions were spaced. However, when concurrent memory load was removed during training, memory chunks developed more efficiently with longer lags between repetitions than shorter lags. From these results, it is proposed that memory chunking requires 2 representations of the same letter string to be maintained simultaneously in short-term memory: 1 representation from the current trial, and the other from an earlier trial that is either retained from the immediately preceding trial or retrieved from long-term memory (i.e., study state retrieval). (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Effectiveness of functional hand splinting and the cognitive orientation to occupational performance (CO-OP) approach in children with cerebral palsy and brain injury: two randomised controlled trial protocols

PubMed Central

2014-01-01

Background Cerebral palsy (CP) and brain injury (BI) are common conditions that have devastating effects on a child’s ability to use their hands. Hand splinting and task-specific training are two interventions that are often used to address deficits in upper limb skills, both in isolation or concurrently. The aim of this paper is to describe the method to be used to conduct two randomised controlled trials (RCT) investigating (a) the immediate effect of functional hand splints, and (b) the effect of functional hand splints used concurrently with task-specific training compared to functional hand splints alone, and to task-specific training alone in children with CP and BI. The Cognitive Orientation to Occupational Performance (CO-OP) approach will be the task-specific training approach used. Methods/Design Two concurrent trials; a two group, parallel design, RCT with a sample size of 30 participants (15 per group); and a three group, parallel design, assessor blinded, RCT with a sample size of 45 participants (15 per group). Inclusion criteria: age 4-15 years; diagnosis of CP or BI; Manual Abilities Classification System (MACS) level I – IV; hand function goals; impaired hand function; the cognitive, language and behavioural ability to participate in CO-OP. Participants will be randomly allocated to one of 3 groups; (1) functional hand splint only (n=15); (2) functional hand splint combined with task-specific training (n=15); (3) task-specific training only (n=15). Allocation concealment will be achieved using sequentially numbered, sealed opaque envelopes opened by an off-site officer after baseline measures. Treatment will be provided for a period of 2 weeks, with outcome measures taken at baseline, 1 hour after randomisation, 2 weeks and 10 weeks. The functional hand splint will be a wrist cock-up splint (+/- thumb support or supination strap). Task-specific training will involve 10 sessions of CO-OP provided in a group of 2-4 children. Primary outcome measures will be the Canadian Occupational Performance Measure (COPM) and the Goal Attainment Scale (GAS). Analysis will be conducted on an intention-to-treat basis. Discussion This paper outlines the protocol for two randomised controlled trials investigating functional hand splints and CO-OP for children with CP and BI. PMID:25023385

Quality of life with cediranib in relapsed ovarian cancer: The ICON6 phase 3 randomized clinical trial.

PubMed

Stark, Dan P; Cook, Adrian; Brown, Julia M; Brundage, Michael D; Embleton, Andrew C; Kaplan, Richard S; Raja, Fharat A; Swart, Ann Marie W; Velikova, Galina; Qian, Wendi; Ledermann, Jonathan A

2017-07-15

The ICON6 trial showed that cediranib, an oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, improved clinical outcomes for patients with platinum-sensitive relapsed ovarian cancer when it was used with chemotherapy and was continued as maintenance therapy. This study describes health-related quality of life (QOL) during the first year of treatment. Four hundred fifty-six women were randomly allocated to receive standard chemotherapy only, chemotherapy with concurrent cediranib, or chemotherapy with cediranib administered concurrently and continued as maintenance. Patients completed QOL questionnaires until disease progression every 3 weeks during chemotherapy and then every 6 weeks to 1 year. Patients alive with disease progression completed a QOL form 1 year after randomization. The primary QOL endpoint was the global score from the Quality of Life Questionnaire Core 30 (of the European Organization for Research and Treatment of Cancer) at 1 year, with the standard chemotherapy group compared with the concurrent-maintenance cediranib group. The rate of questionnaire compliance was 90% at the baseline and 76% at 1 year and was similar across the 3 groups. The mean global QOL score at 1 year was 62.6 points for the standard chemotherapy group and 68.7 points for the concurrent-maintenance group (+4.5; 95% confidence interval, -2.0 to 11.0; P = .18). Sensitivity analyses suggested that this finding was robust to the effect of missing data, and the improvement became statistically significant after adjustments for self-reported diarrhea. The 6th study by the International Collaboration in Ovarian Neoplasm (ICON6) showed a significant improvement in progression-free survival with cediranib as concurrent and maintenance therapy. No QOL detriment with cediranib was found 1 year after treatment was commenced. The maintenance of QOL along with prolonged cancer control suggests that cediranib has a valuable role in the treatment of relapsed ovarian cancer. Cancer 2017;123:2752-61. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Construct, Concurrent and Predictive Validity of the URICA: Data from Two Multi-site Clinical Trials

PubMed Central

Field, Craig A.; Adinoff, Bryon; Harris, T. Robert; Ball, Samuel A.; Carroll, Kathleen M.

2011-01-01

Background A better understanding of how to measure motivation to change and how it relates to behavior change in patients with drug and alcohol dependence would broaden our understanding of the role of motivation in addiction treatment. Methods Two multi-site, randomized clinical trials comparing brief motivational interventions with standard care were conducted in the National Institute on Drug Abuse Clinical Trials Network. Patients with primary drug dependence and alcohol dependence entering outpatient treatment participated in a study of either Motivational Enhancement Therapy (n=431) or Motivational Interviewing (n=423). The construct, concurrent, and predictive validity of two composite measures of motivation to change derived from the University of Rhode Island Change Assessment (URICA): Readiness to Change (RTC) and Committed Action (CA) were evaluated. Results Confirmatory factor analysis confirmed the a priori factor structure of the URICA. RTC was significantly associated with measures of addiction severity at baseline (r=.12-.52, p<.05). Although statistically significant (p<.01), the correlations between treatment outcomes and RTC were low (r=-.15 and -18). Additional analyses did not support a moderating or mediating effect of motivation on treatment retention or substance use. Conclusions The construct validity of the URICA was confirmed separately in a large sample of drug- and alcohol-dependent patients. However, evidence for the predictive validity of composite scores was very limited and there were no moderating or mediating effects of either measure on treatment outcome. Thus, increased motivation to change, as measured by the composite scores of motivation derived from the URICA, does not appear to influence treatment outcome. PMID:19157723

Is heterogeneity in stage 3 non-small cell lung cancer obscuring the potential benefits of dose-escalated concurrent chemo-radiotherapy in clinical trials?

PubMed

Hudson, Andrew; Chan, Clara; Woolf, David; McWilliam, Alan; Hiley, Crispin; O'Connor, James; Bayman, Neil; Blackhall, Fiona; Faivre-Finn, Corinne

2018-04-01

The current standard of care for the management of inoperable stage 3 non-small cell lung cancer (NSCLC) is concurrent chemoradiotherapy (cCRT) using radiotherapy dose-fractionation and chemotherapy regimens that were established 3 decades ago. In an attempt to improve the chances of long-term control from cCRT, dose-escalation of the radiotherapy dose was assessed in the RTOG 0617 randomised control study comparing the standard 60 Gy in 30 fractions with a high-dose arm receiving 74 Gy in 37 fractions. Following the publication of this trial the thoracic oncology community were surprised to learn that there was worse survival in the dose-escalated arm and that for now the standard of care must remain with the lower dose. In this article we review the RTOG 0617 paper with subsequent analyses and studies to explore why the use of dose-escalated cCRT in stage 3 NSCLC has not shown the benefits that were expected. The overarching theme of this opinion piece is how heterogeneity between stage 3 NSCLC cases in terms of patient, tumour, and clinical factors may obscure the potential benefits of dose-escalation by causing imbalances in the arms of studies such as RTOG 0617. We also examine recent advances in the staging, management, and technological delivery of radiotherapy in NSCLC and how these may be employed to optimise cCRT trials in the future and ensure that any potential benefits of dose-escalation can be detected. Copyright © 2018 Elsevier B.V. All rights reserved.

A retrospective analysis of case series using home-prepared and chicken hydrolysate diets in the diagnosis of adverse food reactions in 181 pruritic dogs.

PubMed

Loeffler, Anette; Soares-Magalhaes, Ricardo; Bond, Ross; Lloyd, David H

2006-08-01

The purpose of this retrospective study was to compare home-prepared and chicken hydrolysate diets in the diagnosis of canine adverse food reactions (AFR). Seventy-two dogs were fed home-prepared diets and 109 were fed hydrolysate. Owners chose the type of diet at presentation, and ingredients of home-prepared diets were selected depending on each dog's dietary history. Ectoparasitic infestations and microbial infections were treated during the trials. Cutaneous and gastrointestinal signs and pruritus scores were recorded before starting the diet, 6 weeks into the trials and after provocation with the original diets. AFR was diagnosed if pruritus resolved during the trial and recurred on dietary provocation. The dropout rate was lower for home-prepared diets although not statistically significant (18.1% home prepared; 24.7% hydrolysate, P=0.377). AFR alone was diagnosed in 10 dogs (17%) using home-prepared diets and in 15 (18.3%) fed the hydrolysate. Gastrointestinal problems were more frequent in dogs with AFR than in dogs without AFR (P=0.001). Another 11 dogs (18.6%) in the home-prepared diet group and 20 (24.4%) in the hydrolysate diet group had AFR concurrent with other pruritic diseases, mainly atopy. The similar frequencies of AFR diagnosis in the two groups (P=0.837 AFR; P=0.416 concurrent AFR) indicate that the chicken hydrolysate diet may be a valuable alternative to home-prepared diets in the diagnosis of canine AFR. Prospective cross-over studies are warranted to confirm these findings.

Results of concurrent radio-chemotherapy for the treatment of head and neck squamous cell carcinoma in everyday clinical practice with special reference to early mortality

PubMed Central

2013-01-01

Background Randomized controlled trials have established concurrent chemo-radiotherapy as the preferred treatment option for inoperable local-regionally advanced head and neck squamous cell carcinomas (HNSCCs). Because many patients have multiple co-morbidities and would not fulfill the eligibility criteria of clinical trials, the results need to be re-evaluated in daily clinical practice with special reference to early mortality. Methods 167 consecutive patients with HNSCC who received concurrent chemo-radiotherapy at the Basel University Hospital between 1988 and 2006 were analyzed retrospectively with a special focus on early deaths and risk factors for an unfavorable outcome. Results In our cohort, the 3- and 5-year overall survival rates were 54% and 47%, respectively. The therapy was associated with relevant toxicity and an early mortality rate of 5.4%. Patients dying early were analyzed individually for the cause of death. Patients with elevated white blood cell counts (HR: 2.66 p = 0,016) and vascular co-morbidities (HR: 5.3, p = 0,047) showed significantly worse survival rates. The same factors were associated with a trend toward increased treatment-related mortality. The 3-year survival rate improved from approximately 43% for patients treated before the year 2000 to 65% for patients treated after the year 2000 (Fisher’s exact test p = 0.01). Conclusions Although many patients who received concurrent chemo-radiotherapy would not have qualified for clinical trials, the outcome was favorable and has significantly improved in recent years. However the early mortality was slightly worse than what is described in the literature. PMID:24373220

[Induction chemotherapy with docetaxel plus cisplatin (TP regimen) followed by concurrent chemoradiotherapy with TP regimen versus cisplatin in treating locally advanced nasopharyngeal carcinoma].

PubMed

Xie, Fang-Yun; Zou, Guo-Rong; Hu, Wei-Han; Qi, Shu-Nan; Peng, Miao; Li, Ji-Shi

2009-03-01

Clinical trials on docetaxel plus cisplatin (DDP) (TP regimen) in treating nasopharyngeal carcinoma (NPC) are still uncertain due to limited samples. This study was to compare the short-term efficacy and toxicity of induction chemotherapy with TP regimen followed by concurrent chemoradiotherapy with TP regimen versus DDP in treating locally advanced NPC. Fifty-seven patients with stage T3-4N2-3M0 NPC diagnosed pathologically from December 2005 to December 2006 were randomized into TP group (30 patients) and DDP group (27 patients). Both groups received TP regimen as induction chemotherapy with docetaxel (70 mg/m(2)) on Day 1 and DDP (80 mg/m(2)) on Day 2, repeating every 21 days for 2 cycles. For concurrent chemotherapy, TP group were administered docetaxel (60 mg/m(2)) on Day 1 and DDP (80 mg/m(2)) on Day 2; DDP group were administered DDP (80 mg/m(2)) on Day 1. Both schedules were repeated every 21 days for 2 cycles. Linear accelerator was used as radioactive source. Irradiation field was designed with CT-simulation and conventional fractions. The 57 patients received 111 cycles of induction chemotherapy, and 53 of them received 103 cycles of concurrent chemotherapy; four patients ceased induction chemotherapy and three ceased concurrent chemotherapy. All patients completed radiotherapy. The major toxicity of induction chemotherapy was hematologic toxicity; the main toxicities of concurrent chemoradiotherapy were hematologic toxicity and mucositis. The occurrence rates of Grade 3-4 leucopenia and Grade 3-4 neutropenia were significantly higher in TP group than in DDP groups (p <0.05). In concurrent chemoradiotherapy, the application rate of granulocyte colony stimulating factor (G-CSF) was significantly higher in TP group than in DDP group (100% vs. 72.0%, p<0.05). After concurrent chemoradiotherapy, the complete remission (CR) rates of the nasopharynx and regional lymph nodes were 93.3% and 92.9% in TP group, and were 96.3% and 91.3% in DDP group (p>0.05). The short-term efficacy of induction chemotherapy with TP regimen followed by concurrent chemoradiotherapy with TP regimen on locally advanced NPC is similar to that of TP regimen followed by concurrent chemoradiotherapy with DDP. The toxicity of the former schedule is severer than that of the latter, but it is tolerable with the use of G-CSF. The long-term efficacy of induction chemotherapy with TP regimen followed by concurrent chemoradiotherapy with TP regimen need to be further studied.

THE 6-MINUTE WALK TEST AND OTHER CLINICAL ENDPOINTS IN DUCHENNE MUSCULAR DYSTROPHY: RELIABILITY, CONCURRENT VALIDITY, AND MINIMAL CLINICALLY IMPORTANT DIFFERENCES FROM A MULTICENTER STUDY

PubMed Central

McDonald, Craig M; Henricson, Erik K; Abresch, R Ted; Florence, Julaine; Eagle, Michelle; Gappmaier, Eduard; Glanzman, Allan M; Spiegel, Robert; Barth, Jay; Elfring, Gary; Reha, Allen; Peltz, Stuart W

2013-01-01

Introduction: An international clinical trial enrolled 174 ambulatory males ≥5 years old with nonsense mutation Duchenne muscular dystrophy (nmDMD). Pretreatment data provide insight into reliability, concurrent validity, and minimal clinically important differences (MCIDs) of the 6-minute walk test (6MWT) and other endpoints. Methods: Screening and baseline evaluations included the 6-minute walk distance (6MWD), timed function tests (TFTs), quantitative strength by myometry, the PedsQL, heart rate–determined energy expenditure index, and other exploratory endpoints. Results: The 6MWT proved feasible and reliable in a multicenter context. Concurrent validity with other endpoints was excellent. The MCID for 6MWD was 28.5 and 31.7 meters based on 2 statistical distribution methods. Conclusions: The ratio of MCID to baseline mean is lower for 6MWD than for other endpoints. The 6MWD is an optimal primary endpoint for Duchenne muscular dystrophy (DMD) clinical trials that are focused therapeutically on preservation of ambulation and slowing of disease progression. Muscle Nerve 48: 357–368, 2013 PMID:23674289

Concurrent partnerships and HIV: an inconvenient truth

PubMed Central

2011-01-01

The strength of the evidence linking concurrency to HIV epidemic severity in southern and eastern Africa led the Joint United Nations Programme on HIV/AIDS and the Southern African Development Community in 2006 to conclude that high rates of concurrent sexual partnerships, combined with low rates of male circumcision and infrequent condom use, are major drivers of the AIDS epidemic in southern Africa. In a recent article in the Journal of the International AIDS Society, Larry Sawers and Eileen Stillwaggon attempt to challenge the evidence for the importance of concurrency and call for an end to research on the topic. However, their "systematic review of the evidence" is not an accurate summary of the research on concurrent partnerships and HIV, and it contains factual errors concerning the measurement and mathematical modelling of concurrency. Practical prevention-oriented research on concurrency is only just beginning. Most interventions to raise awareness about the risks of concurrency are less than two years old; few evaluations and no randomized-controlled trials of these programmes have been conducted. Determining whether these interventions can help people better assess their own risks and take steps to reduce them remains an important task for research. This kind of research is indeed the only way to obtain conclusive evidence on the role of concurrency, the programmes needed for effective prevention, the willingness of people to change behaviour, and the obstacles to change. PMID:21406080

Efficacy and safety of anti-EGFR agents administered concurrently with standard therapies for patients with head and neck squamous cell carcinoma: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Tian, Yunhong; Lin, Jie; Tian, Yunming; Zhang, Guoqian; Zeng, Xing; Zheng, Ronghui; Zhang, Weijun; Yuan, Yawei

2018-06-01

Agents targeting epidermal growth factor receptor (EGFR) are used to treat head and neck squamous cell carcinoma (HNSCC); however, their efficacy and safety is poorly understood. Here we evaluated the efficacy and safety of anti-EGFR agents administered concurrently with standard therapies for HNSCC. Randomized controlled trials that evaluated addition of EGFR targeted therapy versus standard therapy alone were included. The primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS), overall response rate (ORR), locoregional control, and severe adverse events (SAEs, grade ≥ 3). Sixteen eligible trials with 4031 patients were included. Addition of anti-EGFR regimens to standard therapy significantly improved OS of patients with HNSCC (HR = 0.89; 95% CI, 0.82-0.96), with a moderately elevated rate of SAEs (RR = 1.08; 95% CI, 1.03-1.13). Subgroup analysis indicated that the survival benefit was observed when cetuximab was administered concurrently with radiotherapy (RT) for stage III/IV patients (HR = 0.76; 95% CI, 0.61-0.94; p = 0.01), or with chemotherapy for recurrent or metastatic (R/M) HNSCC (HR = 0.86; 95% CI, 0.78-0.95; p = 0.005). Significantly increased ORR (RR = 1.51; 95% CI 1.05-2.18) and PFS (HR = 0.72; 95% CI, 0.59-0.88) were found in R/M HNSCC patients treated with anti-EGFR plus chemotherapy, while no significant improvements were found in stage III/IV patients treated with anti-EGFR plus standard therapy. In conclusion, addition of cetuximab to standard therapy may improve outcomes for R/M HNSCC patients, while causing a moderate increase in SAEs. For stage III/IV patients, anti-EGFR mAb plus RT can improve OS compared with RT alone, while replacement of chemotherapy with EGFR mAb or adding EGFR mAb to combined chemotherapy and RT did not improve outcomes. © 2017 UICC.

Concurrent Anemia and Elevated C-Reactive Protein Predicts HIV Clinical Treatment Failure, Including Tuberculosis, After Antiretroviral Therapy Initiation

PubMed Central

Shivakoti, Rupak; Yang, Wei-Teng; Gupte, Nikhil; Berendes, Sima; Rosa, Alberto La; Cardoso, Sandra W.; Mwelase, Noluthando; Kanyama, Cecilia; Pillay, Sandy; Samaneka, Wadzanai; Riviere, Cynthia; Sugandhavesa, Patcharaphan; Santos, Brento; Poongulali, Selvamuthu; Tripathy, Srikanth; Bollinger, Robert C.; Currier, Judith S.; Tang, Alice M.; Semba, Richard D.; Christian, Parul; Campbell, Thomas B.; Gupta, Amita

2015-01-01

Background. Anemia is a known risk factor for clinical failure following antiretroviral therapy (ART). Notably, anemia and inflammation are interrelated, and recent studies have associated elevated C-reactive protein (CRP), an inflammation marker, with adverse human immunodeficiency virus (HIV) treatment outcomes, yet their joint effect is not known. The objective of this study was to assess prevalence and risk factors of anemia in HIV infection and to determine whether anemia and elevated CRP jointly predict clinical failure post-ART. Methods. A case-cohort study (N = 470 [236 cases, 234 controls]) was nested within a multinational randomized trial of ART efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings [PEARLS]). Cases were incident World Health Organization stage 3, 4, or death by 96 weeks of ART treatment (clinical failure). Multivariable logistic regression was used to determine risk factors for pre-ART (baseline) anemia (females: hemoglobin <12.0 g/dL; males: hemoglobin <13.0 g/dL). Association of anemia as well as concurrent baseline anemia and inflammation (CRP ≥10 mg/L) with clinical failure were assessed using multivariable Cox models. Results. Baseline anemia prevalence was 51% with 15% prevalence of concurrent anemia and inflammation. In analysis of clinical failure, multivariate-adjusted hazard ratios were 6.41 (95% confidence interval [CI], 2.82–14.57) for concurrent anemia and inflammation, 0.77 (95% CI, .37–1.58) for anemia without inflammation, and 0.45 (95% CI, .11–1.80) for inflammation without anemia compared to those without anemia and inflammation. Conclusions. ART-naive, HIV-infected individuals with concurrent anemia and inflammation are at particularly high risk of failing treatment, and understanding the pathogenesis could lead to new interventions. Reducing inflammation and anemia will likely improve HIV disease outcomes. Alternatively, concurrent anemia and inflammation could represent individuals with occult opportunistic infections in need of additional screening. PMID:25828994

Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: a multicenter randomized phase III trial.

PubMed

Liang, J; Bi, N; Wu, S; Chen, M; Lv, C; Zhao, L; Shi, A; Jiang, W; Xu, Y; Zhou, Z; Wang, W; Chen, D; Hui, Z; Lv, J; Zhang, H; Feng, Q; Xiao, Z; Wang, X; Liu, L; Zhang, T; Du, L; Chen, W; Shyr, Y; Yin, W; Li, J; He, J; Wang, L

2017-04-01

The optimal chemotherapy regimen administered currently with radiation in patients with stage III non-small cell lung cancer (NSCLC) remains unclear. A multicenter phase III trial was conducted to compare the efficacy of concurrent thoracic radiation therapy with either etoposide/cisplatin (EP) or carboplatin/paclitaxel (PC) in patients with stage III NSCLC. Patients were randomly received 60-66 Gy of thoracic radiation therapy concurrent with either etoposide 50 mg/m2 on days 1-5 and cisplatin 50 mg/m2 on days 1 and 8 every 4 weeks for two cycles (EP arm), or paclitaxel 45 mg/m2 and carboplatin (AUC 2) on day 1 weekly (PC arm). The primary end point was overall survival (OS). The study was designed with 80% power to detect a 17% superiority in 3-year OS with a type I error rate of 0.05. A total of 200 patients were randomized and 191 patients were treated (95 in the EP arm and 96 in the PC arm). With a median follow-up time of 73 months, the 3-year OS was significantly higher in the EP arm than that of the PC arm. The estimated difference was 15.0% (95% CI 2.0%-28.0%) and P value of 0.024. Median survival times were 23.3 months in the EP arm and 20.7 months in the PC arm (log-rank test P = 0.095, HR 0.76, 95%CI 0.55-1.05). The incidence of Grade ≥2 radiation pneumonitis was higher in the PC arm (33.3% versus 18.9%, P = 0.036), while the incidence of Grade ≥3 esophagitis was higher in the EP arm (20.0% versus 6.3%, P = 0.009). EP might be superior to weekly PC in terms of OS in the setting of concurrent chemoradiation for unresectable stage III NSCLC. NCT01494558. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Memory-Guided Attention: Independent Contributions of the Hippocampus and Striatum.

PubMed

Goldfarb, Elizabeth V; Chun, Marvin M; Phelps, Elizabeth A

2016-01-20

Memory can strongly influence how attention is deployed in future encounters. Though memory dependent on the medial temporal lobes has been shown to drive attention, how other memory systems could concurrently and comparably enhance attention is less clear. Here, we demonstrate that both reinforcement learning and context memory facilitate attention in a visual search task. Using functional magnetic resonance imaging, we dissociate the mechanisms by which these memories guide attention: trial by trial, the hippocampus (not the striatum) predicted attention benefits from context memory, while the striatum (not the hippocampus) predicted facilitation from rewarded stimulus-response associations. Responses in these regions were also distinctly correlated with individual differences in each type of memory-guided attention. This study provides novel evidence for the role of the striatum in guiding attention, dissociable from hippocampus-dependent context memory.

Memory-Guided Attention: Independent Contributions of the Hippocampus and Striatum

PubMed Central

Goldfarb, Elizabeth V.; Chun, Marvin M.; Phelps, Elizabeth A.

2015-01-01

SUMMARY Memory can strongly influence how attention is deployed in future encounters. Though memory dependent on the medial temporal lobes has been shown to drive attention, how other memory systems could concurrently and comparably enhance attention is less clear. Here, we demonstrate that both reinforcement learning and context memory facilitate attention in a visual search task. Using functional magnetic resonance imaging, we dissociate the mechanisms by which these memories guide attention: trial by trial, the hippocampus (not the striatum) predicted attention benefits from context memory, while the striatum (not the hippocampus) predicted facilitation from rewarded stimulus-response associations. Responses in these regions were also distinctly correlated with individual differences in each type of memory-guided attention. This study provides novel evidence for the role of the striatum in guiding attention, dissociable from hippocampus-dependent context memory. PMID:26777274

Uncertain responses by humans and rhesus monkeys (Macaca mulatta) in a psychophysical same-different task

NASA Technical Reports Server (NTRS)

Shields, W. E.; Smith, J. D.; Washburn, D. A.; Rumbaugh, D. M. (Principal Investigator)

1997-01-01

The authors asked whether animals, like humans, use an uncertain response adaptively to escape indeterminate stimulus relations. Humans and monkeys were placed in a same-different task, known to be challenging for animals. Its difficulty was increased further by reducing the size of the stimulus differences, thereby making many same and different trials difficult to tell apart. Monkeys do escape selectively from these threshold trials, even while coping with 7 absolute stimulus levels concurrently. Monkeys even adjust their response strategies on short time scales according to the local task conditions. Signal-detection and optimality analyses confirm the similarity of humans' and animals' performances. Whereas associative interpretations account poorly for these results, an intuitive uncertainty construct does so easily. The authors discuss the cognitive processes that allow uncertainty's adaptive use and recommend further comparative studies of metacognition.

Radiation Therapy Intensification for Solid Tumors: A Systematic Review of Randomized Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamoah, Kosj; Showalter, Timothy N.; Ohri, Nitin, E-mail: ohri.nitin@gmail.com

Purpose: To systematically review the outcomes of randomized trials testing radiation therapy (RT) intensification, including both dose escalation and/or the use of altered fractionation, as a strategy to improve disease control for a number of malignancies. Methods and Materials: We performed a literature search to identify randomized trials testing RT intensification for cancers of the central nervous system, head and neck, breast, lung, esophagus, rectum, and prostate. Findings were described qualitatively. Where adequate data were available, pooled estimates for the effect of RT intensification on local control (LC) or overall survival (OS) were obtained using the inverse variance method. Results: Inmore » primary central nervous system tumors, esophageal cancer, and rectal cancer, randomized trials have not demonstrated that RT intensification improves clinical outcomes. In breast cancer and prostate cancer, dose escalation has been shown to improve LC or biochemical disease control but not OS. Radiation therapy intensification may improve LC and OS in head and neck and lung cancers, but these benefits have generally been limited to studies that did not incorporate concurrent chemotherapy. Conclusions: In randomized trials, the benefits of RT intensification have largely been restricted to trials in which concurrent chemotherapy was not used. Novel strategies to optimize the incorporation of RT in the multimodality treatment of solid tumors should be explored.« less

A randomized trial comparing primary angioplasty versus stent placement for symptomatic intracranial stenosis

PubMed Central

Qureshi, Adnan I; Chaudhry, Saqib A; Siddiq, Farhan; Majidi, Shahram; Rodriguez, Gustavo J; Suri, M Fareed K

2013-01-01

Background: Both primary angioplasty alone and angioplasty with a self-expanding stent have been compared in non-randomized concurrent clinical studies that suggest equivalent results. However, there is no randomized trial that has compared the two procedures in patients with symptomatic high grade intracranial stenosis. Objective: The primary aim of the randomized trial was to compare the clinical and angiographic efficacy of primary angioplasty and angioplasty followed by stent placement in preventing restenosis, stroke, requirement for second treatment, and death in patients with symptomatic intracranial stenosis. Methods: The study prospectively evaluated efficacy and safety of the two existing neurointerventional techniques for treatment of moderate intracranial stenosis (stenosis ≥ 50%) with documented failure of medical treatment or severe stenosis (≥70%) with or without failure of medical treatment. Results: A total of 18 patients were recruited in the study (mean age [±SD] was 64.7 ± 15.1 years); out of these, 12 were men. Of these 18, 10 were treated with primary angioplasty and 8 were treated with angioplasty followed by self-expanding stent. The technical success rates of intracranial angioplasty and stent placements defined as ability to achieve <30% residual stenosis when assessed by immediate post-procedure angiography was 5 of 10 and 5 of 8 patients, respectively. The total fluoroscopic time (mean [±SD]) was lower in patients undergoing primary angioplasty 37 [±11] min versus those undergoing angioplasty followed by self-expanding stent 42 [±15] min, P = 0.4321. The stroke and death rate within 1 month was very low in both patient groups (1 of 10 versus 0 of 8 patients). One patient randomized to stent placement continued to have recurrent ischemic symptoms requiring another angioplasty in the vertebral artery on post-procedure Day 2. Conclusions: The trial suggests that a randomized trial comparing primary angioplasty to angioplasty followed by stent placement is feasible. The immediate procedural outcomes with primary angioplasty are comparable to stent placement and warrant further studies. PMID:24358415

The efficacy and safety of neoadjuvant chemotherapy +/- letrozole in postmenopausal women with locally advanced breast cancer: a randomized phase III clinical trial.

PubMed

Mohammadianpanah, Mohammad; Ashouri, Yaghoub; Hoseini, Sare; Amadloo, Niloofar; Talei, Abdolrasoul; Tahmasebi, Sedigheh; Nasrolahi, Hamid; Mosalaei, Ahmad; Omidvari, Shapour; Ansari, Mansour; Mosleh-Shirazi, Mohammad Amin

2012-04-01

This two-arm randomized clinical study aimed to evaluate the efficacy and safety of neoadjuvant concurrent chemotherapy and letrozole in postmenopausal women with locally advanced breast carcinoma. One hundred and one postmenopausal women aged 50-83 years with pathologically proven locally advanced (clinical stage T3, T4 and/or N2, N3) breast cancer were randomly assigned to receive neoadjuvant chemotherapy alone (control arm, n = 51) or neoadjuvant chemotherapy concurrent with letrozole 2.5 mg (study arm, n = 50). Chemotherapy consisted of a median 4 (range 3-5) cycles of intravenous 5-fluorouracil 600 mg/m(2), doxorubicin 60 mg/m(2), and cyclophosphamide 600 mg/m(2), every three weeks. All patients subsequently underwent modified radical mastectomy approximately two weeks after the last cycle of chemotherapy. Pathologic complete response rates were 25.5% and 10.2% in the study and the control group, respectively (P = 0.049). Similarly, clinical complete response rates were 27.6% and 10.2% in the study and the control group, respectively (P = 0.037). In the subgroup analysis of hormone receptor-positive cases, the complete response rates were more prominent in study group compared with control group. Common treatment-related side effects such as nausea, vomiting, bone marrow suppression, and mucositis were similar in both groups, but hot flush was more prevalent in study group compared with control group (P = 0.023). The addition of letrozole concurrently with neoadjuvant chemotherapy provides a higher clinical and pathologic response rates with acceptable toxicity compared with chemotherapy alone in postmenopausal women with locally advanced sensitive breast cancer.

Eating the elephant whole or in slices: views of participants in a smoking cessation intervention trial on multiple behaviour changes as sequential or concurrent tasks

PubMed Central

2012-01-01

Background This paper explores smoking cessation participants’ perceptions of attempting weight management alongside smoking cessation within the context of a health improvement intervention implemented in Glasgow, Scotland. Methods One hundred and thirty-eight participants were recruited from smoking cessation classes in areas of multiple deprivation in Glasgow and randomised to intervention, receiving dietary advice, or to control groups. The primary outcome of the study was to determine the % change in body weight. Semi-structured interviews were conducted with a purposive sample of 15 intervention and 15 control participants at weeks 6 (during the intervention) and 24 (at the end of the intervention). The current paper, though predominantly qualitative, links perceptions of behaviour modification to % weight change and cessation rates at week 24 thereby enabling a better understanding of the mediators influencing multiple behaviour change. Results Our findings suggest that participants who perceive separate behaviour changes as part of a broader approach to a healthier lifestyle, and hence attempt behaviour changes concurrently, may be at comparative advantage in positively achieving dual outcomes. Conclusions These findings highlight the need to assess participants’ preference for attempting multiple behaviour changes sequentially or simultaneously in addition to assessing their readiness to change. Further testing of this hypothesis is warranted. Trial Registration ISRCTN94961361 PMID:22759785

A reanalysis of cluster randomized trials showed interrupted time-series studies were valuable in health system evaluation.

PubMed

Fretheim, Atle; Zhang, Fang; Ross-Degnan, Dennis; Oxman, Andrew D; Cheyne, Helen; Foy, Robbie; Goodacre, Steve; Herrin, Jeph; Kerse, Ngaire; McKinlay, R James; Wright, Adam; Soumerai, Stephen B

2015-03-01

There is often substantial uncertainty about the impacts of health system and policy interventions. Despite that, randomized controlled trials (RCTs) are uncommon in this field, partly because experiments can be difficult to carry out. An alternative method for impact evaluation is the interrupted time-series (ITS) design. Little is known, however, about how results from the two methods compare. Our aim was to explore whether ITS studies yield results that differ from those of randomized trials. We conducted single-arm ITS analyses (segmented regression) based on data from the intervention arm of cluster randomized trials (C-RCTs), that is, discarding control arm data. Secondarily, we included the control group data in the analyses, by subtracting control group data points from intervention group data points, thereby constructing a time series representing the difference between the intervention and control groups. We compared the results from the single-arm and controlled ITS analyses with results based on conventional aggregated analyses of trial data. The findings were largely concordant, yielding effect estimates with overlapping 95% confidence intervals (CI) across different analytical methods. However, our analyses revealed the importance of a concurrent control group and of taking baseline and follow-up trends into account in the analysis of C-RCTs. The ITS design is valuable for evaluation of health systems interventions, both when RCTs are not feasible and in the analysis and interpretation of data from C-RCTs. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

External beam radiation therapy for clinically localized prostate cancer: when and how we optimize with concurrent hormonal deprivation.

PubMed

Koontz, Bridget F; Lee, W Robert

2011-10-01

Androgen deprivation plays a major role in the treatment of prostate cancer.Preclinical studies have shown that androgen deprivation provides both an independent cytotoxic effect and radiosensitization on prostate tumors. For men with non-metastatic prostate cancer, the addition of androgen deprivation to radiotherapy has been shown to improve survival for intermediate and high risk disease compared to radiation alone.This review discusses the clinical trial data regarding combination of androgen deprivation and radiation and provides recommendations for its use in men undergoing radiotherapy for localized prostate cancer.

Phase I Clinical Trial Assessing Temozolomide and Tamoxifen With Concomitant Radiotherapy for Treatment of High-Grade Glioma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patel, Shilpen, E-mail: Shilpenp@uw.edu; DiBiase, Steven; Meisenberg, Barry

2012-02-01

Purpose: The new standard treatment of glioblastoma multiforme is concurrent radiotherapy (RT) and temozolomide. The proliferation of high-grade gliomas might be partly dependent on protein kinase C-mediated pathways. Tamoxifen has been shown in vitro to inhibit protein kinase C through estrogen receptor-independent antineoplastic effects. This Phase I trial was designed to determine the maximal tolerated dose (MTD) of tamoxifen when given with temozolomide and concurrent RT to patients with high-grade gliomas. Methods and Materials: A total of 17 consecutive patients in four cohorts with World Health Organization Grade 3 (n = 2) and 4 (n = 15) gliomas were givenmore » tamoxifen twice daily during 6 weeks of concurrent RT and temozolomide. Eligibility included histologic diagnosis, age >18 years old, Karnofsky performance status {>=}60, and no previous brain RT or chemotherapy. The starting dose was 50 mg/m{sup 2} divided twice daily. If no dose-limiting toxicities (DLTs) occurred in 3 patients, the dose was escalated in 25-mg/m{sup 2} increments until the MTD was reached. When {>=}2 patients within a cohort experienced a DLT, the MTD had been exceeded. Temozolomide was given with RT at 75 mg/m{sup 2}. A dose of 60 Gy in 2 Gy/d fractions to a partial brain field was delivered. Results: A total of 6 patients in Cohort 4 had received tamoxifen at 125 mg/m{sup 2}. One patient was excluded, and the fourth patient developed Grade 4 thrombocytopenia (DLT). Thus, 3 more patients needed to be enrolled. A deep venous thrombosis (DLT) occurred in the sixth patient. Thus, the MTD was 100 mg/m{sup 2}. Conclusions: The MTD of tamoxifen was 100 mg/m{sup 2} when given concurrently with temozolomide 75 mg/m{sup 2} and RT. Tamoxifen might have a role in the initial treatment of high-grade gliomas and should be studied in future Phase II trials building on the newly established platform of concurrent chemoradiotherapy.« less

Induction therapy with carboplatin/paclitaxel followed by concurrent carboplatin/paclitaxel and dose-escalating conformal radiotherapy in the treatment of locally advanced, unresectable non-small cell lung cancer: preliminary report of a phase I trial.

PubMed

Socinski, M A; Clark, J A; Halle, J; Steagall, A; Kaluzny, B; Rosenman, J G

1997-08-01

Locally advanced non-small cell lung cancer is optimally managed with chemotherapy and thoracic irradiation, although the most appropriate strategy is not yet defined. In this phase I trial, we use two 21-day cycles of induction chemotherapy with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (225 mg/m2 over 3 hours) and carboplatin (area under the concentration-time curve = 6) followed by concurrent weekly paclitaxel (45 mg/m2/wk x 6) and carboplatin (area under the concentration-time curve = 2/wk x 6) and thoracic irradiation. Patients undergo three-dimensional treatment planning (conformal radiotherapy) to define the cancer target volume precisely. The phase I question being addressed in this study is the maximum tolerated radiation dose given concurrently with low-dose paclitaxel and carboplatin. The initial radiation dose is 60 Gy, with dose escalations to 66 Gy, 70 Gy, and 74 Gy being planned. Ten patients have been entered thus far (eight men and two women). Their median age is 67 years (range, 59 to 78 years), and none of the patients has had greater than 5% pretreatment weight loss. Seven of 10 are evaluable for response to induction carboplatin and paclitaxel, with a response rate of 57% (three partial responses and one minor response). Three patients had stable disease and none of the patients had evidence of progressive disease during induction chemotherapy. Three patients have completed all treatment at 60 Gy and one has completed all treatment at 66 Gy. Three of the four patients have had partial responses (75%), with the remaining patient having stable disease. Toxicity in the concurrent chemoradiotherapy portion of the trial thus far has consisted of grade 3 neutropenia in one patient and grade 4 lymphocytopenia in all four patients. No grade 3 or 4 nonhematologic toxicity has been seen. The trial data are not yet mature enough to report on survival. Accrual and treatment is continuing at the 66 Gy radiation dose level.

Economic evaluation of the prophylaxis for thromboembolism in critical care trial (E-PROTECT): study protocol for a randomized controlled trial.

PubMed

Fowler, Robert A; Mittmann, Nicole; Geerts, William H; Heels-Ansdell, Diane; Gould, Michael K; Guyatt, Gordon; Krahn, Murray; Finfer, Simon; Pinto, Ruxandra; Chan, Brian; Ormanidhi, Orges; Arabi, Yaseen; Qushmaq, Ismael; Rocha, Marcelo G; Dodek, Peter; McIntyre, Lauralyn; Hall, Richard; Ferguson, Niall D; Mehta, Sangeeta; Marshall, John C; Doig, Christopher James; Muscedere, John; Jacka, Michael J; Klinger, James R; Vlahakis, Nicholas; Orford, Neil; Seppelt, Ian; Skrobik, Yoanna K; Sud, Sachin; Cade, John F; Cooper, Jamie; Cook, Deborah

2014-12-20

Venous thromboembolism (VTE) is a common complication of critical illness with important clinical consequences. The Prophylaxis for ThromboEmbolism in Critical Care Trial (PROTECT) is a multicenter, blinded, randomized controlled trial comparing the effectiveness of the two most common pharmocoprevention strategies, unfractionated heparin (UFH) and low molecular weight heparin (LMWH) dalteparin, in medical-surgical patients in the intensive care unit (ICU). E-PROTECT is a prospective and concurrent economic evaluation of the PROTECT trial. The primary objective of E-PROTECT is to identify and quantify the total (direct and indirect, variable and fixed) costs associated with the management of critically ill patients participating in the PROTECT trial, and, to combine costs and outcome results to determine the incremental cost-effectiveness of LMWH versus UFH, from the acute healthcare system perspective, over a data-rich time horizon of ICU admission and hospital admission. We derive baseline characteristics and probabilities of in-ICU and in-hospital events from all enrolled patients. Total costs are derived from centers, proportional to the numbers of patients enrolled in each country. Direct costs include medication, physician and other personnel costs, diagnostic radiology and laboratory testing, operative and non-operative procedures, costs associated with bleeding, transfusions and treatment-related complications. Indirect costs include ICU and hospital ward overhead costs. Outcomes are the ratio of incremental costs per incremental effects of LMWH versus UFH during hospitalization; incremental cost to prevent a thrombosis at any site (primary outcome); incremental cost to prevent a pulmonary embolism, deep vein thrombosis, major bleeding event or episode of heparin-induced thrombocytopenia (secondary outcomes) and incremental cost per life-year gained (tertiary outcome). Pre-specified subgroups and sensitivity analyses will be performed and confidence intervals for the estimates of incremental cost-effectiveness will be obtained using bootstrapping. This economic evaluation employs a prospective costing methodology concurrent with a randomized controlled blinded clinical trial, with a pre-specified analytic plan, outcome measures, subgroup and sensitivity analyses. This economic evaluation has received only peer-reviewed funding and funders will not play a role in the generation, analysis or decision to submit the manuscripts for publication. Clinicaltrials.gov Identifier: NCT00182143 . Date of registration: 10 September 2005.

Preoperative Radiotherapy of Advanced Rectal Cancer With Capecitabine and Oxaliplatin With or Without Cetuximab: A Pooled Analysis of Three Prospective Phase I-II Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weiss, Christian, E-mail: christian.weiss@kgu.d; Arnold, Dirk; Dellas, Kathrin

2010-10-01

Purpose: A pooled analysis of three prospective trials of preoperative radiochemotherapy (RCT) for rectal cancer by using oxaliplatin and capecitabine with or without cetuximab was performed to evaluate the impact of additional cetuximab on pathologic complete response (pCR) rates and tumor regression (TRG) grades. Methods and Materials: Of 202 patients, 172 patients met the inclusion criteria (primary tumor stage II/III, M0). All patients received concurrent RCT, and 46 patients received additional cetuximab therapy. A correlation of pretreatment clinicopathologic factors and cetuximab treatment with early pCR rates (TRG > 50%) was performed with univariate and multivariate analyses. Toxicity data were recordedmore » for all patients. Results: Of 172 patients, 24 (14%) patients achieved a pCR, and 84 of 172 (71%) patients showed a TRG of >50% in the surgical specimen assessment after preoperative treatment. Age, gender, and T/N stages, as well as localization of the tumor, were not associated with pCR or good TRG. The pCR rate was 16% after preoperative RCT alone and 9% with concurrent cetuximab therapy (p = 0.32). A significantly reduced TRG of >50% was found after RCT with cetuximab compared to RCT alone (p = 0.0035). This was validated by a multivariate analysis with all available clinical factors (p = 0.0037). Acute toxicity and surgical complications were not increased with additional cetuximab. Conclusions: Triple therapy with RCT and cetuximab seems to be feasible, with no unexpected toxicity. Early response assessment (TRG), however, suggests subadditive interaction. A longer follow-up (and finally randomized trials) is needed to draw any firm conclusions with respect to local and distant failure rates.« less

Randomized controlled trial of concurrent hepatitis A and B vaccination.

PubMed

Bryan, J P; McCardle, P; South-Paul, J E; Fogarty, J P; Legters, L J; Perine, P L

2001-02-01

Hepatitis A and B viruses are threats to deployed military forces. The objective of this study was to determine the feasibility of concurrent vaccination against hepatitis A and B viruses. One hundred five healthy persons, 20 to 49 years of age and without serologic markers to hepatitis A or B viruses, were randomized to receive an inactivated hepatitis A vaccine (HEP A; 25 units in 0.5 mL), recombinant hepatitis B vaccine (HEP B; 10 micrograms in 1.0 mL), or both (HEP A & B) concurrently in separate arms. Vaccines were administered intramuscularly at 0, 1, and 6 months. Sera obtained at 1, 2, 6, 7, and 12 months after the first dose were tested for quantitative antibody to hepatitis A virus (anti-HAV) and antibody to hepatitis B surface antigen. Local reactions (e.g., pain) were reported by less than half of the volunteers and were similar at the site of HEP A, whether given alone or concurrently. However, more persons complained of pain (usually mild) at the HEP B site when HEP B was given concurrently with HEP A compared with HEP B alone (43% vs. 15%, 34% vs. 9%, and 42% vs. 15% for doses 1, 2, and 3, respectively; p < 0.05 for each dose). Among persons immunized with HEP A alone or HEP A & B, the proportion with > or = 10 mIU/mL anti-HAV was 83% in both groups 1 month after dose 1 and 100% at months 2, 7, and 12. The geometric mean concentrations of anti-HAV increased from 21 mIU/mL at month 1 to 2,649 and 2,312 mIU/mL in the HEP A and HEP A & B groups, respectively, at month 7. The response to HEP B was similar whether administered alone or concurrently. Antibody responses were similar in those receiving HEP A or HEP B concurrently or alone, but more subjects reported pain (usually mild) at the HEP B site after concurrent vaccination than after HEP B alone. Further work should be conducted to approve HEP A for patients younger than 2 years of age and to develop combined HEP A and HEP B vaccines in the United States.

Preoperative Short-Course Concurrent Chemoradiation Therapy Followed by Delayed Surgery for Locally Advanced Rectal Cancer: A Phase 2 Multicenter Study (KROG 10-01)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yeo, Seung-Gu; Department of Radiation Oncology, Soonchunhyang University College of Medicine, Cheonan; Oh, Jae Hwan

Purpose: A prospective phase 2 multicenter trial was performed to investigate the efficacy and safety of preoperative short-course concurrent chemoradiation therapy (CRT) followed by delayed surgery for patients with locally advanced rectal cancer. Methods and Materials: Seventy-three patients with cT3-4 rectal cancer were enrolled. Radiation therapy of 25 Gy in 5 fractions was delivered over 5 consecutive days using helical tomotherapy. Concurrent chemotherapy was administered on the same 5 days with intravenous bolus injection of 5-fluorouracil (400 mg/m{sup 2}/day) and leucovorin (20 mg/m{sup 2}/day). After 4 to 8 weeks, total mesorectal excision was performed. The primary endpoint was the pathologicmore » downstaging (ypStage 0-I) rate, and secondary endpoints included tumor regression grade, tumor volume reduction rate, and toxicity. Results: Seventy-one patients completed the planned preoperative CRT and surgery. Downstaging occurred in 20 (28.2%) patients, including 1 (1.4%) with a pathologic complete response. Favorable tumor regression (grade 4-3) was observed in 4 (5.6%) patients, and the mean tumor volume reduction rate was 62.5 ± 21.3%. Severe (grade ≥3) treatment toxicities were reported in 27 (38%) patients from CRT until 3 months after surgery. Conclusions: Preoperative short-course concurrent CRT followed by delayed surgery for patients with locally advanced rectal cancer demonstrated poor pathologic responses compared with conventional long-course CRT, and it yielded considerable toxicities despite the use of an advanced radiation therapy technique.« less

Concurrent Chemo-Radiation With or Without Induction Gemcitabine, Carboplatin, and Paclitaxel: A Randomized, Phase 2/3 Trial in Locally Advanced Nasopharyngeal Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tan, Terence, E-mail: trdtwk@nccs.com.sg; Lim, Wan-Teck; Fong, Kam-Weng

Purpose: To compare survival, tumor control, toxicities, and quality of life of patients with locally advanced nasopharyngeal carcinoma (NPC) treated with induction chemotherapy and concurrent chemo-radiation (CCRT), against CCRT alone. Patients and Methods: Patients were stratified by N stage and randomized to induction GCP (3 cycles of gemcitabine 1000 mg/m{sup 2}, carboplatin area under the concentration-time-curve 2.5, and paclitaxel 70 mg/m{sup 2} given days 1 and 8 every 21 days) followed by CCRT (radiation therapy 69.96 Gy with weekly cisplatin 40 mg/m{sup 2}), or CCRT alone. The accrual of 172 was planned to detect a 15% difference in 5-year overall survival (OS) with a 5%more » significance level and 80% power. Results: Between September 2004 and August 2012, 180 patients were accrued, and 172 (GCP 86, control 86) were analyzed by intention to treat. There was no significant difference in OS (3-year OS 94.3% [GCP] vs 92.3% [control]; hazard ratio 1.05; 1-sided P=.494]), disease-free survival (hazard ratio 0.77, 95% confidence interval 0.44-1.35, P=.362), and distant metastases–free survival (hazard ratio 0.80, 95% confidence interval 0.38-1.67, P=.547) between the 2 arms. Treatment compliance in the induction phase was good, but the relative dose intensity for concurrent cisplatin was significantly lower in the GCP arm. Overall, the GCP arm had higher rates of grades 3 and 4 leukopenia (52% vs 37%) and neutropenia (24% vs 12%), but grade 3 and 4 acute radiation toxicities were not statistically different between the 2 arms. The global quality of life scores were comparable in both arms. Conclusion: Induction chemotherapy with GCP before concurrent chemo-irradiation did not improve survival in locally advanced NPC.« less

Randomized Controlled Trial of Osmotic-Release Methylphenidate with CBT in Adolescents with ADHD and Substance Use Disorders

PubMed Central

Riggs, Paula D.; Winhusen, Theresa; Davies, Robert D.; Leimberger, Jeffrey D.; Mikulich-Gilbertson, Susan; Klein, Constance; Macdonald, Marilyn; Lohman, Michelle; Bailey, Genie L.; Haynes, Louise; Jaffee, William B.; Hodgkins, Candace; Whitmore, Elizabeth; Trello-Rishel, Kathlene; Tamm, Leanne; Acosta, Michelle C.; Royer-Malvestuto, Charlotte; Subramaniam, Geetha; Fishman, Marc; Holmes, Beverly W.; Kaye, Mary Elyse; Vargo, Mark A.; Woody, George E.; Nunes, Edward V.; Liu, David

2011-01-01

Objective To evaluate the efficacy and safety of osmotic-release methylphenidate (OROS-MPH) compared to placebo for attention deficit hyperactivity disorder (ADHD) and impact on substance treatment outcomes in adolescents concurrently receiving cognitive behavioral therapy (CBT) for substance use disorders (SUD). Method 16-week randomized controlled multi-site trial of OROS-MPH + CBT versus placebo + CBT in 303 adolescents (aged 13-18), meeting DSM-IV diagnostic criteria for ADHD and SUD. Primary outcomes: (1) ADHD- clinician-administered ADHD Rating Scale (ADHD-RS), adolescent informant; (2) Substance- adolescent reported days of use in the past 28 days. Secondary outcome measures included parent ADHD-RS and weekly urine drug screens (UDS). Results There were no group differences on reduction in ADHD-RS scores (OROS-MPH: −19.2, 95% confidence interval [CI], −17.1 to −21.2; placebo,−21.2, 95% CI, −19.1 to −23.2) or reduction in days of substance use (OROS-MPH: −5.7 days, 95% CI, 4.0-7.4; placebo: −5.2 days, 95% CI, 3.5-7.0). Some secondary outcomes favored OROS-MPH including lower parent ADHD-RS scores at 8 (mean difference [md]=4.4, 95% CI, 0.8-7.9) and 16 weeks (md=6.9; 95% CI, 2.9-10.9) and more negative UDS in OROS-MPH (mean=3.8) compared to placebo (mean=2.8; P=0.04). Conclusions OROS-MPH did not show greater efficacy than placebo for ADHD or on reduction in substance use in adolescents concurrently receiving individual CBT for co-occurring SUD. However, OROS-MPH was relatively well tolerated and was associated with modestly greater clinical improvement on some secondary ADHD and substance outcome measures. PMID:21871372

Simultaneous odour-face presentation strengthens hedonic evaluations and event-related potential responses influenced by unpleasant odour.

PubMed

Cook, Stephanie; Kokmotou, Katerina; Soto, Vicente; Wright, Hazel; Fallon, Nicholas; Thomas, Anna; Giesbrecht, Timo; Field, Matt; Stancak, Andrej

2018-04-13

Odours alter evaluations of concurrently presented visual stimuli, such as faces. Stimulus onset asynchrony (SOA) is known to affect evaluative priming in various sensory modalities. However, effects of SOA on odour priming of visual stimuli are not known. The present study aimed to analyse whether subjective and cortical activation changes during odour priming would vary as a function of SOA between odours and faces. Twenty-eight participants rated faces under pleasant, unpleasant, and no-odour conditions using visual analogue scales. In half of trials, faces appeared one-second after odour offset (SOA 1). In the other half of trials, faces appeared during the odour pulse (SOA 2). EEG was recorded continuously using a 128-channel system, and event-related potentials (ERPs) to face stimuli were evaluated using statistical parametric mapping (SPM). Faces presented during unpleasant-odour stimulation were rated significantly less pleasant than the same faces presented one-second after offset of the unpleasant odour. Scalp-time clusters in the late-positive-potential (LPP) time-range showed an interaction between odour and SOA effects, whereby activation was stronger for faces presented simultaneously with the unpleasant odour, compared to the same faces presented after odour offset. Our results highlight stronger unpleasant odour priming with simultaneous, compared to delayed, odour-face presentation. Such effects were represented in both behavioural and neural data. A greater cortical and subjective response during simultaneous presentation of faces and unpleasant odour may have an adaptive role, allowing for a prompt and focused behavioural reaction to a concurrent stimulus if an aversive odour would signal danger, or unwanted social interaction. Copyright © 2018 Elsevier B.V. All rights reserved.

Phytochemical Pharmacokinetics and Bioactivity of Oat and Barley Flour: A Randomized Crossover Trial

PubMed Central

Sawicki, Caleigh M.; McKay, Diane L.; McKeown, Nicola M.; Dallal, Gerard; Chen, C. -Y. Oliver; Blumberg, Jeffrey B.

2016-01-01

While dietary fiber plays an important role in the health benefits associated with whole grain consumption, other ingredients concentrated in the outer bran layer, including alkylresorcinols, lignans, phenolic acids, phytosterols, and tocols, may also contribute to these outcomes. To determine the acute bioavailability and pharmacokinetics of the major phytochemicals found in barley and oats, we conducted a randomized, three-way crossover trial in 13 healthy subjects, aged 40–70 years with a body mass index (BMI) of 27–35.9 kg/m2. After a two-day run-in period following a diet low in phytochemicals, subjects were randomized to receive muffins made with either 48 g whole oat flour, whole barley flour, or refined wheat flour plus cellulose (control), with a one-week washout period between each intervention. At the same time, an oral glucose tolerance test was administered. In addition to plasma phytochemical concentrations, glucose and insulin responses, biomarkers of antioxidant activity, lipid peroxidation, inflammation, and vascular remodeling were determined over a 24-h period. There was no significant effect on acute bioavailability or pharmacokinetics of major phytochemicals. Administered concurrently with a glucose bolus, the source of whole grains did not attenuate the post-prandial response of markers of glucoregulation and insulin sensitivity, inflammation, nor vascular remodeling compared to the refined grain control. No significant differences were observed in the bioavailability or postprandial effects between whole-oat and whole-barley compared to a refined wheat control when administered with a glucose challenge. These null results may be due, in part, to the inclusion criteria for the subjects, dose of the whole grains, and concurrent acute administration of the whole grains with the glucose bolus. PMID:27983687

Kinetics of matching.

PubMed

Mark, T A; Gallistel, C R

1994-01-01

Rats responded on concurrent variable interval schedules of brain stimulation reward in 2-trial sessions. Between trials, there was a 16-fold reversal in the relative rate of reward. In successive, narrow time windows, the authors compared the ratio of the times spent on the 2 levers to the ratio of the rewards received. Time-allocation ratios tracked wide, random fluctuations in the reward ratio. The adjustment to the midsession reversal in relative rate of reward was largely completed within 1 interreward interval on the leaner schedule. Both results were unaffected by a 16-fold change in the combined rates of reward. The large, rapid, scale-invariant shifts in time-allocation ratios that underlie matching behavior imply that the subjective relative rate of reward can be determined by a very few of the most recent interreward intervals and that this estimate can directly determine the ratio of the expected stay durations.

The Mayo Dysphagia Questionnaire-30: documentation of reliability and validity of a tool for interventional trials in adults with esophageal disease.

PubMed

McElhiney, Judith; Lohse, Matthew R; Arora, Amindra S; Peloquin, Joanna M; Geno, Debra M; Kuntz, Melissa M; Enders, Felicity B; Fredericksen, Mary; Abdalla, Adil A; Khan, Yulia; Talley, Nicholas J; Diehl, Nancy N; Beebe, Timothy J; Harris, Ann M; Farrugia, Gianrico; Graner, Darlene E; Murray, Joseph A; Locke, G Richard; Grothe, Rayna M; Crowell, Michael D; Francis, Dawn L; Grudell, April M B; Dabade, Tushar; Ramirez, Angelica; Alkhatib, MhdMaan; Alexander, Jeffrey A; Kimber, Jessica; Prasad, Ganapathy; Zinsmeister, Alan R; Romero, Yvonne

2010-09-01

The aim of this study was to develop the Mayo Dysphagia Questionnaire-30 Day (MDQ-30), a tool to measure esophageal dysphagia, by adapting items from validated instruments for use in clinical trials, and assess its feasibility, reproducibility, and concurrent validity. Outpatients referred to endoscopy for dysphagia or seen in a specialty clinic were recruited. Feasibility testing was done to identify problematic items. Reproducibility was measured by test-retest format. Concurrent validity reflects agreement between information gathered in a structured interview versus the patients' written responses. The MDQ-30, a 28-item instrument, took 10 min (range = 5-30 min) to complete. Four hundred thirty-one outpatients [210 (49%) men; mean age = 61 years] participated. Overall, most concurrent validity kappa values for dysphagia were very good to excellent with a median of 0.78 (min 0.28, max 0.95). The majority of reproducibility kappa values for dysphagia were moderate to excellent with a median kappa value of 0.66 (min 0.07, max 1.0). Overall, concurrent validity and reproducibility kappa values for gastroesophageal reflux disease (GERD) symptoms were 0.81 (95% CI = 0.72, 0.91) and 0.66 (95% CI = 0.55, 0.77), respectively. Individual item percent agreement was generally very good to excellent. Internal consistency was excellent. We conclude that the MDQ-30 is an easy-to-complete tool to evaluate reliably dysphagia symptoms over the last 30 days.

[Concurrent chemoradiation in lung cancer].

PubMed

Girard, Nicolas; Mornex, Françoise

2005-12-01

Concurrent chemoradiation has become for the 15 last years the standard treatment for locally advanced non-small cell lung cancer, either as a definite therapy in non resectable tumors, or in a neoadjuvant setting in potentially resectable tumors. Associating sequential and concurrent schedules, by administering chemotherapy before or after concurrent chemoradiation, has been recently investigated, but the best sequence remains a matter of controversy. Increasing local control and survival after definite chemoradiation seems possible not only by using optimized radiation fractionation schedules and escalated total doses, but also by associating more convenient and less toxic chemotherapy agents at the right cytotoxic or radio-sensitizing dose. Moreover, recent data have suggested that surgery following induction chemoradiation is feasible and effective in selected patients without mediastinal nodes involvement, if a complete resection can be performed. In patients with localized small cell lung cancer, early concurrent chemoradiation with platinium and etoposide has been recognized as the state-of-the-art treatment. The increasing number of ongoing trials including modern radiation schedules combined with newer chemotherapy agents shows that chemoradiation is one of the most promising therapeutic strategies in thoracic oncology.

The contribution of suggestibility and expectation to placebo analgesia phenomenon in an experimental setting.

PubMed

De Pascalis, Vilfredo; Chiaradia, Carmela; Carotenuto, Eleonora

2002-04-01

This study reports how placebo analgesia was produced by conditioning whereby the intensity of electric stimulation was surreptitiously reduced in order to examine the contribution of psychological factors of suggestibility and expectancy on placebo analgesia. This strategy was used in order to manipulate expectancy for pain reduction. The magnitudes of the placebo effects were estimated after a manipulation procedure and during experimental trials in which stimulus intensities were reset to original baseline levels. Individual differences in suggestibility, verbal expectancy for drug efficacy and manipulation procedure for pain reduction were tested as possible mediators of placebo analgesia. The following dependent variables were measured: (a) subjective expectancy for drug efficacy in pain relief, (b) expected pain intensity and unpleasantness, (c) concurrent pain intensity and unpleasantness and (d) remembered pain intensity and unpleasantness. Statistically significant placebo effects on sensory and affective measures of pain were obtained independently of the extent of the surreptitious lowering of stimulus strength during manipulation trials. The pairing of placebo administration with painful stimulation was sufficient to produce a generalized placebo analgesic effect. However, verbal expectancy for drug efficacy and individual differences in suggestibility were found to contribute significantly to the magnitude of placebo analgesia. The highest placebo effect was shown by the most pronounced reductions in pain ratings in highly suggestible subjects who received suggestions presumed to elicit high expectancy for drug efficacy. The results also demonstrated that placebo effects established on remembered pain were at least twice as great as those obtained on concurrent placebo effects. This was mainly because baseline pain was remembered as being much more intense than it really was. Moreover, remembered placebo effects, like the concurrent placebo effects, were highly correlated with expected pain scores obtained just after manipulation trials. These results indicate that multiple factors contribute to the placebo effect, including suggestibility, expectancy and conditioning, and that the judgement of placebo analgesia is critically determined by whether pain relief is assessed concurrently or after treatment.

Neoadjuvant irinotecan, cisplatin, and concurrent radiation therapy with celecoxib for patients with locally advanced esophageal cancer.

PubMed

Cleary, James M; Mamon, Harvey J; Szymonifka, Jackie; Bueno, Raphael; Choi, Noah; Donahue, Dean M; Fidias, Panos M; Gaissert, Henning A; Jaklitsch, Michael T; Kulke, Matthew H; Lynch, Thomas P; Mentzer, Steven J; Meyerhardt, Jeffrey A; Swanson, Richard S; Wain, John; Fuchs, Charles S; Enzinger, Peter C

2016-07-13

Patients with locally advanced esophageal cancer who are treated with trimodality therapy have a high recurrence rate. Preclinical evidence suggests that inhibition of cyclooxygenase 2 (COX2) increases the effectiveness of chemoradiation, and observational studies in humans suggest that COX-2 inhibition may reduce esophageal cancer risk. This trial tested the safety and efficacy of combining a COX2 inhibitor, celecoxib, with neoadjuvant irinotecan/cisplatin chemoradiation. This single arm phase 2 trial combined irinotecan, cisplatin, and celecoxib with concurrent radiation therapy. Patients with stage IIA-IVA esophageal cancer received weekly cisplatin 30 mg/m(2) plus irinotecan 65 mg/m(2) on weeks 1, 2, 4, and 5 concurrently with 5040 cGy of radiation therapy. Celecoxib 400 mg was taken orally twice daily during chemoradiation, up to 1 week before surgery, and for 6 months following surgery. Forty patients were enrolled with stage IIa (30 %), stage IIb (20 %), stage III (22.5 %), and stage IVA (27.5 %) esophageal or gastroesophageal junction cancer (AJCC, 5th Edition). During chemoradiation, grade 3-4 treatment-related toxicity included dysphagia (20 %), anorexia (17.5 %), dehydration (17.5 %), nausea (15 %), neutropenia (12.5 %), diarrhea (10 %), fatigue (7.5 %), and febrile neutropenia (7.5 %). The pathological complete response rate was 32.5 %. The median progression free survival was 15.7 months and the median overall survival was 34.7 months. 15 % (n = 6) of patients treated on this study developed brain metastases. The addition of celecoxib to neoadjuvant cisplatin-irinotecan chemoradiation was tolerable; however, overall survival appeared comparable to prior studies using neoadjuvant cisplatin-irinotecan chemoradiation alone. Further studies adding celecoxib to neoadjuvant chemoradiation in esophageal cancer are not warranted. Clinicaltrials.gov: NCT00137852 , registered August 29, 2005.

CONCURRENT WHOLE BRAIN RADIOTHERAPY AND SHORT-COURSE CHLOROQUINE IN PATIENTS WITH BRAIN METASTASES: A PILOT TRIAL.

PubMed

Eldredge, Harriet Belding; Denittis, Albert; Duhadaway, James B; Chernick, Michael; Metz, Richard; Prendergast, George C

2013-09-01

The immune modulatory drug chloroquine (CQ) has been demonstrated to enhance survival following radiotherapy in patients with high-grade glioma in a clinical trial, but the efficacy in patients with brain metastases is unknown. We hypothesized that short-course CQ during whole brain radiotherapy (WBRT) would improve response to local therapy in patients with brain metastases. A prospective, single-cohort study was performed combining WBRT with concurrent CQ to assess both the feasibility of and intracranial response to combined therapy in patients with brain metastases. Safety, tolerability and overall survival of this combination was also examined, along with allelic status of IDO2 (indoleamine 2,3-dioxygenase 2), an immune modulatory enzyme inhibited by chloroquine that may affect survival outcomes. CQ therapy (250 mg by mouth daily) was initiated 1 week before WBRT (37.5 Gy in 2.5 Gy daily fractions) in patients with newly diagnosed brain metastases from biopsy-proven, primary lung, breast or ovarian solid tumors (n=20). The primary endpoint was radiologic response 3 months after combined CQ and WBRT therapy. Secondary endpoints included toxicity and overall survival. Patients were stratified by IDO2 allelic status. After a median clinical follow up of 5 months (range, 0.5-31), 16 patients were evaluable for radiologic response which was complete response in two patients, partial response in 13 patients and stable disease in one patient. There were no treatment-related grade≥3 toxicities or treatment interruption due to toxicity. Median and mean overall survival was 5.7 and 8.9 months, respectively (range, 0.8-31). A trend toward increased overall survival was observed in patients with wild-type IDO2 compared to patients with heterozygous or homozygous configurations that ablate IDO2 enzyme activity (10.4 mos vs. 4.1 mos.; p=0.07). WBRT with concurrent, short-course CQ is well tolerated in patients with brain metastases. The high intracranial disease control rate warrants additional study.

Measuring the effects of a visual or auditory Stroop task on dual-task costs during obstacle crossing.

PubMed

Worden, Timothy A; Mendes, Matthew; Singh, Pratham; Vallis, Lori Ann

2016-10-01

Successful planning and execution of motor strategies while concurrently performing a cognitive task has been previously examined, but unfortunately the varied and numerous cognitive tasks studied has limited our fundamental understanding of how the central nervous system successfully integrates and executes these tasks simultaneously. To gain a better understanding of these mechanisms we used a set of cognitive tasks requiring similar central executive function processes and response outputs but requiring different perceptual mechanisms to perform the motor task. Thirteen healthy young adults (20.6±1.6years old) were instrumented with kinematic markers (60Hz) and completed 5 practice, 10 single-task obstacle walking trials and two 40 trial experimental blocks. Each block contained 20 trials of seated (single-task) trials followed by 20 cognitive and obstacle (30% lower leg length) crossing trials (dual-task). Blocks were randomly presented and included either an auditory Stroop task (AST; central interference only) or a visual Stroop task (VST; combined central and structural interference). Higher accuracy rates and shorter response times were observed for the VST versus AST single-task trials (p<0.05). Conversely, for the obstacle stepping performance, larger dual task costs were observed for the VST as compared to the AST for clearance measures (the VST induced larger clearance values for both the leading and trailing feet), indicating VST tasks caused greater interference for obstacle crossing (p<0.05). These results supported the hypothesis that structural interference has a larger effect on motor performance in a dual-task situation compared to cognitive tasks that pose interference at only the central processing stage. Copyright © 2016 Elsevier B.V. All rights reserved.

Should Sponsors and DSMBs Share Interim Results Across Trials?

PubMed Central

Shah, Seema K.; Dawson, Liza; Dixon, Dennis O.; Lie, Reidar K.

2011-01-01

Increasing numbers of multinational clinical trials have generated new ethical obligations of research sponsors and their DSMBs. Although sponsors and DSMBs clearly have ethical obligations to protect subjects in their trials, future patients, and the integrity of their trial, the obligations they have to protect subjects in other trials have been overlooked. When interim results from clinical trials can significantly affect the conduct of other trials and the welfare of the subjects in those trials, sponsors and DSMBs may have obligations to disclose results to the relevant parties. We propose that sponsors and DSMBs routinely work together in advance to develop a plan for disclosing relevant information in cases where it is necessary to protect the welfare of subjects in other trials. Channels of communication between sponsors, DSMBs, IRBs, and others involved in similar and concurrent trials will better protect both research participants and the integrity of the research enterprise. PMID:21937922

Concurrent bariatric operations and association with perioperative outcomes: registry based cohort study.

PubMed

Liu, Jason B; Ban, Kristen A; Berian, Julia R; Hutter, Matthew M; Huffman, Kristopher M; Liu, Yaoming; Hoyt, David B; Hall, Bruce L; Ko, Clifford Y

2017-09-26

Objective  To determine whether perioperative outcomes differ between patients undergoing concurrent compared with non-concurrent bariatric operations in the USA. Design  Retrospective, propensity score matched cohort study. Setting  Hospitals in the US accredited by the American College of Surgeons' metabolic and bariatric surgery accreditation and quality improvement program. Participants  513 167 patients undergoing bariatric operations between 1 January 2014 and 31 December 2016. Main outcome measures  The primary outcome measure was a composite of 30 day death, morbidity, readmission, reoperation, anastomotic or staple line leak, and bleeding events. Operative duration and lengths of stay were also assessed. Operations were defined as concurrent if they overlapped by 60 or more minutes or in their entirety. Results  In this study of 513 167 operations, 739 (29.5%) surgeons at 483 (57.8%) hospitals performed 6087 (1.2%) concurrent operations. The most frequently performed concurrent bariatric operations were sleeve gastrectomy (n=3250, 53.4%) and Roux-en-Y gastric bypass (n=1601, 26.3%). Concurrent operations were more often performed at large academic medical centers with higher operative volumes and numbers of trainees and by higher volume surgeons. Compared with non-concurrent operations, concurrent operations lasted a median of 34 minutes longer (P<0.001) and resulted in 0.3 days longer average length of stay (P<0.001). Perioperative adverse events were not observed to more likely occur in concurrent compared with non-concurrent operations (7.5% v 7.4%; relative risk 1.02, 95% confidence interval 0.90 to 1.15; P=0.84). Conclusions  Concurrent bariatric operations occurred infrequently, but when they did, there was no observable increased risk for adverse perioperative outcomes compared with non-concurrent operations. These results, however, do not argue against improved and more meaningful disclosure of concurrent surgery practices. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Surrogate endpoints for overall survival in chemotherapy and radiotherapy trials in operable and locally advanced lung cancer: a re-analysis of meta-analyses of individual patients' data.

PubMed

Mauguen, Audrey; Pignon, Jean-Pierre; Burdett, Sarah; Domerg, Caroline; Fisher, David; Paulus, Rebecca; Mandrekar, Samithra J; Belani, Chandra P; Shepherd, Frances A; Eisen, Tim; Pang, Herbert; Collette, Laurence; Sause, William T; Dahlberg, Suzanne E; Crawford, Jeffrey; O'Brien, Mary; Schild, Steven E; Parmar, Mahesh; Tierney, Jayne F; Le Pechoux, Cécile; Michiels, Stefan

2013-06-01

The gold standard endpoint in clinical trials of chemotherapy and radiotherapy for lung cancer is overall survival. Although reliable and simple to measure, this endpoint takes years to observe. Surrogate endpoints that would enable earlier assessments of treatment effects would be useful. We assessed the correlations between potential surrogate endpoints and overall survival at individual and trial levels. We analysed individual patients' data from 15,071 patients involved in 60 randomised clinical trials that were assessed in six meta-analyses. Two meta-analyses were of adjuvant chemotherapy in non-small-cell lung cancer, three were of sequential or concurrent chemotherapy, and one was of modified radiotherapy in locally advanced lung cancer. We investigated disease-free survival (DFS) or progression-free survival (PFS), defined as the time from randomisation to local or distant relapse or death, and locoregional control, defined as the time to the first local event, as potential surrogate endpoints. At the individual level we calculated the squared correlations between distributions of these three endpoints and overall survival, and at the trial level we calculated the squared correlation between treatment effects for endpoints. In trials of adjuvant chemotherapy, correlations between DFS and overall survival were very good at the individual level (ρ(2)=0.83, 95% CI 0.83-0.83 in trials without radiotherapy, and 0.87, 0.87-0.87 in trials with radiotherapy) and excellent at trial level (R(2)=0.92, 95% CI 0.88-0.95 in trials without radiotherapy and 0.99, 0.98-1.00 in trials with radiotherapy). In studies of locally advanced disease, correlations between PFS and overall survival were very good at the individual level (ρ(2) range 0.77-0.85, dependent on the regimen being assessed) and trial level (R(2) range 0.89-0.97). In studies with data on locoregional control, individual-level correlations were good (ρ(2)=0.71, 95% CI 0.71-0.71 for concurrent chemotherapy and ρ(2)=0.61, 0.61-0.61 for modified vs standard radiotherapy) and trial-level correlations very good (R(2)=0.85, 95% CI 0.77-0.92 for concurrent chemotherapy and R(2)=0.95, 0.91-0.98 for modified vs standard radiotherapy). We found a high level of evidence that DFS is a valid surrogate endpoint for overall survival in studies of adjuvant chemotherapy involving patients with non-small-cell lung cancers, and PFS in those of chemotherapy and radiotherapy for patients with locally advanced lung cancers. Extrapolation to targeted agents, however, is not automatically warranted. Programme Hospitalier de Recherche Clinique, Ligue Nationale Contre le Cancer, British Medical Research Council, Sanofi-Aventis. Copyright © 2013 Elsevier Ltd. All rights reserved.

Eliminating Hairy Cell Leukemia Minimal Residual Disease

Cancer.gov

In this trial, patients with hairy cell leukemia who have disease-related symptoms that require treatment will be randomly assigned to receive cladribine with either concurrent rituximab or rituximab at least 6 months after completing cladribine therapy.

A Randomized Trial of Contingency Management for Smoking Cessation During Intensive Outpatient Alcohol Treatment.

PubMed

Cooney, Judith L; Cooper, Sharon; Grant, Christoffer; Sevarino, Kevin; Krishnan-Sarin, Suchitra; Gutierrez, Ian A; Cooney, Ned L

2017-01-01

This randomized clinical trial was designed to evaluate the efficacy of contingency management (CM) for smoking cessation for smokers with alcohol abuse or dependence delivered concurrently with intensive outpatient alcohol treatment. The study also explored the indirect effects of CM smoking treatment and smoking cessation on alcohol and drug use outcomes. Alcohol abuse/dependent smokers were randomized to cognitive behavioral therapy plus nicotine replacement therapy plus contingency management (CBT+NRT+CM) or to cognitive behavior therapy plus nicotine replacement therapy (CBT+NRT) delivered concurrent with a three-week intensive outpatient alcohol treatment program. Participants in the CBT+NRT+CM condition were significantly more likely to be cigarette abstinent at the end of treatment (χ 2 (1)=8.48, p=.004) with approximately double the carbon monoxide confirmed quit rate (60%) compared with the CBT+NRT condition (29%). At the one-month and six-month time-points there were nonsignificant differences in smoking abstinence outcomes by condition. Smoking treatment condition did not directly affect alcohol abstinence outcomes, but we observed an indirect effect of smoking treatment on alcohol and drug abstinence at one-month follow-up that was mediated by smoking cessation at the end of treatment. Adding CM to an evidence-based smoking cessation treatment that included medication and behavioral counseling doubled the quit rate at the end of treatment. This finding provides strong evidence for the efficacy of CM for helping alcohol dependent smokers reach the milestone of initial smoking abstinence. Published by Elsevier Inc.

"Straight Talk" for African-American heterosexual men: results of a single-arm behavioral intervention trial.

PubMed

Frye, Victoria; Henny, Kirk; Bonner, Sebastian; Williams, Kim; Bond, Keosha T; Hoover, Donald R; Lucy, Debbie; Greene, Emily; Koblin, Beryl A

2013-01-01

In the United States, heterosexual transmission is the second leading cause of HIV/AIDS, and two-thirds of all heterosexually acquired cases diagnosed between 2005 and 2008 occurred among African-Americans. Few HIV prevention interventions have been designed specifically for African-American heterosexual men not seeking clinical treatment. Here we report results of a single-arm intervention trial of a theory-based HIV prevention intervention designed to increase condom use, reduce concurrent partnering and increase HIV testing among heterosexually active African-American men living in high HIV prevalence areas of New York City. We tested our hypothesis using McNemar discordant pairs exact test for binary variables and paired t-tests for continuous variables. We observed statistically significant declines in mean number of total and new female partners, unprotected sex partners, and partner concurrency in both primary and nonprimary sex partnerships between baseline and 3 months postintervention.

Does Participation in a Randomized Clinical Trial Change Outcomes? An Evaluation of Patients Not Enrolled in the SPRINT Trial.

PubMed

Lin, Carol Alice; Bhandari, Mohit; Guyatt, Gordon; Walter, Stephen D; Schemitsch, Emil H; Swiontkowski, Marc; Sanders, David; Tornetta, Paul

2016-03-01

To determine the extent to which knowledge from clinical trial protocols is transferred to nonparticipating patients. Retrospective review of prospectively collected data from a large clinical trial. Six level-1 international trauma centers. We compared rates and timing of reoperation in a subset of patients enrolled in the Study to Prospectively evaluate Reamed Intramedullary Nails in Patients with Tibial Fractures (SPRINT) to concurrent patients who were eligible but not enrolled. This was a retrospective review of prospectively collected trial data. The records of 6 of the original SPRINT centers were searched for non-SPRINT patients who underwent intramedullary nailing of a closed tibial fracture. The rate and timing of reoperation were compared. A P < 0.05 was considered significant. One hundred fourteen non-SPRINT patients were compared with 328 patients enrolled in SPRINT from those same sites. There were 7 reoperations (6.1%) in non-SPRINT patients versus 18 (5.2%) in SPRINT patients [odds ratio (OR) 1.19, 95% confidence interval (CI) 0.41 to 3.13; P = 0.811]. There was no difference in the time to reoperation between the SPRINT and non-SPRINT patients (6.2 vs. 6.8 months, 95% CI of the difference -3.8 to 2.6; P = 0.685) or in the proportion of patients who underwent reoperation before 6 months (29% vs. 43%; OR 1.75; 95% CI 0.18 to 15.41; P = 0.647). Patients not enrolled in SPRINT had similarly low rates of reoperation for nonunion, and the average time to reoperation for both groups was longer than 6 months. A 6-month waiting period may have allowed slow-to-heal fractures adequate time to heal, thereby reducing the rate of diagnosis of nonunion. As such, this waiting period could contribute to lower-than-expected reoperation rates for nonunion. It is possible that clinical trials may beneficially influence the care of nonenrolled patients.

Concurrent Anemia and Elevated C-Reactive Protein Predicts HIV Clinical Treatment Failure, Including Tuberculosis, After Antiretroviral Therapy Initiation.

PubMed

Shivakoti, Rupak; Yang, Wei-Teng; Gupte, Nikhil; Berendes, Sima; Rosa, Alberto La; Cardoso, Sandra W; Mwelase, Noluthando; Kanyama, Cecilia; Pillay, Sandy; Samaneka, Wadzanai; Riviere, Cynthia; Sugandhavesa, Patcharaphan; Santos, Brento; Poongulali, Selvamuthu; Tripathy, Srikanth; Bollinger, Robert C; Currier, Judith S; Tang, Alice M; Semba, Richard D; Christian, Parul; Campbell, Thomas B; Gupta, Amita

2015-07-01

Anemia is a known risk factor for clinical failure following antiretroviral therapy (ART). Notably, anemia and inflammation are interrelated, and recent studies have associated elevated C-reactive protein (CRP), an inflammation marker, with adverse human immunodeficiency virus (HIV) treatment outcomes, yet their joint effect is not known. The objective of this study was to assess prevalence and risk factors of anemia in HIV infection and to determine whether anemia and elevated CRP jointly predict clinical failure post-ART. A case-cohort study (N = 470 [236 cases, 234 controls]) was nested within a multinational randomized trial of ART efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings [PEARLS]). Cases were incident World Health Organization stage 3, 4, or death by 96 weeks of ART treatment (clinical failure). Multivariable logistic regression was used to determine risk factors for pre-ART (baseline) anemia (females: hemoglobin <12.0 g/dL; males: hemoglobin <13.0 g/dL). Association of anemia as well as concurrent baseline anemia and inflammation (CRP ≥ 10 mg/L) with clinical failure were assessed using multivariable Cox models. Baseline anemia prevalence was 51% with 15% prevalence of concurrent anemia and inflammation. In analysis of clinical failure, multivariate-adjusted hazard ratios were 6.41 (95% confidence interval [CI], 2.82-14.57) for concurrent anemia and inflammation, 0.77 (95% CI, .37-1.58) for anemia without inflammation, and 0.45 (95% CI, .11-1.80) for inflammation without anemia compared to those without anemia and inflammation. ART-naive, HIV-infected individuals with concurrent anemia and inflammation are at particularly high risk of failing treatment, and understanding the pathogenesis could lead to new interventions. Reducing inflammation and anemia will likely improve HIV disease outcomes. Alternatively, concurrent anemia and inflammation could represent individuals with occult opportunistic infections in need of additional screening. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Phase II study. Concurrent chemotherapy and radiotherapy with nitroglycerin in locally advanced non-small cell lung cancer.

PubMed

Arrieta, Oscar; Blake, Mónika; de la Mata-Moya, María Dolores; Corona, Francisco; Turcott, Jenny; Orta, David; Alexander-Alatorre, Jorge; Gallardo-Rincón, Dolores

2014-05-01

Nitroglycerin, a nitric oxide donor agent, reduces the expression of hypoxia-inducible factor-1α (HIF-1α) and could be a normalizer of the tumor microenvironment. Both factors are associated with chemo-radio-resistance. The aim of this study was to determine the safety profile and efficacy of nitroglycerin administration with chemo-radiotherapy in patients with locally advanced non-small cell lung cancer (NSCLC). This is a phase II trial of locally advanced NSCLC patients treated with cisplatin and vinorelbine plus concurrent nitroglycerin with radiotherapy. A 25-mg NTG patch was administered to the patients for 5 days (1 day before and 4 days after chemotherapy induction and consolidation) and all day during chemo-radiotherapy. VEGF plasmatic level was determined before and after two cycles of chemotherapy. Thirty-five patients were enrolled in this trial. Sixty-three percent of patients achieved an overall response after induction of chemotherapy, and 75% achieved an overall response after chemo-radiotherapy. The median progression-free survival was 13.5 months (95% CI, 8.8-18.2), and the median overall survival was 26.9 months (95% CI, 15.3-38.5). Reduction of VEGF level was associated with better OS. The toxicity profile related to nitroglycerin included headache (20%) and hypotension (2.9%). The addition of nitroglycerin to induction chemotherapy and concurrent chemoradiotherapy in patients with locally advanced NSCLC has an acceptable toxicity profile and supports the possibility to add nitroglycerin to chemotherapy and radiotherapy. A randomized trial is warranted to confirm these findings. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Foley Plus Oxytocin Compared With Oxytocin for Induction After Membrane Rupture: A Randomized Controlled Trial.

PubMed

Mackeen, A Dhanya; Durie, Danielle E; Lin, Monique; Huls, Christopher K; Qureshey, Emma; Paglia, Michael J; Sun, Haiyan; Sciscione, Anthony

2018-01-01

To evaluate the use of a transcervical Foley catheter plus oxytocin infusion compared with oxytocin infusion alone for labor induction and cervical ripening in women 34 weeks of gestation or greater with prelabor rupture of membranes. This is a randomized, multicenter trial of women with a live, singleton gestation at 34 weeks of gestation or greater with prelabor rupture of membranes, an unfavorable cervical examination (less than 2 cm or 80% effaced), and no contraindication to labor. Participants were randomly allocated to a transcervical Foley catheter inflated to 30 cc with concurrent oxytocin infusion or oxytocin infusion alone. Oxytocin administration was standardized across sites. The primary study outcome was interval from induction to delivery. To detect a 2.5-hour difference in the interval from induction to delivery, we required outcome data on 194 women, assuming 80% power and a two-tailed α of 5%. Analysis was by intent to treat. We enrolled 201 women: 93 were allocated to Foley and 108 to oxytocin. Demographics were similar between the groups. Time to delivery was not significantly different between groups: in the Foley group, it was 13.9 hours (±6.9 SD) compared with 14.4 hours (±7.9 SD) in the oxytocin group (P=.69). There were more cases of clinical chorioamnionitis (8% compared with 0%, P<.01) in the Foley group compared with the oxytocin group. There were no differences for other infectious morbidities or any other variable studied. In patients with prelabor rupture of membranes, the use of a transcervical Foley catheter in addition to oxytocin does not shorten the time to delivery compared with oxytocin alone, but may increase the incidence of intraamniotic infection. ClinicalTrials.gov, NCT01973036.

Beneficial Effects of Adjuvant Melatonin in Minimizing Oral Mucositis Complications in Head and Neck Cancer Patients Receiving Concurrent Chemoradiation.

PubMed

Onseng, Kittipong; Johns, Nutjaree Pratheepawanit; Khuayjarernpanishk, Thanut; Subongkot, Suphat; Priprem, Aroonsri; Hurst, Cameron; Johns, Jeffrey

2017-12-01

Oral mucositis is a major cause of pain and delayed cancer treatment leading to poor survival in head and neck cancer patients receiving concurrent chemoradiation. The study evaluated the effect of adjuvant melatonin on minimizing oral mucositis complications to reduce these treatment delays and interruptions. A randomized, double-blind, double dummy, placebo-controlled clinical trial. Ubon Ratchathani Cancer Hospital, Thailand. Thirty-nine head and neck cancer patients receiving concurrent chemoradiation (5 days/week of radiation plus chemotherapy three or six cycles). Patients were randomized to receive 20 mg melatonin gargle (or matched placebo) before each irradiation, and 20 mg melatonin capsules (or matched placebo) taken nightly during 7 weeks of concurrent chemoradiation. Endpoints were oral mucositis events (incidence and time to grade 3 mucositis or grade 2 xerostomia), pain medication consumption and quality of life (QOL). Melatonin group reported lower incidence of grade 3 oral mucositis (42% vs. 55%) and grade 2 xerostomia (20% vs. 21%); no statistical significance was detected. Melatonin regimen delayed onset of grade 3 mucositis (median 34 days vs. 50 days; p = 0.0318), allowing median time of 16 more patient visits before its onset and fewer interrupted treatments due to oral mucositis were reported (n = 1 vs. n = 5). There was no difference of grade 2 xerostomia (median 32 days vs. 50 days; p = 0.624). Morphine consumption was also reduced (median 57 mg vs. 0 mg; p = 0.0342), while QOL was comparable during the study period. Adjuvant melatonin delayed the onset of oral mucositis, which enables uninterrupted cancer treatment and reduced the amount of morphine used for pain treatment.

Comparing Estimates of Multiple and Concurrent Partnerships Across Population Based Surveys: Implications for Combination HIV Prevention

PubMed Central

Morris, Martina; Leslie-Cook, Ayn; Akom, Eniko; Stephen, Aloo; Sherard, Donna

2014-01-01

We compare estimates of multiple and concurrent sexual partnerships from Demographic and Health Surveys (DHS) with comparable Population Services International (PSI) surveys in four African countries (Kenya, Lesotho, Uganda, Zambia). DHS data produce significantly lower estimates of all indicators for both sexes in all countries. PSI estimates of multiple partnerships are 1.7 times higher [1.4 for men (M), 3.0 for women (W)], cumulative prevalence of concurrency is 2.4 times higher (2.2 M, 2.7 W), the point prevalence of concurrency is 3.5 times higher (3.5 M, 3.3 W), and the fraction of multi-partnered persons who report concurrency last year is 1.4 times higher (1.6 M, 0.9 W). These findings provide strong empirical evidence that DHS surveys systematically underestimate levels of multiple and concurrent partnerships. The underestimates will contaminate both empirical analyses of the link between sexual behavior and HIV infection, and theoretical models for combination prevention that use these data for inputs. PMID:24077973

Comparing Estimates of Multiple and Concurrent Partnerships Across Population Based Surveys: Implications for Combination HIV Prevention.

PubMed

Morris, Martina; Vu, Lung; Leslie-Cook, Ayn; Akom, Eniko; Stephen, Aloo; Sherard, Donna

2014-04-01

We compare estimates of multiple and concurrent sexual partnerships from Demographic and Health Surveys (DHS) with comparable Population Services International (PSI) surveys in four African countries (Kenya, Lesotho, Uganda, Zambia). DHS data produce significantly lower estimates of all indicators for both sexes in all countries. PSI estimates of multiple partnerships are 1.7 times higher [1.4 for men (M), 3.0 for women (W)], cumulative prevalence of concurrency is 2.4 times higher (2.2 M, 2.7 W), the point prevalence of concurrency is 3.5 times higher (3.5 M, 3.3 W), and the fraction of multi-partnered persons who report concurrency last year is 1.4 times higher (1.6 M, 0.9 W). These findings provide strong empirical evidence that DHS surveys systematically underestimate levels of multiple and concurrent partnerships. The underestimates will contaminate both empirical analyses of the link between sexual behavior and HIV infection, and theoretical models for combination prevention that use these data for inputs.

Prognostic Value of Plasma Epstein-Barr Virus DNA for Local and Regionally Advanced Nasopharyngeal Carcinoma Treated With Cisplatin-Based Concurrent Chemoradiotherapy in Intensity-Modulated Radiotherapy Era.

PubMed

Chen, Wen-Hui; Tang, Lin-Quan; Guo, Shan-Shan; Chen, Qiu-Yan; Zhang, Lu; Liu, Li-Ting; Qian, Chao-Nan; Guo, Xiang; Xie, Dan; Zeng, Mu-Sheng; Mai, Hai-Qiang

2016-02-01

This study aimed to evaluate the prognostic value of plasma Epstein-Barr Virus DNA (EBV DNA) for local and regionally advanced nasopharyngeal carcinoma (NPC) patients treated with concurrent chemoradiotherapy in intensity-modulated radiotherapy (IMRT) era.In this observational study, 404 nonmetastatic local and regionally advanced NPC patients treated with IMRT and cisplatin-based concurrent chemotherapy were recruited. Blood samples were collected before treatment for examination of plasma EBV DNA levels. We evaluated the association of pretreatment plasma EBV DNA levels with progression-free survival rate (PFS), distant metastasis-free survival rate (DMFS), and overall survival rate (OS).Compared to patients with an EBV DNA level < 4000  copies/mL, patients with an EBV DNA ≥ 4000  copies/mL had a lower rate of 3-year PFS (76%, 95% CI [68-84]) versus (93%, 95% CI [90-96], P < 0.001), DMFS (83%, 95% CI [76-89]) versus (97%, 95% CI [94-99], P < 0.001), and OS (85%, 95% CI [78-92]) versus (98%, 95% CI [95-100], P < 0.001). Multivariate analysis showed that pretreatment EBV DNA levels (HR = 3.324, 95% CI, 1.80-6.138, P < 0.001) and clinical stage (HR = 1.878, 95% CI, 1.036-3.404, P = 0.038) were the only independent factor associated with PFS, pretreatment EBV DNA level was the only significant factor to predict DMFS (HR = 6.292, 95% CI, 2.647-14.956, P < 0.001), and pretreatment EBV DNA levels (HR = 3.753, 95% CI, 1.701-8.284, P < 0.001) and clinical stage (HR = 2.577, 95% CI, 1.252-5.050, P = 0.010) were significantly associated with OS. In subgroup analysis, higher plasma EBV DNA levels still predicted a worse PFS, DMFS, and OS for the patients stage III or stage IVa-b, compared with those with low EBV DNA levels.Elevated plasma EBV DNA was still effective prognostic biomarker for local and regionally advanced NPC patients treated with IMRT and cisplatin-based concurrent chemotherapy. Future ramdomized clinical trials are needed to further evaluate whether plasma EBV DNA levels could be applied to guide concurrent chemotherapy regimen for local and regionally advanced NPC patients.

Implications of Pain in Generalized Anxiety Disorder: Efficacy of Duloxetine

PubMed Central

Hartford, James T.; Endicott, Jean; Kornstein, Susan G.; Allgulander, Christer; Wohlreich, Madelaine M.; Russell, James M.; Perahia, David G. S.; Erickson, Janelle S.

2008-01-01

Objective: To conduct a post hoc evaluation of the prevalence of clinically significant pain and the efficacy of duloxetine in patients with generalized anxiety disorder (GAD) and concurrent pain. Method: Data from two 9- to 10-week double-blind, placebo-controlled, randomized clinical trials of duloxetine (60 to 120 mg) in DSM-IV–defined GAD were analyzed (study 1 was conducted from July 2004 to September 2005; study 2 was conducted from August 2004 to June 2005). Efficacy was assessed with the Hamilton Rating Scale for Anxiety (HAM-A), visual analog scales (VAS) for pain, the Hospital Anxiety Depression Scale (HADS), the Clinical Global Impressions-Improvement of Illness (CGI-I) scale, the Patient Global Impressions-Improvement (PGI-I) scale, and the Sheehan Disability Scale (SDS) global functional impairment scale. Results: Of 840 patients randomly assigned to treatment, 61.3% (302 duloxetine, 213 placebo) had VAS scores ≥ 30 mm on at least 1 of the pain scales, indicating clinically significant pain. Among those patients with concurrent pain at baseline, change from baseline to endpoint in the HAM-A total score (42.9% change in mean scores for duloxetine, 31.4% for placebo), HADS anxiety scale (40.3% vs. 22.8%), HADS depression scale (36.1% vs. 20.5%), HAM-A psychic factor (45.9% vs. 29.9%), and SDS global functional improvement score (45.5% vs. 22.1%) was significantly (all p's < .001) greater for duloxetine compared with placebo. Improvement on the CGI-I (p = .003) and PGI-I (p < .001) was also significantly greater for duloxetine. Response (HAM-A total score decrease ≥ 50%) (49% vs. 29%) and remission (HAM-A total score ≤ 7 at endpoint) (29% vs. 18%) rates were significantly greater for duloxetine compared with placebo (p < .001 and p = .041, respectively). Duloxetine demonstrated statistically significantly greater reduction in pain on all 6 VAS pain scales (all p's < .001 except headaches with p < .002) (for duloxetine, percent change in means from baseline to endpoint ranged from 40.1% to 45.2% across the 6 VAS scales; for placebo, 22.0% to 26.3%). Conclusion: Duloxetine, relative to placebo, improves anxiety symptoms, pain, and functional impairment among patients with GAD with concurrent clinically significant pain. Trial Registration: clinicaltrials.gov Identifiers: NCT00122824 (study 1) and NCT00475969 (study 2) PMID:18615176

Benefit of Delayed Fertility Therapy With Preconception Weight Loss Over Immediate Therapy in Obese Women With PCOS

PubMed Central

Dodson, William C.; Kunselman, Allen R.; Stetter, Christy M.; Kris-Etherton, Penny M.; Williams, Nancy I.; Gnatuk, Carol L.; Estes, Stephanie J.; Allison, Kelly C.; Sarwer, David B.; Diamond, Michael P.; Schlaff, William D.; Casson, Peter R.; Christman, Gregory M.; Barnhart, Kurt T.; Bates, G. Wright; Usadi, Rebecca; Lucidi, Scott; Baker, Valerie; Zhang, Heping; Eisenberg, Esther; Coutifaris, Christos; Dokras, Anuja

2016-01-01

Context: In overweight/obese women with polycystic ovary syndrome (PCOS), the relative benefit of delaying infertility treatment to lose weight vs seeking immediate treatment is unknown. Objective: We compared the results of two, multicenter, concurrent clinical trials treating infertility in women with PCOS. Design, Setting, and Participants: This was a secondary analysis of two randomized trials conducted at academic health centers studying women 18–40 years of age who were overweight/obese and infertile with PCOS. Intervention: We compared immediate treatment with clomiphene from the Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) trial (N = 187) to delayed treatment with clomiphene after preconception treatment with continuous oral contraceptives, lifestyle modification (Lifestyle: including caloric restriction, antiobesity medication, behavioral modification, and exercise) or the combination of both (combined) from the Treatment of Hyperandrogenism Versus Insulin Resistance in Infertile Polycystic Ovary Syndrome (OWL PCOS) trial (N = 142). Main Outcome Measures: Live birth, pregnancy loss, and ovulation were measured. Results: In PPCOS II, after four cycles of clomiphene, the cumulative per-cycle ovulation rate was 44.7% (277/619) and the cumulative live birth rate was 10.2% (19/187), nearly identical to that after oral contraceptive pretreatment in the OWL PCOS trial (ovulation 45% [67/149] and live birth: 8.5% [4/47]). In comparison, deferred clomiphene treatment preceded by lifestyle and combined treatment in OWL PCOS offered a significantly better cumulative ovulation rate compared to immediate treatment with clomiphene. (Lifestyle: 62.0% [80/129]; risk ratio compared to PPCOS II = 1.4; 95% confidence interval [CI], 1.1–1.7; P = .003; combined: 64.3% [83/129]; risk ratio compared to PPCOS II = 1.4; 95% CI, 1.2–1.8; P < .001 and a significantly better live birth rate lifestyle: 25.0% [12/48]; risk ratio compared to PPCOS II = 2.5; 95% CI, 1.3–4.7; P = .01 and combined: 25.5% [12/47]; risk ratio compared to PPCOS II = 2.5; 95% CI, 1.3–4.8; P = .01). Conclusions: These data show the benefit of improved ovulation and live birth with delayed infertility treatment with clomiphene citrate when preceded by lifestyle modification with weight loss compared with immediate treatment. Pretreatment with oral contraceptives likely has little effect on the ovulation and live birth rate compared with immediate treatment. PMID:27172435

Benefit of Delayed Fertility Therapy With Preconception Weight Loss Over Immediate Therapy in Obese Women With PCOS.

PubMed

Legro, Richard S; Dodson, William C; Kunselman, Allen R; Stetter, Christy M; Kris-Etherton, Penny M; Williams, Nancy I; Gnatuk, Carol L; Estes, Stephanie J; Allison, Kelly C; Sarwer, David B; Diamond, Michael P; Schlaff, William D; Casson, Peter R; Christman, Gregory M; Barnhart, Kurt T; Bates, G Wright; Usadi, Rebecca; Lucidi, Scott; Baker, Valerie; Zhang, Heping; Eisenberg, Esther; Coutifaris, Christos; Dokras, Anuja

2016-07-01

In overweight/obese women with polycystic ovary syndrome (PCOS), the relative benefit of delaying infertility treatment to lose weight vs seeking immediate treatment is unknown. We compared the results of two, multicenter, concurrent clinical trials treating infertility in women with PCOS. This was a secondary analysis of two randomized trials conducted at academic health centers studying women 18-40 years of age who were overweight/obese and infertile with PCOS. We compared immediate treatment with clomiphene from the Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) trial (N = 187) to delayed treatment with clomiphene after preconception treatment with continuous oral contraceptives, lifestyle modification (Lifestyle: including caloric restriction, antiobesity medication, behavioral modification, and exercise) or the combination of both (combined) from the Treatment of Hyperandrogenism Versus Insulin Resistance in Infertile Polycystic Ovary Syndrome (OWL PCOS) trial (N = 142). Live birth, pregnancy loss, and ovulation were measured. In PPCOS II, after four cycles of clomiphene, the cumulative per-cycle ovulation rate was 44.7% (277/619) and the cumulative live birth rate was 10.2% (19/187), nearly identical to that after oral contraceptive pretreatment in the OWL PCOS trial (ovulation 45% [67/149] and live birth: 8.5% [4/47]). In comparison, deferred clomiphene treatment preceded by lifestyle and combined treatment in OWL PCOS offered a significantly better cumulative ovulation rate compared to immediate treatment with clomiphene. (Lifestyle: 62.0% [80/129]; risk ratio compared to PPCOS II = 1.4; 95% confidence interval [CI], 1.1-1.7; P = .003; combined: 64.3% [83/129]; risk ratio compared to PPCOS II = 1.4; 95% CI, 1.2-1.8; P < .001 and a significantly better live birth rate lifestyle: 25.0% [12/48]; risk ratio compared to PPCOS II = 2.5; 95% CI, 1.3-4.7; P = .01 and combined: 25.5% [12/47]; risk ratio compared to PPCOS II = 2.5; 95% CI, 1.3-4.8; P = .01). These data show the benefit of improved ovulation and live birth with delayed infertility treatment with clomiphene citrate when preceded by lifestyle modification with weight loss compared with immediate treatment. Pretreatment with oral contraceptives likely has little effect on the ovulation and live birth rate compared with immediate treatment.

Effect of restricted protein diet supplemented with keto analogues in chronic kidney disease: a systematic review and meta-analysis.

PubMed

Jiang, Zheng; Zhang, Xiaoyan; Yang, Lichuan; Li, Zi; Qin, Wei

2016-03-01

To evaluate the efficacy and safety of the restricted protein diet (low or very low protein diet) supplemented with keto analogues in the treatment of chronic kidney disease (CKD). The Cochrane library, PubMed, Embase, CBM and CENTRAL databases were searched and reviewed up to April 2015. Clinical trials were analyzed using RevMan 5.3 software. Seven random control trials, one cross-over trial and one non-randomized concurrent control trial were selected and included in this study according to our inclusion and exclusion criteria. The changes of eGFR, BUN, Scr, albumin, PTH, triglyceride, cholesterol, calcium, phosphorus and nutrition indexes (BMI, lean body mass and mid-arm muscular circumference) before and after treatment were analyzed. The meta-analysis results indicated that, comparing with normal protein diet, low protein diet (LPD) or very low protein diet (vLPD) supplemented with keto analogues (s(v)LPD) could significantly prevent the deterioration of eGFR (P < 0.001), hyperparathyroidism (P = 0.04), hypertension (P < 0.01) and hyperphosphatemia (P < 0.001). No differences in BUN, Scr, Albumin, triglyceride, cholesterol, hemoglobin, calcium and nutrition indexes were observed between different protein intake groups. Restricted protein diet supplemented with keto analogues (s(v)LPD) could delay the progression of CKD effectively without causing malnutrition.

Reducing the framing effect in older and younger adults by encouraging analytic processing.

PubMed

Thomas, Ayanna K; Millar, Peter R

2012-03-01

The present study explored whether the framing effect could be reduced in older and younger adults using techniques that influenced the accessibility of information relevant to the decision-making processing. Accessibility was manipulated indirectly in Experiment 1 by having participants engage in concurrent tasks, and directly in Experiment 2, through an instructions manipulation that required participants to maintain a goal of analytic processing throughout the experimental trial. We tested 120 older and 120 younger adults in Experiment 1. Participants completed 28 decision trials while concurrently either performing a probability calculation task or a memory task. In Experiment 2, we tested 136 older and 136 younger adults. Participants completed 48 decision trials after either having been instructed to "think like a scientist" or base decisions on "gut reactions." Results demonstrated that the framing effect was reduced in older and younger adults in the probability calculation task in Experiment 1 and under the "think like a scientist" instructions manipulation in Experiment 2. These results suggest that when information relevant to unbiased decision making was made more accessible, both older and younger adults were able to reduce susceptibility to the framing effect.

Decision Making in Concurrent Multitasking: Do People Adapt to Task Interference?

PubMed Central

Nijboer, Menno; Taatgen, Niels A.; Brands, Annelies; Borst, Jelmer P.; van Rijn, Hedderik

2013-01-01

While multitasking has received a great deal of attention from researchers, we still know little about how well people adapt their behavior to multitasking demands. In three experiments, participants were presented with a multicolumn subtraction task, which required working memory in half of the trials. This primary task had to be combined with a secondary task requiring either working memory or visual attention, resulting in different types of interference. Before each trial, participants were asked to choose which secondary task they wanted to perform concurrently with the primary task. We predicted that if people seek to maximize performance or minimize effort required to perform the dual task, they choose task combinations that minimize interference. While performance data showed that the predicted optimal task combinations indeed resulted in minimal interference between tasks, the preferential choice data showed that a third of participants did not show any adaptation, and for the remainder it took a considerable number of trials before the optimal task combinations were chosen consistently. On the basis of these results we argue that, while in principle people are able to adapt their behavior according to multitasking demands, selection of the most efficient combination of strategies is not an automatic process. PMID:24244527

Sincere but naive: methodological queries concerning the British Columbia polygamy reference trial.

PubMed

Ashley, Sean Matthew

2014-11-01

Academics frequently serve as expert witnesses in legal cases, yet their role as transmitters of social scientific knowledge remains under-examined. The present study analyzes the deployment of social science within British Columbia's polygamy reference trial where research is used to support the assertion that polygamy is inherently harmful to society. Within the trial record and the written decision, the protection of monogamy as an institution is performed in part through the marginalization of qualitative methodology and the concurrent privileging of quantitative studies that purportedly demonstrate widespread social harms associated with the practice of polygyny.

Phase I Trial of Bortezomib and Concurrent External Beam Radiation in Patients With Advanced Solid Malignancies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pugh, Thomas J.; Chen Changhu; Rabinovitch, Rachel

Purpose: To determine the maximal tolerated dose of bortezomib with concurrent external beam radiation therapy in patients with incurable solid malignant tumors requiring palliative therapy. Methods and Materials: An open label, dose escalation, phase I clinical trial evaluated the safety of three dose levels of bortezomib administered intravenously (1.0 mg/m{sup 2}, 1.3 mg/m{sup 2}, and 1.6 mg/m{sup 2}/ dose) once weekly with concurrent radiation in patients with histologically confirmed solid tumors and a radiographically appreciable lesion suitable for palliative radiation therapy. All patients received 40 Gy in 16 fractions to the target lesion. Dose-limiting toxicity was the primary endpoint, definedmore » as any grade 4 hematologic toxicity, any grade {>=}3 nonhematologic toxicity, or any toxicity requiring treatment to be delayed for {>=}2 weeks. Results: A total of 12 patients were enrolled. Primary sites included prostate (3 patients), head and neck (3 patients), uterus (1 patient), abdomen (1 patient), breast (1 patient), kidney (1 patient), lung (1 patient), and colon (1 patient). The maximum tolerated dose was not realized with a maximum dose of 1.6 mg/m{sup 2}. One case of dose-limiting toxicity was appreciated (grade 3 urosepsis) and felt to be unrelated to bortezomib. The most common grade 3 toxicity was lymphopenia (10 patients). Common grade 1 to 2 events included nausea (7 patients), infection without neutropenia (6 patients), diarrhea (5 patients), and fatigue (5 patients). Conclusions: The combination of palliative external beam radiation with concurrent weekly bortezomib therapy at a dose of 1.6 mg/m{sup 2} is well tolerated in patients with metastatic solid tumors. The maximum tolerated dose of once weekly bortezomib delivered concurrently with radiation therapy is greater than 1.6 mg/m{sup 2}.« less

Comparison of sensitivity and reading time for the use of computer aided detection (CAD) of pulmonary nodules at MDCT as concurrent or second reader

NASA Astrophysics Data System (ADS)

Beyer, F.; Zierott, L.; Fallenberg, E. M.; Juergens, K.; Stoeckel, J.; Heindel, W.; Wormanns, D.

2006-03-01

Purpose: To compare sensitivity and reading time when using CAD as second reader resp. concurrent reader. Materials and Methods: Fifty chest MDCT scans due to clinical indication were analysed independently by four radiologists two times: First with CAD as concurrent reader (display of CAD results simultaneously to the primary reading by the radiologist); then after a median of 14 weeks with CAD as second reader (CAD results were shown after completion of a reading session without CAD). A prototype version of Siemens LungCAD (Siemens,Malvern,USA) was used. Sensitivities and reading times for detecting nodules >=4mm of concurrent reading, reading without CAD and second reading were recorded. In a consensus conference false positive findings were eliminated. Student's T-Test was used to compare sensitivities and reading times. Results: 108 true positive nodules were found. Mean sensitivity was .68 for reading without CAD, .68 for concurrent reading and .75 for second reading. Differences of sensitivities were significant between concurrent and second reading (p<.001) resp. reading without CAD and second reading (p=.001). Mean reading time for concurrent reading was significant shorter (274s) compared to reading without CAD (294s;p=.04) and second reading (337sp<.001). New work to be presented: To our knowledge this is the first study that compares sensitivities and reading times between use of CAD as concurrent resp. second reader. Conclusion: CAD can either be used to speed up reading of chest CT cases for pulmonary nodules without loss of sensitivity as concurrent reader -OR (and not AND) to increase sensitivity and reading time as second reader.

Effect of training and lifting equipment for preventing back pain in lifting and handling: systematic review

PubMed Central

2008-01-01

Objectives To determine whether advice and training on working techniques and lifting equipment prevent back pain in jobs that involve heavy lifting. Data sources Medline, Embase, CENTRAL, Cochrane Back Group’s specialised register, CINAHL, Nioshtic, CISdoc, Science Citation Index, and PsychLIT were searched up to September-November 2005. Review methods The primary search focused on randomised controlled trials and the secondary search on cohort studies with a concurrent control group. Interventions aimed to modify techniques for lifting and handling heavy objects or patients and including measurements for back pain, consequent disability, or sick leave as the main outcome were considered for the review. Two authors independently assessed eligibility of the studies and methodological quality of those included. For data synthesis, we summarised the results of studies comparing similar interventions. We used odds ratios and effect sizes to combine the results in a meta-analysis. Finally, we compared the conclusions of the primary and secondary analyses. Results Six randomised trials and five cohort studies met the inclusion criteria. Two randomised trials and all cohort studies were labelled as high quality. Eight studies looked at lifting and moving patients, and three studies were conducted among baggage handlers or postal workers. Those in control groups received no intervention or minimal training, physical exercise, or use of back belts. None of the comparisons in randomised trials (17 720 participants) yielded significant differences. In the secondary analysis, none of the cohort studies (772 participants) had significant results, which supports the results of the randomised trials. Conclusions There is no evidence to support use of advice or training in working techniques with or without lifting equipment for preventing back pain or consequent disability. The findings challenge current widespread practice of advising workers on correct lifting technique. PMID:18244957

Surrogate endpoints for overall survival in chemotherapy and radiotherapy trials in operable and locally advanced lung cancer: a re-analysis of meta-analyses of individual patients' data

PubMed Central

Mauguen, Audrey; Pignon, Jean-Pierre; Burdett, Sarah; Domerg, Caroline; Fisher, David; Paulus, Rebecca; Mandrekar, Samithra J; Belani, Chandra P; Shepherd, Frances A; Eisen, Tim; Pang, Herbert; Collette, Laurence; Sause, William T; Dahlberg, Suzanne E; Crawford, Jeffrey; O'Brien, Mary; Schild, Steven E; Parmar, Mahesh; Tierney, Jayne F; Pechoux, Cécile Le; Michiels, Stefan

2013-01-01

Summary Background The gold standard endpoint in clinical trials of chemotherapy and radiotherapy for lung cancer is overall survival. Although reliable and simple to measure, this endpoint takes years to observe. Surrogate endpoints that would enable earlier assessments of treatment effects would be useful. We assessed the correlations between potential surrogate endpoints and overall survival at individual and trial levels. Methods We analysed individual patients' data from 15 071 patients involved in 60 randomised clinical trials that were assessed in six meta-analyses. Two meta-analyses were of adjuvant chemotherapy in non-small-cell lung cancer, three were of sequential or concurrent chemotherapy, and one was of modified radiotherapy in locally advanced lung cancer. We investigated disease-free survival (DFS) or progression-free survival (PFS), defined as the time from randomisation to local or distant relapse or death, and locoregional control, defined as the time to the first local event, as potential surrogate endpoints. At the individual level we calculated the squared correlations between distributions of these three endpoints and overall survival, and at the trial level we calculated the squared correlation between treatment effects for endpoints. Findings In trials of adjuvant chemotherapy, correlations between DFS and overall survival were very good at the individual level (ρ2=0·83, 95% CI 0·83–0·83 in trials without radiotherapy, and 0·87, 0·87–0·87 in trials with radiotherapy) and excellent at trial level (R2=0·92, 95% CI 0·88–0·95 in trials without radiotherapy and 0·99, 0·98–1·00 in trials with radiotherapy). In studies of locally advanced disease, correlations between PFS and overall survival were very good at the individual level (ρ2 range 0·77–0·85, dependent on the regimen being assessed) and trial level (R2 range 0·89–0·97). In studies with data on locoregional control, individual-level correlations were good (ρ2=0·71, 95% CI 0·71–0·71 for concurrent chemotherapy and ρ2=0·61, 0·61–0·61 for modified vs standard radiotherapy) and trial-level correlations very good (R2=0·85, 95% CI 0·77–0·92 for concurrent chemotherapy and R2=0·95, 0·91–0·98 for modified vs standard radiotherapy). Interpretation We found a high level of evidence that DFS is a valid surrogate endpoint for overall survival in studies of adjuvant chemotherapy involving patients with non-small-cell lung cancers, and PFS in those of chemotherapy and radiotherapy for patients with locally advanced lung cancers. Extrapolation to targeted agents, however, is not automatically warranted. Funding Programme Hospitalier de Recherche Clinique, Ligue Nationale Contre le Cancer, British Medical Research Council, Sanofi-Aventis. PMID:23680111

Consuming a Ketogenic Diet while Receiving Radiation and Chemotherapy for Locally Advanced Lung Cancer and Pancreatic Cancer: The University of Iowa Experience of Two Phase 1 Clinical Trials.

PubMed

Zahra, Amir; Fath, Melissa A; Opat, Emyleigh; Mapuskar, Kranti A; Bhatia, Sudershan K; Ma, Daniel C; Rodman, Samuel N; Snyders, Travis P; Chenard, Catherine A; Eichenberger-Gilmore, Julie M; Bodeker, Kellie L; Ahmann, Logan; Smith, Brian J; Vollstedt, Sandy A; Brown, Heather A; Hejleh, Taher Abu; Clamon, Gerald H; Berg, Daniel J; Szweda, Luke I; Spitz, Douglas R; Buatti, John M; Allen, Bryan G

2017-06-01

Ketogenic diets are low in carbohydrates and high in fat, which forces cells to rely more heavily upon mitochondrial oxidation of fatty acids for energy. Relative to normal cells, cancer cells are believed to exist under a condition of chronic mitochondrial oxidative stress that is compensated for by increases in glucose metabolism to generate reducing equivalents. In this study we tested the hypothesis that a ketogenic diet concurrent with radiation and chemotherapy would be clinically tolerable in locally advanced non-small cell lung cancer (NSCLC) and pancreatic cancer and could potentially exploit cancer cell oxidative metabolism to improve therapeutic outcomes. Mice bearing MIA PaCa-2 pancreatic cancer xenografts were fed either a ketogenic diet or standard rodent chow, treated with conventionally fractionated radiation (2 Gy/fraction), and tumor growth rates were assessed daily. Tumors were assessed for immunoreactive 4-hydroxy-2-nonenal-(4HNE)-modfied proteins as a marker of oxidative stress. Based on this and another previously published preclinical study, phase 1 clinical trials in locally advanced NSCLC and pancreatic cancer were initiated, combining standard radiation and chemotherapy with a ketogenic diet for six weeks (NSCLC) or five weeks (pancreatic cancer). The xenograft experiments demonstrated prolonged survival and increased 4HNE-modfied proteins in animals consuming a ketogenic diet combined with radiation compared to radiation alone. In the phase 1 clinical trial, over a period of three years, seven NSCLC patients enrolled in the study. Of these, four were unable to comply with the diet and withdrew, two completed the study and one was withdrawn due to a dose-limiting toxicity. Over the same time period, two pancreatic cancer patients enrolled in the trial. Of these, one completed the study and the other was withdrawn due to a dose-limiting toxicity. The preclinical experiments demonstrate that a ketogenic diet increases radiation sensitivity in a pancreatic cancer xenograft model. However, patients with locally advanced NSCLC and pancreatic cancer receiving concurrent radiotherapy and chemotherapy had suboptimal compliance to the oral ketogenic diet and thus, poor tolerance.

Phase 1/2 Trial of 5-Fraction Stereotactic Radiosurgery With 5-mm Margins With Concurrent and Adjuvant Temozolomide in Newly Diagnosed Supratentorial Glioblastoma: Health-Related Quality of Life Results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pollom, Erqi L.; Fujimoto, Dylann; Wynne, Jacob

Purpose: We report a longitudinal assessment of health-related quality of life (HRQOL) in patients with glioblastoma (GBM) treated on a prospective dose escalation trial of 5-fraction stereotactic radiosurgery (25-40 Gy in 5 fractions) with concurrent and adjuvant temozolomide. Methods: HRQOL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire core-30 (QLQ-C30) general, the EORTC quality of life questionnaire-brain cancer specific module (QLQ-BN20), and the M.D. Anderson Symptom Inventory–Brain Tumor (MDASI-BT). Questionnaires were completed at baseline and at every follow-up visit after completion of radiosurgery. Changes from baseline for 9 predefined HRQOL measures (globalmore » quality of life, physical functioning, social functioning, emotional functioning, motor dysfunction, communication deficit, fatigue, insomnia, and future uncertainty) were calculated at every time point. Results: With a median follow-up time of 10.4 months (range, 0.4-52 months), 139 total HRQOL questionnaires were completed by the 30 patients on trial. Compliance with HRQOL assessment was 76% at 12 months. Communication deficit significantly worsened over time, with a decline of 1.7 points per month (P=.008). No significant changes over time were detected in the other 8 scales of our primary analysis, including global quality of life. Although 8 patients (27%) experienced adverse radiation effects (ARE) on this dose escalation trial, it was not associated with a statistically significant decline in any of the primary HRQOL scales. Disease progression was associated with communication deficit, with patients experiencing an average worsening of 13.9 points per month after progression compared with 0.7 points per month before progression (P=.01). Conclusion: On this 5-fraction dose escalation protocol for newly diagnosed GBM, overall HRQOL remained stable and appears similar to historical controls of 30 fractions of radiation therapy. Tumor recurrence was associated with worsening communication deficit, and ARE did not correlate with a decline in HRQOL.« less

Cost-effectiveness of Bezlotoxumab Compared With Placebo for the Prevention of Recurrent Clostridium difficile Infection.

PubMed

Prabhu, Vimalanand S; Dubberke, Erik R; Dorr, Mary Beth; Elbasha, Elamin; Cossrow, Nicole; Jiang, Yiling; Marcella, Stephen

2018-01-18

Clostridium difficile infection (CDI) is the most commonly recognized cause of recurrent diarrhea. Bezlotoxumab, administered concurrently with antibiotics directed against C. difficile (standard of care [SoC]), has been shown to reduce the recurrence of CDI, compared with SoC alone. This study aimed to assess the cost-effectiveness of bezlotoxumab administered concurrently with SoC, compared with SoC alone, in subgroups of patients at risk of recurrence of CDI. A computer-based Markov health state transition model was designed to track the natural history of patients infected with CDI. A cohort of patients entered the model with either a mild/moderate or severe CDI episode, and were treated with SoC antibiotics together with either bezlotoxumab or placebo. The cohort was followed over a lifetime horizon, and costs and utilities for the various health states were used to estimate incremental cost-effectiveness ratios (ICERs). Both deterministic and probabilistic sensitivity analyses were used to test the robustness of the results. The cost-effectiveness model showed that, compared with placebo, bezlotoxumab was associated with 0.12 quality-adjusted life-years (QALYs) gained and was cost-effective in preventing CDI recurrences in the entire trial population, with an ICER of $19824/QALY gained. Compared with placebo, bezlotoxumab was also cost-effective in the subgroups of patients aged ≥65 years (ICER of $15298/QALY), immunocompromised patients (ICER of $12597/QALY), and patients with severe CDI (ICER of $21430/QALY). Model-based results demonstrated that bezlotoxumab was cost-effective in the prevention of recurrent CDI compared with placebo, among patients receiving SoC antibiotics for treatment of CDI. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Integrated System-Level Optimization for Concurrent Engineering With Parametric Subsystem Modeling

NASA Technical Reports Server (NTRS)

Schuman, Todd; DeWeck, Oliver L.; Sobieski, Jaroslaw

2005-01-01

The introduction of concurrent design practices to the aerospace industry has greatly increased the productivity of engineers and teams during design sessions as demonstrated by JPL's Team X. Simultaneously, advances in computing power have given rise to a host of potent numerical optimization methods capable of solving complex multidisciplinary optimization problems containing hundreds of variables, constraints, and governing equations. Unfortunately, such methods are tedious to set up and require significant amounts of time and processor power to execute, thus making them unsuitable for rapid concurrent engineering use. This paper proposes a framework for Integration of System-Level Optimization with Concurrent Engineering (ISLOCE). It uses parametric neural-network approximations of the subsystem models. These approximations are then linked to a system-level optimizer that is capable of reaching a solution quickly due to the reduced complexity of the approximations. The integration structure is described in detail and applied to the multiobjective design of a simplified Space Shuttle external fuel tank model. Further, a comparison is made between the new framework and traditional concurrent engineering (without system optimization) through an experimental trial with two groups of engineers. Each method is evaluated in terms of optimizer accuracy, time to solution, and ease of use. The results suggest that system-level optimization, running as a background process during integrated concurrent engineering sessions, is potentially advantageous as long as it is judiciously implemented.

The role of visual representations during the lexical access of spoken words

PubMed Central

Lewis, Gwyneth; Poeppel, David

2015-01-01

Do visual representations contribute to spoken word recognition? We examine, using MEG, the effects of sublexical and lexical variables at superior temporal (ST) areas and the posterior middle temporal gyrus (pMTG) compared with that of word imageability at visual cortices. Embodied accounts predict early modulation of visual areas by imageability - concurrently with or prior to modulation of pMTG by lexical variables. Participants responded to speech stimuli varying continuously in imageability during lexical decision with simultaneous MEG recording. We employed the linguistic variables in a new type of correlational time course analysis to assess trial-by-trial activation in occipital, ST, and pMTG regions of interest (ROIs). The linguistic variables modulated the ROIs during different time windows. Critically, visual regions reflected an imageability effect prior to effects of lexicality on pMTG. This surprising effect supports a view on which sensory aspects of a lexical item are not a consequence of lexical activation. PMID:24814579

A randomized controlled trial testing an adherence-optimized Vitamin D regimen to mitigate bone change in adolescents being treated for acute lymphoblastic leukemia.

PubMed

Orgel, Etan; Mueske, Nicole M; Sposto, Richard; Gilsanz, Vicente; Wren, Tishya A L; Freyer, David R; Butturini, Anna M; Mittelman, Steven D

2017-10-01

Adolescents with acute lymphoblastic leukemia (ALL) develop osteopenia early in therapy, potentially exacerbated by high rates of concurrent Vitamin D deficiency. We conducted a randomized clinical trial testing a Vitamin D-based intervention to improve Vitamin D status and reduce bone density decline. Poor adherence to home supplementation necessitated a change to directly observed therapy (DOT) with intermittent, high-dose Vitamin D3 randomized versus standard of care (SOC). Compared to SOC, DOT Vitamin D3 successfully increased trough Vitamin 25(OH)D levels (p = .026) with no residual Vitamin D deficiency, 100% adherence to DOT Vitamin D3, and without associated toxicity. However, neither Vitamin D status nor supplementation impacted bone density. Thus, this adherence-optimized intervention is feasible and effective to correct Vitamin D deficiency in adolescents during ALL therapy. Repletion of Vitamin D and calcium alone did not mitigate osteopenia, however, and new, comprehensive approaches are needed to address treatment-associated osteopenia during ALL therapy.

The role of visual representations during the lexical access of spoken words.

PubMed

Lewis, Gwyneth; Poeppel, David

2014-07-01

Do visual representations contribute to spoken word recognition? We examine, using MEG, the effects of sublexical and lexical variables at superior temporal (ST) areas and the posterior middle temporal gyrus (pMTG) compared with that of word imageability at visual cortices. Embodied accounts predict early modulation of visual areas by imageability--concurrently with or prior to modulation of pMTG by lexical variables. Participants responded to speech stimuli varying continuously in imageability during lexical decision with simultaneous MEG recording. We employed the linguistic variables in a new type of correlational time course analysis to assess trial-by-trial activation in occipital, ST, and pMTG regions of interest (ROIs). The linguistic variables modulated the ROIs during different time windows. Critically, visual regions reflected an imageability effect prior to effects of lexicality on pMTG. This surprising effect supports a view on which sensory aspects of a lexical item are not a consequence of lexical activation. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparison of concurrent treatment with vitamin K2 and risedronate compared with treatment with risedronate alone in patients with osteoporosis: Japanese Osteoporosis Intervention Trial-03.

PubMed

Tanaka, Shiro; Miyazaki, Teruhiko; Uemura, Yukari; Miyakawa, Nobuaki; Gorai, Itsuo; Nakamura, Toshitaka; Fukunaga, Masao; Ohashi, Yasuo; Ohta, Hiroaki; Mori, Satoshi; Hagino, Hiroshi; Hosoi, Takayuki; Sugimoto, Toshitsugu; Itoi, Eiji; Orimo, Hajime; Shiraki, Masataka

2017-07-01

The aim of this study was to investigate the efficacy of concurrent treatment with vitamin K 2 and risedronate compared with treatment with risedronate alone in patients with osteoporosis and to explore subsets of patients for which concurrent treatment is particularly efficacious. Women with osteoporosis aged 65 years or older were recruited from 123 institutes in Japan and allocated to take either vitamin K 2 (45 mg/day) and risedronate (2.5 mg/day or 17.5 mg/week) or risedronate (2.5 mg/day or 17.5 mg/week) alone. The primary end point was the incidence of any fracture (vertebral and nonvertebral). The secondary end points were bone mineral density, height, undercarboxylated osteocalcin concentration, quality of life, and safety. Over a 2-year follow-up, vertebral or nonvertebral fractures occurred in 117 or 22 sites respectively among 931 patients in the risedronate and vitamin K 2 group and in 104 or 26 sites respectively among 943 patients in the risedronate alone group. The rates of any incident fracture were similar between the two groups (incidence rate ratio 1.074, 95 % confidence interval 0.811-1.422, p = 0.62), implying that the primary end point was not met. There were no differences in the degree of increase in bone mineral density between the two groups. Undercarboxylated osteocalcin concentration decreased from 5.81 ± 3.93 ng/mL to 2.59 ± 1.52 ng/mL at 6 months in the risedronate and vitamin K 2 group, whereas the change in the risedronate alone group was minimal (from 5.96 ± 4.36 ng/mL to 4.05 ± 3.40 ng/mL at 6 months) (p < 0.01). The treatment discontinuation rate was higher in the risedronate and vitamin K 2 group than in the risedronate alone group (10.0 % vs 6.7 %). No unknown adverse drug reactions were reported. In conclusion, concurrent treatment with vitamin K 2 and risedronate was not efficacious compared with monotherapy with risedronate in terms of fracture prevention.

Modeling the Risk of Radiation-Induced Acute Esophagitis for Combined Washington University and RTOG Trial 93-11 Lung Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Ellen X.; Bradley, Jeffrey D.; El Naqa, Issam

2012-04-01

Purpose: To construct a maximally predictive model of the risk of severe acute esophagitis (AE) for patients who receive definitive radiation therapy (RT) for non-small-cell lung cancer. Methods and Materials: The dataset includes Washington University and RTOG 93-11 clinical trial data (events/patients: 120/374, WUSTL = 101/237, RTOG9311 = 19/137). Statistical model building was performed based on dosimetric and clinical parameters (patient age, sex, weight loss, pretreatment chemotherapy, concurrent chemotherapy, fraction size). A wide range of dose-volume parameters were extracted from dearchived treatment plans, including Dx, Vx, MOHx (mean of hottest x% volume), MOCx (mean of coldest x% volume), and gEUDmore » (generalized equivalent uniform dose) values. Results: The most significant single parameters for predicting acute esophagitis (RTOG Grade 2 or greater) were MOH85, mean esophagus dose (MED), and V30. A superior-inferior weighted dose-center position was derived but not found to be significant. Fraction size was found to be significant on univariate logistic analysis (Spearman R = 0.421, p < 0.00001) but not multivariate logistic modeling. Cross-validation model building was used to determine that an optimal model size needed only two parameters (MOH85 and concurrent chemotherapy, robustly selected on bootstrap model-rebuilding). Mean esophagus dose (MED) is preferred instead of MOH85, as it gives nearly the same statistical performance and is easier to compute. AE risk is given as a logistic function of (0.0688 Asterisk-Operator MED+1.50 Asterisk-Operator ConChemo-3.13), where MED is in Gy and ConChemo is either 1 (yes) if concurrent chemotherapy was given, or 0 (no). This model correlates to the observed risk of AE with a Spearman coefficient of 0.629 (p < 0.000001). Conclusions: Multivariate statistical model building with cross-validation suggests that a two-variable logistic model based on mean dose and the use of concurrent chemotherapy robustly predicts acute esophagitis risk in combined-data WUSTL and RTOG 93-11 trial datasets.« less

A randomized controlled trial of single versus multiple health behavior change: promoting physical activity and nutrition among adolescents.

PubMed

Prochaska, Judith J; Sallis, James F

2004-05-01

Targeting multiple behaviors for change may provide significant health benefits. This study compared interventions targeting physical activity and nutrition (PAN) concurrently versus physical activity (PA) alone. Adolescents (N=138) were randomized to the PAN or PA intervention or control condition (n=46 per group). Primary outcomes were change in PA accelerometer and 3-day dietary recording from baseline to 3-month follow-up. The PAN and PA interventions were efficacious in supporting boys' (p<.001) but not girls' (p=.663) PA relative to the control condition. Dietary change was minimal. Although the findings do not reveal a decrement to PA promotion when a nutrition intervention was added, neither do they reveal any additional benefit. More studies comparing single versus multibehavioral interventions are needed. ((c) 2004 APA, all rights reserved)

A randomized problem-solving trial for adolescent brain injury: Changes in social competence.

PubMed

Tlustos, Sarah J; Kirkwood, Michael W; Taylor, H Gerry; Stancin, Terry; Brown, Tanya M; Wade, Shari L

2016-11-01

Traumatic brain injury (TBI) in adolescence has well documented effects on social competence. Few studies have examined the effects of behavioral interventions on social competence or identified factors associated with changes in social competence after injury. Research Method/Design: Adolescents with moderate to severe TBI ages 12-17 years were randomized within 6 months of injury to either a problem solving and communication (CAPS) group that received online counseling (n = 65) or an Internet resources comparison (IRC) group (n = 67) for a comparative effectiveness trial. Parent-report measures of social competence (Child Behavior Checklist, CBCL; Home and Community Social Behavior Scales, HCSBS; Behavioral and Emotional Rating Scale, BERS-2) were administered at baseline (preintervention) and approximately 6 months later. Analyses examined these measures in relation to treatment group, TBI severity, and age. Regression analyses were also conducted to examine baseline measures of cognition as predictors of social competence after TBI. CAPS had a more positive effect than the comparison condition on the HCSBS and BERS-2 for younger teens with moderate TBI and older teens with severe TBI. More parent-rated executive dysfunction at baseline was related to both lower concurrent levels of social competence and less positive gains in competence over time, whereas higher baseline IQ predicted greater gains in competence. CAPS may be effective for improving social competence for teens after TBI, with benefits dependent on the teen's age and injury severity. Parent-rated executive dysfunction, moreover, has utility in predicting both lower concurrent levels of social competence and subsequent postinjury gains in competence. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Cyclosporin and ketoconazole interaction for treatment of perianal fistulas in the dog.

PubMed

Mouatt, J G

2002-04-01

To assess the use of concurrent ketoconazole and low dose cyclosporin administration in a group of dogs with clinical evidence of perianal fistulas, and to determine if this combination could be used to manage perianal fistulas effectively. Prospective clinical trial Sixteen dogs with clinical evidence of perianal fistulas were given ketoconazole (10 mg/kg once daily) and cyclosporin (1 mg/kg twice daily initially) for 16 weeks. Blood cyclosporin assays were performed regularly and cyclosporin doses were altered to achieve a stable blood level above 200 ng/mL. Regular examinations assessed the dogs' general health, changes in clinical behaviour, fistula size and number. A complete blood count and serum biochemical analysis was performed in all dogs before and after the treatment period, and after 8 weeks of treatment in 12 dogs. Dogs were assessed for recurrence of lesions at 1, 3 and 12 months after the trial. All dogs showed marked improvement in lesions and behaviour within 14 days of the medication. Fourteen dogs completed the trial. Two dogs were excluded due to concurrent disease. Thirteen dogs (93%) showed complete resolution of fistulas during the treatment period. Seven dogs (50%) had no recurrence after 12 months. Recurrence was seen in three dogs (21%) at 8, 10 and 12 months after treatment, and in three dogs (21%) within 1 month of treatment. The medication was well tolerated. Side effects included transient anorexia, vomiting and lethargy in some dogs, increased shedding of hair and gingival hyperplasia. Ketoconazole administration allowed a dramatic reduction in cyclosporin dose (over 90% in 12 dogs and 80% in the other two) compared to previously reported cases treated with cyclosporin alone. The use of combined ketoconazole and cyclosporin provided an effective treatment for perianal fistulas. Outcomes were similar to those seen with cyclosporin alone, but allowed a significant reduction in cyclosporin dose and, therefore, cost. The use of immunosuppressive therapy in the treatment of perianal fistulas was effective and avoided many of the problems associated with surgical treament.

'The trial is owned by the team, not by an individual': a qualitative study exploring the role of teamwork in recruitment to randomised controlled trials in surgical oncology.

PubMed

Strong, Sean; Paramasivan, Sangeetha; Mills, Nicola; Wilson, Caroline; Donovan, Jenny L; Blazeby, Jane M

2016-04-26

Challenges exist in recruitment to trials involving interventions delivered by different clinical specialties. Collaboration is required between clinical specialty and research teams. The aim of this study was to explore how teamwork influences recruitment to a multicentre randomised controlled trial (RCT) involving interventions delivered by different clinical specialties. Semi-structured interviews were conducted in three centres with a purposeful sample of members of the surgical, oncology and research teams recruiting to a feasibility RCT comparing definitive chemoradiotherapy with chemoradiotherapy and surgery for oesophageal squamous cell carcinoma. Interviews explored factors known to influence healthcare team effectiveness and were audio-recorded and thematically analysed. Sampling, data collection and analysis were undertaken iteratively and concurrently. Twenty-one interviews were conducted. Factors that influenced how team working impacted upon trial recruitment were centred on: (1) the multidisciplinary team (MDT) meeting, (2) leadership of the trial, and (3) the recruitment process. The weekly MDT meeting was reported as central to successful recruitment and formed the focus for creating a 'study team', bringing together clinical and research teams. Shared study leadership positively influenced healthcare professionals' willingness to participate. Interviewees perceived their clinical colleagues to have strong treatment preferences which led to scepticism regarding whether the treatments were being described to patients in a balanced manner. This study has highlighted a number of aspects of team functioning that are important for recruitment to RCTs that span different clinical specialties. Understanding these issues will aid the production of guidance on team-relevant issues that should be considered in trial management and the development of interventions that will facilitate teamwork and improve recruitment to these challenging RCTs. International Standard Randomised Controlled Trial Number (ISRCTN): ISRCTN89052791 .

Impact of post-remission therapy in patients aged 65–70 years with de novo acute myeloid leukemia: a comparison of two concomitant randomized ALFA trials with overlapping age inclusion criteria

PubMed Central

Itzykson, Raphael; Gardin, Claude; Pautas, Cécile; Thomas, Xavier; Turlure, Pascal; Raffoux, Emmanuel; Terré, Christine; Fenaux, Pierre; Castaigne, Sylvie; Dombret, Hervé; Boissel, Nicolas

2011-01-01

Background There is no standard post-remission therapy in older patients with acute myeloid leukemia. Design and Methods From 1999 to 2006, the Acute Leukemia French Association group ran two concurrent randomized trials with overlapping inclusion criteria for patients aged 65 to 70 with acute myeloid leukemia, with different post-remission strategies: two intensive courses in the 9801 trial, one intensive course or six outpatient courses in the 9803 trial. We analyzed the outcome of these patients per protocol and per post-remission therapy. Results Two hundred and eleven patients aged 65 to 70 years with de novo acute myeloid leukemia were enrolled in trial 9801 (n=76) or 9803 (n=135). The patients in the two trials had comparable white blood cell counts (P=0.3), cytogenetics (P=0.49), and complete remission rates (70% and 57%, respectively; P=0.17). Overall survival was identical in both trials (32% and 34% at 2 years, respectively; P=0.71). Overall survival after complete remission was identical in the 103 of 130 patients who received the planned post-remission courses (n=44 with two intensive courses, n=28 with one intensive course, n=31 with six outpatient courses; 41%, 55%, and 58% at 2 years, respectively; P=0.34). Even in patients with favorable or normal karyotype (n=97), overall survival from complete remission was not improved by more intensive post-remission therapy. Conclusions In patients aged 65 to 70 years with de novo acute myeloid leukemia in complete remission after standard intensive induction chemotherapy, there is no apparent benefit from intensive post-remission therapy. (ClinicalTrials.gov Identifiers: NCT00931138 and NCT00363025) PMID:21459791

Impact of post-remission therapy in patients aged 65-70 years with de novo acute myeloid leukemia: a comparison of two concomitant randomized ALFA trials with overlapping age inclusion criteria.

PubMed

Itzykson, Raphael; Gardin, Claude; Pautas, Cécile; Thomas, Xavier; Turlure, Pascal; Raffoux, Emmanuel; Terré, Christine; Fenaux, Pierre; Castaigne, Sylvie; Dombret, Hervé; Boissel, Nicolas

2011-06-01

There is no standard post-remission therapy in older patients with acute myeloid leukemia. From 1999 to 2006, the Acute Leukemia French Association group ran two concurrent randomized trials with overlapping inclusion criteria for patients aged 65 to 70 with acute myeloid leukemia, with different post-remission strategies: two intensive courses in the 9801 trial, one intensive course or six outpatient courses in the 9803 trial. We analyzed the outcome of these patients per protocol and per post-remission therapy. Two hundred and eleven patients aged 65 to 70 years with de novo acute myeloid leukemia were enrolled in trial 9801 (n=76) or 9803 (n=135). The patients in the two trials had comparable white blood cell counts (P=0.3), cytogenetics (P=0.49), and complete remission rates (70% and 57%, respectively; P=0.17). Overall survival was identical in both trials (32% and 34% at 2 years, respectively; P=0.71). Overall survival after complete remission was identical in the 103 of 130 patients who received the planned post-remission courses (n=44 with two intensive courses, n=28 with one intensive course, n=31 with six outpatient courses; 41%, 55%, and 58% at 2 years, respectively; P=0.34). Even in patients with favorable or normal karyotype (n=97), overall survival from complete remission was not improved by more intensive post-remission therapy. In patients aged 65 to 70 years with de novo acute myeloid leukemia in complete remission after standard intensive induction chemotherapy, there is no apparent benefit from intensive post-remission therapy. (ClinicalTrials.gov Identifiers: NCT00931138 and NCT00363025).

A Phase I Dose Escalation Study of Hypofractionated IMRT Field-in-Field Boost for Newly Diagnosed Glioblastoma Multiforme

DOE Office of Scientific and Technical Information (OSTI.GOV)

Monjazeb, Arta M., E-mail: arta.monjazeb@ucdmc.ucdavis.edu; Ayala, Deandra; Jensen, Courtney

2012-02-01

Objectives: To describe the results of a Phase I dose escalation trial for newly diagnosed glioblastoma multiforme (GBM) using a hypofractionated concurrent intensity-modulated radiotherapy (IMRT) boost. Methods: Twenty-one patients were enrolled between April 1999 and August 2003. Radiotherapy consisted of daily fractions of 1.8 Gy with a concurrent boost of 0.7 Gy (total 2.5 Gy daily) to a total dose of 70, 75, or 80 Gy. Concurrent chemotherapy was not permitted. Seven patients were enrolled at each dose and dose limiting toxicities were defined as irreversible Grade 3 or any Grade 4-5 acute neurotoxicity attributable to radiotherapy. Results: All patientsmore » experienced Grade 1 or 2 acute toxicities. Acutely, 8 patients experienced Grade 3 and 1 patient experienced Grade 3 and 4 toxicities. Of these, only two reversible cases of otitis media were attributable to radiotherapy. No dose-limiting toxicities were encountered. Only 2 patients experienced Grade 3 delayed toxicity and there was no delayed Grade 4 toxicity. Eleven patients requiring repeat resection or biopsy were found to have viable tumor and radiation changes with no cases of radionecrosis alone. Median overall and progression-free survival for this cohort were 13.6 and 6.5 months, respectively. One- and 2-year survival rates were 57% and 19%. At recurrence, 15 patients received chemotherapy, 9 underwent resection, and 5 received radiotherapy. Conclusions: Using a hypofractionated concurrent IMRT boost, we were able to safely treat patients to 80 Gy without any dose-limiting toxicity. Given that local failure still remains the predominant pattern for GBM patients, a trial of dose escalation with IMRT and temozolomide is warranted.« less

Concurrent, but not sequential, PD-1 blockade with a DNA vaccine elicits anti-tumor responses in patients with metastatic, castration-resistant prostate cancer.

PubMed

McNeel, Douglas G; Eickhoff, Jens C; Wargowski, Ellen; Zahm, Christopher; Staab, Mary Jane; Straus, Jane; Liu, Glenn

2018-05-22

T-cell checkpoint inhibitors have demonstrated dramatic clinical activity against multiple cancer types, however little activity in patients with prostate cancer. Conversely, an anti-tumor vaccine was approved for the treatment of prostate cancer, having demonstrated an improvement in overall survival, despite few objective disease responses. In murine studies, we found that PD-1 expression on CD8+ T cells increased following anti-tumor vaccination, and that PD-1/PD-L1 blockade at the time of immunization elicited greater anti-tumor responses. Based on these data we initiated a pilot trial evaluating the immunological and clinical efficacy of a DNA encoding prostatic acid phosphatase (PAP) when delivered in combination with pembrolizumab. 26 patients were treated for 12 weeks with vaccine and received pembrolizumab either during this time or during the subsequent 12 weeks. Adverse events included grade 2 and 3 fatigue, diarrhea, thyroid dysfunction, and hepatitis. Median time to radiographic progression was not different between study arms. 8/13 (62%) of patients treated concurrently, and 1/12 (8%, p=0.01) of patients treated sequentially, experienced PSA declines from baseline. Of these, two were over 50% and one was a complete PSA response. No confirmed CR or PR were observed, however 4/5 patients treated concurrently had measurable decreases in tumor volume at 12 weeks. PSA declines were associated with the development of PAP-specific Th1-biased T cell immunity and CD8+ T cell infiltration in metastatic tumor biopsy specimens. These data are the first report of a clinical trial demonstrating that the efficacy of an anti-tumor vaccine can be augmented by concurrent PD-1 blockade.

Warfarin for prevention of thromboembolism in atrial fibrillation: comparison of patient characteristics and outcomes of the "Real-World" Michigan Anticoagulation Quality Improvement Initiative (MAQI2) registry to the RE-LY, ROCKET-AF, and ARISTOTLE trials.

PubMed

Hughey, Andrew B; Gu, Xiaokui; Haymart, Brian; Kline-Rogers, Eva; Almany, Steve; Kozlowski, Jay; Besley, Dennis; Krol, Gregory D; Ahsan, Syed; Kaatz, Scott; Froehlich, James B; Barnes, Geoffrey D

2018-06-14

Randomized controlled trials (RCTs) examining warfarin use for stroke prevention in atrial fibrillation (AF) may not accurately reflect real-world populations. We aimed to determine the representativeness of the RCT populations to real-world patients and to describe differences in the characteristics of trial populations from trial eligible patients in a real-world setting. We hypothesized that a significant fraction of real-world patients would not qualify for the RE-LY, ROCKET-AF, and ARISTOTLE trials and that real-world patients qualifying for the studies may have more strokes and bleeding events. We compared the inclusion and exclusion criteria, patient characteristics, and clinical outcomes from RE-LY, ROCKET-AF, and ARISTOTLE against data from the Michigan Anticoagulation Quality Improvement Initiative (MAQI 2 ), a regional network of six community- and academic-based anticoagulation clinics. Of the 1446 non-valvular AF patients in the MAQI 2 registry taking warfarin, approximately 40-60% would meet the selection criteria used in RE-LY (788, 54.5%), ROCKET-AF (566, 39.1%), and ARISTOTLE (866, 59.9%). The most common reasons for exclusion from one or more trial were anemia (15.1%), other concurrent medications (11.2%), and chronic kidney disease (9.4%). Trial-eligible MAQI 2 patients were older, more frequently female, with a higher rate of paroxysmal AF, and lower rates of congestive heart failure, previous stroke, and previous myocardial infarction than the trial populations. MAQI 2 patients eligible for each trial had a lower rate of stroke and similar rate of major bleeding than was observed in the trials. A sizable proportion of real-world AF patients managed in anticoagulation clinics would not have been eligible for the RE-LY, ROCKET-AF, and ARISOTLE trials. The expected stroke risk reduction and bleeding risk among real-world AF patients on warfarin may not be congruent with published clinical trial data.

Treatment factors affecting outcomes in HIV-associated non-Hodgkin lymphomas: a pooled analysis of 1546 patients

PubMed Central

Xue, Xiaonan; Wang, Dan; Tamari, Roni; Lee, Jeannette Y.; Mounier, Nicolas; Kaplan, Lawrence D.; Ribera, Josep-Maria; Spina, Michele; Tirelli, Umberto; Weiss, Rudolf; Galicier, Lionel; Boue, Francois; Wilson, Wyndham H.; Wyen, Christoph; Oriol, Albert; Navarro, José-Tomás; Dunleavy, Kieron; Little, Richard F.; Ratner, Lee; Garcia, Olga; Morgades, Mireia; Remick, Scot C.; Noy, Ariela; Sparano, Joseph A.

2013-01-01

Limited comparative data exist for the treatment of HIV-associated non-Hodgkin lymphoma. We analyzed pooled individual patient data for 1546 patients from 19 prospective clinical trials to assess treatment-specific factors (type of chemotherapy, rituximab, and concurrent combination antiretroviral [cART] use) and their influence on the outcomes complete response (CR), progression free survival (PFS), and overall survival (OS). In our analysis, rituximab was associated with a higher CR rate (odds ratio [OR] 2.89; P < .001), improved PFS (hazard ratio [HR] 0.50; P < .001), and OS (HR 0.51; P < .0001). Compared with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), initial therapy with more dose-intense regimens resulted in better CR rates (ACVBP [doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisolone]: OR 1.70; P < .04), PFS (ACVBP: HR 0.72; P = .049; “intensive regimens”: HR 0.35; P < .001) and OS (“intensive regimens”: HR 0.54; P < .001). Infusional etoposide, prednisone, infusional vincristine, infusional doxorubicin, and cyclophosphamide (EPOCH) was associated with significantly better OS in diffuse large B-cell lymphoma (HR 0.33; P = .03). Concurrent use of cART was associated with improved CR rates (OR 1.89; P = .005) and trended toward improved OS (HR 0.78; P = .07). These findings provide supporting evidence for current patterns of care where definitive evidence is unavailable. PMID:24014242

Identification of surrogate endpoints in patients with locoregionally advanced nasopharyngeal carcinoma receiving neoadjuvant chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone.

PubMed

Chen, Yu-Pei; Zhang, Wen-Na; Tang, Ling-Long; Mao, Yan-Ping; Liu, Xu; Chen, Lei; Zhou, Guan-Qun; Mai, Hai-Qiang; Shao, Jian-Yong; Jia, Wei-Hua; Kang, Tie-Bang; Zeng, Mu-Sheng; Sun, Ying; Ma, Jun

2015-11-24

In the era of intensity-modulated radiotherapy (IMRT), the efficacy of additional neoadjuvant chemotherapy (NACT) to concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal carcinoma (NPC) is currently being investigated in ongoing trials. Overall survival (OS) is the gold standard endpoint in NPC trials. We performed this analysis to identify surrogate endpoints for OS, which could shorten follow-up duration and speed up assessment of treatment effects. We retrospectively analysed 208 matched-pair patients with locoregionally advanced NPC receiving NACT+CCRT or CCRT. Progression-free survival (PFS), failure-free survival (FFS), distant failure-free survival (D-FFS) and locoregional failure-free survival (LR-FFS) at 2 and 3 years were assessed as surrogates for 5-year OS according to Prentice's criteria. The strength of the associations were assessed using Spearman's rank correlation coefficient. No significant differences were observed between treatment arms for any surrogate endpoint at 2 years, which rejected Prentice's second criterion. In contrast, 3-year LR-FFS, PFS, FFS and D-FFS were consistent with all four of Prentice's criteria; the rank correlation coefficient (0.730) between 3-year PFS and 5-year OS was highest. 3-year PFS, FFS and D-FFS could be valid surrogate endpoints for 5-year OS; 3-year PFS may be the most accurate.

Concurrent visual and tactile steady-state evoked potentials index allocation of inter-modal attention: a frequency-tagging study.

PubMed

Porcu, Emanuele; Keitel, Christian; Müller, Matthias M

2013-11-27

We investigated effects of inter-modal attention on concurrent visual and tactile stimulus processing by means of stimulus-driven oscillatory brain responses, so-called steady-state evoked potentials (SSEPs). To this end, we frequency-tagged a visual (7.5Hz) and a tactile stimulus (20Hz) and participants were cued, on a trial-by-trial basis, to attend to either vision or touch to perform a detection task in the cued modality. SSEPs driven by the stimulation comprised stimulus frequency-following (i.e. fundamental frequency) as well as frequency-doubling (i.e. second harmonic) responses. We observed that inter-modal attention to vision increased amplitude and phase synchrony of the fundamental frequency component of the visual SSEP while the second harmonic component showed an increase in phase synchrony, only. In contrast, inter-modal attention to touch increased SSEP amplitude of the second harmonic but not of the fundamental frequency, while leaving phase synchrony unaffected in both responses. Our results show that inter-modal attention generally influences concurrent stimulus processing in vision and touch, thus, extending earlier audio-visual findings to a visuo-tactile stimulus situation. The pattern of results, however, suggests differences in the neural implementation of inter-modal attentional influences on visual vs. tactile stimulus processing. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Nomograms Predicting Progression-Free Survival, Overall Survival, and Pelvic Recurrence in Locally Advanced Cervical Cancer Developed From an Analysis of Identifiable Prognostic Factors in Patients From NRG Oncology/Gynecologic Oncology Group Randomized Trials of Chemoradiotherapy

PubMed Central

Rose, Peter G.; Java, James; Whitney, Charles W.; Stehman, Frederick B.; Lanciano, Rachelle; Thomas, Gillian M.; DiSilvestro, Paul A.

2015-01-01

Purpose To evaluate the prognostic factors in locally advanced cervical cancer limited to the pelvis and develop nomograms for 2-year progression-free survival (PFS), 5-year overall survival (OS), and pelvic recurrence. Patients and Methods We retrospectively reviewed 2,042 patients with locally advanced cervical carcinoma enrolled onto Gynecologic Oncology Group clinical trials of concurrent cisplatin-based chemotherapy and radiotherapy. Nomograms for 2-year PFS, five-year OS, and pelvic recurrence were created as visualizations of Cox proportional hazards regression models. The models were validated by bootstrap-corrected, relatively unbiased estimates of discrimination and calibration. Results Multivariable analysis identified prognostic factors including histology, race/ethnicity, performance status, tumor size, International Federation of Gynecology and Obstetrics stage, tumor grade, pelvic node status, and treatment with concurrent cisplatin-based chemotherapy. PFS, OS, and pelvic recurrence nomograms had bootstrap-corrected concordance indices of 0.62, 0.64, and 0.73, respectively, and were well calibrated. Conclusion Prognostic factors were used to develop nomograms for 2-year PFS, 5-year OS, and pelvic recurrence for locally advanced cervical cancer clinically limited to the pelvis treated with concurrent cisplatin-based chemotherapy and radiotherapy. These nomograms can be used to better estimate individual and collective outcomes. PMID:25732170

Concurrent transcranial direct current stimulation and progressive resistance training in Parkinson's disease: study protocol for a randomised controlled trial.

PubMed

Hendy, Ashlee M; Tillman, Alex; Rantalainen, Timo; Muthalib, Makii; Johnson, Liam; Kidgell, Dawson J; Wundersitz, Daniel; Enticott, Peter G; Teo, Wei-Peng

2016-07-19

Parkinson's disease (PD) results from a loss of dopamine in the brain, leading to movement dysfunctions such as bradykinesia, postural instability, resting tremor and muscle rigidity. Furthermore, dopamine deficiency in PD has been shown to result in maladaptive plasticity of the primary motor cortex (M1). Progressive resistance training (PRT) is a popular intervention in PD that improves muscular strength and results in clinically significant improvements on the Unified Parkinson's Disease Rating Scale (UPDRS). In separate studies, the application of anodal transcranial direct current stimulation (a-tDCS) to the M1 has been shown to improve motor function in PD; however, the combined use of tDCS and PRT has not been investigated. We propose a 6-week, double-blind randomised controlled trial combining M1 tDCS and PRT of the lower body in participants (n = 42) with moderate PD (Hoehn and Yahr scale score 2-4). Supervised lower body PRT combined with functional balance tasks will be performed three times per week with concurrent a-tDCS delivered at 2 mA for 20 minutes (a-tDCS group) or with sham tDCS (sham group). Control participants will receive standard care (control group). Outcome measures will include functional strength, gait speed and variability, balance, neurophysiological function at rest and during movement execution, and the UPDRS motor subscale, measured at baseline, 3 weeks (during), 6 weeks (post), and 9 weeks (retention). Ethical approval has been granted by the Deakin University Human Research Ethics Committee (project number 2015-014), and the trial has been registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615001241527). This will be the first randomised controlled trial to combine PRT and a-tDCS targeting balance and gait in people with PD. The study will elucidate the functional, clinical and neurophysiological outcomes of combined PRT and a-tDCS. It is hypothesised that combined PRT and a-tDCS will significantly improve lower limb strength, postural sway, gait speed and stride variability compared with PRT with sham tDCS. Further, we hypothesise that pre-frontal cortex activation during dual-task cognitive and gait/balance activities will be reduced, and that M1 excitability and inhibition will be augmented, following the combined PRT and a-tDCS intervention. Australian New Zealand Clinical Trials Registry ACTRN12615001241527 . Registered on 12 November 2015.

Concurrent design of quasi-random photonic nanostructures

PubMed Central

Lee, Won-Kyu; Yu, Shuangcheng; Engel, Clifford J.; Reese, Thaddeus; Rhee, Dongjoon; Chen, Wei

2017-01-01

Nanostructured surfaces with quasi-random geometries can manipulate light over broadband wavelengths and wide ranges of angles. Optimization and realization of stochastic patterns have typically relied on serial, direct-write fabrication methods combined with real-space design. However, this approach is not suitable for customizable features or scalable nanomanufacturing. Moreover, trial-and-error processing cannot guarantee fabrication feasibility because processing–structure relations are not included in conventional designs. Here, we report wrinkle lithography integrated with concurrent design to produce quasi-random nanostructures in amorphous silicon at wafer scales that achieved over 160% light absorption enhancement from 800 to 1,200 nm. The quasi-periodicity of patterns, materials filling ratio, and feature depths could be independently controlled. We statistically represented the quasi-random patterns by Fourier spectral density functions (SDFs) that could bridge the processing–structure and structure–performance relations. Iterative search of the optimal structure via the SDF representation enabled concurrent design of nanostructures and processing. PMID:28760975

Hyperfractionated Accelerated Radiation Therapy (HART) of 70.6 Gy With Concurrent 5-FU/Mitomycin C Is Superior to HART of 77.6 Gy Alone in Locally Advanced Head and Neck Cancer: Long-term Results of the ARO 95-06 Randomized Phase III Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Budach, Volker, E-mail: volker.budach@charite.de; Stromberger, Carmen; Poettgen, Christoph

2015-04-01

Purpose: To report the long-term results of the ARO 95-06 randomized trial comparing hyperfractionated accelerated chemoradiation with mitomycin C/5-fluorouracil (C-HART) with hyperfractionated accelerated radiation therapy (HART) alone in locally advanced head and neck cancer. Patients and Methods: The primary endpoint was locoregional control (LRC). Three hundred eighty-four patients with stage III (6%) and IV (94%) oropharyngeal (59.4%), hypopharyngeal (32.3%), and oral cavity (8.3%) cancer were randomly assigned to 30 Gy/2 Gy daily followed by twice-daily 1.4 Gy to a total of 70.6 Gy concurrently with mitomycin C/5-FU (C-HART) or 16 Gy/2 Gy daily followed by twice-daily 1.4 Gy to a total dose of 77.6 Gy alone (HART). Statisticalmore » analyses were done with the log-rank test and univariate and multivariate Cox regression analyses. Results: The median follow-up time was 8.7 years (95% confidence interval [CI]: 7.8-9.7 years). At 10 years, the LRC rates were 38.0% (C-HART) versus 26.0% (HART, P=.002). The cancer-specific survival and overall survival rates were 39% and 10% (C-HART) versus 30.0% and 9% (HART, P=.042 and P=.049), respectively. According to multivariate Cox regression analysis, the combined treatment was associated with improved LRC (hazard ratio [HR]: 0.6 [95% CI: 0.5-0.8; P=.002]). The association between combined treatment arm and increased LRC appeared to be limited to oropharyngeal cancer (P=.003) as compared with hypopharyngeal or oral cavity cancer (P=.264). Conclusions: C-HART remains superior to HART in terms of LRC. However, this effect may be limited to oropharyngeal cancer patients.« less

Clinical value of concurrent radiochemotherapy in cervical cancer and comparison of ultrasonography findings before and after radiochemotherapy.

PubMed

Yan, W M; Li, X Z; Yu, Z L; Zhang, J; Sun, X G

2015-04-17

Herein, we investigated the clinical value of concurrent radiochemotherapy for patients with advanced cervical cancer and its effects on adverse clinical symptoms. Forty patients with cervical cancer were recruited from January 2011 to January 2014 for this study. Participants were randomly allocated into a test or control group, with 20 patients in each group. Patients in the test group were treated with concurrent radiochemotherapy, whereas patients in the control group received only traditional radiotherapy. At the end of the observation period, clinical efficacy in the two groups was compared. Patients were followed up for 2 years, and the rates of recurrence, survival, and complications were compared; ultrasonographic findings before and after radiotherapy were also correlated. Patients in the test group who received concurrent radiochemotherapy showed significantly higher clinical efficacy than the control group at the end of treatment cycles. After 2 years of follow-up, the rates of recurrence, mortality, and complications were all significantly lower in the test group than in the control group (P < 0.05). Comparison of ultrasonographic findings before and after radiochemotherapy showed that the size of the tumor was significantly smaller in patients after concurrent radiochemotherapy. Compared with traditional radiotherapy, concurrent radiochemotherapy significantly improved clinical outcomes in patients with advanced cervical cancer. Concurrent radiochemotherapy also enhanced the rate of survival and decreased the rate of relapse, with enhanced clinical safety and no significant side effects. Thus, concurrent radiochemotherapy can be more broadly applied in the treatment of advanced cervical cancer.

Serial MRI and CSF biomarkers in normal aging, MCI, and AD

PubMed Central

Vemuri, P.; Wiste, H.J.; Weigand, S.D.; Knopman, D.S.; Trojanowski, J.Q.; Shaw, L.M.; Bernstein, M.A.; Aisen, P.S.; Weiner, M.; Petersen, R.C; Jack, C.R

2010-01-01

Objective: To compare the annual change in MRI and CSF biomarkers in cognitively normal (CN), amnestic mild cognitive impairment (aMCI), and Alzheimer disease (AD). Comparisons were based on intergroup discrimination, correlation with concurrent cognitive/functional changes, relationships to APOE genotype, and sample sizes for clinical trials. Methods: We used data from the Alzheimer's Disease Neuroimaging Initiative study consisting of CN, aMCI, and AD cohorts with both baseline and 12-month follow-up CSF and MRI. The annual change in CSF (total-tau [t-tau], Aβ1-42) and MRI (change in ventricular volume) was obtained in 312 subjects (92 CN, 149 aMCI, 71 AD). Results: There was no significant average annual change in either CSF biomarker in any clinical group except t-tau in CN; moreover, the annual change did not differ by clinical group in pairwise comparisons. In contrast, annual increase in ventricular volume increased in the following order, AD > aMCI > CN, and differences were significant between all clinical groups in pairwise comparisons. Ventricular volume increase correlated with concurrent worsening on cognitive/functional indices in aMCI and AD whereas evidence of a similar correlation with change in CSF measures was unclear. The annual changes in MRI differed by APOE ε4 status overall and among aMCI while annual changes in CSF biomarkers did not. Estimated sample sizes for clinical trials are notably less for MRI than the CSF or clinical measures. Conclusions: Unlike the CSF biomarkers evaluated, changes in serial structural MRI are correlated with concurrent change on general cognitive and functional indices in impaired subjects, track with clinical disease stage, and are influenced by APOE genotype. GLOSSARY AD = Alzheimer disease; ADAS-Cog = Alzheimer's Disease Assessment Scale–cognitive subscale; ADNI = Alzheimer's Disease Neuroimaging Initiative; aMCI = amnestic mild cognitive impairment; AUROC = area under the receiver operator characteristic curve; BSI = boundary shift integral; CDR-SB = Clinical Dementia Rating–sum of boxes; CN = cognitively normal; MMSE = Mini-Mental State Examination; NFT = neurofibrillary tangle; NT = neuropil thread; PiB = Pittsburgh compound B; t-tau = total-tau. PMID:20625167

A phase 1 trial of ABT-510 concurrent with standard chemoradiation for patients with newly diagnosed glioblastoma.

PubMed

Nabors, Louis B; Fiveash, John B; Markert, James M; Kekan, Manasi S; Gillespie, George Y; Huang, Zhi; Johnson, Martin J; Meleth, Sreelatha; Kuo, Huichien; Gladson, Candece L; Fathallah-Shaykh, Hassan M

2010-03-01

To determine the maximum tolerated dose of ABT-510, a thrombospondin-1 mimetic drug with antiangiogenic properties, when used concurrently with temozolomide and radiotherapy in patients with newly diagnosed glioblastoma. Phase 1 dose-escalation clinical trial. Comprehensive Cancer Center, University of Alabama at Birmingham. Patients A total of 23 patients with newly diagnosed, histologically verified glioblastoma enrolled between April 2005 and January 2007. Four cohorts of 3 patients each received subcutaneous ABT-510 injection at doses of 20, 50, 100, or 200 mg/d. The maximum cohort was expanded to 14 patients to obtain additional safety and gene expression data. The treatment plan included 10 weeks of induction phase (temozolomide and radiotherapy with ABT-510 for 6 weeks plus ABT-510 monotherapy for 4 weeks) followed by a maintenance phase of ABT-510 and monthly temozolomide. Patients were monitored with brain magnetic resonance imaging and laboratory testing for dose-limiting toxicities, defined as grades 3 or 4 nonhematological toxicities and grade 4 hematological toxicities. Therapy was discontinued if 14 maintenance cycles were completed, disease progression occurred, or if the patient requested withdrawal. Disease progression, survival statistics, and gene expression arrays were analyzed. There were no grade 3 or 4 dose-limiting toxicity events that appeared related to ABT-510 for the dose range of 20 to 200 mg/d. A maximum tolerated dose was not defined. Most adverse events were mild, and injection-site reactions. The median time to tumor progression was 45.9 weeks, and the median overall survival time was 64.4 weeks. Gene expression analysis using TaqMan low-density arrays identified angiogenic genes that were differentially expressed in the brains of controls compared with patients with newly diagnosed glioblastoma, and identified FGF-1 and TIE-1 as being downregulated in patients who had better clinical outcomes. ABT-510, at subcutaneous doses up to 200 mg/d, is tolerated well with concurrent temozolomide and radiotherapy in patients with newly diagnosed glioblastoma, and low-density arrays provide a useful method of exploring gene expression profiles.

Analysis and design of randomised clinical trials involving competing risks endpoints.

PubMed

Tai, Bee-Choo; Wee, Joseph; Machin, David

2011-05-19

In randomised clinical trials involving time-to-event outcomes, the failures concerned may be events of an entirely different nature and as such define a classical competing risks framework. In designing and analysing clinical trials involving such endpoints, it is important to account for the competing events, and evaluate how each contributes to the overall failure. An appropriate choice of statistical model is important for adequate determination of sample size. We describe how competing events may be summarised in such trials using cumulative incidence functions and Gray's test. The statistical modelling of competing events using proportional cause-specific and subdistribution hazard functions, and the corresponding procedures for sample size estimation are outlined. These are illustrated using data from a randomised clinical trial (SQNP01) of patients with advanced (non-metastatic) nasopharyngeal cancer. In this trial, treatment has no effect on the competing event of loco-regional recurrence. Thus the effects of treatment on the hazard of distant metastasis were similar via both the cause-specific (unadjusted csHR = 0.43, 95% CI 0.25 - 0.72) and subdistribution (unadjusted subHR 0.43; 95% CI 0.25 - 0.76) hazard analyses, in favour of concurrent chemo-radiotherapy followed by adjuvant chemotherapy. Adjusting for nodal status and tumour size did not alter the results. The results of the logrank test (p = 0.002) comparing the cause-specific hazards and the Gray's test (p = 0.003) comparing the cumulative incidences also led to the same conclusion. However, the subdistribution hazard analysis requires many more subjects than the cause-specific hazard analysis to detect the same magnitude of effect. The cause-specific hazard analysis is appropriate for analysing competing risks outcomes when treatment has no effect on the cause-specific hazard of the competing event. It requires fewer subjects than the subdistribution hazard analysis for a similar effect size. However, if the main and competing events are influenced in opposing directions by an intervention, a subdistribution hazard analysis may be warranted.

The TOPSHOCK study: Effectiveness of radial shockwave therapy compared to focused shockwave therapy for treating patellar tendinopath - design of a randomised controlled trial

PubMed Central

2011-01-01

Background Patellar tendinopathy is a chronic overuse injury of the patellar tendon that is especially prevalent in people who are involved in jumping activities. Extracorporeal Shockwave Therapy is a relatively new treatment modality for tendinopathies. It seems to be a safe and promising part of the rehabilitation program for patellar tendinopathy. Extracorporeal Shockwave Therapy originally used focused shockwaves. Several years ago a new kind of shockwave therapy was introduced: radial shockwave therapy. Studies that investigate the effectiveness of radial shockwave therapy as treatment for patellar tendinopathy are scarce. Therefore the aim of this study is to compare the effectiveness of focussed shockwave therapy and radial shockwave therapy as treatments for patellar tendinopathy. Methods/design The TOPSHOCK study (Tendinopathy Of Patella SHOCKwave) is a two-armed randomised controlled trial in which the effectiveness of focussed shockwave therapy and radial shockwave therapy are directly compared. Outcome assessors and patients are blinded as to which treatment is given. Patients undergo three sessions of either focused shockwave therapy or radial shockwave therapy at 1-week intervals, both in combination with eccentric decline squat training. Follow-up measurements are scheduled just before treatments 2 and 3, and 1, 4, 7 and 12 weeks after the final treatment. The main outcome measure is the Dutch VISA-P questionnaire, which asks for pain, function and sports participation in subjects with patellar tendinopathy. Secondary outcome measures are pain determined with a VAS during ADL, sports and decline squats, rating of subjective improvement and overall satisfaction with the treatment. Patients will also record their sports activities, pain during and after these activities, and concurrent medical treatment on a weekly basis in a web-based diary. Results will be analysed according to the intention-to-treat principle. Discussion The TOPSHOCK study is the first randomised controlled trial that directly compares the effectiveness of focused shockwave therapy and radial shockwave therapy, both in combination with eccentric decline squat training, for treating patellar tendinopathy. Trial registration Trial registration number NTR2774. PMID:21989041

Concurrent cetuximab versus platinum-based chemoradiation for the definitive treatment of locoregionally advanced head and neck cancer.

PubMed

Tang, Chad; Chan, Cato; Jiang, Wen; Murphy, James D; von Eyben, Rie; Colevas, A Dimitrios; Pinto, Harlan; Lee-Enriquez, Nancy; Kong, Christina; Le, Quynh-Thu

2015-03-01

The purpose of this study was to present our experience utilizing cetuximab and platinum-based concurrent chemoradiotherapy for the definitive treatment of head and neck squamous cell carcinoma (HNSCC). Patients (n = 177) who received definitive concurrent chemoradiotherapy for HNSCC were stratified into 3 groups: receiving cetuximab monotherapy (n = 24), cetuximab and chemotherapy combination (n = 33), or platinum-based chemotherapy without cetuximab (n = 120). Primary endpoints were freedom from relapse, event-free survival, and overall survival (OS). Patients receiving cetuximab monotherapy were older with lower Karnofsky performance status (KPS) and higher Charlson comorbidity scores compared with those treated with combination cetuximab and chemotherapy or platinum-based concurrent chemoradiotherapy. Patients treated with platinum-based concurrent chemoradiotherapy exhibited significantly better freedom from relapse, event-free survival, and OS compared with those receiving cetuximab monotherapy or cetuximab and chemotherapy combination therapies (all p < .05). Differences between patients receiving cetuximab monotherapy and platinum-based concurrent chemoradiotherapy held on multivariate Cox regression. This study suggests that platinum-based concurrent chemoradiotherapy is superior to cetuximab-based monotherapy for the definitive treatment of HNSCC. © 2014 Wiley Periodicals, Inc.

Anal Carcinoma: Impact of TN Category of Disease on Survival, Disease Relapse, and Colostomy Failure in US Gastrointestinal Intergroup RTOG 98-11 Phase 3 Trial

PubMed Central

Gunderson, Leonard L.; Moughan, Jennifer; Ajani, Jaffer A.; Pedersen, John E.; Winter, Kathryn A.; Benson, Al B.; Thomas, Charles R.; Mayer, Robert J.; Haddock, Michael G.; Rich, Tyvin A.; Willett, Christopher G.

2013-01-01

Purpose The long-term update of US GI Intergroup RTOG 98-11 anal cancer trial found that concurrent chemoradiation (CCRT) with fluorouracil (5-FU) plus mitomycin had a significant impact on disease-free survival (DFS) and overall survival (OS) compared with induction plus concurrent 5-FU plus cisplatin. The intent of the current analysis was to determine the impact of tumor node (TN) category of disease on survival (DFS and OS), colostomy failure (CF), and relapse (local-regional failure [LRF] and distant metastases [DM]) in this patient group. Methods and Materials DFS and OS were estimated univariately by using the Kaplan-Meier method, and 6 TN categories were compared by the log–rank test (T2N0, T3N0, T4N0, T2N1-3, T3N1-3, and T4N1-3). Time to relapse and colostomy were estimated by the cumulative incidence method, and TN categories were compared using Gray’s test. Results Of 682 patients, 620 were analyzable for outcomes by TN category. All endpoints showed statistically significant differences among the TN categories of disease (OS, P<.0001; DFS, P<.0001; LRF, P<.0001; DM, P=.0011; CF, P=.01). Patients with the poorest OS, DFS, and LRF outcomes were those with T3-4N-positive (+) disease. CF was lowest for T2N0 and T2N+ (11%, 11%, respectively) and worst for the T4N0, T3N+, and T4N+ categories (26%, 27%, 24%, respectively). Conclusions TN category of disease has a statistically significant impact on OS, DFS, LRF, DM, and CF in patients treated with CCRT and provides excellent prognostic information for outcomes in patients with anal carcinoma. Significant challenges remain for patients with T4N0 and T3-4N+ categories of disease with regard to survival, relapse, and CF and lesser challenges for T2-3N0/T2N+ categories. PMID:24035327

Dual sensory loss: development of a dual sensory loss protocol and design of a randomized controlled trial

PubMed Central

2013-01-01

Background Dual sensory loss (DSL) has a negative impact on health and wellbeing and its prevalence is expected to increase due to demographic aging. However, specialized care or rehabilitation programs for DSL are scarce. Until now, low vision rehabilitation does not sufficiently target concurrent impairments in vision and hearing. This study aims to 1) develop a DSL protocol (for occupational therapists working in low vision rehabilitation) which focuses on optimal use of the senses and teaches DSL patients and their communication partners to use effective communication strategies, and 2) describe the multicenter parallel randomized controlled trial (RCT) designed to test the effectiveness and cost-effectiveness of the DSL protocol. Methods/design To develop a DSL protocol, literature was reviewed and content was discussed with professionals in eye/ear care (interviews/focus groups) and DSL patients (interviews). A pilot study was conducted to test and confirm the DSL protocol. In addition, a two-armed international multi-center RCT will evaluate the effectiveness and cost-effectiveness of the DSL protocol compared to waiting list controls, in 124 patients in low vision rehabilitation centers in the Netherlands and Belgium. Discussion This study provides a treatment protocol for rehabilitation of DSL within low vision rehabilitation, which aims to be a valuable addition to the general low vision rehabilitation care. Trial registration Netherlands Trial Register (NTR) identifier: NTR2843 PMID:23941667

Evaluation of insecticides on cotton fleahopper and beneficial arthropod populations

USDA-ARS?s Scientific Manuscript database

An experiment was initiated in 2009 concurrently with a cotton fleahopper insecticide efficacy trial to determine which products were the most and least detrimental to arthropod natural enemies. Insecticides evaluated included Bidrin 8E, Bidrin XP, Centric 40WG, Discipline 2EC, Intruder 70WP, Orthe...

The influence of crumble and mash feed on oral lesions of white leghorn laying hens.

PubMed

Daft, B; Read, D; Manzer, M; Bickford, A; Kinde, H

2001-01-01

The effect of crumble and mash feed on oral lesions in laying hens was investigated. Each of two groups of white leghorn hens (group A, n = 120; group B, n = 120) was separated into crumble- and mash-fed treatments. At the start of the trial, group A chickens were free of oral lesions, whereas group B chickens had nearly 100% prevalence of oral lesions. The trials began at 17.4 and 22 wk of age and ended at 32 and 33 wk of age for groups A and B, respectively. Chickens were housed in cages indoors, fed free choice, and serologically monitored. Oral lesions were periodically evaluated by visual scoring. Lesion prevalence peaked in group A chickens at 23-25 wk of age, concurrently with an outbreak of respiratory disease, and decreased to a low level at the end of the trial. For most of the trial, crumble-fed chickens had significantly lower oral lesion prevalence than mash-fed chickens (P < 0.05). Lesion prevalence in group B chickens decreased after treatments began and maintained this trend to the end of the trial. Compared with mash-fed chickens, crumble-fed chickens in group B had significantly lower oral lesion prevalence throughout the trial (P < 0.001). Neither group had significant differences in oral lesion scores between treatments. Most lesions were on the lower palate, pinpoint to 2 mm in diameter, often multiple, and bilaterally symmetrical. Feed analyses for mycotoxins and heavy metals were within normal limits. The inciting etiology of oral lesions was not elucidated in this trial. However, this work demonstrated that once lesions were present, feed type had a strong effect on persistence of oral lesions.

The compatibility of concurrent high intensity interval training and resistance training for muscular strength and hypertrophy: a systematic review and meta-analysis.

PubMed

Sabag, Angelo; Najafi, Abdolrahman; Michael, Scott; Esgin, Tuguy; Halaki, Mark; Hackett, Daniel

2018-04-16

The purpose of this systematic review and meta-analysis is to assess the effect of concurrent high intensity interval training (HIIT) and resistance training (RT) on strength and hypertrophy. Five electronic databases were searched using terms related to HIIT, RT, and concurrent training. Effect size (ES), calculated as standardised differences in the means, were used to examine the effect of concurrent HIIT and RT compared to RT alone on muscle strength and hypertrophy. Sub-analyses were performed to assess region-specific strength and hypertrophy, HIIT modality (cycling versus running), and inter-modal rest responses. Compared to RT alone, concurrent HIIT and RT led to similar changes in muscle hypertrophy and upper body strength. Concurrent HIIT and RT resulted in a lower increase in lower body strength compared to RT alone (ES = -0.248, p = 0.049). Sub analyses showed a trend for lower body strength to be negatively affected by cycling HIIT (ES = -0.377, p = 0.074) and not running (ES = -0.176, p = 0.261). Data suggests concurrent HIIT and RT does not negatively impact hypertrophy or upper body strength, and that any possible negative effect on lower body strength may be ameliorated by incorporating running based HIIT and longer inter-modal rest periods.

Obtaining real-world evidence: the Salford Lung Study

PubMed Central

New, John P; Bakerly, Nawar Diar; Leather, David; Woodcock, Ashley

2014-01-01

We need to assess clinical treatments in real-life settings outside of randomised controlled trials (RCTs). Pragmatic RCT (pRCT) data can supplement RCTs by providing effectiveness information to support healthcare decisions. Electronic health records can facilitate concurrent safety monitoring and data collection without direct patient contact for large randomised study populations in pRCTs. The Salford Lung Study is the world's first phase III pRCT in asthma and chronic obstructive pulmonary disease (COPD), which aims to randomise over 7000 patients. This paper describes the hurdles overcome and the enormous effort and resource required to establish this comparative effectiveness study of a prelicence intervention. GlaxoSmithKline protocol HZC115151 Asthma study clinicaltrials.gov registration NCT01706198 COPD study clinicaltrials.gov registration NCT01551758 PMID:24603195

Combination Antifungal Therapy for Cryptococcal Meningitis

PubMed Central

Day, Jeremy N.; Chau, Tran T.H.; Wolbers, Marcel; Mai, Pham P.; Dung, Nguyen T.; Mai, Nguyen H.; Phu, Nguyen H.; Nghia, Ho D.; Phong, Nguyen D.; Thai, Cao Q.; Thai, Le H.; Chuong, Ly V.; Sinh, Dinh X.; Duong, Van A.; Hoang, Thu N.; Diep, Pham T.; Campbell, James I.; Sieu, Tran P.M.; Baker, Stephen G.; Chau, Nguyen V.V.; Hien, Tran T.

2014-01-01

BACKGROUND Combination antifungal therapy (amphotericin B deoxycholate and flucytosine) is the recommended treatment for cryptococcal meningitis but has not been shown to reduce mortality, as compared with amphotericin B alone. We performed a randomized, controlled trial to determine whether combining flucytosine or high-dose fluconazole with high-dose amphotericin B improved survival at 14 and 70 days. METHODS We conducted a randomized, three-group, open-label trial of induction therapy for cryptococcal meningitis in patients with human immunodeficiency virus infection. All patients received amphotericin B at a dose of 1 mg per kilogram of body weight per day; patients in group 1 were treated for 4 weeks, and those in groups 2 and 3 for 2 weeks. Patients in group 2 concurrently received flucytosine at a dose of 100 mg per kilogram per day for 2 weeks, and those in group 3 concurrently received fluconazole at a dose of 400 mg twice daily for 2 weeks. RESULTS A total of 299 patients were enrolled. Fewer deaths occurred by days 14 and 70 among patients receiving amphotericin B and flucytosine than among those receiving amphotericin B alone (15 vs. 25 deaths by day 14; hazard ratio, 0.57; 95% confidence interval [CI], 0.30 to 1.08; unadjusted P = 0.08; and 30 vs. 44 deaths by day 70; hazard ratio, 0.61; 95% CI, 0.39 to 0.97; unadjusted P = 0.04). Combination therapy with fluconazole had no significant effect on survival, as compared with monotherapy (hazard ratio for death by 14 days, 0.78; 95% CI, 0.44 to 1.41; P = 0.42; hazard ratio for death by 70 days, 0.71; 95% CI, 0.45 to 1.11; P = 0.13). amphotericin B plus flucytosine was associated with significantly increased rates of yeast clearance from cerebrospinal fluid (−0.42 log10 colony-forming units [CFU] per milliliter per day vs. −0.31 and −0.32 log10 CFU per milliliter per day in groups 1 and 3, respectively; P<0.001 for both comparisons). Rates of adverse events were similar in all groups, although neutropenia was more frequent in patients receiving a combination therapy. CONCLUSIONS Amphotericin B plus flucytosine, as compared with amphotericin B alone, is associated with improved survival among patients with cryptococcal meningitis. A survival benefit of amphotericin B plus fluconazole was not found. (Funded by the Wellcome Trust and the British Infection Society; Controlled-Trials.com number, ISRCTN95123928.) PMID:23550668

Findings from the SASA! Study: a cluster randomized controlled trial to assess the impact of a community mobilization intervention to prevent violence against women and reduce HIV risk in Kampala, Uganda.

PubMed

Abramsky, Tanya; Devries, Karen; Kiss, Ligia; Nakuti, Janet; Kyegombe, Nambusi; Starmann, Elizabeth; Cundill, Bonnie; Francisco, Leilani; Kaye, Dan; Musuya, Tina; Michau, Lori; Watts, Charlotte

2014-07-31

Intimate partner violence (IPV) and HIV are important and interconnected public health concerns. While it is recognized that they share common social drivers, there is limited evidence surrounding the potential of community interventions to reduce violence and HIV risk at the community level. The SASA! study assessed the community-level impact of SASA!, a community mobilization intervention to prevent violence and reduce HIV-risk behaviors. From 2007 to 2012 a pair-matched cluster randomized controlled trial (CRT) was conducted in eight communities (four intervention and four control) in Kampala, Uganda. Cross-sectional surveys of a random sample of community members, 18- to 49-years old, were undertaken at baseline (n = 1,583) and four years post intervention implementation (n = 2,532). Six violence and HIV-related primary outcomes were defined a priori. An adjusted cluster-level intention-to-treat analysis compared outcomes in intervention and control communities at follow-up. The intervention was associated with significantly lower social acceptance of IPV among women (adjusted risk ratio 0.54, 95% confidence interval (CI) 0.38 to 0.79) and lower acceptance among men (0.13, 95% CI 0.01 to 1.15); significantly greater acceptance that a woman can refuse sex among women (1.28, 95% CI 1.07 to 1.52) and men (1.31, 95% CI 1.00 to 1.70); 52% lower past year experience of physical IPV among women (0.48, 95% CI 0.16 to 1.39); and lower levels of past year experience of sexual IPV (0.76, 95% CI 0.33 to 1.72). Women experiencing violence in intervention communities were more likely to receive supportive community responses. Reported past year sexual concurrency by men was significantly lower in intervention compared to control communities (0.57, 95% CI 0.36 to 0.91). This is the first CRT in sub-Saharan Africa to assess the community impact of a mobilization program on the social acceptability of IPV, the past year prevalence of IPV and levels of sexual concurrency. SASA! achieved important community impacts, and is now being delivered in control communities and replicated in 15 countries. ClinicalTrials.gov #NCT00790959.

Changes in Cardiovascular Disease Risk Factors With Immediate Versus Deferred Antiretroviral Therapy Initiation Among HIV-Positive Participants in the START (Strategic Timing of Antiretroviral Treatment) Trial.

PubMed

Baker, Jason V; Sharma, Shweta; Achhra, Amit C; Bernardino, Jose Ignacio; Bogner, Johannes R; Duprez, Daniel; Emery, Sean; Gazzard, Brian; Gordin, Jonathan; Grandits, Greg; Phillips, Andrew N; Schwarze, Siegfried; Soliman, Elsayed Z; Spector, Stephen A; Tambussi, Giuseppe; Lundgren, Jens

2017-05-22

HIV infection and certain antiretroviral therapy (ART) medications increase atherosclerotic cardiovascular disease risk, mediated, in part, through traditional cardiovascular disease risk factors. We studied cardiovascular disease risk factor changes in the START (Strategic Timing of Antiretroviral Treatment) trial, a randomized study of immediate versus deferred ART initiation among HIV-positive persons with CD4 + cell counts >500 cells/mm 3 . Mean change from baseline in risk factors and the incidence of comorbid conditions were compared between groups. The characteristics among 4685 HIV-positive START trial participants include a median age of 36 years, a CD4 cell count of 651 cells/mm 3 , an HIV viral load of 12 759 copies/mL, a current smoking status of 32%, a median systolic/diastolic blood pressure of 120/76 mm Hg, and median levels of total cholesterol of 168 mg/dL, low-density lipoprotein cholesterol of 102 mg/dL, and high-density lipoprotein cholesterol of 41 mg/dL. Mean follow-up was 3.0 years. The immediate and deferred ART groups spent 94% and 28% of follow-up time taking ART, respectively. Compared with patients in the deferral group, patients in the immediate ART group had increased total cholesterol and low-density lipoprotein cholesterol and higher use of lipid-lowering therapy (1.2%; 95% CI, 0.1-2.2). Concurrent increases in high-density lipoprotein cholesterol with immediate ART resulted in a 0.1 lower total cholesterol to high-density lipoprotein cholesterol ratio (95% CI, 0.1-0.2). Immediate ART resulted in 2.3% less BP-lowering therapy use (95% CI, 0.9-3.6), but there were no differences in new-onset hypertension or diabetes mellitus. Among HIV-positive persons with preserved immunity, immediate ART led to increases in total cholesterol and low-density lipoprotein cholesterol but also concurrent increases in high-density lipoprotein cholesterol and decreased use of blood pressure medications. These opposing effects suggest that, in the short term, the net effect of early ART on traditional cardiovascular disease risk factors may be clinically insignificant." URL: http://www.clinicaltrials.gov. Unique identifier: NCT00867048. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Altering Hirsutism Through Ovulation Induction in Women With Polycystic Ovary Syndrome

PubMed Central

Roth, Lauren W.; Huang, Hao; Legro, Richard S.; Diamond, Michael P.; Coutifaris, Christos; Carson, Sandra A.; Steinkampf, Michael P.; Carr, Bruce R.; McGovern, Peter G.; Cataldo, Nicholas A.; Gosman, Gabriella G.; Nestler, John E.; Myers, Evan R.; Zhang, Heping; Schlaff, William D.

2012-01-01

Objective Many women with polycystic ovary syndrome (PCOS) experience infertility and hirsutism and often seek treatment for both concurrently. We investigated whether women who ovulate in response to treatment with clomiphene citrate), metformin, or both would have greater improvement in hirsutism compared to those who did not ovulate. Methods This is a secondary analysis evaluating the change in Ferriman-Gallwey score for the hirsute women (n = 505, 80.7%) from the Pregnancy in Polycystic Ovary Syndrome 1 study. This was a prospective, randomized, doubled-blind trial of 626 women with PCOS and infertility recruited from 12 university sites. They were treated with clomiphene citrate, metformin, or both (combination) for up to six cycles, and hirsutism evaluators were blinded to group assignment. Results There was a significant decrease in the Ferriman-Gallwey score between baseline and completion of the study in each of the three individual groups (clomiphene citrate, p=0.024; metformin, p=0.005; combination, p<0.001). There was no significant difference in the degree to which the hirsutism score changed when comparing the three groups (p=0.44). The change in hirsutism was not associated with the duration of treatment or with the presence or absence of ovulation. Conclusions In infertile hirsute women with PCOS, treatment with clomiphene citrate, metformin, or both for up to 6 cycles does not alter hirsutism. Clinical Trial Registration ClinicalTrials.gov, www.clinicaltrials.gov, NCT00068861. PMID:22617579

Diamorphine for pain relief in labour : a randomised controlled trial comparing intramuscular injection and patient-controlled analgesia.

PubMed

McInnes, Rhona J; Hillan, Edith; Clark, Diana; Gilmour, Harper

2004-10-01

To compare the efficacy of diamorphine administered by a patient-controlled pump (patient-controlled analgesia) with intramuscular administration for pain relief in labour. Randomised controlled trial. The South Glasgow University Hospitals NHS Trust. Primigravidae and multigravidae in labour at term (37-42 weeks). Women were randomised in labour to the study (patient-controlled analgesia) or control group (intramuscular). Randomisation was achieved through a random permuted block design stratified by parity. Study group women were given a loading dose of 1.2 mg diamorphine intravenously and then attached to the pump. Control group women received intramuscular diamorphine as per hospital protocol. Participants were also given 3 mg of buccal Stemetil. Data were collected throughout labour and at six postnatal weeks. Analgesia requirements during labour and women's satisfaction with the method of pain relief. Women in the study group (patient-controlled analgesia) used significantly less diamorphine than women in the control group (intramuscular) but were significantly more likely to state that they were very dissatisfied with their use of diamorphine and were significantly more likely to opt out of the trial before the birth of the baby. The majority of women in both groups used other analgesia concurrent with diamorphine such as Entonox, aromatherapy or TENS. Patient-controlled analgesia administration of diamorphine for the relief of pain in labour offers no significant advantages over intramuscular administration. The results also suggest that diamorphine is a poor analgesic for labour pain irrespective of the mode of administration.

Combined Hydrous Ferric Oxide and Quaternary Ammonium Surfactant Tailoring of Granular Activated Carbon for Concurrent Arsenate and Perchlorate Removal

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jang, M.; Cannon, F; Parette, R

2009-01-01

Activated carbon was tailored with both iron and quaternary ammonium surfactants so as to concurrently remove both arsenate and perchlorate from groundwater. The iron (hydr)oxide preferentially removed the arsenate oxyanion but not perchlorate; while the quaternary ammonium preferentially removed the perchlorate oxyanion, but not the arsenate. The co-sorption of two anionic oxyanions via distinct mechanisms has yielded intriguing phenomena. Rapid small-scale column tests (RSSCTs) with these dually prepared media employed synthetic waters that were concurrently spiked with arsenate and perchlorate; and these trial results showed that the quaternary ammonium surfactants enhanced arsenate removal bed life by 25-50% when compared tomore » activated carbon media that had been preloaded merely with iron (hydr)oxide; and the surfactant also enhanced the diffusion rate of arsenate per the Donnan effect. The authors also employed natural groundwater from Rutland, MA which contained 60 microg/L As and traces of silica, and sulfate; and the authors spiked this with 40 microg/L perchlorate. When processing this water, activated carbon that had been tailored with iron and cationic surfactant could treat 12,500 bed volumes before 10 microg/L arsenic breakthrough, and 4500 bed volumes before 6 microg/L perchlorate breakthrough. Although the quaternary ammonium surfactants exhibited only a slight capacity for removing arsenate, these surfactants did facilitate a more favorably positively charged avenue for the arsenate to diffuse through the media to the iron sorption site (i.e. via the Donnan effect).« less

Mechanisms of Behavior Change in Alcoholics Anonymous: Does AA lead to better alcohol use outcomes by reducing depression symptoms?

PubMed Central

Kelly, John F.; Stout, Robert L.; Magill, Molly; Tonigan, J. Scott; Pagano, Maria E.

2009-01-01

Rationale Indices of negative affect, such as depression, have been implicated in stress-induced pathways to alcohol relapse. Empirically-supported continuing care resources, such as Alcoholics Anonymous (AA), emphasize reducing negative affect to reduce relapse risk, but little research has been conducted to examine putative affective mechanisms of AA’s effects. Method Using lagged, controlled, hierarchical linear modeling and mediational analyses this study investigated whether AA participation mobilized changes in depression symptoms and whether such changes explained subsequent reductions in alcohol use. Alcohol dependent adults (N = 1,706), receiving treatment as part of a clinical trial, were assessed at intake, 3, 6, 9, 12, and 15 months. Results Findings revealed elevated levels of depression compared to the general population, which decreased during treatment and then remained stable over follow-up. Greater AA attendance was associated with better subsequent alcohol use outcomes and decreased depression. Greater depression was associated with heavier and more frequent drinking. Lagged, mediation analyses revealed that the effects of AA on alcohol use was partially mediated by reductions in depression symptoms. However, this salutary effect on depression itself appeared to be explained by AA’s proximal effect on reducing concurrent drinking. Conclusions AA attendance was both concurrently and predictively associated with improved alcohol outcomes. Although AA attendance was additionally associated with subsequent improvements in depression, it did not predict such improvements over and above concurrent alcohol use. AA appears to lead both to improvements in alcohol use and psychological and emotional well-being, which, in turn, may reinforce further abstinence and recovery-related change. PMID:20102345

Is the progression free survival advantage of concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin in patients with advanced cervical cancer worth the additional cost? A cost-effectiveness analysis.

PubMed

Smith, B; Cohn, D E; Clements, A; Tierney, B J; Straughn, J M

2013-09-01

The objective of this study is to determine whether concurrent and adjuvant chemoradiation with gemcitabine/cisplatin is cost-effective in patients with stage IIB to IVA cervical cancer. A cost-effectiveness model compared two arms of the trial performed by Duenas-Gonzalez et al. [1]: concurrent and adjuvant chemoradiation with gemcitabine/cisplatin (RT/GC+GC) versus concurrent radiation with cisplatin (RT/C). Major adverse events (AEs) and progression free survival (PFS) rates of each arm were incorporated in the model. AEs were defined as any hospitalization including grade 4 anemia, grade 4 neutropenia, and death. Medicare data and literature review were used to estimate costs. Incremental cost-effectiveness ratios (ICERs) per progression-free life-year saved (PF-LYS) were calculated. Sensitivity analyses were performed for pertinent uncertainties. For 10,000 women with locally advanced cervical cancer, the cost of therapy and AEs was $173.9 million (M) for RT/C versus $259.8M for RT/GC+GC. There were 879 additional 3-year progression-free survivors in the RT/GC+GC arm. The ICER for RT/GC+GC was $97,799 per PF-LYS. When the rate of hospitalization was equalized to 4.3%, the ICER for RT/GC+GC exceeded $80,000. The resultant ICER when increasing PFS in the RT/GC+GC arm by 5% was $62,605 per PF-LYS. When the cost of chemotherapy was decreased by 50%, the ICER was below $50,000 at $41,774 per PF-LYS. Radiation and gemcitabine/cisplatin for patients with stage IIB to IVA cervical cancer are not cost-effective. The increased financial burden of radiation with gemcitabine/cisplatin and associated toxicities appears to outweigh the benefit of increased 3-year PFS and is primarily dependent on chemotherapy drug costs. Copyright © 2013 Elsevier Inc. All rights reserved.

Institutional Clinical Trial Accrual Volume and Survival of Patients With Head and Neck Cancer

PubMed Central

Wuthrick, Evan J.; Zhang, Qiang; Machtay, Mitchell; Rosenthal, David I.; Nguyen-Tan, Phuc Felix; Fortin, André; Silverman, Craig L.; Raben, Adam; Kim, Harold E.; Horwitz, Eric M.; Read, Nancy E.; Harris, Jonathan; Wu, Qian; Le, Quynh-Thu; Gillison, Maura L.

2015-01-01

Purpose National Comprehensive Cancer Network guidelines recommend patients with head and neck cancer (HNC) receive treatment at centers with expertise, but whether provider experience affects survival is unknown. Patients and Methods The effect of institutional experience on overall survival (OS) in patients with stage III or IV HNC was investigated within a randomized trial of the Radiation Therapy Oncology Group (RTOG 0129), which compared cisplatin concurrent with standard versus accelerated fractionation radiotherapy. As a surrogate for experience, institutions were classified as historically low- (HLACs) or high-accruing centers (HHACs) based on accrual to 21 RTOG HNC trials (1997 to 2002). The effect of accrual volume on OS was estimated by Cox proportional hazards models. Results Median RTOG accrual (1997 to 2002) at HLACs was four versus 65 patients at HHACs. Analysis included 471 patients in RTOG 0129 (2002 to 2005) with known human papillomavirus and smoking status. Patients at HLACs versus HHACs had better performance status (0: 62% v 52%; P = .04) and lower T stage (T4: 26.5% v 35.3%; P = .002) but were otherwise similar. Radiotherapy protocol deviations were higher at HLACs versus HHACs (18% v 6%; P < .001). When compared with HHACs, patients at HLACs had worse OS (5 years: 51.0% v 69.1%; P = .002). Treatment at HLACs was associated with increased death risk of 91% (hazard ratio [HR], 1.91; 95% CI, 1.37 to 2.65) after adjustment for prognostic factors and 72% (HR, 1.72; 95% CI, 1.23 to 2.40) after radiotherapy compliance adjustment. Conclusion OS is worse for patients with HNC treated at HLACs versus HHACs to cooperative group trials after accounting for radiotherapy protocol deviations. Institutional experience substantially influences survival in locally advanced HNC. PMID:25488965

Institutional clinical trial accrual volume and survival of patients with head and neck cancer.

PubMed

Wuthrick, Evan J; Zhang, Qiang; Machtay, Mitchell; Rosenthal, David I; Nguyen-Tan, Phuc Felix; Fortin, André; Silverman, Craig L; Raben, Adam; Kim, Harold E; Horwitz, Eric M; Read, Nancy E; Harris, Jonathan; Wu, Qian; Le, Quynh-Thu; Gillison, Maura L

2015-01-10

National Comprehensive Cancer Network guidelines recommend patients with head and neck cancer (HNC) receive treatment at centers with expertise, but whether provider experience affects survival is unknown. The effect of institutional experience on overall survival (OS) in patients with stage III or IV HNC was investigated within a randomized trial of the Radiation Therapy Oncology Group (RTOG 0129), which compared cisplatin concurrent with standard versus accelerated fractionation radiotherapy. As a surrogate for experience, institutions were classified as historically low- (HLACs) or high-accruing centers (HHACs) based on accrual to 21 RTOG HNC trials (1997 to 2002). The effect of accrual volume on OS was estimated by Cox proportional hazards models. Median RTOG accrual (1997 to 2002) at HLACs was four versus 65 patients at HHACs. Analysis included 471 patients in RTOG 0129 (2002 to 2005) with known human papillomavirus and smoking status. Patients at HLACs versus HHACs had better performance status (0: 62% v 52%; P = .04) and lower T stage (T4: 26.5% v 35.3%; P = .002) but were otherwise similar. Radiotherapy protocol deviations were higher at HLACs versus HHACs (18% v 6%; P < .001). When compared with HHACs, patients at HLACs had worse OS (5 years: 51.0% v 69.1%; P = .002). Treatment at HLACs was associated with increased death risk of 91% (hazard ratio [HR], 1.91; 95% CI, 1.37 to 2.65) after adjustment for prognostic factors and 72% (HR, 1.72; 95% CI, 1.23 to 2.40) after radiotherapy compliance adjustment. OS is worse for patients with HNC treated at HLACs versus HHACs to cooperative group trials after accounting for radiotherapy protocol deviations. Institutional experience substantially influences survival in locally advanced HNC. © 2014 by American Society of Clinical Oncology.

Potential reliability and validity of a modified version of the Unified Parkinson’s Disease Rating Scale that could be administered remotely

PubMed Central

Abdolahi, Amir; Scoglio, Nicholas; Killoran, Annie; Dorsey, Ray; Biglan, Kevin M.

2013-01-01

Background By permitting remote assessments of patients and research participants, telemedicine has the potential to reshape clinical care and clinical trials for Parkinson disease. While the majority of the motor Unified Parkinson’s Disease Rating Scale (UPDRS) items can be conducted visually, rigidity and retropulsion pull testing require hands-on assessment by the rater and are less feasible to perform remotely in patients' homes. Methods In a secondary data analysis of the Comparison of the Agonist pramipexole vs. Levodopa on Motor complications in Parkinson’s Disease (CALM-PD) study, a randomized clinical trial, we assessed the cross-sectional (baseline and 2 years) and longitudinal (change from baseline to 2 years) reliability of a modified motor UPDRS (removing rigidity and retropulsion items) compared to the standard motor UPDRS (all items) using intraclass correlation coefficients (ICC), stratified by treatment group. Internal consistency of the modified UPDRS (mUPDRS) was measured using Cronbach’s alpha, and concurrent validity was assessed using Pearson’s correlation coefficient (r) between the standard motor UPDRS and mUPDRS. Results The mUPDRS versus standard motor UPDRS is cross-sectionally (ICC ≥ 0.92) and longitudinally (ICC ≥ 0.92) reliable for both treatment groups. High internal consistencies were also observed (α ≥ 0.96). The mUPDRS had high concurrent validity with the standard UPDRS at both time points and longitudinally (r ≥ 0.93, p < 0.0001). Conclusions A modified version of the motor UPDRS without rigidity and retropulsion pull testing is reliable and valid and may lay the foundation for its use in remote assessments of patients and research participants. PMID:23102808

Potential reliability and validity of a modified version of the Unified Parkinson's Disease Rating Scale that could be administered remotely.

PubMed

Abdolahi, Amir; Scoglio, Nicholas; Killoran, Annie; Dorsey, E Ray; Biglan, Kevin M

2013-02-01

By permitting remote assessments of patients and research participants, telemedicine has the potential to reshape clinical care and clinical trials for Parkinson disease. While the majority of the motor Unified Parkinson's Disease Rating Scale (UPDRS) items can be conducted visually, rigidity and retropulsion pull testing require hands-on assessment by the rater and are less feasible to perform remotely in patients' homes. In a secondary data analysis of the Comparison of the Agonist pramipexole vs. Levodopa on Motor complications in Parkinson's Disease (CALM-PD) study, a randomized clinical trial, we assessed the cross-sectional (baseline and 2 years) and longitudinal (change from baseline to 2 years) reliability of a modified motor UPDRS (removing rigidity and retropulsion items) compared to the standard motor UPDRS (all items) using intraclass correlation coefficients (ICC), stratified by treatment group. Internal consistency of the modified UPDRS (mUPDRS) was measured using Cronbach's alpha, and concurrent validity was assessed using Pearson's correlation coefficient (r) between the standard motor UPDRS and mUPDRS. The mUPDRS versus standard motor UPDRS is cross-sectionally (ICC ≥ 0.92) and longitudinally (ICC ≥ 0.92) reliable for both treatment groups. High internal consistencies were also observed (α ≥ 0.96). The mUPDRS had high concurrent validity with the standard UPDRS at both time points and longitudinally (r ≥ 0.93, p < 0.0001). A modified version of the motor UPDRS without rigidity and retropulsion pull testing is reliable and valid and may lay the foundation for its use in remote assessments of patients and research participants. Copyright © 2012 Elsevier Ltd. All rights reserved.

Concurrent sexual partnerships among men who have sex with men in Shenzhen, China.

PubMed

Ha, Toan H; Liu, Hongjie; Liu, Hui; Cai, Yumao; Feng, Tiejian

2010-08-01

The HIV epidemic spreads among men who have sex with men (MSM) in China. The objective of this study was to examine and compare HIV/AIDS knowledge and sexual risk for HIV between MSM who engaged in concurrent sexual partnerships and MSM who did not. A cross-sectional study using respondent driven sampling was conducted among 351 MSM in Shenzhen, China. About half (49%) of respondents reported having concurrent sexual partnerships during the past 6 months. Among MSM with concurrent sexual partnerships, 62% had only male partners and 38% had both male and female partners. The proportion of inconsistent condom use was 42% among MSM with concurrent partners and 30% among MSM without. These 2 groups reported a similar level of self-perceived risk for HIV. Compared to MSM without concurrent sexual partners, those with such partners were more likely to work in entertainment venues and had a lower level of HIV/AIDS knowledge. The large number of MSM engaging in concurrent sexual partnerships and the high prevalence of bisexuality could accelerate the spread of HIV to the general population unless effective HIV interventions for MSM are implemented in China.

Efficacy and safety of concurrent chemoradiation with weekly cisplatin ± low-dose celecoxib in locally advanced undifferentiated nasopharyngeal carcinoma: a phase II-III clinical trial.

PubMed

Mohammadianpanah, Mohammad; Razmjou-Ghalaei, Sasan; Shafizad, Amin; Ashouri-Taziani, Yaghoub; Khademi, Bijan; Ahmadloo, Niloofar; Ansari, Mansour; Omidvari, Shapour; Mosalaei, Ahmad; Mosleh-Shirazi, Mohammad Amin

2011-01-01

This is the first study that aimed to determine the efficacy and safety of concurrent chemoradiation with weekly cisplatin ± celecoxib 100 mg twice daily in locally advanced undifferentiated nasopharyngeal carcinoma. Eligible patients had newly diagnosed locally advanced (T3-T4, and/or N2-N3, M0) undifferentiated nasopharyngeal carcinoma, no prior therapy, Karnofsky performance status ≥ 70, and normal organ function. The patients were assigned to receive 7 weeks concurrent chemoradiation (70 Gy) with weekly cisplatin 30 mg/m 2 with either celecoxib 100 mg twice daily, (study group, n = 26) or placebo (control group, n = 27) followed by adjuvant combined chemotherapy with cisplatin 70 mg/m 2 on day 1 plus 5-fluorouracil 750 mg/m 2 /d with 8-h infusion on days 1-3, 3-weekly for 3 cycles. Overall clinical response rate was 100% in both groups. Complete and partial clinical response rates were 64% and 36% in the study group and 44% and 56% in the control group, respectively (P > 0.25). The addition of celecoxib to concurrent chemoradiation was associated with improved 2-year locoregional control rate from 84% to 100% (P = 0.039). The addition of celecoxib 100 mg twice daily to concurrent chemoradiation improved 2-year locoregional control rate.

Concurrent chemoradiotherapy degrades the quality of life of patients with stage II nasopharyngeal carcinoma as compared to radiotherapy

PubMed Central

Pan, Xin-Bin; Huang, Shi-Ting; Chen, Kai-Hua; Jiang, Yan-Ming; Ma, Jia-Lin; Qu, Song; Li, Ling; Chen, Long; Zhu, Xiao-Dong

2017-01-01

The purpose of this study was to compare the quality of life (QoL) of stage II nasopharyngeal carcinoma (NPC) patients treated with radiotherapy (RT) versus concurrent chemoradiotherapy (CCRT). In a cross-sectional study, these patients were treated with RT (n = 55) or CCRT (n = 51) between June 2008 and June 2013. For all subjects, disease-free survival was more than 3 years. QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) questions and the Head and Neck 35 (EORTC QLQ-H&N35) questions. RT had better outcomes than CCRT for global QoL, functional scales, symptom scales of fatigue and insomnia, financial problems, and weight gain. Survivors receiving 1 cycle of concurrent chemotherapy had worse QoL outcomes than survivors receiving 2 cycles of concurrent chemotherapy. Patients receiving 3 cycles of concurrent chemotherapy had the best QoL outcomes. Thus, CCRT adversely affects the QoL of patients with stage II NPC as compared to radiotherapy. PMID:28152511

How to Evaluate Phase Differences between Trial Groups in Ongoing Electrophysiological Signals

PubMed Central

VanRullen, Rufin

2016-01-01

A growing number of studies endeavor to reveal periodicities in sensory and cognitive functions, by comparing the distribution of ongoing (pre-stimulus) oscillatory phases between two (or more) trial groups reflecting distinct experimental outcomes. A systematic relation between the phase of spontaneous electrophysiological signals, before a stimulus is even presented, and the eventual result of sensory or cognitive processing for that stimulus, would be indicative of an intrinsic periodicity in the underlying neural process. Prior studies of phase-dependent perception have used a variety of analytical methods to measure and evaluate phase differences, and there is currently no established standard practice in this field. The present report intends to remediate this need, by systematically comparing the statistical power of various measures of “phase opposition” between two trial groups, in a number of real and simulated experimental situations. Seven measures were evaluated: one parametric test (circular Watson-Williams test), and three distinct measures of phase opposition (phase bifurcation index, phase opposition sum, and phase opposition product) combined with two procedures for non-parametric statistical testing (permutation, or a combination of z-score and permutation). While these are obviously not the only existing or conceivable measures, they have all been used in recent studies. All tested methods performed adequately on a previously published dataset (Busch et al., 2009). On a variety of artificially constructed datasets, no single measure was found to surpass all others, but instead the suitability of each measure was contingent on several experimental factors: the time, frequency, and depth of oscillatory phase modulation; the absolute and relative amplitudes of post-stimulus event-related potentials for the two trial groups; the absolute and relative trial numbers for the two groups; and the number of permutations used for non-parametric testing. The concurrent use of two phase opposition measures, the parametric Watson-Williams test and a non-parametric test based on summing inter-trial coherence values for the two trial groups, appears to provide the most satisfactory outcome in all situations tested. Matlab code is provided to automatically compute these phase opposition measures. PMID:27683543

Millon Clinical Multiaxial Inventory-III Subtypes of Opioid Dependence: Validity and Matching to Behavioral Therapies

ERIC Educational Resources Information Center

Ball, Samuel A.; Nich, Charla; Rounsaville, Bruce J.; Eagan, Dorothy; Carroll, Kathleen M.

2004-01-01

The concurrent and predictive validity of 2 different methods of Millon Clinical Multiaxial Inventory-III subtyping (protocol sorting, cluster analysis) was evaluated in 125 recently detoxified opioid-dependent outpatients in a 12-week randomized clinical trial. Participants received naltrexone and relapse prevention group counseling and were…

Model-Based Reinforcement Learning under Concurrent Schedules of Reinforcement in Rodents

ERIC Educational Resources Information Center

Huh, Namjung; Jo, Suhyun; Kim, Hoseok; Sul, Jung Hoon; Jung, Min Whan

2009-01-01

Reinforcement learning theories postulate that actions are chosen to maximize a long-term sum of positive outcomes based on value functions, which are subjective estimates of future rewards. In simple reinforcement learning algorithms, value functions are updated only by trial-and-error, whereas they are updated according to the decision-maker's…

Towards building high performance medical image management system for clinical trials

NASA Astrophysics Data System (ADS)

Wang, Fusheng; Lee, Rubao; Zhang, Xiaodong; Saltz, Joel

2011-03-01

Medical image based biomarkers are being established for therapeutic cancer clinical trials, where image assessment is among the essential tasks. Large scale image assessment is often performed by a large group of experts by retrieving images from a centralized image repository to workstations to markup and annotate images. In such environment, it is critical to provide a high performance image management system that supports efficient concurrent image retrievals in a distributed environment. There are several major challenges: high throughput of large scale image data over the Internet from the server for multiple concurrent client users, efficient communication protocols for transporting data, and effective management of versioning of data for audit trails. We study the major bottlenecks for such a system, propose and evaluate a solution by using a hybrid image storage with solid state drives and hard disk drives, RESTfulWeb Services based protocols for exchanging image data, and a database based versioning scheme for efficient archive of image revision history. Our experiments show promising results of our methods, and our work provides a guideline for building enterprise level high performance medical image management systems.

Impact of a social-emotional and character development program on school-level indicators of academic achievement, absenteeism, and disciplinary outcomes: A matched-pair, cluster randomized, controlled trial.

PubMed

Snyder, Frank; Flay, Brian; Vuchinich, Samuel; Acock, Alan; Washburn, Isaac; Beets, Michael; Li, Kin-Kit

2010-01-01

This paper reports the effects of a comprehensive elementary school-based social-emotional and character education program on school-level achievement, absenteeism, and disciplinary outcomes utilizing a matched-pair, cluster randomized, controlled design. The Positive Action Hawai'i trial included 20 racially/ethnically diverse schools (mean enrollment = 544) and was conducted from the 2002-03 through the 2005-06 academic years. Using school-level archival data, analyses comparing change from baseline (2002) to one-year post trial (2007) revealed that intervention schools scored 9.8% better on the TerraNova (2 nd ed.) test for reading and 8.8% on math; 20.7% better in Hawai'i Content and Performance Standards scores for reading and 51.4% better in math; and that intervention schools reported 15.2% lower absenteeism and fewer suspensions (72.6%) and retentions (72.7%). Overall, effect sizes were moderate to large (range 0.5-1.1) for all of the examined outcomes. Sensitivity analyses using permutation models and random-intercept growth curve models substantiated results. The results provide evidence that a comprehensive school-based program, specifically developed to target student behavior and character, can positively influence school-level achievement, attendance, and disciplinary outcomes concurrently.

Comorbid psychiatric disorders in depressed outpatients: demographic and clinical features.

PubMed

Rush, A John; Zimmerman, Mark; Wisniewski, Stephen R; Fava, Maurizio; Hollon, Steven D; Warden, Diane; Biggs, Melanie M; Shores-Wilson, Kathy; Shelton, Richard C; Luther, James F; Thomas, Brandi; Trivedi, Madhukar H

2005-07-01

This study evaluated the clinical and sociodemographic features associated with various degrees of concurrent comorbidity in adult outpatients with nonpsychotic major depressive disorder (MDD). Outpatients enrolled in the STAR*D trial completed the Psychiatric Diagnostic Screening Questionnaire (PDSQ). An a priori 90% specificity threshold was set for PDSQ responses to ascertain the presence of 11 different concurrent DSM-IV Axis I disorders. Of 1376 outpatients, 38.2% had no concurrent comorbidities, while 25.6% suffered one, 16.1% suffered two, and 20.2% suffered three or more comorbid conditions. Altogether, 29.3% met threshold for social anxiety disorder, 20.8% for generalized anxiety disorder, 18.8% for posttraumatic stress disorder, 12.4% for bulimia, 11.9% for alcohol abuse/dependence, 13.4% for obsessive-compulsive disorder, 11.1% for panic disorder, 9.4% for agoraphobia, 7.3% for drug abuse/dependence, 3.7% for hypochondriasis, and 2.2% for somatoform disorder. Those with more concurrent Axis I conditions had earlier ages at first onset of MDD, longer histories of MDD, greater depressive symptom severity, more general medical comorbidity (even though they were younger than those with fewer comorbid conditions), poorer physical and mental function, health perceptions, and life satisfaction; and were more likely to be seen in primary care settings. Participants had to meet entry criteria for STAR*D. Ascertainment of comorbid conditions was not based on a structured interview. Concurrent Axis I conditions (most often anxiety disorders) are very common with MDD. Greater numbers of concurrent comorbid conditions were associated with increased severity, morbidity, and chronicity of their MDD.

Increased skills usage statistically mediates symptom reduction in self-guided internet-delivered cognitive-behavioural therapy for depression and anxiety: a randomised controlled trial.

PubMed

Terides, Matthew D; Dear, Blake F; Fogliati, Vincent J; Gandy, Milena; Karin, Eyal; Jones, Michael P; Titov, Nickolai

2018-01-01

Cognitive-behavioural therapy (CBT) is an effective treatment for clinical and subclinical symptoms of depression and general anxiety, and increases life satisfaction. Patients' usage of CBT skills is a core aspect of treatment but there is insufficient empirical evidence suggesting that skills usage behaviours are a mechanism of clinical change. This study investigated if an internet-delivered CBT (iCBT) intervention increased the frequency of CBT skills usage behaviours and if this statistically mediated reductions in symptoms and increased life satisfaction. A two-group randomised controlled trial was conducted comparing internet-delivered CBT (n = 65) with a waitlist control group (n = 75). Participants were individuals experiencing clinically significant symptoms of depression or general anxiety. Mixed-linear models analyses revealed that the treatment group reported a significantly higher frequency of skills usage, lower symptoms, and higher life satisfaction by the end of treatment compared with the control group. Results from bootstrapping mediation analyses revealed that the increased skills usage behaviours statistically mediated symptom reductions and increased life satisfaction. Although skills usage and symptom outcomes were assessed concurrently, these findings support the notion that iCBT increases the frequency of skills usage behaviours and suggest that this may be an important mechanism of change.

A Pecan-Rich Diet Improves Cardiometabolic Risk Factors in Overweight and Obese Adults: A Randomized Controlled Trial.

PubMed

McKay, Diane L; Eliasziw, Misha; Chen, C Y Oliver; Blumberg, Jeffrey B

2018-03-11

Evidence from observational and intervention studies has shown a high intake of tree nuts is associated with a reduced risk of cardiovascular disease (CVD), mortality from type 2 diabetes (T2DM), and all-cause mortality. However, there is limited data regarding their effects on indicators of cardiometabolic risk other than hypercholesterolemia, and little is known about the demonstrable health benefits of pecans ( Carya illinoensis (Wangenh.) K.Koch). We conducted a randomized, controlled feeding trial to compare the effects of a pecan-rich diet with an isocaloric control diet similar in total fat and fiber content, but absent nuts, on biomarkers related to CVD and T2DM risk in healthy middle-aged and older adults who are overweight or obese with central adiposity. After 4 weeks on a pecan-rich diet, changes in serum insulin, insulin resistance (HOMA-IR) and beta cell function (HOMA-β) were significantly greater than after the control diet ( p < 0.05). Pecan consumption also lowered the risk of cardiometabolic disease as indicated by a composite score reflecting changes in clinically relevant markers. Thus, compared to the control diet, the pecan intervention had a concurrent and clinically significant effect on several relevant markers of cardiometabolic risk.

A Pecan-Rich Diet Improves Cardiometabolic Risk Factors in Overweight and Obese Adults: A Randomized Controlled Trial

PubMed Central

McKay, Diane L.; Eliasziw, Misha; Chen, C. Y. Oliver

2018-01-01

Evidence from observational and intervention studies has shown a high intake of tree nuts is associated with a reduced risk of cardiovascular disease (CVD), mortality from type 2 diabetes (T2DM), and all-cause mortality. However, there is limited data regarding their effects on indicators of cardiometabolic risk other than hypercholesterolemia, and little is known about the demonstrable health benefits of pecans (Carya illinoensis (Wangenh.) K.Koch). We conducted a randomized, controlled feeding trial to compare the effects of a pecan-rich diet with an isocaloric control diet similar in total fat and fiber content, but absent nuts, on biomarkers related to CVD and T2DM risk in healthy middle-aged and older adults who are overweight or obese with central adiposity. After 4 weeks on a pecan-rich diet, changes in serum insulin, insulin resistance (HOMA-IR) and beta cell function (HOMA-β) were significantly greater than after the control diet (p < 0.05). Pecan consumption also lowered the risk of cardiometabolic disease as indicated by a composite score reflecting changes in clinically relevant markers. Thus, compared to the control diet, the pecan intervention had a concurrent and clinically significant effect on several relevant markers of cardiometabolic risk. PMID:29534487

Impact of Current Antipsychotic Medications on Comparative Mortality and Adverse Events in People With Parkinson Disease Psychosis.

PubMed

Ballard, Clive; Isaacson, Stuart; Mills, Roger; Williams, Hilde; Corbett, Anne; Coate, Bruce; Pahwa, Rajesh; Rascol, Olivier; Burn, David J

2015-10-01

To establish the mortality risk and adverse events associated with the use of atypical antipsychotic medications in people with Parkinson disease psychosis (PDP) in a clinically defined trial cohort. Post hoc analysis of data from a multicenter, open-label extension study of pimavanserin comparing people taking and not taking current antipsychotics. Primary and secondary care medical centers in the United States, Canada, Europe, and India. A total of 459 people with PDP enrolled in the extension study. Participants were between ages 30 and 80 years, and had an established diagnosis of idiopathic Parkinson disease and moderate to severe psychosis. Participants were categorized into 2 groups: those receiving concomitant antipsychotic medications ("concurrent APD") and those who did not take antipsychotic medications at any time during the study ("no APD"). Participants were receiving 40 mg pimavanserin daily in addition to concurrent antipsychotics and Parkinson disease medications. Safety assessments at 2 weeks; 1, 3, 6, 9, and 12 months; and every 6 months thereafter, including evaluation of adverse events (AEs), vital signs, weight, physical examinations, 12-lead electrocardiograms, clinical laboratory tests (serum chemistry, hematology, and urinalysis), and the Unified Parkinson's Disease Rating Scale Parts II and III (UPDRS-II+III, activities of daily living and motor impairment, respectively). Differences between participants taking and not taking current antipsychotics were evaluated using incidence rate ratios (IRRs) with 95% confidence intervals (CIs). There was significant increase in the mortality rate for participants taking concurrent antipsychotics compared with the group not taking antipsychotic medications (IRR 4.20, 95% CI 2.13-7.96). Participants who received a concurrent antipsychotic were also significantly more likely to experience overall a serious AE (IRR 2.95, 95% CI 2.02-4.24), any antipsychotic-related event (IRR 1.66, 95% CI 1.18-2.29), cognition-related events (IRR 2.70, 95% CI 1.19-5.58), infections (IRR 1.97, 95% CI 1.17-3.16), and edema (IRR 2.61, 95% CI 1.09-5.59). The risk of falls, stroke, sedation, orthostatic hypotension, and thromboembolic events was also increased in these individuals but this was not significant. This study highlights a significant risk of mortality, and severe AEs in patients with Parkinson disease receiving atypical antipsychotics. This is similar to or greater than the risks seen in people with Alzheimer disease, although with a less clear-cut risk of stroke and a longer delay to increased mortality. Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Insect repellents and sunscreen: implications for personal protection strategies against mosquito-borne disease.

PubMed

Webb, Cameron E; Russell, Richard C

2009-10-01

To determine the protection times provided by insect repellent and sunscreen in combined formulations against biting mosquitoes. To determine if concurrent use of repellent and sunscreen influenced protection times. Insect repellent containing comparable concentrations of N, N-diethyl-3-methylbenzamide (DEET) with and without sunscreen were tested on human skin to determine the mean protection time (MPT) against Aedes aegypti (L.) in the laboratory. Further trials were undertaken to determine the effect on MPT of sunscreen reapplication over repellent every two hours. There was no significant difference in the MPT provided by 80% DEET with (MPT+/-SE=770+/-54.8 minutes) and without (MPT+/-SE=830+/-20.2 minutes) sunscreen or 7.14% DEET with (MPT+/-SE =240+/-15.5 minutes) and 6.98% DEET without (MPT+/-SE =230+/-18.4 minutes) sunscreen. Reapplication of sunscreen resulted in a significantly lower MPT of a 17.0% DEET formulation when sunscreen was reapplied concurrently (MPT+/-SE=330+/-25.2 minutes), compared with DEET alone (MPT+/-SE =400+/-12.7 minutes). When combined in a single formulation with sunscreen, the MPT provided by both high and low concentrations of DEET is not reduced. However, if sunscreen is reapplied over insect repellent, protection times can be reduced significantly. In areas of endemic mosquito-borne disease, the reapplication of a low concentration repellent and sunscreen formulation may provide the most effective protection from biting mosquitoes while minimising the risk of overexposure to DEET.

Pharmacological prevention of suicide in patients with major mood disorders.

PubMed

Rihmer, Zoltan; Gonda, Xenia

2013-12-01

The risk of self-destructive behavior in mood disorders is an inherent phenomenon and suicidal behavior in patients with unipolar or bipolar major mood disorders strongly relates to the presence and severity of depressive episodes. Consequently, early recognition, and successful acute and long-term treatment of depressive disorders is essential for suicide prevention in such patients. Large-scale, retrospective and prospective naturalistic long-term clinical studies, including severely ill, frequently suicidal depressives show that appropriate pharmacotherapy markedly reduces suicide morbidity and mortality even in this high-risk population. Supplementary psycho-social interventions further improve the effect. The slightly elevated (but in absolute sense quite low) risk of suicidal behavior among patients taking antidepressants compared to those taking placebo in randomized controlled antidepressant trials on unipolar major depression might be the consequence of the depression-worsening potential of antidepressant monotherapy in subthreshold and mixed bipolar depressed patients included in these trials and falsely diagnosed as suffering from unipolar major depression. Concurrent depression-focused psychotherapies increase the effectiveness of pharmacotherapy and this way contribute to suicide prevention for patients with mood disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

A phase I study of OSI-461 in combination with mitoxantrone in patients with advanced solid tumors potentially responsive to mitoxantrone

PubMed Central

Resta, Lee P.; Pili, Roberto; Eisenberger, Mario A.; Spitz, Avery; King, Serina; Porter, Jennifer; Franke, Amy; Boinpally, Ramesh; Sweeney, Christopher J.

2010-01-01

Purpose To find the maximum tolerated dose (MTD) of OSI-461 in combination with mitoxantrone in patients with advanced solid tumors. Methods This was a Phase I study using cohort dose escalation of OSI-461 dosed orally twice daily in combination with mitoxantrone 12 mg/m2 given on Day 1 of each 21-day cycle. Results OSI-461 dose was escalated to 1,000 mg po bid. One patient experienced a dose-limiting toxicity (DLT). Three patients discontinued the study due to adverse events (AE). Two patients (10%) had a partial response, and ten patients (50%) had stable disease as best response. Conclusion The combination of OSI-461 and mitoxantrone was well tolerated. Dose escalation was stopped because of toxicities in a concurrent Phase I trial. The response rate seen in patients with prostate cancer was comparable to response rates seen in trials of mitoxantrone and prednisone alone, and further studies of the combination of OSI-461 and mitoxantrone were not pursued. PMID:20445979

Associative cueing of attention through implicit feature-location binding.

PubMed

Girardi, Giovanna; Nico, Daniele

2017-09-01

In order to assess associative learning between two task-irrelevant features in cueing spatial attention, we devised a task in which participants have to make an identity comparison between two sequential visual stimuli. Unbeknownst to them, location of the second stimulus could be predicted by the colour of the first or a concurrent sound. Albeit unnecessary to perform the identity-matching judgment the predictive features thus provided an arbitrary association favouring the spatial anticipation of the second stimulus. A significant advantage was found with faster responses at predicted compared to non-predicted locations. Results clearly demonstrated an associative cueing of attention via a second-order arbitrary feature/location association but with a substantial discrepancy depending on the sensory modality of the predictive feature. With colour as predictive feature, significant advantages emerged only after the completion of three blocks of trials. On the contrary, sound affected responses from the first block of trials and significant advantages were manifest from the beginning of the second. The possible mechanisms underlying the associative cueing of attention in both conditions are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluating an audit and feedback intervention for reducing antibiotic prescribing behaviour in general dental practice (the RAPiD trial): a partial factorial cluster randomised trial protocol

PubMed Central

2014-01-01

Background Antibiotic prescribing in dentistry accounts for 9% of total antibiotic prescriptions in Scottish primary care. The Scottish Dental Clinical Effectiveness Programme (SDCEP) published guidance in April 2008 (2nd edition, August 2011) for Drug Prescribing in Dentistry, which aims to assist dentists to make evidence-based antibiotic prescribing decisions. However, wide variation in prescribing persists and the overall use of antibiotics is increasing. Methods RAPiD is a 12-month partial factorial cluster randomised trial conducted in NHS General Dental Practices across Scotland. Its aim is to compare the effectiveness of individualised audit and feedback (A&F) strategies for the translation into practice of SDCEP recommendations on antibiotic prescribing. The trial uses routinely collected electronic healthcare data in five aspects of its design in order to: identify the study population; apply eligibility criteria; carry out stratified randomisation; generate the trial intervention; analyse trial outcomes. Eligibility was determined on contract status and a minimum level of recent NHS treatment provision. All eligible dental practices in Scotland were simultaneously randomised at baseline either to current audit practice or to an intervention group. Randomisation was stratified by single-handed/multi-handed practices. General dental practitioners (GDPs) working at intervention practices will receive individualised graphical representations of their antibiotic prescribing rate from the previous 14 months at baseline and an update at six months. GDPs could not be blinded to their practice allocation. Intervention practices were further randomised using a factorial design to receive feedback with or without: a health board comparator; a supplementary text-based intervention; additional feedback at nine months. The primary outcome is the total antibiotic prescribing rate per 100 courses of treatment over the year following delivery of the baseline intervention. A concurrent qualitative process evaluation will apply theory-based approaches using the Consolidated Framework for Implementation Research to explore the acceptability of the interventions and the Theoretical Domains Framework to identify barriers and enablers to evidence-based antibiotic prescribing behaviour by GDPs. Discussion RAPiD will provide a robust evaluation of A&F in dentistry in Scotland. It also demonstrates that linked administrative datasets have the potential to be used efficiently and effectively across all stages of an randomised controlled trial. Trial registration Current Controlled Trials ISRCTN49204710 PMID:24758164

Effects of acute supplementation of caffeine on cardiorespiratory responses during endurance running in a hot & humid climate.

PubMed

Ping, Wong Chee; Keong, Chen Chee; Bandyopadhyay, Amit

2010-07-01

Athletes in Malaysia need to perform in a hot and humid climate. Chronic supplementation of caffeine on endurance performance have been studied extensively in different populations. However, concurrent research on the effects of acute supplementation of caffeine on cardiorespiratory responses during endurance exercise in the Malaysian context especially in a hot and humid environment is unavailable. Nine heat adapted recreational Malaysian male runners (aged: 25.4+/-6.9 yr) who were nonusers of caffeine (23.7+/-12.6 mg per day) were recruited in this placebo--controlled double--blind randomized study. Caffeine (5 mg per kg of body weight) or placebo was ingested in the form of a capsule one hour prior to the running exercise trial at 70 per cent of VO2max on a motorised treadmill in a heat-controlled laboratory (31 degrees C, 70% relative humidity). Subjects drank 3 ml of cool water per kg of body weight every 20 min during the running trials to avoid the adverse effects of dehydration. Heart rate, core body temperature and rate of perceived exertion (RPE) were recorded at intervals of 10 min, while oxygen consumption was measured at intervals of 20 min. Running time to exhaustion was significantly (P<0.05) higher in the caffeine trial compared to the placebo trial. Heart rate, core body temperature, oxygen uptake and RPE did not show any significant variation between the trials but it increased significantly during exercise from their respective resting values in both trials (P<0.001). Our study showed that ingestion of 5 mg of caffeine per kg of body weight improved the endurance running performance but did not impose any significant effect on other individual cardiorespiratory parameters of heat-acclimated recreational runners in hot and humid conditions.

Effect of Concurrent Visual Feedback Frequency on Postural Control Learning in Adolescents.

PubMed

Marco-Ahulló, Adrià; Sánchez-Tormo, Alexis; García-Pérez, José A; Villarrasa-Sapiña, Israel; González, Luis M; García-Massó, Xavier

2018-04-13

The purpose was to find better augmented visual feedback frequency (100% or 67%) for learning a balance task in adolescents. Thirty subjects were divided randomly into a control group, and 100% and 67% feedback groups. The three groups performed pretest (3 trials), practice (12 trials), posttest (3 trials) and retention (3 trials, 24 hours later). The reduced feedback group showed lower RMS in the posttest than in the pretest (p = 0.04). The control and reduced feedback groups showed significant lower median frequency in the posttest than in the pretest (p < 0.05). Both feedback groups showed lower values in retention than in the pretest (p < 0.05). Even when the effect of feedback frequency could not be detected in motor learning, 67% of the feedback was recommended for motor adaptation.

Prospective Phase I-II Trial of Helical Tomotherapy With or Without Chemotherapy for Postoperative Cervical Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schwarz, Julie K., E-mail: jschwarz@radonc.wustl.edu; Department of Cell Biology and Physiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO; Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO

2011-12-01

Purpose: To investigate, in a prospective trial, the acute and chronic toxicity of patients with cervical cancer treated with surgery and postoperative intensity-modulated radiotherapy (RT) delivered using helical tomotherapy, with or without the administration of concurrent chemotherapy. Patients and Methods: A total of 24 evaluable patients entered the study between March 2006 and August 2009. The indications for postoperative RT were tumor size, lymphovascular space invasion, and the depth of cervical stromal invasion in 15 patients; 9 patients underwent postoperative RT because of surgically positive lymph nodes. All patients underwent pelvic RT delivered with helical tomotherapy and intracavitary high-dose-rate brachytherapy.more » Treatment consisted of concurrent weekly platinum in 17, sequential carboplatin/Taxol in 1, and RT alone in 6. The patients were monitored for acute and chronic toxicity using the Common Toxicity Criteria, version 3.0. Results: The median follow-up was 24 months (range, 4-49). At the last follow-up visit, 23 patients were alive and disease free. Of the 24 patients, 12 (50%) experienced acute Grade 3 gastrointestinal toxicity (anorexia in 5, diarrhea in 4, and nausea in 3). One patient developed acute Grade 4 genitourinary toxicity (vesicovaginal fistula). For patients treated with concurrent chemotherapy, the incidence of acute Grade 3 and 4 hematologic toxicity was 71% and 24%, respectively. For patients treated without concurrent chemotherapy, the incidence of acute Grade 3 and 4 hematologic toxicity was 29% and 14%, respectively. Two long-term toxicities occurred (vesicovaginal fistula at 25 months and small bowel obstruction at 30 months). The overall and progression-free survival rate at 3 years for all patients was 100% and 89%, respectively. Conclusion: The results of our study have shown that postoperative external RT for cervical cancer delivered with helical tomotherapy and high-dose-rate brachytherapy and with or without chemotherapy is feasible, with acceptable acute and chronic toxicity.« less

Enhanced Recovery After Surgery (ERAS®) in Individuals with Diabetes: A Systematic Review.

PubMed

Albalawi, Zaina; Laffin, Michael; Gramlich, Leah; Senior, Peter; McAlister, Finlay A

2017-08-01

Prevalence of diabetes in surgical patients is 10-40%. It is well recognized that they have higher rates of complications, and longer stays in hospital compared to patients without diabetes. Enhanced recovery after surgery (ERAS) is an evidence-based multimodal surgical care pathway that improves postoperative complications and length of stay in patients without diabetes. This review evaluates the evidence on whether individuals with diabetes would benefit from ERAS implementation. MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) and EMBASE searched with no language restrictions applied. Conference proceedings and bibliographies were reviewed. Experts in the field were contacted, and www.clinicaltrials.gov searched for ongoing trials. Randomized controlled trials (RCT) looking at individuals with diabetes undergoing surgery randomized to ERAS ® or conventional care. Non-randomized controlled trials, controlled before-after studies, interrupted time series, and cohort studies with concurrent controls were also considered. Two authors independently screened studies. The electronic search yielded 437 references. After removing duplicates, 376 were screened for eligibility. Conference proceedings and bibliographies identified additional references. Searching www.clinicaltrials.gov yielded 59 references. Contacting experts in the field identified no further studies. Fourteen full articles were assessed and subsequently excluded for the following reasons: used an intervention other than ERAS ® , did not include patients with diabetes, or used an uncontrolled observational design. To date, the effects of ERAS ® on patients with diabetes have not been rigorously evaluated. This review highlights the lack of evidence in this area and provides guidance on design for future studies.

Empowered Diabetes Management: Life Coaching and Pharmacist Counseling for Employed Adults with Diabetes

ERIC Educational Resources Information Center

Nishita, Christy; Cardazone, Gina; Uehara, Denise Lea; Tom, Tammy

2013-01-01

The Hawai'i Demonstration to Maintain Independence and Employment was a randomized controlled trial examining the effect of a participant-driven, multicomponent intervention on 190 employed adults with diabetes, 36% of whom were Asian and 35% of whom were Native Hawaiian or Pacific Islander. A no treatment concurrent control group was used, and…

The efficacy of protein supplementation during recovery from muscle-damaging concurrent exercise.

PubMed

Eddens, Lee; Browne, Sarah; Stevenson, Emma J; Sanderson, Brad; van Someren, Ken; Howatson, Glyn

2017-07-01

This study investigated the effect of protein supplementation on recovery following muscle-damaging exercise, which was induced with a concurrent exercise design. Twenty-four well-trained male cyclists were randomised to 3 independent groups receiving 20 g protein hydrolysate, iso-caloric carbohydrate, or low-calorific placebo supplementation, per serve. Supplement serves were provided twice daily, from the onset of the muscle-damaging exercise, for a total of 4 days and in addition to a controlled diet (6 g·kg -1 ·day -1 carbohydrate, 1.2 g·kg -1 ·day -1 protein, remainder from fat). Following the concurrent exercise session at time-point 0 h, comprising a simulated high-intensity road cycling trial and 100 drop-jumps, recovery of outcome measures was assessed at 24, 48, and 72 h. The concurrent exercise protocol was deemed to have caused exercise-induced muscle damage (EIMD), owing to time effects (p < 0.001), confirming decrements in maximal voluntary contraction (peaking at 15% ± 10%) and countermovement jump performance (peaking at 8% ± 7%), along with increased muscle soreness, creatine kinase, and C-reactive protein concentrations. No group or interaction effects (p > 0.05) were observed for any of the outcome measures. The present results indicate that protein supplementation does not attenuate any of the indirect indices of EIMD imposed by concurrent exercise, when employing great rigour around the provision of a quality habitual diet and the provision of appropriate supplemental controls.

Prospective randomized trial to assess effects of continuing hormone therapy on cerebral function in postmenopausal women at risk for dementia.

PubMed

Rasgon, Natalie L; Geist, Cheri L; Kenna, Heather A; Wroolie, Tonita E; Williams, Katherine E; Silverman, Daniel H S

2014-01-01

The objective of this study was to examine the effects of estrogen-based hormone therapy (HT) on regional cerebral metabolism in postmenopausal women (mean age = 58, SD = 5) at risk for development of dementia. The prospective clinical trial design included pre- and post-intervention neuroimaging of women randomized to continue (HT+) or discontinue (HT-) therapy following an average of 10 years of use. The primary outcome measure was change in brain metabolism during the subsequent two years, as assessed with fluorodeoxyglucose-18 positron emission tomography (FDG-PET). Longitudinal FDG-PET data were available for 45 study completers. Results showed that women randomized to continue HT experienced relative preservation of frontal and parietal cortical metabolism, compared with women randomized to discontinue HT. Women who discontinued 17-β estradiol (17βE)-based HT, as well as women who continued conjugated equine estrogen (CEE)-based HT, exhibited significant decline in metabolism of the precuneus/posterior cingulate cortical (PCC) area. Significant decline in PCC metabolism was additionally seen in women taking concurrent progestins (with either 17βE or CEE). Together, these findings suggest that among postmenopausal subjects at risk for developing dementia, regional cerebral cortical metabolism is relatively preserved for at least two years in women randomized to continue HT, compared with women randomized to discontinue HT. In addition, continuing unopposed 17βE therapy is associated specifically with preservation of metabolism in PCC, known to undergo the most significant decline in the earliest stages of Alzheimer's disease. ClinicalTrials.gov NCT00097058.

Stabilisation splint therapy for temporomandibular pain dysfunction syndrome.

PubMed

Al-Ani, M Z; Davies, S J; Gray, R J M; Sloan, P; Glenny, A M

2004-01-01

Pain dysfunction syndrome (PDS) is the most common temporomandibular disorder (TMD). There are many synonyms for this condition including facial arthromylagia, TMJ dysfunction syndrome, myofacial pain dysfunction syndrome, craniomandibular dysfunction and myofacial pain dysfunction. The aetiology of PDS is multifactorial and many different therapies have been advocated. To establish the effectiveness of stabilisation splint therapy in reducing symptoms in patients with pain dysfunction syndrome. Electronic databases (including the Cochrane Oral Health Group's Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); The Cochrane Library Issue 2, 2003; MEDLINE (1966 to June 2001); EMBASE (1966 to June 2001)) were searched. Handsearching of relevant journals was undertaken and reference lists of included studies screened. Experts in the field were contacted to identify unpublished articles. There was no language restriction. Randomised or quasi-randomised controlled trials (RCTs), in which splint therapy was compared concurrently to no treatment, other occlusal appliances, or any other active intervention. Data extraction was carried out independently and in duplicate. Validity assessment of the included trials was carried out at the same time as data extraction. Discrepancies were discussed and a third reviewer consulted. The author of the primary study was contacted where necessary. The studies were grouped according to treatment type and duration of follow up. Twenty potentially relevant RCTs were identified. Eight trials were excluded leaving 12 RCTs for analysis. Stabilisation splint therapy was compared to: acupuncture, bite plates, biofeedback/stress management, visual feedback, relaxation, jaw exercises, non-occluding appliance and minimal/no treatment. There was no evidence of a statistically significant difference in the effectiveness of stabilisation splint therapy (SS) in reducing symptoms in patients with pain dysfunction syndrome compared with other active treatments. There is weak evidence to suggest that the use of SS for the treatment of PDS may be beneficial for reducing pain severity, at rest and on palpation, when compared to no treatment. There is insufficient evidence either for or against the use of stabilisation splint therapy for the treatment of temporomandibular pain dysfunction syndrome. This review suggests the need for further, well conducted RCTs that pay attention to method of allocation, outcome assessment, large sample size, and enough duration of follow up. A standardisation of the outcomes of the treatment of PDS should be established in the RCTs.

Evaluating an audit and feedback intervention for reducing antibiotic prescribing behaviour in general dental practice (the RAPiD trial): a partial factorial cluster randomised trial protocol.

PubMed

Prior, Maria; Elouafkaoui, Paula; Elders, Andrew; Young, Linda; Duncan, Eilidh M; Newlands, Rumana; Clarkson, Jan E; Ramsay, Craig R

2014-04-24

Antibiotic prescribing in dentistry accounts for 9% of total antibiotic prescriptions in Scottish primary care. The Scottish Dental Clinical Effectiveness Programme (SDCEP) published guidance in April 2008 (2nd edition, August 2011) for Drug Prescribing in Dentistry, which aims to assist dentists to make evidence-based antibiotic prescribing decisions. However, wide variation in prescribing persists and the overall use of antibiotics is increasing. RAPiD is a 12-month partial factorial cluster randomised trial conducted in NHS General Dental Practices across Scotland. Its aim is to compare the effectiveness of individualised audit and feedback (A&F) strategies for the translation into practice of SDCEP recommendations on antibiotic prescribing. The trial uses routinely collected electronic healthcare data in five aspects of its design in order to: identify the study population; apply eligibility criteria; carry out stratified randomisation; generate the trial intervention; analyse trial outcomes. Eligibility was determined on contract status and a minimum level of recent NHS treatment provision. All eligible dental practices in Scotland were simultaneously randomised at baseline either to current audit practice or to an intervention group. Randomisation was stratified by single-handed/multi-handed practices. General dental practitioners (GDPs) working at intervention practices will receive individualised graphical representations of their antibiotic prescribing rate from the previous 14 months at baseline and an update at six months. GDPs could not be blinded to their practice allocation. Intervention practices were further randomised using a factorial design to receive feedback with or without: a health board comparator; a supplementary text-based intervention; additional feedback at nine months. The primary outcome is the total antibiotic prescribing rate per 100 courses of treatment over the year following delivery of the baseline intervention. A concurrent qualitative process evaluation will apply theory-based approaches using the Consolidated Framework for Implementation Research to explore the acceptability of the interventions and the Theoretical Domains Framework to identify barriers and enablers to evidence-based antibiotic prescribing behaviour by GDPs. RAPiD will provide a robust evaluation of A&F in dentistry in Scotland. It also demonstrates that linked administrative datasets have the potential to be used efficiently and effectively across all stages of an randomised controlled trial. Current Controlled Trials ISRCTN49204710.

The effects of concurrent administration of cytochrome P-450 inhibitors on the pharmacokinetics of oral methadone in healthy dogs.

PubMed

Kukanich, Butch; Kukanich, Kate S; Rodriguez, Jessica R

2011-05-01

The objective was to examine the effects of inhibiting cytochrome P450 (CYP) on the pharmacokinetics of oral methadone in dogs. Prospective non-randomized experimental trial. Six healthy Greyhounds (three male and three female). The study was divided into two phases. Oral methadone (mean = 2.1 mg kg(-1) PO) was administered as whole tablets in Phase 1. In Phase 2 oral methadone (2.1 mg kg(-1) PO) was administered concurrently with ketoconazole (13.0 mg kg(-1) PO q 24 hours), chloramphenicol (48.7 mg kg(-1) PO q 12 hours), fluoxetine (1.3 mg kg(-1) PO q 24 hours), and trimethoprim (6.5 mg kg(-1) PO q 24 hours). Blood was obtained for analysis of methadone plasma concentrations by liquid chromatography with mass spectrometry. The maximum plasma concentration (C(max)), time to C(max) (T(max)), and the area under the curve from time 0 to the last measurable time point above the limit of quantification of the analytical assay (AUC(0-LAST)) were compared statistically. The C(max) of methadone was significantly different (p=0.016) for Phase 1 (5.5 ng mL(-1)) and Phase 2 (171.9 ng mL(-1)). The AUC(0-LAST) was also significantly different (p=0.004) for Phase 1 (13.1 hour ng mL(-1)) and Phase 2 (3075.2 hour ng mL(-1)). Concurrent administration of CYP inhibitors with methadone significantly increased the area under the curve and plasma concentrations of methadone after oral administration to dogs. Further studies are needed assessing more clinically relevant combinations of methadone and CYP inhibitors. © 2011 The Authors. Veterinary Anaesthesia and Analgesia © 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

Safety and efficacy of a hydrogel inlay with laser in situ keratomileusis to improve vision in myopic presbyopic patients: one-year results.

PubMed

Garza, Enrique Barragan; Chayet, Arturo

2015-02-01

To study the safety and efficacy of implanting a hydrogel corneal inlay (Raindrop Near Vision Inlay) concurrently with performing laser in situ keratomileusis (LASIK) to treat myopic presbyopia and to compare the results with results of the same treatment in emmetropic and hyperopic patients. Two private clinics, Tijuana and Monterrey, Mexico. Prospective nonrandomized clinical trial. Bilateral myopic LASIK was performed and a corneal inlay was concurrently implanted in the nondominant eye under a flap created using a femtosecond laser. Primary safety outcomes were the retention of corrected distance (CDVA) and near (CNVA) visual acuities. Efficacy was evaluated on the basis of uncorrected near (UNVA), intermediate (UIVA), and distance (UDVA) visual acuities. A patient questionnaire was used to assess the preoperative and postoperative incidence of visual symptoms, the ability to perform common tasks with no correction, and patient satisfaction with vision. Thirty eyes were enrolled. At each postoperative visit, the mean CDVA and CNVA were within one half line of preoperative measurements and no eye lost 2 or more lines of CDVA. The mean binocular UDVA, UIVA, and UNVA were better than 20/25 Snellen at all postoperative visits. By 6 months, 93% of patients had a binocular Snellen acuity of 20/25 or better across all visual ranges. According to patient questionnaires, 1 year after surgery, visual symptoms were at preoperative levels, 98% of all visual tasks could be easily performed without correction, and 90% of patients were satisfied or very satisfied with their overall vision. A hydrogel corneal inlay with concurrent LASIK was safe and effective for treating myopic presbyopia. Drs. Garza and Chayet are consultants to and investigators for Revision Optics, Inc. Copyright © 2015. Published by Elsevier Inc.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jalali, Rakesh, E-mail: rjalali@tmc.gov.i; Raut, Nirmal; Arora, Brijesh

Purpose: To present outcome data in a prospective study of radiotherapy (RT) with concurrent and adjuvant temozolomide (TMZ) in children with diffuse intrinsic pontine gliomas (DIPGs). Methods and Materials: Pediatric patients with newly diagnosed DIPGs were prospectively treated with focal RT to a dose of 54 Gy in 30 fractions along with concurrent daily TMZ (75 mg/m{sup 2}, Days 1-42). Four weeks after completing the initial RT-TMZ schedule, adjuvant TMZ (200 mg/m{sup 2}, Days 1-5) was given every 28 days to a maximum of 12 cycles. Response was evaluated clinically and radiologically with magnetic resonance imaging and positron emission tomographymore » scans. Results: Between March 2005 and November 2006, 20 children (mean age, 8.3 years) were accrued. Eighteen patients have died from disease progression, one patient is alive with progressive disease, and one patient is alive with stable disease. Median overall survival and progression-free survival were 9.15 months and 6.9 months, respectively. Grade III/IV toxicity during the concurrent RT-TMZ phase included thrombocytopenia in 3 patients, leucopenia in 2, and vomiting in 7. Transient Grade II skin toxicity developed in the irradiated fields in 18 patients. During the adjuvant TMZ phase, Grade III/IV leucopenia developed in 2 patients and Grade IV thrombocytopenia in 1 patient. Patients with magnetic resonance imaging diagnosis of a high-grade tumor had worse survival than those with a low-grade tumor (p = 0.001). Patients with neurologic improvement after RT-TMZ had significantly better survival than those who did not (p = 0.048). Conclusions: TMZ with RT has not yielded any improvement in the outcome of DIPG compared with RT alone. Further clinical trials should explore novel treatment modalities.« less

Concurrent Chemoradiotherapy With Paclitaxel and Nedaplatin Followed by Consolidation Chemotherapy in Locally Advanced Squamous Cell Carcinoma of the Uterine Cervix: Preliminary Results of a Phase II Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang Meiqin, E-mail: pianozmq@hotmail.co; Liu Suping; Wang, Xiang-E.

Purpose: To evaluate the efficacy and toxicities of concurrent chemoradiotherapy (CCRT) and consolidation chemotherapy in patients with locally advanced squamous cell cervical carcinoma. Methods and Materials: Patients with LASCC (FIGO Stage IIB-IIIB) were treated with pelvic external beam radiotherapy (45 Gy for Stage IIB and 50 Gy for Stage III) and high-dose-rate intracavitary brachytherapy (50 Gy for Stage IIB and 35 Gy for Stage III). The cumulative dose at point A was 50 Gy for Stage IIB and 65 Gy for Stage III. Concurrent chemotherapy with paclitaxel (35 mg/m{sup 2}) and nedaplatin (20 mg/m{sup 2}) was given every week formore » 6 weeks. Consolidation chemotherapy with paclitaxel (135 mg/m{sup 2}) and nedaplatin (60 mg/m{sup 2}) was administered every 3 weeks for 4 cycles. Results: All patients completed CCRT, and 28 of 34 patients completed consolidation chemotherapy. The complete response rate was 88% (95% CI, 73-96%). The most common Grade 3 or higher toxicities were leukopenia/neutropenia (10.9% of the cycles). During a median follow up of 23 months (range, 14-30 months), 5 patients had locoregional failure and 1 patient had distant metastasis. The estimated 2-year progression-free survival and overall survival were 82% (95% CI, 68-95%) and 93% (95% CI, 83-100%), respectively. Grade 3 late complications occurred in 3 patients (9%). Conclusions: CCRT with paclitaxel and nedaplatin followed by consolidation chemotherapy is well tolerated and effective in patients with locally advanced squamous cell cervical carcinoma. Further randomized trials of comparing this regimen with the standard treatment are worth while.« less

A disease-specific enteral nutrition formula improves nutritional status and functional performance in patients with head and neck and esophageal cancer undergoing chemoradiotherapy: results of a randomized, controlled, multicenter trial.

PubMed

Fietkau, Rainer; Lewitzki, Victor; Kuhnt, Thomas; Hölscher, Tobias; Hess, Clemens-F; Berger, Bernhard; Wiegel, Thomas; Rödel, Claus; Niewald, Marcus; Hermann, Robert M; Lubgan, Dorota

2013-09-15

In patients with head and neck and esophageal tumors, nutritional status may deteriorate during concurrent chemoradiotherapy (CRT). The aim of this study was to investigate the influence of enteral nutrition enriched with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on body composition and nutritional and functional status. In a controlled, randomized, prospective, double-blind, multicenter study, 111 patients with head and neck and esophageal cancer undergoing concurrent CRT received either an enteral standard nutrition (control group) or disease-specific enteral nutrition Supportan®-containing EPA+DHA (experimental group) via percutaneous endoscopic gastrostomy. The primary endpoint was the change of body cell mass (BCM) following CRT at weeks 7 and 14 compared with the baseline value. Secondary endpoints were additional parameters of body composition, anthropometric parameters, and nutritional and functional status. The primary endpoint of the study, improvement in BCM, reached borderline statistical significance. Following CRT, patients with experimental nutrition lost only 0.82 ± 0.64 kg of BCM compared with 2.82 ± 0.77 kg in the control group (P = .055). The objectively measured nutritional parameters, such as body weight and fat-free mass, showed a tendency toward improvement, but the differences were not significant. The subjective parameters, in particular the Kondrup score (P = .0165) and the subjective global assessment score (P = .0065) after follow-up improved significantly in the experimental group, compared with the control group. Both enteral regimens were safe and well tolerated. Enteral nutrition with EPA and DHA may be advantageous in patients with head and neck or esophageal cancer by improving parameters of nutritional and functional status during CRT. © 2013 American Cancer Society.

Effect of concurrent training on risk factors and hepatic steatosis in obese adolescents

PubMed Central

Antunes, Barbara de Moura M.; Monteiro, Paula Alves; Silveira, Loreana Sanches; Cayres, Suziane Ungari; da Silva, Camila Buonani; F., Ismael Forte

2013-01-01

OBJECTIVE To analyze the effects of a 20-week concurrent training on the variables of body composition, lipid profile, and fatty liver diagnosis in obese adolescents. METHODS An open clinical trial was carried out with 34 obese adolescents aged between 12 and 15 years. Total body fat, trunk fat mass, total cholesterol and its fractions (HDL, LDL and VLDL), and triglycerides were analyzed; an upper abdominal ultrasound was performed in order to diagnose fatty liver. The participants underwent concurrent training (association of weight training with aerobic training) three times per week, lasting one hour for 20 weeks. Statistical analysis included paired Studentâ€(tm)s t-test and frequency analysis in order to verify the relative and absolute reductions of fatty liver diagnosis, being significant p<0.05. RESULTS The studied adolescents showed statistically significant improvement in body composition, with a decrease of total body fat percentage, total fat mass, trunk fat, and an a increase in the lean body mass. They also presented reduced size of liver lobes, decrease in total cholesterol and in LDL-cholesterol, with a lower prevalence of fatty liver. CONCLUSIONS The concurrent training was effective for promoting significant improvements in body fat composition and lipid profile variables, besides reducing fatty liver prevalence rate. PMID:24142321

The Multidimensional Card Selection Task: A new way to measure concurrent cognitive flexibility in preschoolers.

PubMed

Podjarny, Gal; Kamawar, Deepthi; Andrews, Katherine

2017-07-01

Most executive function research examining preschoolers' cognitive flexibility, the ability to think about something in more than one way, has focused on preschoolers' facility for sequentially switching their attention from one dimension to another (e.g., sorting bivalent cards first by color and then by shape). We know very little about preschoolers' ability to coordinate more than one dimension simultaneously (concurrent cognitive flexibility). Here we report on a new task, the Multidimensional Card Selection Task, which was designed to measure children's ability to consider two dimensions, and then three dimensions, concurrently (e.g., shape and size, and then shape, size, and color). More than half of the preschoolers in our sample of 107 (50 3-year-olds and 57 4-year-olds) could coordinate three dimensions simultaneously and consistently across three test trials. Furthermore, performance on the Multidimensional Card Selection Task was related, but not identical, to performance on other cognitive tasks, including a widely used measure of switching cognitive flexibility (the Dimensional Change Card Sort). The Multidimensional Card Selection Task provides a new way to measure concurrent cognitive flexibility in preschoolers, and opens another avenue for exploring the emergence of early cognitive flexibility development. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of hyperbaric oxygen on the growth and development of medicinal maggots.

PubMed

Sherman, Ronald A; Khavari, Borna; Werner, Darryl

2013-01-01

Some wound care therapists use both maggot debridement therapy (MDT) and hyperbaric oxygen (HBO2) therapy to treat non-healing wounds. Some practitioners have reported success using both MDT and HBO2 therapy concurrently; others have not. To begin evaluating the utility of using MDT and HBO2 therapy concurrently, we assessed the effects of hyperbaric oxygen (HBO2) on maggot growth and development, as a surrogate for debridement capacity. Replicate sets of medical-grade blowfly larvae were placed on liver-agar wound models and exposed to HBO2 at 2.0 atmospheres absolute (atm abs) for 90 minutes on 0 (control), 1, 2 or 3 sequential days. The effects of HBO2 exposure were quantified by measuring the maggots' subsequent growth and development. Exposure to HBO2 was most lethal to young larvae (second instars), but not to older larvae (third instars). There was no dose-relationship between the number of HBO2 treatments and rate of larval survival. Our findings suggest that maggot therapy and HBO2 therapy may be administered concurrently, as long as the larvae are not too immature (that is, as long as they are beyond the second instar) by the time they take their first dive. A clinical trial evaluating the clinical benefits of concurrent HBO2 therapy and MDT is warranted.

Safety and Immune Responses in Children After Concurrent or Sequential 2009 H1N1 and 2009–2010 Seasonal Trivalent Influenza Vaccinations

PubMed Central

Frey, Sharon E.; Bernstein, David I.; Gerber, Michael A.; Keyserling, Harry L.; Munoz, Flor M.; Winokur, Patricia L.; Turley, Christine B.; Rupp, Richard E.; Hill, Heather; Wolff, Mark; Noah, Diana L.; Ross, Allison C.; Cress, Gretchen; Belshe, Robert B.

2012-01-01

Background. Administering 2 separate vaccines for seasonal and pandemic influenza was necessary in 2009. Therefore, we conducted a randomized trial of monovalent 2009 H1N1 influenza vaccine (2009 H1N1 vaccine) and seasonal trivalent inactivated influenza vaccine (TIV; split virion) given sequentially or concurrently in previously vaccinated children. Methods. Children randomized to 4 study groups and stratified by age received 1 dose of seasonal TIV and 2 doses of 2009 H1N1 vaccine in 1 of 4 combinations. Injections were given at 21-day intervals and serum samples for hemagglutination inhibition antibody responses were obtained prior to and 21 days after each vaccination. Reactogenicity and adverse events were monitored. Results. All combinations of vaccines were safe in the 531 children enrolled. Generally, 1 dose of 2009 H1N1 vaccine and 1 dose of TIV, regardless of sequence or concurrency of administration, was immunogenic in children ≥10 years of age; children <10 years of age required 2 doses of 2009 H1N1 vaccine. Conclusions. Vaccines were generally well tolerated. The immune responses to 2009 H1N1 vaccine were adequate regardless of the sequence of vaccination in all age groups but the sequence affected titers to TIV antigens. Two doses of 2009 H1N1 vaccine were required to achieve a protective immune response in children <10 years of age. Clinical Trials Registration. NCT00943202. PMID:22802432

Exploring Radiotherapy Targeting Strategy and Dose: A Pooled Analysis of Cooperative Group Trials of Combined Modality Therapy for Stage III Non-Small Cell Lung Cancer.

PubMed

Schild, Steven E; Fan, Wen; Stinchcombe, Thomas E; Vokes, Everett E; Ramalingam, Suresh S; Bradley, Jeffrey D; Kelly, Karen; Pang, Herbert H; Wang, Xiaofei

2018-04-21

Concurrent chemoradiotherapy(CRT) is standard therapy for locally-advanced non-small-cell lung cancer(LA-NSCLC)patients. This study was performed to examine thoracic radiotherapy(TRT) parameters and their impact on patient survival. We collected Individual patient data(IPD) from 3600LA-NSCLC patients participating in 16 cooperative group trials of concurrent CRT. The primary TRT parameters examined included field design strategy(elective nodal irradiation(ENI) compared to involved field TRT(IF-TRT)), total dose, and biologically effective dose(BED). Hazard ratios(HRs) for overall survival were calculated with univariable and multivariable Cox models. TRT doses ranged from 60 to 74 Gy with most treatments administered once-daily. ENI was associated with poorer survival than IF-TRT(univariable HR,1.37;95%CI,1.24-1.51,p<0.0001;multivariable HR,1.31;95%CI,1.08-1.59,p=0.002). The median survival of the IF and ENI patients were 24 and 16 months, respectively. Patients were divided into 3 dose groups: low total dose(60 Gy), medium total dose(>60Gy-66Gy) and high total dose(>66Gy-74 Gy). With reference to the low dose group, the multivariable HR's were 1.08 for the medium dose group(95%CI=0.93-1.25) and 1.12 for the high dose group(CI=0.97-1.30).The univariate p=0.054 and multivariable p=0.17. BED was grouped as follows: low(<55.5Gy 10 ), medium(=55.5 Gy 10) , or high(>55.5 Gy 10 ). With reference to the low BED group, the HR was 1.00(95%CI=0.85-1.18) for the medium BED group and 1.10(95%CI=0.93-1.31) for the high BED group. The univariable p=0.076 and multivariable p=0.16. For LA-NSCLC patients treated with concurrent CRT, IF-TRT was associated with significantly better survival than ENI-TRT. TRT total and BED dose levels were not significantly associated with patient survival. Future progress will require research focusing on better systemic therapy and TRT. Copyright © 2018. Published by Elsevier Inc.

Filling in the gaps: reporting of concurrent supportive care therapies in breast cancer chemotherapy trials.

PubMed

Freedman, Orit; Amir, Eitan; Zimmermann, Camilla; Clemons, Mark

2011-03-01

Supportive care interventions can have a substantial impact on side effects of chemotherapy. Consequently, accurate reporting of such interventions is essential when interpreting clinical trial results. This study determined the prevalence and quality of reporting of supportive care treatment for common chemotherapy-induced toxicities in phase III, breast cancer chemotherapy trials. A systematic review of phase III trials of breast cancer trials incorporating chemotherapy published in the last 5 years was undertaken. Trials were identified through MEDLINE, EMBASE, BIOSIS, and the Cochrane Library. Supportive treatments evaluated were use of antiemetics, colony-stimulating growth factors, and antibiotics. Reporting quality was rated as "good", "fair", "poor", or "absent" using predetermined criteria. Sixty-two trials met inclusion criteria. In 41 studies (66%), details regarding prophylactic antiemetic treatment were not provided. Growth factor use was not reported in 20 trials (32%). Instructions for the use of prophylactic antibiotics were absent in 45 trials (72%). There are significant deficiencies in reporting of use of prophylactic supportive care agents in breast cancer trials. Omission of supportive care instructions may impact substantially on patient management and health care system expenditure. Recommendations for the type, dose, and frequency of supportive care drugs should be provided and reported on in trials.

Asian Versus Non-Asian Outcomes in Nasopharyngeal Carcinoma: A North American Population-based Analysis.

PubMed

Hamilton, Sarah N; Ho, Cheryl; Laskin, Janessa; Zhai, Yongliang; Mak, Paul; Wu, Jonn

2016-12-01

The effect of ethnicity on nasopharyngeal cancer (NPC) outcomes is unclear. This retrospective analysis examines survival and the impact of concurrent chemoradiation (chemoRT) among Asian and non-Asian patients. Subjects included 380 consecutive patients with NPC treated at a Canadian institution from 2000 to 2009. Five-year Kaplan-Meier progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS) were compared between Asian (n=279) and non-Asian (n=101) subjects. Multivariable analysis was performed using Cox regression modeling. Two-variable interaction terms with concurrent chemoRT were used to examine whether concurrent chemoRT conferred different effects among subgroups. Asian subjects presented with earlier stage (P=0.005), were younger, had better performance status, and were less likely smokers (all P<0.001). Survival among Asian versus non-Asian subjects with stage I/II NPC were: PFS 68% versus 59% (P=0.04), DSS 87% versus 77% (P=0.08), and OS 84% versus 74% (P=0.003). Corresponding rates with stage III/IVA/IVB disease were PFS 49% versus 42% (P=0.12), DSS 72% versus 46% (P=0.001), and OS 70% versus 44% (P<0.001). On multivariable analysis, Asian ethnicity, age below 65 years, ECOG performance status 0-1, early stage, staging MRI use, and concurrent chemoRT were associated with improved DSS and OS (P<0.05). On testing interactions with concurrent chemoRT, Asian versus non-Asian ethnicity was significant (hazard ratio 3.9), suggesting that concurrent chemoRT conferred more benefit among non-Asian compared with Asian subjects. In this population-based study, Asian ethnicity was associated with improved DSS and OS. Concurrent chemoRT conferred more benefit among non-Asian compared with Asian subjects.

Concurrent risk-reduction surgery in patients with increased lifetime risk for breast and ovarian cancer: an analysis of the National Surgical Quality Improvement Program (NSQIP) database.

PubMed

Elmi, Maryam; Azin, Arash; Elnahas, Ahmad; McCready, David R; Cil, Tulin D

2018-05-14

Patients with genetic susceptibility to breast and ovarian cancer are eligible for risk-reduction surgery. Surgical morbidity of risk-reduction mastectomy (RRM) with concurrent bilateral salpingo-oophorectomy (BSO) is unknown. Outcomes in these patients were compared to patients undergoing RRM without BSO using a large multi-institutional database. A retrospective cohort analysis was conducted using the American College of Surgeon's National Surgical Quality Improvement Program (NSQIP) 2007-2016 datasets, comparing postoperative morbidity between patients undergoing RRM with patients undergoing RRM with concurrent BSO. Patients with genetic susceptibility to breast/ovarian cancer undergoing risk-reduction surgery were identified. The primary outcome was 30-day postoperative major morbidity. Secondary outcomes included surgical site infections, reoperations, readmissions, length of stay, and venous thromboembolic events. A multivariate analysis was performed to determine predictors of postoperative morbidity and the adjusted effect of concurrent BSO on morbidity. Of the 5470 patients undergoing RRM, 149 (2.7%) underwent concurrent BSO. The overall rate of major morbidity and postoperative infections was 4.5% and 4.6%, respectively. There was no significant difference in the rate of postoperative major morbidity (4.5% vs 4.7%, p = 0.91) or any of the secondary outcomes between patients undergoing RRM without BSO vs. those undergoing RRM with concurrent BSO. Multivariable analysis showed Body Mass Index (OR 1.05; p < 0.001) and smoking (OR 1.78; p = 0.003) to be the only predictors associated with major morbidity. Neither immediate breast reconstruction (OR 1.02; p = 0.93) nor concurrent BSO (OR 0.94; p = 0.89) were associated with increased postoperative major morbidity. This study demonstrated that RRM with concurrent BSO was not associated with significant additional morbidity when compared to RRM without BSO. Therefore, this joint approach may be considered for select patients at risk for both breast and ovarian cancer.

Evaluation of the satellite derived snow cover area - Runoff forecasting models for the inaccessible basins of western Himalayas

NASA Technical Reports Server (NTRS)

Dey, B.

1985-01-01

In this study, the existing seasonal snow cover area runoff forecasting models of the Indus, Kabul, Sutlej and Chenab basins were evaluated with the concurrent flow correlation model for the period 1975-79. In all the basins under study, correlation of concurrent flow model explained the variability in flow better than by the snow cover area runoff models. Actually, the concurrent flow correlation model explained more than 90 percent of the variability in the flow of these rivers. Compared to this model, the snow cover area runoff models explained less of the variability in flow. In the Himalayan river basins under study and at least for the period under observation, the concurrent flow correlation model provided a set of results with which to compare the estimates from the snow cover area runoff models.

Feasibility of identifying a cohort of US women at high risk for HIV infection for HIV vaccine efficacy trials: Longitudinal results of HVTN 906

PubMed Central

Koblin, Beryl A.; Metch, Barbara; Novak, Richard M.; Morgan, Cecilia; Lucy, Debbie; Dunbar, Debora; Graham, Parrie; Swann, Edith; Madenwald, Tamra; Escamilia, Gina; Frank, Ian

2013-01-01

Background Identifying cohorts of US women with HIV infection rates sufficient for inclusion in vaccine efficacy trials has been challenging. Using geography and sexual network characteristics to inform recruitment strategies, HVTN 906 determined the feasibility of recruiting a cohort of women at high risk for HIV acquisition. Methods HIV uninfected women who reported unprotected sex in the prior six months, resided or engaged in risk behavior in local geographical high-risk pockets and/or had a male partner who had been incarcerated, injected drugs or had concurrent partners were eligible. Behavioral risk assessment, HIV counseling and testing and pregnancy testing were done at baseline, 6, 12 and 18 months. Results Among 799 women, 71% were from local high-risk pockets and had high-risk male partners. Median age was 37 years; 79% were Black; 15% Latina. Over half (55%) reported a new partner in the prior six months, 57% reported a male partner who had concurrent female sexual partners and 37% reported a male partner who had been incarcerated. Retention at 18 months was 79.5%. Annual pregnancy incidence was 12%. Annual HIV incidence was 0.31% (95% CI: 0.06, 0.91). Risk behaviors decreased between screening and six months with smaller changes thereafter. Discussion This cohort of women recruited using new strategies based on geography and sexual network characteristics did not have an HIV incidence high enough for HIV vaccine efficacy trials, despite high baseline levels of risk and a high pregnancy rate. New strategies to identify cohorts of US women for efficacy trials are needed. PMID:23446497

Relative and absolute reliability of the clinical version of the Narrow Path Walking Test (NPWT) under single and dual task conditions.

PubMed

Gimmon, Yoav; Jacob, Grinshpon; Lenoble-Hoskovec, Constanze; Büla, Christophe; Melzer, Itshak

2013-01-01

Decline in gait stability has been associated with increased fall risk in older adults. Reliable and clinically feasible methods of gait instability assessment are needed. This study evaluated the relative and absolute reliability and concurrent validity of the testing procedure of the clinical version of the Narrow Path Walking Test (NPWT) under single task (ST) and dual task (DT) conditions. Thirty independent community-dwelling older adults (65-87 years) were tested twice. Participants were instructed to walk within the 6-m narrow path without stepping out. Trial time, number of steps, trial velocity, number of step errors, and number of cognitive task errors were determined. Intraclass correlation coefficients (ICCs) were calculated as indices of agreement, and a graphic approach called "mountain plot" was applied to help interpret the direction and magnitude of disagreements between testing procedures. Smallest detectable change and smallest real difference (SRD) were computed to determine clinically relevant improvement at group and individual levels, respectively. Concurrent validity was assessed using Performance Oriented Mobility Assessment Tool (POMA) and the Short Physical Performance Battery (SPPB). Test-retest agreement (ICC1,2) varied from 0.77 to 0.92 in ST and from 0.78 to 0.92 in DT conditions, with no apparent systematic differences between testing procedures demonstrated by the mountain plot graphs. Smallest detectable change and smallest real change were small for motor task performance and larger for cognitive errors. Significant correlations were observed for trial velocity and trial time with POMA and SPPB. The present results indicate that the NPWT testing procedure is highly reliable and reproducible. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Explicit time integration of finite element models on a vectorized, concurrent computer with shared memory

NASA Technical Reports Server (NTRS)

Gilbertsen, Noreen D.; Belytschko, Ted

1990-01-01

The implementation of a nonlinear explicit program on a vectorized, concurrent computer with shared memory is described and studied. The conflict between vectorization and concurrency is described and some guidelines are given for optimal block sizes. Several example problems are summarized to illustrate the types of speed-ups which can be achieved by reprogramming as compared to compiler optimization.

The Education of Attention as Explanation of Variability of Practice Effects : Learning the Final Approach Phase in a Flight Simulator

ERIC Educational Resources Information Center

Huet, Michael; Jacobs, David M.; Camachon, Cyril; Missenard, Olivier; Gray, Rob; Montagne, Gilles

2011-01-01

The present study reports two experiments in which a total of 20 participants without prior flight experience practiced the final approach phase in a fixed-base simulator. All participants received self-controlled concurrent feedback during 180 practice trials. Experiment 1 shows that participants learn more quickly under variable practice…

The Development and Implementation of a Peer-Led Intervention to Prevent Smoking among Secondary School Students Using Their Established Social Networks

ERIC Educational Resources Information Center

Audrey, Suzanne; Cordall, Kathleen; Moore, Laurence; Cohen, David; Campbell, Rona

2004-01-01

Objective: To design, implement and evaluate a peer-led intervention to reduce smoking amongst secondary school students. Design: A health promotion intervention combining peer education with diffusion of innovation theory, to be rigorously evaluated by means of a cluster randomised controlled trial with concurrent process and economic…

Fulfilling Multiple Missions Concurrently: An Ethnographic Study of a Campus Children's Center's Trials and Triumphs in Serving Six Populations

ERIC Educational Resources Information Center

Calica, Corinna Dy-Liacco

2017-01-01

The study is a comprehensive ethnographic investigation into how a campus children's center and laboratory school site can simultaneously serve six major population groups (i.e., parents, college students, teachers, faculty, administrators, and researchers) while maintaining program operations. The study carefully examines the converging and…

Factors Impacting Emergence of Behavioral Control by Underselected Stimuli in Humans after Reduction of Control by Overselected Stimuli

ERIC Educational Resources Information Center

Broomfield, Laura; McHugh, Louise; Reed, Phil

2010-01-01

Stimulus overselectivity occurs when only one of potentially many aspects of the environment controls behavior. Adult participants were trained and tested on a trial-and-error discrimination learning task while engaging in a concurrent load task, and overselectivity emerged. When responding to the overselected stimulus was reduced by reinforcing a…

Is Perruchet's dissociation between eyeblink conditioned responding and outcome expectancy evidence for two learning systems?

PubMed

Weidemann, Gabrielle; Tangen, Jason M; Lovibond, Peter F; Mitchell, Christopher J

2009-04-01

P. Perruchet (1985b) showed a double dissociation of conditioned responses (CRs) and expectancy for an airpuff unconditioned stimulus (US) in a 50% partial reinforcement schedule in human eyeblink conditioning. In the Perruchet effect, participants show an increase in CRs and a concurrent decrease in expectancy for the airpuff across runs of reinforced trials; conversely, participants show a decrease in CRs and a concurrent increase in expectancy for the airpuff across runs of nonreinforced trials. Three eyeblink conditioning experiments investigated whether the linear trend in eyeblink CRs in the Perruchet effect is a result of changes in associative strength of the conditioned stimulus (CS), US sensitization, or learning the precise timing of the US. Experiments 1 and 2 demonstrated that the linear trend in eyeblink CRs is not the result of US sensitization. Experiment 3 showed that the linear trend in eyeblink CRs is present with both a fixed and a variable CS-US interval and so is not the result of learning the precise timing of the US. The results are difficult to reconcile with a single learning process model of associative learning in which expectancy mediates CRs. Copyright (c) 2009 APA, all rights reserved.

Interim analysis of postoperative chemoradiotherapy with capecitabine and oxaliplatin versus capecitabine alone for pathological stage II and III rectal cancer: a randomized multicenter phase III trial.

PubMed

Feng, Yan-Ru; Zhu, Yuan; Liu, Lu-Ying; Wang, Wei-Hu; Wang, Shu-Lian; Song, Yong-Wen; Wang, Xin; Tang, Yuan; Liu, Yue-Ping; Ren, Hua; Fang, Hui; Zhang, Shi-Ping; Liu, Xin-Fan; Yu, Zi-Hao; Li, Ye-Xiong; Jin, Jing

2016-05-03

The aim of this study is to present an interim analysis of a phase III trial (NCT00714077) of postoperative concurrent capecitabine and radiotherapy with or without oxaliplatin for pathological stage II and III rectal cancer. Patients with pathologically confirmed stage II and III rectal cancer were randomized to either radiotherapy with concurrent capecitabine (Cap-RT group) or with capecitabine and oxaliplatin (Capox-RT group). The primary endpoint was 3-year disease-free survival rate (DFS). The 3-year DFS rate was 73.9% in the Capox-RT group and 71.6% in the Cap-RT group (HR 0.92, p = 0.647), respectively. No significant difference was observed in overall survival, cumulative incidence of local recurrence and distant metastasis between the two groups (p > 0.05). More grade 3-4 acute toxicity was observed in the Capox-RT group than in the Cap-RT group (38.1% vs. 29.2%, p = 0.041). Inclusion of oxaliplatin in the capecitabine-based postoperative regimen did not improve DFS but increased toxicities for pathological stage II and III rectal cancer in this interim analysis.

Antibiotic treatment for the sexual partners of women with bacterial vaginosis.

PubMed

Amaya-Guio, Jairo; Viveros-Carreño, David Andres; Sierra-Barrios, Eloisa Mercedes; Martinez-Velasquez, Mercy Yolima; Grillo-Ardila, Carlos F

2016-10-01

Bacterial vaginosis (BV) is an infection that has a prevalence between 10% to 50% worlwide. BV results in an imbalance of the normal vaginal flora. Microorganisms associated with BV have been isolated from the normal flora of the male genital tract, and their presence could be related to the recurrence of BV after antibiotic treatment. Therefore, the treatment of sexual partners could decrease the recurrence of infection and possibly the burden of the disease. To assess the effectiveness in women and the safety in men of concurrent antibiotic treatment for the sexual partners of women treated for BV. We searched the Cochrane Sexually Transmitted Infections Group Specialized Register (23 July 2016), CENTRAL (1991 to 23 July 2016), MEDLINE (1946 to 23 July 2016), Embase (1974 to 23 July 2016), LILACS (1982 to 23 July 2016), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (23 July 2016), ClinicalTrials.gov (23 July 2016) and the Web of Science™ (2001 to 23 July 2016). We also handsearched conference proceedings, contacted trial authors and reviewed the reference lists of retrieved studies. Randomized controlled trials (RCTs) that compared the concurrent use of any antibiotic treatment with placebo, no intervention or any other intervention by the sexual partners of women treated for BV. Three review authors independently assessed trials for inclusion, extracted data and assessed the risk of bias in the included studies. We resolved any disagreements through consensus. We assessed the quality of the evidence using the GRADE approach. Seven RCTs (1026 participants) met our inclusion criteria, and pharmaceutical industry funded four of these trials. Five trials (854 patients) compared any antibiotic treatment of sexual partners with placebo. Based on high quality evidence, antibiotic treatment does not increase the rate of clinical or symptomatic improvement in women during the first week (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.96 to 1.03; 712 participants, four studies; RR 1.06, 95% CI 1.00 to 1.12; 577 patients, three studies, respectively), between the first and fourth week (RR 1.02, 95% CI 0.94 to 1.11; 590 participants, three studies; RR 0.93, 95% CI 0.84 to 1.03; 444 participants, two studies; respectively) or after the fourth week (RR 0.98, 95% CI 0.90 to 1.07; 572 participants, four studies; RR 1.03, 95% CI 0.90 to 1.17; 296 participants, two studies; respectively). Antibiotic treatment does not led to a lower recurrence during the first and fourth week (RR 1.28, 95% CI 0.68 to 2.43; 218 participants, one study; low quality evidence) or after the fourth week of treatment (RR 1.00, 95% CI 0.67 to 1.52; 372 participants, three studies; low quality evidence) in women, but increases the frequency of adverse events (most frequently gastrointestinal symptoms) reported by sexual partners (RR 2.55, 95% CI 1.55 to 4.18; 477 participants, three studies; low quality evidence). Two trials (172 participants) compared any antibiotic treatment for sexual partners with no intervention. When we compared it with no intervention, the effects of antibiotic treatment on recurrence rate after the fourth week (RR 1.71, 95% CI 0.65 to 4.55; 51 participants, one study), clinical improvement between the first and fourth week (RR 0.93, 95% CI 0.70 to 1.25; 152 participants, two studies) and symptomatic improvement after the fourth week (RR 0.66, 95% CI 0.39 to 1.11; 70 participants, one study) were imprecise and there were no differences between groups. We downgraded the quality of the evidence to low or very low. High quality evidence shows that antibiotic treatment for sexual partners of women with BV, compared with placebo, does not increase the rate of clinical or symptomatic improvement during the first, between the first and fourth or after the fourth week into the women. Low quality evidence suggests that antibiotic treatment does not led to a lower recurrence rate during the first and fourth or after the fourth week of treatment into the women, but increases the frequency of adverse events reported by sexual partners. Finally, compared with no intervention, antibiotic treatment does not decrease the recurrence rate after the fourth week and does not increase the frequency of clinical or symptomatic improvement between the first and fourth or after the fourth week into the women, respectively.

Activity Increase Despite Arthritis (AIDA): design of a Phase II randomised controlled trial evaluating an active management booklet for hip and knee osteoarthritis [ISRCTN24554946].

PubMed

Williams, Nefyn H; Amoakwa, Elvis; Burton, Kim; Hendry, Maggie; Belcher, John; Lewis, Ruth; Hood, Kerenza; Jones, Jeremy; Bennett, Paul; Edwards, Rhiannon T; Neal, Richard D; Andrew, Glynne; Wilkinson, Clare

2009-09-04

Hip and knee osteoarthritis is a common cause of pain and disability, which can be improved by exercise interventions. However, regular exercise is uncommon in this group because the low physical activity level in the general population is probably reduced even further by pain related fear of movement. The best method of encouraging increased activity in this patient group is not known. A booklet has been developed for patients with hip or knee osteoarthritis. It focuses on changing disadvantageous beliefs and encouraging increased physical activity. This paper describes the design of a Phase II randomised controlled trial (RCT) to test the effectiveness of this new booklet for patients with hip and knee osteoarthritis in influencing illness and treatment beliefs, and to assess the feasibility of conducting a larger definitive RCT in terms of health status and exercise behaviour. A computerised search of four general medical practice patients' record databases will identify patients older than 50 years of age who have consulted with hip or knee pain in the previous twelve months. A random sample of 120 will be invited to participate in the RCT comparing the new booklet with a control booklet, and we expect 100 to return final questionnaires. This trial will assess the feasibility of recruitment and randomisation, the suitability of the control intervention and outcome measurement tools, and will provide an estimate of effect size. Outcomes will include beliefs about hip and knee pain, beliefs about exercise, fear avoidance, level of physical activity, health status and health service costs. They will be measured at baseline, one month and three months. We discuss the merits of testing effectiveness in a phase II trial, in terms of intermediate outcome measures, whilst testing the processes for a larger definitive trial. We also discuss the advantages and disadvantages of testing the psychometric properties of the primary outcome measures concurrently with the trial. Current Controlled Trials ISRCTN24554946.

Comparing procedures on the acquisition and generalization of tacts for children with autism spectrum disorder.

PubMed

Schnell, Lauren K; Vladescu, Jason C; Kodak, Tiffany; Nottingham, Casey L

2018-06-17

Generalization is a critical outcome for individuals with autism spectrum disorder (ASD) who display new skills in a limited range of contexts. In the absence of proper planning, generalization may not be observed. The purpose of the current study was to directly compare serial to concurrent multiple exemplar training using total training time per exemplar, mean total training time, and exposures to mastery across three children diagnosed with ASD. Additionally, we assessed the efficiency of presenting secondary targets in the antecedent and consequence portions of learning trials and evaluated generalization to tacts not associated with direct teaching. Results suggested that all training conditions produced acquisition and generalization for trained and untrained exemplars. However, the serial multiple exemplar training condition was more efficient for two participants, whereas the instructive feedback condition was the most efficient for the third. Findings are discussed considering previous studies and areas for future research. © 2018 Society for the Experimental Analysis of Behavior.

Percutaneous permeation comparison of repellents picaridin and DEET in concurrent use with sunscreen oxybenzone from commercially available preparations.

PubMed

Chen, T; Burczynski, F J; Miller, D W; Gu, X

2010-11-01

Concurrent application of insect repellent picaridin or DEET with sunscreens has become prevalent due to concerns on West Nile virus and skin cancer. The objectives of this study were to characterize the percutaneous permeation of picaridin and sunscreen oxybenzone from commercially available preparations and to compare the differences in permeability between picaridin and DEET in association with oxybenzone. In vitro diffusion studies were carried out to measure transdermal permeation of picaridin and oxybenzone from four different products, using various application concentrations and sequences. Results were then compared to those of repellent DEET and sunscreen oxybenzone under identical conditions. Transdermal permeation of picaridin across human epidermis was significantly lower than that of DEET, both alone and in combination with oxybenzone. Concurrent use resulted in either no changes or suppression of transdermal permeation of picaridin and oxybenzone. This finding was different from concurrent use of DEET and oxybenzone in which a synergistic permeation enhancement was observed. In addition, permeation of picaridin, DEET and oxybenzone across human epidermis was dependent on application concentration, use sequence, and preparation type. It was concluded from this comparative study that picaridin would be a better candidate for concurrent use with sunscreen preparations in terms of minimizing percutaneous permeation of the chemicals.

Timing and Characteristics of Cumulative Evidence Available on Novel Therapeutic Agents Receiving Food and Drug Administration Accelerated Approval.

PubMed

Naci, Huseyin; Wouters, Olivier J; Gupta, Radhika; Ioannidis, John P A

2017-06-01

Policy Points: Randomized trials-the gold standard of evaluating effectiveness-constitute a small minority of existing evidence on agents given accelerated approval. One-third of randomized trials are in therapeutic areas outside of FDA approval and less than half evaluate the therapeutic benefits of these agents but use them instead as common backbone treatments. Agents receiving accelerated approval are often tested concurrently in several therapeutic areas. For most agents, no substantial time lag is apparent between the average start dates of randomized trials evaluating their effectiveness and those using them as part of background therapies. There appears to be a tendency for therapeutic agents receiving accelerated approval to quickly become an integral component of standard treatment, despite potential shortcomings in their evidence base. Therapeutic agents treating serious conditions are eligible for Food and Drug Administration (FDA) accelerated approval. The clinical evidence accrued on agents receiving accelerated approval has not been systematically evaluated. Our objective was to assess the timing and characteristics of available studies. We first identified clinical studies of novel therapeutic agents receiving accelerated approval. We then (1) categorized those studies as randomized or nonrandomized, (2) explored whether they evaluated the FDA-approved indications, and (3) documented the available treatment comparisons. We also meta-analyzed the difference in start times between randomized studies that (1) did or did not evaluate approved indications and (2) were or were not designed to evaluate the agent's effectiveness. In total, 37 novel therapeutic agents received accelerated approval between 2000 and 2013. Our search of ClinicalTrials.gov identified 7,757 studies, which included 1,258,315 participants. Only one-third of identified studies were randomized controlled trials. Of 1,631 randomized trials with advanced recruitment status, 906 were conducted in therapeutic areas for which agents received initial accelerated approval, 202 were in supplemental indications, and 523 were outside approved indications. Only 411 out of 906 (45.4%) trials were designed to test the effectiveness of agents that received accelerated approval ("evaluation" trials); others used these agents as common background treatment in both arms ("background" trials). There was no detectable lag between average start times of trials conducted within and outside initially approved indications. Evaluation trials started on average 1.52 years (95% CI: 0.87 to 2.17) earlier than background trials. Cumulative evidence on agents with accelerated approvals has major limitations. Most clinical studies including these agents are small and nonrandomized, and about a third are conducted in unapproved areas, typically concurrently with those conducted in approved areas. Most randomized trials including these therapeutic agents are not designed to directly evaluate their clinical benefits but to incorporate them as standard treatment. © 2017 Milbank Memorial Fund.

Time to be BRAVE: is educating surgeons the key to unlocking the potential of randomised clinical trials in surgery? A qualitative study

PubMed Central

2014-01-01

Background Well-designed randomised clinical trials (RCTs) provide the best evidence to inform decision-making and should be the default option for evaluating surgical procedures. Such trials can be challenging, and surgeons’ preferences may influence whether trials are initiated and successfully conducted and their results accepted. Preferences are particularly problematic when surgeons’ views play a key role in procedure selection and patient eligibility. The bases of such preferences have rarely been explored. Our aim in this qualitative study was to investigate surgeons’ preferences regarding the feasibility of surgical RCTs and their understanding of study design issues using breast reconstruction surgery as a case study. Methods Semistructured qualitative interviews were undertaken with a purposive sample of 35 professionals practicing at 15 centres across the United Kingdom. Interviews were transcribed verbatim and analysed thematically using constant comparative techniques. Sampling, data collection and analysis were conducted concurrently and iteratively until data saturation was achieved. Results Surgeons often struggle with the concept of equipoise. We found that if surgeons did not feel ‘in equipoise’, they did not accept randomisation as a method of treatment allocation. The underlying reasons for limited equipoise were limited appreciation of the methodological weaknesses of data derived from nonrandomised studies and little understanding of pragmatic trial design. Their belief in the value of RCTs for generating high-quality data to change or inform practice was not widely held. Conclusion There is a need to help surgeons understand evidence, equipoise and bias. Current National Institute of Health Research/Medical Research Council investment into education and infrastructure for RCTs, combined with strong leadership, may begin to address these issues or more specific interventions may be required. PMID:24628821

A phase I/II clinical trial for the hybrid of intracavitary and interstitial brachytherapy for locally advanced cervical cancer.

PubMed

Murakami, Naoya; Kato, Shingo; Nakano, Takashi; Uno, Takashi; Yamanaka, Takeharu; Sakurai, Hideyuki; Yoshimura, Ryoichi; Hiratsuka, Junichi; Kuroda, Yuki; Yoshio, Kotaro; Itami, Jun

2016-08-17

This paper describes about a study protocol of phase I/II multicenter prospective clinical trial evaluating the feasibility and efficacy of the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced uterine cervical cancer patients. Patients with histologically confirmed FIGO stage IB2, IIA2, IIB, and IIIB uterine cervical carcinoma width of which is larger than 5 cm assessed by MRI will be entered to this clinical trial. Protocol therapy is 30-30.6 Gy in 15-17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP (40 mg/m(2)), followed by 24 Gy in 4 fractions of HBT and central shield EBRT up to 50-50.4 Gy in 25-28 fractions. Tumor width is assessed again within one week before the first HBT and if the tumor width is larger than 4 cm, patients proceed to the secondary registration. In phase I section, feasibility of this will be investigated. If less than 10 % out of 20 patients experienced greater than grade 3 acute non-hematologic adverse effects, the study proceeds to phase II part. In phase II part a total of 55 patients will be accrued and the efficacy of the HBT will be investigated comparing with historical control data. If the lower margin of 90 % confidence interval of the 2-year pelvic progression-free survival of the HBT trial is higher than 64 %, the HBT is considered to be more effective than conventional ICBT. The aim of this study is to demonstrate the feasibility and efficacy of the HBT for locally advanced cervical cancer. This trial will clarify the indication, feasibility, and efficacy of this new technique. UMIN000019081 ; Registration date: 2015/9/30.

Sham-controlled, randomized, feasibility trial of acupuncture for prevention of radiation-induced xerostomia among patients with nasopharyngeal carcinoma

PubMed Central

Meng, Zhiqiang; Garcia, M. Kay; Hu, Chaosu; Chiang, Joseph; Chambers, Mark; Rosenthal, David I.; Peng, Huiting; Wu, Caijun; Zhao, Qi; Zhao, Genming; Liu, Luming; Spelman, Amy; Palmer, J. Lynn; Wei, Qi; Cohen, Lorenzo

2013-01-01

Background Xerostomia (dry mouth) after head/neck radiation is a common problem among cancer patients. Quality of life (QOL) is impaired, and available treatments are of little benefit. This trial determined the feasibility of conducting a sham-controlled trial of acupuncture and whether acupuncture could prevent xerostomia among head/neck patients undergoing radiotherapy. Methods A sham controlled, feasibility trial was conducted at Fudan University Shanghai Cancer Center, Shanghai, China among patients with nasopharyngeal carcinoma undergoing radiotherapy. To determine feasibility of a sham procedure, 23 patients were randomized to real acupuncture (N = 11) or to sham acupuncture (N = 12). Patients were treated 3 times/week during their course of radiotherapy. Subjective measures were the Xerostomia Questionnaire (XQ) and MD Anderson Symptom Inventory for Head and Neck Cancer (MDASI-HN). Objective measures were unstimulated whole salivary flow rates (UWSFR) and stimulated salivary flow rates (SSFR). Patients were followed for 1 month after radiotherapy. Results XQ scores for acupuncture were significantly lower than sham controls starting in week 3 and lasted through the 1-month follow-up (all P’s < 0.001 except for week 3, which was 0.006), with clinically significant differences as follows: week 6 – RR 0.28 [95% CI, 0.10, 0.79]; week 11- RR 0.17 [95% CI, 0.03, 1.07]. Similar findings were seen for MDASI-HN scores and MDASI-Intrusion scores. Group differences for UWSFR and SSFR were not found. Conclusions In this small pilot study, true acupuncture given concurrently with radiotherapy significantly reduced xerostomia symptoms and improved QOL when compared with sham acupuncture. Large-scale, multi-center, randomized, placebo-controlled trials are now needed. PMID:22285177

The use of peripheral vision to guide perturbation-evoked reach-to-grasp balance-recovery reactions

PubMed Central

King, Emily C.; McKay, Sandra M.; Cheng, Kenneth C.

2016-01-01

For a reach-to-grasp reaction to prevent a fall, it must be executed very rapidly, but with sufficient accuracy to achieve a functional grip. Recent findings suggest that the CNS may avoid potential time delays associated with saccade-guided arm movements by instead relying on peripheral vision (PV). However, studies of volitional arm movements have shown that reaching is slower and/or less accurate when guided by PV, rather than central vision (CV). The present study investigated how the CNS resolves speed-accuracy trade-offs when forced to use PV to guide perturbation-evoked reach-to-grasp balance-recovery reactions. These reactions were evoked, in 12 healthy young adults, via sudden unpredictable anteroposterior platform translation (barriers deterred stepping reactions). In PV trials, subjects were required to look straight-ahead at a visual target while a small cylindrical handhold (length 25%> hand-width) moved intermittently and unpredictably along a transverse axis before stopping at a visual angle of 20°, 30°, or 40°. The perturbation was then delivered after a random delay. In CV trials, subjects fixated on the handhold throughout the trial. A concurrent visuo-cognitive task was performed in 50% of PV trials but had little impact on reach-to-grasp timing or accuracy. Forced reliance on PV did not significantly affect response initiation times, but did lead to longer movement times, longer time-after-peak-velocity and less direct trajectories (compared to CV trials) at the larger visual angles. Despite these effects, forced reliance on PV did not compromise ability to achieve a functional grasp and recover equilibrium, for the moderately large perturbations and healthy young adults tested in this initial study. PMID:20957351

Effects of induction docetaxel, platinum, and fluorouracil chemotherapy in patients with stage III or IVA/B nasopharyngeal cancer treated with concurrent chemoradiation therapy: Final results of 2 parallel phase 2 clinical trials.

PubMed

Kong, Lin; Zhang, Youwang; Hu, Chaosu; Guo, Ye; Lu, Jiade J

2017-06-15

The effects of docetaxel, platinum, and fluorouracil (TPF) induction chemotherapy plus concurrent chemoradiotherapy (CCRT) on locoregionally advanced nasopharyngeal cancer (NPC) are unclear. This study examined the long-term outcomes of the addition of this regimen to CCRT for stage III and IVA/B NPC. Two parallel, single-arm phase 2 trials were performed synchronously to evaluate the efficacy and toxicity of TPF-based induction chemotherapy in patients with stage III or IVA/B NPC. The induction chemotherapy, which preceded standard intensity-modulated radiation therapy/platinum-based chemoradiation, consisted of 3 cycles of docetaxel (75 mg/m 2 on day 1), cisplatin (75 mg/m 2 on day 1), and a continuous infusion of fluorouracil (500 mg/m 2 /d on days 1-5) every 4 weeks. The primary endpoint for both trials was 5-year overall survival (OS). Between January 2007 and July 2010, 52 eligible patients with stage III NPC and 64 eligible patients with nonmetastatic stage IV NPC were accrued to the 2 trials. With a median follow-up of 67 months, the 5-year OS, progression-free survival, distant metastasis-free survival, and local progression-free survival (LPFS) rates were all improved in comparison with historical benchmarks for patients with stage III or IVA/IVB NPC. Multivariate analyses indicated that T and N classifications (T1/T2 vs T3/T4 and N3 vs N0-N2) were the only significant prognosticators for OS. The number of induction chemotherapy cycles was the only significant prognostic factor for predicting LPFS. TPF-based induction chemotherapy appears to significantly improve outcomes in comparison with historical data when it is administered before CCRT for locoregionally advanced NPC. A phase 3 trial is currently being performed to confirm this benefit. Cancer 2017;123:2258-2267. © 2017 American Cancer Society. © 2017 American Cancer Society.

Universal Internet-based prevention for alcohol and cannabis use reduces truancy, psychological distress and moral disengagement: a cluster randomised controlled trial.

PubMed

Newton, Nicola C; Andrews, Gavin; Champion, Katrina E; Teesson, Maree

2014-08-01

A universal Internet-based preventive intervention has been shown to reduce alcohol and cannabis use. The aim of this study was to examine if this program could also reduce risk-factors associated with substance use in adolescents. A cluster randomised controlled trial was conducted in Sydney, Australia in 2007-2008 to assess the effectiveness of the Internet-based Climate Schools: Alcohol and Cannabis course. The evidence-based course, aimed at reducing alcohol and cannabis use, consists of two sets of six lessons delivered approximately six months apart. A total of 764 students (mean 13.1years) from 10 secondary schools were randomly allocated to receive the preventive intervention (n=397, five schools), or their usual health classes (n=367, five schools) over the year. Participants were assessed at baseline, immediately post, and six and twelve months following the intervention on their levels of truancy, psychological distress and moral disengagement. Compared to the control group, students in the intervention group showed significant reductions in truancy, psychological distress and moral disengagement up to twelve months following completion of the intervention. These intervention effects indicate that Internet-based preventive interventions designed to prevent alcohol and cannabis use can concurrently reduce risk-factors associated with substance use in adolescents. Australian Clinical Trials Registry ACTRN: 012607000312448. Copyright © 2014 Elsevier Inc. All rights reserved.

Effects of wrist tendon vibration on arm tracking in people poststroke.

PubMed

Conrad, Megan O; Scheidt, Robert A; Schmit, Brian D

2011-09-01

The goal of this study was to evaluate the influence of wrist tendon vibration on a multijoint elbow/shoulder tracking task. We hypothesized that tendon vibration applied at the wrist musculature would improve upper arm tracking performance in chronic stroke survivors through increased, Ia-afferent feedback to the central nervous system (CNS). To test this hypothesis, 10 chronic stroke and 5 neurologically intact subjects grasped the handle of a planar robot as they tracked a target through a horizontal figure-8 pattern. A total of 36 trials were completed by each subject. During the middle trials, 70-Hz tendon vibration was applied at the wrist flexor tendons. Position, velocity, and electromyography data were evaluated to compare the quality of arm movements before, during, and after trials with concurrent vibration. Despite tracking a target that moved at a constant velocity, hand trajectories appeared to be segmented, displaying alternating intervals of acceleration and deceleration. Segments were identifiable in tangential velocity data as single-peaked, bell-shaped speed pulses. When tendon vibration was applied at the wrist musculature, stroke subjects experienced improved tracking performance in that hand path lengths and peak speed variability decreased, whereas movement smoothness increased. These performance improvements were accompanied by decreases in the muscle activity during movement. Possible mechanisms behind improved movement control in response to tendon vibration may include improved sensorimotor integration or improved cortical modulation of spinal reflex activity.

Effects of wrist tendon vibration on arm tracking in people poststroke

PubMed Central

Conrad, Megan O.; Scheidt, Robert A.

2011-01-01

The goal of this study was to evaluate the influence of wrist tendon vibration on a multijoint elbow/shoulder tracking task. We hypothesized that tendon vibration applied at the wrist musculature would improve upper arm tracking performance in chronic stroke survivors through increased, Ia-afferent feedback to the central nervous system (CNS). To test this hypothesis, 10 chronic stroke and 5 neurologically intact subjects grasped the handle of a planar robot as they tracked a target through a horizontal figure-8 pattern. A total of 36 trials were completed by each subject. During the middle trials, 70-Hz tendon vibration was applied at the wrist flexor tendons. Position, velocity, and electromyography data were evaluated to compare the quality of arm movements before, during, and after trials with concurrent vibration. Despite tracking a target that moved at a constant velocity, hand trajectories appeared to be segmented, displaying alternating intervals of acceleration and deceleration. Segments were identifiable in tangential velocity data as single-peaked, bell-shaped speed pulses. When tendon vibration was applied at the wrist musculature, stroke subjects experienced improved tracking performance in that hand path lengths and peak speed variability decreased, whereas movement smoothness increased. These performance improvements were accompanied by decreases in the muscle activity during movement. Possible mechanisms behind improved movement control in response to tendon vibration may include improved sensorimotor integration or improved cortical modulation of spinal reflex activity. PMID:21697444

Collaborative Care for Older Adults with low back pain by family medicine physicians and doctors of chiropractic (COCOA): study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Low back pain is a prevalent and debilitating condition that affects the health and quality of life of older adults. Older people often consult primary care physicians about back pain, with many also receiving concurrent care from complementary and alternative medicine providers, most commonly doctors of chiropractic. However, a collaborative model of treatment coordination between these two provider groups has yet to be tested. The primary aim of the Collaborative Care for Older Adults Clinical Trial is to develop and evaluate the clinical effectiveness and feasibility of a patient-centered, collaborative care model with family medicine physicians and doctors of chiropractic for the treatment of low back pain in older adults. Methods/design This pragmatic, pilot randomized controlled trial will enroll 120 participants, age 65 years or older with subacute or chronic low back pain lasting at least one month, from a community-based sample in the Quad-Cities, Iowa/Illinois, USA. Eligible participants are allocated in a 1:1:1 ratio to receive 12 weeks of medical care, concurrent medical and chiropractic care, or collaborative medical and chiropractic care. Primary outcomes are self-rated back pain and disability. Secondary outcomes include general and functional health status, symptom bothersomeness, expectations for treatment effectiveness and improvement, fear avoidance behaviors, depression, anxiety, satisfaction, medication use and health care utilization. Treatment safety and adverse events also are monitored. Participant-rated outcome measures are collected via self-reported questionnaires and computer-assisted telephone interviews at baseline, and at 4, 8, 12, 24, 36 and 52 weeks post-randomization. Provider-rated expectations for treatment effectiveness and participant improvement also are evaluated. Process outcomes are assessed through qualitative interviews with study participants and research clinicians, chart audits of progress notes and content analysis of clinical trial notes. Discussion This pragmatic, pilot randomized controlled trial uses a mixed method approach to evaluate the clinical effectiveness, feasibility, and participant and provider perceptions of collaborative care between medical doctors and doctors of chiropractic in the treatment of older adults with low back pain. Trial registration This trial registered in ClinicalTrials.gov on 04 March 2011 with the ID number of NCT01312233. PMID:23324133

Angioedema Spotlight: A Closer Examination of Sacubitril/Valsartan Safety Results.

PubMed

Owens, Ryan E; Oliphant, Carrie S

2017-01-01

Incorporation of neprilysin inhibition into heart failure pharmacotherapy regimens has recently been recommended by U.S. guidelines, based on results from the PARADIGM-HF trial comparing sacubitril/valsartan to enalapril. While most of the discussion has focused on efficacy, a closer examination of the safety results, particularly the incidence of angioedema during the run-in and double-blind periods, is also warranted. Although no major safety concerns were identified, an angioedema risk comparable to enalapril was found, primarily in the black population. Therefore, despite combination with an angiotensin receptor blocker, which historically has a lower incidence of angioedema, the addition of neprilysin inhibition yields an angioedema risk profile comparable to angiotensin converting enzyme (ACE) inhibitors. Clinicians should recognize this safety risk when prescribing sacubitril/valsartan and remain vigilant in counseling patients regarding the signs and symptoms of angioedema. As recommended by the guidelines, avoiding sacubitril/valsartan use concurrently or within 36 hours of the last dose of an ACE inhibitor or in patients with a history of angioedema is also crucial to minimize angioedema risk and prevent patient harm. © Copyright 2017 by the American Board of Family Medicine.

Neoadjuvant chemotherapy followed by surgery has no therapeutic advantages over concurrent chemoradiotherapy in International Federation of Gynecology and Obstetrics stage IB-IIB cervical cancer.

PubMed

Lee, Jeongshim; Kim, Tae Hyung; Kim, Gwi Eon; Keum, Ki Chang; Kim, Yong Bae

2016-09-01

We aimed to assess the efficacy of neoadjuvant chemotherapy followed by surgery (NACT+S), and compared the clinical outcome with that of concurrent chemoradiotherapy (CCRT) in patients with International Federation of Gynecology and Obstetrics (FIGO) IB-IIB cervical cancer. We reviewed 85 patients with FIGO IB-IIB cervical cancer who received NACT+S between 1989 and 2012, and compared them to 358 control patients who received CCRT. The clinical application of NACT was classified based on the following possible therapeutic benefits: increasing resectability after NACT by reducing tumor size or negative conversion of node metastasis; downstaging adenocarcinoma regarded as relatively radioresistant; and preservation of fertility through limited surgery after NACT. Of 85 patients in the NACT+S group, the pathologic downstaging and complete response rates were 68.2% and 22.6%, respectively. Only two young patients underwent limited surgery for preservation of fertility. Patients of the NACT+S group were younger, less likely to have node metastasis, and demonstrated a higher proportion of FIGO IB cases than those of the CCRT group (p≤0.001). The 5-year locoregional control, progression-free survival, and overall survival rates in the NACT+S group were 89.7%, 75.6%, and 92.1%, respectively, which were not significantly different from the rates of 92.5%, 74%, and 84.9% observed in the CCRT group, respectively (p>0.05). NACT+S has no therapeutic advantages over CCRT, the standard treatment. Therefore, NACT+S should be considered only in selected patients through multidisciplinary discussion or clinical trial setting.

Acquisition of choice in concurrent chains: Assessing the cumulative decision model.

PubMed

Grace, Randolph C

2016-05-01

Concurrent chains is widely used to study pigeons' choice between terminal links that can vary in delay, magnitude, or probability of reinforcement. We review research on the acquisition of choice in this procedure. Acquisition has been studied with a variety of research designs, and some studies have incorporated no-food trials to allow for timing and choice to be observed concurrently. Results show that: Choice can be acquired rapidly within sessions when terminal links change unpredictably; under steady-state conditions, acquisition depends on both initial- and terminal-link schedules; and initial-link responding is mediated by learning about the terminal-link stimulus-reinforcer relations. The cumulative decision model (CDM) proposed by Christensen and Grace (2010) and Grace and McLean (2006, 2015) provides a good description of within-session acquisition, and correctly predicts the effects of initial and terminal-link schedules in steady-state designs (Grace, 2002a). Questions for future research include how abrupt shifts in preference within individual sessions and temporal control of terminal-link responding can be modeled. Copyright © 2016 Elsevier B.V. All rights reserved.

Neoadjuvant paclitaxel poliglumex, cisplatin, and radiation for esophageal cancer: a phase 2 trial.

PubMed

Dipetrillo, Thomas; Suntharalingam, Mohan; Ng, Thomas; Fontaine, Jacques; Horiba, Naomi; Oldenburg, Nicklas; Perez, Kimberly; Birnbaum, Ari; Battafarano, Richard; Burrows, Whitney; Safran, Howard

2012-02-01

To evaluate the pathologic complete response (CR) rate and safety of paclitaxel poliglumex (PPX), cisplatin, and concurrent radiation for patients with esophageal cancer. Patients with adenocarcinoma or squamous cell carcinoma of the esophagus or gastroesophageal junction with no evidence of distant metastasis received PPX (50 mg/m(2)/wk) and cisplatin (25 mg/m(2)/wk) for 6 weeks with 50.4 Gy concurrent radiation. Six to eight weeks after completion of chemoradiotherapy, patients underwent surgical resection. Forty patients were enrolled, 37 patients with adenocarcinoma and 3 patients with squamous cell cancer. The treatment-related grade 3 nonhematologic toxicities included esophagitis (7%), nausea (7%), and fatigue (5%). Three patients with clinical endoscopic CR (2 with squamous cell cancer) refused surgery. Twelve of the remaining 37 patients (32%) had a pathologic CR. The 12 patients with pathologic CR all had adenocarcinoma. PPX, cisplatin, and concurrent radiation are well tolerated, easily administered regimen for esophageal cancer with a low incidence of significant esophagitis and a high pathologic CR rate consistent with the preclinical data of PPX and radiation.

The prognostic value of concurrent phrenic nerve palsy in newborn babies with neonatal brachial plexus palsy.

PubMed

Yoshida, Kiyoshi; Kawabata, Hidehiko

2015-06-01

To investigate the prognostic value of concurrent phrenic nerve palsy for predicting spontaneous motor recovery in neonatal brachial plexus palsy. We reviewed the records of 366 neonates with brachial plexus palsy. The clinical and follow-up data of patients with and without phrenic nerve palsy were compared. Of 366 newborn babies with neonatal brachial plexus palsy, 21 (6%) had concurrent phrenic nerve palsy. Sixteen of these neonates had upper-type palsy and 5 had total-type palsy. Poor spontaneous motor recovery was observed in 13 neonates with concurrent phrenic nerve palsy (62%) and in 129 without concurrent phrenic nerve palsy (39%). Among neonates born via vertex delivery, poor motor recovery was observed in 7 of 9 (78%) neonates with concurrent phrenic nerve palsy and 115 of 296 (39%) without concurrent phrenic nerve palsy. Concurrent phrenic nerve palsy in neonates with brachial plexus palsy has prognostic value in predicting poor spontaneous motor recovery of the brachial plexus, particularly after vertex delivery. Therapeutic IV. Copyright © 2015 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Evaluation of concurrent priority queue algorithms. Technical report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Q.

1991-02-01

The priority queue is a fundamental data structure that is used in a large variety of parallel algorithms, such as multiprocessor scheduling and parallel best-first search of state-space graphs. This thesis addresses the design and experimental evaluation of two novel concurrent priority queues: a parallel Fibonacci heap and a concurrent priority pool, and compares them with the concurrent binary heap. The parallel Fibonacci heap is based on the sequential Fibonacci heap, which is theoretically the most efficient data structure for sequential priority queues. This scheme not only preserves the efficient operation time bounds of its sequential counterpart, but also hasmore » very low contention by distributing locks over the entire data structure. The experimental results show its linearly scalable throughput and speedup up to as many processors as tested (currently 18). A concurrent access scheme for a doubly linked list is described as part of the implementation of the parallel Fibonacci heap. The concurrent priority pool is based on the concurrent B-tree and the concurrent pool. The concurrent priority pool has the highest throughput among the priority queues studied. Like the parallel Fibonacci heap, the concurrent priority pool scales linearly up to as many processors as tested. The priority queues are evaluated in terms of throughput and speedup. Some applications of concurrent priority queues such as the vertex cover problem and the single source shortest path problem are tested.« less

Repetitive facilitative exercise under continuous electrical stimulation for severe arm impairment after sub-acute stroke: a randomized controlled pilot study.

PubMed

Shimodozono, Megumi; Noma, Tomokazu; Matsumoto, Shuji; Miyata, Ryuji; Etoh, Seiji; Kawahira, Kazumi

2014-01-01

To investigate the effectiveness of repetitive facilitative exercise (RFE) under surface neuromuscular electrical stimulation (NMES) in patients with post-stroke hemiplegia. This randomized, controlled, observer-blinded, pilot trial randomized 27 adults with severe arm impairment [Fugl-Meyer Arm scale (FMA) ≤ 20] due to stroke of 3-13 weeks duration into three groups and provided treatment on a 4-week, 40 minutes/day, 5 days/week schedule. The RFE-under-NMES group were given 100-150 repetitions of standardized movements of shoulder, elbow and wrist joints of their affected arm with concurrent low-amplitude NMES for each corresponding musculature. The RFE group was given the same exercise regimen but without NMES. The control group was treated with a conventional arm rehabilitation programme without NMES. FMA was assessed at baseline and 4 weeks. All 27 participants (nine in each group) completed the trial. At 4 weeks, the RFE-under-NMES group evidenced significantly greater improvement compared with the control group on the FMA (p = 0.003), but not with the RFE group (p = 0.092). The RFE group showed improvement compared with the control group, but it was not significant (p = 0.199). RFE under NMES is feasible in clinical settings and may be more effective than conventional rehabilitation in lessening arm impairment after sub-acute stroke.

Predictors of anger treatment outcomes.

PubMed

Mackintosh, Margaret-Anne; Morland, Leslie A; Kloezeman, Karen; Greene, Carolyn J; Rosen, Craig S; Elhai, Jon D; Frueh, B Christopher

2014-10-01

This study investigated predictors of therapeutic outcomes for veterans who received treatment for dysregulated anger. Data are from a randomized controlled trial investigating the effectiveness of video teleconferencing compared to in-person delivery of anger management therapy (AMT) among 125 military veterans. Multilevel modeling was used to assess 2 types of predictors (demographic characteristics and mental health factors) of changes in anger symptoms after treatment. Results showed that while veterans benefited similarly from treatment across modalities, veterans who received two or more additional mental health services and who had longer commutes to care showed the greatest improvement on a composite measure of self-reported anger symptoms. Results highlight that veterans with a range of psychosocial and mental health characteristics benefited from AMT, while those receiving the most additional concurrent mental health services had better outcomes. © 2014 Wiley Periodicals, Inc.

Effects of serial and concurrent training on receptive identification tasks: A Systematic replication.

PubMed

Wunderlich, Kara L; Vollmer, Timothy R

2017-07-01

The current study compared the use of serial and concurrent methods to train multiple exemplars when teaching receptive language skills, providing a systematic replication of Wunderlich, Vollmer, Donaldson, and Phillips (2014). Five preschoolers diagnosed with developmental delays or autism spectrum disorders were taught to receptively identify letters or letter sounds. Subjects learned the target stimuli slightly faster in concurrent training and a high degree of generalization was obtained following both methods of training, indicating that both the serial and concurrent methods of training are efficient and effective instructional procedures. © 2017 Society for the Experimental Analysis of Behavior.

Preliminary Results of Whole Brain Radiotherapy With Concurrent Trastuzumab for Treatment of Brain Metastases in Breast Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chargari, Cyrus; Idrissi, Hind Riahi; Pierga, Jean-Yves

2011-11-01

Purpose: To assess the use of trastuzumab concurrently with whole brain radiotherapy (WBRT) for patients with brain metastases from human epidermal growth factor receptor-2-positive breast cancer. Methods and Materials: Between April 2001 and April 2007, 31 patients with brain metastases from human epidermal growth factor receptor-2-positive breast cancer were referred for WBRT with concurrent trastuzumab. At brain progression, the median age was 55 years (range, 38-73), and all patients had a performance status of 0-2. The patients received trastuzumab 2 mg/kg weekly (n = 17) or 6 mg/kg repeated every 21 days (n = 14). In 26 patients, concurrent WBRTmore » delivered 30 Gy in 10 daily fractions. In 6 patients, other fractionations were chosen because of either poor performance status or patient convenience. Results: After WBRT, radiologic responses were observed in 23 patients (74.2%), including 6 (19.4%) with a complete radiologic response and 17 (54.8%) with a partial radiologic response. Clinical responses were observed in 27 patients (87.1%). The median survival time from the start of WBRT was 18 months (range, 2-65). The median interval to brain progression was 10.5 months (range, 2-27). No Grade 2 or greater acute toxicity was observed. Conclusion: The low toxicity of trastuzumab concurrently with WBRT should probably not justify delays. Although promising, these preliminary data warrant additional validation of trastuzumab as a potential radiosensitizer for WBRT in brain metastases from breast cancer in the setting of a clinical trial.« less

An Open, Multisite Pilot Study of Cognitive Therapy for Depressed Adolescents

PubMed Central

BELSHER, GAYLE; WILKES, T. C. R.; RUSH, A. J.

1995-01-01

In a 12-session open trial of cognitive therapy, depressed adolescent outpatients showed significant decreases in depressive symptomatology, although there was less improvement in a subgroup with comorbid attention-deficit hyperactivity or schizoid personality disorder. Decreases on measures of depressive symptoms and depressotypic cognition were maintained up to 5 months after acute-phase treatment. Outcome was not associated with age, gender, other comorbid diagnoses, concurrent use of antidepressants, duration of acute-phase therapy, or participation in subsequent booster sessions. Data suggest that cognitive therapy is a promising intervention for depressed adolescents and provide a rationale for pursuit of controlled cognitive therapy trials with this population. PMID:22700213

A Crossover Design for Comparative Efficacy: A 36-Week Randomized Trial of Bevacizumab and Ranibizumab for Diabetic Macular Edema.

PubMed

Wiley, Henry E; Thompson, Darby J S; Bailey, Clare; Chew, Emily Y; Cukras, Catherine A; Jaffe, Glenn J; Lee, Richard W J; Loken, Erin K; Meyerle, Catherine B; Wong, Wai; Ferris, Frederick L

2016-04-01

To investigate the comparative efficacy of bevacizumab (Avastin) and ranibizumab (Lucentis; both Genentech, Inc, South San Francisco, CA) for diabetic macular edema (DME) using a crossover study design. Randomized, double-masked, 36-week, 3-period crossover clinical trial. Fifty-six subjects with DME involving the center of the macula in one or both eyes. Monthly intravitreous injections of bevacizumab (1.25 mg) or ranibizumab (0.3 mg). Comparison of mean changes in visual acuity and central retinal thickness, tested using a linear mixed-effects model. Based on the linear mixed-effects model, the 3-month estimated mean improvement in visual acuity was 5.3 letters for bevacizumab and 6.6 letters for ranibizumab (difference, 1.3 letters; P = 0.039). Estimated change in optical coherence tomography (OCT) central subfield mean thickness (CSMT) was -89 μm for bevacizumab and -137 μm for ranibizumab (difference, 48 μm; P < 0.001). Incorporating cumulative treatment benefit, the model yielded a predicted 36-week (9-month) average improvement in visual acuity of 7.1 letters (95% confidence interval [CI], 5.0-9.2) for bevacizumab and 8.4 letters (95% CI, 6.3-10.5) for ranibizumab, and a change in OCT CSMT of -128 μm (95% CI, -155 to -100) for bevacizumab and -176 μm (95% CI, -202 to -149) for ranibizumab. There was no significant treatment-by-period interaction (i.e., treatment difference was constant in all 3 periods), nor was there a significant differential carryover effect from one period to the next. This trial demonstrated a statistically significant but small relative clinical benefit of ranibizumab compared with bevacizumab for treatment of DME, using a markedly reduced sample size relative to a full comparative efficacy study. The effects on visual acuity and central retinal thickness for the 2 drugs are consistent with those reported at 1 year for the concurrent parallel-group trial by the Diabetic Retinopathy Clinical Research Network testing bevacizumab, ranibizumab, and aflibercept for DME. The 3-period crossover design allowed for meaningful and efficient comparison, suggesting that this approach may be useful for future comparative efficacy studies of anti-vascular endothelial growth factor drugs for DME. Published by Elsevier Inc.

Reliability and Concurrent Validity of the Narrow Path Walking Test in Persons With Multiple Sclerosis.

PubMed

Rosenblum, Uri; Melzer, Itshak

2017-01-01

About 90% of people with multiple sclerosis (PwMS) have gait instability and 50% fall. Reliable and clinically feasible methods of gait instability assessment are needed. The study investigated the reliability and validity of the Narrow Path Walking Test (NPWT) under single-task (ST) and dual-task (DT) conditions for PwMS. Thirty PwMS performed the NPWT on 2 different occasions, a week apart. Number of Steps, Trial Time, Trial Velocity, Step Length, Number of Step Errors, Number of Cognitive Task Errors, and Number of Balance Losses were measured. Intraclass correlation coefficients (ICC2,1) were calculated from the average values of NPWT parameters. Absolute reliability was quantified from standard error of measurement (SEM) and smallest real difference (SRD). Concurrent validity of NPWT with Functional Reach Test, Four Square Step Test (FSST), 12-item Multiple Sclerosis Walking Scale (MSWS-12), and 2 Minute Walking Test (2MWT) was determined using partial correlations. Intraclass correlation coefficients (ICCs) for most NPWT parameters during ST and DT ranged from 0.46-0.94 and 0.55-0.95, respectively. The highest relative reliability was found for Number of Step Errors (ICC = 0.94 and 0.93, for ST and DT, respectively) and Trial Velocity (ICC = 0.83 and 0.86, for ST and DT, respectively). Absolute reliability was high for Number of Step Errors in ST (SEM % = 19.53%) and DT (SEM % = 18.14%) and low for Trial Velocity in ST (SEM % = 6.88%) and DT (SEM % = 7.29%). Significant correlations for Number of Step Errors and Trial Velocity were found with FSST, MSWS-12, and 2MWT. In persons with PwMS performing the NPWT, Number of Step Errors and Trial Velocity were highly reliable parameters. Based on correlations with other measures of gait instability, Number of Step Errors was the most valid parameter of dynamic balance under the conditions of our test.Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A159).

Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial.

PubMed

Faivre-Finn, Corinne; Snee, Michael; Ashcroft, Linda; Appel, Wiebke; Barlesi, Fabrice; Bhatnagar, Adityanarayan; Bezjak, Andrea; Cardenal, Felipe; Fournel, Pierre; Harden, Susan; Le Pechoux, Cecile; McMenemin, Rhona; Mohammed, Nazia; O'Brien, Mary; Pantarotto, Jason; Surmont, Veerle; Van Meerbeeck, Jan P; Woll, Penella J; Lorigan, Paul; Blackhall, Fiona

2017-08-01

Concurrent chemoradiotherapy is the standard of care in limited-stage small-cell lung cancer, but the optimal radiotherapy schedule and dose remains controversial. The aim of this study was to establish a standard chemoradiotherapy treatment regimen in limited-stage small-cell lung cancer. The CONVERT trial was an open-label, phase 3, randomised superiority trial. We enrolled adult patients (aged ≥18 years) who had cytologically or histologically confirmed limited-stage small-cell lung cancer, Eastern Cooperative Oncology Group performance status of 0-2, and adequate pulmonary function. Patients were recruited from 73 centres in eight countries. Patients were randomly assigned to receive either 45 Gy radiotherapy in 30 twice-daily fractions of 1·5 Gy over 19 days, or 66 Gy in 33 once-daily fractions of 2 Gy over 45 days, starting on day 22 after commencing cisplatin-etoposide chemotherapy (given as four to six cycles every 3 weeks in both groups). The allocation method used was minimisation with a random element, stratified by institution, planned number of chemotherapy cycles, and performance status. Treatment group assignments were not masked. The primary endpoint was overall survival, defined as time from randomisation until death from any cause, analysed by modified intention-to-treat. A 12% higher overall survival at 2 years in the once-daily group versus the twice-daily group was considered to be clinically significant to show superiority of the once-daily regimen. The study is registered with ClinicalTrials.gov (NCT00433563) and is currently in follow-up. Between April 7, 2008, and Nov 29, 2013, 547 patients were enrolled and randomly assigned to receive twice-daily concurrent chemoradiotherapy (274 patients) or once-daily concurrent chemoradiotherapy (273 patients). Four patients (one in the twice-daily group and three in the once-daily group) did not return their case report forms and were lost to follow-up; these patients were not included in our analyses. At a median follow-up of 45 months (IQR 35-58), median overall survival was 30 months (95% CI 24-34) in the twice-daily group versus 25 months (21-31) in the once-daily group (hazard ratio for death in the once daily group 1·18 [95% CI 0·95-1·45]; p=0·14). 2-year overall survival was 56% (95% CI 50-62) in the twice-daily group and 51% (45-57) in the once-daily group (absolute difference between the treatment groups 5·3% [95% CI -3·2% to 13·7%]). The most common grade 3-4 adverse event in patients evaluated for chemotherapy toxicity was neutropenia (197 [74%] of 266 patients in the twice-daily group vs 170 [65%] of 263 in the once-daily group). Most toxicities were similar between the groups, except there was significantly more grade 4 neutropenia with twice-daily radiotherapy (129 [49%] vs 101 [38%]; p=0·05). In patients assessed for radiotherapy toxicity, was no difference in grade 3-4 oesophagitis between the groups (47 [19%] of 254 patients in the twice-daily group vs 47 [19%] of 246 in the once-daily group; p=0·85) and grade 3-4 radiation pneumonitis (4 [3%] of 254 vs 4 [2%] of 246; p=0·70). 11 patients died from treatment-related causes (three in the twice-daily group and eight in the once-daily group). Survival outcomes did not differ between twice-daily and once-daily concurrent chemoradiotherapy in patients with limited-stage small-cell lung cancer, and toxicity was similar and lower than expected with both regimens. Since the trial was designed to show superiority of once-daily radiotherapy and was not powered to show equivalence, the implication is that twice-daily radiotherapy should continue to be considered the standard of care in this setting. Cancer Research UK (Clinical Trials Awards and Advisory Committee), French Ministry of Health, Canadian Cancer Society Research Institute, European Organisation for Research and Treatment of Cancer (Cancer Research Fund, Lung Cancer, and Radiation Oncology Groups). Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC-BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

A randomized trial of automated electronic alerts demonstrating improved reimbursable anesthesia time documentation.

PubMed

Freundlich, Robert E; Barnet, Caryn S; Mathis, Michael R; Shanks, Amy M; Tremper, Kevin K; Kheterpal, Sachin

2013-03-01

To investigate whether alerting providers to errors results in improved documentation of reimbursable anesthesia care. Prospective randomized controlled trial. Operating room (OR) of a university hospital. Anesthesia cases were evaluated to determine whether they met the definition for appropriate anesthesia start time over 4 separate, 45-day calendar cycles: the pre-study period, study period, immediate post-study period, and 3-year follow-up period. During the study period, providers were randomly assigned to either a control or an alert group. Providers in the alert cohort received an automated alphanumeric page if the anesthesia start time occurred concurrently with the patient entering the OR, or more than 30 minutes before entering the OR. Three years after the intervention period, overall compliance was analyzed to assess learned behavior. Baseline compliance was 33% ± 5%. During the intervention period, providers in the alert group showed 87% ± 6% compliance compared with 41% ± 7% compliance in the control group (P < 0.001). Long-term follow-up after cessation of the alerts showed 85% ± 4% compliance. Automated electronic reminders for time-based billing charges are effective and result in improved ongoing reimbursement. Copyright © 2013 Elsevier Inc. All rights reserved.

Concurrent functional magnetic resonance imaging and electroencephalography assessment of sensory gating in schizophrenia

PubMed Central

Bak, Nikolaj; Rostrup, Egill; Larsson, Henrik BW; Glenthøj, Birte Y; Oranje, Bob

2014-01-01

Schizophrenia is frequently accompanied by deficits in basic information processing, such as sensory gating. The sources behind deficient sensory gating in schizophrenia patients are, however, still largely unclear. The aim of the current study was to identify the brain structures involved in deficient sensory gating in schizophrenia patients. Twenty healthy male volunteers and 23 male schizophrenia patients were initially assessed in a somatosensory P50 suppression paradigm using concurrent electroencephalography (EEG)/functional magnetic resonance imaging (fMRI) methodology. The trials consisted of single stimuli or pairs of identical stimuli with either 500 ms or 1,000 ms interstimulus intervals. Not all subjects showed a P50 waveform as a result of the somatosensory stimuli: It was detected in 13 schizophrenia patients and 15 control subjects. Significant P50 suppression was found in the 500 ms trials in controls only. Region of interest analyses were performed for a priori chosen regions. Significant negative correlations between P50 ratios and the BOLD response were found bilaterally in the hippocampus, thalamus, anterior and posterior superior temporal gyrus (STG), and in the left inferior frontal gyrus pars opercularis. However, significant group differences were found in the hippocampus and the thalamus only. This is the first study in which P50 suppression was assessed in schizophrenia patients with concurrent fMRI/EEG methodology. The data support that the STG, thalamus, inferior frontal gyrus, and the hippocampus are involved in P50 suppression. However, of these structures only the hippocampus and thalamus appeared involved in the altered sensory processing found in schizophrenia. Hum Brain Mapp 35:3578–3587, 2014. © 2013 Wiley Periodicals, Inc. PMID:24375687

Phase II Trial of Preoperative Irinotecan-Cisplatin Followed by Concurrent Irinotecan-Cisplatin and Radiotherapy for Resectable Locally Advanced Gastric and Esophagogastric Junction Adenocarcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rivera, Fernando, E-mail: oncrhf@humv.e; Galan, Maica; Tabernero, Josep

Purpose: To determine in a Phase II trial whether preoperative irinotecan-cisplatin (IC) followed by concurrent IC therapy and radiotherapy (IC/RT) improved outcome in patients with resectable, locally advanced gastric adenocarcinoma (GC) or esophagogastric junction cancer (EGJC). Patients and Methods: Patients with resectable Stage II-IV, M0 GC or EGJC made up the study population. The primary endpoint was pathologic complete response (pCR). Two courses of IC (irinotecan, 65mg/m{sup 2}; cisplatin, 30mg/m{sup 2} on Days 1 and 8 every 21 days) were given. Patients without progression then received IC/RT, consisting of daily radiotherapy (45Gy) with concurrent IC (irinotecan, 65mg/m{sup 2}; cisplatin, 30mg/m{supmore » 2} on Days 1, 8, 15, and 22). Surgical resection was performed, if feasible, 5-8 weeks after the end of radiotherapy. Results: Twenty-three patients were included in the study: 10 with EGJC and 13 with GC. Two patients (9%) achieved pCR. The incidences of Grade 3-4 toxicities were as follows: IC: neutropenia 35% (febrile 13%), anemia 22%, diarrhea 22%, emesis 8%; IC/RT: neutropenia 52% (febrile 5%), asthenia 19%, anemia 9%, emesis 9%, diarrhea 5%, cardiotoxicity 5%. No patients died during IC or IC/RT. R0 resection was achieved in 15 patients (65%). Median survival was 14.5 months, and the actuarial 2-year survival rate was 35%. Conclusions: Preoperative IC followed by IC/RT resulted in moderate response and resection rates with mild toxicity in patients with GC and EGJC.« less

Meeting the Challenge of Doing an RCT Evaluation of Youth Mentoring in Ireland: A Journey in Mixed Methods

ERIC Educational Resources Information Center

Brady, Bernadine; O'Regan, Connie

2009-01-01

The youth mentoring program Big Brothers Big Sisters is one of the first social interventions involving youth in Ireland to be evaluated using a randomized controlled trial methodology. This article sets out the design process undertaken, describing how the research team came to adopt a concurrent embedded mixed methods design as a means of…

Effects of Cognitive Behavioral Therapy on Daily Living Skills in Children with High-Functioning Autism and Concurrent Anxiety Disorders

ERIC Educational Resources Information Center

Drahota, Amy; Wood, Jeffrey J.; Sze, Karen M.; Van Dyke, Marilyn

2011-01-01

CBT is a promising treatment for children with autism spectrum disorders (ASD) and focuses, in part, on children's independence and self-help skills. In a trial of CBT for anxiety in ASD (Wood et al. in J Child Psychol Psychiatry 50:224-234, "2009"), children's daily living skills and related parental intrusiveness were assessed. Forty children…

RADVAN: a randomised phase 2 trial of WBRT plus vandetanib for melanoma brain metastases - results and lessons learnt.

PubMed

Gupta, Avinash; Roberts, Corran; Tysoe, Finn; Goff, Matthew; Nobes, Jenny; Lester, James; Marshall, Ernie; Corner, Carie; Wolstenholme, Virginia; Kelly, Charles; Wise, Adelyn; Collins, Linda; Love, Sharon; Woodward, Martha; Salisbury, Amanda; Middleton, Mark R

2016-11-08

Brain metastases occur in up to 75% of patients with advanced melanoma. Most are treated with whole-brain radiotherapy (WBRT), with limited effectiveness. Vandetanib, an inhibitor of vascular endothelial growth factor receptor, epidermal growth factor receptor and rearranged during transfection tyrosine kinases, is a potent radiosensitiser in xenograft models. We compared WBRT with WBRT plus vandetanib in the treatment of patients with melanoma brain metastases. In this double-blind, multi-centre, phase 2 trial patients with melanoma brain metastases were randomised to receive WBRT (30 Gy in 10 fractions) plus 3 weeks of concurrent vandetanib 100 mg once daily or placebo. The primary endpoint was progression-free survival in brain (PFS brain). The main study was preceded by a safety run-in phase to confirm tolerability of the combination. A post-hoc analysis and literature review considered barriers to recruiting patients with melanoma brain metastases to clinical trials. Twenty-four patients were recruited, six to the safety phase and 18 to the randomised phase. The study closed early due to poor recruitment. Median PFS brain was 3.3 months (90% confidence interval (CI): 1.6-5.6) in the vandetanib group and 2.5 months (90% CI: 0.2-4.8) in the placebo group (P=0.34). Median overall survival (OS) was 4.6 months (90% CI: 1.6-6.3) and 2.5 months (90% CI: 0.2-7.2), respectively (P=0.54). The most frequent adverse events were fatigue, alopecia, confusion and nausea. The most common barrier to study recruitment was availability of alternative treatments. The combination of WBRT plus vandetanib was well tolerated. Compared with WBRT alone, there was no significant improvement in PFS brain or OS, although we are unable to provide a definitive result due to poor accrual. A review of barriers to trial accrual identified several factors that affect study recruitment in this difficult disease area.

The effectiveness of occlusal splints for sleep bruxism.

PubMed

Jagger, Robert

2008-01-01

Searches were made using the Cochrane Oral Health Group's Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, LILACS (Latin American & Caribbean Health Sciences Literature), Biblioteca Brasileira de Odontologia, and Dissertations, Theses and Abstracts. Hand searches were made of abstracts of particular importance to this review. Additional reports were identified from the reference lists of retrieved reports and from article reviews about treating sleep bruxism. There were no language restrictions. Randomised controlled trials (RCT) or quasi-RCT were chosen that compared splint therapy concurrently with no treatment, other occlusal appliances, or any other intervention in participants who had sleep bruxism. Data extraction was carried out independently and in duplicate. Validity assessment of the included trials was carried out at the same time as data extraction. Discrepancies were discussed and a third review author consulted. The author of the primary study was contacted when necessary. Thirty-two potentially relevant RCT were identified of which five were eventually included. In these, use of an occlusal splint was compared with palatal splint, mandibular advancement device, transcutaneous electric nerve stimulation, and no treatment. There was just one common outcome (arousal index) which was combined in a meta-analysis. No statistically significant difference between the occlusal splint and control groups were found in meta-analysis. There is not enough evidence to state that the occlusal splint is effective for treating sleep bruxism. Indication of its use is questionable with regard to sleep outcomes, but there may be some benefit with regard to tooth wear. This systematic review suggests the need for further investigation in more controlled RCT that pay attention to method of allocation, outcome assessment, large sample size, and sufficient duration of followup. The study design must be parallel in order to eliminate the bias provided by studies of crossover type. A standardisation of the outcomes of the treatment of sleep bruxism should be established in the RCT.

A randomized trial of concurrent smoking-cessation and substance use disorder treatment in stimulant-dependent smokers.

PubMed

Winhusen, Theresa M; Brigham, Gregory S; Kropp, Frankie; Lindblad, Robert; Gardin, John G; Penn, Pat; Hodgkins, Candace; Kelly, Thomas M; Douaihy, Antoine; McCann, Michael; Love, Lee D; DeGravelles, Eliot; Bachrach, Ken; Sonne, Susan C; Hiott, Bob; Haynes, Louise; Sharma, Gaurav; Lewis, Daniel F; VanVeldhuisen, Paul; Theobald, Jeff; Ghitza, Udi

2014-04-01

To evaluate the impact of concurrent treatments for substance use disorder and nicotine-dependence for stimulant-dependent patients. A randomized, 10-week trial with follow-up at 3 and 6 months after smoking quit date conducted at 12 substance use disorder treatment programs between February 2010 and July 2012. Adults meeting DSM-IV-TR criteria for cocaine and/or methamphetamine dependence and interested in quitting smoking were randomized to treatment as usual (n = 271) or treatment as usual with smoking-cessation treatment (n = 267). All participants received treatment as usual for substance use disorder treatment. Participants assigned to treatment as usual with concurrent smoking-cessation treatment received weekly individual smoking cessation counseling and extended-release bupropion (300 mg/d) during weeks 1-10. During post-quit treatment (weeks 4-10), participants assigned to treatment as usual with smoking-cessation treatment received a nicotine inhaler and contingency management for smoking abstinence. Weekly proportion of stimulant-abstinent participants during the treatment phase, as assessed by urine drug screens and self-report, was the primary outcome. Secondary measures included other substance/nicotine use outcomes and treatment attendance. There were no significant treatment effects on stimulant-use outcomes, as measured by the primary outcome and stimulant-free days, on drug-abstinence, or on attendance. Participants assigned to treatment as usual with smoking-cessation treatment, relative to those assigned to treatment as usual, had significantly better outcomes for drug-free days at 6-month follow-up (χ(2)(1) = 4.09, P <.05), with a decrease in drug-free days from baseline of -1.3% in treatment as usual with smoking-cessation treatment and of -7.6% in treatment as usual. Participants receiving treatment as usual with smoking-cessation treatment, relative to those receiving treatment as usual, had significantly better outcomes on smoking point-prevalence abstinence (25.5% vs 2.2%; χ(2)(1) = 44.69, P < .001; OR =18.2). These results suggest that providing smoking-cessation treatment to illicit stimulant-dependent patients in outpatient substance use disorder treatment will not worsen, and may enhance, abstinence from nonnicotine substance use. ClinicalTrials.gov identifier: NCT01077024. © Copyright 2013 Physicians Postgraduate Press, Inc.

Preoperative chemoradiotherapy with capecitabine versus protracted infusion 5-fluorouracil for rectal cancer: A matched-pair analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Das, Prajnan; Lin, Edward H.; Bhatia, Sumita

2006-12-01

Purpose: To retrospectively compare the acute toxicity, pathologic response, relapse rates, and survival in rectal cancer patients treated with preoperative radiotherapy (RT) and either concurrent capecitabine or concurrent protracted infusion 5-fluorouracil (5-FU). Methods: Between June 2001 and February 2004, 89 patients with nonmetastatic rectal adenocarcinoma were treated with preoperative RT and concurrent capecitabine, followed by mesorectal excision. These patients were individually matched by clinical T and N stage (as determined by endoscopic ultrasound and CT scans) with 89 control patients treated with preoperative RT and concurrent protracted infusion 5-FU between September 1997 and August 2002. Results: In each group, 5more » patients (6%) had Grade 3-4 toxicity during chemoradiotherapy. The pathologic complete response rate was 21% with capecitabine and 12% with protracted infusion 5-FU (p = 0.19). Of the 89 patients in the capecitabine group and 89 in the 5-FU group, 46 (52%) and 55 (62%), respectively, had downstaging of the T stage after chemoradiotherapy (p = 0.20). The estimated 3-year local control (p = 0.15), distant control (p = 0.86), and overall survival (p = 0.12) rate was 94.4%, 86.3%, and 89.8% for patients treated with capecitabine and 98.6%, 86.6%, and 96.4% for patients treated with protracted infusion 5-FU, respectively. Conclusion: Preoperative concurrent capecitabine and concurrent protracted infusion 5-FU were both well tolerated, with similar, low rates of Grade 3-4 acute toxicity. No significant differences were seen in the pathologic response, local and distant recurrence, or overall survival among patients treated with preoperative RT and concurrent capecitabine compared with those treated with RT and concurrent protracted infusion 5-FU.« less

The effect of a concurrent working memory task and temporal offsets on the integration of auditory and visual speech information.

PubMed

Buchan, Julie N; Munhall, Kevin G

2012-01-01

Audiovisual speech perception is an everyday occurrence of multisensory integration. Conflicting visual speech information can influence the perception of acoustic speech (namely the McGurk effect), and auditory and visual speech are integrated over a rather wide range of temporal offsets. This research examined whether the addition of a concurrent cognitive load task would affect the audiovisual integration in a McGurk speech task and whether the cognitive load task would cause more interference at increasing offsets. The amount of integration was measured by the proportion of responses in incongruent trials that did not correspond to the audio (McGurk response). An eye-tracker was also used to examine whether the amount of temporal offset and the presence of a concurrent cognitive load task would influence gaze behavior. Results from this experiment show a very modest but statistically significant decrease in the number of McGurk responses when subjects also perform a cognitive load task, and that this effect is relatively constant across the various temporal offsets. Participant's gaze behavior was also influenced by the addition of a cognitive load task. Gaze was less centralized on the face, less time was spent looking at the mouth and more time was spent looking at the eyes, when a concurrent cognitive load task was added to the speech task.

Moderate- vs high-dose methadone in the treatment of opioid dependence: a randomized trial.

PubMed

Strain, E C; Bigelow, G E; Liebson, I A; Stitzer, M L

1999-03-17

Methadone hydrochloride treatment is the most common pharmacological intervention for opioid dependence, and recent interest has focused on expanding methadone treatment availability beyond traditional specially licensed clinics. However, despite recommendations regarding effective dosing of methadone, controlled clinical trials of higher-dose methadone have not been conducted. To compare the relative clinical efficacy of moderate- vs high-dose methadone in the treatment of opioid dependence. A 40-week randomized, double-blind clinical trial starting in June 1992 and ending in October 1995. Outpatient substance abuse treatment research clinic at the Johns Hopkins University Bayview Campus, Baltimore, Md. One hundred ninety-two eligible clinic patients. Daily oral methadone hydrochloride in the dose range of 40 to 50 mg (n = 97) or 80 to 100 mg (n = 95), with concurrent substance abuse counseling. Opioid-positive urinalysis results and retention in treatment. By intent-to-treat analysis through week 30 patients in the high-dose group had significantly lower rates of opioid-positive urine samples compared with patients in the moderate-dose group (53.0% [95% confidence interval [CI], 46.9%-59.2%] vs 61.9% [95% CI, 55.9%-68.0%]; P = .047. These differences persisted during withdrawal from methadone. Through day 210 no significant difference was evident between dose groups in treatment retention (high-dose group mean retention, 159 days; moderate-dose group mean retention, 157 days). Nineteen (33%) of 57 patients in the high-dose group and 11 (20%) of 54 patients in the moderate-dose group completed detoxification. Both moderate- and high-dose methadone treatment resulted in decreased illicit opioid use during methadone maintenance and detoxification. The high-dose group had significantly greater decreases in illicit opioid use.

Effect of music-based multitask training on gait, balance, and fall risk in elderly people: a randomized controlled trial.

PubMed

Trombetti, Andrea; Hars, Mélany; Herrmann, François R; Kressig, Reto W; Ferrari, Serge; Rizzoli, René

2011-03-28

Falls occur mainly while walking or performing concurrent tasks. We determined whether a music-based multitask exercise program improves gait and balance and reduces fall risk in elderly individuals. We conducted a 12-month randomized controlled trial involving 134 community-dwelling individuals older than 65 years, who are at increased risk of falling. They were randomly assigned to an intervention group (n = 66) or a delayed intervention control group scheduled to start the program 6 months later (n = 68). The intervention was a 6-month multitask exercise program performed to the rhythm of piano music. Change in gait variability under dual-task condition from baseline to 6 months was the primary end point. Secondary outcomes included changes in balance, functional performances, and fall risk. At 6 months, there was a reduction in stride length variability (adjusted mean difference, -1.4%; P < .002) under dual-task condition in the intervention group, compared with the delayed intervention control group. Balance and functional tests improved compared with the control group. There were fewer falls in the intervention group (incidence rate ratio, 0.46; 95% confidence interval, 0.27-0.79) and a lower risk of falling (relative risk, 0.61; 95% confidence interval, 0.39-0.96). Similar changes occurred in the delayed intervention control group during the second 6-month period with intervention. The benefit of the intervention on gait variability persisted 6 months later. In community-dwelling older people at increased risk of falling, a 6-month music-based multitask exercise program improved gait under dual-task condition, improved balance, and reduced both the rate of falls and the risk of falling. Trial Registration clinicaltrials.gov Identifier: NCT01107288.

Transcranial direct current stimulation (tDCS) for improving capacity in activities and arm function after stroke: a network meta-analysis of randomised controlled trials.

PubMed

Elsner, Bernhard; Kwakkel, Gert; Kugler, Joachim; Mehrholz, Jan

2017-09-13

Transcranial Direct Current Stimulation (tDCS) is an emerging approach for improving capacity in activities of daily living (ADL) and upper limb function after stroke. However, it remains unclear what type of tDCS stimulation is most effective. Our aim was to give an overview of the evidence network regarding the efficacy and safety of tDCS and to estimate the effectiveness of the different stimulation types. We performed a systematic review of randomised trials using network meta-analysis (NMA), searching the following databases until 5 July 2016: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, AMED, Web of Science, and four other databases. We included studies with adult people with stroke. We compared any kind of active tDCS (anodal, cathodal, or dual, that is applying anodal and cathodal tDCS concurrently) regarding improvement of our primary outcome of ADL capacity, versus control, after stroke. CRD42016042055. We included 26 studies with 754 participants. Our NMA showed evidence of an effect of cathodal tDCS in improving our primary outcome, that of ADL capacity (standardized mean difference, SMD = 0.42; 95% CI 0.14 to 0.70). tDCS did not improve our secondary outcome, that of arm function, measured by the Fugl-Meyer upper extremity assessment (FM-UE). There was no difference in safety between tDCS and its control interventions, measured by the number of dropouts and adverse events. Comparing different forms of tDCS shows that cathodal tDCS is the most promising treatment option to improve ADL capacity in people with stroke.

Radical Cystectomy Compared to Combined Modality Treatment for Muscle-Invasive Bladder Cancer: A Systematic Review and Meta-Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vashistha, Vishal; Wang, Hanzhang; Mazzone, Andrew

Purpose: To perform a comprehensive comparison of overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS), and treatment-related complications between radical cystectomy (RC) and combined modality treatment (CMT—radiation therapy, concurrent chemotherapy, and maximal transurethral resection of bladder tumor) in the setting of muscle-invasive bladder cancer. Methods and Materials: We searched 7 databases (PubMed, Scopus, EMBASE, Proquest, CINAHL, and (ClinicalTrials.gov)) for randomized, controlled trials and prospective and retrospective studies directly comparing RC with CMT from database inception to March 2016. We conducted meta-analyses evaluating OS, DSS, and PFS with hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Nineteen studies evaluating 12,380 subjects weremore » selected. For the 8 studies encompassing 9554 subjects eligible for meta-analyses, we found no difference in OS at 5 years (HR 0.96, favoring CMT, 95% CI 0.72-1.29; P=.778) or 10 years (HR 1.02, favoring cystectomy, 95% CI 0.73-1.42; P=.905). No difference was observed in DSS at 5 years (HR 0.83, favoring radiation, 95% CI 0.54-1.28; P=.390) or 10 years (HR 1.17, favoring cystectomy, 95% CI 0.89-1.55; P=.264), or PFS at 10 years (HR 0.85, favoring CMT, 95% CI 0.43-1.67; P=.639). The cystectomy arms had higher rates of early major complications, whereas rates of minor complications were similar between the 2 treatments. Conclusion: Current meta-analysis reveals no differences in OS, DSS, or PFS between RC and CMT. Further randomized, controlled trials are necessary to identify the optimal treatment for specific patients.« less

Rivaroxaban in the Prevention of Stroke and Systemic Embolism in Patients with Non-Valvular Atrial Fibrillation: Clinical Implications of the ROCKET AF Trial and Its Subanalyses.

PubMed

Spencer, Ryan J; Amerena, John V

2015-12-01

Atrial fibrillation (AF) is an increasingly common cause of stroke and systemic embolism. While warfarin has been the mainstay of stroke prevention in patients with AF, newer novel oral anticoagulant medications are now available. Rivaroxaban, a direct factor Xa inhibitor with a rapid onset and offset after oral administration, offers potential advantages over warfarin, predominantly due to its predictable pharmacokinetics across wide patient populations. It requires no coagulation monitoring, and only two different doses are needed (20 mg daily for patients with normal renal function and 15 mg daily in those with reduced renal function). A large randomized trial (ROCKET AF) has shown non-inferiority to warfarin for preventing stroke or systemic embolism in the per-protocol population and superiority to warfarin in the on-treatment safety population. Several subanalyses confirm that the treatment effect of rivaroxaban is consistent across different patient subgroups, including those with reduced renal function. The tolerability of rivaroxaban appears similar to that of warfarin, with comparable overall bleeding rates in clinical trials. In ROCKET AF, significantly lower rates of fatal and intracranial bleeding were seen with rivaroxaban, while lower rates of gastrointestinal bleeding were seen with warfarin. Important contraindications to rivaroxaban include valvular AF, the presence of a prosthetic valve (mechanical or bioprosthetic) or valve repair, the need for concurrent dual antiplatelet therapy, and creatinine clearance <30 ml/min. Once-daily dosing and the lack of coagulation monitoring may increase utilization and adherence compared with warfarin, potentially decreasing the large burden of care associated with stroke secondary to AF. Overall, rivaroxaban offers a useful alternative to warfarin for stroke prevention in patients with AF.

An Economic Evaluation of Resistance Training and Aerobic Training versus Balance and Toning Exercises in Older Adults with Mild Cognitive Impairment

PubMed Central

Davis, Jennifer C.; Bryan, Stirling; Marra, Carlo A.; Sharma, Devika; Chan, Alison; Beattie, B. Lynn; Graf, Peter; Liu-Ambrose, Teresa

2013-01-01

Background Mild cognitive impairment (MCI) represents a critical window to intervene against dementia. Exercise training is a promising intervention strategy, but the efficiency (i.e., relationship of costs and consequences) of such types of training remains unknown. Thus, we estimated the incremental cost-effectiveness of resistance training or aerobic training compared with balance and tone exercises in terms of changes in executive cognitive function among senior women with probable MCI. Methods Economic evaluation conducted concurrently with a six-month three arm randomized controlled trial including eighty-six community dwelling women aged 70 to 80 years living in Vancouver, Canada. Participants received twice-weekly resistance training (n = 28), twice weekly aerobic training (n = 30) or twice-weekly balance and tone (control group) classes (n = 28) for 6 months. The primary outcome measure of the Exercise for Cognition and Everyday Living (EXCEL) study assessed executive cognitive function, a test of selective attention and conflict resolution (i.e., Stroop Test). We collected healthcare resource utilization costs over six months. Results Based on the bootstrapped estimates from our base case analysis, we found that both the aerobic training and resistance training interventions were less costly than twice weekly balance and tone classes. Compared with the balance and tone group, the resistance-training group had significantly improved performance on the Stroop Test (p = 0.04). Conclusions Resistance training and aerobic training result in health care cost saving and are more effective than balance and tone classes after only 6 months of intervention. Resistance training is a promising strategy to alter the trajectory of cognitive decline in seniors with MCI. Trial Registration ClinicalTrials.gov NCT00958867. PMID:23690976

Maturation of the P3 and concurrent oscillatory processes during adolescence.

PubMed

Mathes, Birgit; Khalaidovski, Ksenia; Wienke, Annika S; Schmiedt-Fehr, Christina; Basar-Eroglu, Canan

2016-07-01

During adolescence event-related modulations of the neural response may increase. For slow event-related components, such as the P3, this developmental change may be masked due to increased amplitude levels of ongoing delta and theta oscillations in adolescents. In a cross-sectional study design, EEG was measured in 51 participants between 13 and 24years. A visual oddball paradigm was used to elicit the P3. Our analysis focused on fronto-parietal activations within the P3 time-window and the concurrent time-frequency characteristics in the delta (∼0.5-4Hz) and theta (∼4-7Hz) band. The parietal P3 amplitude was similar across the investigated age range, while the amplitude at frontal regions increased with age. The pre-stimulus amplitudes of delta and theta oscillations declined with age, while post-stimulus amplitude enhancement and inter-trial phase coherence increased. These changes affected fronto-parietal electrode sites. The parietal P3 maximum seemed comparable for adolescents and young adults. Detailed analysis revealed that within the P3 time-window brain maturation during adolescence may lead to reduced spontaneous slow-wave oscillations, increased amplitude modulation and time precision of event-related oscillations, and altered P3 scalp topography. Time-frequency analyses may help to distinguish selective neurodevelopmental changes within the P3 time window. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Memory and learning with rapid audiovisual sequences

PubMed Central

Keller, Arielle S.; Sekuler, Robert

2015-01-01

We examined short-term memory for sequences of visual stimuli embedded in varying multisensory contexts. In two experiments, subjects judged the structure of the visual sequences while disregarding concurrent, but task-irrelevant auditory sequences. Stimuli were eight-item sequences in which varying luminances and frequencies were presented concurrently and rapidly (at 8 Hz). Subjects judged whether the final four items in a visual sequence identically replicated the first four items. Luminances and frequencies in each sequence were either perceptually correlated (Congruent) or were unrelated to one another (Incongruent). Experiment 1 showed that, despite encouragement to ignore the auditory stream, subjects' categorization of visual sequences was strongly influenced by the accompanying auditory sequences. Moreover, this influence tracked the similarity between a stimulus's separate audio and visual sequences, demonstrating that task-irrelevant auditory sequences underwent a considerable degree of processing. Using a variant of Hebb's repetition design, Experiment 2 compared musically trained subjects and subjects who had little or no musical training on the same task as used in Experiment 1. Test sequences included some that intermittently and randomly recurred, which produced better performance than sequences that were generated anew for each trial. The auditory component of a recurring audiovisual sequence influenced musically trained subjects more than it did other subjects. This result demonstrates that stimulus-selective, task-irrelevant learning of sequences can occur even when such learning is an incidental by-product of the task being performed. PMID:26575193

Memory and learning with rapid audiovisual sequences.

PubMed

Keller, Arielle S; Sekuler, Robert

2015-01-01

We examined short-term memory for sequences of visual stimuli embedded in varying multisensory contexts. In two experiments, subjects judged the structure of the visual sequences while disregarding concurrent, but task-irrelevant auditory sequences. Stimuli were eight-item sequences in which varying luminances and frequencies were presented concurrently and rapidly (at 8 Hz). Subjects judged whether the final four items in a visual sequence identically replicated the first four items. Luminances and frequencies in each sequence were either perceptually correlated (Congruent) or were unrelated to one another (Incongruent). Experiment 1 showed that, despite encouragement to ignore the auditory stream, subjects' categorization of visual sequences was strongly influenced by the accompanying auditory sequences. Moreover, this influence tracked the similarity between a stimulus's separate audio and visual sequences, demonstrating that task-irrelevant auditory sequences underwent a considerable degree of processing. Using a variant of Hebb's repetition design, Experiment 2 compared musically trained subjects and subjects who had little or no musical training on the same task as used in Experiment 1. Test sequences included some that intermittently and randomly recurred, which produced better performance than sequences that were generated anew for each trial. The auditory component of a recurring audiovisual sequence influenced musically trained subjects more than it did other subjects. This result demonstrates that stimulus-selective, task-irrelevant learning of sequences can occur even when such learning is an incidental by-product of the task being performed.

Evaluating treatment of obstructive sleep apnea comorbid with insomnia disorder using an incomplete factorial design

PubMed Central

Crawford, Megan R.; Turner, Arlener D.; Wyatt, James K.; Fogg, Louis F.; Ong, Jason C.

2016-01-01

Chronic insomnia disorder is a prevalent condition and a significant proportion of these individuals also have obstructive sleep apnea (OSA). These two sleep disorders have distinct pathophysiology and are managed with different treatment approaches. High comorbidity rates have been a catalyst for emerging studies examining multidisciplinary treatment for OSA comorbid with insomnia disorder. In this article, we describe a randomized clinical trial of Cognitive Behavioral Treatment for insomnia (CBT-I) and Positive Airway Pressure (PAP) for OSA. Participants are randomized to receive one of three treatment combinations. Individuals randomized to treatment Arm A receive sequential treatment beginning with CBT-I followed by PAP, in treatment Arm B CBT-I and PAP are administered concurrently. These treatment arms are compared to a control condition, treatment Arm C, where individuals receive PAP alone. Adopting an incomplete factorial study design will allow us to evaluate the efficacy of multidisciplinary treatment (Arms A & B) versus standard treatment alone (Arm C). In addition, the random allocation of individuals to the two different combined treatment sequences (Arm A and Arm B) will allow us to understand the benefits of the sequential administration of CBT-I and PAP relative to concurrent treatment of PAP and CBT-I. These findings will provide evidence of the clinical benefits of treating insomnia disorder in the context of OSA. PMID:26733360

Score Distributions of the Balance Outcome Measure for Elder Rehabilitation (BOOMER) in Community-Dwelling Older Adults With Vertebral Fracture.

PubMed

Brown, Zachary M; Gibbs, Jenna C; Adachi, Jonathan D; Ashe, Maureen C; Hill, Keith D; Kendler, David L; Khan, Aliya; Papaioannou, Alexandra; Prasad, Sadhana; Wark, John D; Giangregorio, Lora M

2017-11-28

We sought to evaluate the Balance Outcome Measure for Elder Rehabilitation (BOOMER) in community-dwelling women 65 years and older with vertebral fracture and to describe score distributions and potential ceiling and floor effects. This was a secondary data analysis of baseline data from the Build Better Bones with Exercise randomized controlled trial using the BOOMER. A total of 141 women with osteoporosis and radiographically confirmed vertebral fracture were included. Concurrent validity and internal consistency were assessed in comparison to the Short Physical Performance Battery (SPPB). Normality and ceiling/floor effects of total BOOMER scores and component test items were also assessed. Exploratory analyses of assistive aid use and falls history were performed. Tests for concurrent validity demonstrated moderate correlation between total BOOMER and SPPB scores. The BOOMER component tests showed modest internal consistency. Substantial ceiling effect and nonnormal score distributions were present among overall sample and those not using assistive aids for total BOOMER scores, although scores were normally distributed for those using assistive aids. The static standing with eyes closed test demonstrated the greatest ceiling effects of the component tests, with 92% of participants achieving a maximal score. While the BOOMER compares well with the SPPB in community-dwelling women with vertebral fractures, researchers or clinicians considering using the BOOMER in similar or higher-functioning populations should be aware of the potential for ceiling effects.

Impact of Intensity-Modulated Radiation Therapy Technique for Locally Advanced Non-Small-Cell Lung Cancer: A Secondary Analysis of the NRG Oncology RTOG 0617 Randomized Clinical Trial.

PubMed

Chun, Stephen G; Hu, Chen; Choy, Hak; Komaki, Ritsuko U; Timmerman, Robert D; Schild, Steven E; Bogart, Jeffrey A; Dobelbower, Michael C; Bosch, Walter; Galvin, James M; Kavadi, Vivek S; Narayan, Samir; Iyengar, Puneeth; Robinson, Clifford G; Wynn, Raymond B; Raben, Adam; Augspurger, Mark E; MacRae, Robert M; Paulus, Rebecca; Bradley, Jeffrey D

2017-01-01

Purpose Although intensity-modulated radiation therapy (IMRT) is increasingly used to treat locally advanced non-small-cell lung cancer (NSCLC), IMRT and three-dimensional conformal external beam radiation therapy (3D-CRT) have not been compared prospectively. This study compares 3D-CRT and IMRT outcomes for locally advanced NSCLC in a large prospective clinical trial. Patients and Methods A secondary analysis was performed to compare IMRT with 3D-CRT in NRG Oncology clinical trial RTOG 0617, in which patients received concurrent chemotherapy of carboplatin and paclitaxel with or without cetuximab, and 60- versus 74-Gy radiation doses. Comparisons included 2-year overall survival (OS), progression-free survival, local failure, distant metastasis, and selected Common Terminology Criteria for Adverse Events (version 3) ≥ grade 3 toxicities. Results The median follow-up was 21.3 months. Of 482 patients, 53% were treated with 3D-CRT and 47% with IMRT. The IMRT group had larger planning treatment volumes (median, 427 v 486 mL; P = .005); a larger planning treatment volume/volume of lung ratio (median, 0.13 v 0.15; P = .013); and more stage IIIB disease (30.3% v 38.6%, P = .056). Two-year OS, progression-free survival, local failure, and distant metastasis-free survival were not different between IMRT and 3D-CRT. IMRT was associated with less ≥ grade 3 pneumonitis (7.9% v 3.5%, P = .039) and a reduced risk in adjusted analyses (odds ratio, 0.41; 95% CI, 0.171 to 0.986; P = .046). IMRT also produced lower heart doses ( P < .05), and the volume of heart receiving 40 Gy (V40) was significantly associated with OS on adjusted analysis ( P < .05). The lung V5 was not associated with any ≥ grade 3 toxicity, whereas the lung V20 was associated with increased ≥ grade 3 pneumonitis risk on multivariable analysis ( P = .026). Conclusion IMRT was associated with lower rates of severe pneumonitis and cardiac doses in NRG Oncology clinical trial RTOG 0617, which supports routine use of IMRT for locally advanced NSCLC.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shusharina, N; Khan, F; Sharp, G

Purpose: To determine the dose level and timing of the boost in locally advanced lung cancer patients with confirmed tumor recurrence by comparing different boosting strategies by an impact of dose escalation in improvement of the therapeutic ratio. Methods: We selected eighteen patients with advanced NSCLC and confirmed recurrence. For each patient, a base IMRT plan to 60 Gy prescribed to PTV was created. Then we compared three dose escalation strategies: a uniform escalation to the original PTV, an escalation to a PET-defined target planned sequentially and concurrently. The PET-defined targets were delineated by biologically-weighed regions on a pre-treatment 18F-FDGmore » PET. The maximal achievable dose, without violating the OAR constraints, was identified for each boosting method. The EUD for the target, spinal cord, combined lung, and esophagus was compared for each plan. Results: The average prescribed dose was 70.4±13.9 Gy for the uniform boost, 88.5±15.9 Gy for the sequential boost and 89.1±16.5 Gy for concurrent boost. The size of the boost planning volume was 12.8% (range: 1.4 – 27.9%) of the PTV. The most prescription-limiting dose constraints was the V70 of the esophagus. The EUD within the target increased by 10.6 Gy for the uniform boost, by 31.4 Gy for the sequential boost and by 38.2 for the concurrent boost. The EUD for OARs increased by the following amounts: spinal cord, 3.1 Gy for uniform boost, 2.8 Gy for sequential boost, 5.8 Gy for concurrent boost; combined lung, 1.6 Gy for uniform, 1.1 Gy for sequential, 2.8 Gy for concurrent; esophagus, 4.2 Gy for uniform, 1.3 Gy for sequential, 5.6 Gy for concurrent. Conclusion: Dose escalation to a biologically-weighed gross tumor volume defined on a pre-treatment 18F-FDG PET may provide improved therapeutic ratio without breaching predefined OAR constraints. Sequential boost provides better sparing of OARs as compared with concurrent boost.« less

Implicit attitudes to sexual partner concurrency vary by sexual orientation but not by gender-A cross sectional study of Belgian students.

PubMed

Kenyon, Chris R; Wolfs, Kenny; Osbak, Kara; van Lankveld, Jacques; Van Hal, Guido

2018-01-01

High rates of sexual partner concurrency have been shown to facilitate the spread of various sexually transmitted infections. Assessments of explicit attitudes to concurrency have however found little difference between populations. Implicit attitudes to concurrency may vary between populations and play a role in generating differences in the prevalence of concurrency. We developed a concurrency implicit associations test (C-IAT) to assess if implicit attitudes towards concurrency may vary between individuals and populations and what the correlates of these variations are. A sample of 869 Belgian students (mean age 23, SD 5.1) completed an online version of the C-IAT together with a questionnaire concerning sexual behavior and explicit attitudes to concurrency. The study participants C-IATs demonstrated a strong preference for monogamy (-0.78, SD = 0.41). 93.2% of participants had a pro-monogamy C-IAT. There was no difference in this implicit preference for monogamy between heterosexual men and women. Men who have sex with men and women who have sex with women were more likely to exhibit implicit but not explicit preferences for concurrency compared to heterosexual men and women. Correlates of the C-IAT varied between men and women.

Postoperative Concurrent Chemoradiotherapy Versus Postoperative Radiotherapy in High-Risk Cutaneous Squamous Cell Carcinoma of the Head and Neck: The Randomized Phase III TROG 05.01 Trial.

PubMed

Porceddu, Sandro Virgilio; Bressel, Mathias; Poulsen, Michael Geoffrey; Stoneley, Adam; Veness, Michael John; Kenny, Lizbeth Moira; Wratten, Chris; Corry, June; Cooper, Stephen; Fogarty, Gerald Blaise; Collins, Marnie; Collins, Michael Kevin; Macann, Andrew Martin John; Milross, Christopher Gerard; Penniment, Michael Gordon; Liu, Howard Yu-Hao; King, Madeleine Trudy; Panizza, Benedict James; Rischin, Danny

2018-05-01

Purpose To report the results of the Trans Tasman Radiation Oncology Group randomized phase III trial designed to determine whether the addition of concurrent chemotherapy to postoperative radiotherapy (CRT) improved locoregional control in patients with high-risk cutaneous squamous cell carcinoma of the head and neck. Patients and Methods The primary objective was to determine whether there was a difference in freedom from locoregional relapse (FFLRR) between 60 or 66 Gy (6 to 6.5 weeks) with or without weekly carboplatin (area under the curve 2) after resection of gross disease. Secondary efficacy objectives were to compare disease-free survival and overall survival. Results Three hundred twenty-one patients were randomly assigned, with 310 patients commencing allocated treatment (radiotherapy [RT] alone, n = 157; CRT, n = 153). Two hundred thirty-eight patients (77%) had high-risk nodal disease, 59 (19%) had high-risk primary or in-transit disease, and 13 (4%) had both. Median follow-up was 60 months. Median RT dose was 60 Gy, with 84% of patients randomly assigned to CRT completing six cycles of carboplatin. The 2- and 5-year FFLRR rates were 88% (95% CI, 83% to 93%) and 83% (95% CI, 77% to 90%), respectively, for RT and 89% (95% CI, 84% to 94%) and 87% (95% CI, 81% to 93%; hazard ratio, 0.84; 95% CI, 0.46 to 1.55; P = .58), respectively, for CRT. There were no significant differences in disease-free or overall survival. Locoregional failure was the most common site of first treatment failure, with isolated distant metastases as the first site of failure seen in 7% of both arms. Treatment was well tolerated in both arms, with no observed enhancement of RT toxicity with carboplatin. Grade 3 or 4 late toxicities were infrequent. Conclusion Although surgery and postoperative RT provided excellent FFLRR, there was no observed benefit with the addition of weekly carboplatin.

A Phase I/II Trial of Gefitinib Given Concurrently With Radiotherapy in Patients With Nonmetastatic Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Joensuu, Greetta; International Comprehensive Cancer Center Docrates, Helsinki; Joensuu, Timo

Purpose: To estimate the safety and tolerability of daily administration of 250 mg of gefitinib given concurrently with three-dimensional conformal radiotherapy for patients with nonmetastatic prostate cancer. Methods and Materials: A total of 42 patients with T2-T3N0M0 tumors were treated in a nonrandomized single-center study. A prostate-specific antigen (PSA) level of <20 and a good performance status (WHO, 0-1) were required. Adjuvant or neoadjuvant hormone treatments were not allowed. A daily regimen of 250 mg of gefitinib was started 1 week before radiation therapy began and lasted for the duration of radiation therapy. A dose of 50.4 Gy (1.8 Gy/day)more » was administered to the tumor, prostate, and seminal vesicles, followed by a 22-Gy booster (2 Gy/day) for a total dose of 72.4 Gy. Correlative studies included analysis of epidermal growth factor receptor (EGFR), EGFRvIII, and phosphorylated EGFR in tumors and tumor necrosis factor, interleukin-1{alpha} (IL-1{alpha}), and IL-6 in serum. Results: Maximum tolerated dose was not reached in phase I (12 patients), and 30 additional patients were treated in phase II. Thirty (71.4%) patients completed trial medication. Dose-limiting toxicities were recorded for 16 (38.1%) patients, the most common of which was a grade 3 to 4 increase in transaminase (6 patients). After a median follow-up of 38 months, there were no deaths due to prostate cancer. The estimated PSA relapse-free survival rate at 4 years (Kaplan-Meier) was 97%, the salvage therapy-free survival rate was 91%, and the overall survival rate was 87%. These figures compared favorably with those of matched patients treated with radiation only at higher doses. Conclusions: The combination of gefitinib and radiation is reasonably well tolerated and has promising activity against nonmetastatic prostate cancer.« less

Efficacy and Safety of Low-Dose-Rate Endorectal Brachytherapy as a Boost to Neoadjuvant Chemoradiation in the Treatment of Locally Advanced Distal Rectal Cancer: A Phase-II Clinical Trial

PubMed Central

Omidvari, Shapour; Zohourinia, Shadi; Ansari, Mansour; Ghahramani, Leila; Zare-Bandamiri, Mohammad; Mosalaei, Ahmad; Ahmadloo, Niloofar; Pourahmad, Saeedeh; Nasrolahi, Hamid; Hamedi, Sayed Hasan

2015-01-01

Purpose Despite advances in rectal cancer treatment over the last decade, local control and risk of late side effects due to external beam radiation therapy (EBRT) remain as concerns. The present study aimed to investigate the efficacy and the safety of low-dose-rate endorectal brachytherapy (LDRBT) as a boost to neoadjuvant chemoradiation for use in treating locally advanced distal rectal adenocarcinomas. Methods This phase-II clinical trial included 34 patients (as the study arm) with newly diagnosed, locally advanced (clinical T3-T4 and/or N1/N2, M0) lower rectal cancer. For comparative analysis, 102 matched patients (as the historical control arm) with rectal cancer were also selected. All the patients were treated with LDRBT (15 Gy in 3 fractions) and concurrent chemoradiation (45-50.4 Gy). Concurrent chemotherapy consisted of oxaliplatin 130 mg/m2 intravenously on day 1 plus oral capecitabine 825 mg/m2 twice daily during LDRBT and EBRT. Results The study results revealed a significant differences between the study arm and the control arm in terms in the pathologic tumor size (2.1 cm vs. 3.6 cm, P = 0.001), the pathologic tumor stage (35% T3-4 vs. 65% T3-4, P = 0.003), and the pathologic complete response (29.4% vs. 11.7%, P < 0.028). Moreover, a significantly higher dose of EBRT (P = 0.041) was found in the control arm, and a longer time to surgery was observed in the study arm (P < 0.001). The higher rate of treatment-related toxicities, such as mild proctitis and anemia, in the study arm was tolerable and easily manageable. Conclusion A boost of LDRBT can optimize the pathologic complete response, with acceptable toxicities, in patients with distal rectal cancer. PMID:26361613

Efficacy and Safety of Low-Dose-Rate Endorectal Brachytherapy as a Boost to Neoadjuvant Chemoradiation in the Treatment of Locally Advanced Distal Rectal Cancer: A Phase-II Clinical Trial.

PubMed

Omidvari, Shapour; Zohourinia, Shadi; Ansari, Mansour; Ghahramani, Leila; Zare-Bandamiri, Mohammad; Mosalaei, Ahmad; Ahmadloo, Niloofar; Pourahmad, Saeedeh; Nasrolahi, Hamid; Hamedi, Sayed Hasan; Mohammadianpanah, Mohammad

2015-08-01

Despite advances in rectal cancer treatment over the last decade, local control and risk of late side effects due to external beam radiation therapy (EBRT) remain as concerns. The present study aimed to investigate the efficacy and the safety of low-dose-rate endorectal brachytherapy (LDRBT) as a boost to neoadjuvant chemoradiation for use in treating locally advanced distal rectal adenocarcinomas. This phase-II clinical trial included 34 patients (as the study arm) with newly diagnosed, locally advanced (clinical T3-T4 and/or N1/N2, M0) lower rectal cancer. For comparative analysis, 102 matched patients (as the historical control arm) with rectal cancer were also selected. All the patients were treated with LDRBT (15 Gy in 3 fractions) and concurrent chemoradiation (45-50.4 Gy). Concurrent chemotherapy consisted of oxaliplatin 130 mg/m(2) intravenously on day 1 plus oral capecitabine 825 mg/m(2) twice daily during LDRBT and EBRT. The study results revealed a significant differences between the study arm and the control arm in terms in the pathologic tumor size (2.1 cm vs. 3.6 cm, P = 0.001), the pathologic tumor stage (35% T3-4 vs. 65% T3-4, P = 0.003), and the pathologic complete response (29.4% vs. 11.7%, P < 0.028). Moreover, a significantly higher dose of EBRT (P = 0.041) was found in the control arm, and a longer time to surgery was observed in the study arm (P < 0.001). The higher rate of treatment-related toxicities, such as mild proctitis and anemia, in the study arm was tolerable and easily manageable. A boost of LDRBT can optimize the pathologic complete response, with acceptable toxicities, in patients with distal rectal cancer.

Concurrent radiotherapy with temozolomide vs. concurrent radiotherapy with a cisplatinum-based polychemotherapy regimen : Acute toxicity in pediatric high-grade glioma patients.

PubMed

Seidel, Clemens; von Bueren, André O; Bojko, Sabrina; Hoffmann, Marion; Pietsch, Torsten; Gielen, Gerrit H; Warmuth-Metz, Monika; Bison, Brigitte; Kortmann, Rolf-D; Kramm, Christof M

2018-03-01

As the efficacy of all pediatric high-grade glioma (HGG) treatments is similar and still disappointing, it is essential to also investigate the toxicity of available treatments. Prospectively recorded hematologic and nonhematologic toxicities of children treated with radiochemotherapy in the HIT GBM-C/D and HIT-HGG-2007 trials were compared. Children aged 3-18 years with histologically proven HGG (WHO grade III and IV tumors) or unequivocal radiologic diagnosis of diffuse intrinsic pontine glioma (DIPG) were included in these trials. The HIT-HGG-2007 protocol comprised concomitant radiochemotherapy with temozolomide, while cisplatinum/etoposide (PE) and PE plus ifosfamide (PEI) in combination with weekly vincristine injections were applied during radiochemotherapy in the HIT GBM-C/D protocol. Regular blood counts and information about cellular nadirs were available from 304 patients (leukocytes) and 306 patients (thrombocytes), respectively. Grade 3-4 leukopenia was much more frequent in the HIT GBM-C/D cohort (n = 88, 52%) vs. HIT-HGG-2007 (n = 13, 10%; P <0.001). Grade 3-4 thrombopenia was also more likely in the HIT GBM-C/D cohort (n = 21, 12% vs. n = 3,2%; P <0.001). Grade 3-4 leukopenia appeared more often in children aged 3-7 years (n = 38/85, 45%) than in children aged 8-12 years (n = 39/120, 33%) and 13-18 years (24/100, 24%; P =0.034). In addition, sickness was more frequent in the HIT GBM-C/D cohort (grade 1-2: 44%, grade 3-4: 6% vs. grade 1-2: 28%, grade 3-4: 1%; P <0.001). Radiochemotherapy involving cisplatinum-based polychemotherapy is more toxic than radiotherapy in combination with temozolomide. Without evidence of differences in therapeutic efficacy, the treatment with lower toxicity, i. e., radiotherapy with temozolomide should be used.

Whey protein, amino acids, and vitamin D supplementation with physical activity increases fat-free mass and strength, functionality, and quality of life and decreases inflammation in sarcopenic elderly.

PubMed

Rondanelli, Mariangela; Klersy, Catherine; Terracol, Gilles; Talluri, Jacopo; Maugeri, Roberto; Guido, Davide; Faliva, Milena A; Solerte, Bruno S; Fioravanti, Marisa; Lukaski, Henry; Perna, Simone

2016-03-01

Interventions to attenuate the adverse effects of age-related loss of skeletal muscle and function include increased physical activity and nutritional supplementation. This study tested the hypothesis that nutritional supplementation with whey protein (22 g), essential amino acids (10.9 g, including 4 g leucine), and vitamin D [2.5 μg (100 IU)] concurrent with regular, controlled physical activity would increase fat-free mass, strength, physical function, and quality of life, and reduce the risk of malnutrition in sarcopenic elderly persons. A total of 130 sarcopenic elderly people (53 men and 77 women; mean age: 80.3 y) participated in a 12-wk randomized, double-blind, placebo-controlled supplementation trial. All participants concurrently took part in a controlled physical activity program. We examined body composition with dual-energy X-ray absorptiometry, muscle strength with a handgrip dynamometer, and blood biochemical indexes of nutritional and health status, and evaluated global nutritional status, physical function, and quality of life before and after the 12 wk of intervention. Compared with physical activity and placebo, supplementation plus physical activity increased fat-free mass (1.7-kg gain, P < 0.001), relative skeletal muscle mass (P = 0.009), android distribution of fat (P = 0.021), handgrip strength (P = 0.001), standardized summary scores for physical components (P = 0.030), activities of daily living (P = 0.001), mini nutritional assessment (P = 0.003), and insulin-like growth factor I (P = 0.002), and lowered C-reactive protein (P = 0.038). Supplementation with whey protein, essential amino acids, and vitamin D, in conjunction with age-appropriate exercise, not only boosts fat-free mass and strength but also enhances other aspects that contribute to well-being in sarcopenic elderly. This trial was registered at clinicaltrials.gov as NCT02402608. © 2016 American Society for Nutrition.

Phase 2 Trial of De-intensified Chemoradiation Therapy for Favorable-Risk Human Papillomavirus–Associated Oropharyngeal Squamous Cell Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chera, Bhishamjit S., E-mail: bchera@med.unc.edu; Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina; Amdur, Robert J.

Purpose: To perform a prospective, multi-institutional, phase 2 study of a substantial decrease in concurrent chemoradiation therapy (CRT) intensity as primary treatment for favorable-risk, human papillomavirus–associated oropharyngeal squamous cell carcinoma. Methods and Materials: The major inclusion criteria were: (1) T0 to T3, N0 to N2c, M0; (2) human papillomavirus or p16 positive; and (3) minimal/remote smoking history. Treatment was limited to 60 Gy intensity modulated radiation therapy with concurrent weekly intravenous cisplatinum (30 mg/m{sup 2}). The primary study endpoint was pathologic complete response (pCR) rate based on required biopsy of the primary site and dissection of pretreatment positive lymph node regions, regardless ofmore » radiographic response. Power computations were performed for the null hypothesis that the pCR rate is 87% and n=40, resulting in a type 1 error of 14.2%. Secondary endpoint measures included physician-reported toxicity (Common Toxicity Terminology for Adverse Events, CTCAE), patient-reported symptoms (PRO-CTCAE), and modified barium swallow studies. Results: The study population was 43 patients. The pCR rate was 86% (37 of 43). The incidence of CTCAE grade 3/4 toxicity and PRO-CTCAE severe/very severe symptoms was as follows: mucositis 34%/45%, general pain 5%/48%, nausea 18%/52%, vomiting 5%/34%, dysphagia 39%/55%, and xerostomia 2%/75%. Grade 3/4 hematologic toxicities were 11%. Thirty-nine percent of patients required a feeding tube for a median of 15 weeks (range, 5-22 weeks). There were no significant differences in modified barium swallow studies before and after CRT. Conclusions: The pCR rate with decreased intensity of therapy with 60 Gy of IMRT and weekly low-dose cisplatinum is very high in favorable-risk oropharyngeal squamous cell carcinoma, with evidence of decreased toxicity compared with standard therapies. (ClinicalTrials.gov) ID: (NCT01530997).« less

Adaptive/nonadaptive proton radiation planning and outcomes in a phase II trial for locally advanced non-small cell lung cancer.

PubMed

Koay, Eugene J; Lege, David; Mohan, Radhe; Komaki, Ritsuko; Cox, James D; Chang, Joe Y

2012-12-01

To analyze dosimetric variables and outcomes after adaptive replanning of radiation therapy during concurrent high-dose protons and chemotherapy for locally advanced non-small cell lung cancer (NSCLC). Nine of 44 patients with stage III NSCLC in a prospective phase II trial of concurrent paclitaxel/carboplatin with proton radiation [74 Gy(RBE) in 37 fractions] had modifications to their original treatment plans after re-evaluation revealed changes that would compromise coverage of the target volume or violate dose constraints; plans for the other 35 patients were not changed. We compared patients with adaptive plans with those with nonadaptive plans in terms of dosimetry and outcomes. At a median follow-up of 21.2 months (median overall survival, 29.6 months), no differences were found in local, regional, or distant failure or overall survival between groups. Adaptive planning was used more often for large tumors that shrank to a greater extent (median, 107.1 cm(3) adaptive and 86.4 cm(3) nonadaptive; median changes in volume, 25.3% adaptive and 1.2% nonadaptive; P<.01). The median number of fractions delivered using adaptive planning was 13 (range, 4-22). Adaptive planning generally improved sparing of the esophagus (median absolute decrease in V(70), 1.8%; range, 0%-22.9%) and spinal cord (median absolute change in maximum dose, 3.7 Gy; range, 0-13.8 Gy). Without adaptive replanning, target coverage would have been compromised in 2 cases (57% and 82% coverage without adaptation vs 100% for both with adaptation); neither patient experienced local failure. Radiation-related grade 3 toxicity rates were similar between groups. Adaptive planning can reduce normal tissue doses and prevent target misses, particularly for patients with large tumors that shrink substantially during therapy. Adaptive plans seem to have acceptable toxicity and achieve similar local, regional, and distant control and overall survival, even in patients with larger tumors, vs nonadaptive plans. Copyright © 2012 Elsevier Inc. All rights reserved.

Longitudinal increase in vitamin D binding protein levels after initiation of tenofovir/lamivudine/efavirenz among individuals with HIV.

PubMed

Hsieh, Evelyn; Fraenkel, Liana; Han, Yang; Xia, Weibo; Insogna, Karl L; Yin, Michael T; Zhu, Ting; Cheng, Xinqi; Li, Taisheng

2016-07-31

To examine longitudinal change in vitamin D binding protein (DBP) levels during the first year after initiation of tenofovir disoproxil fumarate (TDF)/lamivudine/efavirenz and compare these findings with concurrent changes in markers of skeletal metabolism. Secondary analysis of plasma samples collected from an ongoing multicenter clinical trial. Plasma samples collected at 0, 24, and 48 weeks after initiation of TDF + lamivudine + efavirenz from 134 adult participants enrolled in a multicenter randomized trial were analyzed. Data regarding sociodemographic and clinical characteristics were obtained as part of the parent study. Laboratory analyses included plasma DBP, intact parathyroid hormone, total 25-hydroxy vitamin D, phosphorus, the bone resorption marker collagen type 1 cross-linked C-telopeptide, and the bone formation marker total procollagen type 1 N-terminal propeptide. Repeated measures analysis of variance was used to measure changes in biomarkers over time. Our sample included 108 men and 26 women (mean age 33.6 ± 9.6 years). Median levels of DBP increased significantly from baseline to 48 weeks [154 (91.8-257.4) versus 198.3 (119.6-351.9) μg/ml, P < 0.001]. A concurrent rise in intact parathyroid hormone levels was observed over the same period [32.3 (24.4-40.9) versus 45.2 (35.1-60.4) pg/ml, P < 0.001]; however, 25-hydroxy vitamin D and phosphorus levels remained stable. Bone resorption and formation markers rapidly increased from 0 to 24 weeks, followed by a slight decline or plateau, but remained significantly elevated at 48 weeks (P < 0.001). Our study provides longitudinal data supporting a potential role for DBP in bone loss associated with TDF-based therapy. Further research to elucidate the mechanistic pathways and clinical impact of these findings is warranted.

Micronutrient supplementation in adults with HIV infection.

PubMed

Visser, Marianne E; Durao, Solange; Sinclair, David; Irlam, James H; Siegfried, Nandi

2017-05-18

Micronutrient deficiencies are common among adults living with HIV disease, particularly in low-income settings where the diet may be low in essential vitamins and minerals. Some micronutrients play critical roles in maintenance of the immune system, and routine supplementation could therefore be beneficial. This is an update of a Cochrane Review previously published in 2010. To assess whether micronutrient supplements are effective and safe in reducing mortality and HIV-related morbidity of HIV-positive adults (excluding pregnant women). We performed literature searches from January 2010 to 18 November 2016 for new randomized controlled trials (RCTs) of micronutrient supplements since the previous review included all trials identified from searches prior to 2010. We searched the CENTRAL (the Cochrane Library), Embase, and PubMed databases. Also we checked the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and the ClinicalTrials.gov trials registers. We also checked the reference lists of all new included trials. We included RCTs that compared supplements that contained either single, dual, or multiple micronutrients with placebo, no treatment, or other supplements. We excluded studies that were primarily designed to investigate the role of micronutrients for the treatment of HIV-positive participants with metabolic morbidity related to highly active antiretroviral therapy (HAART). Primary outcomes included all-cause mortality, morbidity, and disease progression. Two review authors independently selected trials for inclusion, and appraised trial quality for risk of bias. Where possible, we presented results as risk ratios (RR) for dichotomous variables, as hazard ratios (HRs) for time-to-event data, and as mean differences (MD) for continuous variables, each with 95% confidence intervals (CIs). Since we were often unable to pool the outcome data, we tabulated it for each comparison. We assessed the certainty of the evidence using the GRADE approach. We included 33 trials with 10,325 participants, of which 17 trials were new trials. Ten trials compared a daily multiple micronutrient supplement to placebo in doses up to 20 times the dietary reference intake, and one trial compared a daily standard dose with a high daily dose of multivitamins. Nineteen trials compared supplementation with single or dual micronutrients (such as vitamins A and D, zinc, and selenium) to placebo, and three trials compared different dosages or combinations of micronutrients. Multiple micronutrientsWe conducted analyses across antiretroviral therapy (ART)-naive adults (3 trials, 1448 participants), adults on antiretroviral therapy (ART) (1 trial, 400 participants), and ART-naive adults with concurrent active tuberculosis (3 trials, 1429 participants). Routine multiple micronutrient supplementation may have little or no effect on mortality in adults living with HIV (RR 0.91, 95% CI 0.72 to 1.15; 7 trials, 2897 participants, low certainty evidence).Routine supplementation for up to two years may have little or no effect on the average of mean CD4+ cell count (MD 26.40 cells/mm³, 95% CI -22.91 to 75.70; 6 trials, 1581 participants, low certainty evidence), or the average of mean viral load (MD -0.1 log 10 viral copies, 95% CI -0.26 to 0.06; 4 trials, 840 participants, moderate certainty evidence). One additional trial in ART-naïve adults did report an increase in the time to reach a CD4+ cell count < 250 cells/mm³ after two years of high dose supplementation in Botswana (HR 0.48, 95% CI 0.26 to 0.88; 1 trial, 439 participants). However, the trial authors reported this effect only in the trial arm that received multiple micronutrients plus selenium (not either supplementation alone), which is inconsistent with the findings of other trials that used similar combinations of micronutrients and selenium.In one additional trial that compared high-dose multiple micronutrient supplementation with standard doses in people on ART, peripheral neuropathy was lower with high dose supplements compared to standard dose (incidence rate ratio (IRR) 0.81, 95% CI 0.7 to 0.94; 1 trial, 3418 participants), but the trial was stopped early due to increased adverse events (elevated alanine transaminase (ALT) levels) in the high dose group. Single or dual micronutrientsNone of the trials of single or dual micronutrient supplements were adequately powered to assess for effects on mortality or morbidity outcomes. No clinically significant changes in CD4 cell count (data not pooled, 14 trials, 2370 participants, very low or low certainty evidence) or viral load (data not pooled, seven studies, 1334 participants, very low or low certainty evidence), were reported. Supplementation probably does increase blood concentrations of vitamin D and zinc (data not pooled, vitamin D: 4 trials, 299 participants, zinc: 4 trials, 484 participants, moderate certainty evidence) and may also increase blood concentrations of vitamin A (data not pooled, 3 trials, 495 participants, low certainty evidence), especially in those who are deficient. The analyses of the available trials have not revealed consistent clinically important benefits with routine multiple micronutrient supplementation in people living with HIV. Larger trials might reveal small but important effects.These findings should not be interpreted as a reason to deny micronutrient supplements for people living with HIV where specific deficiencies are found or where the person's diet is insufficient to meet the recommended daily allowance of vitamins and minerals.

Symptoms after Ingestion of Pig Whipworm Trichuris suis Eggs in a Randomized Placebo-Controlled Double-Blind Clinical Trial

PubMed Central

Bager, Peter; Kapel, Christian; Roepstorff, Allan; Thamsborg, Stig; Arnved, John; Rønborg, Steen; Kristensen, Bjarne; Poulsen, Lars K.; Wohlfahrt, Jan; Melbye, Mads

2011-01-01

Symptoms after human infection with the helminth Trichuris suis have not previously been described. Exposure to helminths has been suggested as immune therapy against allergy and autoimmune diseases. We randomized adults with allergic rhinitis to ingest a dose of 2500 T. suis eggs or placebo every 21 days for 168 days (total 8 doses) in a double-blind clinical trial. In a previous publication, we reported a lack of efficacy and a high prevalence of adverse gastrointestinal reactions. The aim of the present study was to present a detailed description of the adverse event data and post-hoc analyses of gastrointestinal reactions. Adverse events and severity (mild, moderate, severe) were recorded daily by subjects, classified by organ using MedDRA 10.0, and event rates compared between subjects on T. suis treatment vs. subjects on placebo. T. suis-specific serum IgG antibodies were measured by a fluoroenzymeimmunoassay (Phadia ApS). During 163 days complete follow-up, subjects ingesting T. suis eggs (N = 49) had a three to 19-fold higher rate of events (median duration, 2 days) with gastrointestinal reactions (moderate to severe flatulence, diarrhea, and upper abdominal pain) compared with placebo subjects (N = 47). The highest incidence of affected subjects was seen from the first few days and until day 42 (3rd dose): 63% vs. 29% for placebo; day 163: 76% vs. 49% for placebo. Seroprevalences increased concurrently in the T. suis group: Day 59, 50%; day 90, 91%; day 170, 93%. The combined duration of episodes with onset before day 42 was ≤14 days in 80% of affected subjects. Age, gender, total IgE, and recent intestinal symptoms at baseline did not predict gastrointestinal side effects. In conclusion, during the first 2 months, repeated ingestions of 2500 T. suis eggs caused frequent gastrointestinal reactions lasting up to 14 days, whereas 4 months further treatment mainly provoked a subclinical stimulation. Trial registration University hospital Medical Information Network trial registry Reg. no. R000001298, Trial ID UMIN000001070. PMID:21829616

Effectiveness of concurrent procedures during high tibial osteotomy for medial compartment osteoarthritis: a systematic review and meta-analysis.

PubMed

Lee, O-Sung; Ahn, Soyeon; Ahn, Jin Hwan; Teo, Seow Hui; Lee, Yong Seuk

2018-02-01

The purpose of this systematic review and meta-analysis was to evaluate the efficacy of concurrent cartilage procedures during high tibial osteotomy (HTO) for medial compartment osteoarthritis (OA) by comparing the outcomes of studies that directly compared the use of HTO plus concurrent cartilage procedures versus HTO alone. Results that are possible to be compared in more than two articles were presented as forest plots. A 95% confidence interval was calculated for each effect size, and we calculated the I 2 statistic, which presents the percentage of total variation attributable to the heterogeneity among studies. The random effects model was used to calculate the effect size. Seven articles were included to the final analysis. Case groups were composed of HTO without concurrent procedures and control groups were composed of HTO with concurrent procedures such as marrow stimulation procedure, mesenchymal stem cell transplantation, and injection. The case group showed a higher hospital for special surgery score and mean difference was 4.10 [I 2 80.8%, 95% confidence interval (CI) - 9.02 to 4.82]. Mean difference of the mechanical femorotibial angle in five studies was 0.08° (I 2 0%, 95% CI - 0.26 to 0.43). However, improved arthroscopic, histologic, and MRI results were reported in the control group. Our analysis support that concurrent procedures during HTO for medial compartment OA have little beneficial effect regarding clinical and radiological outcomes. However, they might have some beneficial effects in terms of arthroscopic, histologic, and MRI findings even though the quality of healed cartilage is not good as that of original cartilage. Therefore, until now, concurrent procedures for medial compartment OA have been considered optional. Nevertheless, no conclusions can be drawn for younger patients with focal cartilage defects and concomitant varus deformity. This question needs to be addressed separately.

Comparing Perceived Learning Experiences of Two Concurrent Cohorts under Curriculum Reform in Hong Kong: A Multiple-Group Confirmatory Factor Analysis Approach

ERIC Educational Resources Information Center

Zhao, Yue; Huen, Jenny M. Y.; Prosser, Michael

2017-01-01

Purpose: Hong Kong has undergone extensive curriculum reform and shifted from a three-year to a four-year university system. With a nuanced look at the impact of the curriculum reform, the purpose of the present study was to compare two concurrent cohorts by examining the extent to which the students in each cohort perceived their learning…

An Alternative to the Stay/Switch Equation Assessed When Using a Changeover-Delay

PubMed Central

MacDonall, James S.

2015-01-01

An alternative to the generalized matching equation for understanding concurrent performances is the stay/switch model. For the stay/switch model, the important events are the contingencies and behaviors at each alternative. The current experiment compares the descriptions by two stay/switch equations, the original, empirically derived stay/switch equation and a more theoretically derived equation based on ratios of stay to switch responses matching ratios of stay to switch reinforcers. The present experiment compared descriptions by the original stay/switch equation when using and not using a changeover delay. It also compared descriptions by the more theoretical equation with and without a changeover delay. Finally, it compared descriptions of the concurrent performances by these two equations. Rats were trained in 15 conditions on identical concurrent random-interval schedules in each component of a multiple schedule. A COD operated in only one component. There were no consistent differences in the variance accounted for by each equation of concurrent performances whether or not a COD was used. The simpler equation found greater sensitivity to stay than to switch reinforcers. It also found a COD eliminated the influence of switch reinforcers. Because estimates of parameters were more meaningful when using the more theoretical stay/switch equation it is preferred. PMID:26299548

An alternative to the stay/switch equation assessed when using a changeover-delay.

PubMed

MacDonall, James S

2015-11-01

An alternative to the generalized matching equation for understanding concurrent performances is the stay/switch model. For the stay/switch model, the important events are the contingencies and behaviors at each alternative. The current experiment compares the descriptions by two stay/switch equations, the original, empirically derived stay/switch equation and a more theoretically derived equation based on ratios of stay to switch responses matching ratios of stay to switch reinforcers. The present experiment compared descriptions by the original stay/switch equation when using and not using a changeover delay. It also compared descriptions by the more theoretical equation with and without a changeover delay. Finally, it compared descriptions of the concurrent performances by these two equations. Rats were trained in 15 conditions on identical concurrent random-interval schedules in each component of a multiple schedule. A COD operated in only one component. There were no consistent differences in the variance accounted for by each equation of concurrent performances whether or not a COD was used. The simpler equation found greater sensitivity to stay than to switch reinforcers. It also found a COD eliminated the influence of switch reinforcers. Because estimates of parameters were more meaningful when using the more theoretical stay/switch equation it is preferred. Copyright © 2015 Elsevier B.V. All rights reserved.

Concurrent Disorders and Health Care Utilization Among Homeless and Vulnerably Housed Persons in Canada.

PubMed

Zhang, Linda; Norena, Monica; Gadermann, Anne; Hubley, Anita; Russell, Lara; Aubry, Tim; To, Matthew J; Farrell, Susan; Hwang, Stephen; Palepu, Anita

2018-01-01

Individuals who are homeless or vulnerably housed have a higher prevalence of concurrent disorders, defined as having a mental health diagnosis and problematic substance use, compared to the general housed population. The study objective was to investigate the effect of having concurrent disorders on health care utilization among homeless or vulnerably housed individuals, using longitudinal data from the Health and Housing in Transition Study. In 2009, 1190 homeless or vulnerably housed adults were recruited in Ottawa, Toronto, and Vancouver, Canada. Participants completed baseline interviews and four annual follow-up interviews, providing data on sociodemographics, housing history, mental health diagnoses, problematic drug use with the Drug Abuse Screening Test (DAST-10), problematic alcohol use with the Alcohol Use Disorders Identification Test (AUDIT), chronic health conditions, and utilization of the following health care services: emergency department (ED), hospitalization, and primary care. Concurrent disorders were defined as the participant having ever received a mental health diagnosis at baseline and having problematic substance use (i.e., DAST-10 ≥ 6 and/or AUDIT ≥ 20) at any time during the study period. Three generalized mixed effects logistic regression models were used to examine the independent association of having concurrent disorders and reporting ED use, hospitalization, or primary care visits in the past 12 months. Among our sample of adults who were homeless or vulnerably housed, 22.6% (n = 261) reported having concurrent disorders at baseline. Individuals with concurrent disorders had significantly higher odds of ED use (adjusted odds ratio [AOR] = 1.71; 95% confidence interval [CI], 1.4-2.11), hospitalization (AOR = 1.45; 95% CI, 1.16-1.81), and primary care visits (AOR = 1.34; 95% CI, 1.05-1.71) in the past 12 months over the four-year follow-up period, after adjusting for potential confounders. Concurrent disorders were associated with higher rates of health care utilization when compared to those without concurrent disorders among homeless and vulnerably housed individuals. Comprehensive programs that integrate mental health and addiction services with primary care as well as community-based outreach may better address the unmet health care needs of individuals living with concurrent disorders who are vulnerable to poor health outcomes.

Species-specificity of equine and porcine Lawsonia intracellularis isolates in laboratory animals

PubMed Central

Sampieri, Francesca; Vannucci, Fabio A.; Allen, Andrew L.; Pusterla, Nicola; Antonopoulos, Aphroditi J.; Ball, Katherine R.; Thompson, Julie; Dowling, Patricia M.; Hamilton, Don L.; Gebhart, Connie J.

2013-01-01

Lawsonia intracellularis infection causes proliferative enteropathy (PE) in many mammalian species, with porcine and equine proliferative enteropathy (PPE and EPE) known worldwide. Hamsters are a well-published animal model for PPE infection studies in pigs. There is no laboratory animal model for EPE infection studies and it is not known whether there is species-specificity for equine or porcine isolates of L. intracellularis in animal models. The objective of this study was to determine whether it is possible to generate typical EPE lesions in hamsters after inoculation with an equine strain of L. intracellularis (EPE strain) and whether it is comparatively possible to generate PPE lesions in rabbits after inoculation with a porcine strain of L. intracellularis (PPE strain). In 2 separate trials, 4-week-old and 3-week-old weanling golden Syrian hamsters were challenged with EPE strains and compared to uninfected (both trials) and PPE-infected controls (Trial 2 only). Concurrently, 6 female New Zealand white juvenile rabbits were infected with PPE strain and observed concomitantly to 8 similar rabbits infected with EPE strain for a different experiment. Hamsters and rabbits were observed for 21 to 24 days post-infection (DPI), depending on the experiment. Neither infected species developed clinical signs. The presence of disease was assessed with diagnostic techniques classically used for pigs and horses: immune-peroxidase monolayer assay on sera; quantitative polymerase chain reaction (qPCR) detection of molecular DNA in feces; and hematoxylin and eosin (H&E) stain and immunohistochemistry (IHC) on intestinal tissues. Our results showed that EPE-challenged hamsters do not develop infection when compared with PPE controls (IHC, P = 0.009; qPCR, P = 0.0003). Conversely, PPE-challenged rabbits do not develop typical intestinal lesions in comparison to EPE-challenged rabbits, with serological response at 14 DPI being significantly lower (P = 0.0023). In conclusion, PPE and EPE strains appear to have different host-specificities for hamsters and rabbits, respectively. PMID:24124268

Predictors of pulmonary toxicity in limited stage small cell lung cancer patients treated with induction chemotherapy followed by concurrent platinum-based chemotherapy and 70 Gy daily radiotherapy: CALGB 30904.

PubMed

Salama, Joseph K; Pang, Herbert; Bogart, Jeffrey A; Blackstock, A William; Urbanic, James J; Hogson, Lydia; Crawford, Jeffrey; Vokes, Everett E

2013-12-01

Standard therapy for limited stage small cell lung cancer (L-SCLC) is concurrent chemotherapy and radiotherapy followed by prophylactic cranial radiotherapy. Predictors of post chemoradiotherapy pulmonary toxicity in limited stage (LS) small cell lung cancer (SCLC) patients are not well defined. Current guidelines are derived from non-small cell lung cancer regimens, and do not account for the unique biology of this disease. Therefore, we analyzed patients on three consecutive CALGB LS-SCLC trials treated with concurrent chemotherapy and daily high dose radiotherapy (70 Gy) to determine patient and treatment related factors predicting for post-treatment pulmonary toxicity. Patients treated on CALGB protocols 39808, 30002, 30206 investigating two cycles of chemotherapy followed by concurrent chemotherapy and 70 Gy daily thoracic radiation therapy were pooled. Patient, tumor, and treatment related factors were evaluated to determine predictors of grade 3–5 pulmonary toxicities after concurrent chemoradiotherapy. 100 patients were included. No patient experienced grade 4–5 post-treatment pulmonary toxicity. Patients who experienced post-treatment pulmonary toxicity were more likely to be older (median age 69 vs 60, p = 0.09) and have smaller total lung volumes (2565 cc vs 3530 cc, p = 0.05).). Furthermore,exposure of larger volumes of lung to lower (median V5 = 70%, p = 0.09, median V10 = 63%, p = 0.07), inter-mediate (median V20 = 50, p = 0.04) and high (median V60 = 25%, p = 0.01) doses of radiation were all associated with post-treatment grade 3 pulmonary toxicity, as was a larger mean lung radiation dose(median 31 Gy) p = 0.019. Post-treatment pulmonary toxicity following the completion of 2 cycles of chemotherapy followed by concurrent chemotherapy and high dose daily radiation therapy was uncommon. Care should be taken to minimize mean lung radiation exposure, as well as volumes of low, intermediate and high doses of radiation.

Cost-effectiveness of using a motion-sensor biofeedback treatment approach for the management of sub-acute or chronic low back pain: economic evaluation alongside a randomised trial.

PubMed

Haines, Terry; Bowles, Kelly-Ann

2017-01-17

Low back pain is a common and costly condition internationally. There is high need to identify effective and economically efficient means for managing this problem. This study aimed to explore the cost-effectiveness of a novel motion-sensor biofeedback treatment approach in addition to guidelines-based care compared to guidelines-based care alone, from a societal perspective over a 12 month time horizon. This was an incremental cost-effectiveness analysis conducted concurrently with a pilot, cluster randomized controlled trial. Health care resource use was collected using daily diaries and patient-self report at 3, 6 and 12 month follow-up assessments. Productivity was measured using industry classifications and participant self-reporting of ability to do their normal work with their present pain. Clinical effect was measured using the Patient Global Impression of Change measured at the 12 month follow-up assessment. Data were compared between groups using linear regression clustered by recruitment site. Bootstrap resampling was used to generate a visual representation of the 95% confidence interval for the incremental cost-effectiveness estimate. Two, one-way sensitivity analyses were undertaken to examine the robustness of findings to key assumptions. There were n = 38 participants in the intervention group who completed the 12 month assessment and n = 45 in the control. The intervention group had greater use of trial-related medical and therapy resources [$477 per participant (95% CI: $447, $508)], but lower use of non-trial medical and therapy resources [$-53 per participant (95% CI: $-105, $-0)], and a greater improvement in productivity [$-5123 per participant (95% CI: $-10,174, $-72)]. Overall, the intervention dominated with a saving of $478,100 and an additional 41 participants self-rating as being very or much improved compared to the control. There was >99% confidence in this finding of dominance in both the primary and sensitivity analyses. The motion-sensor biofeedback treatment approach in addition to guidelines- based care appears to be both more clinically effective and economically efficient than guidelines- based care alone. This approach appears to be a viable means to manage low back pain and further research in this area should be a priority. The randomised trial this research was based upon was prospectively registered on March 25th 2009 with the Australian New Zealand Clinical Trials Registry: ACTRN12609000157279 .

Outcome of dialectical behaviour therapy for concurrent eating and substance use disorders.

PubMed

Courbasson, Christine; Nishikawa, Yasunori; Dixon, Lauren

2012-09-01

The current study examined the preliminary efficacy of dialectical behaviour therapy (DBT) adapted for concurrent eating disorders (EDs) and substance use disorders (SUDs). A matched randomized controlled trial was carried out with 25 female outpatients diagnosed with concurrent ED and SUD. Participants randomized to the intervention condition received DBT, whereas those randomized to the control condition received treatment as usual (TAU), both for a period of 1 year. A series of measures related to disordered eating, substance use and depression were administered to the participants at the beginning of treatment and at 3, 6, 9 and 12 months into treatment, followed by 3-month and 6-month follow-up assessments. Participants randomized to the DBT condition evidenced a superior retention rate relative to their counterparts in the TAU condition at various study time points, including post-treatment (80% versus 20%) and follow-up (60% versus 20%). Due to the unexpected elevated dropout rates and the worsening of ED-SUD symptomatology in the TAU condition, recruitment efforts were terminated early. Results from the DBT condition revealed that the intervention had a significant positive effect on behavioural and attitudinal features of disordered eating, substance use severity and use, negative mood regulation and depressive symptoms. Finally, increases in participants' perceived ability to regulate and cope with negative emotional states were significantly associated with decreases in emotional eating and increases in levels of confidence in ability to resist urges for substance use. Results suggest that the adapted DBT might hold promise for treating individuals with concurrent ED and SUD. The current study is the first study to report positive effects of DBT on individuals with concurrent eating and substance use disorders. Although the results require replication and extension, they suggest that the DBT may be promising for this population. The results suggest that clinicians treating individuals with concurrent eating and substance use problems should be particularly cautious of poor treatment retention and treatment complications. The results bear upon the highly salient and important issue of whether individuals with concurrent substance use need to be excluded from research studies and treatment programmes. Copyright © 2011 John Wiley & Sons, Ltd.

Very light smoking and alternative tobacco use among college students.

PubMed

Li, Xiaoyin; Loukas, Alexandra; Perry, Cheryl L

2018-06-01

Concurrent use of cigarettes with alternative tobacco products (ATPs), even among very light smokers, may be harmful. This study examined current use of e-cigarettes, cigars, and hookah, and susceptibility to future use of these products in a sample of college student cigarette smokers. Participants were 1161 18-29 year old (M age = 21.15; SD = 2.72; 52.7% female; 41.2% non-Hispanic white) current, or past 30-day cigarette smokers, drawn from a larger study. Current smokers were categorized as very light smokers [≤5 cigarettes per day (cpd)] and heavier smokers (>5 cpd). 88.6% of all participating college student smokers were very light smokers and 67.7% used at least one ATP concurrently. The prevalence of current use in this sample was 42.9% for e-cigarettes, 36.4% for hookah, and 25.9% for cigars. Compared to heavier smokers, very light smokers were more likely to be younger, racial/ethnic minorities, and four-year versus two-year college students. Multilevel logistic regression models showed that after controlling for socio-demographic characteristics and substance use, being a very light smoker, compared with a heavier smoker, was negatively associated with concurrent e-cigarette use, but positively associated with concurrent cigar use, and not associated with concurrent hookah use. Moreover, compared to heavier smokers, very light smokers reported being more susceptible to future cigar and hookah use, but not e-cigarette use. Concurrent use of cigarettes with ATPs is popular among all college student smokers, but very light smokers are more likely than heavier smokers to use combustible ATPs. Smoking intervention programs and campus policies should caution smokers, especially very light smokers, against ATP use. Copyright © 2018 Elsevier Ltd. All rights reserved.

Reliability and validity of bilateral ankle accelerometer algorithms for activity recognition and walking speed after stroke.

PubMed

Dobkin, Bruce H; Xu, Xiaoyu; Batalin, Maxim; Thomas, Seth; Kaiser, William

2011-08-01

Outcome measures of mobility for large stroke trials are limited to timed walks for short distances in a laboratory, step counters and ordinal scales of disability and quality of life. Continuous monitoring and outcome measurements of the type and quantity of activity in the community would provide direct data about daily performance, including compliance with exercise and skills practice during routine care and clinical trials. Twelve adults with impaired ambulation from hemiparetic stroke and 6 healthy controls wore triaxial accelerometers on their ankles. Walking speed for repeated outdoor walks was determined by machine-learning algorithms and compared to a stopwatch calculation of speed for distances not known to the algorithm. The reliability of recognizing walking, exercise, and cycling by the algorithms was compared to activity logs. A high correlation was found between stopwatch-measured outdoor walking speed and algorithm-calculated speed (Pearson coefficient, 0.98; P=0.001) and for repeated measures of algorithm-derived walking speed (P=0.01). Bouts of walking >5 steps, variations in walking speed, cycling, stair climbing, and leg exercises were correctly identified during a day in the community. Compared to healthy subjects, those with stroke were, as expected, more sedentary and slower, and their gait revealed high paretic-to-unaffected leg swing ratios. Test-retest reliability and concurrent and construct validity are high for activity pattern-recognition Bayesian algorithms developed from inertial sensors. This ratio scale data can provide real-world monitoring and outcome measurements of lower extremity activities and walking speed for stroke and rehabilitation studies.

Audiovisual integration facilitates monkeys' short-term memory.

PubMed

Bigelow, James; Poremba, Amy

2016-07-01

Many human behaviors are known to benefit from audiovisual integration, including language and communication, recognizing individuals, social decision making, and memory. Exceptionally little is known about the contributions of audiovisual integration to behavior in other primates. The current experiment investigated whether short-term memory in nonhuman primates is facilitated by the audiovisual presentation format. Three macaque monkeys that had previously learned an auditory delayed matching-to-sample (DMS) task were trained to perform a similar visual task, after which they were tested with a concurrent audiovisual DMS task with equal proportions of auditory, visual, and audiovisual trials. Parallel to outcomes in human studies, accuracy was higher and response times were faster on audiovisual trials than either unisensory trial type. Unexpectedly, two subjects exhibited superior unimodal performance on auditory trials, a finding that contrasts with previous studies, but likely reflects their training history. Our results provide the first demonstration of a bimodal memory advantage in nonhuman primates, lending further validation to their use as a model for understanding audiovisual integration and memory processing in humans.

Shared motion signals for human perceptual decisions and oculomotor actions

NASA Technical Reports Server (NTRS)

Stone, Leland S.; Krauzlis, Richard J.

2003-01-01

A fundamental question in primate neurobiology is to understand to what extent motor behaviors are driven by shared neural signals that also support conscious perception or by independent subconscious neural signals dedicated to motor control. Although it has clearly been established that cortical areas involved in processing visual motion support both perception and smooth pursuit eye movements, it remains unknown whether the same or different sets of neurons within these structures perform these two functions. Examination of the trial-by-trial variation in human perceptual and pursuit responses during a simultaneous psychophysical and oculomotor task reveals that the direction signals for pursuit and perception are not only similar on average but also co-vary on a trial-by-trial basis, even when performance is at or near chance and the decisions are determined largely by neural noise. We conclude that the neural signal encoding the direction of target motion that drives steady-state pursuit and supports concurrent perceptual judgments emanates from a shared ensemble of cortical neurons.

Associations among comorbid anxiety, psychiatric symptomatology, and diabetic control in a population with serious mental illness and diabetes: Findings from an interventional randomized controlled trial.

PubMed

Aftab, Awais; Bhat, Chetan; Gunzler, Douglas; Cassidy, Kristin; Thomas, Charles; McCormick, Richard; Dawson, Neal V; Sajatovic, Martha

2018-05-01

Objective Serious mental illness and type II diabetes mellitus have a high comorbidity, and both have a higher prevalence of anxiety disorders compared to the general population. Targeted Training in Illness Management is a group-based self-management training approach which targets serious mental illness and type II diabetes mellitus concurrently. This analysis examines data from a randomized controlled trial of Targeted Training in Illness Management intervention to examine the impact of comorbid anxiety on baseline psychiatric symptomatology and diabetic control, and on longitudinal treatment outcomes. Methods We conducted secondary analyses on data from a prospective, 60-week, randomized controlled trial testing Targeted Training in Illness Management versus treatment as usual in 200 individuals with serious mental illness and diabetes. Primary outcomes included measures related to serious mental illness symptoms, functional status, general health status, and diabetes control. Measures were compared between those participants with anxiety disorders versus those without anxiety at baseline as well as over time using linear mixed effects analyses. Results Forty seven percent of the participants had one or more anxiety disorders. At baseline, those with an anxiety diagnosis had higher illness severity, depressive, and other psychiatric symptomatology and disability. Diabetic control (HbA1c) was not significantly different at baseline. In the longitudinal analyses, no significant mean slope differences over time (group-by-time interaction effect) between those with anxiety diagnoses and those without in treatment as usual group were found for primary outcomes. Within the Targeted Training in Illness Management arm, those with anxiety disorders had significantly greater improvement in mental health functioning. Those with anxiety comorbidity in the Targeted Training in Illness Management group demonstrated significantly lower HbA1c levels compared to no anxiety comorbidity and also demonstrated a greater improvement in HbA1c over the first 30 weeks compared to those without anxiety comorbidity. Conclusion Comorbid anxiety in serious mental illness and type II diabetes mellitus population is associated with increased psychiatric symptomatology and greater disability. Individuals from this population appear to experience greater improvement in functioning from baseline with the Targeted Training in Illness Management intervention. Anxiety comorbidity in the serious mental illness and type II diabetes mellitus population does not appear to have a negative impact on diabetic control. These complex relationships need further study. Clinical Trials Registration ClinicalTrials.gov: Improving outcomes for individuals with serious mental illness and diabetes (NCT01410357).

Venetoclax responses of pediatric ALL xenografts reveal sensitivity of MLL-rearranged leukemia.

PubMed

Khaw, Seong Lin; Suryani, Santi; Evans, Kathryn; Richmond, Jennifer; Robbins, Alissa; Kurmasheva, Raushan T; Billups, Catherine A; Erickson, Stephen W; Guo, Yuelong; Houghton, Peter J; Smith, Malcolm A; Carol, Hernan; Roberts, Andrew W; Huang, David C S; Lock, Richard B

2016-09-08

The clinical success of the BCL-2-selective BH3-mimetic venetoclax in patients with poor prognosis chronic lymphocytic leukemia (CLL) highlights the potential of targeting the BCL-2-regulated apoptotic pathway in previously untreatable lymphoid malignancies. By selectively inhibiting BCL-2, venetoclax circumvents the dose-limiting, BCL-XL-mediated thrombocytopenia of its less selective predecessor navitoclax, while enhancing efficacy in CLL. We have previously reported the potent sensitivity of many high-risk childhood acute lymphoblastic leukemia (ALL) xenografts to navitoclax. Given the superior tolerability of venetoclax, here we have investigated its efficacy in childhood ALL. We demonstrate that in contrast to the clear dependence of CLL on BCL-2 alone, effective antileukemic activity in the majority of ALL xenografts requires concurrent inhibition of both BCL-2 and BCL-XL We identify BCL-XL expression as a key predictor of poor response to venetoclax and demonstrate that concurrent inhibition of both BCL-2 and BCL-XL results in synergistic killing in the majority of ALL xenografts. A notable exception is mixed lineage leukemia-rearranged infant ALL, where venetoclax largely recapitulates the activity of navitoclax, identifying this subgroup of patients as potential candidates for clinical trials of venetoclax in childhood ALL. Conversely, our findings provide a clear basis for progressing navitoclax into trials ahead of venetoclax in other subgroups.

A correlational method to concurrently measure envelope and temporal fine structure weights: effects of age, cochlear pathology, and spectral shaping.

PubMed

Fogerty, Daniel; Humes, Larry E

2012-09-01

The speech signal may be divided into spectral frequency-bands, each band containing temporal properties of the envelope and fine structure. This study measured the perceptual weights for the envelope and fine structure in each of three frequency bands for sentence materials in young normal-hearing listeners, older normal-hearing listeners, aided older hearing-impaired listeners, and spectrally matched young normal-hearing listeners. The availability of each acoustic property was independently varied through noisy signal extraction. Thus, the full speech stimulus was presented with noise used to mask six different auditory channels. Perceptual weights were determined by correlating a listener's performance with the signal-to-noise ratio of each acoustic property on a trial-by-trial basis. Results demonstrate that temporal fine structure perceptual weights remain stable across the four listener groups. However, a different weighting typography was observed across the listener groups for envelope cues. Results suggest that spectral shaping used to preserve the audibility of the speech stimulus may alter the allocation of perceptual resources. The relative perceptual weighting of envelope cues may also change with age. Concurrent testing of sentences repeated once on a previous day demonstrated that weighting strategies for all listener groups can change, suggesting an initial stabilization period or susceptibility to auditory training.

Perceptual weighting of individual and concurrent cues for sentence intelligibility: Frequency, envelope, and fine structure

PubMed Central

Fogerty, Daniel

2011-01-01

The speech signal may be divided into frequency bands, each containing temporal properties of the envelope and fine structure. For maximal speech understanding, listeners must allocate their perceptual resources to the most informative acoustic properties. Understanding this perceptual weighting is essential for the design of assistive listening devices that need to preserve these important speech cues. This study measured the perceptual weighting of young normal-hearing listeners for the envelope and fine structure in each of three frequency bands for sentence materials. Perceptual weights were obtained under two listening contexts: (1) when each acoustic property was presented individually and (2) when multiple acoustic properties were available concurrently. The processing method was designed to vary the availability of each acoustic property independently by adding noise at different levels. Perceptual weights were determined by correlating a listener’s performance with the availability of each acoustic property on a trial-by-trial basis. Results demonstrated that weights were (1) equal when acoustic properties were presented individually and (2) biased toward envelope and mid-frequency information when multiple properties were available. Results suggest a complex interaction between the available acoustic properties and the listening context in determining how best to allocate perceptual resources when listening to speech in noise. PMID:21361454

Continuous Activity Monitoring During Concurrent Chemoradiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ohri, Nitin, E-mail: ohri.nitin@gmail.com; Kabarriti, Rafi; Bodner, William R.

Purpose: To perform a prospective trial testing the feasibility and utility of acquiring activity data as a measure of health status during concurrent chemoradiotherapy. Methods and Materials: Ambulatory patients who were planned for treatment with concurrent chemoradiotherapy with curative intent for cancers of the head and neck, lung, or gastrointestinal tract were provided with activity monitors before treatment initiation. Patients were asked to wear the devices continuously throughout the radiation therapy course. Step count data were downloaded weekly during radiation therapy and 2 and 4 weeks after radiation therapy completion. The primary objective was to demonstrate feasibility, defined as collection ofmore » step counts for 80% of the days during study subjects' radiation therapy courses. Secondary objectives included establishing step count as a dynamic predictor of unplanned hospitalization risk. Results: Thirty-eight enrolled patients were treated with concurrent chemoradiotherapy. Primary diagnoses included head and neck cancer (n=11), lung cancer (n=13), and a variety of gastrointestinal cancers (n=14). Step data were collected for 1524 of 1613 days (94%) during patients' radiation therapy courses. Fourteen patients were hospitalized during radiation therapy or within 4 weeks of radiation therapy completion. Cox regression modeling demonstrated a significant association between recent step counts (3-day average) and hospitalization risk, with a 38% reduction in the risk of hospitalization for every 1000 steps taken each day (hazard ratio 0.62, 95% confidence interval 0.46-0.83, P=.002). Inferior quality of life scores and impaired performance status were not associated with increased hospitalization risk. Conclusion: Continuous activity monitoring during concurrent chemoradiotherapy is feasible and well-tolerated. Step counts may serve as powerful, objective, and dynamic indicators of hospitalization risk.« less

Stereotactic body radiation therapy with concurrent full-dose gemcitabine for locally advanced pancreatic cancer: a pilot trial demonstrating safety

PubMed Central

2013-01-01

Background Concurrent chemoradiation is a standard option for locally advanced pancreatic cancer (LAPC). Concurrent conventional radiation with full-dose gemcitabine has significant toxicity. Stereotactic body radiation therapy (SBRT) may provide the opportunity to administer radiation in a shorter time frame with similar efficacy and reduced toxicity. This Pilot study assessed the safety of concurrent full-dose gemcitabine with SBRT for LAPC. Methods Patients received gemcitabine, 1000 mg/m2 for 6 cycles. During week 4 of cycle 1, patients received SBRT (25 Gy delivered in five consecutive daily fractions of 5 Gy prescribed to the 75-83% isodose line). Acute and late toxicities were assessed using NIH CTCAE v3. Tumor response was assessed by RECIST. Patients underwent an esophagogastroduodenoscopy at baseline, 2, and 6 months to assess the duodenal mucosa. Quality of life (QoL) data was collected before and after treatment using the QLQ-C30 and QLQ-PAN26 questionnaires. Results Between September 2009 and February 2011, 11 patients enrolled with one withdrawal during radiation therapy. Patients had grade 1 to 2 gastrointestinal toxicity from the start of SBRT to 2 weeks after treatment. There were no grade 3 or greater radiation-related toxicities or delays for cycle 2 of gemcitabine. On endoscopy, there were no grade 2 or higher mucosal toxicities. Two patients had a partial response. The median progression free and overall survival were 6.8 and 12.2 months, respectively. Global QoL did not change between baseline and immediately after radiation treatment. Conclusions SBRT with concurrent full dose gemcitabine is safe when administered to patients with LAPC. There is no delay in administration of radiation or chemotherapy, and radiation is completed with minimal toxicity. PMID:23452509

Sequential Versus Concurrent Trastuzumab in Adjuvant Chemotherapy for Breast Cancer

PubMed Central

Perez, Edith A.; Suman, Vera J.; Davidson, Nancy E.; Gralow, Julie R.; Kaufman, Peter A.; Visscher, Daniel W.; Chen, Beiyun; Ingle, James N.; Dakhil, Shaker R.; Zujewski, JoAnne; Moreno-Aspitia, Alvaro; Pisansky, Thomas M.; Jenkins, Robert B.

2011-01-01

Purpose NCCTG (North Central Cancer Treatment Group) N9831 is the only randomized phase III trial evaluating trastuzumab added sequentially or used concurrently with chemotherapy in resected stages I to III invasive human epidermal growth factor receptor 2–positive breast cancer. Patients and Methods Patients received doxorubicin and cyclophosphamide every 3 weeks for four cycles, followed by paclitaxel weekly for 12 weeks (arm A), paclitaxel plus sequential trastuzumab weekly for 52 weeks (arm B), or paclitaxel plus concurrent trastuzumab for 12 weeks followed by trastuzumab for 40 weeks (arm C). The primary end point was disease-free survival (DFS). Results Comparison of arm A (n = 1,087) and arm B (n = 1,097), with 6-year median follow-up and 390 events, revealed 5-year DFS rates of 71.8% and 80.1%, respectively. DFS was significantly increased with trastuzumab added sequentially to paclitaxel (log-rank P < .001; arm B/arm A hazard ratio [HR], 0.69; 95% CI, 0.57 to 0.85). Comparison of arm B (n = 954) and arm C (n = 949), with 6-year median follow-up and 313 events, revealed 5-year DFS rates of 80.1% and 84.4%, respectively. There was an increase in DFS with concurrent trastuzumab and paclitaxel relative to sequential administration (arm C/arm B HR, 0.77; 99.9% CI, 0.53 to 1.11), but the P value (.02) did not cross the prespecified O'Brien-Fleming boundary (.00116) for the interim analysis. Conclusion DFS was significantly improved with 52 weeks of trastuzumab added to adjuvant chemotherapy. On the basis of a positive risk-benefit ratio, we recommend that trastuzumab be incorporated into a concurrent regimen with taxane chemotherapy as an important standard-of-care treatment alternative to a sequential regimen. PMID:22042958

A comparison of analysis methods to estimate contingency strength.

PubMed

Lloyd, Blair P; Staubitz, Johanna L; Tapp, Jon T

2018-05-09

To date, several data analysis methods have been used to estimate contingency strength, yet few studies have compared these methods directly. To compare the relative precision and sensitivity of four analysis methods (i.e., exhaustive event-based, nonexhaustive event-based, concurrent interval, concurrent+lag interval), we applied all methods to a simulated data set in which several response-dependent and response-independent schedules of reinforcement were programmed. We evaluated the degree to which contingency strength estimates produced from each method (a) corresponded with expected values for response-dependent schedules and (b) showed sensitivity to parametric manipulations of response-independent reinforcement. Results indicated both event-based methods produced contingency strength estimates that aligned with expected values for response-dependent schedules, but differed in sensitivity to response-independent reinforcement. The precision of interval-based methods varied by analysis method (concurrent vs. concurrent+lag) and schedule type (continuous vs. partial), and showed similar sensitivities to response-independent reinforcement. Recommendations and considerations for measuring contingencies are identified. © 2018 Society for the Experimental Analysis of Behavior.

Tecemotide (L-BLP25) versus placebo after chemoradiotherapy for stage III non-small-cell lung cancer (START): a randomised, double-blind, phase 3 trial.

PubMed

Butts, Charles; Socinski, Mark A; Mitchell, Paul L; Thatcher, Nick; Havel, Libor; Krzakowski, Maciej; Nawrocki, Sergiusz; Ciuleanu, Tudor-Eliade; Bosquée, Lionel; Trigo, José Manuel; Spira, Alexander; Tremblay, Lise; Nyman, Jan; Ramlau, Rodryg; Wickart-Johansson, Gun; Ellis, Peter; Gladkov, Oleg; Pereira, José Rodrigues; Eberhardt, Wilfried Ernst Erich; Helwig, Christoph; Schröder, Andreas; Shepherd, Frances A

2014-01-01

Effective maintenance therapies after chemoradiotherapy for lung cancer are lacking. Our aim was to investigate whether the MUC1 antigen-specific cancer immunotherapy tecemotide improves survival in patients with stage III unresectable non-small-cell lung cancer when given as maintenance therapy after chemoradiation. The phase 3 START trial was an international, randomised, double-blind trial that recruited patients with unresectable stage III non-small-cell lung cancer who had completed chemoradiotherapy within the 4-12 week window before randomisation and received confirmation of stable disease or objective response. Patients were stratified by stage (IIIA vs IIIB), response to chemoradiotherapy (stable disease vs objective response), delivery of chemoradiotherapy (concurrent vs sequential), and region using block randomisation, and were randomly assigned (2:1, double-blind) by a central interactive voice randomisation system to either tecemotide or placebo. Injections of tecemotide (806 μg lipopeptide) or placebo were given every week for 8 weeks, and then every 6 weeks until disease progression or withdrawal. Cyclophosphamide 300 mg/m(2) (before tecemotide) or saline (before placebo) was given once before the first study drug administration. The primary endpoint was overall survival in a modified intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00409188. From Feb 22, 2007, to Nov 15, 2011, 1513 patients were randomly assigned (1006 to tecemotide and 507 to placebo). 274 patients were excluded from the primary analysis population as a result of a clinical hold, resulting in analysis of 829 patients in the tecemotide group and 410 in the placebo group in the modified intention-to-treat population. Median overall survival was 25.6 months (95% CI 22.5-29.2) with tecemotide versus 22.3 months (19.6-25.5) with placebo (adjusted HR 0.88, 0.75-1.03; p=0.123). In the patients who received previous concurrent chemoradiotherapy, median overall survival for the 538 (65%) of 829 patients assigned to tecemotide was 30.8 months (95% CI 25.6-36.8) compared with 20.6 months (17.4-23.9) for the 268 (65%) of 410 patients assigned to placebo (adjusted HR 0.78, 0.64-0.95; p=0.016). In patients who received previous sequential chemoradiotherapy, overall survival did not differ between the 291 (35%) patients in the tecemotide group and the 142 (35%) patients in the placebo group (19.4 months [95% CI 17.6-23.1] vs 24.6 months [18.8-33.0], respectively; adjusted HR 1.12, 0.87-1.44; p=0.38). Grade 3-4 adverse events seen with a greater than 2% frequency with tecemotide were dyspnoea (49 [5%] of 1024 patients in the tecemotide group vs 21 [4%] of 477 patients in the placebo group), metastases to central nervous system (29 [3%] vs 6 [1%]), and pneumonia (23 [2%] vs 12 [3%]). Serious adverse events with a greater than 2% frequency with tecemotide were pneumonia (30 [3%] in the tecemotide group vs 14 [3%] in the placebo group), dyspnoea (29 [3%] vs 13 [3%]), and metastases to central nervous system (32 [3%] vs 9 [2%]). Serious immune-related adverse events did not differ between groups. We found no significant difference in overall survival with the administration of tecemotide after chemoradiotherapy compared with placebo for all patients with unresectable stage III non-small-cell lung cancer. However, tecemotide might have a role for patients who initially receive concurrent chemoradiotherapy, and further study in this population is warranted. Merck KGaA (Darmstadt, Germany). Copyright © 2014 Elsevier Ltd. All rights reserved.

Outcomes research in cancer clinical trial cooperative groups: the RTOG model.

PubMed

Bruner, D W; Movsas, B; Konski, A; Roach, M; Bondy, M; Scarintino, C; Scott, C; Curran, W

2004-08-01

The Radiation Therapy Oncology Group (RTOG), a National Cancer Institute sponsored cancer clinical trials research cooperative, has recently formed an Outcomes Committee to assess a comprehensive array of clinical trial endpoints and factors impacting the net effect of therapy. To study outcomes in a consistent, comprehensive and coordinated manner, the RTOG Outcomes Committee developed a model to assess clinical, humanistic, and economic outcomes important in clinical trials. This paper reviews how the RTOG incorporates outcomes research into cancer clinical trials, and demonstrates utilization of the RTOG Outcomes Model to test hypotheses related to non-small-cell lung cancer (NSCLC). In this example, the clinical component of the model indicates that the addition of chemotherapy to radiotherapy (RT) improves survival but increases the risk of toxicity. The humanistic component indicates that esophagitis is the symptom impacting quality of life the greatest and may outweigh the benefits in elderly (> or =70 years) patients. The economic component of the model indicates that accounting for quality-adjusted survival, concurrent chemoRT for the treatment of NSCLC is within the range of economically acceptable recommendations. The RTOG Outcomes Model guides a comprehensive program of research that systematically measures a triad of endpoints considered important to clinical trials research.

Conceptual framework for behavioral and social science in HIV vaccine clinical research

PubMed Central

Lau, Chuen-Yen; Swann, Edith M.; Singh, Sagri; Kafaar, Zuhayr; Meissner, Helen I.; Stansbury, James P.

2011-01-01

HIV vaccine clinical research occurs within a context where biomedical science and social issues are interlinked. Previous HIV vaccine research has considered behavioral and social issues, but often treated them as independent of clinical research processes. Systematic attention to the intersection of behavioral and social issues within a defined clinical research framework is needed to address gaps, such as those related to participation in trials, completion of trials, and the overall research experience. Rigorous attention to these issues at project inception can inform trial design and conduct by matching research approaches to the context in which trials are to be conducted. Conducting behavioral and social sciences research concurrent with vaccine clinical research is important because it can help identify potential barriers to trial implementation, as well as ultimate acceptance and dissemination of trial results. We therefore propose a conceptual framework for behavioral and social science in HIV vaccine clinical research and use examples from the behavioral and social science literature to demonstrate how the model can facilitate identification of significant areas meriting additional exploration. Standardized use of the conceptual framework could improve HIV vaccine clinical research efficiency and relevance. PMID:21821083

Conceptual framework for behavioral and social science in HIV vaccine clinical research.

PubMed

Lau, Chuen-Yen; Swann, Edith M; Singh, Sagri; Kafaar, Zuhayr; Meissner, Helen I; Stansbury, James P

2011-10-13

HIV vaccine clinical research occurs within a context where biomedical science and social issues are interlinked. Previous HIV vaccine research has considered behavioral and social issues, but often treated them as independent of clinical research processes. Systematic attention to the intersection of behavioral and social issues within a defined clinical research framework is needed to address gaps, such as those related to participation in trials, completion of trials, and the overall research experience. Rigorous attention to these issues at project inception can inform trial design and conduct by matching research approaches to the context in which trials are to be conducted. Conducting behavioral and social sciences research concurrent with vaccine clinical research is important because it can help identify potential barriers to trial implementation, as well as ultimate acceptance and dissemination of trial results. We therefore propose a conceptual framework for behavioral and social science in HIV vaccine clinical research and use examples from the behavioral and social science literature to demonstrate how the model can facilitate identification of significant areas meriting additional exploration. Standardized use of the conceptual framework could improve HIV vaccine clinical research efficiency and relevance. Published by Elsevier Ltd.

Pharmacological interventions for hypertension in children.

PubMed

Chaturvedi, Swasti; Lipszyc, Deborah H; Licht, Christoph; Craig, Jonathan C; Parekh, Rulan

2014-02-01

Hypertension is a major risk factor for stroke, coronary artery disease and kidney damage in adults. There is a paucity of data on the long-term sequelae of persistent hypertension in children, but it is known that children with hypertension have evidence of end organ damage and are at risk of hypertension into adulthood. The prevalence of hypertension in children is rising, most likely due to a concurrent rise in obesity rates. In children with hypertension, non-pharmacological measures are often recommended as first-line therapy, but a significant proportion of children will eventually require pharmacological treatment to reduce blood pressure, especially those with evidence of end organ damage at presentation or during follow-up. A systematic review of the effects of antihypertensive agents in children has not previously been conducted. To determine the dose-related effects of different classes of antihypertensive medications, as monotherapy compared to placebo; as combination therapy compared to placebo or a single medication; or in comparisons of various doses within the same class, on systolic or diastolic blood pressure (or both) in children with hypertension. We searched the Cochrane Hypertension Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 9), Ovid MEDLINE (1946 to October 2013), Ovid EMBASE (1974 to October 2013) and bibliographic citations. The selection criteria were deliberately broad due to there being few clinical trials in children. We included randomised controlled trials (RCTs) of at least two weeks duration comparing antihypertensive agents either as monotherapy or combination therapy with either placebo or another medication, or comparing different doses of the same medication, in children with hypertension. Hypertension was defined as an average (over a minimum of three readings) systolic or diastolic blood pressure (or both) on the 95(th) percentile or above for age, height and gender.  Two authors independently selected relevant studies, extracted data and assessed risk of bias. We summarised data, where possible, using a random-effects model. Formal assessment of heterogeneity was not possible because of insufficient data. A total of 21 trials evaluated antihypertensive medications of various drug classes in 3454 hypertensive children with periods of follow-up ranging from three to 24 weeks. There were five RCTs comparing an antihypertensive drug directly with placebo, 12 dose-finding trials, two trials comparing calcium channel blockers with angiotensin receptor blockers, one trial comparing a centrally acting alpha blocker with a diuretic and one trial comparing an angiotensin-converting enzyme inhibitor with an angiotensin receptor blocker. No randomised trial was identified that evaluated the effectiveness of antihypertensive medications on target end organ damage. The trials were of variable quality and most were funded by pharmaceutical companies.Among the angiotensin receptor blockers, candesartan (one trial, n = 240), when compared to placebo, reduced systolic blood pressure by 6.50 mmHg (95% confidence interval (CI) -9.44 to -3.56) and diastolic blood pressure by 5.50 mmHg (95% CI -9.62 to -1.38) (low-quality evidence). High dose telmisartan (one trial, n = 76), when compared to placebo, reduced systolic blood pressure by -8.50 (95% CI -13.79 to -3.21) but not diastolic blood pressure (-4.80, 95% CI -9.50 to 0.10) (low-quality evidence). Beta blocker (metoprolol, one trial, n = 140), when compared with placebo , significantly reduced systolic blood pressure by 4.20 mmHg (95% CI -8.12 to -0.28) but not diastolic blood pressure (-3.20 mmHg 95% CI -7.12 to 0.72) (low-quality evidence). Beta blocker/diuretic combination (Bisoprolol/hydrochlorothiazide, one trial, n = 94)when compared with placebo , did not result in a significant reduction in systolic blood pressure (-4.0 mmHg, 95% CI -8.99 to -0.19) but did have an effect on diastolic blood pressure (-4.50 mmHg, 95% CI -8.26 to -0.74) (low-quality evidence). Calcium channel blocker (extended-release felodipine,one trial, n = 133) was not effective in reducing systolic blood pressure (-0.62 mmHg, 95% CI -2.97 to 1.73) or diastolic blood pressure (-1.86 mmHg, 95% CI -5.23 to 1.51) when compared with placebo. Further, there was no consistent dose response observed among any of the drug classes. The adverse events associated with the antihypertensive agents were mostly minor and included headaches, dizziness and upper respiratory infections. Overall, there are sparse data informing the use of antihypertensive agents in children, with outcomes reported limited to blood pressure and not end organ damage. The most data are available for candesartan, for which there is low-quality evidence of a modest lowering effect on blood pressure. We did not find evidence of a consistent dose response relationship for escalating doses of angiotensin receptor blockers, calcium channel blockers or angiotensin-converting enzyme inhibitors. All agents appear safe, at least in the short term.

Concurrent sexual partnerships among female sex workers and their non-commercial male partners in Tijuana and Ciudad Juarez, Mexico.

PubMed

Robertson, Angela Marie; Syvertsen, Jennifer L; Rangel, M Gudelia; Staines, Hugo S; Morris, Martina; Patterson, Thomas L; Ulibarri, Monica D; Strathdee, Steffanie A

2013-06-01

To investigate the prevalence and correlates of concurrent (overlapping) sexual partnerships among female sex workers (FSWs) and their non-commercial male partners in two Mexico-US border cities. A cross-sectional survey of FSWs and their non-commercial male partners was conducted in Tijuana and Ciudad Juárez, Mexico (2010-2011). Eligible FSWs and verified non-commercial partners were aged ≥18 years; FSWs had ever used hard drugs (lifetime) and recently exchanged sex for money, drugs or other goods (past month). Participants underwent baseline questionnaires obtaining dates of sex and condom use with ≤5 other recurring partners, including FSWs' regular clients. These dates were compared with dates of sex with enrolled study partners to determine overlap (ie, 'recurring' concurrency). Bivariate probit regression identified recurring concurrency correlates. Among 428 individuals (214 couples), past-year recurring concurrency prevalence was 16% and was higher among women than their non-commercial male partners (26% vs 6%). In 10 couples (5%), both partners reported recurring concurrency. The majority of couples (64%) always had unprotected sex, and most of the individuals (70%) with recurring concurrency 'sometimes' or 'never' used condoms with their concurrent partners. Recurring concurrency was positively associated with FSWs' income, men's caballerismo (a form of traditional masculinity) and men's belief that their FSW partners had sexually transmitted infections (STIs). Recurring concurrency, representing sustained periods of overlapping partnerships in which unprotected sex was common, should be addressed by couple-based STI prevention interventions.

Comparison of Treatment Tolerance and Outcomes in Patients With Cervical Cancer Treated With Concurrent Chemoradiotherapy in a Prospective Randomized Trial or With Standard Treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Torres, Mylin A.; Jhingran, Anuja; Thames, Howard D.

Purpose: To compare the treatment and outcomes of cervical cancer patients treated with concurrent chemoradiotherapy (CT-RT) in a multi-institutional trial or as standard care. Patients and Methods: We reviewed the records of 302 patients treated with CT-RT for locoregionally confined, intact cervical cancer between 1990 and 2005. Of the 302 patients, 76 were treated using cisplatin and 5-fluorouracil (C/F) on Radiation Therapy Oncology Group protocol 90-01 (CT-RT{sub 90-01}); 226 underwent CT-RT as standard care with either C/F [CT-RT{sub SC(C/F)}; n = 115] or weekly cisplatin [CT-RT{sub SC(WC)}; n = 111). Results: The CT-RT{sub 90-01} patients more often had tumors {>=}6more » cm and were less often diabetic than were the CT-RT{sub SC} patients. The CT-RT{sub SC(WC)} patients were more likely than the CT-RT{sub SC(C/F)} patients to be {>=}60 years old or to have Stage III-IV disease. During treatment, CT-RT{sub SC(C/F)} patients experienced more Grade 2-3 neutropenia and were, therefore, less likely to receive 200 mg/m{sup 2} cisplatin than were either CT-RT{sub SC(WC)} or CT-RT{sub 90-01} patients (52% vs. 77% vs. 85%, respectively; p <0.001). At 5 years, the disease-specific survival rates were greater for patients treated with C/F [CT-RT{sub SC(C/F)}, 75%; CT-RT{sub 90-01}, 79%] than for those treated with CT-RT{sub SC(WC)} (58%; p = 0.02). On multivariate analysis, C/F chemotherapy, cisplatin dose {>=}200 mg/m{sup 2}, Stage I-II disease, and negative pelvic lymph nodes were independent predictors of improved disease-specific survival. Conclusions: Even within a large comprehensive cancer center, the high rates of chemotherapy completion achieved on a multi-institutional trial can be difficult to reproduce in standard practice. Although C/F toxicity was greater in the standard care patients, their outcomes were similar to those of patients treated with C/F on Radiation Therapy Oncology Group protocol 90-01.« less

Concurrent Treatment of Substance Use and PTSD.

PubMed

Flanagan, Julianne C; Korte, Kristina J; Killeen, Therese K; Back, Sudie E

2016-08-01

Substance use disorders (SUD) and posttraumatic stress disorder (PTSD) are chronic, debilitating conditions that frequently co-occur. Individuals with co-occurring SUD and PTSD suffer a more complicated course of treatment and less favorable treatment outcomes compared to individuals with either disorder alone. The development of effective psychosocial and pharmacological interventions for co-occurring SUD and PTSD is an active and critically important area of investigation. Several integrated psychosocial treatments for co-occurring SUD and PTSD have demonstrated promising outcomes. While recent studies examining medications to treat co-occurring SUD and PTSD have yielded encouraging findings, there remain substantial gaps in the evidence base regarding the treatment of co-occurring SUD and PTSD. This review will summarize the findings from clinical trials targeting a reduction in SUD and PTSD symptoms simultaneously. These results may improve our knowledge base and subsequently enhance our ability to develop effective interventions for this complex comorbid condition.

Role of citalopram in the treatment of agitation in Alzheimer’s disease

PubMed Central

Porsteinsson, Anton P; Keltz, Melanie A; Smith, Jessica S

2014-01-01

SUMMARY Neuropsychiatric symptoms (NPS) are common among individuals with Alzheimer’s disease (AD), associated with excess morbidity and mortality, greater healthcare use, earlier institutionalization, and caregiver burden. Agitation presents as emotional distress, excessive psychomotor activity, aggressive behaviors, disruptive irritability and dishibition. There is an unmet need to find pharmacologic treatment for agitation in patients with AD that can be safely and effectively used as a concurrent treatment alongside psychosocial interventions. A recent, multicenter, randomized, placebo-controlled trial explored the efficacy of a 30-mg daily dose of citalopram for agitation in patients with AD and showed a significant decrease in agitation for citalopram compared with placebo. Both QTc prolongation and cognitive worsening, as measured by the Mini Mental State Examination, were observed in the citalopram group and present a concern to clinicians. Citalopram at a 20-mg daily dose should be considered as a possible first-line treatment in addition to psychosocial intervention. PMID:25405648

Increasing the power for detecting impairment in older adults with the Faces subtest from Wechsler Memory Scale-III: an empirical trial.

PubMed

Levy, Boaz

2006-10-01

Empirical studies have questioned the validity of the Faces subtest from the WMS-III for detecting impairment in visual memory, particularly among the elderly. A recent examination of the test norms revealed a significant age related floor effect already emerging on Faces I (immediate recall), implying excessive difficulty in the acquisition phase among unimpaired older adults. The current study compared the concurrent validity of the Faces subtest with an alternative measure between 16 Alzheimer's patients and 16 controls. The alternative measure was designed to facilitate acquisition by reducing the sequence of item presentation. Other changes aimed at increasing the retrieval challenge, decreasing error due to guessing and standardizing the administration. Analyses converged to indicate that the alternative measure provided a considerably greater differentiation than the Faces subtest between Alzheimer's patients and controls. Steps for revising the Faces subtest are discussed.

Regressive research: The pitfalls of post hoc data selection in the study of unconscious mental processes.

PubMed

Shanks, David R

2017-06-01

Many studies of unconscious processing involve comparing a performance measure (e.g., some assessment of perception or memory) with an awareness measure (such as a verbal report or a forced-choice response) taken either concurrently or separately. Unconscious processing is inferred when above-chance performance is combined with null awareness. Often, however, aggregate awareness is better than chance, and data analysis therefore employs a form of extreme group analysis focusing post hoc on participants, trials, or items where awareness is absent or at chance. The pitfalls of this analytic approach are described with particular reference to recent research on implicit learning and subliminal perception. Because of regression to the mean, the approach can mislead researchers into erroneous conclusions concerning unconscious influences on behavior. Recommendations are made about future use of post hoc selection in research on unconscious cognition.

The Classroom Observation Schedule to Measure Intentional Communication (COSMIC): an observational measure of the intentional communication of children with autism in an unstructured classroom setting.

PubMed

Pasco, Greg; Gordon, Rosanna K; Howlin, Patricia; Charman, Tony

2008-11-01

The Classroom Observation Schedule to Measure Intentional Communication (COSMIC) was devised to provide ecologically valid outcome measures for a communication-focused intervention trial. Ninety-one children with autism spectrum disorder aged 6 years 10 months (SD 16 months) were videoed during their everyday snack, teaching and free play activities. Inter-rater reliability was high and relevant items showed significant associations with comparable items from concurrent Autism Diagnostic Observation Schedule-Generic (Lord et al. 2000, J Autism Dev Disord 30(3):205-223) assessments. In a subsample of 28 children initial differences in rates of initiations, initiated speech/vocalisation and commenting were predictive of language and communication competence 15 months later. Results suggest that the use of observational measures of intentional communication in natural settings is a valuable assessment strategy for research and clinical practice.

Ghrelin, leptin, adiponectin, and insulin levels and concurrent and future weight change in overweight, postmenopausal women.

PubMed

Soni, Amy C; Conroy, Molly B; Mackey, Rachel H; Kuller, Lewis H

2011-03-01

Weight loss and maintenance can be particularly challenging for postmenopausal women given the changes in body composition, metabolism, and lifestyle that can accompany the menopausal transition. Peptides mediating energy homeostasis (ghrelin, leptin, adiponectin, and insulin) may play an important role in the weight and body composition changes of postmenopausal women and may in turn be affected by hormone therapy (HT) use. This study examines how success with weight loss may be related to peptides mediating energy homeostasis and HT use. The present analysis involves 200 women from a lifestyle intervention trial in overweight, postmenopausal women for whom data on the peptides ghrelin, leptin, adiponectin, and insulin were collected at 0 and 18 months. Peptide levels were compared with changes in weight from 0 to 18 and from 18 to 30 months. Baseline peptide levels were not significantly related to future weight change. From 0 to 18 months, ghrelin (P = 0.0005) and adiponectin (P ≤ 0.0001) levels increased, whereas leptin (P ≤ 0.0001) and insulin (P = 0.0003) levels decreased with increasing amount of weight loss. However, only leptin change was related to 18-30-month weight change. Women who were on HT at 0 months but discontinued by 18 months had a greater increase in ghrelin level from 0 to 18 months compared with women with continuous HT use or nonuse. In overweight, postmenopausal women, changes in energy homeostasis peptides relate to both concurrent and future weight change. Future studies should continue to address how ghrelin, leptin, insulin, and adiponectin contribute to body composition changes and weight loss maintenance after menopause.

Ghrelin, Leptin, Adiponectin, and Insulin Levels and Concurrent and Future Weight Change in Overweight Postmenopausal Women

PubMed Central

Soni, Amy C.; Conroy, Molly B.; Mackey, Rachel H.; Kuller, Lewis H.

2010-01-01

Objective Weight loss and maintenance can be particularly challenging for postmenopausal women given the changes in body composition, metabolism, and lifestyle that can accompany the menopausal transition. Peptides mediating energy homeostasis (i.e., ghrelin, leptin, adiponectin, and insulin) may play an important role in the weight and body composition changes of postmenopausal women, and may in turn be affected by hormone therapy (HT) use. This study examines how success with weight loss may be related to peptides mediating energy homeostasis and HT use. Methods The present analysis involves 200 women from a lifestyle intervention trial in overweight, postmenopausal women for whom data on the peptides ghrelin, leptin, adiponectin, and insulin were collected at 0 and 18 months. Peptide levels were compared to changes in weight from 0-18 and18-30 months. Results Baseline peptide levels were not significantly related to future weight change. From 0-18 months, ghrelin (p=0.0005) and adiponectin (p=<0.0001) levels increased, while leptin (p=<0.0001), and insulin (p=0.0003) decreased with increasing amount of weight loss. However, only leptin change was related to 18-30 month weight change. Women who were on HT at 0 months but discontinued by 18 months had a greater increase in ghrelin from 0-18 months compared to women with continuous HT use or non-use. Conclusions In overweight, postmenopausal women, changes in energy homeostasis peptides relate to both concurrent and future weight change. Future studies should continue to address the how ghrelin, leptin, insulin, and adiponectin contribute to body composition changes and weight loss maintenance after menopause. PMID:21449093

Implicit and Explicit Attention to Pictures and Words: An fMRI-Study of Concurrent Emotional Stimulus Processing.

PubMed

Flaisch, Tobias; Imhof, Martin; Schmälzle, Ralf; Wentz, Klaus-Ulrich; Ibach, Bernd; Schupp, Harald T

2015-01-01

The present study utilized functional magnetic resonance imaging (fMRI) to examine the neural processing of concurrently presented emotional stimuli under varying explicit and implicit attention demands. Specifically, in separate trials, participants indicated the category of either pictures or words. The words were placed over the center of the pictures and the picture-word compound-stimuli were presented for 1500 ms in a rapid event-related design. The results reveal pronounced main effects of task and emotion: the picture categorization task prompted strong activations in visual, parietal, temporal, frontal, and subcortical regions; the word categorization task evoked increased activation only in left extrastriate cortex. Furthermore, beyond replicating key findings regarding emotional picture and word processing, the results point to a dissociation of semantic-affective and sensory-perceptual processes for words: while emotional words engaged semantic-affective networks of the left hemisphere regardless of task, the increased activity in left extrastriate cortex associated with explicitly attending to words was diminished when the word was overlaid over an erotic image. Finally, we observed a significant interaction between Picture Category and Task within dorsal visual-associative regions, inferior parietal, and dorsolateral, and medial prefrontal cortices: during the word categorization task, activation was increased in these regions when the words were overlaid over erotic as compared to romantic pictures. During the picture categorization task, activity in these areas was relatively decreased when categorizing erotic as compared to romantic pictures. Thus, the emotional intensity of the pictures strongly affected brain regions devoted to the control of task-related word or picture processing. These findings are discussed with respect to the interplay of obligatory stimulus processing with task-related attentional control mechanisms.

Implicit and Explicit Attention to Pictures and Words: An fMRI-Study of Concurrent Emotional Stimulus Processing

PubMed Central

Flaisch, Tobias; Imhof, Martin; Schmälzle, Ralf; Wentz, Klaus-Ulrich; Ibach, Bernd; Schupp, Harald T.

2015-01-01

The present study utilized functional magnetic resonance imaging (fMRI) to examine the neural processing of concurrently presented emotional stimuli under varying explicit and implicit attention demands. Specifically, in separate trials, participants indicated the category of either pictures or words. The words were placed over the center of the pictures and the picture-word compound-stimuli were presented for 1500 ms in a rapid event-related design. The results reveal pronounced main effects of task and emotion: the picture categorization task prompted strong activations in visual, parietal, temporal, frontal, and subcortical regions; the word categorization task evoked increased activation only in left extrastriate cortex. Furthermore, beyond replicating key findings regarding emotional picture and word processing, the results point to a dissociation of semantic-affective and sensory-perceptual processes for words: while emotional words engaged semantic-affective networks of the left hemisphere regardless of task, the increased activity in left extrastriate cortex associated with explicitly attending to words was diminished when the word was overlaid over an erotic image. Finally, we observed a significant interaction between Picture Category and Task within dorsal visual-associative regions, inferior parietal, and dorsolateral, and medial prefrontal cortices: during the word categorization task, activation was increased in these regions when the words were overlaid over erotic as compared to romantic pictures. During the picture categorization task, activity in these areas was relatively decreased when categorizing erotic as compared to romantic pictures. Thus, the emotional intensity of the pictures strongly affected brain regions devoted to the control of task-related word or picture processing. These findings are discussed with respect to the interplay of obligatory stimulus processing with task-related attentional control mechanisms. PMID:26733895

Risk of Parkinson's disease following zolpidem use: a retrospective, population-based cohort study.

PubMed

Huang, Hui-Chun; Tsai, Chon-Haw; Muo, Chih-Hsin; Lin, Kang-Hsu; Lu, Ming-Kuei; Sung, Fung-Chang; Kao, Chia-Hung

2015-01-01

To evaluate the influence of long-term zolpidem use on the incidence of developing Parkinson's disease. 2,961 subjects who used zolpidem for the first time longer than 3 months between 1998 and 2000 were identified in the National Health Insurance system of Taiwan. Subjects without a history of zolpidem use were randomly selected as a comparison cohort and frequency matched to zolpidem users based on age, sex, and index date. The diagnosis of Parkinson's disease was based on the criteria of the International Classification of Diseases, Ninth Revision, Clinical Modification. Its incidence until the end of 2009 was calculated and its hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards regression models and Kaplan-Meier analysis. The overall incidence of Parkinson's disease was greater among zolpidem users than in the comparison cohort (HR = 1.88; 95% CI, 1.45-2.45). However, there was no difference in Parkinson's disease incidence between these 2 cohorts after 5 years of observation. The risk of Parkinson's disease increased with increasing zolpidem dose, with an HR of 0.70 for low-dose users (< 400 mg/y) and 2.94 for high-dose users (≥ 1,600 mg/y). The incidence of Parkinson's disease was greater in subjects using zolpidem only (HR = 2.35; 95% CI, 1.66-3.33) compared to those using benzodiazepines only (HR = 1.31; 95% CI, 0.91-1.90). By stratified analysis, zolpidem use with concurrent depression (HR = 4.79) increased the risk of Parkinson's disease compared to that of zolpidem users without concurrent depression. Zolpidem use might unmask preclinical Parkinson's disease, especially in patients with depression. However, large population-based, unbiased, randomized trials are warranted to confirm this finding. © Copyright 2015 Physicians Postgraduate Press, Inc.

Interventions for treating proximal humeral fractures in adults.

PubMed

Handoll, Helen H G; Ollivere, Benjamin J; Rollins, Katie E

2012-12-12

Fractures of the proximal humerus are common injuries. The management, including surgical intervention, of these fractures varies widely. This is an update of a Cochrane review first published in 2001 and last updated in 2010. To review the evidence supporting the various treatment and rehabilitation interventions for proximal humeral fractures. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and other databases, and bibliographies of trial reports. The full search ended in January 2012. All randomised controlled trials pertinent to the management of proximal humeral fractures in adults were selected. Two people performed independent study selection, risk of bias assessment and data extraction. Only limited meta-analysis was performed. Twenty-three small randomised trials with a total of 1238 participants were included. Bias in these trials could not be ruled out. Additionally there is a need for caution in interpreting the results of these small trials, which generally do not provide sufficient evidence to conclude that any non-statistically significant finding is 'evidence of no effect'.Eight trials evaluated conservative treatment. One trial found an arm sling was generally more comfortable than a less commonly used body bandage. There was some evidence that 'immediate' physiotherapy compared with that delayed until after three weeks of immobilisation resulted in less pain and potentially better recovery in people with undisplaced or other stable fractures. Similarly, there was evidence that mobilisation at one week instead of three weeks alleviated short term pain without compromising long term outcome. Two trials provided some evidence that unsupervised patients could generally achieve a satisfactory outcome when given sufficient instruction for an adequate self-directed exercise programme.Six heterogeneous trials, involving a total of 270 participants with displaced and/or complex fractures, compared surgical versus conservative treatment. Pooled results of patient-reported functional scores at one year from three trials (153 participants) showed no statistically significant difference between the two groups (standardised mean difference -0.10, 95% CI -0.42 to 0.22; negative results favour surgery). Quality of life based on the EuroQol results scores from three trials (153 participants) showed non-statistically significant differences between the two groups at three time points up to 12 months. However, the pooled EuroQol results at two years (101 participants) from two trials run concurrently from the same centre were significantly in favour of the surgical group. There was no significant difference between the two groups in mortality (8/98 versus 5/98; RR 1.55, 95% CI 0.55 to 4.36; 4 trials). Significantly more surgical group patients had additional or secondary surgery (18/112 versus 5/111; RR 3.36, 95% CI 1.33 to 8.49; 5 trials). This is equivalent to an extra operation in one of every nine surgically treated patients.Different methods of surgical management were tested in seven small trials. One trial comparing two types of locking plate versus a locking nail for treating two-part surgical neck fractures found some evidence of better function after plate fixation but also of a higher rate of surgically-related complications. One trial comparing a locking plate versus minimally invasive fixation with distally inserted intramedullary nails found some evidence of a short-term benefit for the nailing group. Compared with hemiarthroplasty, tension-band fixation of severe injuries using wires was associated with a higher re-operation rate in one trial. Two trials found no important differences between 'polyaxial' and 'monaxial' screws combined with locking plate fixation. One trial produced some preliminary evidence that tended to support the use of medial support locking screws in locking plate fixation. One trial found better functional results for one of two types of hemiarthroplasty.Very limited evidence suggested similar outcomes from early versus later mobilisation after either surgical fixation (one trial) or hemiarthroplasty (one trial). There is insufficient evidence to inform the management of these fractures. Early physiotherapy, without immobilisation, may be sufficient for some types of undisplaced fractures. It remains unclear whether surgery, even for specific fracture types, will produce consistently better long term outcomes but it is likely to be associated with a higher risk of surgery-related complications and requirement for further surgery.There is insufficient evidence to establish what is the best method of surgical treatment, either in terms of the use of different categories of surgical intervention (such as plate versus nail fixation, or hemiarthroplasty versus tension-wire fixation) or different methods of performing an intervention in the same category (such as different methods of plate fixation). There is insufficient evidence to say when to start mobilisation after either surgical fixation or hemiarthroplasty.

Oncologists’ Perspectives on Concurrent Palliative Care in an NCI-designated Comprehensive Cancer Center

PubMed Central

Bakitas, Marie; Lyons, Kathleen Doyle; Hegel, Mark T.; Ahles, Tim

2013-01-01

Purpose To understand oncology clinicians’ perspectives about the care of advanced cancer patients following the completion of the ENABLE II (Educate, Nurture, Advise, Before Life Ends) randomized clinical trial (RCT) of a concurrent oncology palliative care model. Methods Qualitative interview study of 35 oncology clinicians about their approach to patients with advanced cancer and the effect of the ENABLE II RCT. Results Oncologists believed that integrating palliative care at the time of an advanced cancer diagnosis enhanced patient care and complemented their practice. Self-assessment of their practice with advanced cancer patients comprised four themes: 1) treating the whole patient, 2) focusing on quality versus quantity of life, 3) “some patients just want to fight”, and 4) helping with transitions; timing is everything. Five themes comprised oncologists’ views on the complementary role of palliative care: 1) “refer early and often”, 2) referral challenges: “Palliative” equals hospice; “Heme patients are different”, 3) palliative care as consultants or co-managers, 4) palliative care “shares the load”, and 5) ENABLE II facilitated palliative care integration. Conclusions Oncologists described the RCT as holistic and complementary, and as a significant factor in adopting concurrent care as a standard of care. PMID:23040412

Investigating the Ketogenic Diet As Treatment for Primary Aggressive Brain Cancer: Challenges and Lessons Learned

PubMed Central

Schwartz, Kenneth A.; Noel, Mary; Nikolai, Michele; Chang, Howard T.

2018-01-01

Survival of glioblastoma multiforme (GBM) with the current recommended treatment is poor. Reported median survivals are approximately 8–15 months. Based on recent publications from animal models, combining cancer drugs, radiation, and diet-metabolic treatments may be a new route to better survivals. To investigate this possibility, we have begun a clinical trial that has enrolled 15 subjects using a ketogenic diet (KD) as an addition to current standard treatments that include surgery, radiation therapy, and chemotherapy. Of the 15 enrolled, 10 completed the protocol. This perspective describes the challenges and lessons learned during this clinical trial and discusses the critical elements that are essential for investigating treatment with a KD. We also reviewed and compared various types of KDs. We believe that the diet selected should be standardized within individual clinical trials, and more importantly, the patients’ blood should be monitored for glucose and ketones twice daily so that the supervising dietitian can work with the patient and their caregivers to make appropriate changes in the diet. Compliance with the diet is best in highly motivated patients who have excellent home support from a family member or a friend who can help to overcome administrative, physical, and cognition deficiencies associated with the disease. Treatment of GBM using a KD represents a reasonable investigative approach. This perspective summarizes the challenges and lessons learned implementing and continuing KD therapy while the patients are concurrently being treated with radiation and chemotherapy. PMID:29536011

A comparison of forward and concurrent chaining strategies in teaching laundromat skills to students with severe handicaps.

PubMed

McDonnell, J; McFarland, S

1988-01-01

This study compared the relative efficiency of forward and concurrent chaining strategies in teaching the use of a commercial washing machine and laundry soap dispenser to four high school students with severe handicaps. Acquisition and maintenance of the laundromat skills were assessed through a multielement, alternating treatment within subject design. Results indicated that the concurrent chaining strategy was more efficient than forward chaining in facilitating acquisition of the activities. Four week and eight week follow-up probes indicated that concurrent chaining resulted in better maintenance of the activities. The implications of these results for teaching community activities and future research in building complex chains are discussed.

Concurrent adversities among adolescents with conduct problems: the NAAHS study.

PubMed

Reigstad, Bjørn; Kvernmo, Siv

2016-10-01

Several studies have confirmed that maltreatment and abuse in childhood are related to conduct problems. Less is known about such relationships with concurrent adversities in adolescence and, also, when compared with other severe adversities and possible multiple additive effects. The study encompassed a community population of 4881 adolescents 15-16 years of age 50.1 % boys and 49.9 % girls. Youth with and without conduct problem scores within the deviant range on the Strength and Difficulties Questionnaire (SDQ) was compared on 12 concurrent adversities. Based on self-reports, 4.4 % of the adolescents had conduct problem scores within the deviant range and more girls (5.1 %) than boys (3.7 %). In the deviant conduct problem group, 65.1 % had experienced two or more concurrent adversities compared with 26.3 % of youths in the non-deviant group (OR 5.23, 95 % CI 3.91-7.01). Likewise, the deviant conduct problem group was from 1.71 to 8.43 times more at the risk of experiencing the different adversities. Parental mental health problems and experiences of violence were multivariately strongest associated with conduct problem scores within the deviant range on the SDQ. A strong multiple additive relationship with adversities was found. Two-thirds of youth with SDQ conduct problem scores within the deviant range reported two or more concurrent adversities. Clinicians should seek information about kinds and amount of possible traumatic adversities in youth with conduct problems and offer evidence based treatment.

Adaptive Randomization of Neratinib in Early Breast Cancer

PubMed Central

Park, John W.; Liu, Minetta C.; Yee, Douglas; Yau, Christina; van 't Veer, Laura J.; Symmans, W. Fraser; Paoloni, Melissa; Perlmutter, Jane; Hylton, Nola M.; Hogarth, Michael; DeMichele, Angela; Buxton, Meredith B.; Chien, A. Jo; Wallace, Anne M.; Boughey, Judy C.; Haddad, Tufia C.; Chui, Stephen Y.; Kemmer, Kathleen A.; Kaplan, Henry G.; Liu, Minetta C.; Isaacs, Claudine; Nanda, Rita; Tripathy, Debasish; Albain, Kathy S.; Edmiston, Kirsten K.; Elias, Anthony D.; Northfelt, Donald W.; Pusztai, Lajos; Moulder, Stacy L.; Lang, Julie E.; Viscusi, Rebecca K.; Euhus, David M.; Haley, Barbara B.; Khan, Qamar J.; Wood, William C.; Melisko, Michelle; Schwab, Richard; Lyandres, Julia; Davis, Sarah E.; Hirst, Gillian L.; Sanil, Ashish; Esserman, Laura J.; Berry, Donald A.

2017-01-01

Background I-SPY2, a standing, multicenter, adaptive phase 2 neoadjuvant trial ongoing in high-risk clinical stage II/III breast cancer, is designed to evaluate multiple, novel experimental agents added to standard chemotherapy for their ability to improve the rate of pathologic complete response (pCR). Experimental therapies are compared against a common control arm. We report efficacy for the tyrosine kinase inhibitor neratinib. Methods Eligible women had ≥2.5 cm stage II/III breast cancer, categorized into 8 biomarker subtypes based on HER2, hormone-receptor status (HR), and MammaPrint. Neratinib was evaluated for 10 signatures (prospectively defined subtype combinations), with primary endpoint pCR. MR volume changes inform likelihood of pCR for each patient prior to surgery. Adaptive assignment to experimental arms within disease subtype was based on current Bayesian probabilities of superiority over control. Accrual to experimental arm stop at any time for futility or graduation within a particular signature based on Bayesian predictive probability of success in a confirmatory trial. The maximum sample size in any experimental arm is 120 patients, Results With 115 patients and 78 concurrently randomized controls, neratinib graduated in the HER2+/HR− signature, with mean pCR rate 56% (95% PI: 37 to 73%) vs 33% for controls (11 to 54%). Final predictive probability of success, updated when all pathology data were available, was 79%. Conclusion Adaptive, multi-armed trials can efficiently identify responding tumor subtypes. Neratinib added to standard therapy is highly likely to improve pCR rates in HER2+/HR2212; breast cancer. Confirmation in I-SPY 3, a phase 3 neoadjuvant registration trial, is planned. PMID:27406346

A Randomized Double-blind, Placebo Controlled Trial of Venlafaxine-Extended Release for Co-occurring Cannabis Dependence and Depressive Disorders

PubMed Central

Levin, Frances R.; Mariani, John; Brooks, Daniel J.; Pavlicova, Martina; Nunes, Edward V.; Agosti, Vito; Bisaga, Adam; Sullivan, Maria A.; Carpenter, Kenneth M.

2013-01-01

Aim To evaluate whether venlafaxine-extended release (VEN-XR) is an effective treatment for cannabis dependence with concurrent depressive disorders. Design This was a randomized, 12 week, double-blind, placebo-controlled trial of outpatients (n = 103) with DSM-IV cannabis dependence and major depressive disorder or dysthymia. Participants received up to 375 mg VEN-XR on a fixed-flexible schedule or placebo. All patients received weekly individual cognitive-behavioral psychotherapy that primarily targeted marijuana use. Settings The trial was conducted at two university research centers in the United States. Participants One hundred and three cannabis dependent adults participated in the trial. Measurements The primary outcome measures were 1) abstinence from marijuana defined as at least two consecutive urine-confirmed abstinent weeks and 2) improvement in depressive symptoms based on the Hamilton Depression Rating Scale. Findings The proportion of patients achieving a clinically significant mood improvement [50% decrease in Hamilton Depression score from baseline] was high and did not differ between groups receiving VEN-XR (63%) and placebo (69%) (X12=0.48, p-value= 0.49). The proportion of patients achieving abstinence was low overall, but was significantly worse on VEN-XR (11.8%) compared to placebo (36.5%) (X12=7.46, p-value<0.01; OR = 4.51, 95% CI: 1.53, 13.3). Mood improvement was associated with reduction in marijuana use in the placebo group (F1,179=30.49, p-value<0.01), but not the VEN-XR group (F1,186=0.02, p-value=0.89). Conclusions For depressed, cannabis-dependent patients, venlafaxine-extended release does not appear to be effective at reducing depression and may lead to an increase in cannabis use. PMID:23297841

Tamoxifen with ovarian function suppression versus tamoxifen alone as an adjuvant treatment for premenopausal breast cancer: a meta-analysis of published randomized controlled trials

PubMed Central

Yan, Shunchao; Li, Kai; Jiao, Xin; Zou, Huawei

2015-01-01

Background Ovarian function suppression (OFS) significantly downregulates the concentration of plasma estrogens. However, it is unclear whether it offers any survival benefits if combined with adjuvant tamoxifen treatment in premenopausal women. This meta-analysis was designed to assess data from previous studies involving adjuvant tamoxifen treatment plus OFS in premenopausal breast cancer. Methods Electronic literature databases (PubMed, Embase, the Web of Science, and the Cochrane Library) were searched for relevant randomized controlled trials published prior to February 1, 2015. Only randomized controlled trials that compared tamoxifen alone with tamoxifen plus OFS for premenopausal women with breast cancer were selected. The evaluated endpoints were disease-free survival and overall survival. Results Four randomized controlled trials comprising 6,279 patients (OFS combination, n=3,133; tamoxifen alone, n=3,146) were included in the meta-analysis. There was no significant improvement in disease-free survival or overall survival with addition of OFS in either the whole population or the hormone receptor-positive subgroup. The risk of distant recurrence was not reduced with the addition of OFS in the whole population. A subgroup analysis showed that addition of OFS significantly improved overall survival in patients who were administered chemotherapy. Conclusion Based on the available studies, concurrent administration of OFS and adjuvant tamoxifen treatment for premenopausal women with breast cancer has no effect on prolonging disease-free survival and overall survival, excluding patients who were administered chemotherapy. It should not be widely recommended, except perhaps for women who were hormone-receptor positive and who were also administered adjuvant chemotherapy. PMID:26109867

Experimental Treatment of Ebola Virus Disease with TKM-130803: A Single-Arm Phase 2 Clinical Trial.

PubMed

Dunning, Jake; Sahr, Foday; Rojek, Amanda; Gannon, Fiona; Carson, Gail; Idriss, Baimba; Massaquoi, Thomas; Gandi, Regina; Joseph, Sebatu; Osman, Hassan K; Brooks, Timothy J G; Simpson, Andrew J H; Goodfellow, Ian; Thorne, Lucy; Arias, Armando; Merson, Laura; Castle, Lyndsey; Howell-Jones, Rebecca; Pardinaz-Solis, Raul; Hope-Gill, Benjamin; Ferri, Mauricio; Grove, Jennifer; Kowalski, Mark; Stepniewska, Kasia; Lang, Trudie; Whitehead, John; Olliaro, Piero; Samai, Mohammed; Horby, Peter W

2016-04-01

TKM-130803, a small interfering RNA lipid nanoparticle product, has been developed for the treatment of Ebola virus disease (EVD), but its efficacy and safety in humans has not been evaluated. In this single-arm phase 2 trial, adults with laboratory-confirmed EVD received 0.3 mg/kg of TKM-130803 by intravenous infusion once daily for up to 7 d. On days when trial enrolment capacity was reached, patients were enrolled into a concurrent observational cohort. The primary outcome was survival to day 14 after admission, excluding patients who died within 48 h of admission. After 14 adults with EVD had received TKM-130803, the pre-specified futility boundary was reached, indicating a probability of survival to day 14 of ≤0.55, and enrolment was stopped. Pre-treatment geometric mean Ebola virus load in the 14 TKM-130803 recipients was 2.24 × 109 RNA copies/ml plasma (95% CI 7.52 × 108, 6.66 × 109). Two of the TKM-130803 recipients died within 48 h of admission and were therefore excluded from the primary outcome analysis. Of the remaining 12 TKM-130803 recipients, nine died and three survived. The probability that a TKM-130803 recipient who survived for 48 h will subsequently survive to day 14 was estimated to be 0.27 (95% CI 0.06, 0.58). TKM-130803 infusions were well tolerated, with 56 doses administered and only one possible infusion-related reaction observed. Three patients were enrolled in the observational cohort, of whom two died. Administration of TKM-130803 at a dose of 0.3 mg/kg/d by intravenous infusion to adult patients with severe EVD was not shown to improve survival when compared to historic controls. Pan African Clinical Trials Registry PACTR201501000997429.

Depression in Visual Impairment Trial (DEPVIT): A Randomized Clinical Trial of Depression Treatments in People With Low Vision.

PubMed

Nollett, Claire L; Bray, Nathan; Bunce, Catey; Casten, Robin J; Edwards, Rhiannon T; Hegel, Mark T; Janikoun, Sarah; Jumbe, Sandra E; Ryan, Barbara; Shearn, Julia; Smith, Daniel J; Stanford, Miles; Xing, Wen; Margrain, Tom H

2016-08-01

The purpose of this study was to compare two interventions for depression, problem solving treatment (PST) and referral to the patient's physician, with a waiting-list control group in people with sight loss and depressive symptoms. This was an assessor-masked, exploratory, multicenter, randomized clinical trial, with concurrent economic analysis. Of 1008 consecutive attendees at 14 low-vision rehabilitation centers in Britain, 43% (n = 430) screened positive for depressive symptoms on the Geriatric Depression Scale and 85 of these attendees participated in the trial. Eligible participants were randomized in the ratio 1:1:1 to PST, referral to their physician, or a waiting-list control arm. PST is a manualized talking intervention delivered by a trained therapist who teaches people over six to eight sessions to implement a seven-step method for solving their problems. Referral to the physician involved sending a referral letter to the person's physician, encouraging him or her to consider treatment according to the stepped care protocol recommended by the U.K.'s National Institute of Health and Care Excellence. The primary outcome was change in depressive symptoms (6 months after baseline) as determined by the Beck Depression Inventory. At 6 months, Beck Depression Inventory scores reduced by 1.05 (SD 8.85), 2.11 (SD 7.60), and 2.68 (SD 7.93) in the waiting-list control, referral, and PST arms, respectively. The cost per patient of the PST intervention was £1176 in Wales and £1296 in London. Depressive symptoms improved most in the PST group and least in the control group. However, the change was small and the uncertainty of the measurements relatively large.

Branched-Chain Amino Acids and Arginine Improve Performance in Two Consecutive Days of Simulated Handball Games in Male and Female Athletes: A Randomized Trial

PubMed Central

Chang, Chen-Kang; Chang Chien, Kun-Ming; Chang, Jung-Hsien; Huang, Mei-Hsuan; Liang, Ya-Chuan; Liu, Tsung-Han

2015-01-01

The central nervous system plays a crucial role in the development of physical fatigue. The purpose of this study is to investigate the effect of combined supplementation of branched-chain amino acids (BCAA) and arginine on intermittent sprint performance in simulated handball games on 2 consecutive days. Methods: Fifteen male and seven female handball players consumed 0.17 g/kg BCAA and 0.04 g/kg arginine together (AA trial), or placebo (PB trial) before exercise. Each trial contained two 60-min simulated handball games on consecutive days. The game was consisted of 30 identical 2-min blocks and a 20 m all-out sprint was performed at the end of each block. The performance, measured by percentage changes of sprint time between day 1 and 2, was significantly better in the AA trial (first half: AA trial: -1.34±0.60%, PB trial: -0.21±0.69%; second half: AA trial: -1.68±0.58%, PB trial: 0.49±0.42%). The average ratings of perceive exertion throughout the 2-day trial was significantly lower in the AA trial (14.2±0.3) than the PB trial (15.1±0.4). Concurrently, post-exercise tryptophan/BCAA ratio on both days in the AA trial was significantly lower than the baseline. This study showed that BCAA and arginine supplementation could improve performance in intermittent sprints on the second consecutive day of simulated handball games in well-trained athletes by potentially alleviating central fatigue. PMID:25803783

Concurrent Validity of the Classroom Strategies Scale-Teacher Form: A Preliminary Investigation

ERIC Educational Resources Information Center

Reddy, Linda A.; Dudek, Christopher M.; Rualo, Angelique J.; Fabiano, Gregory A.

2016-01-01

The present study investigated the concurrent validity of the Classroom Strategies Scale-Teacher Form (CSS-T), a multidimensional teacher formative assessment of instructional and behavioral management practices. The CSS-T is compared with the Classroom Assessment Scoring System (CLASS), a well-known teacher assessment of overall classroom…

Effects of Serial and Concurrent Training on Receptive Identification Tasks: A Systematic Replication

ERIC Educational Resources Information Center

Wunderlich, Kara L.; Vollmer, Timothy R.

2017-01-01

The current study compared the use of serial and concurrent methods to train multiple exemplars when teaching receptive language skills, providing a systematic replication of Wunderlich, Vollmer, Donaldson, and Phillips (2014). Five preschoolers diagnosed with developmental delays or autism spectrum disorders were taught to receptively identify…

Linking Item Parameters to a Base Scale

ERIC Educational Resources Information Center

Kang, Taehoon; Petersen, Nancy S.

2012-01-01

This paper compares three methods of item calibration--concurrent calibration, separate calibration with linking, and fixed item parameter calibration--that are frequently used for linking item parameters to a base scale. Concurrent and separate calibrations were implemented using BILOG-MG. The Stocking and Lord in "Appl Psychol Measure"…

Outcomes of Concurrent Operations: Results From the American College of Surgeons' National Surgical Quality Improvement Program.

PubMed

Liu, Jason B; Berian, Julia R; Ban, Kristen A; Liu, Yaoming; Cohen, Mark E; Angelos, Peter; Matthews, Jeffrey B; Hoyt, David B; Hall, Bruce L; Ko, Clifford Y

2017-09-01

To determine whether concurrently performed operations are associated with an increased risk for adverse events. Concurrent operations occur when a surgeon is simultaneously responsible for critical portions of 2 or more operations. How this practice affects patient outcomes is unknown. Using American College of Surgeons' National Surgical Quality Improvement Program data from 2014 to 2015, operations were considered concurrent if they overlapped by ≥60 minutes or in their entirety. Propensity-score-matched cohorts were constructed to compare death or serious morbidity (DSM), unplanned reoperation, and unplanned readmission in concurrent versus non-concurrent operations. Multilevel hierarchical regression was used to account for the clustered nature of the data while controlling for procedure and case mix. There were 1430 (32.3%) surgeons from 390 (77.7%) hospitals who performed 12,010 (2.3%) concurrent operations. Plastic surgery (n = 393 [13.7%]), otolaryngology (n = 470 [11.2%]), and neurosurgery (n = 2067 [8.4%]) were specialties with the highest proportion of concurrent operations. Spine procedures were the most frequent concurrent procedures overall (n = 2059/12,010 [17.1%]). Unadjusted rates of DSM (9.0% vs 7.1%; P < 0.001), reoperation (3.6% vs 2.7%; P < 0.001), and readmission (6.9% vs 5.1%; P < 0.001) were greater in the concurrent operation cohort versus the non-concurrent. After propensity score matching and risk-adjustment, there was no significant association of concurrence with DSM (odds ratio [OR] 1.08; 95% confidence interval [CI] 0.96-1.21), reoperation (OR 1.16; 95% CI 0.96-1.40), or readmission (OR 1.14; 95% CI 0.99-1.29). In these analyses, concurrent operations were not detected to increase the risk for adverse outcomes. These results do not lessen the need for further studies, continuous self-regulation and proactive disclosure to patients.

Selective impairment of auditory selective attention under concurrent cognitive load.

PubMed

Dittrich, Kerstin; Stahl, Christoph

2012-06-01

Load theory predicts that concurrent cognitive load impairs selective attention. For visual stimuli, it has been shown that this impairment can be selective: Distraction was specifically increased when the stimulus material used in the cognitive load task matches that of the selective attention task. Here, we report four experiments that demonstrate such selective load effects for auditory selective attention. The effect of two different cognitive load tasks on two different auditory Stroop tasks was examined, and selective load effects were observed: Interference in a nonverbal-auditory Stroop task was increased under concurrent nonverbal-auditory cognitive load (compared with a no-load condition), but not under concurrent verbal-auditory cognitive load. By contrast, interference in a verbal-auditory Stroop task was increased under concurrent verbal-auditory cognitive load but not under nonverbal-auditory cognitive load. This double-dissociation pattern suggests the existence of different and separable verbal and nonverbal processing resources in the auditory domain.

Collaborative Care for Older Adults with low back pain by family medicine physicians and doctors of chiropractic (COCOA): study protocol for a randomized controlled trial.

PubMed

Goertz, Christine M; Salsbury, Stacie A; Vining, Robert D; Long, Cynthia R; Andresen, Andrew A; Jones, Mark E; Lyons, Kevin J; Hondras, Maria A; Killinger, Lisa Z; Wolinsky, Fredric D; Wallace, Robert B

2013-01-16

Low back pain is a prevalent and debilitating condition that affects the health and quality of life of older adults. Older people often consult primary care physicians about back pain, with many also receiving concurrent care from complementary and alternative medicine providers, most commonly doctors of chiropractic. However, a collaborative model of treatment coordination between these two provider groups has yet to be tested. The primary aim of the Collaborative Care for Older Adults Clinical Trial is to develop and evaluate the clinical effectiveness and feasibility of a patient-centered, collaborative care model with family medicine physicians and doctors of chiropractic for the treatment of low back pain in older adults. This pragmatic, pilot randomized controlled trial will enroll 120 participants, age 65 years or older with subacute or chronic low back pain lasting at least one month, from a community-based sample in the Quad-Cities, Iowa/Illinois, USA. Eligible participants are allocated in a 1:1:1 ratio to receive 12 weeks of medical care, concurrent medical and chiropractic care, or collaborative medical and chiropractic care. Primary outcomes are self-rated back pain and disability. Secondary outcomes include general and functional health status, symptom bothersomeness, expectations for treatment effectiveness and improvement, fear avoidance behaviors, depression, anxiety, satisfaction, medication use and health care utilization. Treatment safety and adverse events also are monitored. Participant-rated outcome measures are collected via self-reported questionnaires and computer-assisted telephone interviews at baseline, and at 4, 8, 12, 24, 36 and 52 weeks post-randomization. Provider-rated expectations for treatment effectiveness and participant improvement also are evaluated. Process outcomes are assessed through qualitative interviews with study participants and research clinicians, chart audits of progress notes and content analysis of clinical trial notes. This pragmatic, pilot randomized controlled trial uses a mixed method approach to evaluate the clinical effectiveness, feasibility, and participant and provider perceptions of collaborative care between medical doctors and doctors of chiropractic in the treatment of older adults with low back pain.

Dose and Fractionation in Radiation Therapy of Curative Intent for Non-Small Cell Lung Cancer: Meta-Analysis of Randomized Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ramroth, Johanna; Cutter, David J.; Darby, Sarah C.

Purpose: The optimum dose and fractionation in radiation therapy of curative intent for non-small cell lung cancer remains uncertain. We undertook a published data meta-analysis of randomized trials to examine whether radiation therapy regimens with higher time-corrected biologically equivalent doses resulted in longer survival, either when given alone or when given with chemotherapy. Methods and Materials: Eligible studies were randomized comparisons of 2 or more radiation therapy regimens, with other treatments identical. Median survival ratios were calculated for each comparison and pooled. Results: 3795 patients in 25 randomized comparisons of radiation therapy dose were studied. The median survival ratio, highermore » versus lower corrected dose, was 1.13 (95% confidence interval [CI] 1.04-1.22) when radiation therapy was given alone and 0.83 (95% CI 0.71-0.97) when it was given with concurrent chemotherapy (P for difference=.001). In comparisons of radiation therapy given alone, the survival benefit increased with increasing dose difference between randomized treatment arms (P for trend=.004). The benefit increased with increasing dose in the lower-dose arm (P for trend=.01) without reaching a level beyond which no further survival benefit was achieved. The survival benefit did not differ significantly between randomized comparisons where the higher-dose arm was hyperfractionated and those where it was not. There was heterogeneity in the median survival ratio by geographic region (P<.001), average age at randomization (P<.001), and year trial started (P for trend=.004), but not for proportion of patients with squamous cell carcinoma (P=.2). Conclusions: In trials with concurrent chemotherapy, higher radiation therapy doses resulted in poorer survival, possibly caused, at least in part, by high levels of toxicity. Where radiation therapy was given without chemotherapy, progressively higher radiation therapy doses resulted in progressively longer survival, and no upper dose level was found above which there was no further benefit. These findings support the consideration of further radiation therapy dose escalation trials, making use of modern treatment methods to reduce toxicity.« less

Differences in results of analyses of concurrent and split stream-water samples collected and analyzed by the US Geological Survey and the Illinois Environmental Protection Agency, 1985-91

USGS Publications Warehouse

Melching, C.S.; Coupe, R.H.

1995-01-01

During water years 1985-91, the U.S. Geological Survey (USGS) and the Illinois Environmental Protection Agency (IEPA) cooperated in the collection and analysis of concurrent and split stream-water samples from selected sites in Illinois. Concurrent samples were collected independently by field personnel from each agency at the same time and sent to the IEPA laboratory, whereas the split samples were collected by USGS field personnel and divided into aliquots that were sent to each agency's laboratory for analysis. The water-quality data from these programs were examined by means of the Wilcoxon signed ranks test to identify statistically significant differences between results of the USGS and IEPA analyses. The data sets for constituents and properties identified by the Wilcoxon test as having significant differences were further examined by use of the paired t-test, mean relative percentage difference, and scattergrams to determine if the differences were important. Of the 63 constituents and properties in the concurrent-sample analysis, differences in only 2 (pH and ammonia) were statistically significant and large enough to concern water-quality engineers and planners. Of the 27 constituents and properties in the split-sample analysis, differences in 9 (turbidity, dissolved potassium, ammonia, total phosphorus, dissolved aluminum, dissolved barium, dissolved iron, dissolved manganese, and dissolved nickel) were statistically significant and large enough to con- cern water-quality engineers and planners. The differences in concentration between pairs of the concurrent samples were compared to the precision of the laboratory or field method used. The differences in concentration between pairs of the concurrent samples were compared to the precision of the laboratory or field method used. The differences in concentration between paris of split samples were compared to the precision of the laboratory method used and the interlaboratory precision of measuring a given concentration or property. Consideration of method precision indicated that differences between concurrent samples were insignificant for all concentrations and properties except pH, and that differences between split samples were significant for all concentrations and properties. Consideration of interlaboratory precision indicated that the differences between the split samples were not unusually large. The results for the split samples illustrate the difficulty in obtaining comparable and accurate water-quality data.

Mitomycin-C- or Cisplatin-Based Chemoradiotherapy for Anal Canal Carcinoma: Long-Term Results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Olivatto, Luis O., E-mail: olivatto@inca.gov.b; Cabral, Vania; Rosa, Arthur

2011-02-01

Purpose: To evaluate the long-term efficacy of concurrent radiotherapy with mitomycin-C (MMC)-based or cisplatin (CP)-based combinations in a cohort of patients with locally advanced anal canal carcinoma. Methods and Materials: Between 1988 and 2000, 179 patients with locally advanced anal canal carcinoma were treated at the Instituto Nacional de Cancer with two cycles of chemotherapy during Weeks 1 and 5 of radiotherapy. 5-Fluorouracil (750 mg/m{sup 2} 120-hour infusion or 1,000 mg/m{sup 2} 96-hour infusion) plus CP (100 mg/m{sup 2}) on the first day of each cycle or MMC (10-15 mg/m{sup 2}) on the first day of Cycle 1 was administeredmore » concurrent with radiotherapy (total dose, 55-59.4 Gy). Of the 179 patients, 60% were included from a randomized trial initiated at the Instituto Nacional de Cancer in 1991 that compared concurrent chemoradiotherapy with MMC vs. CP. Results: The median follow-up for the whole chemoradiotherapy group was 83 months. The median patient age was 58 years, 57% had Stage T3-T4 tumors, and 35% had N-positive disease. The 5-year cumulative colostomy rate was not significantly different between the CP group (22%) and MMC group (29%; p = .28). The actuarial 10-year overall survival and disease-free survival rate for the CP group was 54% and 49% and for the MMC group was 52% and 53%, respectively (p = .32 and p = .92, respectively). On multivariate analysis, male gender (p = .042) and advanced Stage T3-T4 disease (p <.0001) were statistically significant for worse disease-free survival. Stage T3-T4 (p = .039) and N+ (p = .039) disease remained independently significant for overall survival. Conclusion: Long-term follow-up has confirmed the good results of chemoradiotherapy with CP plus 5-fluorouracil, which seem to provide results equivalent to those with MMC plus 5-fluorouracil.« less

Kinesthetic illusions attenuate experimental muscle pain, as do muscle and cutaneous stimulation.

PubMed

Gay, André; Aimonetti, Jean-Marc; Roll, Jean-Pierre; Ribot-Ciscar, Edith

2015-07-30

In the present study, muscle pain was induced experimentally in healthy subjects by administrating hypertonic saline injections into the tibialis anterior (TA) muscle. We first aimed at comparing the analgesic effects of mechanical vibration applied to either cutaneous or muscle receptors of the TA or to both types simultaneously. Secondly, pain alleviation was compared in subjects in whom muscle tendon vibration evoked kinesthetic illusions of the ankle joint. Muscle tendon vibration, which primarily activated muscle receptors, reduced pain intensity by 30% (p<0.01). In addition, tangential skin vibration reduced pain intensity by 33% (p<0.01), primarily by activating cutaneous receptors. Concurrently stimulating both sensory channels induced stronger analgesic effects (-51%, p<0.01), as shown by the lower levels of electrodermal activity. The strongest analgesic effects of the vibration-induced muscle inputs occurred when illusory movements were perceived (-38%, p=0.01). The results suggest that both cutaneous and muscle sensory feedback reduce muscle pain, most likely via segmental and supraspinal processes. Further clinical trials are needed to investigate these new methods of muscle pain relief. Copyright © 2015 Elsevier B.V. All rights reserved.

Immunogenicity and safety of a respiratory syncytial virus fusion protein (RSV F) nanoparticle vaccine in older adults.

PubMed

Fries, Louis; Shinde, Vivek; Stoddard, Jeffrey J; Thomas, D Nigel; Kpamegan, Eloi; Lu, Hanxin; Smith, Gale; Hickman, Somia P; Piedra, Pedro; Glenn, Gregory M

2017-01-01

A preventative strategy for Respiratory Syncytial Virus (RSV) infection constitutes an under-recognized unmet medical need among older adults. Four formulations of a novel recombinant RSV F nanoparticle vaccine (60 or 90 μg RSV F protein, with or without aluminum phosphate adjuvant) administered concurrently with a licensed inactivated trivalent influenza vaccine (TIV) in older adult subjects were evaluated for safety and immunogenicity in this randomized, observer-blinded study. A total of 220 healthy males and females ≥ 60 years of age, without symptomatic cardiopulmonary disease, were vaccinated concurrently with TIV and RSV F vaccine or placebo. All vaccine formulations produced an acceptable safety profile, with no vaccine-related serious adverse events or evidence of systemic toxicity. Vaccine-induced immune responses were rapid, rising as early as 7 days post-vaccination; and were comparable in all formulations in terms of magnitude, with maximal levels attained within 28 (unadjuvanted) or 56 (adjuvanted) days post-vaccination. Peak anti-F protein IgG antibody levels rose 3.6- to 5.6-fold, with an adjuvant effect observed at the 60 μg dose, and a dose-effect observed between the unadjuvanted 60 and 90 μg regimens. The anti-F response persisted through 12 months post-vaccination. Palivizumab-competitive antibodies were below quantifiable levels (<33 μg/mL) at day 0. The rise of antibodies with specificity for Site II peptide, and the palivizumab-competitive binding activity, denoting antibodies binding at, or in proximity to, antigenic Site II on the F protein, closely paralleled the anti-F response. However, a larger proportion of antibodies in adjuvanted vaccine recipients bound to the Site II peptide at high avidity. Day 0 neutralizing antibodies were high in all subjects and rose 1.3- to 1.7-fold in response to vaccination. Importantly, the RSV F vaccine co-administered with TIV did not impact the serum hemagglutination inhibition antibody responses to a standard-dose TIV, and TIV did not impact the immune response to the RSV F vaccine. RSV F protein nanoparticle vaccine induced increases in measures of functional immunity to RSV in older adults and demonstrated an acceptable safety profile. Adjuvanted formulations provided additional immunogenicity benefit as compared to increasing antigen dose alone. This trial was registered with ClinicalTrials.gov number NCT01709019.

How good are GPs at adhering to a pragmatic trial protocol in primary care? Results from the ADDITION-Cambridge cluster-randomised pragmatic trial

PubMed Central

Boothby, Clare E; Griffin, Simon J

2018-01-01

Objective To assess the fidelity of general practitioners’ (GPs) adherence to a long-term pragmatic trial protocol. Design Retrospective analyses of electronic primary care records of participants in the pragmatic cluster-randomised ADDITION (Anglo-Danish-Dutch Study of Intensive Treatment In People with Screen Detected Diabetes in Primary Care)-Cambridge trial, comparing intensive multifactorial treatment (IT) versus routine care (RC). Data were collected from the date of diagnosis until December 2010. Setting Primary care surgeries in the East of England. Study sample/participants A subsample (n=189, RC arm: n=99, IT arm: n=90) of patients from the ADDITION-Cambridge cohort (867 patients), consisting of patients 40–69 years old with screen-detected diabetes mellitus. Interventions In the RC arm treatment was delivered according to concurrent treatment guidelines. Surgeries in the IT arm received funding for additional contacts between GPs/nurses and patients, and GPs were advised to follow more intensive treatment algorithms for the management of glucose, lipids and blood pressure and aspirin therapy than in the RC arm. Outcome measures The number of annual contacts between patients and GPs/nurses, the proportion of patients receiving prescriptions for cardiometabolic medication in years 1–5 after diabetes diagnosis and the adherence to prescription algorithms. Results The difference in the number of annual GP contacts (β=0.65) and nurse contacts (β=−0.15) between the study arms was small and insignificant. Patients in the IT arm were more likely to receive glucose-lowering (OR=3.27), ACE-inhibiting (OR=2.03) and lipid-lowering drugs (OR=2.42, all p values <0.01) than patients in the RC arm. The prescription adherence varied between medication classes, but improved in both trial arms over the 5-year follow-up. Conclusions The adherence of GPs to different aspects of the trial protocol was mixed. Background changes in healthcare policy need to be considered as they have the potential to dilute differences in treatment intensity and hence incremental effects. Trial registration number ISRCTN86769081. PMID:29903781

Induction gemcitabine in standard dose or prolonged low-dose with cisplatin followed by concurrent radiochemotherapy in locally advanced non-small cell lung cancer: a randomized phase II clinical trial

PubMed Central

Vrankar, Martina; Zwitter, Matjaz; Bavcar, Tanja; Milic, Ana; Kovac, Viljem

2014-01-01

Background The optimal combination of chemotherapy with radiation therapy for treatment locally advanced non-small cell lung cancer (NSCLC) remains an open issue. This randomized phase II study compared gemcitabine in two different schedules and cisplatin - as induction chemotherapy, followed by radiation therapy concurrent with cisplatin and etoposid. Patients and methods. Eligible patients had microscopically confirmed inoperable non-metastatic non-small cell lung cancer; fulfilled the standard criteria for platin-based chemotherapy; and signed informed consent. Patients were treated with 3 cycles of induction chemotherapy with gemcitabine and cisplatin. Two different aplications of gemcitabine were compared: patients in arm A received gemcitabine at 1250 mg/m2 in a standard half hour i.v. infusion on days 1 and 8; patients in arm B received gemcitabine at 250 mg/m2 in prolonged 6-hours i.v. infusion on days 1 and 8. In both arms, cisplatin 75 mg/m2 on day 2 was administered. All patients continued treatment with radiation therapy with 60–66 Gy concurrent with cisplatin 50 mg/m2 on days 1, 8, 29 and 36 and etoposid 50 mg/m2 on days 1–5 and 29–33. The primary endpoint was response rate (RR) after induction chemotherapy; secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS). Results From September 2005 to November 2010, 106 patients were recruited to this study. No statistically signifficant differences were found in RR after induction chemotherapy between the two arms (48.1% and 57.4%, p = 0.34). Toxicity profile was comparable and mild with grade 3/4 neutropenia as primary toxicity in both arms. One patient in arm B suffered from acute peripheral ischemia grade 4 and an amputation of lower limb was needed. With a median follow-up of 69.3 months, progression-free survival and median survival in arm A were 15.7 and 24.8 months compared to 18.9 and 28.6 months in arm B. The figures for 1- and 3-year overall survival were 73.1% and 30.8% in arm A, and 81.5 % and 44.4% in arm B, respectively. Conclusions Among the two cisplatin-based doublets of induction chemotherapy for inoperable NSCLC, both schedules of gemcitabine have a comparable toxicity profile. Figures for RR, PFS and OS are among the best reported in current literature. While there is a trend towards better efficacy of the treament with prolonged infusion of gemcitabine, the difference between the two arms did not reach statistical significance. PMID:25435850

Concurrent sexual partnerships among female sex workers and their non-commercial male partners in Tijuana and Ciudad Juárez, Mexico

PubMed Central

Robertson, Angela M.; Syvertsen, Jennifer L.; Rangel, M. Gudelia; Staines, Hugo S.; Morris, Martina; Patterson, Thomas L.; Ulibarri, Monica D.; Strathdee, Steffanie A.

2013-01-01

Objectives To investigate the prevalence and correlates of concurrent (overlapping) sexual partnerships among female sex workers (FSWs) and their non-commercial male partners in two Mexico-U.S. border cities. Methods A cross-sectional survey of FSWs and their non-commercial male partners was conducted in Tijuana and Ciudad Juárez, Mexico (2010–2011). Eligible FSWs and verified non-commercial partners were aged ≥18 years; FSWs had ever used hard drugs (lifetime) and recently exchanged sex for money, drugs, or other goods (past month). Participants underwent baseline questionnaires obtaining dates of sex and condom use with ≤5 other recurring partners, including FSWs’ regular clients. These dates were compared to dates of sex with enrolled study partners to determine overlap (i.e., “recurring” concurrency). Bivariate probit regression identified recurring concurrency correlates. Results Among 428 individuals (214 couples), past-year recurring concurrency prevalence was 16% and was higher among women than their non-commercial male partners (26% vs. 6%). In 10 couples (5%), both partners reported recurring concurrency. The majority of couples (64%) always had unprotected sex, and most of the individuals (70%) with recurring concurrency “sometimes” or “never” used condoms with their concurrent partners. Recurring concurrency was positively associated with FSWs’ income, men’s caballerismo (a form of traditional masculinity), and men’s belief that their FSW-partners had STIs. Conclusions Recurring concurrency, representing sustained periods of overlapping partnerships in which unprotected sex was common, should be addressed by couple-based STI prevention interventions. PMID:23172036

CESAR: conventional ventilatory support vs extracorporeal membrane oxygenation for severe adult respiratory failure.

PubMed

Peek, Giles J; Clemens, Felicity; Elbourne, Diana; Firmin, Richard; Hardy, Pollyanna; Hibbert, Clare; Killer, Hilliary; Mugford, Miranda; Thalanany, Mariamma; Tiruvoipati, Ravin; Truesdale, Ann; Wilson, Andrew

2006-12-23

An estimated 350 adults develop severe, but potentially reversible respiratory failure in the UK annually. Current management uses intermittent positive pressure ventilation, but barotrauma, volutrauma and oxygen toxicity can prevent lung recovery. An alternative treatment, extracorporeal membrane oxygenation, uses cardio-pulmonary bypass technology to temporarily provide gas exchange, allowing ventilator settings to be reduced. While extracorporeal membrane oxygenation is proven to result in improved outcome when compared to conventional ventilation in neonates with severe respiratory failure, there is currently no good evidence from randomised controlled trials to compare these managements for important clinical outcomes in adults, although evidence from case series is promising. The aim of the randomised controlled trial of Conventional ventilatory support vs extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR) is to assess whether, for patients with severe, but potentially reversible, respiratory failure, extracorporeal membrane oxygenation will increase the rate of survival without severe disability ('confined to bed' and 'unable to wash or dress') by six months post-randomisation, and be cost effective from the viewpoints of the NHS and society, compared to conventional ventilatory support. Following assent from a relative, adults (18-65 years) with severe, but potentially reversible, respiratory failure (Murray score >/= 3.0 or hypercapnea with pH < 7.2) will be randomised for consideration of extracorporeal membrane oxygenation at Glenfield Hospital, Leicester or continuing conventional care in a centre providing a high standard of conventional treatment. The central randomisation service will minimise by type of conventional treatment centre, age, duration of high pressure ventilation, hypoxia/hypercapnea, diagnosis and number of organs failed, to ensure balance in key prognostic variables. Extracorporeal membrane oxygenation will not be available for patients meeting entry criteria outside the trial. 180 patients will be recruited to have 80% power to be able to detect a one third reduction in the primary outcome from 65% at 5% level of statistical significance (2-sided test). Secondary outcomes include patient morbidity and health status at 6 months. Analysis will be based on intention to treat. A concurrent economic evaluation will also be performed to compare the costs and outcomes of both treatments.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gunderson, Leonard L., E-mail: gunderson.leonard@mayo.edu; Moughan, Jennifer; Ajani, Jaffer A.

Purpose: The long-term update of US GI Intergroup RTOG 98-11 anal cancer trial found that concurrent chemoradiation (CCRT) with fluorouracil (5-FU) plus mitomycin had a significant impact on disease-free survival (DFS) and overall survival (OS) compared with induction plus concurrent 5-FU plus cisplatin. The intent of the current analysis was to determine the impact of tumor node (TN) category of disease on survival (DFS and OS), colostomy failure (CF), and relapse (local-regional failure [LRF] and distant metastases [DM]) in this patient group. Methods and Materials: DFS and OS were estimated univariately by using the Kaplan-Meier method, and 6 TN categoriesmore » were compared by the log–rank test (T2N0, T3N0, T4N0, T2N1-3, T3N1-3, and T4N1-3). Time to relapse and colostomy were estimated by the cumulative incidence method, and TN categories were compared using Gray's test. Results: Of 682 patients, 620 were analyzable for outcomes by TN category. All endpoints showed statistically significant differences among the TN categories of disease (OS, P<.0001; DFS, P<.0001; LRF, P<.0001; DM, P=.0011; CF, P=.01). Patients with the poorest OS, DFS, and LRF outcomes were those with T3-4N-positive (+) disease. CF was lowest for T2N0 and T2N+ (11%, 11%, respectively) and worst for the T4N0, T3N+, and T4N+ categories (26%, 27%, 24%, respectively). Conclusions: TN category of disease has a statistically significant impact on OS, DFS, LRF, DM, and CF in patients treated with CCRT and provides excellent prognostic information for outcomes in patients with anal carcinoma. Significant challenges remain for patients with T4N0 and T3-4N+ categories of disease with regard to survival, relapse, and CF and lesser challenges for T2-3N0/T2N+ categories.« less

Neck pain and postural balance among workers with high postural demands - a cross-sectional study

PubMed Central

2011-01-01

Background Neck pain is related to impaired postural balance among patients and is highly prevalent among workers with high postural demands, for example, cleaners. We therefore hypothesised, that cleaners with neck pain suffer from postural dysfunction. This cross-sectional study tested if cleaners with neck pain have an impaired postural balance compared with cleaners without neck pain. Methods Postural balance of 194 cleaners with (n = 85) and without (N = 109) neck pain was studied using three different tests. Success or failure to maintain the standing position for 30 s in unilateral stance was recorded. Participants were asked to stand on a force platform for 30 s in the Romberg position with eyes open and closed. The centre of pressure of the sway was calculated, and separated into a slow (rambling) and fast (trembling) component. Subsequently, the 95% confidence ellipse area (CEA) was calculated. Furthermore a perturbation test was performed. Results More cleaners with neck pain (81%) failed the unilateral stance compared with cleaners without neck pain (61%) (p < 0.01). However, the risk of failure in unilateral stance was statistically elevated in cleaners with concurrent neck/low back pain compared to cleaners without neck/low back pain (p < 0.01), whereas pain at only neck or only low back did not increase the risk. Impaired postural balance, measured as CEA (p < 0.01), rambling (p < 0.05) and trembling (p < 0.05) was observed among cleaners with neck pain in comparison with cleaners without neck pain in the Romberg position with eyes closed, but not with eyes open. Conclusions Postural balance is impaired among cleaners with neck pain and the current study suggests a particular role of the slow component of postural sway. Furthermore, the unilateral stance test is a simple test to illustrate functional impairment among cleaners with concurrent neck and low back pain. Trial registration ISRCTN96241850 PMID:21806796

Therapist guided internet based cognitive behavioural therapy for body dysmorphic disorder: single blind randomised controlled trial.

PubMed

Enander, Jesper; Andersson, Erik; Mataix-Cols, David; Lichtenstein, Linn; Alström, Katarina; Andersson, Gerhard; Ljótsson, Brjánn; Rück, Christian

2016-02-02

To evaluate the efficacy of therapist guided internet based cognitive behavioural therapy (CBT) programme for body dysmorphic disorder (BDD-NET) compared with online supportive therapy. A 12 week single blind parallel group randomised controlled trial. Academic medical centre. 94 self referred adult outpatients with a diagnosis of body dysmorphic disorder and a modified Yale-Brown obsessive compulsive scale (BDD-YBOCS) score of ≥ 20. Concurrent psychotropic drug treatment was permitted if the dose had been stable for at least two months before enrolment and remained unchanged during the trial. Participants received either BDD-NET (n=47) or supportive therapy (n=47) delivered via the internet for 12 weeks. The primary outcome was the BDD-YBOCS score after treatment and follow-up (three and six months from baseline) as evaluated by a masked assessor. Responder status was defined as a ≥ 30% reduction in symptoms on the scale. Secondary outcomes were measures of depression (MADRS-S), global functioning (GAF), clinical global improvement (CGI-I), and quality of life (EQ5D). The six month follow-up time and all outcomes other than BDD-YBOCS and MADRS-S at 3 months were not pre-specified in the registration at clinicaltrials.gov because of an administrative error but were included in the original trial protocol approved by the regional ethics committee before the start of the trial. BDD-NET was superior to supportive therapy and was associated with significant improvements in severity of symptoms of body dysmorphic disorder (BDD-YBOCS group difference -7.1 points, 95% confidence interval -9.8 to -4.4), depression (MADRS-S group difference -4.5 points, -7.5 to -1.4), and other secondary measures. At follow-up, 56% of those receiving BDD-NET were classed as responders, compared with 13% receiving supportive therapy. The number needed to treat was 2.34 (1.71 to 4.35). Self reported satisfaction was high. CBT can be delivered safely via the internet to patients with body dysmorphic disorder. BDD-NET has the potential to increase access to evidence based psychiatric care for this mental disorder, in line with NICE priority recommendations. It could be particularly useful in a stepped care approach, in which general practitioner or other mental health professionals can offer treatment to people with mild to moderate symptoms at low risk of suicide.Trial registration ClinicalTrials.gov ID: NCT02010619. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Therapist guided internet based cognitive behavioural therapy for body dysmorphic disorder: single blind randomised controlled trial

PubMed Central

Andersson, Erik; Mataix-Cols, David; Lichtenstein, Linn; Alström, Katarina; Andersson, Gerhard; Ljótsson, Brjánn; Rück, Christian

2016-01-01

Objectives To evaluate the efficacy of therapist guided internet based cognitive behavioural therapy (CBT) programme for body dysmorphic disorder (BDD-NET) compared with online supportive therapy. Design A 12 week single blind parallel group randomised controlled trial. Setting Academic medical centre. Participants 94 self referred adult outpatients with a diagnosis of body dysmorphic disorder and a modified Yale-Brown obsessive compulsive scale (BDD-YBOCS) score of ≥20. Concurrent psychotropic drug treatment was permitted if the dose had been stable for at least two months before enrolment and remained unchanged during the trial. Interventions Participants received either BDD-NET (n=47) or supportive therapy (n=47) delivered via the internet for 12 weeks. Main outcome measures The primary outcome was the BDD-YBOCS score after treatment and follow-up (three and six months from baseline) as evaluated by a masked assessor. Responder status was defined as a ≥30% reduction in symptoms on the scale. Secondary outcomes were measures of depression (MADRS-S), global functioning (GAF), clinical global improvement (CGI-I), and quality of life (EQ5D). The six month follow-up time and all outcomes other than BDD-YBOCS and MADRS-S at 3 months were not pre-specified in the registration at clinicaltrials.gov because of an administrative error but were included in the original trial protocol approved by the regional ethics committee before the start of the trial. Results BDD-NET was superior to supportive therapy and was associated with significant improvements in severity of symptoms of body dysmorphic disorder (BDD-YBOCS group difference −7.1 points, 95% confidence interval −9.8 to −4.4), depression (MADRS-S group difference −4.5 points, −7.5 to −1.4), and other secondary measures. At follow-up, 56% of those receiving BDD-NET were classed as responders, compared with 13% receiving supportive therapy. The number needed to treat was 2.34 (1.71 to 4.35). Self reported satisfaction was high. Conclusions CBT can be delivered safely via the internet to patients with body dysmorphic disorder. BDD-NET has the potential to increase access to evidence based psychiatric care for this mental disorder, in line with NICE priority recommendations. It could be particularly useful in a stepped care approach, in which general practitioner or other mental health professionals can offer treatment to people with mild to moderate symptoms at low risk of suicide. Trial registration ClinicalTrials.gov ID: NCT02010619. PMID:26837684

Discrete physiological effects of beetroot juice and potassium nitrate supplementation following 4-wk sprint interval training.

PubMed

Thompson, Christopher; Vanhatalo, Anni; Kadach, Stefan; Wylie, Lee J; Fulford, Jonathan; Ferguson, Scott K; Blackwell, Jamie R; Bailey, Stephen J; Jones, Andrew M

2018-06-01

The physiological and exercise performance adaptations to sprint interval training (SIT) may be modified by dietary nitrate ([Formula: see text]) supplementation. However, it is possible that different types of [Formula: see text] supplementation evoke divergent physiological and performance adaptations to SIT. The purpose of this study was to compare the effects of 4-wk SIT with and without concurrent dietary [Formula: see text] supplementation administered as either [Formula: see text]-rich beetroot juice (BR) or potassium [Formula: see text] (KNO 3 ). Thirty recreationally active subjects completed a battery of exercise tests before and after a 4-wk intervention in which they were allocated to one of three groups: 1) SIT undertaken without dietary [Formula: see text] supplementation (SIT); 2) SIT accompanied by concurrent BR supplementation (SIT + BR); or 3) SIT accompanied by concurrent KNO 3 supplementation (SIT + KNO 3 ). During severe-intensity exercise, V̇o 2peak and time to task failure were improved to a greater extent with SIT + BR than SIT and SIT + KNO 3 ( P < 0.05). There was also a greater reduction in the accumulation of muscle lactate at 3 min of severe-intensity exercise in SIT + BR compared with SIT + KNO 3 ( P < 0.05). Plasma [Formula: see text] concentration fell to a greater extent during severe-intensity exercise in SIT + BR compared with SIT and SIT + KNO 3 ( P < 0.05). There were no differences between groups in the reduction in the muscle phosphocreatine recovery time constant from pre- to postintervention ( P > 0.05). These findings indicate that 4-wk SIT with concurrent BR supplementation results in greater exercise capacity adaptations compared with SIT alone and SIT with concurrent KNO 3 supplementation. This may be the result of greater NO-mediated signaling in SIT + BR compared with SIT + KNO 3 . NEW & NOTEWORTHY We compared the influence of different forms of dietary nitrate supplementation on the physiological and performance adaptations to sprint interval training (SIT). Compared with SIT alone, supplementation with nitrate-rich beetroot juice, but not potassium [Formula: see text], enhanced some physiological adaptations to training.

CT colonography: investigation of the optimum reader paradigm by using computer-aided detection software.

PubMed

Taylor, Stuart A; Charman, Susan C; Lefere, Philippe; McFarland, Elizabeth G; Paulson, Erik K; Yee, Judy; Aslam, Rizwan; Barlow, John M; Gupta, Arun; Kim, David H; Miller, Chad M; Halligan, Steve

2008-02-01

To prospectively compare the diagnostic performance and time efficiency of both second and concurrent computer-aided detection (CAD) reading paradigms for retrospectively obtained computed tomographic (CT) colonography data sets by using consensus reading (three radiologists) of colonoscopic findings as a reference standard. Ethical permission, HIPAA compliance (for U.S. institutions), and patient consent were obtained from all institutions for use of CT colonography data sets in this study. Ten radiologists each read 25 CT colonography data sets (12 men, 13 women; mean age, 61 years) containing 69 polyps (28 were 1-5 mm, 41 were >or=6 mm) by using workstations integrated with CAD software. Reading was randomized to either "second read" CAD (applied only after initial unassisted assessment) or "concurrent read" CAD (applied at the start of assessment). Data sets were reread 6 weeks later by using the opposing paradigm. Polyp sensitivity and reading times were compared by using multilevel logistic and linear regression, respectively. Receiver operating characteristic (ROC) curves were generated. Compared with the unassisted read, odds of improved polyp (>or=6 mm) detection were 1.5 (95% confidence interval [CI]: 1.0, 2.2) and 1.3 (95% CI: 0.9, 1.9) by using CAD as second and concurrent reader, respectively. Detection odds by using CAD concurrently were 0.87 (95% CI: 0.59, 1.3) and 0.76 (95% CI: 0.57, 1.01) those of second read CAD, excluding and including polyps 1-5 mm, respectively. The concurrent read took 2.9 minutes (95% CI: -3.8, -1.9) less than did second read. The mean areas under the ROC curve (95% CI) for the unassisted read, second read CAD, and concurrent read CAD were 0.83 (95% CI: 0.78, 0.87), 0.86 (95% CI: 0.82, 0.90), and 0.88 (95% CI: 0.83, 0.92), respectively. CAD is more time efficient when used concurrently than when used as a second reader, with similar sensitivity for polyps 6 mm or larger. However, use of second read CAD maximizes sensitivity, particularly for smaller lesions. (c) RSNA, 2007.

An investigation of emotion recognition training to reduce symptoms of social anxiety in adolescence.

PubMed

Rawdon, Caroline; Murphy, Daria; Motyer, Gillian; Munafò, Marcus R; Penton-Voak, Ian; Fitzgerald, Amanda

2018-05-01

This study aimed to examine the effect of emotion recognition training on social anxiety symptoms among adolescents, aged 15-18 years. The study included a screening session, which identified participants who scored above a cut-off on a self-report measure of social anxiety for enrolment into a randomized controlled trial (Clinical Trials ID: NCT02550379). Participants were randomized to an intervention condition designed to increase the perception of happiness over disgust in ambiguous facial expressions or a sham intervention control condition, and completed self-report measures of social anxiety, fear of negative evaluation, anxiety-related disorders, and depressive symptoms. The intervention group demonstrated a strong shift in the balance point at which they perceived happiness over disgust in ambiguous facial expressions. This increase in positive perception was not associated with any changes in the primary outcome of social anxiety; however, some evidence of improvement in symptomatology was observed on one of a number of secondary outcomes. Those in the intervention group had lower depression symptoms at 2-week follow-up, compared to those in the control group who received the sham intervention training. Potential reasons for why the shift in balance point measurement was not associated with a concurrent shift in symptoms of social anxiety are discussed. Copyright © 2018 Elsevier B.V. All rights reserved.

Assessing the robustness of passive scattering proton therapy with regard to local recurrence in stage III non-small cell lung cancer: a secondary analysis of a phase II trial.

PubMed

Zhu, Zhengfei; Liu, Wei; Gillin, Michael; Gomez, Daniel R; Komaki, Ritsuko; Cox, James D; Mohan, Radhe; Chang, Joe Y

2014-05-06

We assessed the robustness of passive scattering proton therapy (PSPT) plans for patients in a phase II trial of PSPT for stage III non-small cell lung cancer (NSCLC) by using the worst-case scenario method, and compared the worst-case dose distributions with the appearance of locally recurrent lesions. Worst-case dose distributions were generated for each of 9 patients who experienced recurrence after concurrent chemotherapy and PSPT to 74 Gy(RBE) for stage III NSCLC by simulating and incorporating uncertainties associated with set-up, respiration-induced organ motion, and proton range in the planning process. The worst-case CT scans were then fused with the positron emission tomography (PET) scans to locate the recurrence. Although the volumes enclosed by the prescription isodose lines in the worst-case dose distributions were consistently smaller than enclosed volumes in the nominal plans, the target dose coverage was not significantly affected: only one patient had a recurrence outside the prescription isodose lines in the worst-case plan. PSPT is a relatively robust technique. Local recurrence was not associated with target underdosage resulting from estimated uncertainties in 8 of 9 cases.

Curcumin for Radiation Dermatitis: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Thirty Breast Cancer Patients

PubMed Central

Ryan, Julie L.; Heckler, Charles E.; Ling, Marilyn; Katz, Alan; Williams, Jacqueline P.; Pentland, Alice P.; Morrow, Gary R.

2014-01-01

Radiation dermatitis occurs in approximately 95% of patients receiving radiotherapy (RT) for breast cancer. We conducted a randomized, double-blind, placebo-controlled clinical trial to assess the ability of curcumin to reduce radiation dermatitis severity in 30 breast cancer patients. Eligible patients were adult females with noninflammatory breast cancer or carcinoma in situ prescribed RT without concurrent chemotherapy. Randomized patients took 2.0 grams of curcumin or placebo orally three times per day (i.e., 6.0 grams daily) throughout their course of RT. Weekly assessments included Radiation Dermatitis Severity (RDS) score, presence of moist desquamation, redness measurement, McGill Pain Questionnaire-Short Form and Symptom Inventory questionnaire. The 30 evaluable patients were primarily white (90%) and had a mean age of 58.1 years. Standard pooled variances t test showed that curcumin reduced RDS at end of treatment compared to placebo (mean RDS =2.6 vs. 3.4; P =0.008). Fisher’s exact test revealed that fewer curcumin-treated patients had moist desquamation (28.6% vs. 87.5%; P =0.002). No significant differences were observed between arms for demographics, compliance, radiation skin dose, redness, pain or symptoms. In conclusion, oral curcumin, 6.0 g daily during radiotherapy, reduced the severity of radiation dermatitis in breast cancer patients. PMID:23745991

Concurrent vaccination of boars with type 1 and type 2 porcine reproductive and respiratory syndrome virus (PRRSV) reduces seminal shedding of type 1 and type 2 PRRSV

PubMed Central

Jeong, Jiwoon; Park, Changhoon; Kang, Ikjae; Park, Su-Jin; Chae, Chanhee

2017-01-01

The objective of the present study was to determine the effect of concurrent vaccination of boars with type 1 and type 2 porcine reproductive and respiratory syndrome virus (PRRSV) on seminal shedding of both genotypes. The boars tolerated well concurrent administration of 2 commercial PRRSV vaccines, and no adverse reactions were observed. No interference in the humoral immune response (measured as the level of anti-PRRSV antibodies) or the cell-mediated immune response (measured as the level of PRRSV-specific interferon-γ-secreting cells) was observed after concurrent administration compared with single administration of the same vaccines. Concurrent vaccination significantly reduced the load of type 1 and type 2 PRRSV in blood and semen after singular (type 1 or type 2) and dual (type 1 and type 2) PRRSV challenge, and it did not significantly affect the efficacy of each vaccine. The results demonstrate that concurrent vaccination of boars with type 1 and type 2 PRRSV reduces shedding of both genotypes in semen. PMID:28408778

CHANGING ATTITUDES ABOUT CONCURRENCY AMONG YOUNG AFRICAN AMERICANS: RESULTS OF A RADIO CAMPAIGN

PubMed Central

Adimora, Adaora A.; Schoenbach, Victor J.; Cates, Joan R.; Cope, Anna B.; Ramirez, Catalina; Powell, Wizdom; Agans, Robert P.

2018-01-01

We created and evaluated an 8-month campaign of provocative radio ads to change attitudes about concurrent (overlapping) sexual partnerships among young African Americans. Using focus groups, vignette-based items, and factor analysis, we created a concurrency attitude scale and compared its score distributions in independent samples of African Americans, ages 18-34 years, interviewed by telephone before (n=678) and after (n=479) the campaign. Pre-and post-campaign samples reflected similar response rates (pre: 32.6%; post: 31.8%) and distributions of personal characteristics. Reported exposure to concurrency messages was greater after the campaign (pre: 6.3%, post: 30.9%), and mean scores became less accepting of concurrency (pre: 3.40 (95% confidence interval: 3.23, 3.57); post: 2.62 (2.46, 2.78)). Score differences were not a function of differences in composition of the two samples (adjusted means: pre: 3.37 (3.21, 3.53); post: 2.62 (2.47, 2.76)). Findings demonstrate that a carefully targeted, intensive mass media campaign can change attitudes about concurrency, which should facilitate behavior change. PMID:28825864

The psychometric properties of Observer OPTION(5), an observer measure of shared decision making.

PubMed

Barr, Paul J; O'Malley, Alistair James; Tsulukidze, Maka; Gionfriddo, Michael R; Montori, Victor; Elwyn, Glyn

2015-08-01

Observer OPTION(5) was designed as a more efficient version of OPTION(12), the most commonly used measure of shared decision making (SDM). The current paper assesses the psychometric properties of OPTION(5). Two raters used OPTION(5) to rate recordings of clinical encounters from two previous patient decision aid (PDA) trials (n=201; n=110). A subsample was re-rated two weeks later. We assessed discriminative validity, inter-rater reliability, intra-rater reliability, and concurrent validity. OPTION(5) demonstrated discriminative validity, with increases in SDM between usual care and PDA arms. OPTION(5) also demonstrated concurrent validity with OPTION(12), r=0.61 (95%CI 0.54, 0.68) and intra-rater reliability, r=0.93 (0.83, 0.97). The mean difference in rater score was 8.89 (95% Credibility Interval, 7.5, 10.3), with intraclass correlation (ICC) of 0.67 (95% Credibility Interval, 0.51, 0.91) for the accuracy of rater scores and 0.70 (95% Credibility Interval, 0.56, 0.94) for the consistency of rater scores across encounters, indicating good inter-rater reliability. Raters reported lower cognitive burden when using OPTION(5) compared to OPTION(12). OPTION(5) is a brief, theoretically grounded observer measure of SDM with promising psychometric properties in this sample and low burden on raters. OPTION(5) has potential to provide reliable, valid assessment of SDM in clinical encounters. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Performing concurrent operations in academic vascular neurosurgery does not affect patient outcomes.

PubMed

Zygourakis, Corinna C; Lee, Janelle; Barba, Julio; Lobo, Errol; Lawton, Michael T

2017-11-01

OBJECTIVE Concurrent surgeries, also known as "running two rooms" or simultaneous/overlapping operations, have recently come under intense scrutiny. The goal of this study was to evaluate the operative time and outcomes of concurrent versus nonconcurrent vascular neurosurgical procedures. METHODS The authors retrospectively reviewed 1219 procedures performed by 1 vascular neurosurgeon from 2012 to 2015 at the University of California, San Francisco. Data were collected on patient age, sex, severity of illness, risk of mortality, American Society of Anesthesiologists (ASA) status, procedure type, admission type, insurance, transfer source, procedure time, presence of resident or fellow in operating room (OR), number of co-surgeons, estimated blood loss (EBL), concurrent vs nonconcurrent case, severe sepsis, acute respiratory failure, postoperative stroke causing neurological deficit, unplanned return to OR, 30-day mortality, and 30-day unplanned readmission. For aneurysm clipping cases, data were also obtained on intraoperative aneurysm rupture and postoperative residual aneurysm. Chi-square and t-tests were performed to compare concurrent versus nonconcurrent cases, and then mixed-effects models were created to adjust for different procedure types, patient demographics, and clinical indicators between the 2 groups. RESULTS There was a significant difference in procedure type for concurrent (n = 828) versus nonconcurrent (n = 391) cases. Concurrent cases were more likely to be routine/elective admissions (53% vs 35%, p < 0.001) and physician referrals (59% vs 38%, p < 0.001). This difference in patient/case type was also reflected in the lower severity of illness, risk of death, and ASA class in the concurrent versus nonconcurrent cases (p < 0.01). Concurrent cases had significantly longer procedural times (243 vs 213 minutes) and more unplanned 30-day readmissions (5.7% vs 3.1%), but shorter mean length of hospital stay (11.2 vs 13.7 days), higher rates of discharge to home (66% vs 51%), lower 30-day mortality rates (3.1% vs 6.1%), lower rates of acute respiratory failure (4.3% vs 8.2%), and decreased 30-day unplanned returns to the OR (3.3% vs 6.9%; all p < 0.05). Rates of severe sepsis, postoperative stroke, intraoperative aneurysm rupture, and postoperative aneurysm residual were equivalent between the concurrent and nonconcurrent groups (all p values nonsignificant). Mixed-effects models showed that after controlling for procedure type, patient demographics, and clinical indicators, there was no significant difference in acute respiratory failure, severe sepsis, 30-day readmission, postoperative stroke, EBL, length of stay, discharge status, or intraoperative aneurysm rupture between concurrent and nonconcurrent cases. Unplanned return to the OR and 30-day mortality were significantly lower in concurrent cases (odds ratio 0.55, 95% confidence interval 0.31-0.98, p = 0.0431, and odds ratio 0.81, p < 0.001, respectively), but concurrent cases had significantly longer procedure durations (odds ratio 21.73; p < 0.001). CONCLUSIONS Overall, there was a significant difference in the types of concurrent versus nonconcurrent cases, with more routine/elective cases for less sick patients scheduled in an overlapping fashion. After adjusting for patient demographics, procedure type, and clinical indicators, concurrent cases had longer procedure times, but equivalent patient outcomes, as compared with nonconcurrent vascular neurosurgical procedures.

Concurrent rib and pelvic fractures as an indicator of solid abdominal organ injury.

PubMed

Al-Hassani, Ammar; Afifi, Ibrahim; Abdelrahman, Husham; El-Menyar, Ayman; Almadani, Ammar; Recicar, Jan; Al-Thani, Hassan; Maull, Kimball; Latifi, Rifat

2013-01-01

To study the association of solid organ injuries (SOIs) in patients with concurrent rib and pelvic fractures. Retrospective analysis of prospectively collected data from November 2007 to May 2010. Patients' demographics, mechanism of injury, Injury severity scoring, pelvic fracture, and SOIs were analyzed. Patients with SOIs were compared in rib fractures with and without pelvic fracture. The study included 829 patients (460 with rib fractures ± pelvic fracture and 369 with pelvic fracture alone) with mean age of 35 ± 12.7 years. Motor vehicle crashes (45%) and falls from height (30%) were the most common mechanism of injury. The overall incidence of SOIs in this study was 22% (185/829). Further, 15% of patient with rib fractures had associated pelvic fracture. SOI was predominant in patients with concurrent rib fracture and pelvic fracture compared to ribs or pelvic fractures alone (42% vs. 26% vs. 15%, respectively, p = 0.02). Concurrent multiple rib fractures and pelvic fracture increases the risk of SOI compared to either group alone. Lower RFs and pelvic fracture had higher association for SOI and could be used as an early indicator of the presence of SOIs. Copyright © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Postural stability and the influence of concurrent muscle activation--Beneficial effects of jaw and fist clenching.

PubMed

Ringhof, Steffen; Leibold, Timo; Hellmann, Daniel; Stein, Thorsten

2015-10-01

Recent studies reported on the potential benefits of submaximum clenching of the jaw on human postural control in upright unperturbed stance. However, it remained unclear whether these effects might also be observed among active controls. The purpose of the present study, therefore, was to comparatively examine the influence of concurrent muscle activation in terms of submaximum clenching of the jaw and submaximum clenching of the fists on postural stability. Posturographic analyses were conducted with 17 healthy young adults on firm and foam surfaces while either clenching the jaw (JAW) or clenching the fists (FIST), whereas habitual standing served as the control condition (CON). Both submaximum tasks were performed at 25% maximum voluntary contraction, assessed, and visualized in real time by means of electromyography. Statistical analyses revealed that center of pressure (COP) displacements were significantly reduced during JAW and FIST, but with no differences between both concurrent clenching activities. Further, a significant increase in COP displacements was observed for the foam as compared to the firm condition. The results showed that concurrent muscle activation significantly improved postural stability compared with habitual standing, and thus emphasize the beneficial effects of jaw and fist clenching for static postural control. It is suggested that concurrent activities contribute to the facilitation of human motor excitability, finally increasing the neural drive to the distal muscles. Future studies should evaluate whether elderly or patients with compromised postural control might benefit from these physiological responses, e.g., in the form of a reduced risk of falling. Copyright © 2015 Elsevier B.V. All rights reserved.

Comparative effects of copper sulfate or potassium permanganate on channel catfish concurrently infected with Flavobacterium columnare and Ichthyobodo necator

USDA-ARS?s Scientific Manuscript database

An opportunistic study was conducted to determine the effects of two chemical therapeutants on channel catfish (CCF) Ictalurus punctatus concurrently infected Flavobacterium columnare and Ichthyobodo necator. Copper sulfate (CuSO4) and potassium permanganate (KMnO4) were investigated for their abil...

The Concurrent Development of Spelling Skills in Two Languages

ERIC Educational Resources Information Center

Joy, Rhonda

2011-01-01

The study reported on in this paper investigated the concurrent development of spelling in children learning two languages. The study compared over time and between languages the types of spelling errors made in English as a first language and French as a second. Fortyseven grade one English-speaking children completed an English and French…

The Stay/Switch Model of Concurrent Choice

ERIC Educational Resources Information Center

MacDonall, James S.

2009-01-01

This experiment compared descriptions of concurrent choice by the stay/switch model, which says choice is a function of the reinforcers obtained for staying at and for switching from each alternative, and the generalized matching law, which says choice is a function of the total reinforcers obtained at each alternative. For the stay/switch model…

Linking Item Parameters to a Base Scale. ACT Research Report Series, 2009-2

ERIC Educational Resources Information Center

Kang, Taehoon; Petersen, Nancy S.

2009-01-01

This paper compares three methods of item calibration--concurrent calibration, separate calibration with linking, and fixed item parameter calibration--that are frequently used for linking item parameters to a base scale. Concurrent and separate calibrations were implemented using BILOG-MG. The Stocking and Lord (1983) characteristic curve method…

Rater reliability and concurrent validity of the Keyboard Personal Computer Style instrument (K-PeCS).

PubMed

Baker, Nancy A; Cook, James R; Redfern, Mark S

2009-01-01

This paper describes the inter-rater and intra-rater reliability, and the concurrent validity of an observational instrument, the Keyboard Personal Computer Style instrument (K-PeCS), which assesses stereotypical postures and movements associated with computer keyboard use. Three trained raters independently rated the video clips of 45 computer keyboard users to ascertain inter-rater reliability, and then re-rated a sub-sample of 15 video clips to ascertain intra-rater reliability. Concurrent validity was assessed by comparing the ratings obtained using the K-PeCS to scores developed from a 3D motion analysis system. The overall K-PeCS had excellent reliability [inter-rater: intra-class correlation coefficients (ICC)=.90; intra-rater: ICC=.92]. Most individual items on the K-PeCS had from good to excellent reliability, although six items fell below ICC=.75. Those K-PeCS items that were assessed for concurrent validity compared favorably to the motion analysis data for all but two items. These results suggest that most items on the K-PeCS can be used to reliably document computer keyboarding style.

Experimental Treatment of Ebola Virus Disease with TKM-130803: A Single-Arm Phase 2 Clinical Trial

PubMed Central

Rojek, Amanda; Gannon, Fiona; Carson, Gail; Idriss, Baimba; Massaquoi, Thomas; Gandi, Regina; Joseph, Sebatu; Osman, Hassan K.; Brooks, Timothy J. G.; Simpson, Andrew J. H.; Goodfellow, Ian; Thorne, Lucy; Arias, Armando; Merson, Laura; Castle, Lyndsey; Howell-Jones, Rebecca; Pardinaz-Solis, Raul; Hope-Gill, Benjamin; Ferri, Mauricio; Grove, Jennifer; Kowalski, Mark; Stepniewska, Kasia; Lang, Trudie; Whitehead, John; Olliaro, Piero; Samai, Mohammed; Horby, Peter W.

2016-01-01

Background TKM-130803, a small interfering RNA lipid nanoparticle product, has been developed for the treatment of Ebola virus disease (EVD), but its efficacy and safety in humans has not been evaluated. Methods and Findings In this single-arm phase 2 trial, adults with laboratory-confirmed EVD received 0.3 mg/kg of TKM-130803 by intravenous infusion once daily for up to 7 d. On days when trial enrolment capacity was reached, patients were enrolled into a concurrent observational cohort. The primary outcome was survival to day 14 after admission, excluding patients who died within 48 h of admission. After 14 adults with EVD had received TKM-130803, the pre-specified futility boundary was reached, indicating a probability of survival to day 14 of ≤0.55, and enrolment was stopped. Pre-treatment geometric mean Ebola virus load in the 14 TKM-130803 recipients was 2.24 × 109 RNA copies/ml plasma (95% CI 7.52 × 108, 6.66 × 109). Two of the TKM-130803 recipients died within 48 h of admission and were therefore excluded from the primary outcome analysis. Of the remaining 12 TKM-130803 recipients, nine died and three survived. The probability that a TKM-130803 recipient who survived for 48 h will subsequently survive to day 14 was estimated to be 0.27 (95% CI 0.06, 0.58). TKM-130803 infusions were well tolerated, with 56 doses administered and only one possible infusion-related reaction observed. Three patients were enrolled in the observational cohort, of whom two died. Conclusions Administration of TKM-130803 at a dose of 0.3 mg/kg/d by intravenous infusion to adult patients with severe EVD was not shown to improve survival when compared to historic controls. Trial registration Pan African Clinical Trials Registry PACTR201501000997429 PMID:27093560

Comparison of two independent systematic reviews of trials of recombinant human bone morphogenetic protein-2 (rhBMP-2): the Yale Open Data Access Medtronic Project.

PubMed

Low, Jeffrey; Ross, Joseph S; Ritchie, Jessica D; Gross, Cary P; Lehman, Richard; Lin, Haiqun; Fu, Rongwei; Stewart, Lesley A; Krumholz, Harlan M

2017-02-15

It is uncertain whether the replication of systematic reviews, particularly those with the same objectives and resources, would employ similar methods and/or arrive at identical findings. We compared the results and conclusions of two concurrent systematic reviews undertaken by two independent research teams provided with the same objectives, resources, and individual participant-level data. Two centers in the USA and UK were each provided with participant-level data on 17 multi-site clinical trials of recombinant human bone morphogenetic protein-2 (rhBMP-2). The teams were blinded to each other's methods and findings until after publication. We conducted a retrospective structured comparison of the results of the two systematic reviews. The main outcome measures included (1) trial inclusion criteria; (2) statistical methods; (3) summary efficacy and risk estimates; and (4) conclusions. The two research teams' meta-analyses inclusion criteria were broadly similar but differed slightly in trial inclusion and research methodology. They obtained similar results in summary estimates of most clinical outcomes and adverse events. Center A incorporated all trials into summary estimates of efficacy and harms, while Center B concentrated on analyses stratified by surgical approach. Center A found a statistically significant, but small, benefit whereas Center B reported no advantage. In the analysis of harms, neither showed an increased cancer risk at 48 months, although Center B reported a significant increase at 24 months. Conclusions reflected these differences in summary estimates of benefit balanced with small but potentially important risk of harm. Two independent groups given the same research objectives, data, resources, funding, and time produced broad general agreement but differed in several areas. These differences, the importance of which is debatable, indicate the value of the availability of data to allow for more than a single approach and a single interpretation of the data. PROSPERO CRD42012002040 and CRD42012001907 .

Omitting elective nodal irradiation during thoracic irradiation in limited-stage small cell lung cancer--evidence from a phase II trial.

PubMed

Colaco, Rovel; Sheikh, Hamid; Lorigan, Paul; Blackhall, Fiona; Hulse, Paul; Califano, Raffaele; Ashcroft, Linda; Taylor, Paul; Thatcher, Nicholas; Faivre-Finn, Corinne

2012-04-01

Omitting elective nodal irradiation (ENI) in limited-stage disease small cell lung cancer (LD-SCLC) is expected to result in smaller radiation fields. We report on data from a randomised phase II trial that omitted ENI in patients receiving concurrent chemo-radiotherapy for LD-SCLC. 38 patients with LD-SCLC were randomised to receive once-daily (66 Gy in 33 fractions) or twice-daily (45 Gy in 30 fractions) radiotherapy (RT). 3D-conformal RT was given concurrently with cisplatin and etoposide starting with the second cycle of a total of four cycles. The gross tumour volume was defined as primary tumour with involved lymph nodes (nodes ≥1 cm in short axis) identifiable with CT imaging. ENI was not used. Six recurrence patterns were identified: recurrence within planning target volume (PTV) only, recurrence within PTV+regional nodal recurrence and/or distant recurrence, isolated nodal recurrence outside PTV, nodal recurrence outside PTV+distant recurrence, distant metastases only and no recurrence. At median follow-up 16.9 months, 31/38 patients were evaluable and 14/31 patients had relapsed. There were no isolated nodal recurrences. Eight patients relapsed with intra-thoracic disease: 2 within PTV only, 4 within PTV and distantly and 2 with nodal recurrence outside PTV plus distant metastases. Rates of grade 3+ acute oesophagitis and pneumonitis in the 31 evaluable patients were 23 and 3% respectively. In our study of LD-SCLC, omitting ENI based on CT imaging was not associated with a high risk of isolated nodal recurrence, although further prospective studies are needed to confirm this. Routine ENI omission will be further evaluated prospectively in the ongoing phase III CONVERT trial (NCT00433563). Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Effect of Preventive Supplementation with Zinc and Other Micronutrients on Non-Malarial Morbidity in Tanzanian Pre-School Children: A Randomized Trial

PubMed Central

Veenemans, Jacobien; Schouten, Laura R. A.; Ottenhof, Maarten J.; Mank, Theo G.; Uges, Donald R. A.; Mbugi, Erasto V.; Demir, Ayşe Y.; Kraaijenhagen, Rob J.; Savelkoul, Huub F. J.; Verhoef, Hans

2012-01-01

Background The efficacy of preventive zinc supplementation against diarrhea and respiratory illness may depend on simultaneous supplementation with other micronutrients. We aimed to assess the effect of supplementation with zinc and multiple micronutrients on diarrhea and other causes of non-malarial morbidity. Methods and Findings Rural Tanzanian children (n = 612) aged 6–60 months and with height-for-age z-score < –1.5 SD were randomized to daily supplementation with zinc (10 mg) alone, multi-nutrients without zinc, multi-nutrients with zinc, or placebo. Children were followed for an average of 45 weeks. During follow-up, we recorded morbidity episodes. We found no evidence that concurrent supplementation with multi-nutrients influenced the magnitude of the effect of zinc on rates of diarrhea, respiratory illness, fever without localizing signs, or other illness (guardian-reported illness with symptoms involving skin, ears, eyes and abscesses, but excluding trauma or burns). Zinc supplementation reduced the hazard rate of diarrhea by 24% (4%–40%). By contrast, multi-nutrients seemed to increase this rate (HR; 95% CI: 1.19; 0.94–1.50), particularly in children with asymptomatic Giardia infection at baseline (2.03; 1.24–3.32). Zinc also protected against episodes of fever without localizing signs (0.75; 0.57–0.96), but we found no evidence that it reduced the overall number of clinic visits. Conclusions We found no evidence that the efficacy of zinc supplements in reducing diarrhea rates is enhanced by concurrent supplementation with other micronutrients. By reducing rates of fever without localizing signs, supplementation with zinc may reduce inappropriate drug use with anti-malarial medications and antibiotics. Trial Registration ClinicalTrials.gov NCT00623857 PMID:22870238

Effects of vitamin C supplementation on blood pressure: a meta-analysis of randomized controlled trials123

PubMed Central

Juraschek, Stephen P; Guallar, Eliseo; Appel, Lawrence J

2012-01-01

Background: In observational studies, increased vitamin C intake, vitamin C supplementation, and higher blood concentrations of vitamin C are associated with lower blood pressure (BP). However, evidence for blood pressure–lowering effects of vitamin C in clinical trials is inconsistent. Objective: The objective was to conduct a systematic review and meta-analysis of clinical trials that examined the effects of vitamin C supplementation on BP. Design: We searched Medline, EMBASE, and Central databases from 1966 to 2011. Prespecified inclusion criteria were as follows: 1) use of a randomized controlled trial design; 2) trial reported effects on systolic BP (SBP) or diastolic BP (DBP) or both; 3) trial used oral vitamin C and concurrent control groups; and 4) trial had a minimum duration of 2 wk. BP effects were pooled by random-effects models, with trials weighted by inverse variance. Results: Twenty-nine trials met eligibility criteria for the primary analysis. The median dose was 500 mg/d, the median duration was 8 wk, and trial sizes ranged from 10 to 120 participants. The pooled changes in SBP and DBP were −3.84 mm Hg (95% CI: −5.29, −2.38 mm Hg; P < 0.01) and −1.48 mm Hg (95% CI: −2.86, −0.10 mm Hg; P = 0.04), respectively. In trials in hypertensive participants, corresponding reductions in SBP and DBP were −4.85 mm Hg (P < 0.01) and −1.67 mm Hg (P = 0.17). After the inclusion of 9 trials with imputed BP effects, BP effects were attenuated but remained significant. Conclusions: In short-term trials, vitamin C supplementation reduced SBP and DBP. Long-term trials on the effects of vitamin C supplementation on BP and clinical events are needed. PMID:22492364

The acceptability of an injectable, once-a-month male contraceptive in China.

PubMed

Zhang, Liying; Shah, Iqbal H; Liu, Yunrong; Vogelsong, Kirsten M; Zhang, Lihong

2006-05-01

An acceptability study of an injectable preparation of the synthetic steroid testosterone undecanoate as a once-a-month male contraceptive method was carried out concurrently with, but independently from, a clinical safety and efficacy trial of this preparation in China, from 1997 to 1999. Three hundred eight men, the entire group of volunteers enrolled in the clinical trial, were interviewed using a structured questionnaire. In addition, 24 sessions of focus group discussions and 54 in-depth interviews were conducted with a broad range of stakeholders, including men enrolled in the trial and their wives, potential users, service providers, principal investigators of the six participating clinical trial centers, provincial and national policy makers, and experts engaged in research and development of male methods of contraception. Overall, men found the regimen to be acceptable, and most reported no change or an improvement in their well-being as a result of participating in the clinical study. The frequency of the injections, monthly semen analyses and the need to use another contraceptive method during the period of sperm suppression were reported inconveniences of the trial. Further research is needed to assess the long-term safety, continuation rates, satisfaction among users and issues related to service delivery.

Concurrent validity and reliability of the Simple Goniometer iPhone app compared with the Universal Goniometer.

PubMed

Jones, Anne; Sealey, Rebecca; Crowe, Michael; Gordon, Susan

2014-10-01

The aim of this study was to assess the concurrent validity and reliability of the Simple Goniometer (SG) iPhone® app compared to the Universal Goniometer (UG). Within subject comparison design comparing the UG with the SG app. James Cook University, Townsville, Queensland, Australia. Thirty-six volunteer participants, with a mean age of 60.6 years (SD 6.2). Not applicable. Thirty-six participants performed three standing lunges during which the knee joint angle was measured with the SG app and the UG. There were no significant differences in the measures of individual knee joint angles between the UG and the SG app. Pearson correlations of 0.96-0.98 and intraclass correlation coefficients of 0.97-0.99 (95% confidence interval: 0.95-1.00) were recorded for all measures. Using the Bland-Altman method, the standard error of the mean of the differences and the standard deviation of the mean of the differences were low. The measurements from the SG iPhone® app were reliable and possessed concurrent validity for this sample and protocol when compared to the UG.

Quality of Life Analysis of a Radiation Dose-Escalation Study of Patients With Non-Small-Cell Lung Cancer: A Secondary Analysis of the Radiation Therapy Oncology Group 0617 Randomized Clinical Trial.

PubMed

Movsas, Benjamin; Hu, Chen; Sloan, Jeffrey; Bradley, Jeffrey; Komaki, Ritsuko; Masters, Gregory; Kavadi, Vivek; Narayan, Samir; Michalski, Jeff; Johnson, Douglas W; Koprowski, Christopher; Curran, Walter J; Garces, Yolanda I; Gaur, Rakesh; Wynn, Raymond B; Schallenkamp, John; Gelblum, Daphna Y; MacRae, Robert M; Paulus, Rebecca; Choy, Hak

2016-03-01

A recent randomized radiation dose-escalation trial in unresectable stage III non-small-cell lung cancer (NSCLC) (Radiation Therapy Oncology Group [RTOG] 0617) showed a lower survival rate in the high-dose radiation therapy (RT) arm (74 Gy) than in the low-dose arm (60 Gy) with concurrent chemotherapy. The primary QOL hypothesis predicted a clinically meaningful decline in quality of life (QOL) via the Functional Assessment of Cancer Therapy (FACT)-Lung Cancer Subscale (LCS) in the high-dose RT arm at 3 months. The RTOG 0617 trial was a randomized phase 3 study (conducted from November 2007 to November 2011) in stage III NSCLC using a 2 × 2 factorial design and stratified by histology, positron emission tomography staging, performance status, and irradiation technique (3-dimensional conformal RT [3D-CRT] vs intensity-modulated RT [IMRT]). A total of 185 institutions in the United States and Canada took part. Of 424 eligible patients with stage III NSCLC randomized, 360 (85%) consented to QOL evaluation, of whom 313 (88%) completed baseline QOL assessments. Treatment with 74-Gy vs 60-Gy RT with concurrent and consolidation carboplatin/paclitaxel with or without cetuximab. The QOL data were collected prospectively via FACT Trial Outcome Index (FACT-TOI), calculated as the sum of the following measures: Physical Well Being (PWB), Functional Well Being (FWB), and the LCS. Data are presented at baseline and 3 and 12 months via minimal clinically meaningful changes of 2 points or more for PWB, FWB, and LCS or 5 points or more for TOI. Of the 313 patients who completed baseline QOL assessments, 219 patients (70%) completed the 3-month QOL assessments, and 137 of the living patients (57%) completed the 12-month assessment. Patient demographics and baseline QOL scores were comparable between the 74-Gy and 60-Gy arms. Significantly more patients in the 74-Gy arm than in the 60-Gy arm had clinically meaningful decline in FACT-LCS at 3 months (45% vs 30%; P = .02). At 12 months, fewer patients who received IMRT (vs 3D-CRT) had clinically meaningful decline in FACT-LCS (21% vs 46%; P = .003). Baseline FACT-TOI was associated with overall survival in multivariate analysis. Despite few differences in clinician-reported toxic effects between treatment arms, QOL analysis demonstrated a clinically meaningful decline in QOL in the 74-Gy arm at 3 months, confirming the primary QOL hypothesis. Baseline QOL was an independent prognostic factor for survival. clinicaltrials.gov Identifier: NCT00533949.

Children concurrently wasted and stunted: A meta‐analysis of prevalence data of children 6–59 months from 84 countries

PubMed Central

Khara, Tanya; Mwangome, Martha; Ngari, Moses

2017-01-01

Abstract Children can be stunted and wasted at the same time. Having both deficits greatly elevates risk of mortality. The analysis aimed to estimate the prevalence and burden of children aged 6–59 months concurrently wasted and stunted. Data from demographic and health survey and Multi‐indicator Cluster Surveys datasets from 84 countries were analysed. Overall prevalence for being wasted, stunted, and concurrently wasted and stunted among children 6 to 59 months was calculated. A pooled prevalence of concurrence was estimated and reported by gender, age, United Nations regions, and contextual categories. Burden was calculated using population figures from the global joint estimates database. The pooled prevalence of concurrence in the 84 countries was 3.0%, 95% CI [2.97, 3.06], ranging from 0% to 8.0%. Nine countries reported a concurrence prevalence greater than 5%. The estimated burden was 5,963,940 children. Prevalence of concurrence was highest in the 12‐ to 24‐month age group 4.2%, 95% CI [4.1, 4.3], and was significantly higher among boys 3.54%, 95% CI [3.47, 3.61], compared to girls; 2.46%, 95% CI [2.41, 2.52]. Fragile and conflict‐affected states reported significantly higher concurrence 3.6%, 95% CI [3.5, 3.6], than those defined as stable 2.24%, 95% CI [2.18, 2.30]. This analysis represents the first multiple country estimation of the prevalence and burden of children concurrently wasted and stunted. Given the high risk of mortality associated with concurrence, the findings indicate a need to report on this condition as well as investigate whether these children are being reached through existing programmes. PMID:28944990

Effect of health promotion and fluoride varnish on dental caries among Australian Aboriginal children: results from a community-randomized controlled trial*

PubMed Central

Slade, Gary D; Bailie, Ross S; Roberts-Thomson, Kaye; Leach, Amanda J; Raye, Iris; Endean, Colin; Simmons, Bruce; Morris, Peter

2011-01-01

Objectives We tested a dental health program in remote Aboriginal communities of Australia's Northern Territory, hypothesizing that it would reduce dental caries in preschool children. Methods In this 2-year, prospective, cluster-randomized, concurrent controlled, open trial of the dental health program compared to no such program, 30 communities were allocated at random to intervention and control groups. All residents aged 18–47 months were invited to participate. Twice per year for 2 years in the 15 intervention communities, fluoride varnish was applied to children's teeth, water consumption and daily tooth cleaning with toothpaste were advocated, dental health was promoted in community settings, and primary health care workers were trained in preventive dental care. Data from dental examinations at baseline and after 2 years were used to compute net dental caries increment per child (d3mfs). A multi-level statistical model compared d3mfs between intervention and control groups with adjustment for the clustered randomization design; four other models used additional variables for adjustment. Results At baseline, 666 children were examined; 543 of them (82%) were re-examined 2 years later. The adjusted d3mfs increment was significantly lower in the intervention group compared to the control group by an average of 3.0 surfaces per child (95% CI = 1.2, 4.9), a prevented fraction of 31%. Adjustment for additional variables yielded caries reductions ranging from 2.3 to 3.5 surfaces per child and prevented fractions of 24–36%. Conclusions These results corroborate findings from other studies where fluoride varnish was efficacious in preventing dental caries in young children. PMID:20707872

A correlational method to concurrently measure envelope and temporal fine structure weights: Effects of age, cochlear pathology, and spectral shaping1

PubMed Central

Fogerty, Daniel; Humes, Larry E.

2012-01-01

The speech signal may be divided into spectral frequency-bands, each band containing temporal properties of the envelope and fine structure. This study measured the perceptual weights for the envelope and fine structure in each of three frequency bands for sentence materials in young normal-hearing listeners, older normal-hearing listeners, aided older hearing-impaired listeners, and spectrally matched young normal-hearing listeners. The availability of each acoustic property was independently varied through noisy signal extraction. Thus, the full speech stimulus was presented with noise used to mask six different auditory channels. Perceptual weights were determined by correlating a listener’s performance with the signal-to-noise ratio of each acoustic property on a trial-by-trial basis. Results demonstrate that temporal fine structure perceptual weights remain stable across the four listener groups. However, a different weighting typography was observed across the listener groups for envelope cues. Results suggest that spectral shaping used to preserve the audibility of the speech stimulus may alter the allocation of perceptual resources. The relative perceptual weighting of envelope cues may also change with age. Concurrent testing of sentences repeated once on a previous day demonstrated that weighting strategies for all listener groups can change, suggesting an initial stabilization period or susceptibility to auditory training. PMID:22978896

Venetoclax responses of pediatric ALL xenografts reveal sensitivity of MLL-rearranged leukemia

PubMed Central

Khaw, Seong Lin; Suryani, Santi; Evans, Kathryn; Richmond, Jennifer; Robbins, Alissa; Kurmasheva, Raushan T.; Billups, Catherine A.; Erickson, Stephen W.; Guo, Yuelong; Houghton, Peter J.; Smith, Malcolm A.; Carol, Hernan; Roberts, Andrew W.; Huang, David C. S.

2016-01-01

The clinical success of the BCL-2-selective BH3-mimetic venetoclax in patients with poor prognosis chronic lymphocytic leukemia (CLL) highlights the potential of targeting the BCL-2-regulated apoptotic pathway in previously untreatable lymphoid malignancies. By selectively inhibiting BCL-2, venetoclax circumvents the dose-limiting, BCL-XL-mediated thrombocytopenia of its less selective predecessor navitoclax, while enhancing efficacy in CLL. We have previously reported the potent sensitivity of many high-risk childhood acute lymphoblastic leukemia (ALL) xenografts to navitoclax. Given the superior tolerability of venetoclax, here we have investigated its efficacy in childhood ALL. We demonstrate that in contrast to the clear dependence of CLL on BCL-2 alone, effective antileukemic activity in the majority of ALL xenografts requires concurrent inhibition of both BCL-2 and BCL-XL. We identify BCL-XL expression as a key predictor of poor response to venetoclax and demonstrate that concurrent inhibition of both BCL-2 and BCL-XL results in synergistic killing in the majority of ALL xenografts. A notable exception is mixed lineage leukemia–rearranged infant ALL, where venetoclax largely recapitulates the activity of navitoclax, identifying this subgroup of patients as potential candidates for clinical trials of venetoclax in childhood ALL. Conversely, our findings provide a clear basis for progressing navitoclax into trials ahead of venetoclax in other subgroups. PMID:27343252

Evidence for two concurrent inhibitory mechanisms during response preparation

PubMed Central

Duque, Julie; Lew, David; Mazzocchio, Riccardo; Olivier, Etienne; Ivry, Richard B.

2010-01-01

Inhibitory mechanisms are critically involved in goal-directed behaviors. To gain further insight into how such mechanisms shape motor representations during response preparation, motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) and H-reflexes were recorded from left hand muscles during choice reaction time tasks. The imperative signal, which indicated the required response, was always preceded by a preparatory cue. During the post-cue delay period, left MEPs were suppressed when the left hand had been cued for the forthcoming response, suggestive of a form of inhibition specifically directed at selected response representations. H-reflexes were also suppressed on these trials, indicating that the effects of this inhibition extend to spinal circuits. In addition, left MEPs were suppressed when the right hand was cued, but only when left hand movements were a possible response option before the onset of the cue. Notably, left hand H-reflexes were not modulated on these trials, consistent with a cortical locus of inhibition that lowers the activation of task-relevant, but non-selected responses. These results suggest the concurrent operation of two inhibitory mechanisms during response preparation: one decreases the activation of selected responses at the spinal level, helping to control when selected movements should be initiated by preventing their premature release; a second, upstream mechanism helps to determine what response to make during a competitive selection process. PMID:20220014

Cortical Components of Reaction-Time during Perceptual Decisions in Humans.

PubMed

Dmochowski, Jacek P; Norcia, Anthony M

2015-01-01

The mechanisms of perceptual decision-making are frequently studied through measurements of reaction time (RT). Classical sequential-sampling models (SSMs) of decision-making posit RT as the sum of non-overlapping sensory, evidence accumulation, and motor delays. In contrast, recent empirical evidence hints at a continuous-flow paradigm in which multiple motor plans evolve concurrently with the accumulation of sensory evidence. Here we employ a trial-to-trial reliability-based component analysis of encephalographic data acquired during a random-dot motion task to directly image continuous flow in the human brain. We identify three topographically distinct neural sources whose dynamics exhibit contemporaneous ramping to time-of-response, with the rate and duration of ramping discriminating fast and slow responses. Only one of these sources, a parietal component, exhibits dependence on strength-of-evidence. The remaining two components possess topographies consistent with origins in the motor system, and their covariation with RT overlaps in time with the evidence accumulation process. After fitting the behavioral data to a popular SSM, we find that the model decision variable is more closely matched to the combined activity of the three components than to their individual activity. Our results emphasize the role of motor variability in shaping RT distributions on perceptual decision tasks, suggesting that physiologically plausible computational accounts of perceptual decision-making must model the concurrent nature of evidence accumulation and motor planning.

International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial: Rationale and design.

PubMed

Maron, David J; Hochman, Judith S; O'Brien, Sean M; Reynolds, Harmony R; Boden, William E; Stone, Gregg W; Bangalore, Sripal; Spertus, John A; Mark, Daniel B; Alexander, Karen P; Shaw, Leslee; Berger, Jeffrey S; Ferguson, T Bruce; Williams, David O; Harrington, Robert A; Rosenberg, Yves

2018-07-01

Prior trials comparing a strategy of optimal medical therapy with or without revascularization have not shown that revascularization reduces cardiovascular events in patients with stable ischemic heart disease (SIHD). However, those trials only included participants in whom coronary anatomy was known prior to randomization and did not include sufficient numbers of participants with significant ischemia. It remains unknown whether a routine invasive approach offers incremental value over a conservative approach with catheterization reserved for failure of medical therapy in patients with moderate or severe ischemia. The ISCHEMIA trial is a National Heart, Lung, and Blood Institute supported trial, designed to compare an initial invasive or conservative treatment strategy for managing SIHD patients with moderate or severe ischemia on stress testing. Five thousand one-hundred seventy-nine participants have been randomized. Key exclusion criteria included estimated glomerular filtration rate (eGFR) <30 mL/min, recent myocardial infarction (MI), left ventricular ejection fraction <35%, left main stenosis >50%, or unacceptable angina at baseline. Most enrolled participants with normal renal function first underwent blinded coronary computed tomography angiography (CCTA) to exclude those with left main coronary artery disease (CAD) and without obstructive CAD. All randomized participants receive secondary prevention that includes lifestyle advice and pharmacologic interventions referred to as optimal medical therapy (OMT). Participants randomized to the invasive strategy underwent routine cardiac catheterization followed by revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery, when feasible, as selected by the local Heart Team to achieve optimal revascularization. Participants randomized to the conservative strategy undergo cardiac catheterization only for failure of OMT. The primary endpoint is a composite of cardiovascular (CV) death, nonfatal myocardial infarction (MI), hospitalization for unstable angina, hospitalization for heart failure, or resuscitated cardiac arrest. Assuming the primary endpoint will occur in 16% of the conservative group within 4 years, estimated power exceeds 80% to detect an 18.5% reduction in the primary endpoint. Major secondary endpoints include the composite of CV death and nonfatal MI, net clinical benefit (primary and secondary endpoints combined with stroke), angina-related symptoms and disease-specific quality of life, as well as a cost-effectiveness assessment in North American participants. Ancillary studies of patients with advanced chronic kidney disease and those with documented ischemia and non-obstructive coronary artery disease are being conducted concurrently. ISCHEMIA will provide new scientific evidence regarding whether an invasive management strategy improves clinical outcomes when added to optimal medical therapy in patients with SIHD and moderate or severe ischemia. Copyright © 2018 Elsevier Inc. All rights reserved.

A Multicenter Phase II Trial of S-1 With Concurrent Radiation Therapy for Locally Advanced Pancreatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ikeda, Masafumi, E-mail: masikeda@east.ncc.go.jp; Ioka, Tatsuya; Ito, Yoshinori

2013-01-01

Purpose: The aim of this trial was to evaluate the efficacy and toxicity of S-1 and concurrent radiation therapy for locally advanced pancreatic cancer (PC). Methods and Materials: Locally advanced PC patients with histologically or cytologically confirmed adenocarcinoma or adenosquamous carcinoma, who had no previous therapy were enrolled. Radiation therapy was delivered through 3 or more fields at a total dose of 50.4 Gy in 28 fractions over 5.5 weeks. S-1 was administered orally at a dose of 80 mg/m{sup 2} twice daily on the day of irradiation during radiation therapy. After a 2- to 8-week break, patients received amore » maintenance dose of S-1 (80 mg/m{sup 2}/day for 28 consecutive days, followed by a 14-day rest period) was then administered until the appearance of disease progression or unacceptable toxicity. The primary efficacy endpoint was survival, and the secondary efficacy endpoints were progression-free survival, response rate, and serum carbohydrate antigen 19-9 (CA19-9) response; the safety endpoint was toxicity. Results: Of the 60 evaluable patients, 16 patients achieved a partial response (27%; 95% confidence interval [CI], 16%-40%). The median progression-free survival period, overall survival period, and 1-year survival rate of the evaluable patients were 9.7 months (95% CI, 6.9-11.6 months), 16.2 months (95% CI, 13.5-21.3 months), and 72% (95%CI, 59%-82%), respectively. Of the 42 patients with a pretreatment serum CA19-9 level of {>=}100 U/ml, 34 (81%) patients showed a decrease of greater than 50%. Leukopenia (6 patients, 10%) and anorexia (4 patients, 7%) were the major grade 3-4 toxicities with chemoradiation therapy. Conclusions: The effect of S-1 with concurrent radiation therapy in patients with locally advanced PC was found to be very favorable, with only mild toxicity.« less

Initial Results of a Phase I Dose-Escalation Trial of Concurrent and Maintenance Erlotinib and Reirradiation for Recurrent and New Primary Head-and-Neck Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rusthoven, Kyle E.; Feigenberg, Steven J.; Raben, David

2010-11-15

Purpose: To present the first report of a Phase I trial evaluating concurrent and maintenance erlotinib and reirradiation in patients with recurrent or secondary primary head-and-neck cancer (HNC). Methods and Materials: Patients with recurrent or new primary HNC with an interval of at least 6 months since prior radiation were eligible. Patients were treated in 3 sequential cohorts: Cohort I, 100 mg of erlotinib daily with reirradiation at 61.6 Gy in 28 fractions; Cohort II, 150 mg of erlotinib with 61.6 Gy in 28 fractions; and Cohort III, 150 mg of erlotinib with 66 Gy in 30 fractions. Maintenance erlotinibmore » started immediately after reirradiation at 150 mg daily and was continued for 2 years or until disease progression or dose-limiting toxicity. Dose-limiting toxicities were defined as any Grade 4 or 5 toxicity or a toxicity-related delay in radiation therapy of greater than 7 days. Results: Fourteen patients were accrued, 3 to Cohort I, 4 to Cohort II, and 7 to Cohort III. Thirteen patients were evaluable for toxicity. Median follow-up was 8.4 months overall and 15.1 months for surviving patients. One patient had a dose-limiting toxicity in Cohort III. This patient declined initial percutaneous endoscopic gastrostomy tube placement, was hospitalized with Grade 3 dysphagia and aspiration, and required a delay in radiation therapy of greater than 7 days. No Grade 4 acute toxicity was observed. Acute Grade 3 toxicity occurred in 9 of 13 patients. No erlotinib-related toxicity of Grade 3 or greater was observed during maintenance therapy. One patient had Grade 5 carotid hemorrhage 6 months after reirradiation, and another patient had Grade 3 osteoradionecrosis. Conclusions: Reirradiation (66 Gy in 2.2 Gy fractions) with concurrent and maintenance erlotinib (150 mg daily) for recurrent or new primary HNC is feasible.« less

IDEAL-CRT: A Phase 1/2 Trial of Isotoxic Dose-Escalated Radiation Therapy and Concurrent Chemotherapy in Patients With Stage II/III Non-Small Cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Landau, David B., E-mail: david.landau@kcl.ac.uk; Hughes, Laura; Baker, Angela

2016-08-01

Purpose: To report toxicity and early survival data for IDEAL-CRT, a trial of dose-escalated concurrent chemoradiotherapy (CRT) for non-small cell lung cancer. Patients and Methods: Patients received tumor doses of 63 to 73 Gy in 30 once-daily fractions over 6 weeks with 2 concurrent cycles of cisplatin and vinorelbine. They were assigned to 1 of 2 groups according to esophageal dose. In group 1, tumor doses were determined by an experimental constraint on maximum esophageal dose, which was escalated following a 6 + 6 design from 65 Gy through 68 Gy to 71 Gy, allowing an esophageal maximum tolerated dose to be determined from early and late toxicities. Tumormore » doses for group 2 patients were determined by other tissue constraints, often lung. Overall survival, progression-free survival, tumor response, and toxicity were evaluated for both groups combined. Results: Eight centers recruited 84 patients: 13, 12, and 10, respectively, in the 65-Gy, 68-Gy, and 71-Gy cohorts of group 1; and 49 in group 2. The mean prescribed tumor dose was 67.7 Gy. Five grade 3 esophagitis and 3 grade 3 pneumonitis events were observed across both groups. After 1 fatal esophageal perforation in the 71-Gy cohort, 68 Gy was declared the esophageal maximum tolerated dose. With a median follow-up of 35 months, median overall survival was 36.9 months, and overall survival and progression-free survival were 87.8% and 72.0%, respectively, at 1 year and 68.0% and 48.5% at 2 years. Conclusions: IDEAL-CRT achieved significant treatment intensification with acceptable toxicity and promising survival. The isotoxic design allowed the esophageal maximum tolerated dose to be identified from relatively few patients.« less

Multidisciplinary Concurrent Design Optimization via the Internet

NASA Technical Reports Server (NTRS)

Woodard, Stanley E.; Kelkar, Atul G.; Koganti, Gopichand

2001-01-01

A methodology is presented which uses commercial design and analysis software and the Internet to perform concurrent multidisciplinary optimization. The methodology provides a means to develop multidisciplinary designs without requiring that all software be accessible from the same local network. The procedures are amenable to design and development teams whose members, expertise and respective software are not geographically located together. This methodology facilitates multidisciplinary teams working concurrently on a design problem of common interest. Partition of design software to different machines allows each constituent software to be used on the machine that provides the most economy and efficiency. The methodology is demonstrated on the concurrent design of a spacecraft structure and attitude control system. Results are compared to those derived from performing the design with an autonomous FORTRAN program.

Cumulative Impact of HIV and Multiple Concurrent Human Papillomavirus Infections on the Risk of Cervical Dysplasia

PubMed Central

Adler, David H.; Wallace, Melissa; Bennie, Thola; Abar, Beau; Meiring, Tracy L.; Williamson, Anna-Lise; Bekker, Linda-Gail

2016-01-01

Infection with HIV is known to increase the risk of cervical cancer. In addition, evidence suggests that concurrent infection with multiple human papillomavirus (HPV) genotypes increases the risk of cervical dysplasia more than infection with a single HPV genotype. However, the impact of the combination of HIV coinfection and presence of multiple concurrent HPV infections on the risk of cervical dysplasia is uncertain. We compared the results of HPV testing and Pap smears between HIV-infected and HIV-uninfected young women to assess the cumulative impact of these two conditions. We found that both HIV and the presence of multiple concurrent HPV infections are associated with increased risk of associated Pap smear abnormality and that the impact of these two risk factors may be additive. PMID:26997954

Radiation Dose Escalation in Esophageal Cancer Revisited: A Contemporary Analysis of the National Cancer Data Base, 2004 to 2012

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brower, Jeffrey V.; Chen, Shuai; Bassetti, Michael F.

Purpose: To evaluate the effect of radiation dose escalation on overall survival (OS) for patients with nonmetastatic esophageal cancer treated with concurrent radiation and chemotherapy. Methods and Materials: Patients diagnosed with stage I to III esophageal cancer treated from 2004 to 2012 were identified from the National Cancer Data Base. Patients who received concurrent radiation and chemotherapy with radiation doses of ≥50 Gy and did not undergo surgery were included. OS was compared using Cox proportional hazards regression and propensity score matching. Results: A total of 6854 patients were included; 3821 (55.7%) received 50 to 50.4 Gy and 3033 (44.3%) received dosesmore » >50.4 Gy. Univariate analysis revealed no significant difference in OS between patients receiving 50 to 50.4 Gy and those receiving >50.4 Gy (P=.53). The dose analysis, binned as 50 to 50.4, 51 to 54, 55 to 60, and >60 Gy, revealed no appreciable difference in OS within any group compared with 50 to 50.4 Gy. Subgroup analyses investigating the effect of dose escalation by histologic type and in the setting of intensity modulated radiation therapy also failed to reveal a benefit. Propensity score matching confirmed the absence of a statistically significant difference in OS among the dose levels. The factors associated with improved OS on multivariable analysis included female sex, lower Charlson-Deyo comorbidity score, private insurance, cervical/upper esophagus location, squamous cell histologic type, lower T stage, and node-negative status (P<.01 for all analyses). Conclusions: In this large national cohort, dose escalation >50.4 Gy did not result in improved OS among patients with stage I to III esophageal cancer treated with definitive concurrent radiation and chemotherapy. These data suggest that despite advanced contemporary treatment techniques, OS for patients with esophageal cancer remains unaltered by escalation of radiation dose >50.4 Gy, consistent with the results of the INT-0123 trial. Furthermore, these data highlight that many radiation oncologists have not embraced the concept that dose escalation does not improve OS. Although local control, not investigated in the present study, might benefit from dose escalation, novel therapies are needed to improve the OS of patients with esophageal cancer.« less

Changes in pain and concurrent pain medication use following compounded topical analgesic treatment for chronic pain: 3- and 6-month follow-up results from the prospective, observational Optimizing Patient Experience and Response to Topical Analgesics study

PubMed Central

Gudin, Jeffrey A; Brennan, Michael J; Harris, E Dennis; Hurwitz, Peter L; Dietze, Derek T; Strader, James D

2017-01-01

Background Opioids and other controlled substances prescribed for chronic pain are associated with abuse, addiction, and death, prompting national initiatives to identify safe and effective pain management strategies including topical analgesics. Methods This prospective, observational study evaluated changes from baseline in overall mean severity and interference scores on the Brief Pain Inventory scale and the use of concurrent pain medications at 3- and 6-month follow-up assessments in chronic pain patients treated with topical analgesics. Changes in pain severity and interference and medication usage were compared between treated patients and unmatched and matched controls. Results The unmatched intervention group (unmatched-IG) included 631 patients who completed baseline and 3-month follow-up surveys (3-month unmatched-IG) and 158 who completed baseline and 6-month follow-up assessments (6-month unmatched-IG). Baseline and 3-month follow-up data were provided by 76 unmatched controls and 76 matched controls (3-month unmatched-CG and matched-CG), and 51 unmatched and 36 matched patients completed baseline and 6-month follow-up surveys (6-month unmatched-CG and matched-CG). Baseline demographic characteristics and mean pain severity and interference scores were similar between groups. There were statistically significant decreases from baseline in mean pain severity and interference scores within the 3- and 6-month unmatched-IG (all P<0.001). Significantly greater decreases in the mean change from baseline in pain severity and interference scores were evident for the 3- and 6-month unmatched-IG versus unmatched-CG (all P<0.001), with similar results when the 3- and 6-month matched-IG and matched-CG were compared. A higher percentage of the 3- and 6-month unmatched-IG and matched-IG de-escalated use of concurrent pain medications (all P<0.001), while significantly higher percentages of the unmatched-CG and matched-CG escalated medication use. Side effects were reported by <1% of the unmatched-IG. Conclusion Topical analgesics appear to be effective and safe for the treatment of chronic pain, with randomized controlled trials needed to confirm these findings. PMID:29042810

Radiation Dose Escalation in Esophageal Cancer Revisited: A Contemporary Analysis of the National Cancer Data Base, 2004 to 2012.

PubMed

Brower, Jeffrey V; Chen, Shuai; Bassetti, Michael F; Yu, Menggang; Harari, Paul M; Ritter, Mark A; Baschnagel, Andrew M

2016-12-01

To evaluate the effect of radiation dose escalation on overall survival (OS) for patients with nonmetastatic esophageal cancer treated with concurrent radiation and chemotherapy. Patients diagnosed with stage I to III esophageal cancer treated from 2004 to 2012 were identified from the National Cancer Data Base. Patients who received concurrent radiation and chemotherapy with radiation doses of ≥50 Gy and did not undergo surgery were included. OS was compared using Cox proportional hazards regression and propensity score matching. A total of 6854 patients were included; 3821 (55.7%) received 50 to 50.4 Gy and 3033 (44.3%) received doses >50.4 Gy. Univariate analysis revealed no significant difference in OS between patients receiving 50 to 50.4 Gy and those receiving >50.4 Gy (P=.53). The dose analysis, binned as 50 to 50.4, 51 to 54, 55 to 60, and >60 Gy, revealed no appreciable difference in OS within any group compared with 50 to 50.4 Gy. Subgroup analyses investigating the effect of dose escalation by histologic type and in the setting of intensity modulated radiation therapy also failed to reveal a benefit. Propensity score matching confirmed the absence of a statistically significant difference in OS among the dose levels. The factors associated with improved OS on multivariable analysis included female sex, lower Charlson-Deyo comorbidity score, private insurance, cervical/upper esophagus location, squamous cell histologic type, lower T stage, and node-negative status (P<.01 for all analyses). In this large national cohort, dose escalation >50.4 Gy did not result in improved OS among patients with stage I to III esophageal cancer treated with definitive concurrent radiation and chemotherapy. These data suggest that despite advanced contemporary treatment techniques, OS for patients with esophageal cancer remains unaltered by escalation of radiation dose >50.4 Gy, consistent with the results of the INT-0123 trial. Furthermore, these data highlight that many radiation oncologists have not embraced the concept that dose escalation does not improve OS. Although local control, not investigated in the present study, might benefit from dose escalation, novel therapies are needed to improve the OS of patients with esophageal cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Concurrent Validity of the Classroom Strategies Scale for Elementary School--Observer Form

ERIC Educational Resources Information Center

Reddy, Linda A.; Fabiano, Gregory A.; Dudek, Christopher M.

2013-01-01

The present study is an initial investigation of the concurrent validity of a new assessment, the Classroom Strategies Scale (CSS version 2.0) for Elementary School--Observer Form. The CSS assesses teachers' use of instructional and behavioral management strategies. In the present study, the CSS is compared to the Classroom Assessment Scoring…

Phase 1 Dose Escalation Study of Accelerated Radiation Therapy With Concurrent Chemotherapy for Locally Advanced Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kelsey, Chris R., E-mail: christopher.kelsey@duke.edu; Das, Shiva; Gu, Lin

2015-12-01

Purpose: To determine the maximum tolerated dose of radiation therapy (RT) given in an accelerated fashion with concurrent chemotherapy using intensity modulated RT. Methods and Materials: Patients with locally advanced lung cancer (non-small cell and small cell) with good performance status and minimal weight loss received concurrent cisplatin and etoposide with RT. Intensity modulated RT with daily image guidance was used to facilitate esophageal avoidance and delivered using 6 fractions per week (twice daily on Fridays with a 6-hour interval). The dose was escalated from 58 Gy to a planned maximum dose of 74 Gy in 4 Gy increments in a standardmore » 3 + 3 trial design. Dose-limiting toxicity (DLT) was defined as acute grade 3-5 nonhematologic toxicity attributed to RT. Results: A total of 24 patients were enrolled, filling all dose cohorts, all completing RT and chemotherapy as prescribed. Dose-limiting toxicity occurred in 1 patient at 58 Gy (grade 3 esophagitis) and 1 patient at 70 Gy (grade 3 esophageal fistula). Both patients with DLTs had large tumors (12 cm and 10 cm, respectively) adjacent to the esophagus. Three additional patients were enrolled at both dose cohorts without further DLT. In the final 74-Gy cohort, no DLTs were observed (0 of 6). Conclusions: Dose escalation and acceleration to 74 Gy with intensity modulated RT and concurrent chemotherapy was tolerable, with a low rate of grade ≥3 acute esophageal reactions.« less

Phase II Trial of Radiosurgery to Magnetic Resonance Spectroscopy-Defined High-Risk Tumor Volumes in Patients With Glioblastoma Multiforme

DOE Office of Scientific and Technical Information (OSTI.GOV)

Einstein, Douglas B., E-mail: douglas.einstein@khnetwork.org; Wessels, Barry; Bangert, Barbara

2012-11-01

Purpose: To determine the efficacy of a Gamma Knife stereotactic radiosurgery (SRS) boost to areas of high risk determined by magnetic resonance spectroscopy (MRS) functional imaging in addition to standard radiotherapy for patients with glioblastoma (GBM). Methods and Materials: Thirty-five patients in this prospective Phase II trial underwent surgical resection or biopsy for a GBM followed by SRS directed toward areas of MRS-determined high biological activity within 2 cm of the postoperative enhancing surgical bed. The MRS regions were determined by identifying those voxels within the postoperative T2 magnetic resonance imaging volume that contained an elevated choline/N-acetylaspartate ratio in excessmore » of 2:1. These voxels were marked, digitally fused with the SRS planning magnetic resonance image, targeted with an 8-mm isocenter per voxel, and treated using Radiation Therapy Oncology Group SRS dose guidelines. All patients then received conformal radiotherapy to a total dose of 60 Gy in 2-Gy daily fractions. The primary endpoint was overall survival. Results: The median survival for the entire cohort was 15.8 months. With 75% of recursive partitioning analysis (RPA) Class 3 patients still alive 18 months after treatment, the median survival for RPA Class 3 has not yet been reached. The median survivals for RPA Class 4, 5, and 6 patients were 18.7, 12.5, and 3.9 months, respectively, compared with Radiation Therapy Oncology Group radiotherapy-alone historical control survivals of 11.1, 8.9, and 4.6 months. For the 16 of 35 patients who received concurrent temozolomide in addition to protocol radiotherapeutic treatment, the median survival was 20.8 months, compared with European Organization for Research and Treatment of Cancer historical controls of 14.6 months using radiotherapy and temozolomide. Grade 3/4 toxicities possibly attributable to treatment were 11%. Conclusions: This represents the first prospective trial using selective MRS-targeted functional SRS combined with radiotherapy for patients with GBM. This treatment is feasible, with acceptable toxicity and patient survivals higher than in historical controls. This study can form the basis for a multicenter, randomized trial.« less

RADVAN: a randomised phase 2 trial of WBRT plus vandetanib for melanoma brain metastases – results and lessons learnt

PubMed Central

Gupta, Avinash; Roberts, Corran; Tysoe, Finn; Goff, Matthew; Nobes, Jenny; Lester, James; Marshall, Ernie; Corner, Carie; Wolstenholme, Virginia; Kelly, Charles; Wise, Adelyn; Collins, Linda; Love, Sharon; Woodward, Martha; Salisbury, Amanda; Middleton, Mark R

2016-01-01

Background: Brain metastases occur in up to 75% of patients with advanced melanoma. Most are treated with whole-brain radiotherapy (WBRT), with limited effectiveness. Vandetanib, an inhibitor of vascular endothelial growth factor receptor, epidermal growth factor receptor and rearranged during transfection tyrosine kinases, is a potent radiosensitiser in xenograft models. We compared WBRT with WBRT plus vandetanib in the treatment of patients with melanoma brain metastases. Methods: In this double-blind, multi-centre, phase 2 trial patients with melanoma brain metastases were randomised to receive WBRT (30 Gy in 10 fractions) plus 3 weeks of concurrent vandetanib 100 mg once daily or placebo. The primary endpoint was progression-free survival in brain (PFS brain). The main study was preceded by a safety run-in phase to confirm tolerability of the combination. A post-hoc analysis and literature review considered barriers to recruiting patients with melanoma brain metastases to clinical trials. Results: Twenty-four patients were recruited, six to the safety phase and 18 to the randomised phase. The study closed early due to poor recruitment. Median PFS brain was 3.3 months (90% confidence interval (CI): 1.6–5.6) in the vandetanib group and 2.5 months (90% CI: 0.2–4.8) in the placebo group (P=0.34). Median overall survival (OS) was 4.6 months (90% CI: 1.6–6.3) and 2.5 months (90% CI: 0.2–7.2), respectively (P=0.54). The most frequent adverse events were fatigue, alopecia, confusion and nausea. The most common barrier to study recruitment was availability of alternative treatments. Conclusions: The combination of WBRT plus vandetanib was well tolerated. Compared with WBRT alone, there was no significant improvement in PFS brain or OS, although we are unable to provide a definitive result due to poor accrual. A review of barriers to trial accrual identified several factors that affect study recruitment in this difficult disease area. PMID:27711083

Symptoms after ingestion of pig whipworm Trichuris suis eggs in a randomized placebo-controlled double-blind clinical trial.

PubMed

Bager, Peter; Kapel, Christian; Roepstorff, Allan; Thamsborg, Stig; Arnved, John; Rønborg, Steen; Kristensen, Bjarne; Poulsen, Lars K; Wohlfahrt, Jan; Melbye, Mads

2011-01-01

Symptoms after human infection with the helminth Trichuris suis have not previously been described. Exposure to helminths has been suggested as immune therapy against allergy and autoimmune diseases. We randomized adults with allergic rhinitis to ingest a dose of 2500 T. suis eggs or placebo every 21 days for 168 days (total 8 doses) in a double-blind clinical trial. In a previous publication, we reported a lack of efficacy and a high prevalence of adverse gastrointestinal reactions. The aim of the present study was to present a detailed description of the adverse event data and post-hoc analyses of gastrointestinal reactions. Adverse events and severity (mild, moderate, severe) were recorded daily by subjects, classified by organ using MedDRA 10.0, and event rates compared between subjects on T. suis treatment vs. subjects on placebo. T. suis-specific serum IgG antibodies were measured by a fluoroenzymeimmunoassay (Phadia ApS). During 163 days complete follow-up, subjects ingesting T. suis eggs (N = 49) had a three to 19-fold higher rate of events (median duration, 2 days) with gastrointestinal reactions (moderate to severe flatulence, diarrhea, and upper abdominal pain) compared with placebo subjects (N = 47). The highest incidence of affected subjects was seen from the first few days and until day 42 (3(rd) dose): 63% vs. 29% for placebo; day 163: 76% vs. 49% for placebo. Seroprevalences increased concurrently in the T. suis group: Day 59, 50%; day 90, 91%; day 170, 93%. The combined duration of episodes with onset before day 42 was ≤ 14 days in 80% of affected subjects. Age, gender, total IgE, and recent intestinal symptoms at baseline did not predict gastrointestinal side effects. In conclusion, during the first 2 months, repeated ingestions of 2500 T. suis eggs caused frequent gastrointestinal reactions lasting up to 14 days, whereas 4 months further treatment mainly provoked a subclinical stimulation. University hospital Medical Information Network trial registry Reg. no. R000001298, Trial ID UMIN000001070.

Evaluating a multicomponent social behaviour change communication strategy to reduce intimate partner violence among married couples: study protocol for a cluster randomized trial in Nepal.

PubMed

Clark, Cari Jo; Spencer, Rachael A; Shrestha, Binita; Ferguson, Gemma; Oakes, J Michael; Gupta, Jhumka

2017-01-13

Intimate partner violence (IPV) is a significant public health issue that affects 1 in 3 women globally and a similarly large number of women in Nepal. Over the past decade, important policy and programmatic steps have been taken to address violence against women in Nepal. There remains a dearth of evidence on the effectiveness of primary violence prevention strategies. The Change Starts at Home study begins to fill this gap by utilizing a multi-component social behaviour change communication (SBCC) strategy involving a radio drama and community mobilization to shift attitudes, norms and behaviours that underpin IPV perpetration in Nepal. The study uses a concurrent mixed-methods design. The quantitative aspect of the evaluation is a pair-matched, repeated cross-sectional 2-armed, single-blinded cluster trial (RCT: N = 36 clusters, 1440 individuals), comparing a social behaviour change communication (SBCC) strategy to radio programming alone for its impact on physical and / or sexual IPV at the end of programming (12 months' post-baseline) and 6-months post the cessation of project activities (18-months post baseline). The qualitative aspects of the design include several longitudinal approaches to understand the impact of the intervention and to examine mechanisms of change including in-depth interviews with participants (N = 18 couples), and focus group discussions with community leaders (N = 3 groups), and family members of participants (N = 12 groups). Treatment effects will be estimated with generalized logistic mixed models specified to compare differences in primary outcome from baseline to 12-month follow-up, and baseline to 18-months follow-up in accordance with intention-to-treat principles. The study rigorously evaluates the effectiveness of a promising strategy to prevent IPV. The results of the trial will be immediately useful for governmental, nongovernmental, and donor funded programs targeting partner violence or social norms that underpin it. Findings of the study will also contribute to global knowledge on the effectiveness of media and community engagement as a primary prevention strategy for IPV. Trial was registered in clinicaltrials.gov, NCT02942433 , 10/13/2016, retrospectively registered.

Validating Neuro-QoL short forms and targeted scales with people who have multiple sclerosis.

PubMed

Miller, Deborah M; Bethoux, Francois; Victorson, David; Nowinski, Cindy J; Buono, Sarah; Lai, Jin-Shei; Wortman, Katy; Burns, James L; Moy, Claudia; Cella, David

2016-05-01

Multiple sclerosis (MS) is a chronic, progressive, and disabling disease of the central nervous system with dramatic variations in the combination and severity of symptoms it can produce. The lack of reliable disease-specific health-related quality of life (HRQL) measures for use in clinical trials prompted the development of the Neurology Quality of Life (Neuro-QOL) instrument, which includes 13 scales that assess physical, emotional, cognitive, and social domains, for use in a variety of neurological illnesses. The objective of this research paper is to conduct an initial assessment of the reliability and validation of the Neuro-QOL short forms (SFs) in MS. We assessed reliability, concurrent validity, known groups validity, and responsiveness between cross-sectional and longitudinal data in 161 recruited MS patients. Internal consistency was high for all measures (α = 0.81-0.95) and ICCs were within the acceptable range (0.76-0.91); concurrent and known groups validity were highest with the Global HRQL question. Longitudinal assessment was limited by the lack of disease progression in the group. The Neuro-QOL SFs demonstrate good internal consistency, test-re-test reliability, and concurrent and known groups validity in this MS population, supporting the validity of Neuro-QOL in adults with MS. © The Author(s), 2015.

Comparing host and target environments for distributed Ada programs

NASA Technical Reports Server (NTRS)

Paulk, Mark C.

1986-01-01

The Ada programming language provides a means of specifying logical concurrency by using multitasking. Extending the Ada multitasking concurrency mechanism into a physically concurrent distributed environment which imposes its own requirements can lead to incompatibilities. These problems are discussed. Using distributed Ada for a target system may be appropriate, but when using the Ada language in a host environment, a multiprocessing model may be more suitable than retargeting an Ada compiler for the distributed environment. The tradeoffs between multitasking on distributed targets and multiprocessing on distributed hosts are discussed. Comparisons of the multitasking and multiprocessing models indicate different areas of application.

Occlusal splints for treating sleep bruxism (tooth grinding).

PubMed

Macedo, C R; Silva, A B; Machado, M A; Saconato, H; Prado, G F

2007-10-17

Sleep bruxism is an oral activity characterised by teeth grinding or clenching during sleep. Several treatments for sleep bruxism have been proposed such as pharmacological, psychological, and dental. To evaluate the effectiveness of occlusal splints for the treatment of sleep bruxism with alternative interventions, placebo or no treatment. We searched the Cochrane Oral Health Group's Trials Register (to May 2007); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 1); MEDLINE (1966 to May 2007); EMBASE (1980 to May 2007); LILACS (1982 to May 2007); Biblioteca Brasileira de Odontologia (1982 to May 2007); Dissertation, Theses and Abstracts (1981 to May 2007); and handsearched abstracts of particular importance to this review. Additional reports were identified from the reference lists of retrieved reports and from article reviews about treating sleep bruxism. There were no language restrictions. We selected randomised or quasi-randomised controlled trials (RCTs), in which splint therapy was compared concurrently to no treatment, other occlusal appliances, or any other intervention in participants with sleep bruxism. Data extraction was carried out independently and in duplicate. Validity assessment of the included trials was carried out at the same time as data extraction. Discrepancies were discussed and a third review author consulted. The author of the primary study was contacted when necessary. Thirty-two potentially relevant RCTs were identified. Twenty-four trials were excluded. Five RCTs were included. Occlusal splint was compared to: palatal splint, mandibular advancement device, transcutaneous electric nerve stimulation, and no treatment. There was just one common outcome (arousal index) which was combined in a meta-analysis. No statistically significant differences between the occlusal splint and control groups were found in the meta-analyses. There is not sufficient evidence to state that the occlusal splint is effective for treating sleep bruxism. Indication of its use is questionable with regard to sleep outcomes, but it may be that there is some benefit with regard to tooth wear. This systematic review suggests the need for further investigation in more controlled RCTs that pay attention to method of allocation, outcome assessment, large sample size, and sufficient duration of follow up. The study design must be parallel, in order to eliminate the bias provided by studies of cross-over type. A standardisation of the outcomes of the treatment of sleep bruxism should be established in the RCTs.

Procarbazine and CCNU Chemotherapy for Recurrent Glioblastoma with MGMT Promoter Methylation.

PubMed

Kim, Se-Hyuk; Yoo, Heon; Chang, Jong Hee; Kim, Chae-Yong; Chung, Dong Sup; Kim, Se Hoon; Park, Sung-Hae; Lee, Youn Soo; Yang, Seung Ho

2018-06-11

While procarbazine, CCNU (lomustine), and vincristine (PCV) has been an alternative chemotherapy option for malignant gliomas, it is worth investigating whether the combination of only procarbazine and CCNU is comparable because vincristine adds toxicity with uncertain benefit. The purpose of this study was to evaluate the feasibility of procarbazine and CCNU chemotherapy for recurrent glioblastoma multiforme (GBM) with O 6 -methylguanine-DNA-methyltransferase (MGMT) promoter methylation. Eight patients with recurrent GBM following concurrent chemoradiotherapy and temozolomide (TMZ) adjuvant therapy were enrolled in this trial; they received no other chemotherapeutic agents or target therapy. They received CCNU (75 mg/m 2 ) on day 1 and procarbazine (60 mg/m 2 ) through days 11 and 24 every 4 weeks. The median cycle of CCNU and procarbazine was 3.5 (range: 2-6). One patient achieved stable disease. The median progression-free survival (PFS) with procarbazine and CCNU chemotherapy was eight weeks (range: 5-73), and the PFS rates were 25% and 12.5% at 16 and 30 weeks, respectively. The median overall survival (OS) from the initial diagnosis to death was 40 months, and the median OS from the administration of procarbazine and CCNU chemotherapy to death was 9.7 months (95% confidence interval: 6.7-12.7). Serious adverse events were found at six visits, and two cases were considered to be grade 3 toxicities. The efficacy of procarbazine and CCNU chemotherapy is not satisfactory. This study suggests the need to develop other treatment strategies for recurrent and TMZ-refractory GBM. Trial registry at ClinicalTrials.gov, NCT017337346.

The Stochastic Early Reaction, Inhibition, and late Action (SERIA) model for antisaccades

PubMed Central

2017-01-01

The antisaccade task is a classic paradigm used to study the voluntary control of eye movements. It requires participants to suppress a reactive eye movement to a visual target and to concurrently initiate a saccade in the opposite direction. Although several models have been proposed to explain error rates and reaction times in this task, no formal model comparison has yet been performed. Here, we describe a Bayesian modeling approach to the antisaccade task that allows us to formally compare different models on the basis of their evidence. First, we provide a formal likelihood function of actions (pro- and antisaccades) and reaction times based on previously published models. Second, we introduce the Stochastic Early Reaction, Inhibition, and late Action model (SERIA), a novel model postulating two different mechanisms that interact in the antisaccade task: an early GO/NO-GO race decision process and a late GO/GO decision process. Third, we apply these models to a data set from an experiment with three mixed blocks of pro- and antisaccade trials. Bayesian model comparison demonstrates that the SERIA model explains the data better than competing models that do not incorporate a late decision process. Moreover, we show that the early decision process postulated by the SERIA model is, to a large extent, insensitive to the cue presented in a single trial. Finally, we use parameter estimates to demonstrate that changes in reaction time and error rate due to the probability of a trial type (pro- or antisaccade) are best explained by faster or slower inhibition and the probability of generating late voluntary prosaccades. PMID:28767650

Evidence for Neuroplastic Compensation in the Cerebral Cortex of Persons with Depressive Illness

PubMed Central

Bansal, Ravi; Hellerstein, David J.; Peterson, Bradley S.

2017-01-01

We yoked anatomical brain Magnetic Resonance Imaging to a randomized, double-blind, placebo-controlled trial (RCT) of antidepressant medication for 10-week’s duration in patients with dysthymia. The RCT study design mitigated ascertainment bias by randomizing patients to receive either duloxetine or placebo, and it supported true causal inferences about treatment effects on the brain by controlling treatment assignment experimentally. We acquired 121 anatomical scans: at baseline and endpoint in 41 patients, and once in 39 healthy controls. At baseline, patients had diffusely thicker cortices than did healthy participants, and patients who had thicker cortices had proportionately less severe symptoms. During the trial, symptoms improved significantly more in medication- compared with placebo-treated patients; concurrently, thicknesses in medication-treated patients declined toward values in healthy controls, but they increased slightly, away from control values, in placebo-treated patients. Changes in symptom severity during the trial mediated the association of treatment assignment with the change in thickness, suggesting that the beneficial effects of medication on symptom severity were at least partially responsible for normalizing cortical thickness. Together our findings suggest that baseline cortical hypertrophy in medication-free patients likely represented a compensatory, neuroplastic response that attenuated symptom severity. Medication then reduced symptoms and lessened the need for compensation, thereby normalizing thickness. This is to the best of our knowledge the first study to report within an RCT a differential change in cortical morphology during medication treatment for depressive illness and the first to provide within an RCT in vivo evidence for the presence of neuroanatomical plasticity in humans. PMID:28265119

Pancreatic Lipase Immunoreactivity in Serum of Dogs with Diabetic Ketoacidosis.

PubMed

Bolton, T A; Cook, A; Steiner, J M; Fosgate, G T

2016-07-01

Diabetic ketoacidosis (DKA) is a relatively common endocrine disorder in dogs and is routinely associated with concurrent pancreatic injury. The aims of this study were to determine the prevalence of pancreatic injury in dogs with DKA based on measurement of pancreatic lipase immunoreactivity in serum (PLI); compare demographic, clinicopathologic, and ultrasonographic findings in dogs with and without evidence of concurrent pancreatic injury; determine the impact of pancreatic injury on duration of hospitalization and short-term outcome. One hundred and nineteen dogs with DKA with or without concurrent pancreatic injury. Retrospective study. Dogs with DKA were divided into three groups on the basis of PLI results: positive for pancreatic injury (PLIpos ), negative for pancreatic injury (PLIneg ), and not tested (PLIna ). Demographics, clinicopathologic test results, findings on abdominal ultrasonography (AUS), duration of hospitalization, and short-term outcome were compared between the three groups. Based on serum PLI activity, 45 dogs (73%) with DKA had evidence of concurrent pancreatic injury. Median total carbon dioxide was significantly lower in the PLIpos dogs compared to the PLIneg dogs. There was fair agreement (κ = 0.26) between serum PLI activity and AUS. Evidence of pancreatic injury was not associated with significantly longer periods of hospitalization (PLIpos median 6 days, range 4-7 days, PLIneg median 4 days, range 3-6 days) and did not influence short-term outcome (PLIpos failure to survive to discharge 11/45, 24%, PLIneg failure to survive to discharge 2/17, 12%). Concurrent pancreatic injury is common in dogs with DKA, but did not affect prognosis in this population of dogs. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Telavancin in the Treatment of Concurrent Staphylococcus aureus Bacteremia: A Retrospective Analysis of ATLAS and ATTAIN Studies.

PubMed

Wilson, Samuel E; Graham, Donald R; Wang, Whedy; Bruss, Jon B; Castaneda-Ruiz, Bibiana

2017-09-01

Concurrent Staphylococcus aureus bacteremia (SAB) worsens outcomes and increases mortality in patients with complicated skin and skin structure infections (cSSSI), hospital-acquired bacterial pneumonia, and ventilator-associated bacterial pneumonia (HABP/VABP). These challenges highlight the need for alternative treatments. Telavancin (TLV), a bactericidal lipoglycopeptide with high in vitro potency, effectively treats patients with cSSSI and HABP/VABP caused by Gram-positive pathogens, particularly S. aureus. This retrospective analysis evaluated patients from the Assessment of Telavancin in Complicated Skin and Skin Structure Infections and Assessment of Telavancin for Treatment of Hospital-Acquired Pneumonia studies with baseline, concurrent SAB. Differences in the clinical cure rates at test-of-cure and safety outcomes were compared for TLV vs vancomycin (VAN) treatment groups. A total of 105 patients, 32 cSSSI and 73 HABP/VABP, had baseline, concurrent SAB. The clinical cure rates for all-treated SAB patients in the cSSSI (TLV 57.1% and VAN 54.5%) and HABP/VABP (TLV 54.3% and VAN 47.2%) groups were comparable. For both types of infections, the safety profile of TLV and VAN showed similar incidences of adverse events (AEs), serious AEs, or AEs leading to discontinuation. One VAN-treated patient died in the cSSSI group, and there were 13 deaths in each treatment arm of the HABP/VABP group. This retrospective analysis demonstrated that TLV is clinically comparable in both efficacy and safety to VAN, and, therefore, may be an appropriate therapeutic option for the treatment of patients with HABP/VABP or cSSSI and concurrent SAB. Given the limited sample size in this subgroup, the interpretation of these results is limited. Theravance Biopharma Antibiotics, Inc.

Weight loss versus muscle loss: re-evaluating inclusion criteria for future cancer cachexia interventional trials.

PubMed

Roeland, Eric J; Ma, Joseph D; Nelson, Sandahl H; Seibert, Tyler; Heavey, Sean; Revta, Carolyn; Gallivan, Andrea; Baracos, Vickie E

2017-02-01

Participation in cancer cachexia clinical trials requires a defined weight loss (WL) over time. A loss in skeletal muscle mass, measured by cross-sectional computed tomography (CT) image analysis, represents a possible alternative. Our aim was to compare WL versus muscle loss in patients who were screened to participate in a cancer cachexia clinical trial. This was a single-center, retrospective analysis in metastatic colorectal cancer patients screened for an interventional cancer cachexia trial requiring a ≥5 % WL over the preceding 6 months. Concurrent CT images obtained as part of standard oncology care were analyzed for changes in total muscle and fat (visceral, subcutaneous, and total). Of patients screened (n = 36), 3 (8 %) enrolled in the trial, 17 (47 %) were excluded due to insufficient WL (<5 %), 3 (8 %) were excluded due to excessive WL (>20 %), and 16 (44 %) met inclusion criteria for WL. Patients who met screening criteria for WL (5-20 %) had a mean ± SD of 7.7 ± 8.7 % muscle loss, 24.4 ± 37.5 % visceral adipose loss, 21.6 ± 22.3 % subcutaneous adipose loss, and 22.1 ± 24.7 % total adipose loss. Patients excluded due to insufficient WL had 2 ± 6.4 % muscle loss, but a gain of 8.5 ± 39.8 % visceral adipose, and 4.2 ± 28.2 % subcutaneous adipose loss and 0.8 ± 28.4 % total adipose loss. Of the patients excluded due to WL <5 % (n = 17), 7 (41 %) had a skeletal muscle loss >5 %. Defining cancer cachexia by WL over time may be limited as it does not capture skeletal muscle loss. Cross-sectional CT body composition analysis may improve early detection of muscle loss and patient participation in future cancer cachexia clinical trials.

Concurrent immunomodulator therapy is associated with higher adalimumab trough levels during scheduled maintenance therapy.

PubMed

Bond, Ashley; Dodd, Susanna; Fisher, Gareth; Skouras, Thomas; Subramanian, Sreedhar

2017-02-01

Combination therapy with infliximab and immunomodulators is superior to monotherapy, resulting in better outcomes and higher trough levels of infliximab. The role of concurrent immunomodulatory therapy on adalimumab trough levels has not been adequately investigated. We evaluated the impact of concomitant immunomodulation on adalimumab trough levels in patients on scheduled maintenance therapy. We conducted a prospective observational, cross-sectional study of all inflammatory bowel disease patients on maintenance therapy who had adalimumab trough levels measured between January 2013 and January 2016. Drug level and anti-drug antibody measurements were performed on sera using a solid phase assay. Pairwise comparison of means was used to compare trough levels in patients with and without concomitant immune modulator therapy. In total, 79 patients were included. Twenty-three patients (29.1%) were on weekly dosing whereas 56 (70.9%) were on alternate weeks. Median adalimumab trough levels were comparable in patients with and without clinical remission (6.8 μg/ml (IQR 5.6-8.1) versus 6.7 μg/ml (IQR 3.9-8.1), respectively. Patients with an elevated faecal calprotectin >250 μg/g had lower adalimumab trough levels (median 6.7, IQR 3.9-8) compared to patients with faecal calprotectin <250 μg/g (median 7.7, IQR 6.1-8.1) though this did not achieve statistical significance (p = .062). Median adalimumab trough levels among patients on concurrent immunomodulators was 7.2 μg/ml (IQR 5.7-8.1) compared to those not on concurrent immunomodulator, 6.1 μg/ml (IQR 2.7-7.7, p = .0297). Adalimumab trough levels were significantly higher in patients on concurrent immunomodulators during maintenance therapy. There was a trend towards a lower adalimumab trough level in patients with elevated calprotectin.

Assessing Specific Cognitive Deficits Associated with Dementia in Older Adults with Down Syndrome: Use and Validity of the Arizona Cognitive Test Battery (ACTB)

PubMed Central

Sinai, Amanda; Hassiotis, Angela; Rantell, Khadija; Strydom, Andre

2016-01-01

Background Down syndrome is associated with specific cognitive deficits. Alongside this, older adults with Down syndrome are a high risk group for dementia. The Arizona Cognitive Test Battery (ACTB), a cognitive assessment battery specifically developed for use with individuals with Down syndrome, has been proposed for use as outcome measures for clinical trials in this population. It has not been validated in older adults with Down syndrome. This study aims to assess the use and validity of the ACTB in older adults with Down syndrome. Methods Participants with Down syndrome aged 45 and over were assessed using the ACTB, standard tabletop tests and informant ratings. Results Assessment outcomes of 49 participants were analysed. Of these, 19 (39%) had a diagnosis of dementia or possible dementia. Most participants were able to attempt most of the tasks, although some tasks had high floor effects (including CANTAB Intra-Extra Dimensional shift stages completed and Modified Dots Task). Of the ACTB tasks, statistically significant differences were observed between the dementia and no dementia groups on CANTAB Simple Reaction Time median latency, NEPSY Visuomotor Precision—Car and Motorbike and CANTAB Paired Associates Learning stages completed. No significant differences were observed for CANTAB Intra-Extra Dimensional Shift, Modified Dots Task, Finger Sequencing, NEPSY Visuomotor precision—Train and Car and CANTAB Paired Associates Learning first trial memory score. Several of the tasks in the ACTB can be used in older adults with Down syndrome and have mild to moderate concurrent validity when compared to tabletop tests and informant ratings, although this varies on a test by test basis. Conclusions Overall, scores for a number of tests in the ACTB were similar when comparing dementia and no dementia groups of older adults with Down syndrome, suggesting that it would not be an appropriate outcome measure of cognitive function for clinical trials of dementia treatments without further modification and validation. PMID:27171413

Assessing Specific Cognitive Deficits Associated with Dementia in Older Adults with Down Syndrome: Use and Validity of the Arizona Cognitive Test Battery (ACTB).

PubMed

Sinai, Amanda; Hassiotis, Angela; Rantell, Khadija; Strydom, Andre

2016-01-01

Down syndrome is associated with specific cognitive deficits. Alongside this, older adults with Down syndrome are a high risk group for dementia. The Arizona Cognitive Test Battery (ACTB), a cognitive assessment battery specifically developed for use with individuals with Down syndrome, has been proposed for use as outcome measures for clinical trials in this population. It has not been validated in older adults with Down syndrome. This study aims to assess the use and validity of the ACTB in older adults with Down syndrome. Participants with Down syndrome aged 45 and over were assessed using the ACTB, standard tabletop tests and informant ratings. Assessment outcomes of 49 participants were analysed. Of these, 19 (39%) had a diagnosis of dementia or possible dementia. Most participants were able to attempt most of the tasks, although some tasks had high floor effects (including CANTAB Intra-Extra Dimensional shift stages completed and Modified Dots Task). Of the ACTB tasks, statistically significant differences were observed between the dementia and no dementia groups on CANTAB Simple Reaction Time median latency, NEPSY Visuomotor Precision-Car and Motorbike and CANTAB Paired Associates Learning stages completed. No significant differences were observed for CANTAB Intra-Extra Dimensional Shift, Modified Dots Task, Finger Sequencing, NEPSY Visuomotor precision-Train and Car and CANTAB Paired Associates Learning first trial memory score. Several of the tasks in the ACTB can be used in older adults with Down syndrome and have mild to moderate concurrent validity when compared to tabletop tests and informant ratings, although this varies on a test by test basis. Overall, scores for a number of tests in the ACTB were similar when comparing dementia and no dementia groups of older adults with Down syndrome, suggesting that it would not be an appropriate outcome measure of cognitive function for clinical trials of dementia treatments without further modification and validation.

A qualitative understanding of the effects of reusable sanitary pads and puberty education: implications for future research and practice.

PubMed

Hennegan, Julie; Dolan, Catherine; Steinfield, Laurel; Montgomery, Paul

2017-06-27

The management of menstruation has come to the fore as a barrier to girls' education attainment in low income contexts. Interventions have been proposed and piloted, but the emerging nature of the field means limited evidence is available to understand their pathways of effect. This study describes and compares schoolgirls' experiences of menstruation in rural Uganda at the conclusion of a controlled trial of puberty education and sanitary pad provision to elucidate pathways of effect in the interventions. Semi-structured interviews were undertaken with schoolgirls who participated in the Menstruation and the Cycle of Poverty trial concurrent with the final set of quantitative surveys. A framework approach and cross-case analysis were employed to describe and compare the experiences of 27 menstruating girls across the four intervention conditions; education (n = 8), reusable sanitary pads (n = 8), education with reusable sanitary pads (n = 6), and control (n = 5). Themes included: menstrual hygiene, soiling, irritation and infection, physical experience, knowledge of menstruation, psychological, social and cultural factors, and support from others. Those receiving reusable pads experienced improvements in comfort and reliability. This translated into reduced fears around garment soiling and related school absenteeism. Other menstrual hygiene challenges of washing, drying and privacy remained prominent. Puberty education improved girls' confidence to discuss menstruation and prompted additional support from teachers and peers. Findings have important implications for the development and evaluation of future interventions. Results suggest the provision of menstrual absorbents addresses one core barrier to menstrual health, but that interventions addressing broader needs such as privacy may improve effectiveness. Puberty education sessions should increase attention to body awareness and include strategies to address a wider range of practical menstrual challenges, including pain management. Interviews revealed possibilities for improving quantitative surveys in future research. Pan-African Clinical Trials Registry PACTR201503001044408.

Impact of a board-game approach on current smokers: a randomized controlled trial

PubMed Central

2013-01-01

Background The main objective of our study was to assess the impact of a board game on smoking status and smoking-related variables in current smokers. To accomplish this objective, we conducted a randomized controlled trial comparing the game group with a psychoeducation group and a waiting-list control group. Methods The following measures were performed at participant inclusion, as well as after a 2-week and a 3-month follow-up period: “Attitudes Towards Smoking Scale” (ATS-18), “Smoking Self-Efficacy Questionnaire” (SEQ-12), “Attitudes Towards Nicotine Replacement Therapy” scale (ANRT-12), number of cigarettes smoked per day, stages of change, quit attempts, and smoking status. Furthermore, participants were assessed for concurrent psychiatric disorders and for the severity of nicotine dependence with the Fagerström Test for Nicotine Dependence (FTND). Results A time × group effect was observed for subscales of the ANRT-12, ATS-18 and SEQ-12, as well as for the number of cigarettes smoked per day. At three months follow-up, compared to the participants allocated to the waiting list group, those on Pick-Klop group were less likely to remain smoker. Outcomes at 3 months were not predicted by gender, age, FTND, stage of change, or psychiatric disorders at inclusion. Conclusions The board game seems to be a good option for smokers. The game led to improvements in variables known to predict quitting in smokers. Furthermore, it increased smoking-cessation rates at 3-months follow-up. The game is also an interesting alternative for smokers in the precontemplation stage. PMID:23327643

Endometriosis is the independent prognostic factor for survival in Chinese patients with epithelial ovarian carcinoma.

PubMed

Ren, Tong; Wang, Shu; Sun, Jian; Qu, Ji-Min; Xiang, Yang; Shen, Keng; Lang, Jing He

2017-10-03

Clinico-pathological characteristics and possible prognostic factors among women with epithelial ovarian carcinoma (EOC) with or without concurrent endometriosis were explored. We retrospectively identified 304 patients with EOC treated primarily at Peking Union Medical College Hospital with median follow-up time of 60 months. Of 304 patients with EOC, concurrent endometriosis was identified in 69 (22.7%). The patients with concurrent endometriosis were younger and more probably post-menopausal at onset, were less likely to have abdominal distension, with significantly lower level of pre-surgery serum Ca125 and less possibility of having the history of tubal ligation. The women with concurrent endometriosis group were more likely to have early stage tumors (88.41% versus 52.77%), receive optimal cytoreductive surgery (92.75% versus 71.06%), and less likely to have lymph node metastasis or to develop platinum resistance disease (7.25% versus 14.89%, and 7.35% versus 20%), when compared with women without coexisting endometriosis. The univariate analysis showed that concurrent endometriosis was a prognostic factor for overall survival (OS) and disease-free survival (DFS), but this association just remained in the DFS by multivariate analysis. Besides, multivariate analysis also showed that FIGO stage, residual disease, chemotherapy cycles, chemotherapy resistance and concomitant hypertension were the independent impact factors of OS for EOC patients; whereas FIGO stage, lymphadenectomy, residual disease, coexisting endometriosis and chemoresistance were independent impact factors of DFS for those patients. EOC patients with concurrent endometriosis showed distinct characteristics and had longer overall survival and disease-free survival when compared with those without endometriosis. Endometriosis was the independent prognostic factor for DFS for patients in this series.

Comparing two methods to promote generalization of receptive identification in children with autism spectrum disorders.

PubMed

Dufour, Marie-Michèle; Lanovaz, Marc J

2017-11-01

The purpose of our study was to compare the effects of serial and concurrent training on the generalization of receptive identification in children with autism spectrum disorders (ASD). We taught one to three pairs of stimulus sets to nine children with ASD between the ages of three and six. One stimulus set within each pair was taught using concurrent training and the other using serial training. We alternated the training sessions within a multielement design and staggered the introduction of subsequent pairs for each participant as in a multiple baseline design. Overall, six participants generalized at least one stimulus set more rapidly with concurrent training whereas two participants showed generalization more rapidly with serial training. Our results differ from other comparison studies on the topic and indicate that practitioners should consider assessing the effects of both procedures prior to teaching receptive identification to children with ASD.

Impaired Behavior Regulation under Conditions of Concurrent Variable Schedules of Reinforcement in Children with ADHD

ERIC Educational Resources Information Center

Taylor, David; Lincoln, Alan J.; Foster, Sharon L.

2010-01-01

Objective: To bridge theory of response inhibition and learning in children with ADHD. Method: Thirty ADHD and 30 non-ADHD children (ages 9-12) were compared under concurrent variable interval (VI-15 sec., VI-30 sec. and VI- 45 sec.) reinforcement schedules that required the child to switch between the three schedules under conditions of…

Investigating Separate and Concurrent Approaches for Item Parameter Drift in 3PL Item Response Theory Equating

ERIC Educational Resources Information Center

Arce-Ferrer, Alvaro J.; Bulut, Okan

2017-01-01

This study examines separate and concurrent approaches to combine the detection of item parameter drift (IPD) and the estimation of scale transformation coefficients in the context of the common item nonequivalent groups design with the three-parameter item response theory equating. The study uses real and synthetic data sets to compare the two…

Bullying and Victimization in Adolescence: Concurrent and Stable Roles and Psychological Health Symptoms

ERIC Educational Resources Information Center

Menesini, Ersilia; Modena, Marco; Tani, Franca

2009-01-01

From an initial sample of 1,278 Italian students, the authors selected 537 on the basis of their responses to a self-report bully and victim questionnaire. Participants' ages ranged from 13 to 20 years (M = 15.12 years, SD = 1.08 years). The authors compared the concurrent psychological symptoms of 4 participant groups (bullies, victims,…

Acquiring Reading and Vocabulary in Dutch and English: The Effect of Concurrent Instruction

ERIC Educational Resources Information Center

van der Leij, Aryan; Bekebrede, Judith; Kotterink, Mieke

2010-01-01

To investigate the effect of concurrent instruction in Dutch and English on reading acquisition in both languages, 23 pupils were selected from a school with bilingual education, and 23 from a school with education in Dutch only. The pupils had a Dutch majority language background and were comparable with regard to social-economic status (SES).…

Comparing the Effectiveness of Two Models of Initial Teacher Education Programmes in Israel: Concurrent vs. Consecutive

ERIC Educational Resources Information Center

Zuzovsky, Ruth; Donitsa-Schmidt, Smadar

2017-01-01

The purpose of the present study was to examine the effectiveness of two common models of initial teacher education programmes that are prevalent in many countries, including Israel. The two are: the concurrent model, in which disciplinary studies and pedagogical studies are integrated and taught at the same time; and the consecutive model, which…

Translatability of helminth therapy in inflammatory bowel diseases

PubMed Central

Weinstock, Joel V; Elliott, David E.

2013-01-01

Modern hygienic lifestyles are associated with the emergence of inflammatory bowel disease (IBD) which now afflicts millions of people in highly-developed countries. Meticulous hygiene interrupts conduits of transmission required for ubiquitous exposure to parasitic worms (helminths). We proposed that loss of exposure to helminths permits development of IBD. Early clinical trials suggested that exposure to helminths such as Trichuris suis or Necator americanus can improve IBD. Over the last several years, processes to “medicinalize” T. suis have been developed and use of this helminth is now being studied in large multi-center clinical trials. Concurrently, we and others have identified some of the immune regulatory mechanisms elicited by helminth exposure that suppress inappropriate intestinal inflammation. These efforts could soon result in new therapies for patients with IBD. PMID:23178819

Prediction of concurrent endometrial carcinoma in women with endometrial hyperplasia.

PubMed

Matsuo, Koji; Ramzan, Amin A; Gualtieri, Marc R; Mhawech-Fauceglia, Paulette; Machida, Hiroko; Moeini, Aida; Dancz, Christina E; Ueda, Yutaka; Roman, Lynda D

2015-11-01

Although a fraction of endometrial hyperplasia cases have concurrent endometrial carcinoma, patient characteristics associated with concurrent malignancy are not well described. The aim of our study was to identify predictive clinico-pathologic factors for concurrent endometrial carcinoma among patients with endometrial hyperplasia. A case-control study was conducted to compare endometrial hyperplasia in both preoperative endometrial biopsy and hysterectomy specimens (n=168) and endometrial carcinoma in hysterectomy specimen but endometrial hyperplasia in preoperative endometrial biopsy (n=43). Clinico-pathologic factors were examined to identify independent risk factors of concurrent endometrial carcinoma in a multivariate logistic regression model. The most common histologic subtype in preoperative endometrial biopsy was complex hyperplasia with atypia [CAH] (n=129) followed by complex hyperplasia without atypia (n=58) and simple hyperplasia with or without atypia (n=24). The majority of endometrial carcinomas were grade 1 (86.0%) and stage I (83.7%). In multivariate analysis, age 40-59 (odds ratio [OR] 3.07, p=0.021), age≥60 (OR 6.65, p=0.005), BMI≥35kg/m(2) (OR 2.32, p=0.029), diabetes mellitus (OR 2.51, p=0.019), and CAH (OR 9.01, p=0.042) were independent predictors of concurrent endometrial carcinoma. The risk of concurrent endometrial carcinoma rose dramatically with increasing number of risk factors identified in multivariate model (none 0%, 1 risk factor 7.0%, 2 risk factors 17.6%, 3 risk factors 35.8%, and 4 risk factors 45.5%, p<0.001). Hormonal treatment was associated with decreased risk of concurrent endometrial cancer in those with ≥3 risk factors. Older age, obesity, diabetes mellitus, and CAH are predictive of concurrent endometrial carcinoma in endometrial hyperplasia patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Rationale for a preliminary operational definition of physical frailty and sarcopenia in the SPRINTT trial.

PubMed

Cesari, Matteo; Landi, Francesco; Calvani, Riccardo; Cherubini, Antonio; Di Bari, Mauro; Kortebein, Patrick; Del Signore, Susanna; Le Lain, Regis; Vellas, Bruno; Pahor, Marco; Roubenoff, Ronenn; Bernabei, Roberto; Marzetti, Emanuele

2017-02-01

In the present article, the rationale that guided the operationalization of the theoretical concept of physical frailty and sarcopenia (PF&S), the condition of interest for the "Sarcopenia and Physical Frailty in Older People: Multicomponent Treatment Strategies" (SPRINTT) trial, is presented. In particular, the decisions lead to the choice of the adopted instruments, and the reasons for setting the relevant thresholds are explained. In SPRINTT, the concept of physical frailty is translated with a Short Physical Performance Battery score of ≥3 and ≤9. Concurrently, sarcopenia is defined according to the recent definitions of low muscle mass proposed by the Foundation for the National Institutes of Health-Sarcopenia Project. Given the preventive purpose of SPRINTT, older persons with mobility disability (operationalized as incapacity to complete a 400-m walk test within 15 min; primary outcome of the trial) at the baseline are not included within the diagnostic spectrum of PF&S.

Internet-Based Acceptance and Commitment Therapy for Psychological Distress Experienced by People With Hearing Problems: Study Protocol for a Randomized Controlled Trial.

PubMed

Molander, Peter; Hesser, Hugo; Weineland, Sandra; Bergwall, Kajsa; Buck, Sonia; Hansson-Malmlöf, Johan; Lantz, Henning; Lunner, Thomas; Andersson, Gerhard

2015-09-01

Psychological distress and psychiatric symptoms are prevalent among people with hearing loss or other audiological conditions, but psychological interventions for these groups are rare. This article describes the study protocol for a randomized controlled trial for evaluating the effect of a psychological treatment delivered over the Internet for individuals with hearing problems and concurrent psychological distress. Participants who are significantly distressed will be randomized to either an 8-week Internet-delivered acceptance-based cognitive behavioral therapy (i.e., acceptance and commitment therapy [ACT]), or wa it-list control. We aim to include measures of distress associated with hearing difficulties, anxiety, and depression. In addition, we aim to measure acceptance associated with hearing difficulties as well as quality of life. The results of the trial may further our understanding of how to best treat people who present problems with both psychological distress and hearing in using the Internet.

Is clarithromycin a potential treatment for cachexia in people with lung cancer? A feasibility study.

PubMed

Awan, Sarah; Crosby, Vincent; Potter, Vanessa; Hennig, Ivo; Baldwin, David; Ndlovu, Mehluli; Paradine, Sharon; Wilcock, Andrew

2017-02-01

Clarithromycin may improve cachexia and survival in non-small cell lung cancer (NSCLC), but adequately controlled data are lacking. This study was undertaken primarily to inform the feasibility and scale of a phase III trial. Eligible consenting patients with stage IV NSCLC and cachexia were to be randomized to receive either clarithromycin 250mg twice daily or placebo for eight weeks. Aspects of trial feasibility recorded included numbers eligible, approached and recruited, together with adherence and completion of treatment and assessments. Over 6 months, none of 125 patients identified fulfilled the entry criteria. The commonest reasons for ineligibility were the use of an excluded concurrent drug (45, 36%), brain metastases (22, 18%), poor performance status (21, 17%) and current chemotherapy (15, 12%). A phase III trial of clarithromycin using these entry criteria is not feasible in this setting. Other macrolides that have a lower risk of a drug-drug interaction may be more practical to pursue. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The curse of planning: dissecting multiple reinforcement-learning systems by taxing the central executive.

PubMed

Otto, A Ross; Gershman, Samuel J; Markman, Arthur B; Daw, Nathaniel D

2013-05-01

A number of accounts of human and animal behavior posit the operation of parallel and competing valuation systems in the control of choice behavior. In these accounts, a flexible but computationally expensive model-based reinforcement-learning system has been contrasted with a less flexible but more efficient model-free reinforcement-learning system. The factors governing which system controls behavior-and under what circumstances-are still unclear. Following the hypothesis that model-based reinforcement learning requires cognitive resources, we demonstrated that having human decision makers perform a demanding secondary task engenders increased reliance on a model-free reinforcement-learning strategy. Further, we showed that, across trials, people negotiate the trade-off between the two systems dynamically as a function of concurrent executive-function demands, and people's choice latencies reflect the computational expenses of the strategy they employ. These results demonstrate that competition between multiple learning systems can be controlled on a trial-by-trial basis by modulating the availability of cognitive resources.

The Curse of Planning: Dissecting multiple reinforcement learning systems by taxing the central executive

PubMed Central

Otto, A. Ross; Gershman, Samuel J.; Markman, Arthur B.; Daw, Nathaniel D.

2013-01-01

A number of accounts of human and animal behavior posit the operation of parallel and competing valuation systems in the control of choice behavior. Along these lines, a flexible but computationally expensive model-based reinforcement learning system has been contrasted with a less flexible but more efficient model-free reinforcement learning system. The factors governing which system controls behavior—and under what circumstances—are still unclear. Based on the hypothesis that model-based reinforcement learning requires cognitive resources, we demonstrate that having human decision-makers perform a demanding secondary task engenders increased reliance on a model-free reinforcement learning strategy. Further, we show that across trials, people negotiate this tradeoff dynamically as a function of concurrent executive function demands and their choice latencies reflect the computational expenses of the strategy employed. These results demonstrate that competition between multiple learning systems can be controlled on a trial-by-trial basis by modulating the availability of cognitive resources. PMID:23558545

The effects of a concurrent task on walking in persons with transfemoral amputation compared to persons without limb loss.

PubMed

Morgan, Sara J; Hafner, Brian J; Kelly, Valerie E

2016-08-01

Many people with lower limb loss report the need to concentrate on walking. This may indicate increased reliance on cognitive resources when walking compared to individuals without limb loss. This study quantified changes in walking associated with addition of a concurrent cognitive task in persons with transfemoral amputation using microprocessor knees compared to age- and sex-matched controls. Observational, cross-sectional study. Quantitative motion analysis was used to assess walking under both single-task (walking alone) and dual-task (walking while performing a cognitive task) conditions. Primary outcomes were walking speed, step width, step time asymmetry, and cognitive task response latency and accuracy. Repeated-measures analysis of variance was used to examine the effects of task (single-task and dual-task) and group (transfemoral amputation and control) for each outcome. No significant interactions between task and group were observed (all p > 0.11) indicating that a cognitive task did not differentially affect walking between groups. However, walking was slower with wider steps and more asymmetry in people with transfemoral amputation compared to controls under both conditions. Although there were significant differences in walking between people with transfemoral amputation and matched controls, the effects of a concurrent cognitive task on walking were similar between groups. The addition of a concurrent task did not differentially affect walking outcomes in people with and without transfemoral amputation. However, compared to people without limb loss, people with transfemoral amputation adopted a conservative walking strategy. This strategy may reduce the need to concentrate on walking but also contributed to notable gait deviations. © The International Society for Prosthetics and Orthotics 2015.

External cooling methods for treatment of fever in adults: a systematic review.

PubMed

Chan, E Y; Chen, W T; Assam, P N

It is unclear if the use of external cooling to treat fever contributes to better patient outcomes. Despite this, it is a common practice to treat febrile patients using external cooling methods alone or in combination with pharmacological antipyretics. The objective of this systematic review was to evaluate the effectiveness and complications of external cooling methods in febrile adults in acute care settings. We included adults admitted to acute care settings and developed elevated body temperature.We considered any external cooling method compared to no cooling.We considered randomised control trials (RCTs), quasi-randomised trials and controlled trials with concurrent control groups SEARCH STRATEGY: We searched relevant published or unpublished studies up to October 2009 regardless of language. We searched major databases, reference lists, bibliographies of all relevant articles, and contacted experts in the field for additional studies. Two reviewers independently screened titles and abstracts, and retrieved all potentially relevant studies. Two reviewers independently conducted the assessment of methodological quality of included studies. The results of studies where appropriate was quantitatively summarised. Relative risks or weighted mean difference and their 95% confidence intervals were calculated using the random effects model in Review Manager 5. For each pooled comparison, heterogeneity was assessed using the chi-squared test at the 5% level of statistical significance, with I statistic used to assess the impact of statistical heterogeneity on study results. Where statistical summary was not appropriate or possible, the findings were summarised in narrative form. We found six RCTs that compared the effectiveness and complications of external cooling methods against no external cooling. There was wide variation in the outcome measures between the included trials. We performed meta-analyses on data from two RCTs totalling 356 patients testing external cooling combined with antipyretics versus antipyretics alone, for the resolution of fever. The results did not show a statistically significant reduction in fever (relative risk 1.12, 95% CI 0.95 to 1.31; P=0.35; I =0%).The evidence from four trials suggested that there was no difference in the mean drop in body temperature post treatment initiation, between external cooling and no cooling groups. The results of most other outcomes also did not demonstrate a statistically significant difference. However summarising the results of five trials consisting of 371 patients found that the external cooling group was more likely to shiver when compared to the no cooling group (relative risk 6.37, 95% CI 2.01 to 20.11; P=0.61; I =0%).Overall this review suggested that external cooling methods (whether used alone or in combination with pharmacologic methods) were not effective in treating fever among adults admitted to acute care settings. Yet they were associated with higher incidences of shivering. These results should be interpreted in light of the methodological limitations of available trials. Given the current available evidence, the routine use of external cooling methods to treat fever in adults may not be warranted until further evidence is available. They could be considered for patients whose conditions are unable to tolerate even slight increase in temperature or who request for them. Whenever they are used, shivering should be prevented. Well-designed, adequately powered, randomised trials comparing external cooling methods against no cooling are needed.

Actual versus perceived peer sexual risk behavior in online youth social networks.

PubMed

Black, Sandra R; Schmiege, Sarah; Bull, Sheana

2013-09-01

Perception of peer behaviors is an important predictor of actual risk behaviors among youth. However, we lack understanding of peer influence through social media and of actual and perceived peer behavior concordance. The purpose of this research is to document the relationship between individual perception of and actual peer sexual risk behavior using online social networks. The data are a result of a secondary analysis of baseline self-reported and peer-reported sexual risk behavior from a cluster randomized trial including 1,029 persons from 162 virtual networks. Individuals (seeds) recruited up to three friends who then recruited additional friends, extending three waves from the seed. ANOVA models compared network means of actual participant behavior across categories of perceived behavior. Concordance varied between reported and perceived behavior, with higher concordance between perceived and reported condom use, multiple partners, concurrent partners, sexual pressure, and drug and alcohol use during sex. Individuals significantly over-reported risk and under-reported protective peer behaviors related to sex.

Metoclopramide: an analgesic adjunct to patient-controlled analgesia.

PubMed

Rosenblatt, W H; Cioffi, A M; Sinatra, R; Saberski, L R; Silverman, D G

1991-11-01

This randomized, double-blind trial evaluated the effect of metoclopramide on the pain and analgesic requirements associated with prostaglandin-induced labor for second-trimester termination of pregnancy. After receiving intrauterine prostaglandin, seven women were given intravenous metoclopramide (10 mg), and eight received saline, concurrent with initiation of patient controlled analgesia (PCA). Group differences were assessed with serial visual analogue scale for pain, interval PCA-morphine consumption, and time to fetal delivery. The metoclopramide group used 54% less PCA morphine (24.1 vs 52.0 mg), had lower visual analogue scale scores, and interval morphine consumption at 2, 4, and 6 h after PCA had been initiated, as well as earlier delivery of the fetus when compared with the control group (P less than 0.05). We conclude that a single dose of metoclopramide reduces the pain and PCA-morphine requirements of patients undergoing prostaglandin-induced labor and may facilitate passage of the fetus. Metoclopramide may have a similar application in treating other types of gynecologic pain.

Note on concurrent validation of the personality assessment inventory in law enforcement.

PubMed

Hays, J R

1997-08-01

This study compared the Personality Assessment Inventory and MMPI-168 profiles of 9 law enforcement applicants with published MMPI profiles to provide concurrent validation for the use of the Personality Assessment Inventory to assess personality pathology of peace officer applicants. The sample showed subclinical elevations of the Positive Impression and Treatment Rejection scales on the Personality Assessment Inventory and subclinical elevations on the MMPI validity scales of Lie and Correction and the clinical scales of Psychopathic Deviate and Hypomania. The applicants' mean MMPI profile provided concurrent validation for the use of the Personality Assessment Inventory in this decision on fitness to serve.

Concurrent validity and reliability of torso-worn inertial measurement unit for jump power and height estimation.

PubMed

Rantalainen, Timo; Gastin, Paul B; Spangler, Rhys; Wundersitz, Daniel

2018-09-01

The purpose of the present study was to evaluate the concurrent validity and test-retest repeatability of torso-worn IMU-derived power and jump height in a counter-movement jump test. Twenty-seven healthy recreationally active males (age, 21.9 [SD 2.0] y, height, 1.76 [0.7] m, mass, 73.7 [10.3] kg) wore an IMU and completed three counter-movement jumps a week apart. A force platform and a 3D motion analysis system were used to concurrently measure the jumps and subsequently derive power and jump height (based on take-off velocity and flight time). The IMU significantly overestimated power (mean difference = 7.3 W/kg; P < 0.001) compared to force-platform-derived power but good correspondence between methods was observed (Intra-class correlation coefficient [ICC] = 0.69). IMU-derived power exhibited good reliability (ICC = 0.67). Velocity-derived jump heights exhibited poorer concurrent validity (ICC = 0.72 to 0.78) and repeatability (ICC = 0.68) than flight-time-derived jump heights, which exhibited excellent validity (ICC = 0.93 to 0.96) and reliability (ICC = 0.91). Since jump height and power are closely related, and flight-time-derived jump height exhibits excellent concurrent validity and reliability, flight-time-derived jump height could provide a more desirable measure compared to power when assessing athletic performance in a counter-movement jump with IMUs.

Effects of concurrent and aerobic exercises on postexercise hypotension in elderly hypertensive men.

PubMed

Ferrari, Rodrigo; Umpierre, Daniel; Vogel, Guilherme; Vieira, Paulo J C; Santos, Lucas P; de Mello, Renato Bandeira; Tanaka, Hirofumi; Fuchs, Sandra C

2017-11-01

Despite the fact that simultaneous performance of resistance and aerobic exercises (i.e., concurrent exercise) has become a standard exercise prescription for the elderly, no information is available on its effects on post-exercise hypotension (PEH) in elderly men with hypertension. To compare the effects of different types of exercise on PEH in elderly men with hypertension. Twenty elderly men with essential hypertension participated in three crossover interventions, in random order, and on separate days: a non-exercise control session at seated rest, aerobic exercise performed for 45min, and 45min of concurrent resistance and aerobic exercise consisted of 4 sets of 8 repetitions at 70% 1RM of resistance exercise followed by aerobic exercise on treadmill. After each session, blood pressure (BP) was measured continuously for 1h in the laboratory and for 24h under ambulatory conditions. During the first hour in laboratory, diastolic BP was lower after aerobic (-5mmHg) and concurrent exercise (-6mmHg) in comparison with Control. Day-time diastolic BP was significantly lower after aerobic exercise (-7mmHg) when compared to the control. No significant differences were found among the three experimental sessions for night-time and 24-hour diastolic BP, as well as day-time, night-time and 24-hour systolic BP. Concurrent exercise produced acute PEH similar to aerobic exercise but such effect did not last as long as aerobic exercise in elderly patients with essential hypertension. Copyright © 2017 Elsevier Inc. All rights reserved.

Socioeconomic Inequality in Concurrent Tobacco and Alcohol Consumption

PubMed Central

Intarut, Nirun; Pukdeesamai, Piyalak

2017-01-01

Background: Whilst several studies have examined inequity of tobacco use and inequity of alcohol drinking individually, comparatively little is known about concurrent tobacco and alcohol consumption. The present study therefore investigated inequity of concurrent tobacco and alcohol consumption in Thailand. Methods: The 2015 Health and Welfare Survey was obtained from Thailand’s National Statistical Office and used as a source of national representative data. Concurrent tobacco and alcohol consumption was defined as current and concurrent use of both tobacco and alcohol. The wealth assets index was used as an indicator of socioeconomic inequity. Socioeconomic status included 5 groups ranging from poorest (Q1) to richest (Q5). A total of 55,920 households and 113,705 participants aged 15 years or over were included and analyzed. A weighted multiple logistic regression was performed. Results: The prevalence of concurrent tobacco and alcohol consumption, tobacco consumption only, and alcohol consumption only were 15.2% (95% CI: 14.9, 15.4), 4.7% (95% CI: 4.5, 4.8), and 18.9% (95% CI: 18.7, 19.1), respectively. Weighted multiple logistic regression showed that concurrent tobacco and alcohol consumption was high in the poorest socioeconomic group (P for trend <0.001), and tobacco consumption only was also high in the poorest group (P for trend <0.001). A high prevalence of alcohol consumption was observed in the richest group (P for trend <0.001). Conclusions: These findings suggest that tobacco and alcohol consumption prevention programs would be more effective if they considered socioeconomic inequities in concurrent tobacco and alcohol consumption rather than focusing on single drug use. PMID:28749620

Cardiac Autonomic and Blood Pressure Responses to an Acute Foam Rolling Session.

PubMed

Lastova, Kevin; Nordvall, Michael; Walters-Edwards, Michelle; Allnutt, Amy; Wong, Alexei

2018-03-22

Foam Rolling (FR) is a self-myofascial release method that has become extremely popular among athletes and fitness enthusiasts for its ability to improve flexibility and range of motion and alleviate delayed onset muscle soreness. However, the cardiac autonomic modulation and blood pressure (BP) responses induced by an acute FR session are currently unknown. The present study evaluated the effects of an acute session of FR exercise on heart rate variability (HRV) and BP responses in healthy individuals. Fifteen (M=8, F=7) healthy subjects completed either a FR or non-exercise control trial in randomized order. HRV and BP measurements were collected at baseline, 10 and 30 min after each trial. There were significant increases (P < 0.01) in markers of vagal tone (nHF) for 30 min after the FR trial, while no changes from baseline were observed following control. There were also significant decreases (P < 0.05) in markers of sympathetic activity (nLF), sympathovagal balance (nLF/nHF), systolic BP and diastolic BP at 10 and 30 min after the trial KB trial while no changes from baseline were observed after the control trial. Our findings indicate that FR decreases sympathovagal balance for 30 min post-intervention which is concurrent with an important hypotensive effect. Further research is warranted to evaluate the potential cardiovascular protective effects of FR in diverse populations.

Invasive Cortical Stimulation to Promote Recovery of Function After Stroke

PubMed Central

Plow, Ela B.; Carey, James R.; Nudo, Randolph J.; Pascual-Leone, Alvaro

2011-01-01

Background and Purpose Residual motor deficits frequently linger after stroke. Search for newer effective strategies to promote functional recovery is ongoing. Brain stimulation, as a means of directing adaptive plasticity, is appealing. Animal studies and Phase I and II trials in humans have indicated safety, feasibility, and efficacy of combining rehabilitation and concurrent invasive cortical stimulation. However, a recent Phase III trial showed no advantage of the combination. We critically review results of various trials and discuss the factors that contributed to the distinctive result. Summary of Review Regarding cortical stimulation, it is important to determine the (1) location of peri-infarct representations by integrating multiple neuroanatomical and physiological techniques; (2) role of other mechanisms of stroke recovery; (3) viability of peri-infarct tissue and descending pathways; (4) lesion geometry to ensure no alteration/displacement of current density; and (5) applicability of lessons generated from noninvasive brain stimulation studies in humans. In terms of combining stimulation with rehabilitation, we should understand (1) the principle of homeostatic plasticity; (2) the effect of ongoing cortical activity and phases of learning; and (3) that subject-specific intervention may be necessary. Conclusions Future cortical stimulation trials should consider the factors that may have contributed to the peculiar results of the Phase III trial and address those in future study designs. PMID:19359643

Roles of posttherapy 18F-FDG PET/CT in patients with advanced squamous cell carcinoma of the uterine cervix receiving concurrent chemoradiotherapy.

PubMed

Liu, Feng-Yuan; Su, Tzu-Pei; Wang, Chun-Chieh; Chao, Angel; Chou, Hung-Hsueh; Chang, Yu-Chen; Yen, Tzu-Chen; Lai, Chyong-Huey

2018-07-01

To assess the clinical roles of [ 18 F]fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) performed 2-3 months after completion of concurrent chemoradiotherapy (CCRT), along with pretherapy characteristics, in patients with advanced squamous cell carcinoma of the uterine cervix enrolled in a prospective randomized clinical trial. Posttherapy PET/CT in patients with advanced FIGO stage or positive pelvic or para-aortic lymph node (PALN) defined on pretherapy PET/CT was classified as positive, equivocal, or negative. Overall survival (OS) rates between patients with different PET/CT results are compared. Pretherapy characteristics are examined for association with posttherapy PET/CT results and for prognostic significance in patients with equivocal or negative PET/CT. PET/CT scans (n = 55) were positive, equivocal and negative in 9, 13 and 33 patients, respectively. All patients with positive scans were confirmed to have residual or metastatic disease and died despite salvage therapies. There is a significant OS difference between patients with positive and equivocal scans (P < .001) but not between patients with equivocal and negative scans (P = .411). Positive pretherapy PALN is associated with positive posttherapy PET/CT (P = .033) and predicts a poorer survival in patients with equivocal or negative posttherapy PET/CT (P < .001). Positive PET/CT 2-3 months posttherapy implies treatment failure and novel therapy is necessary to improve outcomes for such patients. A more intense posttherapy surveillance may be warranted in patients with positive pretherapy PALN.

Cost-effectiveness of low-level laser therapy (LLLT) in head and neck cancer patients receiving concurrent chemoradiation.

PubMed

Antunes, Héliton S; Schluckebier, Luciene Fontes; Herchenhorn, Daniel; Small, Isabele A; Araújo, Carlos M M; Viégas, Celia Maria Pais; Rampini, Mariana P; Ferreira, Elza M S; Dias, Fernando L; Teich, Vanessa; Teich, Nelson; Ferreira, Carlos G

2016-01-01

Oral mucositis is a major event increasing treatment costs of head and neck squamous cell carcinoma (HNSCC) patients treated with chemoradiation (CRT). This study was designed to estimate the cost-effectiveness of low-level laser therapy (LLLT) to prevent oral mucositis in HNSCC patients receiving CRT. From June 2007 to December 2010, 94 patients with HNSCC of nasopharynx, oropharynx, and hypopharynx entered a prospective, randomized, double blind, placebo-controlled, phase III trial. CRT consisted of conventional radiotherapy (RT: 70.2 Gy, 1.8 Gy/d, 5 times/wk)+concurrent cisplatin (100mg/m2) every 3 weeks. An InGaAlP (660 nm-100 mW-4J/cm2) laser diode was used for LLLT. From the perspective of Brazil's public health care system (SUS), total costs were higher in Placebo Group (PG) than Laser Group (LG) for opioid use (LG=US$ 9.08, PG=US$ 44.28), gastrostomy feeding (LG=US$ 50.50, PG=US$ 129.86), and hospitalization (PG=US$ 77.03). In LG, the cost was higher for laser therapy only (US$ 1880.57). The total incremental cost associated with the use of LLLT was US$ 1689.00 per patient. The incremental cost-effectiveness ratio (ICER) was US$ 4961.37 per grade 3-4 OM case prevented compared to no treatment. Our results indicate that morbidity was lower in the Laser Group and that LLLT was more cost-effective than placebo up to a threshold of at least US$ 5000 per mucositis case prevented. NCT01439724. Copyright © 2015 Elsevier Ltd. All rights reserved.

Concurrent Data Elicitation Procedures, Processes, and the Early Stages of L2 Learning: A Critical Overview

ERIC Educational Resources Information Center

Leow, Ronald P.; Grey, Sarah; Marijuan, Silvia; Moorman, Colleen

2014-01-01

Given the current methodological interest in eliciting direct data on the cognitive processes L2 learners employ as they interact with L2 data during the early stages of the learning process, this article takes a critical and comparative look at three concurrent data elicitation procedures currently employed in the SLA literature: Think aloud (TA)…

Parenting and the Behavior Problems of Young Children with an Intellectual Disability: Concurrent and Longitudinal Relationships in a Population-Based Study

ERIC Educational Resources Information Center

Totsika, Vasiliki; Hastings, Richard Patrick; Vagenas, Dimitrios; Emerson, Eric

2014-01-01

We examined parenting behaviors, and their association with concurrent and later child behavior problems. Children with an intellectual disability (ID) were identified from a UK birth cohort (N = 516 at age 5). Compared to parents of children without an ID, parents of children with an ID used discipline less frequently, but reported a more…

Impaired preparatory re-mapping of stimulus-response associations and rule-implementation in schizophrenic patients--the role for differences in early processing.

PubMed

Finke, Mareike; Barceló, Francisco; Garolera, Maite; Cortiñas, Miriam; Garrido, Gemma; Pajares, Marta; Escera, Carles

2011-07-01

An accurate representation of task-set information is needed for successful goal directed behavior. Recent studies point to disturbances in the early processing stages as plausible causes for task-switching deficits in schizophrenia. A task-cueing protocol was administered to a group of schizophrenic patients and compared with a sample of age-matched healthy controls. Patients responded slower and less accurate compared with controls in all conditions. The concurrent recording of event-related brain potentials to contextual cues and target events revealed abnormalities in the early processing of both cue-locked and target-locked N1 potentials. Abnormally enhanced target-locked P2 amplitudes were observed in schizophrenic patients for task-switch trials only, suggesting disrupted stimulus evaluation and memory retrieval processes. The endogenous P3 potentials discriminated between task conditions but without further differences between groups. These results suggest that the observed impairments in task-switching behavior were not specifically related to anticipatory set-shifting, but derived from a deficit in the implementation of task-set representations at target onset in the presence of irrelevant and conflicting information. Copyright © 2011 Elsevier B.V. All rights reserved.

Combined universal and selective prevention for adolescent alcohol use: a cluster randomized controlled trial.

PubMed

Teesson, M; Newton, N C; Slade, T; Carragher, N; Barrett, E L; Champion, K E; Kelly, E V; Nair, N K; Stapinski, L A; Conrod, P J

2017-07-01

No existing models of alcohol prevention concurrently adopt universal and selective approaches. This study aims to evaluate the first combined universal and selective approach to alcohol prevention. A total of 26 Australian schools with 2190 students (mean age: 13.3 years) were randomized to receive: universal prevention (Climate Schools); selective prevention (Preventure); combined prevention (Climate Schools and Preventure; CAP); or health education as usual (control). Primary outcomes were alcohol use, binge drinking and alcohol-related harms at 6, 12 and 24 months. Climate, Preventure and CAP students demonstrated significantly lower growth in their likelihood to drink and binge drink, relative to controls over 24 months. Preventure students displayed significantly lower growth in their likelihood to experience alcohol harms, relative to controls. While adolescents in both the CAP and Climate groups demonstrated slower growth in drinking compared with adolescents in the control group over the 2-year study period, CAP adolescents demonstrated faster growth in drinking compared with Climate adolescents. Findings support universal, selective and combined approaches to alcohol prevention. Particularly novel are the findings of no advantage of the combined approach over universal or selective prevention alone.

Decision-theoretic designs for a series of trials with correlated treatment effects using the Sarmanov multivariate beta-binomial distribution.

PubMed

Hee, Siew Wan; Parsons, Nicholas; Stallard, Nigel

2018-03-01

The motivation for the work in this article is the setting in which a number of treatments are available for evaluation in phase II clinical trials and where it may be infeasible to try them concurrently because the intended population is small. This paper introduces an extension of previous work on decision-theoretic designs for a series of phase II trials. The program encompasses a series of sequential phase II trials with interim decision making and a single two-arm phase III trial. The design is based on a hybrid approach where the final analysis of the phase III data is based on a classical frequentist hypothesis test, whereas the trials are designed using a Bayesian decision-theoretic approach in which the unknown treatment effect is assumed to follow a known prior distribution. In addition, as treatments are intended for the same population it is not unrealistic to consider treatment effects to be correlated. Thus, the prior distribution will reflect this. Data from a randomized trial of severe arthritis of the hip are used to test the application of the design. We show that the design on average requires fewer patients in phase II than when the correlation is ignored. Correspondingly, the time required to recommend an efficacious treatment for phase III is quicker. © 2017 The Author. Biometrical Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Axillary, Oral and Rectal Routes of Temperature Measurement During Treatment of Acute Kawasaki Disease.

PubMed

Kanegaye, John T; Jones, Jefferson M; Burns, Jane C; Jain, Sonia; Sun, Xiaoying; Jimenez-Fernandez, Susan; Berry, Erika; Pancheri, Joan M; Jaggi, Preeti; Ramilo, Octavio; Tremoulet, Adriana H

2016-01-01

Important therapeutic decisions are made based on the presence or absence of fever in patients with Kawasaki disease (KD), yet no standard method or threshold exists for temperature measurement during the diagnosis and treatment of these patients. We sought to compare surface and internal (rectal or oral) routes of temperature measurement for the detection of fever as a marker of treatment resistance. From a randomized, placebo-controlled trial of infliximab as an adjunct to primary intravenous immunoglobulin treatment for acute KD, we collected concurrent (within 5 minutes) axillary and internal temperature measurements and performed receiver-operating characteristic and Bland-Altman analyses. We also determined the ability of surface temperatures to detect treatment resistance defined by internal temperature measurements. Among 452 oral-axillary and 439 rectal-axillary pairs from 159 patients, mean axillary temperatures were 0.25 and 0.43 °C lower than oral and rectal temperatures and had high receiver-operating characteristic areas under curves. However, axillary temperatures ≥ 38.0 °C had limited sensitivity to detect fever defined by internal temperatures. Axillary thresholds of 37.5 and 37.2 °C provided maximal sensitivity and specificity to detect oral and rectal temperatures ≥ 38.0 °C, respectively. Axillary temperatures are an insensitive metric for fevers defining treatment resistance. Clinical trials should adopt temperature measurement by the oral or rectal routes for adjudication of treatment resistance in KD.

A changing picture of shigellosis in southern Vietnam: shifting species dominance, antimicrobial susceptibility and clinical presentation

PubMed Central

2009-01-01

Background Shigellosis remains considerable public health problem in some developing countries. The nature of Shigellae suggests that they are highly adaptable when placed under selective pressure in a human population. This is demonstrated by variation and fluctuations in serotypes and antimicrobial resistance profile of organisms circulating in differing setting in endemic locations. Antimicrobial resistance in the genus Shigella is a constant threat, with reports of organisms in Asia being resistant to multiple antimicrobials and new generation therapies. Methods Here we compare microbiological, clinical and epidemiological data from patients with shigellosis over three different periods in southern Vietnam spanning14 years. Results Our data demonstrates a shift in dominant infecting species (S. flexneri to S. sonnei) and resistance profile of the organisms circulating in southern Vietnam. We find that there was no significant variation in the syndromes associated with either S. sonnei or S. flexneri, yet the clinical features of the disease are more severe in later observations. Conclusions Our findings show a change in clinical presentation of shigellosis in this setting, as the disease may be now more pronounced, this is concurrent with a change in antimicrobial resistance profile. These data highlight the socio-economic development of southern Vietnam and should guide future vaccine development and deployment strategies. Trial Registration Current Controlled Trials ISRCTN55945881 PMID:20003464

Scaling sexual behavior or "sexual risk propensity" among men at risk for HIV in Kisumu, Kenya.

PubMed

Mattson, C L; Campbell, Richard T; Karabatsos, George; Agot, Kawango; Ndinya-Achola, J O; Moses, Stephen; Bailey, Robert C

2010-02-01

We present a scale to measure sexual risk behavior or "sexual risk propensity" to evaluate risk compensation among men engaged in a randomized clinical trial of male circumcision. This statistical approach can be used to represent each respondent's level of sexual risk behavior as the sum of his responses on multiple dichotomous and rating scale (i.e. ordinal) items. This summary "score" can be used to summarize information on many sexual behaviors or to evaluate changes in sexual behavior with respect to an intervention. Our 18 item scale demonstrated very good reliability (Cronbach's alpha of 0.87) and produced a logical, unidimensional continuum to represent sexual risk behavior. We found no evidence of differential item function at different time points (except for reporting a concurrent partners when comparing 6 and 12 month follow-up visits) or with respect to the language with which the instrument was administered. Further, we established criterion validity by demonstrating a statistically significant association between the risk scale and the acquisition of incident sexually transmitted infections (STIs) at the 6 month follow-up and HIV at the 12 month follow-up visits. This method has broad applicability to evaluate sexual risk behavior in the context of other HIV and STI prevention interventions (e.g. microbicide or vaccine trials), or in response to treatment provision (e.g., anti-retroviral therapy).

Multilocation trial of ceftiofur for treatment of postpartum cows with fever.

PubMed

Zhou, C; Boucher, J F; Dame, K J; Moreira, M; Graham, R; Nantel, J; Zuidhof, S; Arfi, L; Flores, R; Neubauer, G; Olson, J

2001-09-15

To evaluate the effect of ceftiofur for treatment of postpartum cows with fever. Multilocation randomized complete block design trial. 330 cows. Cows with rectal temperature > or = 39.5 C (103.1 F) during the first 10 postpartum days were randomly assigned to a treatment (ceftiofur; 1 mg/kg [0.45 mg/lb] of body weight daily for 3 days) or untreated control group. Cure (no additional or alternative antimicrobial treatment used, rectal temperature < 39.5 C, and no other concurrent clinical signs of disease when evaluated at 9 or 10 days after enrollment), milk production, and rectal temperature were evaluated. Ceftiofur-treated cows were significantly more likely to be cured than control cows (56.0 vs 28.9%, respectively), with an odds ratio of 3.14 when vaginal discharge (a factor with moderate interaction with treatment) was present at enrollment. Among cows that had an abnormal calving (a significant interaction factor), treated cows had first milking yield 2.27 kg (5 lb) greater than control cows. Treated cows had a significantly greater reduction in rectal temperature (1.19 C [2.14 Fl), compared with control cows (1.04 C [1.87 F]). Parenteral administration of ceftiofur significantly improved cure rate, milk yield, and rectal temperature in postpartum cows with fever and vaginal discharge or dystocia. These findings provide information to determine appropriate treatment for postpartum cows, which for years has been debated in the dairy industry.

A phase II study of nab-paclitaxel plus carboplatin in combination with thoracic radiation in patients with locally advanced non–small-cell lung cancer

PubMed Central

Hasegawa, Takaaki; Futamura, Yohei; Horiba, Akane; Yoshida, Tsutomu; Suzuki, Toshitaka; Kato, Tatsuo; Kaito, Daizo; Ohno, Yasuhi; Iida, Takayoshi; Hayashi, Shinya; Sawa, Toshiyuki

2016-01-01

We investigated the efficacy and safety of albumin-bound paclitaxel (nab-PTX) and carboplatin (CBDCA) with concurrent radiotherapy for unresectable locally advanced non–small-cell lung cancer (NSCLC). Patients with Stage III NSCLC and an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible. Concurrent chemoradiotherapy consisted of weekly administration of nab-PTX (40 mg/m2) plus CBDCA (area under the plasma concentration time curve (AUC) 2) and thoracic radiotherapy (60 Gy/30 fractions) for a total of 6 weeks. After concurrent chemoradiotherapy, patients received an additional two cycles of consolidation phase chemotherapy that consisted of 4-week cycles of nab-PTX (100 mg/m2 on Days 1, 8 and 15)/CBDCA (AUC 5 mg/ml/min on Day 1). Response was evaluated in accordance with the Response Evaluation Criteria in Solid Tumors. Progression-free survival and overall survival were estimated using the Kaplan–Meier method. Toxicity was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events. A total of 10 patients were enrolled in this trial between September 2013 and January 2014 from three institutes. The overall response rate was 40.0% and the median progression-free survival was 6.7 months. Treatment-related death occurred in two patients. Grade 2 or worse severe radiation pneumonitis was observed in all three patients that had the volume of lung receiving at least 20 Gy (V20) >30%. The results of this study indicate that no further investigation is warranted into nab-PTX and CBDCA with concurrent thoracic radiation for Stage III NSCLC with V20 > 30% due to severe toxicity. PMID:26442970

High-dose versus standard-dose radiotherapy with concurrent chemotherapy in stages II-III esophageal cancer.

PubMed

Suh, Yang-Gun; Lee, Ik Jae; Koom, Wong Sub; Cha, Jihye; Lee, Jong Young; Kim, Soo Kon; Lee, Chang Geol

2014-06-01

In this study, we investigated the effects of radiotherapy ≥60 Gy in the setting of concurrent chemo-radiotherapy for treating patients with Stages II-III esophageal cancer. A total of 126 patients treated with 5-fluorouracilbased concurrent chemo-radiotherapy between January 1998 and February 2008 were retrospectively reviewed. Among these patients, 49 received a total radiation dose of <60 Gy (standard-dose group), while 77 received a total radiation dose of ≥60 Gy (high-dose group). The median doses in the standard- and high-dose groups were 54 Gy (range, 45-59.4 Gy) and 63 Gy (range, 60-81 Gy), respectively. The high-dose group showed significantly improved locoregional control (2-year locoregional control rate, 69 versus 32%, P < 0.01) and progression-free survival (2-year progression-free survival, 47 versus 20%, P = 0.01) than the standard-dose group. Median overall survival in the high- and the standard-dose groups was 28 and 18 months, respectively (P = 0.26). In multivariate analysis, 60 Gy or higher radiotherapy was a significant prognostic factor for improved locoregional control, progression-free survival and overall survival. No significant differences were found in frequencies of late radiation pneumonitis, post-treatment esophageal stricture or treatment-related mortality between the two groups. High-dose radiotherapy of 60 Gy or higher with concurrent chemotherapy improved locoregional control and progression-free survival without a significant increase of in treatment-related toxicity in patients with Stages II-III esophageal cancer. Our study could provide the basis for future randomized clinical trials. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Choice and conditioned reinforcement.

PubMed Central

Fantino, E; Freed, D; Preston, R A; Williams, W A

1991-01-01

A potential weakness of one formulation of delay-reduction theory is its failure to include a term for rate of conditioned reinforcement, that is, the rate at which the terminal-link stimuli occur in concurrent-chains schedules. The present studies assessed whether or not rate of conditioned reinforcement has an independent effect upon choice. Pigeons responded on either modified concurrent-chains schedules or on comparable concurrent-tandem schedules. The initial link was shortened on only one of two concurrent-chains schedules and on only one of two corresponding concurrent-tandem schedules. This manipulation increased rate of conditioned reinforcement sharply in the chain but not in the tandem schedule. According to a formulation of delay-reduction theory, when the outcomes chosen (the terminal links) are equal, as in Experiment 1, choice should depend only on rate of primary reinforcement; thus, choice should be equivalent for the tandem and chain schedules despite a large difference in rate of conditioned reinforcement. When the outcomes chosen are unequal, however, as in Experiment 2, choice should depend upon both rate of primary reinforcement and relative signaled delay reduction; thus, larger preferences should occur in the chain than in the tandem schedules. These predictions were confirmed, suggesting that increasing the rate of conditioned reinforcement on concurrent-chains schedules may have no independent effect on choice. PMID:2037826

Acute pancreatitis in cats with hepatic lipidosis.

PubMed

Akol, K G; Washabau, R J; Saunders, H M; Hendrick, M J

1993-01-01

The purpose of this study was to characterize the incidence, clinical features, and prognosis of acute pancreatitis in cats with hepatic lipidosis. Of 13 cats histologically diagnosed with hepatic lipidosis between July 1988, and November 1989, 5(38%) were also histologically diagnosed with acute pancreatitis. In cats with hepatic lipidosis alone, the signalment, history, physical examination, and clinicopathologic findings were generally indistinguishable from those of cats with concurrent acute pancreatitis except that cats with acute pancreatitis were more likely to be cachectic and to have coagulation abnormalities. Hepatomegaly was seen on abdominal radiographs in both groups. Of the 5 cats with concurrent acute pancreatitis, abdominal ultrasonography detected 1 cat with a hypoechoic pancreas and 5 with peritoneal effusion; those abnormalities were not seen in cats without concurrent acute pancreatitis. Cats with concurrent acute pancreatitis had only a 20% recovery rate, compared with a 50% recovery rate in cats with hepatic lipidosis alone. We conclude that cats with hepatic lipidosis should be rigorously evaluated for concurrent acute pancreatitis because of 1) the rate of disease coincidence, 2) the inability of signalment, history, physical examination, and clinicopathologic findings to adequately distinguish between hepatic lipidosis and acute pancreatitis, 3) the worse prognosis associated with concurrent acute pancreatitis, and 4) the opposing nutritional strategies for hepatic lipidosis and acute pancreatitis.

Prediction of response to PPI therapy and factors influencing treatment outcome in patients with GORD: a prospective pragmatic trial using pantoprazole

PubMed Central

2011-01-01

Background Management of patients with gastro-oesophageal reflux disease (GORD) can be assisted by information predicting the likely response to proton pump inhibitor (PPI) treatment. The aim was to undertake a study of GORD patients designed to approximate ordinary clinical practice that would identify patient characteristics predicting symptomatic response to pantoprazole treatment. Methods 1888 patients with symptoms of GORD were enrolled in a multicentre, multinational, prospective, open study of 8 weeks pantoprazole treatment, 40 mg daily. Response was assessed by using the ReQuest™ questionnaire, by the investigator making conventional clinical enquiry and by asking patients about their satisfaction with symptom control. Factors including pre-treatment oesophagitis, gender, age, body mass index (BMI), Helicobacter pylori status, anxiety and depression, and concurrent IBS symptoms were examined using logistic regression to determine if they were related to response, judged from the ReQuest™-GI score. Results Poorer treatment responses were associated with non-erosive reflux disease, female gender, lower BMI, anxiety and concurrent irritable bowel syndrome symptoms before treatment. No association was found with age, Helicobacter pylori status or oesophagitis grade. Some reflux-related symptoms were still present in 14% of patients who declared themselves 'well-satisfied' with their symptom control. Conclusions Some readily identifiable features help to predict symptomatic responses to a PPI and consequently may help in managing patient expectation. ClinicalTrial.gov identifier: NCT00312806. PMID:21569313

Inefficient conjunction search made efficient by concurrent spoken delivery of target identity.

PubMed

Reali, Florencia; Spivey, Michael J; Tyler, Melinda J; Terranova, Joseph

2006-08-01

Visual search based on a conjunction of two features typically elicits reaction times that increase linearly as a function of the number of distractors, whereas search based on a single feature is essentially unaffected by set size. These and related findings have often been interpreted as evidence of a serial search stage that follows a parallel search stage. However, a wide range of studies has been showing a form of blending of these two processes. For example, when a spoken instruction identifies the conjunction target concurrently with the visual display, the effect of set size is significantly reduced, suggesting that incremental linguistic processing of the first feature adjective and then the second feature adjective may facilitate something approximating a parallel extraction of objects during search for the target. Here, we extend these results to a variety of experimental designs. First, we replicate the result with a mixed-trials design (ruling out potential strategies associated with the blocked design of the original study). Second, in a mixed-trials experiment, the order of adjective types in the spoken query varies randomly across conditions. In a third experiment, we extend the effect to a triple-conjunction search task. A fourth (control) experiment demonstrates that these effects are not due to an efficient odd-one-out search that ignores the linguistic input. This series of experiments, along with attractor-network simulations of the phenomena, provide further evidence toward understanding linguistically mediated influences in real-time visual search processing.

Concurrent treatment with a macrocyclic lactone and benzimidazole provides season long performance advantages in grazing cattle harboring macrocyclic lactone resistant nematodes.

PubMed

Edmonds, M D; Vatta, A F; Marchiondo, A A; Vanimisetti, H B; Edmonds, J D

2018-03-15

In 2013, a 118-day study was initiated to investigate the efficacy of concurrent treatment at pasture turnout with an injectable macrocyclic lactone with activity up to 28 days and an oral benzimidazole, referred to as "conventional" anthelmintics, when compared to treatment with conventional macrocyclic lactone alone or an injectable macrocyclic lactone with extended activity of 100 days or longer. A group of 210 steers were obtained from a ranch in California and transported to Idaho, USA. A total of 176 steers with the highest fecal egg counts were blocked by pre-treatment body weights and pasture location. A total of 44 pasture paddocks were assigned with 4 steers per paddock with 12 paddocks per therapeutic treatment group and 8 paddocks per controls. The four treatments were injectable doramectin (Dectomax ® , Zoetis Inc., 0.2 mg kg -1 BW, SC), injectable doramectin concurrently with oral albendazole (Valbazen ® , Zoetis Inc., 10 mg kg -1 BW, PO), extended release injectable eprinomectin (LongRange™, Merial Limited, 1 mg kg -1 BW, SC) or saline. Cattle were individually weighed and sampled for fecal egg count on Days 0, 31/32, 61, 88, and 117/118 with an additional fecal sample on Day 14. At conclusion, one steer per paddock was euthanized for nematode recovery. The results from the first 32 days found evidence of macrocyclic lactone resistance against injectable doramectin and extended release eprinomectin. During this period the concurrent therapy provided nearly 100% efficacy based on fecal egg count reduction and a 19.98% improvement in total weight gain compared to controls (P = 0.039). At the conclusion of the 118-day study and past the approved efficacy for the conventional anthelmintics, the concurrent therapy with conventional anthelmintics provided a 22.98% improvement in total weight gain compared to controls (P = 0.004). The 118-day improvement in weight gain for the extended release eprinomectin group (29.06% compared to control) was not statistically different from the concurrent therapy with conventional anthelmintics. The results indicate that concurrent treatment with a conventional macrocyclic lactone and benzimidazole may provide production benefits early in the grazing period that continue throughout the entire period for cattle harboring macrocyclic lactone resistant nematodes. By using two different anthelmintic classes together, macrocyclic lactone resistant parasites were effectively controlled early in the period. Furthermore, the use of an effective conventional anthelmintic treatment regimen without an extended period of drug release may help to promote refugia and decrease the further selection for anthelmintic resistant parasites. Copyright © 2018 Elsevier B.V. All rights reserved.

Size matters: concurrency and the epidemic potential of HIV in small networks.

PubMed

Carnegie, Nicole Bohme; Morris, Martina

2012-01-01

Generalized heterosexual epidemics are responsible for the largest share of the global burden of HIV. These occur in populations that do not have high rates of partner acquisition, and research suggests that a pattern of fewer, but concurrent, partnerships may be the mechanism that provides the connectivity necessary for sustained transmission. We examine how network size affects the impact of concurrency on network connectivity. We use a stochastic network model to generate a sample of networks, varying the size of the network and the level of concurrency, and compare the largest components for each scenario to the asymptotic expected values. While the threshold for the growth of a giant component does not change, the transition is more gradual in the smaller networks. As a result, low levels of concurrency generate more connectivity in small networks. Generalized HIV epidemics are by definition those that spread to a larger fraction of the population, but the mechanism may rely in part on the dynamics of transmission in a set of linked small networks. Examples include rural populations in sub-Saharan Africa and segregated minority populations in the US, where the effective size of the sexual network may well be in the hundreds, rather than thousands. Connectivity emerges at lower levels of concurrency in smaller networks, but these networks can still be disconnected with small changes in behavior. Concurrency remains a strategic target for HIV combination prevention programs in this context.

Racial-ethnic differences in all-cause and HIV mortality, Florida, 2000–2011

PubMed Central

Trepka, Mary Jo; Fennie, Kristopher P.; Sheehan, Diana M.; Niyonsenga, Theophile; Lieb, Spencer; Maddox, Lorene M.

2016-01-01

Purpose We compared all-cause and human immunodeficiency virus (HIV) mortality in a population-based, HIV-infected cohort. Methods Using records of people diagnosed with HIV during 2000–2009 from the Florida Enhanced HIV/Acquired Immunodeficiency Syndrome (AIDS) Reporting System, we conducted a proportional hazards analysis for all-cause mortality and a competing risk analysis for HIV mortality through 2011 controlling for individual level factors, neighborhood poverty, and rural/urban status and stratifying by concurrent AIDS status (AIDS within 3 months of HIV diagnosis). Results Of 59,880 HIV-infected people, 32.2% had concurrent AIDS, and 19.3% died. Adjusting for period of diagnosis, age group, sex, country of birth, HIV transmission mode, area level poverty and rural/urban status, non-Hispanic Black (NHB) and Hispanic people had an elevated adjusted hazards ratio (aHR) for HIV mortality relative to non-Hispanic whites (NHB concurrent AIDS: aHR 1.34, 95% CI 1.23–1.47; NHB without concurrent AIDS: aHR 1.41, 95% CI 1.26–1.57; Hispanic concurrent AIDS: aHR 1.18, 95% CI 1.05–1.32; Hispanic without concurrent AIDS: aHR 1.18, 95% CI 1.03–1.36). Conclusions Considering competing causes of death, NHB and Hispanic people had a higher risk of HIV mortality even among those without concurrent AIDS, indicating a need to identify and address barriers to HIV care in these populations. PMID:26948103

Trial-to-trial adaptation in control of arm reaching and standing posture

PubMed Central

Pienciak-Siewert, Alison; Horan, Dylan P.

2016-01-01

Classical theories of motor learning hypothesize that adaptation is driven by sensorimotor error; this is supported by studies of arm and eye movements that have shown that trial-to-trial adaptation increases with error. Studies of postural control have shown that anticipatory postural adjustments increase with the magnitude of a perturbation. However, differences in adaptation have been observed between the two modalities, possibly due to either the inherent instability or sensory uncertainty in standing posture. Therefore, we hypothesized that trial-to-trial adaptation in posture should be driven by error, similar to what is observed in arm reaching, but the nature of the relationship between error and adaptation may differ. Here we investigated trial-to-trial adaptation of arm reaching and postural control concurrently; subjects made reaching movements in a novel dynamic environment of varying strengths, while standing and holding the handle of a force-generating robotic arm. We found that error and adaptation increased with perturbation strength in both arm and posture. Furthermore, in both modalities, adaptation showed a significant correlation with error magnitude. Our results indicate that adaptation scales proportionally with error in the arm and near proportionally in posture. In posture only, adaptation was not sensitive to small error sizes, which were similar in size to errors experienced in unperturbed baseline movements due to inherent variability. This finding may be explained as an effect of uncertainty about the source of small errors. Our findings suggest that in rehabilitation, postural error size should be considered relative to the magnitude of inherent movement variability. PMID:27683888

Trial-to-trial adaptation in control of arm reaching and standing posture.

PubMed

Pienciak-Siewert, Alison; Horan, Dylan P; Ahmed, Alaa A

2016-12-01

Classical theories of motor learning hypothesize that adaptation is driven by sensorimotor error; this is supported by studies of arm and eye movements that have shown that trial-to-trial adaptation increases with error. Studies of postural control have shown that anticipatory postural adjustments increase with the magnitude of a perturbation. However, differences in adaptation have been observed between the two modalities, possibly due to either the inherent instability or sensory uncertainty in standing posture. Therefore, we hypothesized that trial-to-trial adaptation in posture should be driven by error, similar to what is observed in arm reaching, but the nature of the relationship between error and adaptation may differ. Here we investigated trial-to-trial adaptation of arm reaching and postural control concurrently; subjects made reaching movements in a novel dynamic environment of varying strengths, while standing and holding the handle of a force-generating robotic arm. We found that error and adaptation increased with perturbation strength in both arm and posture. Furthermore, in both modalities, adaptation showed a significant correlation with error magnitude. Our results indicate that adaptation scales proportionally with error in the arm and near proportionally in posture. In posture only, adaptation was not sensitive to small error sizes, which were similar in size to errors experienced in unperturbed baseline movements due to inherent variability. This finding may be explained as an effect of uncertainty about the source of small errors. Our findings suggest that in rehabilitation, postural error size should be considered relative to the magnitude of inherent movement variability. Copyright © 2016 the American Physiological Society.

Cardiac Autonomic and Blood Pressure Responses to an Acute Bout of Kettlebell Exercise.

PubMed

Wong, Alexei; Nordvall, Michael; Walters-Edwards, Michelle; Lastova, Kevin; Francavillo, Gwendolyn; Summerfield, Liane; Sanchez-Gonzalez, Marcos

2017-10-07

Kettlebell (KB) training has become an extremely popular exercise program for improving both muscle strength and aerobic fitness. However, the cardiac autonomic modulation and blood pressure (BP) responses induced by an acute KB exercise session are currently unknown. Understanding the impact of this exercise modality on the post-exercise autonomic modulation and BP would facilitate appropriate exercise prescription in susceptible populations. The present study evaluated the effects of an acute session of KB exercise on heart rate variability (HRV) and BP responses in healthy individuals. Seventeen (M=10, F=7) healthy subjects completed either a KB or non-exercise control trial in randomized order. HRV and BP measurements were collected at baseline, 3, 10 and 30 min after each trial. There were significant increases (P < 0.01) in heart rate, markers of sympathetic activity (nLF) and sympathovagal balance (nLF/nHF) for 30 min after the trial KB trial, while no changes from baseline were observed after the control trial. There were also significant decreases (P < 0.01) in markers of vagal tone (RMMSD, nHF) for 30 min as well as (P < 0.01) systolic BP and diastolic BP at 10 and 30 min after the trial KB trial while no changes from baseline were observed after the control trial. Our findings indicate that KB exercise increases sympathovagal balance for 30 min post-intervention which is concurrent with an important hypotensive effect. Further research is warranted to evaluate the potential clinical application of KB training in populations that might benefit from post-exercise hypotension, such as hypertensives.

Task choice and semantic interference in picture naming.

PubMed

Piai, Vitória; Roelofs, Ardi; Schriefers, Herbert

2015-05-01

Evidence from dual-task performance indicates that speakers prefer not to select simultaneous responses in picture naming and another unrelated task, suggesting a response selection bottleneck in naming. In particular, when participants respond to tones with a manual response and name pictures with superimposed semantically related or unrelated distractor words, semantic interference in naming tends to be constant across stimulus onset asynchronies (SOAs) between the tone stimulus and the picture-word stimulus. In the present study, we examine whether semantic interference in picture naming depends on SOA in case of a task choice (naming the picture vs reading the word of a picture-word stimulus) based on tones. This situation requires concurrent processing of the tone stimulus and the picture-word stimulus, but not a manual response to the tones. On each trial, participants either named a picture or read aloud a word depending on the pitch of a tone, which was presented simultaneously with picture-word onset or 350 ms or 1000 ms before picture-word onset. Semantic interference was present with tone pre-exposure, but absent when tone and picture-word stimulus were presented simultaneously. Against the background of the available studies, these results support an account according to which speakers tend to avoid concurrent response selection, but can engage in other types of concurrent processing, such as task choices. Copyright © 2015 Elsevier B.V. All rights reserved.

Chemoradiation for ductal pancreatic carcinoma: principles of combining chemotherapy with radiation, definition of target volume and radiation dose.

PubMed

Wilkowski, Ralf; Thoma, Martin; Weingandt, Helmut; Dühmke, Eckhart; Heinemann, Volker

2005-05-10

Review of the role of chemoradiotherapy in the treatment of locally advanced pancreatic cancer with a specific focus on the technical feasibility and the integration of chemoradiotherapy into multimodal treatment concepts. Combined chemoradiotherapy of pancreatic cancer is a safe treatment with an acceptable profile of side effects when applied with modern planning and radiation techniques as well as considering tissue tolerance. Conventionally fractionated radiation regimens with total doses of 45-50 Gy and small-volume boost radiation with 5.4 Gy have found the greatest acceptance. Locoregional lymphatic drainage should be included in the planning of target volumes because the risk of tumor involvement and local or loco-regional recurrence is high. Up to now, 5-fluorouracil has been considered the "standard" agent for concurrent chemoradiotherapy. The role of gemcitabine given concurrently with radiation has not yet been defined, since high local efficacy may also be accompanied by enhanced toxicities. In addition, no dose or administration form has been determined to be "standard" up to now. The focus of presently ongoing research is to define an effective and feasible regimen of concurrent chemoradiotherapy. While preliminary results indicate promising results using gemcitabine-based chemoradiotherapy, reliable data derived from mature phase III trials are greatly needed. Intensity-modulated radiotherapy has been developed to improve target-specific radiation and to reduce organ toxicity. Its clinical relevance still needs to be defined.

Preoperative chemoradiation of locally advanced T3 rectal cancer combined with an endorectal boost

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jakobsen, Anders; Mortensen, John P.; Bisgaard, Claus

2006-02-01

Purpose: To investigate the effect and feasibility of concurrent radiation and chemotherapy combined with endorectal brachytherapy in T3 rectal cancer with complete pathologic remission as end point. Methods and Materials: The study included 50 patients with rectal adenocarcinoma. All patients had T3 tumor with a circumferential margin 0-5 mm on a magnetic resonance imaging scan. The radiotherapy was delivered by a technique including two planning target volumes. Clinical target volume 1 (CTV1) received 60 Gy/30 fractions, and CTV2 received 48.6 Gy/27 fractions. The tumor dose was raised to 65 Gy with endorectal brachytherapy 5 Gy/1 fraction to the tumor bed.more » On treatment days, the patients received uracil and tegafur 300 mg/m2 concurrently with radiotherapy. Results: Forty-eight patients underwent operation. Histopathologic tumor regression was assessed by the Tumor Regression Grade (TRG) system. TRG1 was recorded in 27% of the patients, and a further 27% were classified as TRG2. TRG3 was found in 40%, and 6% had TRG4. The toxicity was low. Conclusion: The results indicate that high-dose radiation with concurrent chemotherapy and endorectal brachytherapy is feasible with a high rate of complete response, but further trials are needed to define its possible role as treatment option.« less