Nitrates and bone turnover (NABT) - trial to select the best nitrate preparation: study protocol for a randomized controlled trial.

PubMed

Bucur, Roxana C; Reid, Lauren S; Hamilton, Celeste J; Cummings, Steven R; Jamal, Sophie A

2013-09-08

Organic nitrates uncouple bone turnover, improve bone mineral density, and improve trabecular and cortical components of bone. These changes in turnover, strength and geometry may translate into an important reduction in fractures. However, before proceeding with a large fracture trial, there is a need to identify the nitrate formulation that has both the greatest efficacy (with regards to bone turnover markers) and gives the fewest headaches. Ascertaining which nitrate formulation this may be is the purpose of the current study. This will be an open-label randomized, controlled trial conducted at Women's College Hospital comparing five formulations of nitrates for their effects on bone turnover markers and headache. We will recruit postmenopausal women age 50 years or older with no contraindications to nitroglycerin. Our trial will consist of a run-in phase and a treatment phase. We will enroll 420 women in the run-in phase, each to receive all of the 5 potential treatments in random order for 2 days, each with a 2-day washout period between treatments. Those who tolerate all formulations will enter the 12-week treatment phase and be randomly assigned to one of five groups: 0.3 mg sublingual nitroglycerin tablet, 0.6 mg of the sublingual tablet, a 20 mg tablet of isosorbide mononitrate, a 160 mg nitroglycerin transdermal patch (used for 8 h), and 15 mg of nitroglycerin ointment as used in a previous trial by our group. We will continue enrolment until we have randomized 210 women or 35 women per group. Concentrations of bone formation (bone-specific alkaline phosphatase and procollagen type I N-terminal propeptide) and bone resorption (C-telopeptides of collagen crosslinks and N-terminal crosslinks of collagen) agents will be measured in samples taken at study entry (the start of the run in phase) and 12 weeks. Subjects will record the frequency and severity of headaches daily during the run-in phase and then monthly after that. We will use the 'multiple comparisons with the best' approach for data analyses, as this strategy allows practical considerations of ease of use and tolerability to guide selection of the preparation for future studies. Data from this protocol will be used to develop a randomized, controlled trial of nitrates to prevent osteoporotic fractures. ClinicalTrials.gov Identifier: NCT01387672. Controlled-Trials.com: ISRCTN08860742.

Randomized clinical trial of bright light therapy for antepartum depression: preliminary findings.

PubMed

Epperson, C Neill; Terman, Michael; Terman, Jiuan Su; Hanusa, Barbara H; Oren, Dan A; Peindl, Kathleen S; Wisner, Katherine L

2004-03-01

Bright light therapy was shown to be a promising treatment for depression during pregnancy in a recent open-label study. In an extension of this work, we report findings from a double-blind placebo-controlled pilot study. Ten pregnant women with DSM-IV major depressive disorder were randomly assigned from April 2000 to January 2002 to a 5-week clinical trial with either a 7000 lux (active) or 500 lux (placebo) light box. At the end of the randomized controlled trial, subjects had the option of continuing in a 5-week extension phase. The Structured Interview Guide for the Hamilton Depression Scale-Seasonal Affective Disorder Version was administered to assess changes in clinical status. Salivary melatonin was used to index circadian rhythm phase for comparison with antidepressant results. Although there was a small mean group advantage of active treatment throughout the randomized controlled trial, it was not statistically significant. However, in the longer 10-week trial, the presence of active versus placebo light produced a clear treatment effect (p =.001) with an effect size (0.43) similar to that seen in antidepressant drug trials. Successful treatment with bright light was associated with phase advances of the melatonin rhythm. These findings provide additional evidence for an active effect of bright light therapy for antepartum depression and underscore the need for an expanded randomized clinical trial.

One session of high-intensity interval training (HIIT) every 5 days, improves muscle power but not static balance in lifelong sedentary ageing men: A randomized controlled trial.

PubMed

Sculthorpe, Nicholas F; Herbert, Peter; Grace, Fergal

2017-02-01

Declining muscle power during advancing age predicts falls and loss of independence. High-intensity interval training (HIIT) may improve muscle power, but remains largely unstudied in ageing participants. This randomized controlled trial (RCT) investigated the efficacy of a low-frequency HIIT (LfHIIT) intervention on peak muscle power (peak power output [PPO]), body composition, and balance in lifelong sedentary but otherwise healthy males. Thirty-three lifelong sedentary ageing men were randomly assigned to either intervention (INT; n = 22, age 62.3 ± 4.1 years) or control (n = 11, age 61.6 ± 5.0 years) who were both assessed at 3 distinct measurement points (phase A), after 6 weeks of conditioning exercise (phase B), and after 6 weeks of HIIT once every 5 days in INT (phase C), where control remained inactive throughout the study. Static balance remained unaffected, and both absolute and relative PPO were not different between groups at phases A or B, but increased significantly in INT after LfHIIT (P < 0.01). Lean body mass displayed a significant interaction (P < 0.01) due to an increase in INT between phases B and C (P < 0.05). 6 weeks of LfHIIT exercise feasible and effective method to induce clinically relevant improvements in absolute and relative PPO, but does not improve static balance in sedentary ageing men.

Systems Characterization of Combustor Instabilities With Controls Design Emphasis

NASA Technical Reports Server (NTRS)

Kopasakis, George

2004-01-01

This effort performed test data analysis in order to characterize the general behavior of combustor instabilities with emphasis on controls design. The analysis is performed on data obtained from two configurations of a laboratory combustor rig and from a developmental aero-engine combustor. The study has characterized several dynamic behaviors associated with combustor instabilities. These are: frequency and phase randomness, amplitude modulations, net random phase walks, random noise, exponential growth and intra-harmonic couplings. Finally, the very cause of combustor instabilities was explored and it could be attributed to a more general source-load type impedance interaction that includes the thermo-acoustic coupling. Performing these characterizations on different combustors allows for more accurate identification of the cause of these phenomena and their effect on instability.

Current randomized control trials, observational studies and meta analysis in off-pump coronary surgery.

PubMed

Parissis, Haralabos; Lau, Man Chi; Parissis, Mondrian; Lampridis, Savvas; Graham, Victoria; Al-Saudi, Reza; Mhandu, Peter

2015-12-17

The off-pump literature is divided into three eras: the "early phase" with results favouring off-pump surgery supported with randomized control trials (RCTs) mainly from Bristol, UK; an "intermediate phase" dominated by the results of the ROOBY trial and finally a more "contemporary phase" whereby the off/on-pump argument is unsettled. Although the literature has failed to project an overall superiority of off-pump versus on-pump surgery, nevertheless, small randomized control trials and large meta-analysis studies are concluding that the incidence of a stroke is less than 1 % when an aortic off-pump techniques (especially the non-touch technique) are advocated in patients with diseased ascending aorta. Furthermore, off-pump combined with hybrid procedures may lead to a reduction of adverse outcome in the aged high-risk population with concomitant poor left ventricular function and co-morbidities.The current review attempts to bring an insight onto the last ten years knowledge on the on/off-pump debate, with an aim to draw some clear conclusions in order to allow practitioners to reflect on the subject.

Experimental demonstration of spatially coherent beam combining using optical parametric amplification.

PubMed

Kurita, Takashi; Sueda, Keiichi; Tsubakimoto, Koji; Miyanaga, Noriaki

2010-07-05

We experimentally demonstrated coherent beam combining using optical parametric amplification with a nonlinear crystal pumped by random-phased multiple-beam array of the second harmonic of a Nd:YAG laser at 10-Hz repetition rate. In the proof-of-principle experiment, the phase jump between two pump beams was precisely controlled by a motorized actuator. For the demonstration of multiple-beam combining a random phase plate was used to create random-phased beamlets as a pump pulse. Far-field patterns of the pump, the signal, and the idler indicated that the spatially coherent signal beams were obtained on both cases. This approach allows scaling of the intensity of optical parametric chirped pulse amplification up to the exa-watt level while maintaining diffraction-limited beam quality.

Random technique to encode complex valued holograms with on axis reconstruction onto phase-only displays.

PubMed

Luis Martínez Fuentes, Jose; Moreno, Ignacio

2018-03-05

A new technique for encoding the amplitude and phase of diffracted fields in digital holography is proposed. It is based on a random spatial multiplexing of two phase-only diffractive patterns. The first one is the phase information of the intended pattern, while the second one is a diverging optical element whose purpose is the control of the amplitude. A random number determines the choice between these two diffractive patterns at each pixel, and the amplitude information of the desired field governs its discrimination threshold. This proposed technique is computationally fast and does not require iterative methods, and the complex field reconstruction appears on axis. We experimentally demonstrate this new encoding technique with holograms implemented onto a flicker-free phase-only spatial light modulator (SLM), which allows the axial generation of such holograms. The experimental verification includes the phase measurement of generated patterns with a phase-shifting polarization interferometer implemented in the same experimental setup.

Discontinuing Oxytocin Infusion in the Active Phase of Labor: A Systematic Review and Meta-analysis.

PubMed

Saccone, Gabriele; Ciardulli, Andrea; Baxter, Jason K; Quiñones, Joanne N; Diven, Liany C; Pinar, Bor; Maruotti, Giuseppe Maria; Martinelli, Pasquale; Berghella, Vincenzo

2017-11-01

To evaluate the benefits and harms of discontinuation of oxytocin after the active phase of labor is reached. Electronic databases (ie, MEDLINE, Scopus, ClinicalTrials.gov, EMBASE, ScienceDirect, the Cochrane Library at the CENTRAL Register of Controlled Trials, Scielo) were searched from their inception until April 2017. We included all randomized controlled trials comparing discontinuation (ie, intervention group) and continuation (ie, control group) of oxytocin infusion after the active phase of labor is reached, either after induction or augmentation of labor. Discontinuation of oxytocin infusion was defined as discontinuing oxytocin infusion when the active phase of labor was achieved. Continuation of oxytocin infusion was defined as continuing oxytocin infusion until delivery. Only trials in singleton gestations with vertex presentation at term were included. The primary outcome was the incidence of cesarean delivery. Nine randomized controlled trials, including 1,538 singleton gestations, were identified as relevant and included in the meta-analysis. All nine trials included only women undergoing induction of labor. In the discontinuation group, if arrest of labor occurred, usually defined as no cervical dilation in 2 hours or inadequate uterine contractions for 2 hours or more, oxytocin infusion was restarted. Women in the control group had oxytocin continued until delivery usually at the same dose used at the time the active phase was reached. Women who were randomized to have discontinuation of oxytocin infusion after the active phase of labor was reached had a significantly lower risk of cesarean delivery (9.3% compared with 14.7%; relative risk 0.64, 95% CI 0.48-0.87) and of uterine tachysystole (6.2% compared with 13.1%; relative risk 0.53, 95% CI 0.33-0.84) compared with those who were randomized to have continuation of oxytocin infusion until delivery. Discontinuation of oxytocin infusion was associated with an increase in the duration of the active phase of labor (mean difference 27.65 minutes, 95% CI 3.94-51.36). In singleton gestations with cephalic presentation at term undergoing induction, discontinuation of oxytocin infusion after the active phase of labor at approximately 5 cm is reached reduces the risk of cesarean delivery and of uterine tachysystole compared with continuous oxytocin infusion. Given this evidence, discontinuation of oxytocin infusion once the active stage of labor is established in women being induced should be considered as an alternative management plan.

Activity monitor intervention to promote physical activity of physicians-in-training: randomized controlled trial.

PubMed

Thorndike, Anne N; Mills, Sarah; Sonnenberg, Lillian; Palakshappa, Deepak; Gao, Tian; Pau, Cindy T; Regan, Susan

2014-01-01

Physicians are expected to serve as role models for healthy lifestyles, but long work hours reduce time for healthy behaviors. A hospital-based physical activity intervention could improve physician health and increase counseling about exercise. We conducted a two-phase intervention among 104 medical residents at a large hospital in Boston, Massachusetts. Phase 1 was a 6-week randomized controlled trial comparing daily steps of residents assigned to an activity monitor displaying feedback about steps and energy consumed (intervention) or to a blinded monitor (control). Phase 2 immediately followed and was a 6-week non-randomized team steps competition in which all participants wore monitors with feedback. Phase 1 outcomes were: 1) median steps/day and 2) proportion of days activity monitor worn. The Phase 2 outcome was mean steps/day on days monitor worn (≥500 steps/day). Physiologic measurements were collected at baseline and study end. Median steps/day were compared using Wilcoxon rank-sum tests. Mean steps were compared using repeated measures regression analyses. In Phase 1, intervention and control groups had similar activity (6369 vs. 6063 steps/day, p = 0.16) and compliance with wearing the monitor (77% vs. 77% of days, p = 0.73). In Phase 2 (team competition), residents recorded more steps/day than during Phase 1 (CONTROL: 7,971 vs. 7,567, p = 0.002; 7,832 vs. 7,739, p = 0.13). Mean compliance with wearing the activity monitor decreased for both groups during Phase 2 compared to Phase 1 (60% vs. 77%, p<0.001). Mean systolic blood pressure decreased (p = 0.004) and HDL cholesterol increased (p<0.001) among all participants at end of study compared to baseline. Although the activity monitor intervention did not have a major impact on activity or health, the high participation rates of busy residents and modest changes in steps, blood pressure, and HDL suggest that more intensive hospital-based wellness programs have potential for promoting healthier lifestyles among physicians. Clinicaltrials.gov NCT01287208.

Activity Monitor Intervention to Promote Physical Activity of Physicians-In-Training: Randomized Controlled Trial

PubMed Central

Thorndike, Anne N.; Mills, Sarah; Sonnenberg, Lillian; Palakshappa, Deepak; Gao, Tian; Pau, Cindy T.; Regan, Susan

2014-01-01

Background Physicians are expected to serve as role models for healthy lifestyles, but long work hours reduce time for healthy behaviors. A hospital-based physical activity intervention could improve physician health and increase counseling about exercise. Methods We conducted a two-phase intervention among 104 medical residents at a large hospital in Boston, Massachusetts. Phase 1 was a 6-week randomized controlled trial comparing daily steps of residents assigned to an activity monitor displaying feedback about steps and energy consumed (intervention) or to a blinded monitor (control). Phase 2 immediately followed and was a 6-week non-randomized team steps competition in which all participants wore monitors with feedback. Phase 1 outcomes were: 1) median steps/day and 2) proportion of days activity monitor worn. The Phase 2 outcome was mean steps/day on days monitor worn (≥500 steps/day). Physiologic measurements were collected at baseline and study end. Median steps/day were compared using Wilcoxon rank-sum tests. Mean steps were compared using repeated measures regression analyses. Results In Phase 1, intervention and control groups had similar activity (6369 vs. 6063 steps/day, p = 0.16) and compliance with wearing the monitor (77% vs. 77% of days, p = 0.73). In Phase 2 (team competition), residents recorded more steps/day than during Phase 1 (Control: 7,971 vs. 7,567, p = 0.002; Intervention: 7,832 vs. 7,739, p = 0.13). Mean compliance with wearing the activity monitor decreased for both groups during Phase 2 compared to Phase 1 (60% vs. 77%, p<0.001). Mean systolic blood pressure decreased (p = 0.004) and HDL cholesterol increased (p<0.001) among all participants at end of study compared to baseline. Conclusions Although the activity monitor intervention did not have a major impact on activity or health, the high participation rates of busy residents and modest changes in steps, blood pressure, and HDL suggest that more intensive hospital-based wellness programs have potential for promoting healthier lifestyles among physicians. Trial Registration Clinicaltrials.gov NCT01287208. PMID:24950218

Can we alter pregnancy outcome by adjusting progesterone treatment at mid-luteal phase: a randomized controlled trial.

PubMed

Aslih, Nardin; Ellenbogen, Adrian; Shavit, Tal; Michaeli, Medeia; Yakobi, Devora; Shalom-Paz, Einat

2017-08-01

Our study aimed to determine whether mid-luteal serum P concentrations can serve as a predictive factor for in vitro fertilization (IVF) outcomes and whether increasing P dosage for patients with low levels at mid-luteal phase may improve pregnancy rates. It was a prospective, randomized controlled study. A total of 146 patients undergoing IVF treatment were prospectively enrolled and received routine luteal phase support (LPS) regimen of Endometrin® (progesterone) 200 mg/day. Serum P levels were measured 7 days after embryo transfer (ET). Considering a cutoff level of 15 ng/ml on this day, patients with higher levels continued the same dosage until pregnancy test (control group). Patients with lower levels were randomly allocated to continue Endometrin® 200 mg/day (Group A) or to increase Endometrin® dosage to 300 mg/day (Group B). The Main Outcome Measures were pregnancy rates. Both biochemical and clinical pregnancy and live birth rates were comparable between all groups regardless of P level on day 7 of luteal phase and regardless of dose adjustment. ROC analysis determined that mid-luteal P levels of 17 ng/ml can be a better predictor of cycle outcome. In conclusion raising the P dose at mid-luteal phase to 300 mg daily did not improve cycle outcomes.

An Examination of Strategy Implementation During Abstract Nonlinguistic Category Learning in Aphasia.

PubMed

Vallila-Rohter, Sofia; Kiran, Swathi

2015-08-01

Our purpose was to study strategy use during nonlinguistic category learning in aphasia. Twelve control participants without aphasia and 53 participants with aphasia (PWA) completed a computerized feedback-based category learning task consisting of training and testing phases. Accuracy rates of categorization in testing phases were calculated. To evaluate strategy use, strategy analyses were conducted over training and testing phases. Participant data were compared with model data that simulated complex multi-cue, single feature, and random pattern strategies. Learning success and strategy use were evaluated within the context of standardized cognitive-linguistic assessments. Categorization accuracy was higher among control participants than among PWA. The majority of control participants implemented suboptimal or optimal multi-cue and single-feature strategies by testing phases of the experiment. In contrast, a large subgroup of PWA implemented random patterns, or no strategy, during both training and testing phases of the experiment. Person-to-person variability arises not only in category learning ability but also in the strategies implemented to complete category learning tasks. PWA less frequently developed effective strategies during category learning tasks than control participants. Certain PWA may have impairments of strategy development or feedback processing not captured by language and currently probed cognitive abilities.

Effect of hyoscine-N-butyl bromide rectal suppository on labor progress in primigravid women: a randomized double-blind placebo-controlled clinical trial

PubMed Central

Makvandi, Somayeh; Tadayon, Mitra; Abbaspour, Mohammadreza

2011-01-01

Aim To determine the effects of hyoscine-N-butyl bromide (HBB) rectal suppository on labor progress in primigravid women. Methods A randomized double-blind placebo-controlled clinical trial was carried out on 130 primigravid women admitted for spontaneous labor. The women were recruited based on the inclusion and exclusion criteria and randomized into the experimental (n = 65) and control group (n = 65). In the beginning of the active phase of labor, 20 mg of HBB rectal suppository was administered to the experimental group, while a placebo suppository was administered to the control group. Cervical dilatation and duration of active phase and second stage of labor were recorded. Results The rate of cervical dilatation was 2.6 cm/h in the experimental and 1.5 cm/h in the control group (P < 0.001). The active phase and the second stage of labor were significantly shorter in the experimental group (P = 0.001 and P < 0.001, respectively). There was no significant difference between the two groups in the fetal heart rate, maternal pulse rate, blood pressure, and the APGAR score 1 and 5 minutes after birth. Conclusion Use of HBB rectal suppository in the active management of labor can shorten both the active phase and second stage of labor without significant side-effects. Registration No IRCT138804282204N1. PMID:21495198

Many-body localization in a long range XXZ model with random-field

NASA Astrophysics Data System (ADS)

Li, Bo

2016-12-01

Many-body localization (MBL) in a long range interaction XXZ model with random field are investigated. Using the exact diagonal method, the MBL phase diagram with different tuning parameters and interaction range is obtained. It is found that the phase diagram of finite size results supplies strong evidence to confirm that the threshold interaction exponent α = 2. The tuning parameter Δ can efficiently change the MBL edge in high energy density stats, thus the system can be controlled to transfer from thermal phase to MBL phase by changing Δ. The energy level statistics data are consistent with result of the MBL phase diagram. However energy level statistics data cannot detect the thermal phase correctly in extreme long range case.

Current Trend Towards Using Soft Computing Approaches to Phase Synchronization in Communication Systems

NASA Technical Reports Server (NTRS)

Drake, Jeffrey T.; Prasad, Nadipuram R.

1999-01-01

This paper surveys recent advances in communications that utilize soft computing approaches to phase synchronization. Soft computing, as opposed to hard computing, is a collection of complementary methodologies that act in producing the most desirable control, decision, or estimation strategies. Recently, the communications area has explored the use of the principal constituents of soft computing, namely, fuzzy logic, neural networks, and genetic algorithms, for modeling, control, and most recently for the estimation of phase in phase-coherent communications. If the receiver in a digital communications system is phase-coherent, as is often the case, phase synchronization is required. Synchronization thus requires estimation and/or control at the receiver of an unknown or random phase offset.

Efficacy of extended-release tramadol for treatment of prescription opioid withdrawal: A two-phase randomized controlled trial*

PubMed Central

Lofwall, Michelle R.; Babalonis, Shanna; Nuzzo, Paul A.; Siegel, Anthony; Campbell, Charles; Walsh, Sharon L.

2013-01-01

Background Tramadol is an atypical analgesic with monoamine and modest mu opioid agonist activity. The purpose of this study was to evaluate: 1) the efficacy of extended-release (ER) tramadol in treating prescription opioid withdrawal and 2) whether cessation of ER tramadol produces opioid withdrawal. Methods Prescription opioid users with current opioid dependence and observed withdrawal participated in this inpatient, two-phase double blind, randomized placebo-controlled trial. In Phase 1 (days 1-7), participants were randomly assigned to matched oral placebo or ER tramadol (200 or 600 mg daily). In Phase 2 (days 8-13), all participants underwent double blind crossover to placebo. Breakthrough withdrawal medications were available for all subjects. Enrollment continued until 12 completers/group was achieved. Results Use of breakthrough withdrawal medication differed significantly (p<0.05) among groups in both phases; the 200 mg group received the least amount in Phase 1, and the 600 mg group received the most in both phases. In Phase 1, tramadol 200 mg produced significantly lower peak ratings than placebo on ratings of insomnia, lacrimation, muscular tension, and sneezing. Only tramadol 600 mg produced miosis in Phase 1. In Phase 2, tramadol 600 mg produced higher peak ratings of rhinorrhea, irritable, depressed, heavy/sluggish, and hot/cold flashes than placebo. There were no serious adverse events and no signal of abuse liability for tramadol. Conclusions ER tramadol 200 mg modestly attenuated opioid withdrawal. Mild opioid withdrawal occurred after cessation of treatment with 600 mg tramadol. These data support the continued investigation of tramadol as a treatment for opioid withdrawal. PMID:23755929

Multicenter Randomized Controlled Trial on Duration of Therapy for Thrombosis in Children and Young Adults (Kids-DOTT): Pilot/Feasibility Phase Findings

PubMed Central

Goldenberg, N.A.; Abshire, T.; Blatchford, P.J.; Fenton, L.Z.; Halperin, J.L.; Hiatt, W.R.; Kessler, C.M.; Kittelson, J.M.; Manco-Johnson, M.J.; Spyropoulos, A.C.; Steg, P.G.; Stence, N.V.; Turpie, A.G.G.; Schulman, S.

2015-01-01

BACKGROUND Randomized controlled trials (RCTs) in pediatric venous thromboembolism (VTE) treatment have been challenged by unsubstantiated design assumptions and/or poor accrual. Pilot/feasibility (P/F) studies are critical to future RCT success. METHODS Kids-DOTT is a multicenter RCT investigating non-inferiority of a 6-week (shortened) vs. 3-month (conventional) duration of anticoagulation in patients <21 years old with provoked venous thrombosis. Primary efficacy and safety endpoints are symptomatic recurrent VTE at 1 year and anticoagulant-related, clinically-relevant bleeding. In the P/F phase, 100 participants were enrolled in an open, blinded endpoint, parallel-cohort RCT design. RESULTS No eligibility violations or randomization errors occurred. Of enrolled patients, 69% were randomized, 3% missed the randomization window, and 28% were followed in pre-specified observational cohorts for completely occlusive thrombosis or persistent antiphospholipid antibodies. Retention at 1 year was 82%. Inter-observer agreement between local vs. blinded central determination of venous occlusion by imaging at 6 weeks post-diagnosis was strong (κ-statistic=0.75; 95% confidence interval [CI] 0.48–1.0). Primary efficacy and safety event rates were 3.3% (95% CI 0.3–11.5%) and 1.4% (0.03–7.4%). CONCLUSIONS The P/F phase of Kids-DOTT has demonstrated validity of vascular imaging findings of occlusion as a randomization criterion, and defined randomization, retention, and endpoint rates to inform the fully-powered RCT. PMID:26118944

Transient Oscilliations in Mechanical Systems of Automatic Control with Random Parameters

NASA Astrophysics Data System (ADS)

Royev, B.; Vinokur, A.; Kulikov, G.

2018-04-01

Transient oscillations in mechanical systems of automatic control with random parameters is a relevant but insufficiently studied issue. In this paper, a modified spectral method was applied to investigate the problem. The nature of dynamic processes and the phase portraits are analyzed depending on the amplitude and frequency of external influence. It is evident from the obtained results, that the dynamic phenomena occurring in the systems with random parameters under external influence are complex, and their study requires further investigation.

Efficacy and safety of teneligliptin, a novel dipeptidyl peptidase-4 inhibitor, in Korean patients with type 2 diabetes mellitus: a 24-week multicentre, randomized, double-blind, placebo-controlled phase III trial.

PubMed

Hong, S; Park, C-Y; Han, K A; Chung, C H; Ku, B J; Jang, H C; Ahn, C W; Lee, M-K; Moon, M K; Son, H S; Lee, C B; Cho, Y-W; Park, S-W

2016-05-01

We assessed the 24-week efficacy and safety of teneligliptin, a novel dipeptidyl peptidase-4 inhibitor, in Korean patients with type 2 diabetes mellitus (T2DM) that was inadequately controlled with diet and exercise. The present study was designed as a multicentre, randomized, double-blind, placebo-controlled, parallel-group, phase III study. Patients (n = 142) were randomized 2 : 1 into two different treatment groups as follows: 99 received teneligliptin (20 mg) and 43 received placebo. The primary endpoint was change in glycated haemoglobin (HbA1c) level from baseline to week 24. Teneligliptin significantly reduced the HbA1c level from baseline compared with placebo after 24 weeks. At week 24, the differences between changes in HbA1c and fasting plasma glucose (FBG) in the teneligliptin and placebo groups were -0.94% [least-squares (LS) mean -1.22, -0.65] and -1.21 mmol/l (-1.72, -0.70), respectively (all p < 0.001). The incidence of hypoglycaemia and adverse events were not significantly different between the two groups. This phase III, randomized, placebo-controlled study provides evidence of the safety and efficacy of 24 weeks of treatment with teneligliptin as a monotherapy in Korean patients with T2DM. © 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Nitrates and bone turnover (NABT) - trial to select the best nitrate preparation: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Organic nitrates uncouple bone turnover, improve bone mineral density, and improve trabecular and cortical components of bone. These changes in turnover, strength and geometry may translate into an important reduction in fractures. However, before proceeding with a large fracture trial, there is a need to identify the nitrate formulation that has both the greatest efficacy (with regards to bone turnover markers) and gives the fewest headaches. Ascertaining which nitrate formulation this may be is the purpose of the current study. Methods and design This will be an open-label randomized, controlled trial conducted at Women’s College Hospital comparing five formulations of nitrates for their effects on bone turnover markers and headache. We will recruit postmenopausal women age 50 years or older with no contraindications to nitroglycerin. Our trial will consist of a run-in phase and a treatment phase. We will enroll 420 women in the run-in phase, each to receive all of the 5 potential treatments in random order for 2 days, each with a 2-day washout period between treatments. Those who tolerate all formulations will enter the 12-week treatment phase and be randomly assigned to one of five groups: 0.3 mg sublingual nitroglycerin tablet, 0.6 mg of the sublingual tablet, a 20 mg tablet of isosorbide mononitrate, a 160 mg nitroglycerin transdermal patch (used for 8 h), and 15 mg of nitroglycerin ointment as used in a previous trial by our group. We will continue enrolment until we have randomized 210 women or 35 women per group. Concentrations of bone formation (bone-specific alkaline phosphatase and procollagen type I N-terminal propeptide) and bone resorption (C-telopeptides of collagen crosslinks and N-terminal crosslinks of collagen) agents will be measured in samples taken at study entry (the start of the run in phase) and 12 weeks. Subjects will record the frequency and severity of headaches daily during the run-in phase and then monthly after that. We will use the ‘multiple comparisons with the best’ approach for data analyses, as this strategy allows practical considerations of ease of use and tolerability to guide selection of the preparation for future studies. Discussion Data from this protocol will be used to develop a randomized, controlled trial of nitrates to prevent osteoporotic fractures. Trial registration ClinicalTrials.gov Identifier: NCT01387672. Controlled-Trials.com: ISRCTN08860742. PMID:24010992

Financial incentive strategies for maintenance of weight loss: results from an internet-based randomized controlled trial.

PubMed

Yancy, William S; Shaw, Pamela A; Wesby, Lisa; Hilbert, Victoria; Yang, Lin; Zhu, Jingsan; Troxel, Andrea; Huffman, David; Foster, Gary D; Wojtanowski, Alexis C; Volpp, Kevin G

2018-05-25

Financial incentives can improve initial weight loss; we examined whether financial incentives can improve weight loss maintenance. Participants aged 30-80 years who lost at least 5 kg during the first 4-6 months in a nationally available commercial weight loss program were recruited via the internet into a three-arm randomized trial of two types of financial incentives versus active control during months 1-6 (Phase I) followed by passive monitoring during months 7-12 (Phase II). Interventions were daily self-weighing and text messaging feedback alone (control) or combined with a lottery-based incentive or a direct incentive. The primary outcome was weight change 6 months after initial weight loss. Secondary outcomes included weight change 12 months after initial weight loss (6 months after cessation of maintenance intervention), and self-reported physical activity and eating behaviors. Of 191 participants randomized, the mean age was 49.0 (SD = 10.5) years and weight loss prior to randomization was 11.4 (4.7) kg; 92% were women and 89% were White. Mean weight changes during the next 6 months (Phase I) were: lottery -3.0 (5.8) kg; direct -2.8 (5.8) kg; and control -1.4 (5.8) kg (all pairwise comparisons p > 0.1). Weight changes through the end of 12 months post-weight loss (Phase II) were: lottery -1.8 (10.5) kg; direct -0.7 (10.7) kg; and control -0.3 (9.4) kg (all pairwise comparisons p > 0.1). The percentages of participants who maintained their weight loss (defined as gaining ≤1.36 kg) were: lottery 79%, direct 76%, and control 67% at 6 months and lottery 66%, direct 62%, and control 59% at 12 months (all pairwise comparisons p > 0.1). At 6 and 12 months after initial weight loss, changes in self-reported physical activity or eating behaviors did not differ across arms. Compared with the active control of daily texting based on daily home weighing, lottery-based and direct monetary incentives provided no additional benefit for weight loss maintenance.

An Examination of Strategy Implementation During Abstract Nonlinguistic Category Learning in Aphasia

PubMed Central

Kiran, Swathi

2015-01-01

Purpose Our purpose was to study strategy use during nonlinguistic category learning in aphasia. Method Twelve control participants without aphasia and 53 participants with aphasia (PWA) completed a computerized feedback-based category learning task consisting of training and testing phases. Accuracy rates of categorization in testing phases were calculated. To evaluate strategy use, strategy analyses were conducted over training and testing phases. Participant data were compared with model data that simulated complex multi-cue, single feature, and random pattern strategies. Learning success and strategy use were evaluated within the context of standardized cognitive–linguistic assessments. Results Categorization accuracy was higher among control participants than among PWA. The majority of control participants implemented suboptimal or optimal multi-cue and single-feature strategies by testing phases of the experiment. In contrast, a large subgroup of PWA implemented random patterns, or no strategy, during both training and testing phases of the experiment. Conclusions Person-to-person variability arises not only in category learning ability but also in the strategies implemented to complete category learning tasks. PWA less frequently developed effective strategies during category learning tasks than control participants. Certain PWA may have impairments of strategy development or feedback processing not captured by language and currently probed cognitive abilities. PMID:25908438

Controlling total spot power from holographic laser by superimposing a binary phase grating.

PubMed

Liu, Xiang; Zhang, Jian; Gan, Yu; Wu, Liying

2011-04-25

By superimposing a tunable binary phase grating with a conventional computer-generated hologram, the total power of multiple holographic 3D spots can be easily controlled by changing the phase depth of grating with high accuracy to a random power value for real-time optical manipulation without extra power loss. Simulation and experiment results indicate that a resolution of 0.002 can be achieved at a lower time cost for normalized total spot power.

Active control on high-order coherence and statistic characterization on random phase fluctuation of two classical point sources.

PubMed

Hong, Peilong; Li, Liming; Liu, Jianji; Zhang, Guoquan

2016-03-29

Young's double-slit or two-beam interference is of fundamental importance to understand various interference effects, in which the stationary phase difference between two beams plays the key role in the first-order coherence. Different from the case of first-order coherence, in the high-order optical coherence the statistic behavior of the optical phase will play the key role. In this article, by employing a fundamental interfering configuration with two classical point sources, we showed that the high- order optical coherence between two classical point sources can be actively designed by controlling the statistic behavior of the relative phase difference between two point sources. Synchronous position Nth-order subwavelength interference with an effective wavelength of λ/M was demonstrated, in which λ is the wavelength of point sources and M is an integer not larger than N. Interestingly, we found that the synchronous position Nth-order interference fringe fingerprints the statistic trace of random phase fluctuation of two classical point sources, therefore, it provides an effective way to characterize the statistic properties of phase fluctuation for incoherent light sources.

The dressed atom as binary phase modulator: towards attojoule/edge optical phase-shift keying.

PubMed

Kerckhoff, Joseph; Armen, Michael A; Pavlichin, Dmitri S; Mabuchi, Hideo

2011-03-28

We use a single 133Cs atom strongly coupled to an optical resonator to induce random binary phase modulation of a near infra-red, ∼ 500 pW laser beam, with each modulation edge caused by the dissipation of a single photon (≈ 0.23 aJ) by the atom. While our ability to deterministically induce phase edges with an additional optical control beam is limited thus far, theoretical analysis of an analogous, solid-state system indicates that efficient external control should be achievable in demonstrated nanophotonic systems.

The PEDALS Stationary Cycling Intervention and Health-Related Quality of Life in Children with Cerebral Palsy: A Randomized Controlled Trial

ERIC Educational Resources Information Center

DeMuth, Sharon K.; Knutson, Loretta M.; Fowler, Eileen G.

2012-01-01

Aim: The aim of this study was to assess health-related quality of life (HRQOL) following a stationary cycling intervention in children with cerebral palsy (CP). Method: This was a phase I multisite randomized controlled trial with single blinding. HRQOL was evaluated using the Pediatric Quality of Life Inventory SF15 (PedsQL; children) and…

Randomized trial of anaesthetic interventions in external cephalic version for breech presentation.

PubMed

Khaw, K S; Lee, S W Y; Ngan Kee, W D; Law, L W; Lau, T K; Ng, F F; Leung, T Y

2015-06-01

Successful external cephalic version (ECV) for breech presenting fetus reduces the need for Caesarean section (CS). We aimed to compare the success rate of ECV with either spinal anaesthesia (SA) or i.v. analgesia using remifentanil. In a double-phased, stratified randomized blinded controlled study we compared the success rates of ECV, performed under spinal anaesthesia (SA), i.v. analgesia (IVA) using remifentanil or no anaesthetic interventions. In phase I, 189 patients were stratified by parity before randomization to ECV, performed by blinded operators, under SA using either hyperbaric bupivacaine 9 mg with fentanyl 15 µg, i.v. remifentanil infusion 0.1 µg kg min(-1), or Control (no anaesthetic intervention). Operators performing ECV were blinded to the treatment allocation. In phase 2, patients in the Control group in whom the initial ECV failed were further randomized to receive either SA (n=9) or IVA (n=9) for a re-attempt. The primary outcome was the incidence of successful ECV. The success rate in Phase 1 was greatest using SA [52/63 (83%)], compared with IVA [40/63 (64%)] and Control [40/63 (64%)], (P=0.027). Median [IQR] pain scores on a visual analogue scale (range 0-100), were 0 [0-0] with SA, 35 [0-60] with IVA and 50 [30-75] in the Control group (P<0.001). Median [IQR] VAS sedation scores were highest with IVA [75 (50-80)], followed by SA, [0 (0-50)] and Control [0 (0-0)]. In phase 2, 7/9 (78%) of ECV re-attempts were successful with SA, whereas all re-attempts using IVA failed (P=0.0007). The incidence of fetal bradycardia necessitating emergency CS within 30 min, was similar among groups; 1.6% (1/63) in the SA and IVA groups and 3.2% (2/63) in the Control group. SA increased the success rate and reduced pain for both primary and re-attempts of ECV, whereas IVA using remifentanil infusion only reduced the pain. There was no significant increase in the incidence of fetal bradycardia or emergency CS, with ECV performed under anaesthetic interventions. Relaxation of the abdominal muscles from SA appears to underlie the improved outcomes for ECV. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Prolonged Follow-Up of Patients in the U.S. Multicenter Trial of Ursodeoxycholic Acid for Primary Biliary Cirrhosis

PubMed Central

Combes, Burton; Luketic, Velimir A.; Peters, Marion G.; Zetterman, Rowen K.; Garcia-Tsao, Guadalupe; Munoz, Santiago J.; Lin, Danyu; Flye, Nancy; Carithers, Robert L.

2013-01-01

OBJECTIVE Randomized, double-blind, placebo-controlled trials of ursodeoxycholic acid (UDCA) in patients with primary biliary cirrhosis (PBC) have not demonstrated improvement in survival during the placebo-controlled phases of these trials. Analyses purporting to demonstrate a survival advantage of UDCA are largely dependent on data obtained after the placebo phases were terminated, and placebo-treated patients were offered open-label UDCA. After completion of our 2-yr placebo-controlled trial of UDCA in which we observed no survival benefit for UDCA, we provided the patients with open-label UDCA to see if delay in providing UDCA for 2 yr had any effect on subsequent liver transplantation or death without liver transplantation. METHODS In our previously reported 2-yr placebo-controlled trial, 151 patients with PBC were randomized to receive either UDCA (n = 77) or placebo (n = 74). The number of patients who progressed to liver transplantation or death without transplantation were similar in both the groups, 12 (16%) in the UDCA-treated and 11 (15%) in placebo-treated patients. All the patients were then offered open-label UDCA, with 61 original UDCA and 56 original placebo-treated patients now taking UDCA in an extended open-label phase of the trial. RESULTS No significant differences were observed in the number of patients who underwent liver transplantation or died without liver transplantation in the open-label phase of the trial. Moreover, no difference in the time to these endpoints was seen over the period of observation of as long as 6 yr from the time of initial randomization. CONCLUSIONS Results of open-label extensions of previous conducted placebo-controlled trials of UDCA in PBC leave uncertain whether UDCA impacts significantly on liver transplantation and death without liver transplantation in patients with PBC. PMID:15046215

GPS-Like Phasing Control of the Space Solar Power System Transmission Array

NASA Technical Reports Server (NTRS)

Psiaki, Mark L.

2003-01-01

The problem of phasing of the Space Solar Power System's transmission array has been addressed by developing a GPS-like radio navigation system. The goal of this system is to provide power transmission phasing control for each node of the array that causes the power signals to add constructively at the ground reception station. The phasing control system operates in a distributed manner, which makes it practical to implement. A leader node and two radio navigation beacons are used to control the power transmission phasing of multiple follower nodes. The necessary one-way communications to the follower nodes are implemented using the RF beacon signals. The phasing control system uses differential carrier phase relative navigation/timing techniques. A special feature of the system is an integer ambiguity resolution procedure that periodically resolves carrier phase cycle count ambiguities via encoding of pseudo-random number codes on the power transmission signals. The system is capable of achieving phasing accuracies on the order of 3 mm down to 0.4 mm depending on whether the radio navigation beacons operate in the L or C bands.

The effect of ursodeoxycholic acid in liver functional restoration of patients with obstructive jaundice after endoscopic treatment: a prospective, randomized, and controlled study.

PubMed

Fekaj, Enver; Gjata, Arben; Maxhuni, Mehmet

2013-09-22

In patients with obstructive jaundice, multi-organ dysfunction may develop. This trial is a prospective, open-label, randomized, and controlled study with the objective to evaluate the effect of ursodeoxycholic acid in liver functional restoration in patients with obstructive jaundice after endoscopic treatment. The aim of this study is to evaluate the effect of ursodeoxycholic acid in liver functional restoration of patients with obstructive jaundice after endoscopic treatment. The hypothesis of this trial is that patients with obstructive jaundice, in which will be administered UDCA, in the early phase after endoscopic intervention will have better and faster functional restoration of the liver than patients in the control group.Patients with obstructive jaundice, randomly, will be divided into two groups: (A) test group in which will be administered ursodeoxycholic acid twenty-four hours after endoscopic procedure and will last fourteen days, and (B) control group.Serum-testing will include determination of bilirubin, alanine transaminase, aspartate transaminase, gama-glutamil transpeptidase, alkaline phosphatase, albumin, and cholesterol levels. These parameters will be determined one day prior endoscopic procedure, and on the third, fifth, seventh, tenth, twelfth and fourteenth days after endoscopic intervention. This trial is a prospective, open-label, randomized, and controlled study to asses the effect of ursodeoxycholic acid in liver functional restoration of patients with obstructive jaundice in the early phase after endoscopic treatment.

Enhancing evidence-based diabetes and chronic disease control among local health departments: a multi-phase dissemination study with a stepped-wedge cluster randomized trial component.

PubMed

Parks, Renee G; Tabak, Rachel G; Allen, Peg; Baker, Elizabeth A; Stamatakis, Katherine A; Poehler, Allison R; Yan, Yan; Chin, Marshall H; Harris, Jenine K; Dobbins, Maureen; Brownson, Ross C

2017-10-18

The rates of diabetes and prediabetes in the USA are growing, significantly impacting the quality and length of life of those diagnosed and financially burdening society. Premature death and disability can be prevented through implementation of evidence-based programs and policies (EBPPs). Local health departments (LHDs) are uniquely positioned to implement diabetes control EBPPs because of their knowledge of, and focus on, community-level needs, contexts, and resources. There is a significant gap, however, between known diabetes control EBPPs and actual diabetes control activities conducted by LHDs. The purpose of this study is to determine how best to support the use of evidence-based public health for diabetes (and related chronic diseases) control among local-level public health practitioners. This paper describes the methods for a two-phase study with a stepped-wedge cluster randomized trial that will evaluate dissemination strategies to increase the uptake of public health knowledge and EBPPs for diabetes control among LHDs. Phase 1 includes development of measures to assess practitioner views on and organizational supports for evidence-based public health, data collection using a national online survey of LHD chronic disease practitioners, and a needs assessment of factors influencing the uptake of diabetes control EBPPs among LHDs within one state in the USA. Phase 2 involves conducting a stepped-wedge cluster randomized trial to assess effectiveness of dissemination strategies with local-level practitioners at LHDs to enhance capacity and organizational support for evidence-based diabetes prevention and control. Twelve LHDs will be selected and randomly assigned to one of the three groups that cross over from usual practice to receive the intervention (dissemination) strategies at 8-month intervals; the intervention duration for groups ranges from 8 to 24 months. Intervention (dissemination) strategies may include multi-day in-person workshops, electronic information exchange methods, technical assistance through a knowledge broker, and organizational changes to support evidence-based public health approaches. Evaluation methods comprise surveys at baseline and the three crossover time points, abstraction of local-level diabetes and chronic disease control program plans and progress reports, and social network analysis to understand the relationships and contextual issues that influence EBPP adoption. ClinicalTrial.gov, NCT03211832.

On the predictive control of foveal eye tracking and slow phases of optokinetic and vestibular nystagmus.

PubMed Central

Yasui, S; Young, L R

1984-01-01

Smooth pursuit and saccadic components of foveal visual tracking as well as more involuntary ocular movements of optokinetic (o.k.n.) and vestibular nystagmus slow phase components were investigated in man, with particular attention given to their possible input-adaptive or predictive behaviour. Each component in question was isolated from the eye movement records through a computer-aided procedure. The frequency response method was used with sinusoidal (predictable) and pseudo-random (unpredictable) stimuli. When the target motion was pseudo-random, the frequency response of pursuit eye movements revealed a large phase lead (up to about 90 degrees) at low stimulus frequencies. It is possible to interpret this result as a predictive effect, even though the stimulation was pseudo-random and thus 'unpredictable'. The pseudo-random-input frequency response intrinsic to the saccadic system was estimated in an indirect way from the pursuit and composite (pursuit + saccade) frequency response data. The result was fitted well by a servo-mechanism model, which has a simple anticipatory mechanism to compensate for the inherent neuromuscular saccadic delay by utilizing the retinal slip velocity signal. The o.k.n. slow phase also exhibited a predictive effect with sinusoidal inputs; however, pseudo-random stimuli did not produce such phase lead as found in the pursuit case. The vestibular nystagmus slow phase showed no noticeable sign of prediction in the frequency range examined (0 approximately 0.7 Hz), in contrast to the results of the visually driven eye movements (i.e. saccade, pursuit and o.k.n. slow phase) at comparable stimulus frequencies. PMID:6707954

Evaluation of a Two-Phase Experimental Study of a Small Group ("MultiLit") Reading Intervention for Older Low-Progress Readers

ERIC Educational Resources Information Center

Buckingham, Jennifer; Beaman-Wheldall, Robyn; Wheldall, Kevin

2014-01-01

The study reported here examined the efficacy of a small group (Tier 2 in a three-tier Response to Intervention model) literacy intervention for older low-progress readers (in Years 3-6). This article focuses on the second phase of a two-phase, crossover randomized control trial involving 26 students. In Phase 1, the experimental group (E1)…

Prevention of endometrial apoptosis: randomized prospective comparison of human chorionic gonadotropin versus progesterone treatment in the luteal phase.

PubMed

Lovely, Laurie P; Fazleabas, Asgerally T; Fritz, Marc A; McAdams, Devin G; Lessey, Bruce A

2005-04-01

To study control of apoptosis in human endometrium, we examined late luteal-phase endometrial biopsies obtained in the late luteal phase for evidence of apoptosis and compared the effects of exogenous human chorionic gonadotropin (hCG) and progesterone on this process. Using a controlled, prospective, and randomized study design, 12 healthy, fertile, reproductive-age women (ages 20-34 yr) with regular menstrual cycles (range, 26-32 d) were recruited. Each underwent an endometrial biopsy 12 d after a urinary LH surge in a control and treatment cycle. After biopsy in a natural cycle, subjects were randomized to receive luteal doses of either 200 mg intravaginal progesterone (d 18-27) or a single im injection of 10,000 IU of hCG (d 19) followed by repeat endometrial biopsy and collection of serum on d 26. Apoptosis was assessed by DNA laddering, localizing apoptotic bodies using immunofluorescent labeling of DNA fragments (the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling method), and immunohistochemical assessment of apoptosis markers bcl-2, bcl-x, and bax. Serum progesterone levels were compared between treatment groups. Evidence of apoptosis in control cycles was significantly reduced in endometrium after both luteal-phase treatments. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling results demonstrated significantly less apoptosis in the hCG treatment group compared with controls. Immunostaining for bcl-2 was higher in hCG- and progesterone-treated cycles, whereas bax expression was decreased and bcl-x immunostaining was not different between treatments. Serum progesterone levels were highest in the hCG-treated group, although statistical significance was not reached (P = 0.08). These results demonstrate that signs of apoptosis, already apparent by d 26 of the menstrual cycle can be reduced with either hCG or progesterone treatment. The clinical utility of these findings includes a rational use of luteal-phase support for treatment of women with infertility and/or recurrent pregnancy loss.

Effectiveness of the addition of citicoline to patching in the treatment of amblyopia around visual maturity: A randomized controlled trial

PubMed Central

Pawar, Prachee Vasant; Mumbare, Sachin S; Patil, Mrunal Suresh; Ramakrishnan, Seema

2014-01-01

Aim: To study the effectiveness of the addition of citicoline to patching in the treatment of amblyopia in the age group of 4-13 years. Materials and Methods: A randomized controlled trial, which included patients who were randomly divided into two groups. Both the groups received patching therapy till plateau was achieved in phase 1 of the study. Then in phase 2, group I received citicoline plus patching and group II continued to receive only patching. Outcome Measures: Outcome was measured by the visual acuity in logMAR every month in phase 1 till plateau was achieved and then for 12 months in phase 2. Results: No significant difference was found in the mean visual acuities in these two groups in phase 1 till plateau was reached. In phase 2, for the initial four months, there was no significant difference in the visual acuities in these two groups, at the respective intervals. However, five months onward, up to 12 months, there was a significant difference in the visual acuities in these groups. The result was the same in younger patients (< seven years of age) as well as in older patients (> seven years of age). In phase 2, the mean proportional improvement in group I was significantly more than that in group II, at two months and onward, at the respective intervals. Conclusion: The improvement in visual acuity with citicoline plus patching was significantly more than that with patching alone, in one year of treatment. PMID:24618483

Pediatric endurance and limb strengthening for children with cerebral palsy (PEDALS) – a randomized controlled trial protocol for a stationary cycling intervention

PubMed Central

Fowler, Eileen G; Knutson, Loretta M; DeMuth, Sharon K; Sugi, Mia; Siebert, Kara; Simms, Victoria; Azen, Stanley P; Winstein, Carolee J

2007-01-01

Background In the past, effortful exercises were considered inappropriate for children with spastic cerebral palsy (CP) due to concern that they would escalate abnormalities including spasticity and abnormal movement patterns. Current scientific evidence indicates that these concerns were unfounded and that therapeutic interventions focused on muscle strengthening can lead to improved functional ability. However, few studies have examined the potential benefits of cardiorespiratory fitness exercises in this patient population. Methods/design The rationale and design of a randomized controlled trial examining the effects of a stationary cycling intervention for children with CP are outlined here. Sixty children with spastic diplegic CP between the ages of 7 and 18 years and Gross Motor Function Classification System (GMFCS) levels of I, II, or III will be recruited for this study. Participants will be randomly assigned to either an intervention (cycling) or a control (no cycling) group. The cycling intervention will be divided into strengthening and cardiorespiratory endurance exercise phases. During the strengthening phase, the resistance to lower extremity cycling will be progressively increased using a uniquely designed limb-loaded mechanism. The cardiorespiratory endurance phase will focus on increasing the intensity and duration of cycling. Children will be encouraged to exercise within a target heart rate (HR) range (70 – 80% maximum HR). Thirty sessions will take place over a 10–12 week period. All children will be evaluated before (baseline) and after (follow-up) the intervention period. Primary outcome measures are: knee joint extensor and flexor moments, or torque; the Gross Motor Function Measure (GMFM); the 600 Yard Walk-Run test and the Thirty-Second Walk test (30 sec WT). Discussion This paper presents the rationale, design and protocol for Pediatric Endurance and Limb Strengthening (PEDALS); a Phase I randomized controlled trial evaluating the efficacy of a stationary cycling intervention for children with spastic diplegic cerebral palsy. PMID:17374171

Effect of Oral Carbohydrate Intake on Labor Progress: Randomized Controlled Trial

PubMed Central

Rahmani, R; Khakbazan, Z; Yavari, P; Granmayeh, M; Yavari, L

2012-01-01

Background Lack of information regarding biochemical changes in women during labor and its outcomes on maternal and neonatal health still is an unanswered question. This study aims to explore the effectiveness of oral carbohydrate intake during labor on the duration of the active phase and other maternal and neonatal outcomes. Methods: A parallel prospective randomized controlled trial, conducted at the University Affiliated Teaching Hospital in Gonabad. Totally, 190 women were randomly assigned to an intervention (N=87) or control (N=90) group. Inclusion criteria were low-risk women with singleton cephalic presentation; and cervical dilatation 3–4 cm. Randomization was used by random number generator on every day. Odd numbers was used for intervention and even numbers for control group. Intervention was based on the preferences between: 3 medium dates plus 110 ml water; 3 dates plus 110 ml light tea without sugar; or 110 ml orange juice. The protocol is only run once but women ate and drank gradually before second stage of labor. Control group were fasted as routine practice. Neither participants nor care givers or staff could be blinded to group allocation. Differences between duration of the active phase of labor were assessed as primary outcome measure. Results: There was significant difference in the length of second stage of labor (P <.05). The effect size for this variable was 0.48. There were no significant differences in other maternal and neonatal outcomes. Conclusions: Oral intake of carbohydrate was an effective method for shortening the duration of second stage of labor in low-risk women. PMID:23304677

Canadian Phase III Randomized Trial of Stereotactic Body Radiotherapy Versus Conventionally Hypofractionated Radiotherapy for Stage I, Medically Inoperable Non-Small-Cell Lung Cancer - Rationale and Protocol Design for the Ontario Clinical Oncology Group (OCOG)-LUSTRE Trial.

PubMed

Swaminath, Anand; Wierzbicki, Marcin; Parpia, Sameer; Wright, James R; Tsakiridis, Theodoros K; Okawara, Gordon S; Kundapur, Vijayananda; Bujold, Alexis; Ahmed, Naseer; Hirmiz, Khalid; Kurien, Elizabeth; Filion, Edith; Gabos, Zsolt; Faria, Sergio; Louie, Alexander V; Owen, Timothy; Wai, Elaine; Ramchandar, Kevin; Chan, Elisa K; Julian, Jim; Cline, Kathryn; Whelan, Timothy J

2017-03-01

We describe a Canadian phase III randomized controlled trial of stereotactic body radiotherapy (SBRT) versus conventionally hypofractionated radiotherapy (CRT) for the treatment of stage I medically inoperable non-small-cell lung cancer (OCOG-LUSTRE Trial). Eligible patients are randomized in a 2:1 fashion to either SBRT (48 Gy in 4 fractions for peripherally located lesions; 60 Gy in 8 fractions for centrally located lesions) or CRT (60 Gy in 15 fractions). The primary outcome of the study is 3-year local control, which we hypothesize will improve from 75% with CRT to 87.5% with SBRT. With 85% power to detect a difference of this magnitude (hazard ratio = 0.46), a 2-sided α = 0.05 and a 2:1 randomization, we require a sample size of 324 patients (216 SBRT, 108 CRT). Important secondary outcomes include overall survival, disease-free survival, toxicity, radiation-related treatment death, quality of life, and cost-effectiveness. A robust radiation therapy quality assurance program has been established to assure consistent and high quality SBRT and CRT delivery. Despite widespread interest and adoption of SBRT, there still remains a concern regarding long-term control and risks of toxicity (particularly in patients with centrally located lesions). The OCOG-LUSTRE study is the only randomized phase III trial testing SBRT in a medically inoperable population, and the results of this trial will attempt to prove that the benefits of SBRT outweigh the potential risks. Copyright © 2016 Elsevier Inc. All rights reserved.

Tapering off long-term opioid therapy in chronic non-cancer pain patients: a randomized clinical trial.

PubMed

Kurita, Geana Paula; Højsted, Jette; Sjøgren, Per

2018-05-13

The indications for initiating long-term opioid treatment (L-TOT) for chronic non-cancer pain (CNCP) are often unclear and associated with problematic use. This study aimed at evaluating the efficacy of stabilizing opioid therapy followed by a sequential opioid tapering off program in CNCP patients. A randomized clinical trial with a medications stabilization period (Phase 1) followed by a opioid tapering off program (Phase 2). In Phase 2, patients were randomized to Control Group (stable treatment) or Taper off Group (sequential opioid dose reduction) and assessed at baseline, after stabilization and up to six months. Primary outcomes: measures of cognitive function; secondary outcomes: pain, sleep, rest, quality of life, depression, anxiety, opioid misuse, and opioid withdrawal symptoms. Two hundred seventy-four patients were screened; 75 were included, out of which 40 dropped out before Phase 2. Those who succeeded Phase 1 (n=35) had weak/moderate improvements of psychomotor function (p=0.020), sleeping hours (p=0.031), opioid withdrawal symptoms (p=0.019), measures of quality of life (p≤0.043) and opioid misuse scores (p=0.003). In Phase 2, patients in Taper off Group (n=15) experienced stable pain intensity and felt significantly more rested at third assessment than the Control Group (n=20). The opioid tapering off program was not successful due to the vast number of dropouts. Phase 1 was associated with weak to moderate improvements on psychomotor function, sleeping, opioid withdrawal symptoms, quality of life, and reduced risk of opioid misuse. In the intervention group of Phase 2, pain intensity was stable and patients felt more rested. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Regular and Random Components in Aiming-Point Trajectory During Rifle Aiming and Shooting

PubMed Central

Goodman, Simon; Haufler, Amy; Shim, Jae Kun; Hatfield, Bradley

2009-01-01

The authors examined the kinematic qualities of the aiming trajectory as related to expertise. In all, 2 phases of the trajectory were discriminated. The first phase was regular approximation to the target accompanied by substantial fluctuations obeying the Weber–Fechner law. During the first phase, shooters did not initiate the triggering despite any random closeness of the aiming point (AP) to the target. In the second phase, beginning at 0.6–0.8 s before the trigger pull, shooters applied a different control strategy: They waited until the following random fluctuation brought the AP closer to the target and then initiated triggering. This strategy is tenable when sensitivity of perception is greater than precision of the motor action, and could be considered a case of stochastic resonance. The strategies that novices and experts used distinguished only in the values of parameters. The authors present an analytical model explaining the main properties of shooting. PMID:19508963

Efficacy and safety of rifaximin in Japanese patients with hepatic encephalopathy: A phase II/III, multicenter, randomized, evaluator-blinded, active-controlled trial and a phase III, multicenter, open trial.

PubMed

Suzuki, Kazuyuki; Endo, Ryujin; Takikawa, Yasuhiro; Moriyasu, Fuminori; Aoyagi, Yutaka; Moriwaki, Hisataka; Terai, Shuji; Sakaida, Isao; Sakai, Yoshiyuki; Nishiguchi, Shuhei; Ishikawa, Toru; Takagi, Hitoshi; Naganuma, Atsushi; Genda, Takuya; Ichida, Takafumi; Takaguchi, Koichi; Miyazawa, Katsuhiko; Okita, Kiwamu

2018-05-01

The efficacy and safety of rifaximin in the treatment of hepatic encephalopathy (HE) are widely known, but they have not been confirmed in Japanese patients with HE. Thus, two prospective, randomized studies (a phase II/III study and a phase III study) were carried out. Subjects with grade I or II HE and hyperammonemia were enrolled. The phase II/III study, which was a randomized, evaluator-blinded, active-comparator, parallel-group study, was undertaken at 37 institutions in Japan. Treatment periods were 14 days. Eligible patients were randomized to the rifaximin group (1200 mg/day) or the lactitol group (18-36 g/day). The phase III study was carried out in the same patients previously enrolled in the phase II/III study, and they were all treated with rifaximin (1200 mg/day) for 10 weeks. In the phase II/III study, 172 patients were enrolled. Blood ammonia (B-NH 3 ) concentration was significantly improved in the rifaximin group, but the difference between the two groups was not significant. The portal systemic encephalopathy index (PSE index), including HE grade, was significantly improved in both groups. In the phase III study, 87.3% of enrolled patients completed the treatment. The improved B-NH 3 concentration and PSE index were well maintained from the phase II/III study during the treatment period of the phase III study. Adverse drug reactions (ADRs) were seen in 13.4% of patients who received rifaximin, but there were no severe ADRs leading to death. The efficacy of rifaximin is sufficient and treatment is well tolerated in Japanese patients with HE and hyperammonemia. © 2017 The Japan Society of Hepatology.

Ethinylestradiol 20 μg/drospirenone 3 mg in a flexible extended regimen for the management of endometriosis-associated pelvic pain: a randomized controlled trial.

PubMed

Harada, Tasuku; Kosaka, Saori; Elliesen, Joerg; Yasuda, Masanobu; Ito, Makoto; Momoeda, Mikio

2017-11-01

To investigate the efficacy and safety of ethinylestradiol 20 μg/drospirenone 3 mg in a flexible extended regimen (Flexible MIB ) compared with placebo to treat endometriosis-associated pelvic pain (EAPP). A phase 3, randomized, double-blind, placebo-controlled, parallel-group study, consisting of a 24-week double-blind treatment phase followed by a 28-week open-label extension phase with an unblinded reference arm. Thirty-two centers. A total of 312 patients with endometriosis. Patients were randomized to Flexible MIB , placebo, or dienogest. The Flexible MIB and placebo arms received 1 tablet per day continuously for 120 days, with a 4-day tablet-free interval either after 120 days or after ≥3 consecutive days of spotting and/or bleeding on days 25-120. After 24 weeks, placebo recipients were changed to Flexible MIB . Patients randomized to dienogest received 2 mg/d for 52 weeks in an unblinded reference arm. Absolute change in the most severe EAPP based on visual analog scale scores from the baseline observation phase to the end of the double-blind treatment phase. Compared with placebo, Flexible MIB significantly reduced the most severe EAPP (mean difference in visual analog scale score: -26.3 mm). Flexible MIB also improved other endometriosis-associated pain and gynecologic findings and reduced the size of endometriomas. Flexible MIB improved EAPP and was well tolerated, suggesting it may be a new alternative for managing endometriosis. NCT01697111. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

A single-blinded, randomized, parallel group superiority trial investigating the effects of footwear and custom foot orthoses versus footwear alone in individuals with patellofemoral joint osteoarthritis: a phase II pilot trial protocol.

PubMed

Wyndow, Narelle; Crossley, Kay M; Vicenzino, Bill; Tucker, Kylie; Collins, Natalie J

2017-01-01

Patellofemoral joint osteoarthritis is a common condition, yet information regarding conservative management is lacking. Foot orthoses are an effective intervention for improving pain and function in younger individuals with patellofemoral pain and may be effective in those with patellofemoral osteoarthritis. This pilot study will seek to establish the feasibility of a phase III randomised controlled trial to investigate whether foot orthoses worn in prescribed motion controlled footwear are superior to prescribed motion control footwear alone in the management of patellofemoral osteoarthritis. This phase II pilot clinical trial is designed as a randomized, single-blind, parallel group, two arm, superiority trial. The trial will recruit 44 participants from Queensland and Tasmania, Australia. Volunteers aged 40 years and over must have clinical symptoms and radiographic evidence of patellofemoral osteoarthritis to be eligible for inclusion. Those eligible will be randomized to receive either foot orthoses and prescribed motion control shoes, or prescribed motion control shoes alone, to be worn for a period of 4 months. The feasibility of a phase III clinical trial will be evaluated by assessing factors such as recruitment rate, number of eligible participants, participant compliance with the study protocol, adverse events, and drop-out rate. A secondary aim of the study will be to determine completion rates and calculate effect sizes for patient reported outcome measures such as knee-related symptoms, function, quality of life, kinesiophobia, self-efficacy, general and mental health, and physical activity at 2 and 4 months. Primary outcomes will be reported descriptively while effect sizes and 95% confidence intervals will be calculated for the secondary outcome measures. Data will be analysed using an intention-to-treat principle. The results of this pilot trial will help determine the feasibility of a phase III clinical trial investigating whether foot orthoses plus motion control footwear are superior to motion control footwear alone in individuals with patellofemoral osteoarthritis. A Phase III clinical trial will help guide footwear and foot orthoses recommendations in the clinical management of this disorder. Retrospectively registered with the Australian New Zealand Clinical Trials Registry: ACTRN12615000002583. Date registered: 07/01/15.

Investigator-reported efficacy of azelaic acid foam 15% in patients with papulopustular rosacea: secondary efficacy outcomes from a randomized, controlled, double-blind, phase 3 trial.

PubMed

Solomon, James A; Tyring, Stephen; Staedtler, Gerald; Sand, Meike; Nkulikiyinka, Richard; Shakery, Kaweh

2016-09-01

Papulopustular rosacea (PPR) is characterized by centrofacial papules and pustules commonly associated with erythema. To compare investigator-reported efficacy outcomes for azelaic acid (AzA) foam 15% versus vehicle foam in PPR, a randomized, vehicle-controlled, double-blind phase 3 clinical trial was conducted at 48 US sites. Participants received AzA foam or vehicle foam for 12 weeks. Secondary efficacy outcomes included change in inflammatory lesion count (ILC), therapeutic response rate according to investigator global assessment (IGA), and change in erythema rating. This study was comprised of 961 participants with PPR. The results support the therapeutic superiority of AzA foam over vehicle foam.

Metadisorder for designer light in random systems

PubMed Central

Yu, Sunkyu; Piao, Xianji; Hong, Jiho; Park, Namkyoo

2016-01-01

Disorder plays a critical role in signal transport by controlling the correlation of a system, as demonstrated in various complex networks. In wave physics, disordered potentials suppress wave transport, because of their localized eigenstates, from the interference between multiple scattering paths. Although the variation of localization with tunable disorder has been intensively studied as a bridge between ordered and disordered media, the general trend of disorder-enhanced localization has remained unchanged, and the existence of complete delocalization in highly disordered potentials has not been explored. We propose the concept of “metadisorder”: randomly coupled optical systems in which eigenstates can be engineered to achieve unusual localization. We demonstrate that one of the eigenstates in a randomly coupled system can always be arbitrarily molded, regardless of the degree of disorder, by adjusting the self-energy of each element. Ordered waves with the desired form are then achieved in randomly coupled systems, including plane waves and globally collective resonances. We also devise counterintuitive functionalities in disordered systems, such as “small-world–like” transport from non–Anderson-type localization, phase-conserving disorder, and phase-controlled beam steering. PMID:27757414

Aprepitant as an add-on therapy in children receiving highly emetogenic chemotherapy: a randomized, double-blind, placebo-controlled trial.

PubMed

Bakhshi, Sameer; Batra, Atul; Biswas, Bivas; Dhawan, Deepa; Paul, Reeja; Sreenivas, Vishnubhatla

2015-11-01

Aprepitant, a neurokinin-1 receptor antagonist, in combination with 5 HT-3 antagonist and dexamethasone is recommended in adults receiving moderately and highly emetogenic chemotherapy to reduce chemotherapy-induced vomiting (CIV). Data for use of aprepitant in children is limited and hence aprepitant is not recommended by Pediatric Oncology Group of Ontario guidelines for prevention of CIV in children <12 years. A randomized, double-blind, placebo-controlled trial was conducted at a single center in chemotherapy naïve children (5-18 years) receiving highly emetogenic chemotherapy. All patients received intravenous ondansetron (0.15 mg/kg) and dexamethasone (0.15 mg/kg) prior to chemotherapy followed by oral ondansetron and dexamethasone. Patients randomly assigned to aprepitant arm received oral aprepitant (15-40 kg = days 1-3, 80 mg; 41-65 kg = day 1, 125 mg and days 2-3, 80 mg) 1 h before chemotherapy. Control group received placebo as add-on therapy. Primary outcome measure was the incidence of acute moderate to severe vomiting, which was defined as more than two vomiting episodes within 24 h after the administration of the first chemotherapy dose until 24 h after the last chemotherapy dose in the block. Complete response (CR) was defined as absence of vomiting and retching during the specified phase. Of the 96 randomized patients, three were excluded from analysis; 93 patients were analyzed (50 in aprepitant arm and 43 in placebo arm). Acute moderate and severe vomiting was reported in 72 % patients receiving placebo and 38 % patients receiving aprepitant (p = 0.001). Complete response rates during acute phase were significantly higher in aprepitant arm (48 vs. 12 %, p < 0.001). No major adverse effects were reported by patients/guardians. This double-blind, randomized, placebo-controlled trial shows that aprepitant significantly decreases the incidence of CIV during acute phase when used as an add-on drug with ondansetron and dexamethasone in children receiving highly emetogenic chemotherapy.

Familias Unidas for high risk adolescents: Study design of a cultural adaptation and randomized controlled trial of a U.S. drug and sexual risk behavior intervention in Ecuador.

PubMed

Jacobs, Petra; Estrada, Yannine A; Tapia, Maria I; Quevedo Terán, Ana M; Condo Tamayo, Cecilia; Albán García, Mónica; Valenzuela Triviño, Gilda M; Pantin, Hilda; Velazquez, Maria R; Horigian, Viviana E; Alonso, Elizabeth; Prado, Guillermo

2016-03-01

Developing, testing and implementing evidence-based prevention interventions are important in decreasing substance use and sexual risk behavior among adolescents. This process requires research expertise, infrastructure, resources and decades of research testing, which might not always be feasible for low resource countries. Adapting and testing interventions proven to be efficacious in similar cultures might circumvent the time and costs of implementing evidence-based interventions in new settings. This paper describes the two-phase study, including training and development of the research infrastructure in the Ecuadorian university necessary to implement a randomized controlled trial. Familias Unidas is a multilevel parent-centered intervention designed in the U.S. to prevent drug use and sexual risk behaviors in Hispanic adolescents. The current study consisted of Phase 1 feasibility study (n=38) which adapted the intervention and study procedures within a single-site school setting in an area with a high prevalence of drug use and unprotected sexual behavior among adolescents in Ecuador, and Phase 2 randomized controlled trial of the adapted intervention in two public high schools with a target population of families with adolescents from 12 to 14 years old. The trial is currently in Phase 2. Study recruitment was completed with 239 parent-youth dyads enrolling. The intervention phase and the first follow-up assessment have been completed. The second and third follow-up assessments will be completed in 2016. This project has the potential of benefitting a large population of families in areas of Ecuador that are disproportionally affected by drug trafficking and its consequences. MSP-DIS-2015-0055-0, Ministry of Public Health (MSP), Quito, Ecuador. Copyright © 2016 Elsevier Inc. All rights reserved.

Measuring Outcomes of Digital Technology-Assisted Nursing Postpartum: A Randomized Controlled Trial.

PubMed

Mccarter, Deborah E; Demidenko, Eugene; Hegel, Mark T

2018-05-17

To determine if delivering electronic messages from nurses during the first six months postpartum is feasible, acceptable and effective in improving mood and decreasing parenting stress. Competing demands during the postpartum hospitalization make focused time for nurses to provide education and support difficult. Unmet needs following discharge may increase the incidence of postpartum depression. Untreated depression negatively affects families, especially for vulnerable women with limited access to health care. This is a longitudinal cohort study in three phases. Feasibility and acceptability were assessed during Phases 1 & 2. Phase 3 is a randomized controlled trial (RCT) with three conditions. This protocol was approved by the Institutional Review Board of the maternity hospital on 12 May 2015 and reviewed annually. Women are enrolled during the maternity hospitalization, after which randomization occurs. The control group receives usual care. Intervention I participants receive a standardized electronic message four times/week for six months postpartum. Intervention II participants receive the messages and the option to request a call from a nurse. Electronic surveys at 3 weeks, 3 months and 6 months postpartum measure depressive symptoms using the Edinburgh Postnatal Depression Scale and parenting stress using the Parenting Stress Index-Short form. Patient satisfaction, nursing time and expertise required are also measured. Phase 1 and 2 have demonstrated the intervention is feasible and acceptable to women. Phase 3 enrollment is completed, and the last follow-up surveys were emailed to participants in February 2018. Results will help inform efforts to continue nursing care after hospital discharge. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Efficacy and safety of aprepitant for the prevention of chemotherapy-induced nausea and vomiting during the first cycle of moderately emetogenic chemotherapy in Korean patients with a broad range of tumor types.

PubMed

Kim, Jeong Eun; Jang, Joung-Soon; Kim, Jae-Weon; Sung, Yong Lee; Cho, Chi-Heum; Lee, Myung-Ah; Kim, Do-Jin; Ahn, Myung-Ju; Lee, Kil Yeon; Sym, Sun Jin; Lim, Myong Choel; Jung, Hun; Cho, Eun Kim; Min, Kyung Wan

2017-03-01

This study evaluated the efficacy and safety of a 3-day aprepitant regimen for the prevention of chemotherapy-induced nausea and vomiting (CINV) during the first cycle of non-anthracycline plus cyclophosphamide (AC)-based moderately emetogenic chemotherapy (MEC) based on government guidelines in Korean patients. This multicenter, randomized, double-blind, phase IV trial (NCT01636947) enrolled adult South Korean patients with a broad range of tumor types who were scheduled to receive a single dose of ≥1 MEC agent. Patients were randomized to a 3-day regimen of aprepitant (aprepitant regimen) or placebo (control regimen) on top of ondansetron plus dexamethasone. The primary and key secondary efficacy endpoints were the proportions of subjects who achieved no vomiting and complete response (CR) during the overall phase. Of the 494 randomized subjects, 480 were included in the modified intent-to-treat population. Response rates for no vomiting and CR in the overall phase were numerically higher for the aprepitant regimen compared with the control regimen groups, but failed to reach statistical significance (no vomiting 77.2 vs 72.0%; p = 0.191; CR 73.4 vs 70.4%; p = 0.458). Both the aprepitant and control regimens were generally well tolerated. A 3-day aprepitant regimen was numerically better but not statistically superior to a control regimen with respect to the achievement of no vomiting or CR during the overall phase in a non-AC MEC Korean population based on government reimbursement guidelines. ClinicalTrials.gov NCT01636947 ( https://clinicaltrials.Gov/ct2/show/NCT01636947 ).

Pasireotide treatment significantly improves clinical signs and symptoms in patients with Cushing's disease: results from a Phase III study.

PubMed

Pivonello, Rosario; Petersenn, Stephan; Newell-Price, John; Findling, James W; Gu, Feng; Maldonado, Mario; Trovato, Andrew; Hughes, Gareth; Salgado, Luiz R; Lacroix, André; Schopohl, Jochen; Biller, Beverly M K

2014-09-01

Signs and symptoms of Cushing's disease are associated with high burden of illness. In this analysis, we evaluated the effect of pasireotide treatment on signs and symptoms in patients with Cushing's disease. Phase III study with double-blind randomization of two pasireotide doses. Patients (n = 162) with persistent/recurrent or de novo Cushing's disease and urinary free cortisol (UFC) levels ≥1·5× upper limit of normal (ULN) were randomized to receive subcutaneous pasireotide (600/900 μg bid). At month 3, patients with UFC ≤2 × ULN and not exceeding the baseline value continued their randomized dose; all others received 300 μg bid uptitration. At month 6, patients could enter an open-label phase until month 12 with a maximal dose of 1200 μg bid. Changes in signs and symptoms of hypercortisolism over 12 months' treatment in patients still enroled in the study and with evaluable measurements were assessed in relation to degree of UFC control. Reductions in blood pressure were observed even without full UFC control and were greatest in patients who did not receive antihypertensive medications during the study. Significant reductions in total cholesterol and low-density lipoprotein (LDL)-cholesterol were observed in patients who achieved UFC control. Reductions in BMI, weight and waist circumference occurred during the study even without full UFC control. Adverse effects were typical of somatostatin analogues except for hyperglycaemia-related events, which were experienced by 72·8% of patients. In the largest Phase III study of medical therapy in Cushing's disease, significant improvements in signs and symptoms were seen during 12 months of pasireotide treatment, as UFC levels decreased. © 2014 John Wiley & Sons Ltd.

Development of control systems for space shuttle vehicles. Volume 2: Appendixes

NASA Technical Reports Server (NTRS)

Stone, C. R.; Chase, T. W.; Kiziloz, B. M.; Ward, M. D.

1971-01-01

A launch phase random normal wind model is presented for delta wing, two-stage, space shuttle control system studies. Equations, data, and simulations for conventional launch studies are given as well as pitch and lateral equations and data for covariance analyses of the launch phase of MSFC vehicle B. Lateral equations and data for North American 130G and 134D are also included along with a high-altitude abort simulation.

Does maintenance CBT contribute to long-term treatment response of panic disorder with or without agoraphobia? A randomized controlled clinical trial.

PubMed

White, Kamila S; Payne, Laura A; Gorman, Jack M; Shear, M Katherine; Woods, Scott W; Saksa, John R; Barlow, David H

2013-02-01

We examined the possibility that maintenance cognitive behavior therapy (M-CBT) may improve the likelihood of sustained improvement and reduced relapse in a multi-site randomized controlled clinical trial of patients who met criteria for panic disorder with or without agoraphobia. Participants were all patients (N = 379) who first began an open trial of acute-phase CBT. Patients completing and responding to acute-phase treatment were randomized to receive either 9 monthly sessions of M-CBT (n = 79) or assessment only (n = 78) and were then followed for an additional 12 months without treatment. M-CBT produced significantly lower relapse rates (5.2%) and reduced work and social impairment compared to the assessment only condition (18.4%) at a 21-month follow-up. Multivariate Cox proportional hazards models showed that residual symptoms of agoraphobia at the end of acute-phase treatment were independently predictive of time to relapse during 21-month follow-up (hazards ratio = 1.15, p < .01). M-CBT aimed at reinforcing acute treatment gains to prevent relapse and offset disorder recurrence may improve long-term outcome for panic disorder with and without agoraphobia.

Does Maintenance CBT Contribute to Long-Term Treatment Response of Panic Disorder With or Without Agoraphobia? A Randomized Controlled Clinical Trial

PubMed Central

White, Kamila S.; Payne, Laura A.; Gorman, Jack M.; Shear, M. Katherine; Woods, Scott W.; Saksa, John R.; Barlow, David H.

2012-01-01

Objective To examine the possibility that maintenance cognitive behavior therapy (M–CBT) may improve the likelihood of sustained improvement and reduced relapse in a multi-site randomized controlled clinical trial of patients who met criteria for panic disorder with or without agoraphobia. Method Participants were all patients (N = 379) who first began an open trial of acute-phase CBT. Patients completing and responding to acute-phase treatment were randomized to receive either nine monthly sessions of M-CBT (n = 79) or assessment only (n = 78) and were then followed for an additional 12 months without treatment. Results M–CBT produced significantly lower relapse rates (5.2%) and reduced work and social impairment compared to the assessment only condition (18.4%) at a 21-month follow-up (MFU). Multivariate Cox proportional hazards models showed that residual symptoms of agoraphobia at the end of acute-phase treatment were independently predictive of time to relapse during 21-MFU (HR = 1.15, p < .01). Conclusions M–CBT aimed at reinforcing acute treatment gains to prevent relapse and offset disorder recurrence may improve long-term outcome in PD/A. PMID:23127290

Providing additional money to food-insecure households and its effect on food expenditure: a randomized controlled trial.

PubMed

Smith, Claire; Parnell, Winsome Ruth; Brown, Rachel Clare; Gray, Andrew Robert

2013-08-01

Financial constraint is the underpinning determinant of household food insecurity; however, there has been little research examining the impact that increasing the ‘money available’ to food-insecure households could have on food purchasing. The main objective of the present study was to examine the effect of additional money (in the form of supermarket vouchers) on food expenditure in food-insecure households with children. A parallel randomized controlled trial with a 4-week baseline phase followed by a 4-week intervention phase. Households were randomized to either receive vouchers (coupons) for 4 weeks or a control group that did not receive any vouchers. Dunedin, New Zealand. Low-income households with children ≥ 18 years) reporting food insecurity (n 214). The mean monetary value of the vouchers received by households was $NZ 17?00 per week. The voucher group spent ≥ NZ 15.20 (95% CI 1.46, 28.94) more per week on food during the intervention phase compared with the control group (P50.030). There were no differences in expenditure between the voucher and the control group for the food groups ‘fruit and vegetables’ (mean difference: ≥ NZ 0?46; 95% CI 21.97, 2.89; P50.709), ‘meat and poultry’ (mean difference: ≥ NZ 0.29; 95% CI 23.07, 3.64; P50.866) and ‘dairy’ (mean difference: ≥ NZ 0.82; 95% CI 20.75, 2.42; P50.302). Providing money via supermarket vouchers to food-insecure resulted in an increase in overall expenditure on food.

A double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD oromucosal spray in combination with the existing treatment regimen, in the relief of central neuropathic pain in patients with multiple sclerosis.

PubMed

Langford, R M; Mares, J; Novotna, A; Vachova, M; Novakova, I; Notcutt, W; Ratcliffe, S

2013-04-01

Central neuropathic pain (CNP) occurs in many multiple sclerosis (MS) patients. The provision of adequate pain relief to these patients can very difficult. Here we report the first phase III placebo-controlled study of the efficacy of the endocannabinoid system modulator delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (USAN name, nabiximols; Sativex, GW Pharmaceuticals, Salisbury, Wiltshire, UK), to alleviate CNP. Patients who had failed to gain adequate analgesia from existing medication were treated with THC/CBD spray or placebo as an add-on treatment, in a double-blind manner, for 14 weeks to investigate the efficacy of the medication in MS-induced neuropathic pain. This parallel-group phase of the study was then followed by an 18-week randomized-withdrawal study (14-week open-label treatment period plus a double-blind 4-week randomized-withdrawal phase) to investigate time to treatment failure and show maintenance of efficacy. A total of 339 patients were randomized to phase A (167 received THC/CBD spray and 172 received placebo). Of those who completed phase A, 58 entered the randomized-withdrawal phase. The primary endpoint of responder analysis at the 30 % level at week 14 of phase A of the study was not met, with 50 % of patients on THC/CBD spray classed as responders at the 30 % level compared to 45 % of patients on placebo (p = 0.234). However, an interim analysis at week 10 showed a statistically significant treatment difference in favor of THC/CBD spray at this time point (p = 0.046). During the randomized-withdrawal phase, the primary endpoint of time to treatment failure was statistically significant in favor of THC/CBD spray, with 57 % of patients receiving placebo failing treatment versus 24 % of patients from the THC/CBD spray group (p = 0.04). The mean change from baseline in Pain Numerical Rating Scale (NRS) (p = 0.028) and sleep quality NRS (p = 0.015) scores, both secondary endpoints in phase B, were also statistically significant compared to placebo, with estimated treatment differences of -0.79 and 0.99 points, respectively, in favor of THC/CBD spray treatment. The results of the current investigation were equivocal, with conflicting findings in the two phases of the study. While there were a large proportion of responders to THC/CBD spray treatment during the phase A double-blind period, the primary endpoint was not met due to a similarly large number of placebo responders. In contrast, there was a marked effect in phase B of the study, with an increased time to treatment failure in the THC/CBD spray group compared to placebo. These findings suggest that further studies are required to explore the full potential of THC/CBD spray in these patients.

Randomized Phase II Trial of High-Dose Melatonin and Radiation Therapy for RPA Class 2 Patients With Brain Metastases (RTOG 0119)

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

Berk, Lawrence; Berkey, Brian; Rich, Tyvin

Purpose: To determine if high-dose melatonin for Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) Class 2 patients with brain metastases improved survival over historical controls, and to determine if the time of day melatonin was given affected its toxicity or efficacy. RTOG 0119 was a phase II randomized trial for this group of patients. Methods and Materials: RTOG RPA Class 2 patients with brain metastases were randomized to 20 mg of melatonin, given either in the morning (8-9 AM) or in the evening (8-9 PM). All patients received radiation therapy (30 Gy in 10 fractions) in the afternoon.more » Melatonin was continued until neurologic deterioration or death. The primary endpoint was overall survival time. Neurologic deterioration, as reflected by the Mini-Mental Status Examination, was also measured. Results: Neither of the randomized groups had survival distributions that differed significantly from the historic controls of patients treated with whole-brain radiotherapy. The median survivals of the morning and evening melatonin treatments were 3.4 and 2.8 months, while the RTOG historical control survival was 4.1 months. Conclusions: High-dose melatonin did not show any beneficial effect in this group of patients.« less

Upper-limb robot-assisted therapy in rehabilitation of acute stroke patients: focused review and results of new randomized controlled trial.

PubMed

Masiero, Stefano; Armani, Mario; Rosati, Giulio

2011-01-01

The successful motor rehabilitation of stroke patients requires early intensive and task-specific therapy. A recent Cochrane Review, although based on a limited number of randomized controlled trials (RCTs), showed that early robotic training of the upper limb (i.e., during acute or subacute phase) can enhance motor learning and improve functional abilities more than chronic-phase training. In this article, a new subacute-phase RCT with the Neuro-Rehabilitation-roBot (NeReBot) is presented. While in our first study we used the NeReBot in addition to conventional therapy, in this new trial we used the same device in substitution of standard proximal upper-limb rehabilitation. With this protocol, robot patients achieved similar reductions in motor impairment and enhancements in paretic upper-limb function to those gained by patients in a control group. By analyzing these results and those of previous studies, we hypothesize a new robotic protocol for acute and subacute stroke patients based on both treatment modalities (in addition and in substitution).

A randomized, placebo-controlled trial of controlled release melatonin treatment of delayed sleep phase syndrome and impaired sleep maintenance in children with neurodevelopmental disabilities.

PubMed

Wasdell, Michael B; Jan, James E; Bomben, Melissa M; Freeman, Roger D; Rietveld, Wop J; Tai, Joseph; Hamilton, Donald; Weiss, Margaret D

2008-01-01

The purpose of this study was to determine the efficacy of controlled-release (CR) melatonin in the treatment of delayed sleep phase syndrome and impaired sleep maintenance of children with neurodevelopmental disabilities including autistic spectrum disorders. A randomized double-blind, placebo-controlled crossover trial of CR melatonin (5 mg) followed by a 3-month open-label study was conducted during which the dose was gradually increased until the therapy showed optimal beneficial effects. Sleep characteristics were measured by caregiver who completed somnologs and wrist actigraphs. Clinician rating of severity of the sleep disorder and improvement from baseline, along with caregiver ratings of global functioning and family stress were also obtained. Fifty-one children (age range 2-18 years) who did not respond to sleep hygiene intervention were enrolled. Fifty patients completed the crossover trial and 47 completed the open-label phase. Recordings of total night-time sleep and sleep latency showed significant improvement of approximately 30 min. Similarly, significant improvement was observed in clinician and parent ratings. There was additional improvement in the open-label somnolog measures of sleep efficiency and the longest sleep episode in the open-label phase. Overall, the therapy improved the sleep of 47 children and was effective in reducing family stress. Children with neurodevelopmental disabilities, who had treatment resistant chronic delayed sleep phase syndrome and impaired sleep maintenance, showed improvement in melatonin therapy.

Experimental sleep restriction causes endothelial dysfunction in healthy humans.

PubMed

Calvin, Andrew D; Covassin, Naima; Kremers, Walter K; Adachi, Taro; Macedo, Paula; Albuquerque, Felipe N; Bukartyk, Jan; Davison, Diane E; Levine, James A; Singh, Prachi; Wang, Shihan; Somers, Virend K

2014-11-25

Epidemiologic evidence suggests a link between short sleep duration and cardiovascular risk, although the nature of any relationship and mechanisms remain unclear. Short sleep duration has also been linked to an increase in cardiovascular events. Endothelial dysfunction has itself been implicated as a mediator of heightened cardiovascular risk. We sought to determine the effect of 8 days/8 nights of partial sleep restriction on endothelial function in healthy humans. Sixteen healthy volunteers underwent a randomized study of usual sleep versus sleep restriction of two-thirds normal sleep time for 8 days/8 nights in a hospital-based clinical research unit. The main outcome was endothelial function measured by flow-mediated brachial artery vasodilatation (FMD). Those randomized to sleep restriction slept 5.1 hours/night during the experimental period compared with 6.9 hours/night in the control group. Sleep restriction was associated with significant impairment in FMD (8.6±4.6% during the initial pre-randomization acclimation phase versus 5.2±3.4% during the randomized experimental phase, P=0.01) whereas no change was seen in the control group (5.0±3.0 during the acclimation phase versus 6.73±2.9% during the experimental phase, P=0.10) for a between-groups difference of -4.40% (95% CI -7.00 to -1.81%, P=0.003). No change was seen in non-flow mediated vasodilatation (NFMD) in either group. In healthy individuals, moderate sleep restriction causes endothelial dysfunction. ClinicalTrials.gov. Unique identifier: NCT01334788. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Implementation of treat-to-target in rheumatoid arthritis through a Learning Collaborative: Rationale and design of the TRACTION trial.

PubMed

Solomon, Daniel H; Lee, Sara B; Zak, Agnes; Corrigan, Cassandra; Agosti, Jenifer; Bitton, Asaf; Harrold, Leslie; Losina, Elena; Lu, Bing; Pincus, Ted; Radner, Helga; Smolen, Josef; Katz, Jeffrey N; Fraenkel, Liana

2016-08-01

Treat-to-target (TTT) is a recommended strategy in the management of rheumatoid arthritis (RA), but various data sources suggest that its uptake in routine care in the US is suboptimal. Herein, we describe the design of a randomized controlled trial of a Learning Collaborative to facilitate implementation of TTT. We recruited 11 rheumatology sites from across the US and randomized them into the following two groups: one received the Learning Collaborative intervention in Phase 1 (month 1-9) and the second formed a wait-list control group to receive the intervention in Phase 2 (months 10-18). The Learning Collaborative intervention was designed using the Model for Improvement, consisting of a Change Package with corresponding principles and action phases. Phase 1 intervention practices had nine learning sessions, collaborated using a web-based tool, and shared results of plan-do-study-act cycles and monthly improvement metrics collected at each practice. The wait-list control group sites had no intervention during Phase 1. The primary trial outcome is the implementation of TTT as measured by chart review, comparing the differences from baseline to end of Phase 1, between intervention and control sites. All intervention sites remained engaged in the Learning Collaborative throughout Phase 1, with a total of 38 providers participating. The primary trial outcome measures are currently being collected by the study team through medical record review. If the Learning Collaborative is an effective means for improving implementation of TTT, this strategy could serve as a way of implementing disseminating TTT more widely. Copyright © 2016 Elsevier Inc. All rights reserved.

Clinical feasibility of interactive motion-controlled games for stroke rehabilitation.

PubMed

Bower, Kelly J; Louie, Julie; Landesrocha, Yoseph; Seedy, Paul; Gorelik, Alexandra; Bernhardt, Julie

2015-08-02

Active gaming technologies, including the Nintendo Wii and Xbox Kinect, have become increasingly popular for use in stroke rehabilitation. However, these systems are not specifically designed for this purpose and have limitations. The aim of this study was to investigate the feasibility of using a suite of motion-controlled games in individuals with stroke undergoing rehabilitation. Four games, which utilised a depth-sensing camera (PrimeSense), were developed and tested. The games could be played in a seated or standing position. Three games were controlled by movement of the torso and one by upper limb movement. Phase 1 involved consecutive recruitment of 40 individuals with stroke who were able to sit unsupported. Participants were randomly assigned to trial one game during a single session. Sixteen individuals from Phase 1 were recruited to Phase 2. These participants were randomly assigned to an intervention or control group. Intervention participants performed an additional eight sessions over four weeks using all four game activities. Feasibility was assessed by examining recruitment, adherence, acceptability and safety in both phases of the study. Forty individuals (mean age 63 years) completed Phase 1, with an average session time of 34 min. The majority of Phase 1 participants reported the session to be enjoyable (93 %), helpful (80 %) and something they would like to include in their therapy (88 %). Sixteen individuals (mean age 61 years) took part in Phase 2, with an average of seven 26-min sessions over four weeks. Reported acceptability was high for the intervention group and improvements over time were seen in several functional outcome measures. There were no serious adverse safety events reported in either phase of the study; however, a number of participants reported minor increases in pain. A post-stroke intervention using interactive motion-controlled games shows promise as a feasible and potentially effective treatment approach. This paper presents important recommendations for future game development and research to further explore long-term adherence, acceptability, safety and efficacy. Australian and New Zealand Clinical Trials Registry ( ACTRN12613000220763 ).

Improving practice in community-based settings: a randomized trial of supervision - study protocol.

PubMed

Dorsey, Shannon; Pullmann, Michael D; Deblinger, Esther; Berliner, Lucy; Kerns, Suzanne E; Thompson, Kelly; Unützer, Jürgen; Weisz, John R; Garland, Ann F

2013-08-10

Evidence-based treatments for child mental health problems are not consistently available in public mental health settings. Expanding availability requires workforce training. However, research has demonstrated that training alone is not sufficient for changing provider behavior, suggesting that ongoing intervention-specific supervision or consultation is required. Supervision is notably under-investigated, particularly as provided in public mental health. The degree to which supervision in this setting includes 'gold standard' supervision elements from efficacy trials (e.g., session review, model fidelity, outcome monitoring, skill-building) is unknown. The current federally-funded investigation leverages the Washington State Trauma-focused Cognitive Behavioral Therapy Initiative to describe usual supervision practices and test the impact of systematic implementation of gold standard supervision strategies on treatment fidelity and clinical outcomes. The study has two phases. We will conduct an initial descriptive study (Phase I) of supervision practices within public mental health in Washington State followed by a randomized controlled trial of gold standard supervision strategies (Phase II), with randomization at the clinician level (i.e., supervisors provide both conditions). Study participants will be 35 supervisors and 130 clinicians in community mental health centers. We will enroll one child per clinician in Phase I (N = 130) and three children per clinician in Phase II (N = 390). We use a multi-level mixed within- and between-subjects longitudinal design. Audio recordings of supervision and therapy sessions will be collected and coded throughout both phases. Child outcome data will be collected at the beginning of treatment and at three and six months into treatment. This study will provide insight into how supervisors can optimally support clinicians delivering evidence-based treatments. Phase I will provide descriptive information, currently unavailable in the literature, about commonly used supervision strategies in community mental health. The Phase II randomized controlled trial of gold standard supervision strategies is, to our knowledge, the first experimental study of gold standard supervision strategies in community mental health and will yield needed information about how to leverage supervision to improve clinician fidelity and client outcomes. ClinicalTrials.gov NCT01800266.

Improving practice in community-based settings: a randomized trial of supervision – study protocol

PubMed Central

2013-01-01

Background Evidence-based treatments for child mental health problems are not consistently available in public mental health settings. Expanding availability requires workforce training. However, research has demonstrated that training alone is not sufficient for changing provider behavior, suggesting that ongoing intervention-specific supervision or consultation is required. Supervision is notably under-investigated, particularly as provided in public mental health. The degree to which supervision in this setting includes ‘gold standard’ supervision elements from efficacy trials (e.g., session review, model fidelity, outcome monitoring, skill-building) is unknown. The current federally-funded investigation leverages the Washington State Trauma-focused Cognitive Behavioral Therapy Initiative to describe usual supervision practices and test the impact of systematic implementation of gold standard supervision strategies on treatment fidelity and clinical outcomes. Methods/Design The study has two phases. We will conduct an initial descriptive study (Phase I) of supervision practices within public mental health in Washington State followed by a randomized controlled trial of gold standard supervision strategies (Phase II), with randomization at the clinician level (i.e., supervisors provide both conditions). Study participants will be 35 supervisors and 130 clinicians in community mental health centers. We will enroll one child per clinician in Phase I (N = 130) and three children per clinician in Phase II (N = 390). We use a multi-level mixed within- and between-subjects longitudinal design. Audio recordings of supervision and therapy sessions will be collected and coded throughout both phases. Child outcome data will be collected at the beginning of treatment and at three and six months into treatment. Discussion This study will provide insight into how supervisors can optimally support clinicians delivering evidence-based treatments. Phase I will provide descriptive information, currently unavailable in the literature, about commonly used supervision strategies in community mental health. The Phase II randomized controlled trial of gold standard supervision strategies is, to our knowledge, the first experimental study of gold standard supervision strategies in community mental health and will yield needed information about how to leverage supervision to improve clinician fidelity and client outcomes. Trial registration ClinicalTrials.gov NCT01800266 PMID:23937766

Immunogenicity and safety of the new reduced-dose tetanus-diphtheria vaccine in healthy Korean adolescents: A comparative active control, double-blind, randomized, multicenter phase III study.

PubMed

Han, Seung Beom; Rhim, Jung-Woo; Shin, Hye Jo; Kim, Sang Yong; Kim, Jong-Hyun; Kim, Hyun-Hee; Lee, Kyung-Yil; Kim, Hwang Min; Choi, Young Youn; Ma, Sang Hyuk; Kim, Chun Soo; Kim, Dong Ho; Ahn, Dong Ho; Kang, Jin Han

2017-04-01

A new reduced-dose tetanus-diphtheria (Td) vaccine was developed in Korea, and phase I and II clinical trials were successfully undertaken. We conducted this double-blind, randomized, multicenter phase III clinical trial to assess the immunogenicity and safety of the new Td vaccine. Healthy adolescents 11-12 years of age were enrolled and randomized to receive the new Td vaccine (study group) or a commercially available Td vaccine (control group). Blood samples were collected prior to and 4 weeks after the vaccination. Between the study and control groups, seroprotection rate, booster response, and geometric mean titer of antibodies against diphtheria and tetanus toxoids were compared after the vaccination. All solicited and unsolicited adverse events and serious adverse events during the 6-week study period were monitored. A total of 164 adolescents received vaccination, and 156 of them were evaluated to assess immunogenicity. The seroprotection rate and geometric mean titer for antibodies against diphtheria were significantly higher in the study group, whereas those against tetanus were significantly higher in the control group. However, all seroprotection rates against diphtheria and tetanus in the study and control groups were high: 100% against diphtheria and tetanus in the study group, and 98.7% against diphtheria and 100% against tetanus in the control group. No significant differences in the frequency of solicited and unsolicited adverse events were observed between the two vaccine groups. The new Td vaccine is highly immunogenic and safe, and this new Td vaccine can be effectively used for preventing diphtheria and tetanus. Copyright © 2015. Published by Elsevier B.V.

Improving comprehension in adolescents with severe receptive language impairments: a randomized control trial of intervention for coordinating conjunctions.

PubMed

Ebbels, Susan H; Marić, Nataša; Murphy, Aoife; Turner, Gail

2014-01-01

Little evidence exists for the effectiveness of therapy for children with receptive language difficulties, particularly those whose difficulties are severe and persistent. To establish the effectiveness of explicit speech and language therapy with visual support for secondary school-aged children with language impairments focusing on comprehension of coordinating conjunctions in a randomized control trial with an assessor blind to group status. Fourteen participants (aged 11;3-16;1) with severe RELI (mean standard scores: CELF4 ELS = 48, CELF4 RLS = 53 and TROG-2 = 57), but higher non-verbal (Matrices = 83) and visual perceptual skills (Test of Visual Perceptual Skills (TVPS) = 86) were randomly assigned to two groups: therapy versus waiting controls. In Phase 1, the therapy group received eight 30-min individual sessions of explicit teaching with visual support (Shape Coding) with their usual SLT. In Phase 2, the waiting controls received the same therapy. The participants' comprehension was tested pre-, post-Phase 1 and post-Phase 2 therapy on (1) a specific test of the targeted conjunctions, (2) the TROG-2 and (3) a test of passives. After Phase 1, the therapy group showed significantly more progress than the waiting controls on the targeted conjunctions (d = 1.6) and overall TROG-2 standard score (d = 1.4). The two groups did not differ on the passives test. After Phase 2, the waiting controls made similar progress to those in the original therapy group, who maintained their previous progress. Neither group showed progress on passives. When the two groups were combined, significant progress was found on the specific conjunctions (d = 1.3) and TROG-2 raw (d = 1.1) and standard scores (d = 0.9). Correlations showed no measures taken (including Matrices and TVPS) correlated significantly with progress on the targeted conjunctions or the TROG-2. Four hours of Shape Coding therapy led to significant gains on comprehension of coordinating conjunctions which were maintained after 4 months. Given the significant progress at a group level and the lack of reliable predictors of progress, this approach could be offered to other children with similar difficulties to the participants. However, the intervention was delivered one-to-one by speech and language therapists, thus the effectiveness of this therapy method with other methods of delivery remains to be evaluated. © 2013 Royal College of Speech and Language Therapists.

Evaluation of a simplified modified Atkins diet for use by parents with low levels of literacy in children with refractory epilepsy: A randomized controlled trial.

PubMed

Sharma, Suvasini; Goel, Shaiphali; Jain, Puneet; Agarwala, Anuja; Aneja, Satinder

2016-11-01

This study was planned to develop and evaluate a simple, easy-to-understand variation of the modified Atkins diet, for use by parents with low levels of literacy in children with refractory epilepsy. This study was conducted in two phases. In the first phase, a simplified version of the modified Atkins diet was developed. In the second phase this was evaluated in children aged 2-14 years who had daily seizures despite the appropriate use of at least two anticonvulsant drugs, in an open-label randomized-controlled-trial. Children were randomized to receive either the simplified modified Atkins diet or no dietary intervention for a period of 3 months with the ongoing anticonvulsant medications being continued unchanged in both the groups. Reduction in seizure frequency was the primary outcome-measure. Data was analyzed using intention to treat approach. Adverse effects were also studied. (Clinical trial identifier NCT0189989). Forty-one children were randomly assigned to the diet-group, and 40 were assigned to the control-group. Two patients discontinued the diet during the study period. The proportion of children with>50% seizure reduction was significantly higher in the diet group as compared to the control group (56.1% vs 7.5%, p<0.0001). The proportion of children with 90% seizure reduction was also higher in the diet group (19.5% vs 2%, p=0.09). Six children in the diet group were seizure free at 3 months compared with two in the control group (p=0.26). At 3 months, 6 children had constipation and 5 had weight loss. A simplified version of the modified Atkins diet was developed for use by parents with low levels literacy. This diet was found to be feasible, efficacious and well tolerated in children with refractory epilepsy. Copyright © 2016 Elsevier B.V. All rights reserved.

Random search optimization based on genetic algorithm and discriminant function

NASA Technical Reports Server (NTRS)

Kiciman, M. O.; Akgul, M.; Erarslanoglu, G.

1990-01-01

The general problem of optimization with arbitrary merit and constraint functions, which could be convex, concave, monotonic, or non-monotonic, is treated using stochastic methods. To improve the efficiency of the random search methods, a genetic algorithm for the search phase and a discriminant function for the constraint-control phase were utilized. The validity of the technique is demonstrated by comparing the results to published test problem results. Numerical experimentation indicated that for cases where a quick near optimum solution is desired, a general, user-friendly optimization code can be developed without serious penalties in both total computer time and accuracy.

Correcting Classifiers for Sample Selection Bias in Two-Phase Case-Control Studies

PubMed Central

Theis, Fabian J.

2017-01-01

Epidemiological studies often utilize stratified data in which rare outcomes or exposures are artificially enriched. This design can increase precision in association tests but distorts predictions when applying classifiers on nonstratified data. Several methods correct for this so-called sample selection bias, but their performance remains unclear especially for machine learning classifiers. With an emphasis on two-phase case-control studies, we aim to assess which corrections to perform in which setting and to obtain methods suitable for machine learning techniques, especially the random forest. We propose two new resampling-based methods to resemble the original data and covariance structure: stochastic inverse-probability oversampling and parametric inverse-probability bagging. We compare all techniques for the random forest and other classifiers, both theoretically and on simulated and real data. Empirical results show that the random forest profits from only the parametric inverse-probability bagging proposed by us. For other classifiers, correction is mostly advantageous, and methods perform uniformly. We discuss consequences of inappropriate distribution assumptions and reason for different behaviors between the random forest and other classifiers. In conclusion, we provide guidance for choosing correction methods when training classifiers on biased samples. For random forests, our method outperforms state-of-the-art procedures if distribution assumptions are roughly fulfilled. We provide our implementation in the R package sambia. PMID:29312464

Heart rate variability is enhanced in controls but not maladaptive perfectionists during brief mindfulness meditation following stress-induction: A stratified-randomized trial.

PubMed

Azam, Muhammad Abid; Katz, Joel; Fashler, Samantha R; Changoor, Tina; Azargive, Saam; Ritvo, Paul

2015-10-01

Heart rate variability (HRV) is a vagal nerve-mediated biomarker of cardiac function used to investigate chronic illness, psychopathology, stress and, more recently, attention-regulation processes such as meditation. This study investigated HRV in relation to maladaptive perfectionism, a stress-related personality factor, and mindfulness meditation, a stress coping practice expected to elevate HRV, and thereby promote relaxation. Maladaptive perfectionists (n=21) and Controls (n=39) were exposed to a lab-based assessment in which HRV was measured during (1) a 5-minute baseline resting phase, (2) a 5-minute cognitive stress-induction phase, and (3) a post-stress phase. In the post-stress phase, participants were randomly assigned to a 10-minute audio-instructed mindfulness meditation condition or a 10-minute rest condition with audio-description of mindfulness meditation. Analyses revealed a significant elevation in HRV during meditation for Controls but not for Perfectionists. These results suggest that mindfulness meditation promotes relaxation following cognitive stress and that the perfectionist personality hinders relaxation possibly because of decreased cardiac vagal tone. The results are discussed in the context of developing psychophysiological models to advance therapeutic interventions for distressed populations. Copyright © 2015 Elsevier B.V. All rights reserved.

Bioengineered Temporomandibular Joint Disk Implants: Study Protocol for a Two-Phase Exploratory Randomized Preclinical Pilot Trial in 18 Black Merino Sheep (TEMPOJIMS)

PubMed Central

Monje, Florencio Gil; González-García, Raúl; Little, Christopher B; Mónico, Lisete; Pinho, Mário; Santos, Fábio Abade; Carrapiço, Belmira; Gonçalves, Sandra Cavaco; Morouço, Pedro; Alves, Nuno; Moura, Carla; Wang, Yadong; Jeffries, Eric; Gao, Jin; Sousa, Rita; Neto, Lia Lucas; Caldeira, Daniel; Salvado, Francisco

2017-01-01

Background Preclinical trials are essential to test efficacious options to substitute the temporomandibular joint (TMJ) disk. The contemporary absence of an ideal treatment for patients with severe TMJ disorders can be related to difficulties concerning the appropriate study design to conduct preclinical trials in the TMJ field. These difficulties can be associated with the use of heterogeneous animal models, the use of the contralateral TMJ as control, the absence of rigorous randomized controlled preclinical trials with blinded outcomes assessors, and difficulties involving multidisciplinary teams. Objective This study aims to develop a new, reproducible, and effective study design for preclinical research in the TMJ domain, obtaining rigorous data related to (1) identify the impact of bilateral discectomy in black Merino sheep, (2) identify the impact of bilateral discopexy in black Merino sheep, and (3) identify the impact of three different bioengineering TMJ discs in black Merino sheep. Methods A two-phase exploratory randomized controlled preclinical trial with blinded outcomes is proposed. In the first phase, nine sheep are randomized into three different surgical bilateral procedures: bilateral discectomy, bilateral discopexy, and sham surgery. In the second phase, nine sheep are randomized to bilaterally test three different TMJ bioengineering disk implants. The primary outcome is the histological gradation of TMJ. Secondary outcomes are imaging changes, absolute masticatory time, ruminant time per cycle, ruminant kinetics, ruminant area, and sheep weight. Results Previous preclinical studies in this field have used the contralateral unoperated side as a control, different animal models ranging from mice to a canine model, with nonrandomized, nonblinded and uncontrolled study designs and limited outcomes measures. The main goal of this exploratory preclinical protocol is to set a new standard for future preclinical trials in oromaxillofacial surgery, particularly in the TMJ field, by proposing a rigorous design in black Merino sheep. The authors also intend to test the feasibility of pilot outcomes. The authors expect to increase the quality of further studies in this field and to progress in future treatment options for patients undergoing surgery for TMJ disk replacement. Conclusions The study has commenced, but it is too early to provide results or conclusions. PMID:28254733

Exactly solvable random graph ensemble with extensively many short cycles

NASA Astrophysics Data System (ADS)

Aguirre López, Fabián; Barucca, Paolo; Fekom, Mathilde; Coolen, Anthony C. C.

2018-02-01

We introduce and analyse ensembles of 2-regular random graphs with a tuneable distribution of short cycles. The phenomenology of these graphs depends critically on the scaling of the ensembles’ control parameters relative to the number of nodes. A phase diagram is presented, showing a second order phase transition from a connected to a disconnected phase. We study both the canonical formulation, where the size is large but fixed, and the grand canonical formulation, where the size is sampled from a discrete distribution, and show their equivalence in the thermodynamical limit. We also compute analytically the spectral density, which consists of a discrete set of isolated eigenvalues, representing short cycles, and a continuous part, representing cycles of diverging size.

A phase 1, randomized, controlled dose-escalation study of EP-1300 polyepitope DNA vaccine against Plasmodium falciparum malaria administered via electroporation.

PubMed

Spearman, Paul; Mulligan, Mark; Anderson, Evan J; Shane, Andi L; Stephens, Kathy; Gibson, Theda; Hartwell, Brooke; Hannaman, Drew; Watson, Nora L; Singh, Karnail

2016-11-04

Plasmodium falciparum malaria is one of the leading infectious causes of childhood mortality in Africa. EP-1300 is a polyepitope plasmid DNA vaccine expressing 38 cytotoxic T cell epitopes and 16 helper T cell epitopes derived from P. falciparum antigens expressed predominantly in the liver phase of the parasite's life cycle. We performed a phase 1 randomized, placebo-controlled, dose escalation clinical trial of the EP-1300 DNA vaccine administered via electroporation using the TriGrid Delivery System device (Ichor Medical Systems). Although the delivery of the EP-1300 DNA vaccine via electroporation was safe, tolerability was less than that usually observed with standard needle and syringe intramuscular administration. This was primarily due to acute local discomfort at the administration site during electroporation. Despite the use of electroporation, the vaccine was poorly immunogenic. The reasons for the poor immunogenicity of this polyepitope DNA vaccine remain uncertain. ClinicalTrials.gov NCT01169077. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Mixed-Methods, Randomized, Controlled Feasibility Trial to Inform the Design of a Phase III Trial to Test the Effect of the Handheld Fan on Physical Activity and Carer Anxiety in Patients With Refractory Breathlessness.

PubMed

Johnson, Miriam J; Booth, Sara; Currow, David C; Lam, Lawrence T; Phillips, Jane L

2016-05-01

The handheld fan is an inexpensive and safe way to provide facial airflow, which may reduce the sensation of chronic refractory breathlessness, a frequently encountered symptom. To test the feasibility of developing an adequately powered, multicenter, multinational randomized controlled trial comparing the efficacy of a handheld fan and exercise advice with advice alone in increasing activity in people with chronic refractory breathlessness from a variety of medical conditions, measuring recruitment rates; data quality; and potential primary outcome measures. This was a Phase II, multisite, international, parallel, nonblinded, mixed-methods randomized controlled trial. Participants were centrally randomized to fan or control. All received breathlessness self-management/exercise advice and were followed up weekly for four weeks. Participants/carers were invited to participate in a semistructured interview at the study's conclusion. Ninety-seven people were screened, 49 randomized (mean age 68 years; 49% men), and 43 completed the study. Site recruitment varied from 0.25 to 3.3/month and screening:randomization from 1.1:1 to 8.5:1. There were few missing data except for the Chronic Obstructive Pulmonary Disease Self-Efficacy Scale (two-thirds of data missing). No harms were observed. Three interview themes included 1) a fan is a helpful self-management strategy, 2) a fan aids recovery, and 3) a symptom control trial was welcome. A definitive, multisite trial to study the use of the handheld fan as part of self-management of chronic refractory breathlessness is feasible. Participants found the fan useful. However, the value of information for changing practice or policy is unlikely to justify the expense of such a trial, given perceived benefits, the minimal costs, and an absence of harms demonstrated in this study. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Comparative Efficacy and Durability of Continuation Phase Cognitive Therapy for Preventing Recurrent Depression: Design of a Double-Blinded, Fluoxetine- and Pill-Placebo–Controlled, Randomized Trial with 2-Year Follow-up

PubMed Central

Thase, Michael E.

2010-01-01

Background Major depressive disorder (MDD) is highly prevalent and associated with disability and chronicity. Although cognitive therapy (CT) is an effective short-term treatment for MDD, a significant proportion of responders subsequently suffer relapses or recurrences. Purpose This design prospectively evaluates: 1) a method to discriminate CT-treated responders at lower versus higher risk for relapse; and 2) the subsequent durability of 8-month continuation phase therapies in randomized higher risk responders followed for an additional 24-months. The primary prediction is: after protocol treatments are stopped, higher risk patients randomly assigned to continuation phase CT (C-CT) will have a lower risk of relapse/recurrence than those randomized to fluoxetine (FLX). Methods Outpatients, aged 18 to 70 years, with recurrent MDD received 12–14 weeks of CT provided by 15 experienced therapists from two sites. Responders (i.e., no MDD and 17-item Hamilton Rating Scale for Depression ≤ 12) were stratified into higher and lower risk groups based on stability of remission during the last 6 weeks of CT. The lower risk group entered follow-up for 32 months; the higher risk group was randomized to 8 months of continuation phase therapy with either C-CT or clinical management plus either double-blinded FLX or pill placebo. Following the continuation phase, higher risk patients were followed by blinded evaluators for 24 months. Results The trial began in 2000. Enrollment is complete (N=523). The follow-up continues. Conclusions The trial evaluates the preventive effects and durability of acute and continuation phase treatments in the largest known sample of CT responders collected worldwide. PMID:20451668

Pilot randomized controlled trial of dialectical behavior therapy group skills training for ADHD among college students.

PubMed

Fleming, Andrew P; McMahon, Robert J; Moran, Lyndsey R; Peterson, A Paige; Dreessen, Anthony

2015-03-01

ADHD affects between 2% and 8% of college students and is associated with broad functional impairment. No prior randomized controlled trials with this population have been published. The present study is a pilot randomized controlled trial evaluating dialectical behavior therapy (DBT) group skills training adapted for college students with ADHD. Thirty-three undergraduates with ADHD between ages 18 and 24 were randomized to receive either DBT group skills training or skills handouts during an 8-week intervention phase. ADHD symptoms, executive functioning (EF), and related outcomes were assessed at baseline, post-treatment, and 3-month follow-up. Participants receiving DBT group skills training showed greater treatment response rates (59-65% vs. 19-25%) and clinical recovery rates (53-59% vs. 6-13%) on ADHD symptoms and EF, and greater improvements in quality of life. DBT group skills training may be efficacious, acceptable, and feasible for treating ADHD among college students. A larger randomized trial is needed for further evaluation. © 2014 SAGE Publications.

A randomized trial to evaluate the effect of a trace mineral premix on the incidence of active digital dermatitis lesions in cattle.

PubMed

Gomez, A; Bernardoni, N; Rieman, J; Dusick, A; Hartshorn, R; Read, D H; Socha, M T; Cook, N B; Döpfer, D

2014-10-01

A balanced, parallel-group, single-blinded randomized efficacy study divided into 2 periods was conducted to evaluate the effect of a premix containing higher than typically recommended levels of organic trace minerals and iodine (HOTMI) in reducing the incidence of active digital dermatitis (DD) lesions acquired naturally and induced by an experimental infection challenge model. For the natural exposure phase of the study, 120 healthy Holstein steers 5 to 7 mo of age without signs of hoof disease were randomized into 2 groups of 60 animals. The control group was fed a standard trace mineral supplement and the treatment group was fed the HOTMI premix, both for a period of 60 d. On d 60, 15 steers free of macroscopic DD lesions were randomly selected from each group for the challenge phase and transported to an experimental facility, where they were acclimated and then challenged within a DD infection model. The same diet group allocation was maintained during the 60 d of the challenge phase. The primary outcome measured was the development of an active DD lesion greater than 20mm in diameter across its largest dimension. No lesions were identified during the natural exposure phase. During the challenge phase, 55% (11/20) and 30% (6/20) of feet were diagnosed with an active DD lesion in the control and treatment groups, respectively. Diagnosis of DD was confirmed by histopathologic demonstration of invasive Treponema spp. within eroded and hyperplastic epidermis and ulcerated papillary dermis. All DD confirmed lesions had dark-field microscopic features compatible with DD and were positive for Treponema spp. by PCR. As a secondary outcome, the average DD lesion size observed in all feet was also evaluated. Overall mean (standard deviation) lesion size was 17.1 (2.36) mm and 11.1 (3.33) mm for the control and treatment groups, respectively, with this difference being driven by acute DD lesions >20mm. A trend existed for the HOTMI premix to reduce the total DD infection rate and the average size of the experimentally induced lesions. Further research is needed to validate the effect of this intervention strategy in the field and to generate prevention and control measures aimed at optimizing claw health based on nutritional programs. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Impact of nursing interventions on adherence to treatment with antituberculosis drugs in children and young people: A non-randomized controlled trial.

PubMed

Guix-Comellas, Eva Maria; Rozas-Quesada, Librada; Velasco-Arnaiz, Eneritz; Ferres-Canals, Ariadna; Estrada-Masllorens, Joan Maria; Force-Sanmartín, Enriqueta; Noguera-Julian, Antoni

2018-05-03

To evaluate the association of a new nursing intervention on the adherence to antituberculosis treatment in a pediatric cohort (<18 years). Tuberculosis remains a public health problem worldwide. The risk of developing tuberculosis after primary infection and its severity are higher in children. Proper adherence to antituberculosis treatment is critical for disease control. Non-randomized controlled trial; Phase 1, retrospective (2011-2013), compared with Phase 2, prospective with intervention (2015-2016), in a referral center for pediatric tuberculosis in Spain (NCT03230409). A total of 359 patients who received antituberculosis drugs after close contact with a smear-positive patient (primary chemoprophylaxis) or were treated for latent tuberculosis infection or tuberculosis disease were included, 261 in Phase 1 and 98 in Phase 2. In phase 2, a new nurse-led intervention was implemented in all patients and included two educational steps (written information in the child's native language and follow-up telephone calls) and two monitoring steps (Eidus-Hamilton test and follow-up questionnaire) that were exclusively carried out by nurses. Adherence to antituberculosis treatment increased from 74.7% in Phase 1 to 87.8% in Phase 2 (p=0.014; Chi-square test), after the implementation of the nurse-led intervention. In Phase 2, non-adherence was only associated with being born abroad (28.6% versus 7.8%; p=0.019; Chi-square test) and with foreign origin families (27.3% versus 0%; p<0.0001; Chi-square test). The nurse-led intervention was associated to an increase in adherence to antituberculosis treatment. Immigrant-related variables remained major risk factors for sub-optimal adherence in a low-endemic setting. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Nurse Home Visits Improve Maternal-Infant Interaction and Decrease Severity of Postpartum Depression

PubMed Central

Horowitz, June Andrews; Murphy, Christine A.; Gregory, Katherine; Wojcik, Joanne; Pulcini, Joyce; Solon, Lori

2013-01-01

Objective To test the efficacy of the relationship-focused behavioral coaching intervention Communicating and Relating Effectively (CARE) in increasing maternal-infant relational effectiveness between depressed mothers and their infants during the first nine months postpartum. Design Randomized clinical trial (RCT) with three phases. Methods In this three-phase study, women were screened for postpartum depression (PPD) in Phase I at 6 weeks postpartum. In Phase II, women were randomly assigned to treatment or control conditions and maternal-infant interaction was video-recorded at four intervals postpartum: 6 weeks, 3 months, 6 months, and 9 months. Phase III involved focus group and individual interviews with study participants. Setting Phase I mothers were recruited from obstetric units of two major medical centers. Phase II involved the RCT, a series of nurse-led home visits beginning at 6 weeks and ending at 9 months postpartum. Phase III focus groups were conducted at the university and personal interviews were conducted by telephone or in participants’ homes. Participants Postpartum mother-infant dyads (134) representative of southeastern New England, United States participated in the RCT. One hundred and twenty-five mother-infant dyads were fully retained in the 9-month protocol. Results Treatment and control groups had significant increases in quality of mother-infant interaction and decreases in depression severity. Qualitative findings indicated presence of the nurse, empathic listening, focused attention and self-reflection during data collection, directions for video-recorded interaction, and assistance with referrals likely contributed to improvements for both groups. Conclusions Efficacy of the CARE intervention was only partially supported. Nurse attention given to the control group and the data collection process likely confounded results and constituted an unintentional treatment. Results suggest that nurse-led home visits had a positive effect on outcomes for all participants. PMID:23682696

Benefits and Sustainability of a Learning Collaborative for Implementation of Treat to Target in Rheumatoid Arthritis: Results of the TRACTION Trial Phase II.

PubMed

Solomon, Daniel H; Lu, Bing; Yu, Zhi; Corrigan, Cassandra; Harrold, Leslie R; Smolen, Josef S; Fraenkel, Liana; Katz, Jeffrey N; Losina, Elena

2018-01-05

We conducted a two-phase randomized controlled trial of a Learning Collaborative (LC) to facilitate implementation of treat to target (TTT) to manage rheumatoid arthritis (RA). We found substantial improvement in implementation of TTT in Phase I. Herein, we report on a second 9 months (Phase II) where we examined maintenance of response in Phase I and predictors of greater improvement in TTT adherence. We recruited 11 rheumatology sites and randomized them to either receive the LC during Phase I or to a wait-list control group that received the LC intervention during Phase II. The outcome was change in TTT implementation score (0 to 100, 100 is best) from pre- to post-intervention. TTT implementation score is defined as a percent of components documented in visit notes. Analyses examined: 1) the extent that the Phase I intervention teams sustained improvement in TTT; and, 2) predictors of TTT improvement. The analysis included 636 RA patients. At baseline, mean TTT implementation score was 11% in Phase I intervention sites and 13% in Phase II sites. After the intervention, TTT implementation score improved to 57% in the Phase I intervention sites and to 58% in the Phase II sites. Intervention sites from Phase I sustained the improvement during the Phase II (52%). Predictors of greater TTT improvement included only having rheumatologist providers at the site, academic affiliation of the site, fewer providers per site, and the rheumatologist provider being a trainee. Improvement in TTT remained relatively stable over a post-intervention period. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Exploring the statistical and clinical impact of two interim analyses on the Phase II design with option for direct assignment.

PubMed

An, Ming-Wen; Mandrekar, Sumithra J; Edelman, Martin J; Sargent, Daniel J

2014-07-01

The primary goal of Phase II clinical trials is to understand better a treatment's safety and efficacy to inform a Phase III go/no-go decision. Many Phase II designs have been proposed, incorporating randomization, interim analyses, adaptation, and patient selection. The Phase II design with an option for direct assignment (i.e. stop randomization and assign all patients to the experimental arm based on a single interim analysis (IA) at 50% accrual) was recently proposed [An et al., 2012]. We discuss this design in the context of existing designs, and extend it from a single-IA to a two-IA design. We compared the statistical properties and clinical relevance of the direct assignment design with two IA (DAD-2) versus a balanced randomized design with two IA (BRD-2) and a direct assignment design with one IA (DAD-1), over a range of response rate ratios (2.0-3.0). The DAD-2 has minimal loss in power (<2.2%) and minimal increase in T1ER (<1.6%) compared to a BRD-2. As many as 80% more patients were treated with experimental vs. control in the DAD-2 than with the BRD-2 (experimental vs. control ratio: 1.8 vs. 1.0), and as many as 64% more in the DAD-2 than with the DAD-1 (1.8 vs. 1.1). We illustrate the DAD-2 using a case study in lung cancer. In the spectrum of Phase II designs, the direct assignment design, especially with two IA, provides a middle ground with desirable statistical properties and likely appeal to both clinicians and patients. Copyright © 2014 Elsevier Inc. All rights reserved.

Once daily controlled-release pregabalin in the treatment of patients with fibromyalgia: a phase III, double-blind, randomized withdrawal, placebo-controlled study.

PubMed

Arnold, Lesley M; Arsenault, Pierre; Huffman, Cynthia; Patrick, Jeffrey L; Messig, Michael; Chew, Marci L; Sanin, Luis; Scavone, Joseph M; Pauer, Lynne; Clair, Andrew G

2014-10-01

Safety and efficacy of a once daily controlled-released (CR) formulation of pregabalin was evaluated in patients with fibromyalgia using a placebo-controlled, randomized withdrawal design. This multicenter study included 6 week single-blind pregabalin CR treatment followed by 13 week double-blind treatment with placebo or pregabalin CR. The starting dose of 165 mg/day was escalated during the first 3 weeks, up to 495 mg/day based on efficacy and tolerability. Patients with ≥50% reduction in average daily pain score at the end of the single-blind phase were randomized to continue pregabalin CR at the optimized dose (330-495 mg/day) or to placebo. The primary endpoint was time to loss of therapeutic response (LTR), defined as <30% pain reduction relative to single-blind baseline or discontinuation owing to lack of efficacy or adverse event (AE). Secondary endpoints included measures of pain severity, global assessment, functional status, tiredness/fatigue, and sleep. ClinicalTrials.gov NCT01271933. A total of 441 patients entered the single-blind phase, and 63 were randomized to pregabalin CR and 58 to placebo. The median time to LTR (Kaplan-Meier analysis) was significantly longer in the pregabalin CR group than placebo (58 vs. 22 days, p = 0.02). By trial end, 34/63 (54.0%) pregabalin CR and 41/58 (70.7%) placebo patients experienced LTR. Significantly more patients reported 'benefit from treatment' (Benefit, Satisfaction, and Willingness to Continue Scale) in the pregabalin CR group; no other secondary endpoints were statistically significant. Most AEs were mild to moderate in severity (most frequent: dizziness, somnolence). The percentage of pregabalin CR patients discontinuing because of AEs was 12.2% and 4.8% in the single-blind and double-blind phases, respectively (placebo, 0%). Time to LTR was significantly longer with pregabalin CR versus placebo in fibromyalgia patients who initially showed improvement with pregabalin CR, indicating maintenance of response. Pregabalin CR was well tolerated in most patients. Generalizability may be limited by study duration and selective population.

Randomly displaced phase distribution design and its advantage in page-data recording of Fourier transform holograms.

PubMed

Emoto, Akira; Fukuda, Takashi

2013-02-20

For Fourier transform holography, an effective random phase distribution with randomly displaced phase segments is proposed for obtaining a smooth finite optical intensity distribution in the Fourier transform plane. Since unitary phase segments are randomly distributed in-plane, the blanks give various spatial frequency components to an image, and thus smooth the spectrum. Moreover, by randomly changing the phase segment size, spike generation from the unitary phase segment size in the spectrum can be reduced significantly. As a result, a smooth spectrum including sidebands can be formed at a relatively narrow extent. The proposed phase distribution sustains the primary functions of a random phase mask for holographic-data recording and reconstruction. Therefore, this distribution is expected to find applications in high-density holographic memory systems, replacing conventional random phase mask patterns.

Antitumor Effects of Somatostatin Analogs in Neuroendocrine Tumors

PubMed Central

Dubé, Pierre; Rinke, Anja

2012-01-01

Background. For decades, somatostatin analogs (including octreotide and lanreotide) have been indicated for relief of the symptoms of flushing, diarrhea, and wheezing associated with secretory neuroendocrine tumors (NETs). Recently, it has been suggested that somatostatin analogs may provide direct and indirect antitumor effects in secretory and nonsecretory NETs in addition to symptom control in secretory NETs. Methods. A systematic review of MEDLINE was conducted to identify studies that investigated the antitumor effects of octreotide or lanreotide for patients with NETs. Additional studies not published in the peer-reviewed literature were identified by searching online abstracts. Results. In all, 17 octreotide trials and 11 lanreotide trials that included antitumor effects were identified. Partial response rates were between 0% and 31%, and stable disease rates were between 15% and 89%. Octreotide was the only somatostatin analog for which results of a phase III, randomized, placebo-controlled clinical trial that investigated antitumor effects were published. After 6 months of treatment in this randomized phase III trial, stable disease was observed in 67% of patients (hazard ratio for time to disease progression: 0.34; 95% confidence interval: 0.20–0.59; p = .000072). Conclusions. In addition to symptom control for NETs, the data support an antitumor effect of somatostatin analogs and suggest that they may slow tumor growth. Long-acting repeatable octreotide has been shown to have an antitumor effect in a randomized phase III trial in midgut NETs, whereas results are pending in a corresponding controlled trial with lanreotide for patients with intestinal and pancreatic primary NETs. PMID:22628056

Memantine as an Adjuvant Treatment for Obsessive Compulsive Symptoms in Manic Phase of Bipolar Disorder: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

PubMed

Sahraian, Ali; Jahromi, Leila Razeghian; Ghanizadeh, Ahmad; Mowla, Arash

2017-04-01

The aim of this study is to examine the effects of memantine as an adjuvant treatment for obsessive compulsive (OC) symptoms in patients with bipolar disorder (BD) type I, manic phase. In this 16-week double-blind placebo-controlled randomized clinical trial, 58 patients in the manic phase of BD who had OC symptoms were randomly allocated to receive memantine or placebo plus their routine medications (lithium + olanzapine + clonazepam). The Yale Brown Obsessive Compulsive Behavior Scale was used to assess the outcomes. Adverse effects were also recorded. Thirty-eight patients (19 in the memantine group and 19 in the placebo group) completed the trial. Throughout the trial, the mean score decreased from 20.26 ± 5.91 to 9.73 ± 5.44 in the memantine group (P < 0.000) and from 22.89 ± 5.70 to 16.63 ± 4.00 in the placebo group (P < 0.000). At the end of the study, 15 (78.94%) patients in the memantine group and 7 (36.84%) patients in the placebo group demonstrated more than 34% decline in the Yale Brown Obsessive Compulsive Behavior Scale score (P < 0.01). No serious adverse effects were reported. Our double-blind controlled clinical trial showed that memantine is an effective adjuvant agent for reducing OC symptoms in patients with BD. However, it needs to be noted that our study is preliminary, and larger double-blind controlled studies are needed to confirm the results.

Efficacy and safety of Lian-Ju-Gan-Mao capsules for treating the common cold with wind-heat syndrome: study protocol for a randomized controlled trial.

PubMed

Wang, Shengjun; Jiang, Hongli; Yu, Qin; She, Bin; Mao, Bing

2017-01-05

The common cold is a common and frequent respiratory disease mainly caused by viral infection of the upper respiratory tract. Chinese herbal medicine has been increasingly prescribed to treat the common cold; however, there is a lack of evidence to support the wide utility of this regimen. This protocol describes an ongoing phase II randomized controlled clinical trial, based on the theory of traditional Chinese medicine (TCM), with the objective of evaluating the efficacy and safety of Lian-Ju-Gan-Mao capsules (LJGMC), a Chinese patent medicine, compared with placebo in patients suffering from the common cold with wind-heat syndrome (CCWHS). This is a multicenter, randomized, double-blind, placebo-controlled phase II clinical trial. A total of 240 patients will be recruited and randomly assigned to a high-dose group, medium-dose group, low-dose group, and placebo-matched group in a 1:1:1:1 ratio. The treatment course is 3 consecutive days, with a 5-day follow-up. The primary outcome is time to all symptoms' clearance. Secondary outcomes include time to the disappearance of primary symptoms and each secondary symptom, time to fever relief, time to fever clearance, and change in TCM symptom and sign scores. This trial is a well-designed study according to principles and regulations issued by the China Food and Drug Administration (CFDA). The results will provide high-quality evidence on the efficacy and safety of LJGMC in treating CCWHS and help to optimize the dose for the next phase III clinical trial. Moreover, the protocol presents a detailed and practical methodology for future clinical trials of drugs developed based on TCM. Chinese Clinical Trial Registry, ChiCTR-IPR-15006504 . Registered on 4 June 2015.

Effects of rye bread enriched with green tea extract on weight maintenance and the characteristics of metabolic syndrome following weight loss: a pilot study.

PubMed

Bajerska, Joanna; Mildner-Szkudlarz, Sylwia; Walkowiak, Jarosław

2015-06-01

We examined whether the incorporation of green tea extract enriched rye bread (GTRB) into the diet can improve weight loss (WL) maintenance and control of abnormalities linked to metabolic syndrome (MS). A total of 55 obese men and women (mean age: 53.0±7.0 years, body mass index: 35.0±5.5 kg m(-2)) were recruited. The study had a single-blind randomized study design and consisted of an 8-week WL phase with low-energy calorie diet, followed by a 12-week weight maintenance (WM) phase. During the WM phase, the subjects were randomized into two groups, receiving either the control rye bread (control group) or the GTRB (intervention group). The ingestion of 280 and 360 g GTRB provided daily totals of 123.2 and 158.4 mg caffeine, and 188.3 and 242.1 mg of epigallocatechin gallate, for women and men, respectively. After the WL phase, subjects lost 7.3±3.1 kg of their baseline body weight. GTRB intake did not significantly influence the maintenance of WL, high-density lipoprotein-cholesterol, triglycerides, and glucose concentrations. Although, it resulted in significant differences (mean difference [95% confidence interval]) between the treatment groups in the maintenance of waist circumference (-1.22 cm [-2.4, -0.02; P=.04]), the results were not clinically meaningful. Nevertheless, the ingestion of GTRB led to the maintenance of lower blood pressure (BP), also the proportion of subjects fulfilling the criteria of MS after the WM phase was lower in the intervention group than in the control group. Although GTRB consumption did not improve significantly the WL maintenance, it resulted in a better control of BP.

A 12-Week Physical and Cognitive Exercise Program Can Improve Cognitive Function and Neural Efficiency in Community-Dwelling Older Adults: A Randomized Controlled Trial.

PubMed

Nishiguchi, Shu; Yamada, Minoru; Tanigawa, Takanori; Sekiyama, Kaoru; Kawagoe, Toshikazu; Suzuki, Maki; Yoshikawa, Sakiko; Abe, Nobuhito; Otsuka, Yuki; Nakai, Ryusuke; Aoyama, Tomoki; Tsuboyama, Tadao

2015-07-01

To investigate whether a 12-week physical and cognitive exercise program can improve cognitive function and brain activation efficiency in community-dwelling older adults. Randomized controlled trial. Kyoto, Japan. Community-dwelling older adults (N = 48) were randomized into an exercise group (n = 24) and a control group (n = 24). Exercise group participants received a weekly dual task-based multimodal exercise class in combination with pedometer-based daily walking exercise during the 12-week intervention phase. Control group participants did not receive any intervention and were instructed to spend their time as usual during the intervention phase. The outcome measures were global cognitive function, memory function, executive function, and brain activation (measured using functional magnetic resonance imaging) associated with visual short-term memory. Exercise group participants had significantly greater postintervention improvement in memory and executive functions than the control group (P < .05). In addition, after the intervention, less activation was found in several brain regions associated with visual short-term memory, including the prefrontal cortex, in the exercise group (P < .001, uncorrected). A 12-week physical and cognitive exercise program can improve the efficiency of brain activation during cognitive tasks in older adults, which is associated with improvements in memory and executive function. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

Intravenous tranexamic acid for hyperacute primary intracerebral hemorrhage: Protocol for a randomized, placebo-controlled trial.

PubMed

Sprigg, Nikola; Robson, Katie; Bath, Philip; Dineen, Robert; Roberts, Ian; Robinson, Tom; Roffe, Christine; Werring, David; Al-Shahi Salman, Rustam; Pocock, Stuart; Duley, Lelia; England, Tim; Whynes, David; Ciccone, Alfonso; Laska, Ann Charlotte; Christensen, Hanne; Ozturk, Serefnur; Collins, Ronan; Bereczki, Daniel; Egea-Guerrero, Juan Jose; Law, Zhe Kang; Czlonkowska, Anna; Seiffge, David; Beredzie, Maia

2016-08-01

Outcome after intracerebral hemorrhage remains poor. Tranexamic acid is easy to administer, readily available, inexpensive, and effective in other hemorrhagic conditions. This randomized trial aims to test the hypothesis that intravenous tranexamic acid given within 8 h of spontaneous intracerebral hemorrhage reduces death or dependency. Phase III prospective double-blind randomized placebo-controlled trial. Participants within 8 h of spontaneous intracerebral hemorrhage are randomized to receive either intravenous tranexamic acid 1 g 10 min bolus followed by 1 g 8 h infusion, or placebo. A trial of 2000 participants (300 from start-up phase and 1700 from main phase) will have 90% power to detect an ordinal shift of the modified Rankin Scale with odds ratio 0.79. The primary outcome is death or dependency measured by ordinal shift analysis of the 7 level mRS at day 90. Secondary outcomes are neurological impairment at day 7 and disability, quality of life, cognition, and mood at day 90. Safety outcomes are death, serious adverse events, thromboembolic events, and seizures. Cost outcomes are length of stay in hospital, readmission, and institutionalization. This pragmatic trial is assessing efficacy of tranexamic acid after spontaneous intracerebral hemorrhage. Recruitment started in 2013; as of 15th January 2016 1355 participants have been enrolled, from 95 centers in seven countries. Recruitment is due to end in 2017. TICH-2 Trial is registered as ISRCTN93732214. © 2016 World Stroke Organization.

Safety, tolerability, and immunogenicity of the novel antituberculous vaccine RUTI: randomized, placebo-controlled phase II clinical trial in patients with latent tuberculosis infection.

PubMed

Nell, Andre S; D'lom, Eva; Bouic, Patrick; Sabaté, Montserrat; Bosser, Ramon; Picas, Jordi; Amat, Mercè; Churchyard, Gavin; Cardona, Pere-Joan

2014-01-01

To evaluate the safety, tolerability and immunogenicity of three different doses (5, 25 and 50 µg) of the novel antituberculous vaccine RUTI compared to placebo in subjects with latent tuberculosis infection. Double-blind, randomized, placebo-controlled Phase II Clinical Trial (95 patients randomized). Three different RUTI doses and placebo were tested, randomized both in HIV-positive (n = 47) and HIV-negative subjects (n = 48), after completion of one month isoniazid (INH) pre-vaccination. Each subject received two vaccine administrations, 28 Days apart. Five patients withdrew and 90 patients completed the study. Assessment of safety showed no deaths during study. Two subjects had serious adverse events one had a retinal detachment while taking INH and was not randomized and the other had a severe local injection site abscess on each arm and was hospitalized; causality was assessed as very likely and by the end of the study the outcome had resolved. All the patients except 5 (21%) patients of the placebo group (3 HIV+ and 2 HIV-) reported at least one adverse event (AE) during the study. The most frequently occurring AEs among RUTI recipients were (% in HIV+/-): injection site reactions [erythema (91/92), induration (94/92), local nodules (46/25), local pain (66/75), sterile abscess (6/6), swelling (74/83), ulcer (20/11), headache (17/22) and nasopharyngitis (20/5)]. These events were mostly mild and well tolerated. Overall, a polyantigenic response was observed, which differed by HIV- status. The best polyantigenic response was obtained when administrating 25 µg RUTI, especially in HIV-positive subjects which was not increased after the second inoculation. This Phase II clinical trial demonstrates reasonable tolerability of RUTI. The immunogenicity profile of RUTI vaccine in LTBI subjects, even being variable among groups, allows us considering one single injection of one of the highest doses in future trials, preceded by an extended safety clinical phase. ClinicalTrials.gov NCT01136161.

Mashing up metals with carbothermal shock

NASA Astrophysics Data System (ADS)

Skrabalak, Sara E.

2018-03-01

Different materials and the capabilities they enabled have marked the ages of civilization. For example, the malleable copper alloys of the Bronze Age provided harder and more durable tools. Most exploration of new alloys has focused on random alloys, in which the alloying metal sites have no metal preference. In binary and ternary metal systems, dissimilar elements do not mix readily at high concentrations, which has limited alloying studies to intermetallics (ordered multimetallic phases) and random alloys, in which minor components are added to a principal element. In 2004, crystalline metal alloys consisting of five or more principal elements in equal or nearly equal amounts (1, 2) were reported that were stabilized by their high configurational entropy. Unlike most random alloys, the “high-entropy” alloys (3, 4) reside in the centers of their multidimensional phase diagrams (see the figure, right). On page 1489 of this issue, Yao et al. (5) present an innovative and general route to high-entropy alloys that can mix up to eight elements into single-phase, size-controlled nanoparticles (NPs).

Comparing the Levels of Acute-Phase Reactants Between Smoker and Nonsmoker Diabetic Patients: More Predicted Risk for Cardiovascular Diseases in Smoker Compared to Nonsmoker Diabetics.

PubMed

Rezaei-Adl, Sepideh; Ghahroudi Tali, Arash; Saffar, Hiva; Rajabiani, Afsaneh; Abdollahi, Alireza

2017-09-01

 Due to a close link between cardiovascular disorders and increased acute phase responses, it is now proposed the relation of total sialic acid (TSA) and C Reactive Protein (CRP) as main components of acute phase proteins and cardiovascular risk profiles such as diabetes mellitus and smoking. We hypothesized that the elevation in the level of TSA along with other prototype acute phase reactants such as CRP is expected more in the coexistence of diabetes and smoking than in diabetes mellitus alone. Ninety diabetic patients were randomly selected and entered into this case-control study. Using block randomization method, the patients were randomly assigned into smokers (n=45) and nonsmokers (n=45). A group of ten healthy individuals was also included as the control. The serum levels of TSA, CRP, iron, and hemoglobin were measured by the specific techniques. Comparing laboratory parameters across the three groups indicated significantly higher levels of TSA and CRP in smoker diabetics as compared to non-smoker diabetics and the healthy controls, while there was no difference in other parameters including serum iron and hemoglobin. A significant positive correlation was also revealed between TCA and CRP (r=0.324, P=0.030), but no significant association was found between other parameters. In the background of smoking, increasing the level of both TSA and CRP is predicted more than the existence of diabetes mellitus alone. In fact, the increase in these biomarkers is more predictable in smoker than in nonsmoker diabetics. This finding emphasizes the increased risk for cardiovascular disorders in smoker compared to non-smoker diabetics.

A randomized controlled trial investigating the safety and efficacy of aripiprazole in the long-term maintenance treatment of pediatric patients with irritability associated with autistic disorder.

PubMed

Findling, Robert L; Mankoski, Raymond; Timko, Karen; Lears, Katherine; McCartney, Theresa; McQuade, Robert D; Eudicone, James M; Amatniek, Joan; Marcus, Ronald N; Sheehan, John J

2014-01-01

To evaluate the efficacy and safety of aripiprazole versus placebo in preventing relapse of irritability symptoms associated with autistic disorder in pediatric patients. This multicenter, double-blind, randomized, placebo-controlled, relapse-prevention trial enrolled patients (6-17 years) who met the current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DMS-IV-TR) criteria for autistic disorder and who also had serious behavioral problems (ie, tantrums, aggression, self-injurious behavior, or a combination of these behavioral problems) between March 2011 and June 2012. In phase 1, single-blind aripiprazole was flexibly dosed (2-15 mg/d) for 13-26 weeks. Patients with a stable response (≥ 25% decrease in Aberrant Behavior Checklist-irritability subscale score and a rating of "much improved" or "very much improved" on the Clinical Global Impressions-Improvement scale) for 12 consecutive weeks were randomized into phase 2 to continue aripiprazole or switch to placebo. Treatment was continued until relapse or up to 16 weeks. The primary end point was time from randomization to relapse. Eighty-five patients were randomized in phase 2. The difference in time to relapse between aripiprazole and placebo was not statistically significant (P = .097). Kaplan-Meier relapse rates at week 16 were 35% for aripiprazole and 52% for placebo (hazard ratio [HR] = 0.57; number needed to treat [NNT] = 6). The most common adverse events during phase 1 were weight increase (25.2%), somnolence (14.8%), and vomiting (14.2%); and, during phase 2 (aripiprazole vs placebo), they were upper respiratory tract infection (10.3% vs 2.3%), constipation (5.1% vs 0%), and movement disorder (5.1% vs 0%). In this study, there was no statistically significant difference between aripiprazole and placebo in time to relapse during maintenance therapy. However, the HR and NNT suggest some patients will benefit from maintenance treatment. Patients receiving aripiprazole should be periodically reassessed to determine the continued need for treatment. ClinicalTrials.gov identifier: NCT01227668. © Copyright 2014 Physicians Postgraduate Press, Inc.

Triadic Gaze Intervention for Young Children with Physical Disabilities

PubMed Central

Olswang, Lesley B.; Dowden, Patricia; Feuerstein, Julie; Greenslade, Kathryn; Pinder, Gay Lloyd; Fleming, Kandace

2018-01-01

Purpose This randomized controlled study investigated whether a supplemental treatment designed to teach triadic gaze (TG) as a signal of coordinated joint attention (CJA) would yield a significantly greater increase in TG in the experimental versus control group. Method Eighteen 10- to 24-month-old children with severe motor impairments were randomly assigned to an experimental (n=9) or control group (n=9). For approximately 29 sessions over 17 weeks, experimental participants received TG treatment twice weekly with a speech-language pathologist (SLP) in addition to standard practice. Controls received only standard practice from birth-to-three therapists. Coders masked to group assignment coded TG productions with an unfamiliar SLP at baseline, every three weeks during the experimental phase, and at the final measurement session. Results TG increased across groups from baseline to final measurement, with the experimental group showing slightly greater change. Performance trends were examined using experimental phase moving averages. Comparisons revealed significant differences between groups at two time points (at 12 weeks, r= .30, a medium effect and at the end of the phase r=.50, large effect). Conclusion Results suggest the promise of a short-term, focused treatment to teach TG as a behavioral manifestation of CJA to children with severe physical disabilities. PMID:24686825

Maintenance N-acetyl cysteine treatment for bipolar disorder: a double-blind randomized placebo controlled trial.

PubMed

Berk, Michael; Dean, Olivia M; Cotton, Sue M; Gama, Clarissa S; Kapczinski, Flavio; Fernandes, Brisa; Kohlmann, Kristy; Jeavons, Susan; Hewitt, Karen; Moss, Kirsteen; Allwang, Christine; Schapkaitz, Ian; Cobb, Heidi; Bush, Ashley I; Dodd, Seetal; Malhi, Gin S

2012-08-14

N-acetyl cysteine (NAC) is a glutathione precursor that has been shown to have antidepressant efficacy in a placebo-controlled trial. The current study aimed to investigate the maintenance effects of NAC following eight weeks of open-label treatment for bipolar disorder. The efficacy of a double blind randomized placebo controlled trial of 2 g/day NAC as adjunct maintenance treatment for bipolar disorder was examined. Participants (n = 149) had a Montgomery Asberg Depression Rating Score of ≥12 at trial entry and, after eight weeks of open-label NAC treatment, were randomized to adjunctive NAC or placebo, in addition to treatment as usual. Participants (primarily outpatients) were recruited through public and private services and through newspaper advertisements. Time to intervention for a mood episode was the primary endpoint of the study, and changes in mood symptoms, functionality and quality of life measures were secondary outcomes. There was a substantial decrease in symptoms during the eight-week open-label NAC treatment phase. During the subsequent double-blind phase, there was minimal further change in outcome measures with scores remaining low. Consequently, from this low plateau, between-group differences did not emerge on recurrence, clinical functioning or quality of life measures. There were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial; however, these findings may be confounded by limitations. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000074493).

Effect of Weight Maintenance on Symptoms of Knee Osteoarthritis in Obese Patients: A Twelve-Month Randomized Controlled Trial

PubMed Central

Christensen, Robin; Henriksen, Marius; Leeds, Anthony R; Gudbergsen, Henrik; Christensen, Pia; Sørensen, Tina J; Bartels, Else M; Riecke, Birgit F; Aaboe, Jens; Frederiksen, Rikke; Boesen, Mikael; Lohmander, L Stefan; Astrup, Arne; Bliddal, Henning

2015-01-01

Objective To compare results of obese patients with knee osteoarthritis (OA) who, after an intensive weight loss regimen, received 1 year of either dietary support (D), a knee-exercise program (E), or “no attention” (C; control group). Methods We conducted a randomized, 2-phase, parallel-group trial. A total of 192 obese participants with knee OA were enrolled; the mean age was 62.5 years and 81% were women with a mean entry weight of 103.2 kg. In phase 1, all participants were randomly assigned to 1 of 3 groups and began a dietary regimen of 400–810 and 1,250 kcal/day for 16 weeks (2 8-week phases) to achieve a major weight loss. Phase 2 consisted of 52 weeks' maintenance in either group D, E, or C. Outcomes were changes from randomization in pain on a 100-mm visual analog scale, weight, and response according to the Outcome Measures in Rheumatology-Osteoarthritis Research Society International criteria. Results Mean weight loss for phase 1 was 12.8 kg. After 1 year on maintenance therapy, the D group sustained a lower weight (11.0 kg, 95% confidence interval [95% CI] 9.0, 12.8 kg) than those in the E (6.2, 95% CI 4.4, 8.1 kg) and C (8.2, 95% CI 6.4, 10.1 kg) groups (P = 0.002 by analysis of covariance [ANCOVA]). Adherence was low in the E group. All groups had statistically significant pain reduction (D: 6.1; E: 5.6; and C: 5.5 mm) with no difference between groups (P = 0.98 by ANCOVA). In each group 32 (50%), 26 (41%), and 33 (52%) participants responded to treatment in the D, E, and C groups, respectively, with no statistically significant difference in the number of responders (P = 0.41). Conclusion A significant weight reduction with a 1-year maintenance program improves knee OA symptoms irrespective of maintenance program. PMID:25370359

A randomized-controlled trial focusing on socio-economic status for promoting vegetable intake among adults using a web-based nutrition intervention programme: study protocol.

PubMed

Nakamura, Saki; Inayama, Takayo; Arao, Takashi

2017-01-13

Web-based nutritional education programmes appear to be comparable to those delivered face-to-face. However, no existing web-based nutrition education or similar programme has yet been evaluated with consideration of socio-economic status. The objective of a nutritional education programme of promoting vegetable intake designed a randomized controlled trial (RCT) is to evaluate the results of intervention and to determine how socio-economic status influences the programme effects. Participants will be randomly sampled individuals (aged 30-59) stratified according national population statistics for sex, age, and household income. Participants were consented to survey participation (n = 1500), and will be randomly divided into intervention and control groups. The intervention period is 5 weeks with one step of diet-related education per week. The main outcome of the programme is dietary behaviour as eating vegetable (350 g per day, five small bowl). To encourage behavioural changes, the programme contents are prepared using behavioural theories and techniques tailored to the assumed group stages of behavioural change. In the first step, we employ the health belief model to encourage a shift from the pre-contemplative to the contemplative phase; in the second and third steps, social cognitive theory is used to encourage transition to the preparatory phase; in the fourth step, social cognitive theory and strengthening social support are used to promote progression to the execution phase; finally, in the fifth step, strengthening social capital and social support are used to promote the shift to the maintenance phase. The baseline, post intervention and follow-up survey was assessed using a self-administered questionnaire. For process evaluation, we use five items relating to programme participation and satisfaction. A follow-up survey of participants will be carried out 3 months after intervention completion. The fact that this study is an RCT with an established control group is a strong advantage. Information and communications technology is not limited by time or place. If we could show this web-based nutrition education programmes has a positive effect, it may be an appropriate tool for reaching individuals in lower socio-economic state. Current Controlled Trials UMIN-ICDR UMIN 000019376 (Registered October 16, 2015).

Hypothermia for Traumatic Brain Injury in Children-A Phase II Randomized Controlled Trial.

PubMed

Beca, John; McSharry, Brent; Erickson, Simon; Yung, Michael; Schibler, Andreas; Slater, Anthony; Wilkins, Barry; Singhal, Ash; Williams, Gary; Sherring, Claire; Butt, Warwick

2015-07-01

To perform a pilot study to assess the feasibility of performing a phase III trial of therapeutic hypothermia started early and continued for at least 72 hours in children with severe traumatic brain injury. Multicenter prospective randomized controlled phase II trial. All eight of the PICUs in Australia and New Zealand and one in Canada. Children 1-15 years old with severe traumatic brain injury and who could be randomized within 6 hours of injury. The control group had strict normothermia to a temperature of 36-37°C for 72 hours. The intervention group had therapeutic hypothermia to a temperature of 32-33°C for 72 hours followed by slow rewarming at a rate compatible with maintaining intracranial pressure and cerebral perfusion pressure. Of 764 children admitted to PICU with traumatic brain injury, 92 (12%) were eligible and 55 (7.2%) were recruited. There were five major protocol violations (9%): three related to recruitment and consent processes and two to incorrect temperature management. Rewarming took a median of 21.5 hours (16-35 hr) and was performed without compromise in the cerebral perfusion pressure. There was no increase in any complications, including infections, bleeding, and arrhythmias. There was no difference in outcomes 12 months after injury; in the therapeutic hypothermia group, four (17%) had a bad outcome (pediatric cerebral performance category, 4-6) and three (13%) died, whereas in the normothermia group, three (12%) had a bad outcome and one (4%) died. Early therapeutic hypothermia in children with severe traumatic brain injury does not improve outcome and should not be used outside a clinical trial. Recruitment rates were lower and outcomes were better than expected. Conventional randomized controlled trials in children with severe traumatic brain injury are unlikely to be feasible. A large international trials group and alternative approaches to trial design will be required to further inform practice.

One session of high-intensity interval training (HIIT) every 5 days, improves muscle power but not static balance in lifelong sedentary ageing men

PubMed Central

Sculthorpe, Nicholas F.; Herbert, Peter; Grace, Fergal

2017-01-01

Abstract Background: Declining muscle power during advancing age predicts falls and loss of independence. High-intensity interval training (HIIT) may improve muscle power, but remains largely unstudied in ageing participants. Methods: This randomized controlled trial (RCT) investigated the efficacy of a low-frequency HIIT (LfHIIT) intervention on peak muscle power (peak power output [PPO]), body composition, and balance in lifelong sedentary but otherwise healthy males. Methods: Thirty-three lifelong sedentary ageing men were randomly assigned to either intervention (INT; n = 22, age 62.3 ± 4.1 years) or control (n = 11, age 61.6 ± 5.0 years) who were both assessed at 3 distinct measurement points (phase A), after 6 weeks of conditioning exercise (phase B), and after 6 weeks of HIIT once every 5 days in INT (phase C), where control remained inactive throughout the study. Results: Static balance remained unaffected, and both absolute and relative PPO were not different between groups at phases A or B, but increased significantly in INT after LfHIIT (P < 0.01). Lean body mass displayed a significant interaction (P < 0.01) due to an increase in INT between phases B and C (P < 0.05). Conclusions: 6 weeks of LfHIIT exercise feasible and effective method to induce clinically relevant improvements in absolute and relative PPO, but does not improve static balance in sedentary ageing men. PMID:28178145

THE LONG-TERM EFFICACY OF ACUTE-PHASE PSYCHOTHERAPY FOR DEPRESSION: A META-ANALYSIS OF RANDOMIZED TRIALS.

PubMed

Karyotaki, Eirini; Smit, Yolba; de Beurs, Derek P; Henningsen, Kirsten Holdt; Robays, Jo; Huibers, Marcus J H; Weitz, Erica; Cuijpers, Pim

2016-05-01

Understanding the effectiveness of treatment for depression in both the short term and long term is essential for clinical decision making. The present meta-analysis examined treatment effects on depression and quality of life in acute-phase psychotherapeutic interventions compared to no treatment control groups for adult depression at 6 months or longer postrandomization. A systematic literature search resulted in 44 randomized controlled trials with 6,096 participants. Acute-phase psychotherapy was compared to control groups at 6-month or longer postrandomization. Odds ratios of a positive outcome were calculated. Psychotherapy outperformed control groups at 6 months or longer postrandomization (OR = 1.92, 95% CI: 1.60-2.31, P < .001). Heterogeneity was moderate (I²: 65, 95% CI: 53-74, P < .001). However, effects significantly decreased with longer follow-up periods. Additionally, a small positive effect of psychotherapy was observed for quality of life, while similar effects were obtained in separate analyses of each type of psychotherapy, with the exception of nondirective supportive therapy. Studies that provided booster sessions had better treatment results compared with studies that did not provide any further sessions. Finally, we found that trials on psychotherapy aimed at major depressive disorder (MDD) had better outcomes than those that were aimed at elevated depressive symptoms. There is substantial evidence that acute-phase psychotherapy results in a better treatment effects on depression and quality of life in the long term for adult patients with depression. © 2016 Wiley Periodicals, Inc.

[Development of an orphan drug to treat a genetic disease: the paradigm of agalsidase beta].

PubMed

Germain, Dominique P; Benistan, Karelle

2007-03-01

Preclinical and phase I/II studies gave the proof of principle of enzyme replacement therapy (ERT) with recombinant alpha-galactosidase A through the demonstration of the clearance of the accumulated subtrate from plasma and tissues. In a multicenter, randomized, placebo-controlled, double-blind phase Ill study, the biological efficacy of recombinant alpha-galactosidose A (agalsidase beta 1 mg/kg/714 days) was demonstrated on the basis of complete clearance of accumulated globotriaosylceramide from the endothelia of the kidney, heart and skin. The phase III extension study data gives additional results: kidney function appears to be stabilized after 54 to 60 months of treatment with agolsidase beta in most patients. Intent-to-treat analysis of a double-blind, randomized, placebo-controlled, phase IV study, showed that, adjusted for on imbalance in baseline proteinuria, agalsidase beta significantly reduces by 53% the risk of a first clinical event (renal, cardiac and cerebrovascular), compared with placebo. Clinical benefits of ERT depend on patients' clinical status at baseline, therefore prompting for onset of ERT before irreversible damage occur and underlying the need to stratify patients' populations to better understand the outcome of ERT.

[Randomized, controlled clinical trials with observational follow-up investigations for evaluating efficacy of antihyperglycaemic treatment. I. Main results of the studies].

PubMed

Jermendy, György

2018-04-01

The effect of antihyperglycaemic (antidiabetic) treatment on the late diabetic complications is one of the most important research areas in clinical diabetology. The relationship between glycaemic control and late micro- and macrovascular complications was highlighted by the results of the DCCT (Diabetes Control and Complications Trial) with type 1 and by the UKPDS (United Kingdom Prospective Diabetes Study) with type 2 diabetic patients. In these studies, observational follow-up investigations were also performed after the close-out of the randomized phase of the trial. In addition to these landmark studies, other randomized, controlled efficacy trials were also performed with observational follow-up investigations resulting in the development of the concept of metabolic memory or metabolic legacy. In this article, the main results of the studies are summarized. Orv Hetil. 2018; 159(15): 575-582.

Lorcaserin plus lifestyle modification for weight loss maintenance: Rationale and design for a randomized controlled trial.

PubMed

Tronieri, Jena Shaw; Alfaris, Nasreen; Chao, Ariana M; Pearl, Rebecca L; Alamuddin, Naji; Bakizada, Zayna M; Berkowitz, Robert I; Wadden, Thomas A

2017-08-01

Few studies have examined the efficacy of recently approved medications for chronic weight management in facilitating the maintenance of lost weight. This paper provides an overview of the design and rationale for a trial investigating whether lorcaserin, when combined with behavioral weight loss maintenance sessions (WLM), will facilitate the maintenance of losses of ≥5% of initial weight. In this two-phase trial, participants with obesity will enroll in a 14-week run-in diet program consisting of weekly group lifestyle modification sessions and a 1000-1200kcal/d meal replacement diet. Participants who complete this weight induction phase and lose at least 5% of initial weight will then be randomized to 52weeks of WLM plus lorcaserin or WLM plus placebo. We hypothesize that at 52weeks post randomization, participants assigned to WLM plus lorcaserin will achieve significantly better maintenance of the prior 5% weight loss. We will recruit 182 adults with obesity to participate in the diet run-in, 136 of whom (75%) are expected to become eligible for the randomized controlled trial. Co-primary outcomes include the percentage of participants who maintain a loss of at least 5% of initial weight at week 52 and change in weight (kg) from randomization to week 52. This two-phase design will allow us to determine the potential efficacy of chronic weight management using lorcaserin for maintaining initial losses of at least 5% body weight, induced by the use of a structured meal-replacement diet. This combined approach holds promise of achieving larger long-term weight losses. NCT02388568 on ClinicalTrials.gov. Copyright © 2017 Elsevier Inc. All rights reserved.

A Short-Term, Multicenter, Placebo-Controlled, Randomized Withdrawal Study of a Metabotropic Glutamate 2/3 Receptor Agonist Using an Electronic Patient-Reported Outcome Device in Patients With Schizophrenia

PubMed Central

Stauffer, Virginia L.; Baygani, Simin K.; Kinon, Bruce J.; Krikke-Workel, Judith O.

2014-01-01

Abstract This 6-week, multicenter, randomized withdrawal, placebo-controlled trial sought to determine whether symptoms of physical dependence occur after abrupt cessation of pomaglumetad methionil (LY2140023 monohydrate), a metabotropic glutamate 2/3 receptor agonist, in patients with schizophrenia. Eligible outpatients, 18 to 65 years old who required a modification or initiation of antipsychotic medication received 4 weeks of pomaglumetad methionil during open-label treatment and then were randomized, double-blind, to continue pomaglumetad methionil or receive placebo for 2 weeks. The primary outcome compared results of the 3-day moving mean of the total score on the Discontinuation Symptom Checklist-Modified Rickels for pomaglumetad methionil-treated patients with those on placebo during the randomized withdrawal phase. An electronic patient-reported outcome (ePRO) device was used daily to record these results. During the withdrawal phase, 103 patients were randomized, and 98 patients completed the trial. There was no statistically significant evidence of withdrawal symptoms associated with placebo compared with pomaglumetad methionil continuation as measured by Discontinuation Symptom Checklist-Modified Rickels (P = 0.170). The results are supported by secondary analyses with the clinician-rated, Clinical Institute Withdrawal Assessment of Alcohol Scale Revised, which showed no statistically significant differences between treatment groups. Using the ePRO device, 82.5% of the patients achieved 75% to 100% of compliance. No discontinuations due to worsening of schizophrenia, serious adverse events, deaths, or seizures were reported during either phase of the study. These findings suggest that there is no evidence of withdrawal symptoms associated with the abrupt discontinuation of pomaglumetad methionil and that an ePRO device can be successfully used in a multicenter schizophrenia trial. PMID:25006819

Study protocol of the Diabetes and Depression Study (DAD): a multi-center randomized controlled trial to compare the efficacy of a diabetes-specific cognitive behavioral group therapy versus sertraline in patients with major depression and poorly controlled diabetes mellitus.

PubMed

Petrak, Frank; Herpertz, Stephan; Albus, Christian; Hermanns, Norbert; Hiemke, Christoph; Hiller, Wolfgang; Kronfeld, Kai; Kruse, Johannes; Kulzer, Bernd; Ruckes, Christian; Müller, Matthias J

2013-08-06

Depression is common in diabetes and associated with hyperglycemia, diabetes related complications and mortality. No single intervention has been identified that consistently leads to simultaneous improvement of depression and glycemic control. Our aim is to analyze the efficacy of a diabetes-specific cognitive behavioral group therapy (CBT) compared to sertraline (SER) in adults with depression and poorly controlled diabetes. This study is a multi-center parallel arm randomized controlled trial currently in its data analysis phase. We included 251 patients in 70 secondary care centers across Germany. Key inclusion criteria were: type 1 or 2 diabetes, major depression (diagnosed with the Structured Clinical Interview for DSM-IV, SCID) and hemoglobin A1C >7.5% despite current insulin therapy. During the initial phase, patients received either 50-200 mg/d sertraline or 10 CBT sessions aiming at the remission of depression and enhanced adherence to diabetes treatment and coping with diabetes. Both groups received diabetes treatment as usual. After 12 weeks of this initial open-label therapy, only the treatment-responders (50% depression symptoms reduction, Hamilton Depression Rating Scale, 17-item version [HAMD]) were included in the subsequent one year study phase and represented the primary analysis population. CBT-responders received no further treatment, while SER-responders obtained a continuous, flexible-dose SER regimen as relapse prevention. Adherence to treatment was analyzed using therapeutic drug monitoring (measurement of sertraline and N-desmethylsertraline concentrations in blood serum) and by counting the numbers of CBT sessions received. Outcome assessments were conducted by trained psychologists blinded to group assignment. Group differences in HbA1c (primary outcome) and depression (HAMD, secondary outcome) between 1-year follow-up and baseline will be analyzed by ANCOVA controlling for baseline values. As primary hypothesis we expect that CBT leads to significantly greater improvement of glycemic control in the one year follow-up in treatment responders of the short term phase. The DAD study is the first randomized controlled trial comparing antidepressants to a psychological treatment in diabetes patients with depression. Current controlled trials ISRCTN89333241.

Efficacy of aromatherapy for reducing pain during labor: a randomized controlled trial.

PubMed

Tanvisut, Rajavadi; Traisrisilp, Kuntharee; Tongsong, Theera

2018-05-01

Many strategies for labor pain management have been studied, including aromatherapy, which is a noninvasive, alternative medicine used as an adjunct for labor pain control. Nevertheless, the results were contradictory. Therefore, we conducted this study to determine the effectiveness of aromatherapy for reducing pain during labor. A randomized controlled trial was carried out on Thai laboring primigravidae who were a low-risk singleton pregnancy undergoing vaginal delivery. All participants, both study and control group, received standard obstetric care. Aromatherapy was only provided to the study group during the first stage of labor. The women rated their pain intensity by rating scales at different stages of labor. The primary outcome was pain scores and the secondary outcomes were necessity of painkiller usage, labor time, aromatherapy-associated complications, route of delivery, and Apgar scores. A total of 104 women were recruited, 52 in each group. Baseline characteristics and baseline pain scores were comparable. The median pain score of latent and early active phase was lower in the aromatherapy group, 5 vs 6 and 7 vs 8, respectively. The mean differences of pain scores between latent and early active phase and the baseline were significantly lower in the aromatherapy group, 1.88 vs 2.6 (p = 0.010) and 3.82 vs 4.39 (p = 0.031), respectively. Late active phase pain scores and other perinatal outcomes were not significantly different. Aromatherapy is helpful in reducing pain in latent and early active phase, and can probably be used as an adjunctive method for labor pain control without serious side effects.

Implementation of adiabatic geometric gates with superconducting phase qubits.

PubMed

Peng, Z H; Chu, H F; Wang, Z D; Zheng, D N

2009-01-28

We present an adiabatic geometric quantum computation strategy based on the non-degenerate energy eigenstates in (but not limited to) superconducting phase qubit systems. The fidelity of the designed quantum gate was evaluated in the presence of simulated thermal fluctuations in a superconducting phase qubits circuit and was found to be quite robust against random errors. In addition, it was elucidated that the Berry phase in the designed adiabatic evolution may be detected directly via the quantum state tomography developed for superconducting qubits. We also analyze the effects of control parameter fluctuations on the experimental detection of the Berry phase.

Acupressure in Controlling Nausea in Young Patients Receiving Highly Emetogenic Chemotherapy | Division of Cancer Prevention

Cancer.gov

RATIONALE: Acupressure wristbands may prevent or reduce nausea and caused by chemotherapy. It is not yet known whether standard care is more effective with or without acupressure wristbands in controlling acute and delayed nausea. PURPOSE: This randomized phase III trial is studying how well acupressure wristbands work with or without standard care in controlling nausea in

Efficacy and safety of tolvaptan in heart failure patients with volume overload despite the standard treatment with conventional diuretics: a phase III, randomized, double-blind, placebo-controlled study (QUEST study).

PubMed

Matsuzaki, Masunori; Hori, Masatsugu; Izumi, Tohru; Fukunami, Masatake

2011-12-01

Diuretics are recommended to treat volume overload with heart failure (HF), however, they may cause serum electrolyte imbalance, limiting their use. Moreover, patients with advanced HF could poorly respond to these diuretics. In this study, we evaluated the efficacy and safety of Tolvaptan, a competitive vasopressin V2-receptor antagonist developed as a new drug to treat volume overload in HF patients. A phase III, multicenter, randomized, double-blind, placebo-controlled parallel study was performed to assess the efficacy and safety of tolvaptan in treating HF patients with volume overload despite the use of conventional diuretics. One hundred and ten patients were randomly assigned to receive either placebo or 15 mg/day tolvaptan for 7 consecutive days. Compared with placebo, tolvaptan administered for 7 days significantly reduced body weight and improved symptoms associated with volume overload. The safety profile of tolvaptan was considered acceptable for clinical use with minimal adverse effects. Tolvaptan reduced volume overload and improved congestive symptoms associated with HF by a potent water diuresis (aquaresis).

Safety and hemostatic efficacy of fibrin pad in partial nephrectomy: Results of an open-label Phase I and a randomized, standard-of-care-controlled Phase I/II study

PubMed Central

2012-01-01

Background Bleeding severity, anatomic location, tissue characteristics, and visibility are common challenges encountered while managing intraoperative bleeding, and conventional hemostatic measures (suture, ligature, and cautery) may sometimes be ineffective or impractical. While topical absorbable hemostats (TAH) are useful hemostatic adjuvants, each TAH has associated disadvantages. Methods We evaluated the safety and hemostatic efficacy of a new advanced biologic combination product―fibrin pad―to potentially address some gaps associated with TAHs. Fibrin pad was assessed as adjunctive hemostat in open partial nephrectomy in single-center, open-label, Phase I study (N = 10), and as primary hemostat in multicenter, single-blind, randomized, standard-of-care (SOC)-controlled Phase I/II study (N = 7) in Israel. It was used to control mild-to-moderate bleeding in Phase I and also spurting arterial bleeding in Phase I/II study. Phase I study assessed safety and Phase I/II study, proportion of successes at 10 min following randomization, analyzed by Fisher exact tests at 5% significance level. Results Phase I (N = 10): All patients completed the study. Hemostasis was achieved within 3–4 min (average = 3.1 min) of a single application in all patients. Fibrin pad was found to be safe for human use, with no product-related adverse events reported. Phase I/II (N = 7): Hemostatic success at 10 min (primary endpoint) was achieved in 3/4 patients treated with fibrin pad versus 0/3 patients treated with SOC. No clinically significant change in laboratory or coagulation parameters was recorded, except a case of post-procedural hemorrhage with fibrin pad, which was considered serious and related to the fibrin pad treatment, and required re-operation. Although Data Safety Monitoring Board authorized trial continuation, the sponsor decided against proceeding toward an indication for primary treatment of severe arterial hemorrhage as a replacement for sutures. The study was suspended after 7/30 planned subjects were enrolled. Conclusions The first-in-man trial of fibrin pad demonstrated its safety and efficacy as an adjunctive hemostatic technique for mild-to-moderate bleeding in partial nephrectomy. The study also suggested that the product should not replace sutures or meticulous surgical techniques for the treatment of severe arterial hemorrhage. Trial registration Phase I/II trial, NCT00598130 PMID:23137020

Mechanisms of behavioural maintenance: Long-term effects of theory-based interventions to promote safe water consumption.

PubMed

Inauen, Jennifer; Mosler, Hans-Joachim

2016-01-01

Theory-based interventions can enhance people's safe water consumption, but the sustainability of these interventions and the mechanisms of maintenance remain unclear. We investigated these questions based on an extended theory of planned behaviour. Seven hundred and ten (445 analysed) randomly selected households participated in two cluster-randomised controlled trials in Bangladesh. Study 1 promoted switching to neighbours' arsenic-safe wells, and Study 2 promoted switching to arsenic-safe deep wells. Both studies included two intervention phases. Structured interviews were conducted at baseline (T1), and at 1-month (T2), 2-month (T3) and 9-month (T4) follow-ups. In intervention phase 1 (between T1 and T2), commitment-based behaviour change techniques--reminders, implementation intentions and public commitment--were combined with information and compared to an information-only control group. In phase 2 (between T2 and T3), half of each phase 1 intervention group was randomly assigned to receive either commitment-based techniques once more or coping planning with reminders and information. Initial well-switching rates of up to 60% significantly declined by T4: 38.3% of T2 safe water users stopped consuming arsenic-safe water. The decline depended on the intervention. Perceived behavioural control, intentions, commitment strength and coping planning were associated with maintenance. In line with previous studies, the results indicate that commitment and reminders engender long-term behavioural change.

Effects of the Opioid Receptor Antagonist Naltrexone on Smoking and Related Behaviors in Smokers Preparing to Quit: A Randomized Controlled Trial

PubMed Central

King, Andrea; Cao, Dingcai; Zhang, Lingjiao; Rueger, Sandra Yu

2013-01-01

Aims To determine if naltrexone affects smoking behaviours in smokers preparing to quit, and whether such pre-quit responses predict post-quit date outcomes. Design Double-blind, placebo-controlled, randomized study. Current study focused on smoking-related outcomes in the pre-quit phase, which was one week prior to the quit date, and these findings were linked with reductions in same outcomes demonstrated in the post-quit phase previously published for this RCT in mediation analyses. Setting Community sample of adult smokers desiring to quit in Chicago, Illinois USA. Participants Participants were 315 smokers randomized to naltrexone (n=161; mean age=42.6 years; 60% white) or placebo (n=154; mean age=41.3 years; 55% white). Measurements Difference from baseline in the number of cigarettes smoked during pre-quit phase interval was the primary outcome. Secondary pre-quit outcomes were assessed using Likert scales of subjective responses and consumption of cigarettes, alcohol, and food. Number of cigarettes smoked, alcoholic drinks consumed, and the Brief Questionnaire of Smoking Urges were assessed in the post-quit phase. Findings Relative to placebo, naltrexone decreased the number of cigarettes smoked (−4.21 vs. −2.93, p<.05), smoking urge (p=.02), and number of alcoholic drinks consumed (p=.04). Exploratory mediation analyses linking outcomes of the pre quit and post quit phases found that naltrexone’s effects on reducing smoking urge, cigarettes smoked and alcoholic drinks consumed in the pre-quit phase demonstrated full mediation of their respective effects during the post-quit phase. Conclusions Naltrexone taken in the week before a quit attempt appears to reduce cigarette consumption, urges to smoke and alcohol consumption relative to placebo. The size of the effect statistically mediates the size of similar effects after the quit date. PMID:23714324

Effect of low-level laser therapy (LLLT) and light-emitting diodes (LEDT) applied during combined training on performance and post-exercise recovery: protocol for a randomized placebo-controlled trial.

PubMed

Machado, Aryane Flauzino; Micheletti, Jéssica Kirsch; Vanderlei, Franciele Marques; Nakamura, Fabio Yuzo; Leal-Junior, Ernesto Cesar Pinto; Netto Junior, Jayme; Pastre, Carlos Marcelo

Previous studies have shown positive results of phototherapy for improving performance and accelerating recovery; however, the effects of phototherapy during training and after a primary adaptation remain unclear. The aim of this randomized controlled trial is to analyze the effects of phototherapy and combined training on clinical, functional, and psychological outcomes and on vascular endothelial growth factor. This randomized placebo-controlled trial by stratified sample will involve 45 healthy male participants. In phase 1, the participants will undergo six weeks of combined training (sprints and squats). In phase 2, participants will be allocated through stratified randomization (based on adaptation capacity) into three groups: active phototherapy group (AG), placebo group (PG), and non-treatment control group (CG). A new six-week training program will then start and the participants will receive the recovery strategy between sprints and squats. The primary outcome will be maximal isometric contraction. The secondary outcomes include strength and power testing, maximal incremental test, squat jump, sprint test, muscle soreness, pain threshold, perceptions of exertion and recovery, psychological questionnaire, and vascular endothelial growth factor. This will be the first trial to include phototherapy during training. We believe that this strategy will combine the ergogenic and prophylactic effects in the same session. Furthermore, an application protocol performed after primary adaptation may reflect the real effect of the technique. Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

Design and Methods of a Randomized Trial of Continuous Glucose Monitoring in Persons With Type 1 Diabetes With Impaired Glycemic Control Treated With Multiple Daily Insulin Injections (GOLD Study).

PubMed

Lind, Marcus; Polonsky, William; Hirsch, Irl B; Heise, Tim; Bolinder, Jan; Dahlqvist, Sofia; Pehrsson, Nils-Gunnar; Moström, Peter

2016-05-01

The majority of individuals with type 1 diabetes today have glucose levels exceeding guidelines. The primary aim of this study was to evaluate whether continuous glucose monitoring (CGM), using the Dexcom G4 stand-alone system, improves glycemic control in adults with type 1 diabetes treated with multiple daily insulin injections (MDI). Individuals with type 1 diabetes and inadequate glycemic control (HbA1c ≥ 7.5% = 58 mmol/mol) treated with MDI were randomized in a cross-over design to the Dexcom G4 versus conventional care for 6 months followed by a 4-month wash-out period. Masked CGM was performed before randomization, during conventional treatment, and during the wash-out period to evaluate effects on hypoglycemia, hyperglycemia, and glycemic variability. Questionnaires were used to evaluate diabetes treatment satisfaction, fear of hypoglycemia, hypoglycemia confidence, diabetes-related distress, overall well-being, and physical activity during the different phases of the trial. The primary endpoint was the difference in HbA1c at the end of each treatment phase. A total of 205 patients were screened, of whom 161 were randomized between February and December 2014. Study completion is anticipated in April 2016. It is expected that the results of this study will establish whether using the Dexcom G4 stand-alone system in individuals with type 1 diabetes treated with MDI improves glycemic control, reduces hypoglycemia, and influences quality-of-life indicators and glycemic variability. © 2016 Diabetes Technology Society.

Speckle phase near random surfaces

NASA Astrophysics Data System (ADS)

Chen, Xiaoyi; Cheng, Chuanfu; An, Guoqiang; Han, Yujing; Rong, Zhenyu; Zhang, Li; Zhang, Meina

2018-03-01

Based on Kirchhoff approximation theory, the speckle phase near random surfaces with different roughness is numerically simulated. As expected, the properties of the speckle phase near the random surfaces are different from that in far field. In addition, as scattering distances and roughness increase, the average fluctuations of the speckle phase become larger. Unusually, the speckle phase is somewhat similar to the corresponding surface topography. We have performed experiments to verify the theoretical simulation results. Studies in this paper contribute to understanding the evolution of speckle phase near a random surface and provide a possible way to identify a random surface structure based on its speckle phase.

Quantum Glass of Interacting Bosons with Off-Diagonal Disorder

NASA Astrophysics Data System (ADS)

Piekarska, A. M.; Kopeć, T. K.

2018-04-01

We study disordered interacting bosons described by the Bose-Hubbard model with Gaussian-distributed random tunneling amplitudes. It is shown that the off-diagonal disorder induces a spin-glass-like ground state, characterized by randomly frozen quantum-mechanical U(1) phases of bosons. To access criticality, we employ the "n -replica trick," as in the spin-glass theory, and the Trotter-Suzuki method for decomposition of the statistical density operator, along with numerical calculations. The interplay between disorder, quantum, and thermal fluctuations leads to phase diagrams exhibiting a glassy state of bosons, which are studied as a function of model parameters. The considered system may be relevant for quantum simulators of optical-lattice bosons, where the randomness can be introduced in a controlled way. The latter is supported by a proposition of experimental realization of the system in question.

Effects of a mobility monitoring system on the cost of care in relation to reimbursement at Swiss nursing homes: learnings from a randomized controlled trial.

PubMed

Stark, Mario; Tietz, Rigo; Gattinger, Heidrun; Hantikainen, Virpi; Ott, Stefan

2017-12-01

Nursing homes in Switzerland are under pressure to efficiently coordinate staff activities to cover their personnel costs under the care financing system. In this study, the use of a mobility monitoring system accompanied with case conferences was investigated in order to improve sleep quality and estimate the cost benefit of this intervention. In an open two-phase randomized controlled trial at three nursing homes, residents with cognitive impairment were randomly assigned to an intervention group and a control group. In the intervention group, a 10-week period of intensive use of the monitoring system and case conferences led by an advanced nurse practitioner (Phase I) was followed by 3 months of reduced use of the monitoring system and case conferences led by an internal registered nurse (Phase II). In the control group, the monitoring system was only used for data acquisition. Nurses reported the activities with a specifically developed tool. Based on the recorded activities, the cost of care was calculated. The correlating reimbursement per patient was calculated from the care levels in the Swiss reimbursement system. Data from 44 residents was included in the analysis with a linear mixed model. Although analysis revealed no statistically significant effects, results indicate that the use of a monitoring system can guide nurses in organizing their tasks to increase effectiveness. Information systems such as the mobility monitor can help to identify single outliers that do not correspond with the overall situation. In the health care system, problematic individual cases can account for a disproportionally high cost levels. It was shown that information systems can have a significant economic impact in the long run. The study is registered at the German Clinical Trials Register under the Nr. DRKS00006829 .

Safety of Bifidobacterium animalis subsp. lactis (B. lactis) strain BB-12-supplemented yogurt in healthy adults on antibiotics: a phase I safety study.

PubMed

Merenstein, Daniel J; Tan, Tina P; Molokin, Aleksey; Smith, Keisha Herbin; Roberts, Robert F; Shara, Nawar M; Mete, Mihriye; Sanders, Mary Ellen; Solano-Aguilar, Gloria

2015-01-01

Probiotics are live microorganisms that, when administered in sufficient doses, provide health benefits on the host. The United States Food and Drug Administration (FDA) requires phase I safety studies for probiotics when the intended use of the product is as a drug. The purpose of the study was to determine the safety of Bifidobacterium animalis subsp lactis (B. lactis) strain BB-12 (BB-12)-supplemented yogurt when consumed by a generally healthy group of adults who were prescribed a 10-day course of antibiotics for a respiratory infection. Secondary aims were to assess the ability of BB-12 to affect the expression of whole blood immune markers associated with cell activation and inflammatory response. A phase I, double-blinded, randomized controlled study was conducted in compliance with FDA guidelines for an Investigational New Drug (IND). Forty participants were randomly assigned to consume 4 ounces of either BB-12 -supplemented yogurt or non-supplemented control yogurt daily for 10 d. The primary outcome was to assess safety and tolerability, assessed by the number of reported adverse events. A total of 165 non-serious adverse events were reported, with no differences between the control and BB-12 groups. When compared to the control group, B lactis fecal levels were modestly higher in the BB-12-supplemented group. In a small subset of patients, changes in whole blood expression of genes associated with regulation and activation of immune cells were detected in the BB-12-supplemented group. BB-12-supplemented yogurt is safe and well tolerated when consumed by healthy adults concurrently taking antibiotics. This study will form the basis for future randomized clinical trials investigating the potential immunomodulatory effects of BB-12-supplemented yogurt in a variety of disease states.

Dietary Soy Supplement on Fibromyalgia Symptoms: A Randomized, Double-Blind, Placebo-Controlled, Early Phase Trial

PubMed Central

Wahner-Roedler, Dietlind L.; Thompson, Jeffrey M.; Luedtke, Connie A.; King, Susan M.; Cha, Stephen S.; Elkin, Peter L.; Bruce, Barbara K.; Townsend, Cynthia O.; Bergeson, Jody R.; Eickhoff, Andrea L.; Loehrer, Laura L.; Sood, Amit; Bauer, Brent A.

2011-01-01

Most patients with fibromyalgia use complementary and alternative medicine (CAM). Properly designed controlled trials are necessary to assess the effectiveness of these practices. This study was a randomized, double-blind, placebo-controlled, early phase trial. Fifty patients seen at a fibromyalgia outpatient treatment program were randomly assigned to a daily soy or placebo (casein) shake. Outcome measures were scores of the Fibromyalgia Impact Questionnaire (FIQ) and the Center for Epidemiologic Studies Depression Scale (CES-D) at baseline and after 6 weeks of intervention. Analysis was with standard statistics based on the null hypothesis, and separation test for early phase CAM comparative trials. Twenty-eight patients completed the study. Use of standard statistics with intent-to-treat analysis showed that total FIQ scores decreased by 14% in the soy group (P = .02) and by 18% in the placebo group (P < .001). The difference in change in scores between the groups was not significant (P = .16). With the same analysis, CES-D scores decreased in the soy group by 16% (P = .004) and in the placebo group by 15% (P = .05). The change in scores was similar in the groups (P = .83). Results of statistical analysis using the separation test and intent-to-treat analysis revealed no benefit of soy compared with placebo. Shakes that contain soy and shakes that contain casein, when combined with a multidisciplinary fibromyalgia treatment program, provide a decrease in fibromyalgia symptoms. Separation between the effects of soy and casein (control) shakes did not favor the intervention. Therefore, large-sample studies using soy for patients with fibromyalgia are probably not indicated. PMID:18990724

Oxcarbazepine in migraine headache: a double-blind, randomized, placebo-controlled study.

PubMed

Silberstein, S; Saper, J; Berenson, F; Somogyi, M; McCague, K; D'Souza, J

2008-02-12

To evaluate the efficacy, safety, and tolerability of oxcarbazepine (1,200 mg/day) vs placebo as prophylactic therapy for patients with migraine headaches. This multicenter, double-blind, randomized, placebo-controlled, parallel-group trial consisted of a 4-week single-blind baseline phase and a 15-week double-blind phase consisting of a 6-week titration period, an 8-week maintenance period, and a 1-week down-titration period, after which patients could enter a 13-week open-label extension phase. During the 6-week titration period, oxcarbazepine was initiated at 150 mg/day and increased by 150 mg/day every 5 days to a maximum tolerated dose of 1,200 mg/day. The primary outcome measure was change from baseline in the number of migraine attacks during the last 28-day period of the double-blind phase. Eighty-five patients were randomized to receive oxcarbazepine and 85 to receive placebo. There was no difference between the oxcarbazepine (-1.30) and placebo groups in mean change in number of migraine attacks from baseline during the last 28 days of double-blind phase (-1.74; p = 0.2274). Adverse events were reported for 68 oxcarbazepine-treated patients (80%) and 55 placebo-treated patients (65%). The majority of adverse events were mild or moderate in severity. The most common adverse events (>or=15% of patients) in the oxcarbazepine-treated group were fatigue (20.0%), dizziness (17.6%), and nausea (16.5%); no adverse event occurred in more than 15% of the placebo-treated patients. Overall, oxcarbazepine was safe and well tolerated; however, oxcarbazepine did not show efficacy in the prophylactic treatment of migraine headaches.

The Effects of Intrapartum Supportive Care on Fear of Delivery and Labor Outcomes: A Single-Blind Randomized Controlled Trial.

PubMed

İsbir, Gözde Gökçe; Serçekuş, Pinar

2017-04-01

Supportive care during labor, the primary role of intrapartum nurses and midwives, provides comfort to prepartum women and helps facilitate a positive labor experience. It has been argued that supportive care during labor reduces fear and anxiety as well as the resultant side effects. However, evidence supporting this argument is insufficient. The aim of this study was to assess the effects of intrapartum supportive care on fear of delivery and on the key parameters of the labor process. This study used a single-blind randomized controlled trial approach. Randomized block assignment was used to assign 72 participants to either the intervention group (n = 36) or the control group (n = 36). Three women in the intervention group and six in the control group were later excluded from the study because they received emergency cesarean delivery. The intervention group received continuous supportive care, and the control group received routine hospital care. No significant differences were identified between the two groups at baseline. The intervention group reported less fear of delivery during the active and transient phases of labor, higher perceived support and control during delivery, lower pain scores during the transient phase of labor, and a shorter delivery period than the control group (p < .05). However, no significant difference in the use of oxytocin during delivery between the two groups was reported. The results of this evidence-based study suggest that continuous support during labor has clinically meaningful benefits for women and that all women should receive this support throughout their labor and delivery process.

The feasibility of conducting a randomised controlled trial comparing arthroscopic hip surgery to conservative care for patients with femoroacetabular impingement syndrome: the FASHIoN feasibility study.

PubMed

Griffin, D R; Dickenson, E J; Wall, P D H; Realpe, A; Adams, A; Parsons, N; Hobson, R; Achten, J; Costa, M L; Foster, N E; Hutchinson, C E; Petrou, S; Donovan, J L

2016-10-01

To determine whether it was feasible to perform a randomized controlled trial (RCT) comparing arthroscopic hip surgery to conservative care in patients with femoroacetabular impingement (FAI). This study had two phases: a pre-pilot and pilot RCT. In the pre-pilot, we conducted interviews with clinicians who treated FAI and with FAI patients to determine their views about an RCT. We developed protocols for operative and conservative care. In the pilot RCT, we determined the rates of patient eligibility, recruitment and retention, to investigate the feasibility of the protocol and we established methods to assess treatment fidelity. In the pre-pilot phase, 32 clinicians were interviewed, of which 26 reported theoretical equipoise, but in example scenarios 7 failed to show clinical equipoise. Eighteen patients treated for FAI were also interviewed, the majority of whom felt that surgery and conservative care were acceptable treatments. Surgery was viewed by patients as a 'definitive solution'. Patients were motivated to participate in research but were uncomfortable about randomization. Randomization was more acceptable if the alternative was available at the end of the trial. In the pilot phase, 151 patients were assessed for eligibility. Sixty were eligible and invited to take part in the pilot RCT; 42 consented to randomization. Follow-up was 100% at 12 months. Assessments of treatment fidelity were satisfactory. An RCT to compare arthroscopic hip surgery with conservative care in patients with FAI is challenging but feasible. Recruitment has started for a full RCT.

Bayesian randomized clinical trials: From fixed to adaptive design.

PubMed

Yin, Guosheng; Lam, Chi Kin; Shi, Haolun

2017-08-01

Randomized controlled studies are the gold standard for phase III clinical trials. Using α-spending functions to control the overall type I error rate, group sequential methods are well established and have been dominating phase III studies. Bayesian randomized design, on the other hand, can be viewed as a complement instead of competitive approach to the frequentist methods. For the fixed Bayesian design, the hypothesis testing can be cast in the posterior probability or Bayes factor framework, which has a direct link to the frequentist type I error rate. Bayesian group sequential design relies upon Bayesian decision-theoretic approaches based on backward induction, which is often computationally intensive. Compared with the frequentist approaches, Bayesian methods have several advantages. The posterior predictive probability serves as a useful and convenient tool for trial monitoring, and can be updated at any time as the data accrue during the trial. The Bayesian decision-theoretic framework possesses a direct link to the decision making in the practical setting, and can be modeled more realistically to reflect the actual cost-benefit analysis during the drug development process. Other merits include the possibility of hierarchical modeling and the use of informative priors, which would lead to a more comprehensive utilization of information from both historical and longitudinal data. From fixed to adaptive design, we focus on Bayesian randomized controlled clinical trials and make extensive comparisons with frequentist counterparts through numerical studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Design of the randomized, Phase III, QUAZAR AML Maintenance trial of CC-486 (oral azacitidine) maintenance therapy in acute myeloid leukemia.

PubMed

Roboz, Gail J; Montesinos, Pau; Selleslag, Dominik; Wei, Andrew; Jang, Jun-Ho; Falantes, Jose; Voso, Maria T; Sayar, Hamid; Porkka, Kimmo; Marlton, Paula; Almeida, Antonio; Mohan, Sanjay; Ravandi, Farhad; Garcia-Manero, Guillermo; Skikne, Barry; Kantarjian, Hagop

2016-02-01

Older patients with acute myeloid leukemia (AML) have worse rates of complete remission and shorter overall survival than younger patients. The epigenetic modifier CC-486 is an oral formulation of azacitidine with promising clinical activity in patients with AML in Phase I studies. The Phase III, randomized, double-blind, placebo-controlled QUAZAR AML Maintenance trial (CC-486-AML-001) examines CC-486 maintenance therapy (300 mg/day for 14 days of 28-day treatment cycles) for patients aged ≥55 years with AML in first complete remission. The primary end point is overall survival. Secondary end points include relapse-free survival, safety, health-related quality of life and healthcare resource utilization. This trial will investigate whether CC-486 maintenance can prolong remission and improve survival for older patients with AML.

An organic khorasan wheat-based replacement diet improves risk profile of patients with acute coronary syndrome: a randomized crossover trial.

PubMed

Whittaker, Anne; Sofi, Francesco; Luisi, Maria Luisa Eliana; Rafanelli, Elena; Fiorillo, Claudia; Becatti, Matteo; Abbate, Rosanna; Casini, Alessandro; Gensini, Gian Franco; Benedettelli, Stefano

2015-05-11

Khorasan wheat is an ancient grain with previously reported health benefits in clinically healthy subjects. The aim of this study was to examine whether a replacement diet, thereby substituting all other cereal grains, with products made with organic khorasan wheat could provide additive protective effects in reducing lipid, oxidative and inflammatory risk factors, in patients with Acute Coronary Syndromes (ACS) in comparison to a similar replacement diet using products made from organic modern wheat. A randomized double-blinded crossover trial with two intervention phases was conducted on 22 ACS patients (9 F; 13 M). The patients were assigned to consume products (bread, pasta, biscuits and crackers) made either from organic semi-whole khorasan wheat or organic semi-whole control wheat for eight weeks in a random order. On average, patients ingested 62.0 g dry weight (DW) day-1 khorasan or control semolina; and 140.5 g DW day-1 khorasan or control flour, respectively. An eight-week washout period was implemented between the respective interventions. Blood analyses were performed both at the beginning and end of each intervention phase; thereby permitting a comparison of both the khorasan and control intervention phases, respectively, on circulatory risk factors for the same patient. Consumption of products made with khorasan wheat resulted in a significant amelioration in total cholesterol (-6.8%), low-density lipoprotein cholesterol (LDL-C) (-8.1%) glucose (-8%) and insulin (-24.6%) from baseline levels, independently of age, sex, traditional risk factors, medication and diet quality. Moreover, there was a significant reduction in reactive oxygen species (ROS), lipoperoxidation of circulating monocytes and lymphocytes, as well as in the levels of Tumor Necrosis Factor-alpha. No significant differences from baseline in the same patients were observed after the conventional control wheat intervention phase. The present results suggest that a replacement diet with cereal products made from organic khorasan wheat provides additional protection in patients with ACS. Circulating cardiovascular risk factors, including lipid parameters, and markers of both oxidative stress and inflammatory status, were reduced, irrespective of the number and combination of medicinal therapies with proven efficacy in secondary prevention.

Oestrual Phase at first exposure to Predator-induced Stress Determines Pattern of Alterations in Oestrous Cycle and Endocrine Response in the Rat.

PubMed

Medubi, O O; Iranloye, B O; Adegoke, O A

2017-06-30

Stress has been acknowledged as one of the aetiologies of female reproductive dysfunction, yet the mechanismsinvolved are not totally elucidated. Based on the paucity of information on how predator-induced stress (PS) affects oestrouscycle in rats, this study was designed to investigate the effect of PS on the oestrous cycle in rats. Forty-eight (48) SpragueDawley rats were used for this study. They were randomly divided into Control and PS group. Each group was divided intofour subgroups (n=6/group) according to the phases of oestrous cycle. Stress was induced by exposing rats to cat (predator)for 60 minutes/day for 14 consecutive days. PS caused significant disruption of the oestrous cycle. In animals subjected toPS at proestrus (PS-proestrus) and oestrus (PS-oestrus), percentage occurrence of proestrus, oestrus and metestrus phaseswere significantly reduced compared with control. In animals subjected to PS at metestrus (PS-metestrus) and diestrus (PSdiestrus), percentage occurrence of oestrus phase was not significantly affected. In all animals exposed to PS, percentageoccurrence of diestrus was significantly increased regardless of the phase of first exposure compared with control.Corticosterone and prolactin levels were significantly elevated in PS groups compared with control. Progesterone wassignificantly increased in animals at diestrus phase compared with oestrus phase and respective phases in control. Oestradiolwas significantly reduced in PS group compared with control at oestrus phase but not significantly different at diestrus phase.Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels were significantly lower in PS groups at oestrusphase compared with diestrus phase. This study shows that PS disrupts the oestrous cycle secondary to perturbation ofhormonal control of female reproduction and is influenced by the phase at first exposure to stress.

Does Assessing Suicidality Frequently and Repeatedly Cause Harm? A Randomized Control Study

PubMed Central

Law, Mary Kate; Furr, R. Michael; Arnold, Elizabeth Mayfield; Mneimne, Malek; Jaquett, Caroline; Fleeson, William

2015-01-01

Assessing suicidality is common in mental health practice and is fundamental to suicide research. Although necessary, there is significant concern that such assessments have unintended harmful consequences. Using a longitudinal randomized control design, we evaluated whether repeated and frequent assessments of suicide-related thoughts and behaviors negatively affected individuals, including those at-risk for suicide-related outcomes. Adults (N = 282), including many diagnosed with Borderline Personality Disorder (BPD), were recruited through psychiatric outpatient clinics and from the community at large, and were randomly assigned to assessment groups. A Control Assessment group responded to questions regarding negative psychological experiences several times each day during a 2-week Main Observation phase. During the same observation period, an Intensive Suicide Assessment group responded to the same questions, along with questions regarding suicidal behavior and ideation. Negative psychological outcomes were measured during the Main Observation phase (for BPD symptoms unrelated to suicide and for BPD-relevant emotions) and/or at the end of each week during the Main Observation phase and monthly for 6 months thereafter (for all outcomes, including suicidal ideation and behavior). Results revealed little evidence that intensive suicide assessment triggered negative outcomes, including suicidal ideation or behavior, even among people with BPD. A handful of effects did reach or approach significance, though these were temporary and non-robust. However, given the seriousness of some outcomes, we recommend that researchers or clinicians who implement experience sampling methods including suicide-related items carefully consider the benefits of asking about suicide and to inform participants about possible risks. PMID:25894705

Maintenance N-acetyl cysteine treatment for bipolar disorder: A double-blind randomized placebo controlled trial

PubMed Central

2012-01-01

Background N-acetyl cysteine (NAC) is a glutathione precursor that has been shown to have antidepressant efficacy in a placebo-controlled trial. The current study aimed to investigate the maintenance effects of NAC following eight weeks of open-label treatment for bipolar disorder. Method The efficacy of a double blind randomized placebo controlled trial of 2 g/day NAC as adjunct maintenance treatment for bipolar disorder was examined. Participants (n = 149) had a Montgomery Asberg Depression Rating Score of ≥12 at trial entry and, after eight weeks of open-label NAC treatment, were randomized to adjunctive NAC or placebo, in addition to treatment as usual. Participants (primarily outpatients) were recruited through public and private services and through newspaper advertisements. Time to intervention for a mood episode was the primary endpoint of the study, and changes in mood symptoms, functionality and quality of life measures were secondary outcomes. Results There was a substantial decrease in symptoms during the eight-week open-label NAC treatment phase. During the subsequent double-blind phase, there was minimal further change in outcome measures with scores remaining low. Consequently, from this low plateau, between-group differences did not emerge on recurrence, clinical functioning or quality of life measures. Conclusions There were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial; however, these findings may be confounded by limitations. Trial Registration The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000074493). PMID:22891797

A 12-week interdisciplinary rehabilitation trial in patients with gliomas - a feasibility study.

PubMed

Hansen, Anders; Søgaard, Karen; Minet, Lisbeth Rosenbek; Jarden, Jens Ole

2018-06-01

This report aims to assess the safety and feasibility of using an interdisciplinary rehabilitation intervention for a future randomized controlled trial in patients with gliomas in the initial treatment phase. We conducted an outpatient two-part rehabilitation intervention that involved six weeks of therapeutic supervised training (part one) and six weeks of unsupervised training in a local gym following a training protocol (part two). Predefined feasibility objectives of safety (100%), consent rate (>80%), drop-out (<20%), adherence (>80%) and patient satisfaction (>80%) was achieved at part one. However, the failure to meet predefined feasibility objectives of drop-out, adherence and patient satisfaction of the unsupervised intervention at part two have led to a protocol revision for a future randomized controlled trial. This study demonstrates that an intensive rehabilitation intervention of physical therapy and occupational therapy in the initial treatment phase of patients with gliomas whose Karnofsky performance status is ≥70 is safe and feasible, if relevant inclusion criteria and precautionary screening are made. With the revised protocol, we are confident that the foundation for conducting a successful randomized controlled trial among these vulnerable patients has been established. Implications for rehabilitation Brain tumors constitute some of the most challenging cancer diagnoses presenting for rehabilitation intervention. Patients with gliomas experiences limitations in physical functioning, cognition, and emotional wellbeing. In a relatively small sample this study shows that supervised physical- and occupational therapy in patients with gliomas is safe and feasible in the initial treatment phase. Patients with gliomas can potentially improve functioning through interdisciplinary rehabilitation.

The effects of physical therapy with neuromuscular electrical stimulation in patients with septic shock: Study protocol for a randomized cross-over design.

PubMed

Lago, Alessandra Fabiane; de Oliveira, Anamaria Siriani; de Souza, Hugo Celso Dutra; da Silva, João Santana; Basile-Filho, Anibal; Gastaldi, Ada Clarice

2018-02-01

Septic shock is a potentially fatal organ dysfunction caused by an imbalance of the host response to infection. The changes in microcirculation during sepsis can be explained by the alterations in the endothelial barrier function. Endothelial progenitor cells (EPCs) are a potential recovery index of endothelial function and it an increase in response to neuromuscular electrical stimulation (NMES) was demonstrated. Therefore, the objective of this study is to investigate the effects of NMES in patients with septic shock. It is a study protocol for a randomized cross-over design in an intensive care unit of a tertiary University hospital. Thirty-one patients aged 18 to 65 years. The study will be divided in 2 phases: the phase one will be held in the first 72 hours of septic shock and the phase two after 3 days of first assessment. Patients will be randomly selected to the intervention protocol (decubitus position with the limbs raised and NMES) and control protocol (decubitus position with the limbs raised without NMES). After this procedure, the patients will be allocated in group 1 (intervention and control protocol) or group 2 (control and intervention protocol) with a wash-out period of 4 to 6 hours between them. The main outcome is mobilization of EPCs. The secondary outcome is metabolic and hemodynamic data. A linear mixed model will be used for analysis of dependent variables and estimated values of the mean of the differences of each effect.

Does assessing suicidality frequently and repeatedly cause harm? A randomized control study.

PubMed

Law, Mary Kate; Furr, R Michael; Arnold, Elizabeth Mayfield; Mneimne, Malek; Jaquett, Caroline; Fleeson, William

2015-12-01

Assessing suicidality is common in mental health practice and is fundamental to suicide research. Although necessary, there is significant concern that such assessments have unintended harmful consequences. Using a longitudinal randomized control design, the authors evaluated whether repeated and frequent assessments of suicide-related thoughts and behaviors negatively affected individuals, including those at-risk for suicide-related outcomes. Adults (N = 282), including many diagnosed with borderline personality disorder (BPD), were recruited through psychiatric outpatient clinics and from the community at large, and were randomly assigned to assessment groups. A control assessment group responded to questions regarding negative psychological experiences several times each day during a 2-week main observation phase. During the same observation period, an intensive suicide assessment group responded to the same questions, along with questions regarding suicidal behavior and ideation. Negative psychological outcomes were measured during the main observation phase (for BPD symptoms unrelated to suicide and for BPD-relevant emotions) and/or at the end of each week during the main observation phase and monthly for 6 months thereafter (for all outcomes, including suicidal ideation and behavior). Results revealed little evidence that intensive suicide assessment triggered negative outcomes, including suicidal ideation or behavior, even among people with BPD. A handful of effects did reach or approach significance, though these were temporary and nonrobust. However, given the seriousness of some outcomes, the authors recommend that researchers or clinicians who implement experience sampling methods including suicide-related items carefully consider the benefits of asking about suicide and to inform participants about possible risks. (c) 2015 APA, all rights reserved).

Consequences of anorectal cancer atlas implementation in the cooperative group setting: radiobiologic analysis of a prospective randomized in silico target delineation study.

PubMed

Mavroidis, Panayiotis; Giantsoudis, Drosoula; Awan, Musaddiq J; Nijkamp, Jasper; Rasch, Coen R N; Duppen, Joop C; Thomas, Charles R; Okunieff, Paul; Jones, William E; Kachnic, Lisa A; Papanikolaou, Niko; Fuller, Clifton D

2014-09-01

The aim of this study is to ascertain the subsequent radiobiological impact of using a consensus guideline target volume delineation atlas. Using a representative case and target volume delineation instructions derived from a proposed IMRT rectal cancer clinical trial, gross tumor volume (GTV) and clinical/planning target volumes (CTV/PTV) were contoured by 13 physician observers (Phase 1). The observers were then randomly assigned to follow (atlas) or not-follow (control) a consensus guideline/atlas for anorectal cancers, and instructed to re-contour the same case (Phase 2). The atlas group was found to have increased tumor control probability (TCP) after the atlas intervention for both the CTV (p<0.0001) and PTV1 (p=0.0011) with decreasing normal tissue complication probability (NTCP) for small intestine, while the control group did not. Additionally, the atlas group had reduced variance in TCP for all target volumes and reduced variance in NTCP for the bowel. In Phase 2, the atlas group had increased TCP relative to the control for CTV (p=0.03). Visual atlas and consensus treatment guideline usage in the development of rectal cancer IMRT treatment plans reduced the inter-observer radiobiological variation, with clinically relevant TCP alteration for CTV and PTV volumes. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

A phase II flexible screening design allowing for interim analysis and comparison with historical control.

PubMed

Wu, Wenting; Bot, Brian; Hu, Yan; Geyer, Susan M; Sargent, Daniel J

2013-07-01

Sargent and Goldberg [1] proposed a randomized phase II flexible screening design (SG design) which took multiple characteristics of candidate regimens into consideration in selecting a regimen for further phase III testing. In this paper, we extend the SG design by including provisions for an interim analysis and/or a comparison to a historical control. By including a comparison with a historical control, a modified SG design not only identifies a more promising treatment but also assures that the regimen has a clinically meaningful level of efficacy as compared to a historical control. By including an interim analysis, a modified SG design could reduce the number of patients exposed to inferior treatment regimens. When compared to the original SG design, the modified designs increase the sample size moderately, but expand the utility of the flexible screening design substantially. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of a capacitive-resistive electric transfer therapy on physiological and biomechanical parameters in recreational runners: A randomized controlled crossover trial.

PubMed

Duñabeitia, Iratxe; Arrieta, Haritz; Torres-Unda, Jon; Gil, Javier; Santos-Concejero, Jordan; Gil, Susana M; Irazusta, Jon; Bidaurrazaga-Letona, Iraia

2018-05-26

This study compared the effects of a capacitive-resistive electric transfer therapy (Tecar) and passive rest on physiological and biomechanical parameters in recreational runners when performed shortly after an exhausting training session. Randomized controlled crossover trial. University biomechanical research laboratory. Fourteen trained male runners MAIN OUTCOME MEASURES: Physiological (running economy, oxygen uptake, respiratory exchange ratio, ventilation, heart rate, blood lactate concentration) and biomechanical (step length; stride angle, height, frequency, and contact time; swing time; contact phase; support phase; push-off phase) parameters were measured during two incremental treadmill running tests performed two days apart after an exhaustive training session. When running at 14 km/h and 16 km/h, the Tecar treatment group presented greater increases in stride length (p < 0.001), angle (p < 0.05) and height (p < 0.001) between the first and second tests than the control group and, accordingly, greater decreases in stride frequency (p < 0.05). Physiological parameters were similar between groups. The present study suggests that a Tecar therapy intervention enhances biomechanical parameters in recreational runners after an exhaustive training session more than passive rest, generating a more efficient running pattern without affecting selected physiological parameters. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effects of sensorimotor foot training on the symmetry of weight distribution on the lower extremities of patients in the chronic phase after stroke

PubMed Central

Goliwas, Magdalena; Kocur, Piotr; Furmaniuk, Lech; Majchrzycki, Marian; Wiernicka, Marzena; Lewandowski, Jacek

2015-01-01

[Purpose] To assess the effects of sensorimotor foot stimulation on the symmetry of weight distribution on the feet of patients in the chronic post-stroke phase. [Subjects and Methods] This study was a prospective, single blind, randomized controlled trial. In the study we examined patients with chronic stroke (post-stroke duration > 1 year). They were randomly allocated to the study group (n=8) or to the control group (n=12). Both groups completed a standard six-week rehabilitation programme. In the study group, the standard rehabilitation programme was supplemented with sensorimotor foot stimulation training. Each patient underwent two assessments of symmetry of weight distribution on the lower extremities with and without visual control, on a treadmill, with stabilometry measurements, and under static conditions. [Results] Only the study group demonstrated a significant increase in the weight placed on the leg directly affected by stroke, and a reduction in asymmetry of weight-bearing on the lower extremities. [Conclusion] Sensorimotor stimulation of the feet enhanced of weight bearing on the foot on the side of the body directly affected by stroke, and a decreased asymmetry of weight distribution on the lower extremities of patients in the chronic post-stroke phase. PMID:26504326

Effects of sensorimotor foot training on the symmetry of weight distribution on the lower extremities of patients in the chronic phase after stroke.

PubMed

Goliwas, Magdalena; Kocur, Piotr; Furmaniuk, Lech; Majchrzycki, Marian; Wiernicka, Marzena; Lewandowski, Jacek

2015-09-01

[Purpose] To assess the effects of sensorimotor foot stimulation on the symmetry of weight distribution on the feet of patients in the chronic post-stroke phase. [Subjects and Methods] This study was a prospective, single blind, randomized controlled trial. In the study we examined patients with chronic stroke (post-stroke duration > 1 year). They were randomly allocated to the study group (n=8) or to the control group (n=12). Both groups completed a standard six-week rehabilitation programme. In the study group, the standard rehabilitation programme was supplemented with sensorimotor foot stimulation training. Each patient underwent two assessments of symmetry of weight distribution on the lower extremities with and without visual control, on a treadmill, with stabilometry measurements, and under static conditions. [Results] Only the study group demonstrated a significant increase in the weight placed on the leg directly affected by stroke, and a reduction in asymmetry of weight-bearing on the lower extremities. [Conclusion] Sensorimotor stimulation of the feet enhanced of weight bearing on the foot on the side of the body directly affected by stroke, and a decreased asymmetry of weight distribution on the lower extremities of patients in the chronic post-stroke phase.

A randomized controlled trial with bright light and melatonin for delayed sleep phase disorder: effects on subjective and objective sleep.

PubMed

Saxvig, Ingvild West; Wilhelmsen-Langeland, Ane; Pallesen, Ståle; Vedaa, Oystein; Nordhus, Inger Hilde; Bjorvatn, Bjørn

2014-02-01

Delayed sleep phase disorder (DSPD) is assumed to be common amongst adolescents, with potentially severe consequences in terms of school attendance and daytime functioning. The most common treatment approaches for DSPD are based on the administration of bright light and/or exogenous melatonin with or without adjunct behavioural instructions. Much is generally known about the chronobiological effects of light and melatonin. However, placebo-controlled treatment studies for DSPD are scarce, in particular in adolescents and young adults, and no standardized guidelines exist regarding treatment. The aim of the present study was, therefore, to investigate the short- and long-term effects on sleep of a DSPD treatment protocol involving administration of timed bright light and melatonin alongside gradual advancement of rise time in adolescents and young adults with DSPD in a randomized controlled trial and an open label follow-up study. A total of 40 adolescents and young adults (age range 16-25 years) diagnosed with DSPD were recruited to participate in the study. The participants were randomized to receive treatment for two weeks in one of four treatment conditions: dim light and placebo capsules, bright light and placebo capsules, dim light and melatonin capsules or bright light and melatonin capsules. In a follow-up study, participants were re-randomized to either receive treatment with the combination of bright light and melatonin or no treatment in an open label trial for approximately three months. Light and capsules were administered alongside gradual advancement of rise times. The main end points were sleep as assessed by sleep diaries and actigraphy recordings and circadian phase as assessed by salivary dim light melatonin onset (DLMO). During the two-week intervention, the timing of sleep and DLMO was advanced in all treatment conditions as seen by about 1 h advance of bed time, 2 h advance of rise time and 2 h advance of DLMO in all four groups. Sleep duration was reduced with approximately 1 h. At three-month follow-up, only the treatment group had maintained an advanced sleep phase. Sleep duration had returned to baseline levels in both groups. In conclusion, gradual advancement of rise time produced a phase advance during the two-week intervention, irrespective of treatment condition. Termination of treatment caused relapse into delayed sleep times, whereas long-term treatment with bright light and melatonin (three months) allowed maintenance of the advanced sleep phase.

Luteal Phase Support in the Intrauterine Insemination (IUI) Cycles: A Randomized Double Blind, Placebo Controlled Study

PubMed Central

Hossein Rashidi, Batool; Davari Tanha, Fatemeh; Rahmanpour, Haleh; Ghazizadeh, Mahya

2014-01-01

Objective: To evaluate the impact of luteal phase support with vaginal progesterone on pregnancy rates in the intrauterine insemination (IUI) cycles, stimulated with clomiphene citrate and human menopausal gonadotropin (hMG), in sub fertile couples. Materials and methods: This prospective, randomized, double blind study was performed in a tertiary infertility center from March 2011 to January 2012. It consisted of 253 sub fertile couples undergoing ovarian stimulation for IUI cycles. They underwent ovarian stimulation with clomiphene citrate (100 mg) and hMG (75 IU) in preparation for the IUI cycle. Study group (n = 127) received luteal phase support in the form of vaginal progesterone (400 mg twice a day), and control group (n = 126) received placebo. Clinical pregnancy and abortion rates were assessed and compared between the two groups. Results: The clinical pregnancy rate was not significantly higher for supported cycles than that for the unsupported ones (15.75% vs. 12.69%, p = 0.3). The abortion rate in the patients with progesterone luteal support compared to placebo group was not statistically different (10% vs. 18.75%, p = 0.45). Conclusion: It seems that luteal phase support with vaginal progesterone was not enhanced the success of IUI cycles outcomes, when clomiphene citrate and hMG were used for ovulation stimulation. PMID:25530766

A Robust Parameterization of Human Gait Patterns Across Phase-Shifting Perturbations

PubMed Central

Villarreal, Dario J.; Poonawala, Hasan A.; Gregg, Robert D.

2016-01-01

The phase of human gait is difficult to quantify accurately in the presence of disturbances. In contrast, recent bipedal robots use time-independent controllers relying on a mechanical phase variable to synchronize joint patterns through the gait cycle. This concept has inspired studies to determine if human joint patterns can also be parameterized by a mechanical variable. Although many phase variable candidates have been proposed, it remains unclear which, if any, provide a robust representation of phase for human gait analysis or control. In this paper we analytically derive an ideal phase variable (the hip phase angle) that is provably monotonic and bounded throughout the gait cycle. To examine the robustness of this phase variable, ten able-bodied human subjects walked over a platform that randomly applied phase-shifting perturbations to the stance leg. A statistical analysis found the correlations between nominal and perturbed joint trajectories to be significantly greater when parameterized by the hip phase angle (0.95+) than by time or a different phase variable. The hip phase angle also best parameterized the transient errors about the nominal periodic orbit. Finally, interlimb phasing was best explained by local (ipsilateral) hip phase angles that are synchronized during the double-support period. PMID:27187967

Analysis of force profile during a maximum voluntary isometric contraction task.

PubMed

Househam, Elizabeth; McAuley, John; Charles, Thompson; Lightfoot, Timothy; Swash, Michael

2004-03-01

This study analyses maximum voluntary isometric contraction (MVIC) and its measurement by recording the force profile during maximal-effort, 7-s hand-grip contractions. Six healthy subjects each performed three trials repeated at short intervals to study variation from fatigue. These three trials were performed during three separate sessions at daily intervals to look at random variation. A pattern of force development during a trial was identified. An initiation phase, with or without an initiation peak, was followed by a maintenance phase, sometimes with secondary pulses and an underlying decline in force. Of these three MVIC parameters, maximum force during the maintenance phase showed less random variability compared to intertrial fatigue variability than did maximum force during the initiation phase or absolute maximum force. Analysis of MVIC as a task, rather than a single, maximal value reveals deeper levels of motor control in its generation. Thus, force parameters other than the absolute maximum force may be better suited to quantification of muscle performance in health and disease.

Review of Random Phase Encoding in Volume Holographic Storage

PubMed Central

Su, Wei-Chia; Sun, Ching-Cherng

2012-01-01

Random phase encoding is a unique technique for volume hologram which can be applied to various applications such as holographic multiplexing storage, image encryption, and optical sensing. In this review article, we first review and discuss diffraction selectivity of random phase encoding in volume holograms, which is the most important parameter related to multiplexing capacity of volume holographic storage. We then review an image encryption system based on random phase encoding. The alignment of phase key for decryption of the encoded image stored in holographic memory is analyzed and discussed. In the latter part of the review, an all-optical sensing system implemented by random phase encoding and holographic interconnection is presented.

The MOnitoring Resynchronization dEvices and CARdiac patiEnts (MORE-CARE) randomized controlled trial: phase 1 results on dynamics of early intervention with remote monitoring.

PubMed

Boriani, Giuseppe; Da Costa, Antoine; Ricci, Renato Pietro; Quesada, Aurelio; Favale, Stefano; Iacopino, Saverio; Romeo, Francesco; Risi, Arnaldo; Mangoni di S Stefano, Lorenza; Navarro, Xavier; Biffi, Mauro; Santini, Massimo; Burri, Haran

2013-08-21

Remote monitoring (RM) in patients with advanced heart failure and cardiac resynchronization therapy defibrillators (CRT-D) may reduce delays in clinical decisions by transmitting automatic alerts. However, this strategy has never been tested specifically in this patient population, with alerts for lung fluid overload, and in a European setting. The main objective of Phase 1 (presented here) is to evaluate if RM strategy is able to reduce time from device-detected events to clinical decisions. In this multicenter randomized controlled trial, patients with moderate to severe heart failure implanted with CRT-D devices were randomized to a Remote group (with remote follow-up and wireless automatic alerts) or to a Control group (with standard follow-up without alerts). The primary endpoint of Phase 1 was the delay between an alert event and clinical decisions related to the event in the first 154 enrolled patients followed for 1 year. The median delay from device-detected events to clinical decisions was considerably shorter in the Remote group compared to the Control group: 2 (25(th)-75(th) percentile, 1-4) days vs 29 (25(th)-75(th) percentile, 3-51) days respectively, P=.004. In-hospital visits were reduced in the Remote group (2.0 visits/patient/year vs 3.2 visits/patient/year in the Control group, 37.5% relative reduction, P<.001). Automatic alerts were successfully transmitted in 93% of events occurring outside the hospital in the Remote group. The annual rate of all-cause hospitalizations per patient did not differ between the two groups (P=.65). RM in CRT-D patients with advanced heart failure allows physicians to promptly react to clinically relevant automatic alerts and significantly reduces the burden of in-hospital visits. Clinicaltrials.gov NCT00885677; http://clinicaltrials.gov/show/NCT00885677 (Archived by WebCite at http://www.webcitation.org/6IkcCJ7NF).

The MOnitoring Resynchronization dEvices and CARdiac patiEnts (MORE-CARE) Randomized Controlled Trial: Phase 1 Results on Dynamics of Early Intervention With Remote Monitoring

PubMed Central

Da Costa, Antoine; Ricci, Renato Pietro; Quesada, Aurelio; Favale, Stefano; Iacopino, Saverio; Romeo, Francesco; Risi, Arnaldo; Mangoni di S Stefano, Lorenza; Navarro, Xavier; Biffi, Mauro; Santini, Massimo; Burri, Haran

2013-01-01

Background Remote monitoring (RM) in patients with advanced heart failure and cardiac resynchronization therapy defibrillators (CRT-D) may reduce delays in clinical decisions by transmitting automatic alerts. However, this strategy has never been tested specifically in this patient population, with alerts for lung fluid overload, and in a European setting. Objective The main objective of Phase 1 (presented here) is to evaluate if RM strategy is able to reduce time from device-detected events to clinical decisions. Methods In this multicenter randomized controlled trial, patients with moderate to severe heart failure implanted with CRT-D devices were randomized to a Remote group (with remote follow-up and wireless automatic alerts) or to a Control group (with standard follow-up without alerts). The primary endpoint of Phase 1 was the delay between an alert event and clinical decisions related to the event in the first 154 enrolled patients followed for 1 year. Results The median delay from device-detected events to clinical decisions was considerably shorter in the Remote group compared to the Control group: 2 (25th-75th percentile, 1-4) days vs 29 (25th-75th percentile, 3-51) days respectively, P=.004. In-hospital visits were reduced in the Remote group (2.0 visits/patient/year vs 3.2 visits/patient/year in the Control group, 37.5% relative reduction, P<.001). Automatic alerts were successfully transmitted in 93% of events occurring outside the hospital in the Remote group. The annual rate of all-cause hospitalizations per patient did not differ between the two groups (P=.65). Conclusions RM in CRT-D patients with advanced heart failure allows physicians to promptly react to clinically relevant automatic alerts and significantly reduces the burden of in-hospital visits. Trial Registration Clinicaltrials.gov NCT00885677; http://clinicaltrials.gov/show/NCT00885677 (Archived by WebCite at http://www.webcitation.org/6IkcCJ7NF). PMID:23965236

Phase and amplitude modification of a laser beam by two deformable mirrors using conventional 4f image encryption techniques

NASA Astrophysics Data System (ADS)

Wu, Chensheng; Ko, Jonathan; Rzasa, John Robertson; Davis, Christopher C.

2017-08-01

The image encryption and decryption technique using lens components and random phase screens has attracted a great deal of research interest in the past few years. In general, the optical encryption technique can translate a positive image into an image with nearly a white speckle pattern that is impossible to decrypt. However, with the right keys as conjugated random phase screens, the white noise speckle pattern can be decoded into the original image. We find that the fundamental ideas in image encryption can be borrowed and applied to carry out beam corrections through turbulent channels. Based on our detailed analysis, we show that by using two deformable mirrors arranged in similar fashions as in the image encryption technique, a large number of controllable phase and amplitude distribution patterns can be generated from a collimated Gaussian beam. Such a result can be further coupled with wavefront sensing techniques to achieve laser beam correction against turbulence distortions. In application, our approach leads to a new type of phase conjugation mirror that could be beneficial for directed energy systems.

A Derivation of the Long-Term Degradation of a Pulsed Atomic Frequency Standard from a Control-Loop Model

NASA Technical Reports Server (NTRS)

Greenhall, C. A.

1996-01-01

The phase of a frequency standard that uses periodic interrogation and control of a local oscillator (LO) is degraded by a long-term random-walk component induced by downconversion of LO noise into the loop passband. The Dick formula for the noise level of this degradation is derived from an explicit solution of an LO control-loop model.

Nonequilibrium Statistical Mechanics in One Dimension

NASA Astrophysics Data System (ADS)

Privman, Vladimir

2005-08-01

Part I. Reaction-Diffusion Systems and Models of Catalysis; 1. Scaling theories of diffusion-controlled and ballistically-controlled bimolecular reactions S. Redner; 2. The coalescence process, A+A->A, and the method of interparticle distribution functions D. ben-Avraham; 3. Critical phenomena at absorbing states R. Dickman; Part II. Kinetic Ising Models; 4. Kinetic ising models with competing dynamics: mappings, correlations, steady states, and phase transitions Z. Racz; 5. Glauber dynamics of the ising model N. Ito; 6. 1D Kinetic ising models at low temperatures - critical dynamics, domain growth, and freezing S. Cornell; Part III. Ordering, Coagulation, Phase Separation; 7. Phase-ordering dynamics in one dimension A. J. Bray; 8. Phase separation, cluster growth, and reaction kinetics in models with synchronous dynamics V. Privman; 9. Stochastic models of aggregation with injection H. Takayasu and M. Takayasu; Part IV. Random Sequential Adsorption and Relaxation Processes; 10. Random and cooperative sequential adsorption: exactly solvable problems on 1D lattices, continuum limits, and 2D extensions J. W. Evans; 11. Lattice models of irreversible adsorption and diffusion P. Nielaba; 12. Deposition-evaporation dynamics: jamming, conservation laws and dynamical diversity M. Barma; Part V. Fluctuations In Particle and Surface Systems; 13. Microscopic models of macroscopic shocks S. A. Janowsky and J. L. Lebowitz; 14. The asymmetric exclusion model: exact results through a matrix approach B. Derrida and M. R. Evans; 15. Nonequilibrium surface dynamics with volume conservation J. Krug; 16. Directed walks models of polymers and wetting J. Yeomans; Part VI. Diffusion and Transport In One Dimension; 17. Some recent exact solutions of the Fokker-Planck equation H. L. Frisch; 18. Random walks, resonance, and ratchets C. R. Doering and T. C. Elston; 19. One-dimensional random walks in random environment K. Ziegler; Part VII. Experimental Results; 20. Diffusion-limited exciton kinetics in one-dimensional systems R. Kroon and R. Sprik; 21. Experimental investigations of molecular and excitonic elementary reaction kinetics in one-dimensional systems R. Kopelman and A. L. Lin; 22. Luminescence quenching as a probe of particle distribution S. H. Bossmann and L. S. Schulman; Index.

Safety, Tolerability, and Immunogenicity of the Novel Antituberculous Vaccine RUTI: Randomized, Placebo-Controlled Phase II Clinical Trial in Patients with Latent Tuberculosis Infection

PubMed Central

Nell, Andre S.; D’lom, Eva; Bouic, Patrick; Sabaté, Montserrat; Bosser, Ramon; Picas, Jordi; Amat, Mercè; Churchyard, Gavin; Cardona, Pere-Joan

2014-01-01

Objectives To evaluate the safety, tolerability and immunogenicity of three different doses (5, 25 and 50 µg) of the novel antituberculous vaccine RUTI compared to placebo in subjects with latent tuberculosis infection. Methods and Findings Double-blind, randomized, placebo-controlled Phase II Clinical Trial (95 patients randomized). Three different RUTI doses and placebo were tested, randomized both in HIV-positive (n = 47) and HIV-negative subjects (n = 48), after completion of one month isoniazid (INH) pre-vaccination. Each subject received two vaccine administrations, 28 Days apart. Five patients withdrew and 90 patients completed the study. Assessment of safety showed no deaths during study. Two subjects had serious adverse events one had a retinal detachment while taking INH and was not randomized and the other had a severe local injection site abscess on each arm and was hospitalized; causality was assessed as very likely and by the end of the study the outcome had resolved. All the patients except 5 (21%) patients of the placebo group (3 HIV+ and 2 HIV−) reported at least one adverse event (AE) during the study. The most frequently occurring AEs among RUTI recipients were (% in HIV+/−): injection site reactions [erythema (91/92), induration (94/92), local nodules (46/25), local pain (66/75), sterile abscess (6/6), swelling (74/83), ulcer (20/11), headache (17/22) and nasopharyngitis (20/5)]. These events were mostly mild and well tolerated. Overall, a polyantigenic response was observed, which differed by HIV− status. The best polyantigenic response was obtained when administrating 25 µg RUTI, especially in HIV-positive subjects which was not increased after the second inoculation. Conclusion This Phase II clinical trial demonstrates reasonable tolerability of RUTI. The immunogenicity profile of RUTI vaccine in LTBI subjects, even being variable among groups, allows us considering one single injection of one of the highest doses in future trials, preceded by an extended safety clinical phase. Trial Registration ClinicalTrials.gov NCT01136161 PMID:24586912

Controlling memory impairment in elderly adults using virtual reality memory training: a randomized controlled pilot study.

PubMed

Optale, Gabriele; Urgesi, Cosimo; Busato, Valentina; Marin, Silvia; Piron, Lamberto; Priftis, Konstantinos; Gamberini, Luciano; Capodieci, Salvatore; Bordin, Adalberto

2010-05-01

Memory decline is a prevalent aspect of aging but may also be the first sign of cognitive pathology. Virtual reality (VR) using immersion and interaction may provide new approaches to the treatment of memory deficits in elderly individuals. The authors implemented a VR training intervention to try to lessen cognitive decline and improve memory functions. The authors randomly assigned 36 elderly residents of a rest care facility (median age 80 years) who were impaired on the Verbal Story Recall Test either to the experimental group (EG) or the control group (CG). The EG underwent 6 months of VR memory training (VRMT) that involved auditory stimulation and VR experiences in path finding. The initial training phase lasted 3 months (3 auditory and 3 VR sessions every 2 weeks), and there was a booster training phase during the following 3 months (1 auditory and 1 VR session per week). The CG underwent equivalent face-to-face training sessions using music therapy. Both groups participated in social and creative and assisted-mobility activities. Neuropsychological and functional evaluations were performed at baseline, after the initial training phase, and after the booster training phase. The EG showed significant improvements in memory tests, especially in long-term recall with an effect size of 0.7 and in several other aspects of cognition. In contrast, the CG showed progressive decline. The authors suggest that VRMT may improve memory function in elderly adults by enhancing focused attention.

Impact of a multidimensional infection control approach on catheter-associated urinary tract infection rates in an adult intensive care unit in Lebanon: International Nosocomial Infection Control Consortium (INICC) findings.

PubMed

Kanj, Souha S; Zahreddine, Nada; Rosenthal, Victor Daniel; Alamuddin, Lamia; Kanafani, Zeina; Molaeb, Bassel

2013-09-01

The objective of this study was to assess the impact of a multidimensional infection control approach for the reduction of catheter-associated urinary tract infection (CAUTI) in an adult intensive care unit (ICU) of a hospital member of the International Nosocomial Infection Control Consortium (INICC) in Lebanon. A before-after prospective active surveillance study was carried out to determine rates of CAUTI in 1506 ICU patients, hospitalized during 10 291 bed-days. The study period was divided into two phases: phase 1 (baseline) and phase 2 (intervention). During phase 1, surveillance was performed applying the definitions of the US Centers for Disease Control and Prevention National Healthcare Safety Network (CDC/NHSN). In phase 2, we adopted a multidimensional approach that included: (1) a bundle of infection control interventions, (2) education, (3) surveillance of CAUTI rates, (4) feedback on CAUTI rates, (5) process surveillance, and (6) performance feedback. We used random effects Poisson regression to account for clustering of CAUTI rates across time-periods. We recorded a total of 9829 urinary catheter-days: 306 in phase 1 and 9523 in phase 2. The rate of CAUTI was 13.07 per 1000 urinary catheter-days in phase 1, and was decreased by 83% in phase 2 to 2.21 per 1000 urinary catheter-days (risk ratio 0.17; 95% confidence interval 0.06-0.5; p=0.0002). Our multidimensional approach was associated with a significant reduction in the CAUTI rate. Copyright © 2013. Published by Elsevier Ltd.

Safety and efficacy of topical E6005, a phosphodiesterase 4 inhibitor, in Japanese adult patients with atopic dermatitis: results of a randomized, vehicle-controlled, multicenter clinical trial.

PubMed

Furue, Masutaka; Kitahara, Yasumi; Akama, Hideto; Hojo, Seiichiro; Hayashi, Nobukazu; Nakagawa, Hidemi

2014-07-01

The safety and efficacy of topical E6005, a novel phosphodiesterase 4 inhibitor, in Japanese adults with atopic dermatitis were evaluated. A total of 78 patients were randomized to receive either the 0.2% E6005 ointment or vehicle control (without E6005) at an allocation ratio of 2:1. The randomization phase of 4 weeks was followed by an extension phase of 8 weeks. In the extension phase, all 67 subjects who completed the randomization phase were treated with 0.2% E6005 ointment. The 4-week application of topical E6005 twice daily was safe and well tolerated. The safety profile for up to 12 weeks was similar to that for the first 4 weeks. No deaths or other serious adverse effects were observed during the entire study period of 12 weeks. Plasma E6005 was undetectable in all subjects at all sampling points while very low plasma concentrations of an E6005 metabolite were detected in 47% of subjects receiving E6005 treatment. At the end of week 4, Eczema Area and Severity Index (EASI), Severity Scoring Atopic Dermatitis (SCORAD)-objective, SCORAD-C (visual analog scales for pruritus and sleep loss), itch Behavioral Rating Scale, and the severity of the targeted eczematous lesions in the topical E6005 group showed trends toward improvement compared with those in the vehicle group (not statistically significant). However, the group receiving topical E6005 for 12 weeks showed significant score reductions from baselines for EASI (P = 0.030), SCORAD-objective (P < 0.001) and SCORAD-C (P = 0.038). These results further support the development of topical E6005 for the treatment of atopic dermatitis. © 2014 Japanese Dermatological Association.

mActive: A Randomized Clinical Trial of an Automated mHealth Intervention for Physical Activity Promotion.

PubMed

Martin, Seth S; Feldman, David I; Blumenthal, Roger S; Jones, Steven R; Post, Wendy S; McKibben, Rebeccah A; Michos, Erin D; Ndumele, Chiadi E; Ratchford, Elizabeth V; Coresh, Josef; Blaha, Michael J

2015-11-09

We hypothesized that a fully automated mobile health (mHealth) intervention with tracking and texting components would increase physical activity. mActive enrolled smartphone users aged 18 to 69 years at an ambulatory cardiology center in Baltimore, Maryland. We used sequential randomization to evaluate the intervention's 2 core components. After establishing baseline activity during a blinded run-in (week 1), in phase I (weeks 2 to 3), we randomized 2:1 to unblinded versus blinded tracking. Unblinding allowed continuous access to activity data through a smartphone interface. In phase II (weeks 4 to 5), we randomized unblinded participants 1:1 to smart texts versus no texts. Smart texts provided smartphone-delivered coaching 3 times/day aimed at individual encouragement and fostering feedback loops by a fully automated, physician-written, theory-based algorithm using real-time activity data and 16 personal factors with a 10 000 steps/day goal. Forty-eight outpatients (46% women, 21% nonwhite) enrolled with a mean±SD age of 58±8 years, body mass index of 31±6 kg/m(2), and baseline activity of 9670±4350 steps/day. Daily activity data capture was 97.4%. The phase I change in activity was nonsignificantly higher in unblinded participants versus blinded controls by 1024 daily steps (95% confidence interval [CI], -580 to 2628; P=0.21). In phase II, participants receiving texts increased their daily steps over those not receiving texts by 2534 (95% CI, 1318 to 3750; P<0.001) and over blinded controls by 3376 (95% CI, 1951 to 4801; P<0.001). An automated tracking-texting intervention increased physical activity with, but not without, the texting component. These results support new mHealth tracking technologies as facilitators in need of behavior change drivers. URL: http://ClinicalTrials.gov/. Unique identifier: NCT01917812. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

A randomized phase II study comparing paclitaxel-carboplatin-bevacizumab with or without nitroglycerin patches in patients with stage IV nonsquamous nonsmall-cell lung cancer: NVALT12 (NCT01171170)†.

PubMed

Dingemans, A-M C; Groen, H J M; Herder, G J M; Stigt, J A; Smit, E F; Bahce, I; Burgers, J A; van den Borne, B E E M; Biesma, B; Vincent, A; van der Noort, V; Aerts, J G

2015-11-01

Nitroglycerin (NTG) increases tumor blood flow and oxygenation by inhibiting hypoxia-inducible-factor (HIF)-1. A randomized phase II study has shown improved outcome when NTG patches were added to vinorelbine/cisplatin in patients with advanced nonsmall-cell lung cancer (NSCLC). In addition, there is evidence that the combination of bevacizumab and HIF-1 inhibitors increases antitumor activity. In this randomized phase II trial, chemo-naive patients with stage IV nonsquamous NSCLC were randomized to four cycles of carboplatin (area under the curve 6)-paclitaxel (200 mg/m(2))-bevacizumab 15 mg/kg on day 1 every 3 weeks with or without NTG patches 15 mg (day -2 to +2) followed by bevacizumab with or without NTG until progression. Response was assessed every two cycles. Primary end point was progression-free survival (PFS). The study was powered (80%) to detect a decrease in the hazard of tumor progression of 33% at α = 0.05 with a two-sided log-rank test when 222 patients were enrolled and followed until 195 events were observed. Between 1 January 2011 and 1 January 2013, a total of 223 patients were randomized; 112 control arm and 111 experimental arm; response rate was 54% in control arm and 38% in experimental arm. Median [95% confidence interval (CI)] PFS in control arm was 6.8 months (5.6-7.3) and 5.1 months (4.2-5.8) in experimental arm, hazard ratio (HR) 1.27 (95% CI 0.96-1.67). Overall survival (OS) was 11.6 months (8.8-13.6) in control arm and 9.4 months (7.8-11.3) in experimental arm, HR 1.02 (95% CI 0.71-1.46). In the experimental arm, no additional toxicity was observed except headache (6% versus 52% in patients treated with NTG). Adding NTG to first-line carboplatin-paclitaxel-bevacizumab did not improve PFS and OS in patients with stage IV nonsquamous NSCLC. © The Author 2015. 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.

Randomized Controlled Trial of Nuevo Amanecer: A Peer-delivered Stress Management Intervention for Spanish-speaking Latinas with Breast Cancer

PubMed Central

Nápoles, Anna María; Santoyo-Olsson, Jasmine; Ortiz, Carmen; Gregorich, Steven; Lee, Howard E.; Duron, Ysabel; Graves, Kristi; Luce, Judith A.; McGuire, Peggy; Díaz-Méndez, Marynieves; Stewart, Anita L.

2014-01-01

Background Latinas with breast cancer suffer symptom and psychosocial health disparities. Effective interventions have not been developed for or tested in this population. Purpose We describe community-based participatory research methods used to develop and implement the Nuevo Amanecer program, a culturally tailored, peer-delivered cognitive-behavioral stress management intervention for low-income Spanish-speaking Latinas with breast cancer, and unique considerations in implementing a randomized controlled trial to test the program in community settings. Methods We applied an implementation science framework to delineate the methodological phases used to develop and implement the Nuevo Amanecer program and trial, emphasizing community engagement processes. Results In phase 1, we established project infrastructure: academic and community Co-Principal Investigators, community partners, community advisory board, steering committee, and funding. In phase 2, we identified three program inputs: formative research, a community best practices model, and an evidence-based intervention tested in non-Latinas. In phase 3, we created the new program by integrating and adapting intervention components from the three sources, making adaptations to accommodate low-literacy, Spanish language, cultural factors, community context, and population needs. In phase 4, we built community capacity for the program and trial by training field staff (recruiters and interventionists embedded in community sites), compensating field staff, and creating a system for identifying potential participants. In phase 5, we implemented and monitored the program and trial. Engaging community partners in all phases has resulted in a new, culturally tailored program that is suitable for newly diagnosed Latinas with breast cancer and a trial that is acceptable and supported by community and clinical partners. Lessons Learned Engagement of community-based organizations and cancer survivors as research partners and hiring recruiters and interventionists from the community were critical to successful implementation in community settings. Having culturally and linguistically competent research staff with excellent interpersonal skills facilitated implementation. Facilitating and maintaining excellent communication among community partners was imperative to troubleshoot implementation issues. Randomization was challenging due to community concerns about assigning women to a control group. Patient privacy regulations and the need for extensive outreach to establish relationships between community partners and clinical sites hampered initial recruitment. Limitations These were resource-intensive processes to develop and implement the program that need to be compared to less intensive alternatives. Conclusions Engaging community members in design and implementation of community-based programs and trials enhances cultural appropriateness and congruence with the community context. If the randomized trial demonstrates that the intervention is effective, it will fill a gap in evidence-based programs to address ethnic disparities in quality of life among Spanish-speaking Latinas with breast cancer. PMID:24577971

Study protocol of the Diabetes and Depression Study (DAD): a multi-center randomized controlled trial to compare the efficacy of a diabetes-specific cognitive behavioral group therapy versus sertraline in patients with major depression and poorly controlled diabetes mellitus

PubMed Central

2013-01-01

Background Depression is common in diabetes and associated with hyperglycemia, diabetes related complications and mortality. No single intervention has been identified that consistently leads to simultaneous improvement of depression and glycemic control. Our aim is to analyze the efficacy of a diabetes-specific cognitive behavioral group therapy (CBT) compared to sertraline (SER) in adults with depression and poorly controlled diabetes. Methods/Design This study is a multi-center parallel arm randomized controlled trial currently in its data analysis phase. We included 251 patients in 70 secondary care centers across Germany. Key inclusion criteria were: type 1 or 2 diabetes, major depression (diagnosed with the Structured Clinical Interview for DSM-IV, SCID) and hemoglobin A1C >7.5% despite current insulin therapy. During the initial phase, patients received either 50–200 mg/d sertraline or 10 CBT sessions aiming at the remission of depression and enhanced adherence to diabetes treatment and coping with diabetes. Both groups received diabetes treatment as usual. After 12 weeks of this initial open-label therapy, only the treatment-responders (50% depression symptoms reduction, Hamilton Depression Rating Scale, 17-item version [HAMD]) were included in the subsequent one year study phase and represented the primary analysis population. CBT-responders received no further treatment, while SER-responders obtained a continuous, flexible-dose SER regimen as relapse prevention. Adherence to treatment was analyzed using therapeutic drug monitoring (measurement of sertraline and N-desmethylsertraline concentrations in blood serum) and by counting the numbers of CBT sessions received. Outcome assessments were conducted by trained psychologists blinded to group assignment. Group differences in HbA1c (primary outcome) and depression (HAMD, secondary outcome) between 1-year follow-up and baseline will be analyzed by ANCOVA controlling for baseline values. As primary hypothesis we expect that CBT leads to significantly greater improvement of glycemic control in the one year follow-up in treatment responders of the short term phase. Discussion The DAD study is the first randomized controlled trial comparing antidepressants to a psychological treatment in diabetes patients with depression. The study is investigator initiated and was supported by the ‘Förderprogramm Klinische Studien (Clinical Trials)’ and the ‘Competence Network for Diabetes mellitus’ funded by the Federal Ministry of Education and Research (FKZ 01KG0505). Trial registration Current controlled trials ISRCTN89333241. PMID:23915015

Trauma-Informed Mindfulness-Based Stress Reduction for Female Survivors of Interpersonal Violence: Results From a Stage I RCT.

PubMed

Kelly, Amber; Garland, Eric L

2016-04-01

This pilot randomized controlled trial evaluated a novel trauma-informed model of mindfulness-based stress reduction (TI-MBSR) as a phase I trauma intervention for female survivors of interpersonal violence (IPV). A community-based sample of women (mean age = 41.5, standard deviation = 14.6) with a history of IPV was randomly assigned to an 8-week TI-MBSR intervention (n = 23) or a waitlist control group (n = 22). Symptoms of posttraumatic stress disorder (PTSD) and depression as well as anxious and avoidant attachment were assessed pre- and postintervention. Relative to the control group, participation in TI-MBSR was associated with statistically and clinically significant decreases in PTSD and depressive symptoms and significant reductions in anxious attachment. Retention in the intervention was high, with most participants completing at least 5 of the 8 sessions for the intervention. Minutes of mindfulness practice per week significantly predicted reductions in PTSD symptoms. TI-MBSR appears to be a promising and feasible phase I intervention for female survivors of interpersonal trauma. © 2016 Wiley Periodicals, Inc.

Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial.

PubMed

van Laar, Jacob M; Farge, Dominique; Sont, Jacob K; Naraghi, Kamran; Marjanovic, Zora; Larghero, Jérôme; Schuerwegh, Annemie J; Marijt, Erik W A; Vonk, Madelon C; Schattenberg, Anton V; Matucci-Cerinic, Marco; Voskuyl, Alexandre E; van de Loosdrecht, Arjan A; Daikeler, Thomas; Kötter, Ina; Schmalzing, Marc; Martin, Thierry; Lioure, Bruno; Weiner, Stefan M; Kreuter, Alexander; Deligny, Christophe; Durand, Jean-Marc; Emery, Paul; Machold, Klaus P; Sarrot-Reynauld, Francoise; Warnatz, Klaus; Adoue, Daniel F P; Constans, Joël; Tony, Hans-Peter; Del Papa, Nicoletta; Fassas, Athanasios; Himsel, Andrea; Launay, David; Lo Monaco, Andrea; Philippe, Pierre; Quéré, Isabelle; Rich, Éric; Westhovens, Rene; Griffiths, Bridget; Saccardi, Riccardo; van den Hoogen, Frank H; Fibbe, Willem E; Socié, Gérard; Gratwohl, Alois; Tyndall, Alan

2014-06-25

High-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation (HSCT) have shown efficacy in systemic sclerosis in phase 1 and small phase 2 trials. To compare efficacy and safety of HSCT vs 12 successive monthly intravenous pulses of cyclophosphamide. The Autologous Stem Cell Transplantation International Scleroderma (ASTIS) trial, a phase 3, multicenter, randomized (1:1), open-label, parallel-group, clinical trial conducted in 10 countries at 29 centers with access to a European Group for Blood and Marrow Transplantation-registered transplant facility. From March 2001 to October 2009, 156 patients with early diffuse cutaneous systemic sclerosis were recruited and followed up until October 31, 2013. HSCT vs intravenous pulse cyclophosphamide. The primary end point was event-free survival, defined as time from randomization until the occurrence of death or persistent major organ failure. A total of 156 patients were randomly assigned to receive HSCT (n = 79) or cyclophosphamide (n = 77). During a median follow-up of 5.8 years, 53 events occurred: 22 in the HSCT group (19 deaths and 3 irreversible organ failures) and 31 in the control group (23 deaths and 8 irreversible organ failures). During the first year, there were more events in the HSCT group (13 events [16.5%], including 8 treatment-related deaths) than in the control group (8 events [10.4%], with no treatment-related deaths). At 2 years, 14 events (17.7%) had occurred cumulatively in the HSCT group vs 14 events (18.2%) in the control group; at 4 years, 15 events (19%) had occurred cumulatively in the HSCT group vs 20 events (26%) in the control group. Time-varying hazard ratios (modeled with treatment × time interaction) for event-free survival were 0.35 (95% CI, 0.16-0.74) at 2 years and 0.34 (95% CI, 0.16-0.74) at 4 years. Among patients with early diffuse cutaneous systemic sclerosis, HSCT was associated with increased treatment-related mortality in the first year after treatment. However, HCST conferred a significant long-term event-free survival benefit. isrctn.org Identifier: ISRCTN54371254.

A Phase II/III Randomized, Placebo-Controlled, Double-Blind Clinical Trial of Ginger (Zingiber officinale) for Nausea Caused by Chemotherapy for Cancer: A Currently Accruing URCC CCOP Cancer Control Study.

PubMed

Hickok, Jane T; Roscoe, Joseph A; Morrow, Gary R; Ryan, Julie L

2007-09-01

Despite the widespread use of 5-HT3 receptor antagonist antiemetics such as ondansetron and granistron, up to 70% of patients with cancer receiving highly emetogenic chemotherapy agents experience postchemotherapy nausea and vomiting. Delayed postchemotherapy nausea (nausea that occurs >/= 24 hours after chemotherapy administration) and anticipatory nausea (nausea that develops before chemotherapy administration, in anticipation of it) are poorly controlled by currently available antiemetic agents. Scientific studies suggest that ginger (Zingiber officinale) might have beneficial effects on nausea and vomiting associated with motion sickness, surgery, and pregnancy. In 2 small studies of patients with cancer receiving chemotherapy, addition of ginger to standard antiemetic medication further reduced the severity of postchemotherapy nausea. This article describes a phase II/III randomized, dose-finding, placebo-controlled, double-blind clinical trial to assess the efficacy of ginger for nausea associated with chemotherapy for cancer. The study is currently being conducted by private practice oncology groups that are funded by the National Cancer Institute's Community Clinical Oncology Program and affiliated with the University of Rochester Cancer Center Community Clinical Oncology Program Research Base.

Randomized controlled trial of ethyl-eicosapentaenoic acid in Huntington disease: the TREND-HD study.

PubMed

2008-12-01

To determine whether ethyl-eicosapentaenoic acid (ethyl-EPA), an omega-3 fatty acid, improves the motor features of Huntington disease. Six-month multicenter, randomized, double-blind, placebo-controlled trial followed by a 6-month open-label phase without disclosing initial treatment assignments. Forty-one research sites in the United States and Canada. Three hundred sixteen adults with Huntington disease, enriched for a population with shorter trinucleotide (cytosine-adenine-guanine) repeat length expansions. Random assignment to placebo or ethyl-EPA, 1 g twice a day, followed by open-label treatment with ethyl-EPA. Six-month change in the Total Motor Score 4 component of the Unified Huntington's Disease Rating Scale analyzed for all research participants and those with shorter cytosine-adenine-guanine repeat length expansions (<45). At 6 months, the Total Motor Score 4 point change for patients receiving ethyl-EPA did not differ from that for those receiving placebo. No differences were found in measures of function, cognition, or global impression. Before public disclosure of the 6-month placebo-controlled results, 192 individuals completed the open-label phase. The Total Motor Score 4 change did not worsen for those who received active treatment for 12 continuous months compared with those who received active treatment for only 6 months (2.0-point worsening; P=.02). Ethyl-EPA was not beneficial in patients with Huntington disease during 6 months of placebo-controlled evaluation. Clinical Trial Registry clinicaltrials.gov Identifier: NCT00146211.

Efficacy and tolerability of the single-pill combination of aliskiren 300 mg/amlodipine 10 mg in hypertensive patients not controlled by olmesartan 40 mg/amlodipine 10 mg.

PubMed

Axthelm, Christoph; Sieder, Christian; Meister, Franziska; Kaiser, Edelgard

2012-01-01

We aimed to investigate whether the single pill combination (SPC) of aliskiren 300 mg and amlodipine 10 mg (ALIS 300/AMLO 10) improves blood pressure (BP) reduction in hypertensive patients not adequately controlled by the SPC olmesartan 40 mg and amlodipine 10 mg (OLM 40/AMLO 10). Open-label, non-randomized single-arm study. Patients with stage 2 hypertension were titrated to the SPC OLM 40/AMLO 10 (4-week Phase 1). If hypertension was not controlled they were switched to the SPC ALIS 300/AMLO 10 (4-week Phase 2). In the optional 4-week study extension hydrochlorothiazide (HCT) 12.5 mg was added. EudraCT 2009-016693-33. In the 342 patients treated, OLM 40/AMLO 10 reduced systolic BP (SBP)/diastolic BP (DBP) by 24.5/14.5 mmHg by end of Phase 1. Those 187 patients with uncontrolled hypertension at the end of Phase 1 switched to ALIS 300/AMLO 10 experienced a further SBP reduction of 5.1 mmHg (95% confidence interval [CI] 3.7 to 6.5, p < 0.0001) and a DBP reduction of 4.8 mmHg (95% CI 3.8 to 5.8; p < 0.0001) in Phase 2. DBP or SBP responder rates were achieved by 51.3% or 44.4%, respectively, SBP and DBP normalization by 36.4%. In 65 patients whose BP was not controlled in Phase 2, SPC ALIS 300/AMLO 10/HCT 12.5 mg decreased SBP/DBP by further 8.1/6.7 mmHg (p < 0.0001 each). No deaths or serious adverse events were noted. Significant adverse events leading to study discontinuation were reported in 2.6% (Phase 1), 2.7% (Phase 2), and 0% (extension). Limitations included the open-label, single-arm non-randomized design, and the relatively short duration. In this switch study reflecting clinical practice, patients with moderate hypertension not controlled by the SPC OLM 40/AMLO 10 achieved a clinically and statistically significant reduction of blood pressure from the SPC ALIS 300/AMLO 10 and the optional addition of HCT. All drug combinations were well tolerated.

A Randomized Phase IV Control Trial of Single High Dose Oral Vitamin D3 in Pediatric Patients Undergoing HSCT

ClinicalTrials.gov

2017-06-01

Vitamin D Deficiency; Stem Cell Transplant Complications; Pediatric Cancer; Blood Disorder; Pediatric Acute Myeloid Leukemia; Pediatric Acute Lymphoid Leukemia; Myelodysplastic Syndromes; Sickle Cell Anemia in Children; Aplastic Anemia; Thalassemia in Children

Transition from nonresonant to resonant random lasers by the geometrical confinement of disorder.

PubMed

Ghofraniha, N; Viola, I; Zacheo, A; Arima, V; Gigli, G; Conti, C

2013-12-01

We report on a transition in random lasers that is induced by the geometrical confinement of the emitting material. Different dye doped paper devices with controlled geometry are fabricated by soft lithography and show two distinguished behaviors in the stimulated emission: in the absence of boundary constraints, the energy threshold decreases for larger laser volumes showing the typical trend of diffusive nonresonant random lasers, while when the same material is lithographed into channels, the walls act as cavity and the resonant behavior typical of standard lasers is observed. The experimental results are consistent with the general theories of random and standard lasers and a clear phase diagram of the transition is reported.

Comprehensive behavioral-motivational nutrition education improves depressive symptoms following bariatric surgery: a randomized, controlled trial of obese Hispanic Americans.

PubMed

Petasne Nijamkin, Monica; Campa, Adriana; Samiri Nijamkin, Shani; Sosa, Jorge

2013-01-01

To evaluate the effect of 2 post-bariatric support interventions on depressive symptoms of Hispanic Americans treated with gastric bypass for morbid or severe obesity. Prospective randomized, controlled trial conducted in a laparoscopic institution. During the Phase 1 clinical trial (from preoperative evaluation to 6 months after surgery), all participants received standard care. During Phase 2 (6-12 months after surgery), participants were randomly assigned to receive either standard care (n = 72) or comprehensive support (n = 72). Comprehensive group participants received 6 educational sessions focused on behavior change strategies and motivation with nutrition counseling. Depression scores and weight change over time. Independent samples t tests and regression analysis assessed relationships among depression scores and excess weight loss. Participants receiving behavioral-motivational intervention scored significantly lower on Beck's Depression Inventory questionnaire scores than those receiving standard care. For those with depressive symptoms at randomization, 24% of participants who received the comprehensive intervention reported no depressive symptoms at 12 months after surgery, compared with 6% of those who received standard care (P < .001). Patients' depressive mood improvement was significantly and positively associated with excess weight loss and attendance at educational sessions (P < .001). Findings support the importance of post-bariatric comprehensive behavioral-motivational nutrition education for decreasing risk for depression and improving weight loss. Copyright © 2013 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

Comparative Effectiveness of PCI Education's "PCI Reading Program": Phase 2--A Report of a Comparison Group Study in Brevard Public Schools and Miami-Dade County Public Schools. Research Summary

ERIC Educational Resources Information Center

Empirical Education Inc., 2010

2010-01-01

PCI Education sought scientifically based evidence on the comparative effectiveness of the "PCI Reading Program" through a five-year longitudinal study. Phase 1 of the study consisted of a randomized control trial studying the efficacy of the "PCI Reading Program-Level One" that was conducted in the 2007-2008 in Miami-Dade…

The effects of a rhythm and music-based therapy program and therapeutic riding in late recovery phase following stroke: a study protocol for a three-armed randomized controlled trial

PubMed Central

2012-01-01

Background Stroke represents one of the most costly and long-term disabling conditions in adulthood worldwide and there is a need to determine the effectiveness of rehabilitation programs in the late phase after stroke. Limited scientific support exists for training incorporating rhythm and music as well as therapeutic riding and well-designed trials to determine the effectiveness of these treatment modalities are warranted. Methods/Design A single blinded three-armed randomized controlled trial is described with the aim to evaluate whether it is possible to improve the overall health status and functioning of individuals in the late phase of stroke (1-5 years after stroke) through a rhythm and music-based therapy program or therapeutic riding. About 120 individuals will be consecutively and randomly allocated to one of three groups: (T1) rhythm and music-based therapy program; (T2) therapeutic riding; or (T3) control group receiving the T1 training program a year later. Evaluation is conducted prior to and after the 12-week long intervention as well as three and six months later. The evaluation comprises a comprehensive functional and cognitive assessment (both qualitative and quantitative), and questionnaires. Based on the International classification of functioning, disability, and health (ICF), the outcome measures are classified into six comprehensive domains, with participation as the primary outcome measure assessed by the Stroke Impact Scale (SIS, version 2.0.). The secondary outcome measures are grouped within the following domains: body function, activity, environmental factors and personal factors. Life satisfaction and health related quality of life constitute an additional domain. Current status A total of 84 participants were randomised and have completed the intervention. Recruitment proceeds and follow-up is on-going, trial results are expected in early 2014. Discussion This study will ascertain whether any of the two intervention programs can improve overall health status and functioning in the late phase of stroke. A positive outcome would increase the scientific basis for the use of such interventions in the late phase after stroke. Trial registration Clinical Trials.gov Identifier: NCT01372059 PMID:23171380

The effects of a rhythm and music-based therapy program and therapeutic riding in late recovery phase following stroke: a study protocol for a three-armed randomized controlled trial.

PubMed

Bunketorp Käll, Lina; Lundgren-Nilsson, Åsa; Blomstrand, Christian; Pekna, Marcela; Pekny, Milos; Nilsson, Michael

2012-11-21

Stroke represents one of the most costly and long-term disabling conditions in adulthood worldwide and there is a need to determine the effectiveness of rehabilitation programs in the late phase after stroke. Limited scientific support exists for training incorporating rhythm and music as well as therapeutic riding and well-designed trials to determine the effectiveness of these treatment modalities are warranted. A single blinded three-armed randomized controlled trial is described with the aim to evaluate whether it is possible to improve the overall health status and functioning of individuals in the late phase of stroke (1-5 years after stroke) through a rhythm and music-based therapy program or therapeutic riding. About 120 individuals will be consecutively and randomly allocated to one of three groups: (T1) rhythm and music-based therapy program; (T2) therapeutic riding; or (T3) control group receiving the T1 training program a year later. Evaluation is conducted prior to and after the 12-week long intervention as well as three and six months later. The evaluation comprises a comprehensive functional and cognitive assessment (both qualitative and quantitative), and questionnaires. Based on the International classification of functioning, disability, and health (ICF), the outcome measures are classified into six comprehensive domains, with participation as the primary outcome measure assessed by the Stroke Impact Scale (SIS, version 2.0.). The secondary outcome measures are grouped within the following domains: body function, activity, environmental factors and personal factors. Life satisfaction and health related quality of life constitute an additional domain. A total of 84 participants were randomised and have completed the intervention. Recruitment proceeds and follow-up is on-going, trial results are expected in early 2014. This study will ascertain whether any of the two intervention programs can improve overall health status and functioning in the late phase of stroke. A positive outcome would increase the scientific basis for the use of such interventions in the late phase after stroke. Clinical Trials.gov Identifier: NCT01372059.

Telemonitoring of home exercise cycle training in patients with COPD

PubMed Central

Franke, Karl-Josef; Domanski, Ulrike; Schroeder, Maik; Jansen, Volker; Artmann, Frank; Weber, Uwe; Ettler, Rainer; Nilius, Georg

2016-01-01

Background Regular physical activity is associated with reduced mortality in patients with chronic obstructive pulmonary disease (COPD). Interventions to reduce time spent in sedentary behavior could improve outcomes. The primary purpose was to investigate the impact of telemonitoring with supportive phone calls on daily exercise times with newly established home exercise bicycle training. The secondary aim was to examine the potential improvement in health-related quality of life and physical activity compared to baseline. Methods This prospective crossover-randomized study was performed over 6 months in stable COPD patients. The intervention phase (domiciliary training with supporting telephone calls) and the control phase (training without phone calls) were randomly assigned to the first or the last 3 months. In the intervention phase, patients were called once a week if they did not achieve a real-time monitored daily cycle time of 20 minutes. Secondary aims were evaluated at baseline and after 3 and 6 months. Health-related quality of life was measured by the COPD Assessment Test (CAT), physical activity by the Godin Leisure Time Exercise Questionnaire (GLTEQ). Results Of the 53 included patients, 44 patients completed the study (forced expiratory volume in 1 second 47.5%±15.8% predicted). In the intervention phase, daily exercise time was significantly higher compared to the control phase (24.2±9.4 versus 19.6±10.3 minutes). Compared to baseline (17.6±6.1), the CAT-score improved in the intervention phase to 15.3±7.6 and in the control phase to 15.7±7.3 units. The GLTEQ-score increased from 12.2±12.1 points to 36.3±16.3 and 33.7±17.3. Conclusion Telemonitoring is a simple method to enhance home exercise training and physical activity, improving health-related quality of life. PMID:27956829

Focusing light through random scattering media by four-element division algorithm

NASA Astrophysics Data System (ADS)

Fang, Longjie; Zhang, Xicheng; Zuo, Haoyi; Pang, Lin

2018-01-01

The focusing of light through random scattering materials using wavefront shaping is studied in detail. We propose a newfangled approach namely four-element division algorithm to improve the average convergence rate and signal-to-noise ratio of focusing. Using 4096 independently controlled segments of light, the intensity at the target is 72 times enhanced over the original intensity at the same position. The four-element division algorithm and existing phase control algorithms of focusing through scattering media are compared by both of the numerical simulation and the experiment. It is found that four-element division algorithm is particularly advantageous to improve the average convergence rate of focusing.

Clustering and phase transitions on a neutral landscape

NASA Astrophysics Data System (ADS)

Scott, Adam D.; King, Dawn M.; Marić, Nevena; Bahar, Sonya

2013-06-01

Recent computational studies have shown that speciation can occur under neutral conditions, i.e., when the simulated organisms all have identical fitness. These works bear comparison with mathematical studies of clustering on neutral landscapes in the context of branching and coalescing random walks. Here, we show that sympatric clustering/speciation can occur on a neutral landscape whose dimensions specify only the simulated organisms’ phenotypes. We demonstrate that clustering occurs not only in the case of assortative mating, but also in the case of asexual fission; it is not observed in the control case of random mating. We find that the population size and the number of clusters undergo a second-order non-equilibrium phase transition as the maximum mutation size is varied.

Physiological and psychological effects of testosterone during severe energy deficit and recovery: A study protocol for a randomized, placebo-controlled trial for Optimizing Performance for Soldiers (OPS).

PubMed

Pasiakos, Stefan M; Berryman, Claire E; Karl, J Philip; Lieberman, Harris R; Orr, Jeb S; Margolis, Lee M; Caldwell, John A; Young, Andrew J; Montano, Monty A; Evans, William J; Vartanian, Oshin; Carmichael, Owen T; Gadde, Kishore M; Harris, Melissa; Rood, Jennifer C

2017-07-01

The physiological consequences of severe energy deficit include hypogonadism and the loss of fat-free mass. Prolonged energy deficit also impacts physical performance, mood, attentiveness, and decision-making capabilities. This study will determine whether maintaining a eugonadal state during severe, sustained energy deficit attenuates physiological decrements and maintains mental performance. This study will also assess the effects of normalizing testosterone levels during severe energy deficit and recovery on gut health and appetite regulation. Fifty physically active men will participate in a 3-phase, randomized, placebo-controlled study. After completing a 14-d, energy-adequate, diet acclimation phase (protein: 1.6g∙kg -1 ∙d -1 ; fat: 30% total energy intake), participants will be randomized to undergo a 28-d, 55% energy deficit phase with (DEF+TEST: 200mg testosterone enanthate per week) or without (DEF) exogenous testosterone. Diet and physical activity will be rigorously controlled. Recovery from the energy deficit (ad libitum diet, no testosterone) will be assessed until body mass has been recovered within ±2.5% of initial body mass. Body composition, stable isotope methodologies, proteomics, muscle biopsies, whole-room calorimetry, molecular biology, activity/sleep monitoring, personality and cognitive function assessments, functional MRI, and comprehensive biochemistries will be used to assess physiological and psychological responses to energy restriction and recovery feeding while volunteers are in an expected hypogonadal versus eugonadal state. The Optimizing Performance for Soldiers (OPS) study aims to determine whether preventing hypogonadism will mitigate declines in physical and mental function that typically occur during prolonged energy deficit, and the efficacy of testosterone replacement on recovery from severe underfeeding. NCT02734238. Copyright © 2017. Published by Elsevier Inc.

The Use of Concept Map as a Consolidation Phase Based STAD to Enhance Students’ Comprehension about Environmental Pollution

NASA Astrophysics Data System (ADS)

Nugroho, O. F.; Chandra, D. T.; Sanjaya, Y.; Pendidikan Indonesia, Universitas

2017-02-01

The purpose of this study was to improve students’ concept comprehension using concept map as a consolidation phase based STAD. This study was conducted by randomized control group pretest-posttest. Data was collected by using an instrument test to evaluate the effect of concept map as a consolidation phase based STAD on students’understanding about environmental pollution. Data was analyzed using normalized gain (n-gain) and independent t-test. The n-gain analysis shows the increased of students’s understanding about environmental pollution at experimental group arehigher than at the control group. The result of this study showed that students’ comprehension at the experimental class (0,53) higher compared to the control group (0,23). Whilst the t-test analysis shows that there is a significant effect of mapping concept as a consolidation phase based STAD towards students’ concept comprehension. It can be concluded that the implementation of mapping concept based STAD may improve the students’s understanding on science concept.

Clinical efficacy of edaravone for the treatment of amyotrophic lateral sclerosis.

PubMed

Sawada, Hideyuki

2017-05-01

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal, neurodegenerative disease. Although the pathogenesis remains unresolved, oxidative stress is known to play a pivotal role. Edaravone works in the central nervous system as a potent scavenger of oxygen radicals. In ALS mouse models, edaravone suppresses motor functional decline and nitration of tyrosine residues in the cerebrospinal fluid. Areas covered: Three clinical trials, one phase II open-label trial, and two phase III placebo-control randomized trials were reviewed. In all trials, the primary outcome measure was the changes in scores on the revised ALS functional rating scale (ALSFRS-R) to evaluate motor function of patients. Expert opinion: The phase II open label trial suggested that edaravone is safe and effective in ALS, markedly reducing 3-nitrotyrosine levels in the cerebrospinal fluid. One of the two randomized controlled trials showed beneficial effects in ALSFRS-R, although the differences were not significant. The last trial demonstrated that edaravone provided significant efficacy in ALSFRS-R scores over 24 weeks where concomitant use of riluzole was permitted. Eligibility was restricted to patients with a relatively short disease duration and preserved vital capacity. Therefore, combination therapy with edaravone and riluzole should be considered earlier.

Prostate cancer, comorbidity, and participation in randomized controlled trials of therapy.

PubMed

Chao, Herta H; Mayer, Tina; Concato, John; Rose, Michal G; Uchio, Edward; Kelly, Wm Kevin

2010-03-01

Randomized controlled trials (RCTs) evaluate the potential benefits of chemotherapy regimens and guide clinical care for patients with cancer. Inclusion criteria for RCTs are usually stringent and may exclude many patients seen in clinical practice. Our objective was to determine the proportion of men with castrate-resistant prostate cancer (CRPC) in a clinical setting that would have been excluded from major phase 3 RCTs. We reviewed eligibility criteria from 24 phase 3 clinical trials evaluating chemotherapy for CRPC active from January, 2004, through April, 2008. We created a common list of criteria used in at least 3 studies and separately considered the criteria from a prominent RCT (TAX 327). We applied these criteria to a population of patients with CRPC treated during 2004 to 2006 at the Veterans Affairs Connecticut Healthcare System. Among 106 patients with CRPC, 99 (93%) had complete medical records, and 45 (45%) of the 99 would have been excluded from RCTs. Common reasons for exclusion were abnormal laboratory values, other malignancies, and other serious medical conditions including cardiac disease. Almost half of the CRPC patients examined in a clinical setting would have been ineligible for phase 3 RCTs, highlighting that such trials may not be applicable to general oncology practice.

Virtual reality exercise on a home-based phase III cardiac rehabilitation program, effect on executive function, quality of life and depression, anxiety and stress: a randomized controlled trial.

PubMed

Vieira, Ágata; Melo, Cristina; Machado, Jorge; Gabriel, Joaquim

2018-02-01

To analyse the effect of a six-month home-based phase III cardiac rehabilitation (CR) specific exercise program, performed in a virtual reality (Kinect) or conventional (booklet) environment, on executive function, quality of life and depression, anxiety and stress of subjects with coronary artery disease. A randomized controlled trial was conducted with subjects, who had completed phase II, randomly assigned to intervention group 1 (IG1), whose program encompassed the use of Kinect (n = 11); or intervention group 2 (IG2), a paper booklet (n = 11); or a control group (CG), only subjected to the usual care (n = 11). The three groups received education on cardiovascular risk factors. The assessed parameters, at baseline (M0), 3 (M1) and 6 months (M2), were executive function, control and integration in the implementation of an adequate behaviour in relation to a certain objective, specifically the ability to switch information (Trail Making Test), working memory (Verbal Digit Span test), and selective attention and conflict resolution ability (Stroop test), quality of life (MacNew questionnaire) and depression, anxiety and stress (Depression, Anxiety and Stress Scale 21). Descriptive and inferential statistical measures were used, significance level was set at .05. The IG1 revealed significant improvements, in the selective attention and conflict resolution ability, in comparison with the CG in the variable difference M0 - M2 (p = .021) and in comparison with the IG2 in the variable difference M1 - M2 and M0 - M2 (p = .001 and p = .002, respectively). No significant differences were found in the quality of life, and depression, anxiety and stress. The virtual reality format had improved selective attention and conflict resolution ability, revealing the potential of CR, specifically with virtual reality exercise, on executive function. Implications for Rehabilitation In cardiac rehabilitation, especially in phase III, it is important to develop and to present alternative strategies, as virtual reality using the Kinect in a home context. Taking into account the relationship between the improvement of the executive function with physical exercise, it is relevant to access the impact of a cardiac rehabilitation program on the executive function. Enhancing the value of the phase III of cardiac rehabilitation.

A randomized double-blinded controlled trial of hCG as luteal phase support in natural cycle frozen embryo transfer.

PubMed

Lee, Vivian Chi Yan; Li, Raymond Hang Wun; Yeung, William Shu Biu; Pak Chung, H O; Ng, Ernest Hung Yu

2017-05-01

Does the use of hCG as luteal phase support in natural cycle frozen embryo transfer (FET) increase the ongoing pregnancy rate? The use of hCG in natural cycle FET did not improve the ongoing pregnancy rate. The use of luteal phase support in stimulated cycles has been associated with higher live-birth rates and the results are similar when using hCG or progesterone. This is a randomized double-blinded controlled trial of 450 women recruited between August 2013 and October 2015. Women with regular cycles undergoing natural cycle FET were recruited. Serial serum hormonal concentrations were used to time natural ovulation and at least Day 2 cleavage embryos were replaced. Patients were randomized into either: (i) the treatment group, receiving 1500 IU hCG on the day of FET and 6 days after FET, or (ii) the control group, receiving normal saline on these 2 days. The ongoing pregnancy rate [60/225 (26.7%) in the treatment group vs 70/225 (31.3%) in the control group, odds ratio 1.242 (95% CI 0.825-1.869)], implantation rate and miscarriage rate were comparable between the two groups. In the treatment group, there were significantly more cycles with top quality embryos transferred and a significantly higher serum oestradiol level, but a comparable serum progesterone level, 6 days after FET. However, no significant differences were observed in serum oestradiol and progesterone levels 6 days after FET between the pregnant and non-pregnant women. In the multivariate logistic regression, the number of embryos transferred was the only significant factor predictive of the ongoing pregnancy rate after natural cycle FET. This study only included FET with cleavage stage embryos and only hCG, not vaginal progesterone, was used as luteal phase support. The findings in this study do not support the use of hCG for luteal phase support in natural cycle FET. No external funding was used and there were no competing interests. clinicaltrial.gov identifier: NCT01931384. 23/8/2013. 30/8/2013. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

A Derivation of the Dick Effect from Control-Loop Models for Periodically Interrogated Passive Frequency Standards

NASA Technical Reports Server (NTRS)

Greenhall, Charles A.

1996-01-01

The phase of a frequency standard that uses periodic interrogation and control of a local oscillator (LO) is degraded by a long-term random-walk component induced by downconversion of LO noise into the loop passband. The Dick formula for the noise level of this degradation can be derived from explicit solotions of two LO control-loop models. A summary of the derivations is given here.

Socio-Ecological Intervention to Promote Active Commuting to Work: Protocol and Baseline Findings of a Cluster Randomized Controlled Trial in Finland

PubMed Central

Aittasalo, Minna; Tiilikainen, Johanna; Tokola, Kari; Seimelä, Timo; Sarjala, Satu-Maaria; Metsäpuro, Pasi; Suni, Jaana; Vähä-Ypyä, Henri; Vaismaa, Kalle; Vakkala, Olli; Foster, Charlie; Titze, Sylvia; Vasankari, Tommi

2017-01-01

Active commuting to work (ACW) is beneficial to traffic, environment and population health. More evidence is needed on effective ways to promote ACW. This paper describes the protocol and baseline findings of a cluster-randomized controlled study, which aims to promote ACW with multilevel strategies in two large workplace areas in Tampere, Finland. In Phase 1, the impacts of environmental strategies (trail improvements) were evaluated in 11 workplaces within Area 1. In Phase 2, five more workplaces were recruited from Area 2 to evaluate the impacts of social and behavioral strategies customized for each workplace. For this purpose, the workplaces in both areas were randomly assigned into experimental group (EXP, n = 6 + 2), which promoted ACW with social and behavioral strategies or into comparison group (COM, n = 5 + 3), which participated in the data collection only. The primary indicator in both phases is the change in employees’ ACW. Secondary indicators are e.g., changes in employees’ self-rated health, wellbeing at work, restrictions to and motivation for ACW, adverse effects due to ACW and the use and quality of the main walking and cycling trails. Also process, efficiency and environmental evaluation is included. The study is the first one in Finland to combine interdisciplinary collaboration between practitioners and researchers working in the fields of transportation, urban design, physical activity and sustainable development to promote ACW. The findings benefit all stakeholders interested in promoting ACW in urban context.

Controlling the stability of nonlinear optical modes via electromagnetically induced transparency

NASA Astrophysics Data System (ADS)

Zhang, Kun; Liang, Yi-zeng; Lin, Ji; Li, Hui-jun

2018-02-01

We propose a scheme to generate and stabilize the high-dimensional spatial solitons via electromagnetically induced transparency (EIT). The system we consider is a resonant atomic ensemble having Λ configuration. We illustrate that under EIT conditions the equation satisfied by the probe field envelope is reduced to a saturable nonlinear Schrödinger equation with the trapping potential, provided by a far-detuned laser field and a random magnetic field. We present high-dimensional soliton solutions exhibiting many interesting characteristics, including diversity (i.e., many different types of soliton solutions can be found, including bright, ring multipole bright, ring multipole defect mode, multiring bright, multiring defect mode, and vortices solitons), the phase transition between bright soliton and higher-order defect modes (i.e., the phase transition can be realized by controlling the nonlinear coefficient or the intensity of the trapping potential), and stability (i.e., various solitons can be stabilized by the Gaussian potential provided by the far detuned laser field, or the random potential provided by the magnetic field). We also find that some solitons are the extension of the linear eigenmode, whereas others entirely derive from the role of nonlinearity. Compared with previous studies, we not only show the diverse soliton solutions in the same system but also find the boundary of the phase transition for the type of solitons. In addition, we present the possibility of using the random potential to stabilize various solitons and vortices.

Nandrolone decanoate as anabolic therapy in chronic kidney disease: a randomized phase II dose-finding study.

PubMed

Macdonald, Jamie H; Marcora, Samuele M; Jibani, Mahdi M; Kumwenda, Mick J; Ahmed, Wasim; Lemmey, Andrew B

2007-01-01

In patients with chronic kidney disease (CKD) receiving adequate erythropoietin therapy, the ideal dose of nandrolone decanoate (ND) to enhance muscle mass is not known. In this phase II dose-finding study, 54 patients with CKD stage 5 were randomized to either low, medium or high doses of ND (50, 100 or 200 mg/week for 24 weeks, respectively, in males; doses halved in females), while 7 patients acted as non-randomized controls. The primary outcome measure was appendicular lean mass (ALM) by dual-energy X-ray absorptiometry. Fluid overload (hydration of the fat-free mass) and indicators of physical functioning were secondary measures. Harms were also recorded. Data were analysed using Quade's (1967) non-parametric analysis of covariance. ND increased ALM in a dose-responsive manner (change scores = 0.3 +/- 0.3 vs. 0.8 +/- 0.3 vs. 1.5 +/- 0.5 vs. 2.1 +/- 0.4 kg, control vs. low vs. medium vs. high dose groups, respectively, p < 0.001) with no increases in fluid overload but no consistent effect on physical functioning. The highest dose of ND (100 mg/week) was intolerable in females because of virilizing effects. If goals of future studies are to improve body composition, dosing of ND up to 200 mg/week in males and 50 mg/week in females should be investigated. However, to realize improvements in physical functioning, future phase III trials of ND may require additional interventions such as exercise training. Copyright 2007 S. Karger AG, Basel.

Efficacy and safety of intravenous belimumab in Japanese patients with systemic lupus erythematosus: a subgroup analysis of a Phase 3 randomized placebo-controlled trial.

PubMed

Tanaka, Yoshiya; Bass, Damon; Chu, Myron; Egginton, Sally; Ji, Beulah; Struemper, Herbert; Roth, David

2018-05-24

To assess the efficacy and safety of intravenous belimumab plus standard systemic lupus erythematosus (SLE) therapy (SoC) in Japanese patients with SLE. A Phase 3, multicenter, double-blind, placebo-controlled, 52-week study (BEL 113750; NCT01345253) in patients with SLE, randomized 2:1 to belimumab 10 mg/kg plus SoC or placebo plus SoC to Week 48. Sixty of 707 randomized patients were enrolled from study centers in Japan (belimumab, n = 39; placebo, n = 21). In this cohort, more patients achieved SLE Responder Index 4 response at Week 52 in the belimumab group compared with placebo (46.2% [18/39] vs 25.0% [5/20]; odds ratio, 2.57 [95% confidence interval: 0.78, 8.47]; p = 0.1204). Fewer patients receiving belimumab experienced a severe flare through Week 52, with longer median time to flare compared with placebo. More patients with baseline prednisone dose >7.5 mg/day receiving belimumab had a dose reduction of ≥25% from baseline to ≤7.5 mg/day during Weeks 40 to 52, compared with placebo. No new safety issues were identified within the Japanese cohort. In Japanese patients with SLE, belimumab improved disease activity, with efficacy and safety results similar and consistent to the pivotal Phase 3 trials, suggesting that belimumab is a potential treatment option in this population.

Behavioral effects of environmental enrichment on harbor seals (Phoca vitulina concolor) and gray seals (Hafichoerus grypus)

USGS Publications Warehouse

Hunter, S.A.; Bay, M.S.; Martin, M.L.; Hatfield, J.S.

2002-01-01

Zoos and aquariums have been incorporating environmental enrichment into their animal care programs for the past 30 years to increase mental stimulation and promote natural behaviors. However, most attempts to document the effects of enrichment on animal behavior have focused on terrestrial mammals. Staff at the National Aquarium in Baltimore conducted an investigation of the behavioral effects of enrichment on the seven harbor seals and two gray seals housed in the aquarium's outdoor seal exhibit. We expected that enrichment would change the amount of time the animals spent engaged in specific behaviors. The behaviors recorded were: resting in water, resting hauled out, maintenance, breeding display, breeding behavior, aggression, pattern swimming, random swimming, exploration, and out of sight. Activity levels (random swimming and exploration) were expected to increase, while stereotypic behaviors (pattern swimming) were expected to decrease. The frequency and duration of behaviors were documented for 90 hr in both the control phase (without enrichment) and the experimental phase (with enrichment). Statistically significant differences (P<0.05) in the time spent in pattern swimming, random swimming, exploration, and out of sight were observed between the two phases. With enrichment, pattern swimming and out of sight decreased, while random swimming and exploration behavior increased. These findings demonstrate that enrichment can promote behaviors (random swimming and exploration) that are likely to be normal for phocids in the wild, and that may contribute to the behavioral complexity of these seals in captivity.

Behavioral effects of environmental enrichment on harbor seals (Phoca vitulina concolor) and gray seals (Halichoerus grypus)

USGS Publications Warehouse

Hunter, S.A.; Bay, M.S.; Martin, M.L.; Hatfield, J.S.

2002-01-01

Zoos and aquariums have been incorporating environmental enrichment into their animal care programs for the past 30 years to increase mental stimulation and promote natural behaviors. However, most attempts to document the effects of enrichment on animal behavior have focused on terrestrial mammals. Staff at the National Aquarium in Baltimore conducted an investigation of the behavioral effects of enrichment on the seven harbor seals and two gray seals housed in the aquarium's outdoor seal exhibit. We expected that enrichment would change the amount of time the animals spent engaged in specific behaviors. The behaviors recorded were: resting in water, resting hauled out, maintenance, breeding display, breeding behavior, aggression, pattern swimming, random swimming, exploration, and out of sight. Activity levels (random swimming and exploration) were expected to increase, while stereotypic behaviors (pattern swimming) were expected to decrease. The frequency and duration of behaviors were documented for 90 hr in both the control phase (without enrichment) and the experimental phase (with enrichment). Statistically significant differences (P < 0.05) in the time spent in pattern swimming, random swimming, exploration, and out of sight were observed between the two phases. With enrichment, pattern swimming and out of sight decreased, while random swimming and exploration behavior increased. These findings demonstrate that enrichment can promote behaviors (random swimming and exploration) that are likely to be normal for phocids in the wild, and that may contribute to the behavioral complexity of these seals in captivity. ?? 2002 Wiley-Liss, Inc.

Long-Term Improvements After Multimodal Rehabilitation in Late Phase After Stroke: A Randomized Controlled Trial.

PubMed

Bunketorp-Käll, Lina; Lundgren-Nilsson, Åsa; Samuelsson, Hans; Pekny, Tulen; Blomvé, Karin; Pekna, Marcela; Pekny, Milos; Blomstrand, Christian; Nilsson, Michael

2017-07-01

Treatments that improve function in late phase after stroke are urgently needed. We assessed whether multimodal interventions based on rhythm-and-music therapy or horse-riding therapy could lead to increased perceived recovery and functional improvement in a mixed population of individuals in late phase after stroke. Participants were assigned to rhythm-and-music therapy, horse-riding therapy, or control using concealed randomization, stratified with respect to sex and stroke laterality. Therapy was given twice a week for 12 weeks. The primary outcome was change in participants' perception of stroke recovery as assessed by the Stroke Impact Scale with an intention-to-treat analysis. Secondary objective outcome measures were changes in balance, gait, grip strength, and cognition. Blinded assessments were performed at baseline, postintervention, and at 3- and 6-month follow-up. One hundred twenty-three participants were assigned to rhythm-and-music therapy (n=41), horse-riding therapy (n=41), or control (n=41). Post-intervention, the perception of stroke recovery (mean change from baseline on a scale ranging from 1 to 100) was higher among rhythm-and-music therapy (5.2 [95% confidence interval, 0.79-9.61]) and horse-riding therapy participants (9.8 [95% confidence interval, 6.00-13.66]), compared with controls (-0.5 [-3.20 to 2.28]); P =0.001 (1-way ANOVA). The improvements were sustained in both intervention groups 6 months later, and corresponding gains were observed for the secondary outcomes. Multimodal interventions can improve long-term perception of recovery, as well as balance, gait, grip strength, and working memory in a mixed population of individuals in late phase after stroke. URL: http//www.ClinicalTrials.gov. Unique identifier: NCT01372059. © 2017 American Heart Association, Inc.

Robotic Resistance Treadmill Training Improves Locomotor Function in Children With Cerebral Palsy: A Randomized Controlled Pilot Study.

PubMed

Wu, Ming; Kim, Janis; Gaebler-Spira, Deborah J; Schmit, Brian D; Arora, Pooja

2017-11-01

To determine whether applying controlled resistance forces to the legs during the swing phase of gait may improve the efficacy of treadmill training as compared with applying controlled assistance forces in children with cerebral palsy (CP). Randomized controlled study. Research unit of a rehabilitation hospital. Children with spastic CP (N=23; mean age, 10.6y; range, 6-14y; Gross Motor Function Classification System levels, I-IV). Participants were randomly assigned to receive controlled assistance (n=11) or resistance (n=12) loads applied to the legs at the ankle. Participants underwent robotic treadmill training 3 times a week for 6 weeks (18 sessions). A controlled swing assistance/resistance load was applied to both legs starting from the toe-off to mid-swing phase of gait during training. Outcome measures consisted of overground walking speed, 6-minute walk distance, and Gross Motor Function Measure scores and were assessed pre and post 6 weeks of training and 8 weeks after the end of training. After 6 weeks of treadmill training in participants from the resistance training group, fast walking speed and 6-minute walk distance significantly improved (18% and 30% increases, respectively), and 6-minute walk distance was still significantly greater than that at baseline (35% increase) 8 weeks after the end of training. In contrast, overground gait speed and 6-minute walk distance had no significant changes after robotic assistance training. The results of the present study indicated that robotic resistance treadmill training is more effective than assistance training in improving locomotor function in children with CP. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Design of the Lifestyle Improvement through Food and Exercise (LIFE) study: a randomized controlled trial of self-management of type 2 diabetes among African American patients from safety net health centers.

PubMed

Lynch, Elizabeth B; Liebman, Rebecca; Ventrelle, Jennifer; Keim, Kathryn; Appelhans, Bradley M; Avery, Elizabeth F; Tahsin, Bettina; Li, Hong; Shapera, Merle; Fogelfeld, Leon

2014-11-01

The Lifestyle Improvement through Food and Exercise (LIFE) study is a community-based randomized-controlled trial to measure the effectiveness of a lifestyle intervention to improve glycemic control among African Americans with type 2 diabetes attending safety net clinics. The study enrolled African American adults with a diagnosis of type 2 diabetes and HbA1c ≥ 7.0 who had attended specific safety net community clinics in the prior year. 210 patients will be enrolled and randomized to either the LIFE intervention or a standard of care control group, which consists of two dietitian-led diabetes self-management classes. The LIFE intervention was delivered in 28 group sessions over 12 months and focused on improving diet through dietitian-led culturally-tailored nutrition education, increasing physical activity through self-monitoring using an accelerometer, increasing ability to manage blood sugar through modifications to lifestyle, and providing social support for behavior change. In addition to the group sessions, peer supporters made regular telephone calls to participants to monitor progress toward behavioral goals and provide social support. The 12-month intervention phase was followed by a six-month maintenance phase consisting of two group sessions. The primary outcome of the study is change in A1C from baseline to 12 months, and an additional follow-up will occur at 18 months. The hypothesis of the study is that the participants in the LIFE intervention will show a greater improvement in glycemic control over 12 months than participants in the control group. Copyright © 2014 Elsevier Inc. All rights reserved.

Random phase encoding for optical security

NASA Astrophysics Data System (ADS)

Wang, RuiKang K.; Watson, Ian A.; Chatwin, Christopher R.

1996-09-01

A new optical encoding method for security applications is proposed. The encoded image (encrypted into the security products) is merely a random phase image statistically and randomly generated by a random number generator using a computer, which contains no information from the reference pattern (stored for verification) or the frequency plane filter (a phase-only function for decoding). The phase function in the frequency plane is obtained using a modified phase retrieval algorithm. The proposed method uses two phase-only functions (images) at both the input and frequency planes of the optical processor leading to maximum optical efficiency. Computer simulation shows that the proposed method is robust for optical security applications.

Luteal phase hyperprolactinemia.

PubMed

Falk, R J; Anderson, L

1994-01-01

To determine the incidence of both isolated and repetitive prolactin elevations in the luteal phase of otherwise normoprolactinemic women. To see if sporadic luteal-phase hyperprolactinemia is associated with progesterone deficiency, and to explore a possible physiological basis for sporadic hyperprolactinemia by TRH challenge. Hospital-based reproductive endocrinology/infertility service. Prospective measurement of luteal phase serum progesterone and prolactin in normoprolactinemic ovulatory women. TRH stimulation testing in volunteers with repetitive luteal phase hyperprolactinemia and normoprolactinemic controls. 133 sequentially selected infertile, ovulatory women with normal prolactin levels in the proliferative phase of the cycle. Measurement of serum progesterone and prolactin during the luteal phase, based on the day of the LH surge. TRH testing in the midluteal phase of the cycle in patients with two or more luteal phase prolactin elevations, and in five normoprolactinemic volunteers in both the preovulatory and midluteal phase. Of 133 subjects, 85 (64%) had no prolactin level exceeding 20 ng/mL in the luteal phase. Thirty-three (25%) had two or more elevated levels, and were considered to have repetitive luteal phase hyperprolactinemia (LPH). TRH testing in control subjects resulted in a greater prolactin response in the preovulatory phase. The group with LPH demonstrated an initial elevation of prolactin greater than that of the normoprolactinemic controls, but a subsequent drop to levels lower than both preovulatory and midluteal normoprolactinemic controls by 45 minutes. Sporadic luteal-phase hyperprolactinemia is a relatively common event (36% of 133 subjects in the present series). Of these 48 women, 33 (69%) had repetitive elevations, suggesting the elevation in these subjects to be more than a random event. The physiological validity of this observation is further demonstrated by an abnormal response to TRH stimulation, but the normal levels of luteal phase progesterone leave questions as to its pathological importance.

Luteal phase clomiphene citrate for ovulation induction in women with polycystic ovary syndrome: a systematic review and meta-analysis.

PubMed

Ding, Nan; Chang, Jianbo; Jian, Qiliang; Liang, Xuefei; Liang, Zhongzhen; Wang, Fang

2016-11-01

To assess the efficacy of late luteal phase clomiphene citrate (CC) administration relative to early follicular phase CC for ovulation induction for polycystic ovary syndrome (PCOS). Review. A complete electronic databases including PubMed, Embase, The Cochrane Library, Web of Science, and CBM were searched for relevant randomized controlled trials (RCTs). The search was not restricted by language and publication time. Two reviewers selected trials and assessed trial quality by the Cochrane Handbook 5.1.0 independently. Four eligible RCT studies involving 708 women (934 cycles) were included. The results of the Meta-analysis: Late luteal phase group was associated with a number of higher total follicles (MD 1.82; 95% CI 0.86-2.78, p < 0.00001) and significant higher endometrial thickness on the day of HCG (MD 0.88; 95% CI 0.78-0.99, p < 0.00001) compared with early follicular group. There were no significant differences in the rate of pregnancy (RR 1.29; 95% CI 0.83-2.01, p = 0.26), ovulation rate (RR 0.99; 95% CI 0.86-1.14, p = 0.87), and abortion rate (RR 1.12; 95% CI 0.38 to 3.29, p = 0.84) between the two groups. It appeared that late luteal phase CC for ovulation induction might be an effective method for ovulation induction in women with PCOS compared to conventional CC administration. Further intensive randomized-controlled studies should be warranted to define the efficacy of CC used in late luteal phase.

Long-Term Follow-up of Participants with Heart Failure in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

PubMed Central

Piller, Linda B.; Baraniuk, Sarah; Simpson, Lara M.; Cushman, William C.; Massie, Barry M.; Einhorn, Paula T.; Oparil, Suzanne; Ford, Charles E.; Graumlich, James F.; Dart, Richard A.; Parish, David C.; Retta, Tamrat M.; Cuyjet, Aloysius B.; Jafri, Syed Z.; Furberg, Curt D.; Saklayen, Mohammad G.; Thadani, Udho; Probstfield, Jeffrey L.; Davis, Barry R.

2011-01-01

Background In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind, practice-based, active-control, comparative effectiveness trial in high-risk hypertensive participants, risk of new-onset heart failure (HF) was higher in the amlodipine (2.5-10 mg/day) and lisinopril (10-40 mg/day) arms compared with the chlorthalidone (12.5-25 mg/day) arm . Similar to other studies, mortality rates following new-onset HF were very high (≥50% at 5 years), and were similar across randomized treatment arms. After the randomized phase of the trial ended in 2002, outcomes were determined from administrative databases. Methods and Results Using national databases, post-trial follow-up mortality through 2006 was obtained on participants who developed new-onset HF during the randomized (in-trial) phase of ALLHAT. Mean follow-up for the entire period was 8.9 years. Of 1761 participants with incident HF in-trial, 1348 died. Post-HF all-cause mortality was similar across treatment groups with adjusted hazard ratios (95% confidence intervals) of 0.95 (0.81-1.12) and 1.05 (0.89-1.25), respectively, for amlodipine and lisinopril compared with chlorthalidone, and 10-year adjusted rates of 86%, 87%, and 83%, respectively. All-cause mortality rates were also similar among those with reduced ejection fractions (84%) and preserved ejection fractions (81%) with no significant differences by randomized treatment arm. Conclusions Once HF develops, risk of death is high and consistent across randomized treatment groups. Measures to prevent the development of HF, especially blood pressure control, must be a priority if mortality associated with development of HF is to be addressed. PMID:21969009

Lifestyle interventions and independence for elders study: Recruitment and baseline characteristics

USDA-ARS?s Scientific Manuscript database

Recruitment of older adults into long-term clinical trials involving behavioral interventions is a significant challenge. The Lifestyle Interventions and Independence for Elders (LIFE) Study is a Phase 3 multicenter randomized controlled multisite trial, designed to compare the effects of a moderate...

Open-label dose optimization of methylphenidate modified release long acting (MPH-LA): a post hoc analysis of real-life titration from a 40-week randomized trial.

PubMed

Huss, Michael; Ginsberg, Ylva; Arngrim, Torben; Philipsen, Alexandra; Carter, Katherine; Chen, Chien-Wei; Gandhi, Preetam; Kumar, Vinod

2014-09-01

In the management of attention-deficit hyperactivity disorder (ADHD) in adults it is important to recognize that individual patients respond to a wide range of methylphenidate doses. Studies with methylphenidate modified release long acting (MPH-LA) in children have reported the need for treatment optimization for improved outcomes. We report the results from a post hoc analysis of a 5-week dose optimization phase from a large randomized, placebo-controlled, multicenter 40-week study (9-week double-blind dose confirmation phase, 5-week open-label dose optimization phase, and 26-week double-blind maintenance of effect phase). Patients entering the open-label dose optimization phase initiated treatment with MPH-LA 20 mg/day; up/down titrated to their optimal dose (at which there was balance between control of symptoms and side effects) of 40, 60, or 80 mg/day in increments of 20 mg/week by week 12 or 13. Safety was assessed by monitoring the adverse events (AEs) and serious AEs. Efficacy was assessed by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, Attention-Deficit Hyperactivity Disorder Rating Scale (DSM-IV ADHD RS) and Sheehan Disability Scale (SDS) total scores. At the end of the dose confirmation phase, similar numbers of patients were treated optimally with each of the 40, 60, and 80 mg/day doses (152, 177, and 160, respectively) for MPH-LA. Mean improvement from baseline in the dose confirmation phase in total scores of DSM-IV ADHD RS and SDS were 23.5 ± 9.90 and 9.7 ± 7.36, respectively. Dose optimization with MPH-LA (40, 60, or 80 mg/day) improved treatment outcomes and was well-tolerated in adult ADHD patients.

The effect of systemic antibiotics administered during the active phase of non-surgical periodontal therapy or after the healing phase: a systematic review.

PubMed

Fritoli, Aretuza; Gonçalves, Cristiane; Faveri, Marcelo; Figueiredo, Luciene Cristina; Pérez-Chaparro, Paula Juliana; Fermiano, Daiane; Feres, Magda

2015-01-01

The aim of this systematic review was to compare the clinical effectiveness of systemic antibiotics administered in the active stage of periodontal treatment or after the healing phase. An electronic search was performed in the databases EMBASE, MEDLINE and Cochrane Central Register of Controlled Trials (CENTRAL), in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. A manual search of the reference list of selected studies and of review articles was also performed up to November 2013. Randomized Clinical Trials (RCT) that evaluated the systemic administration of antibiotics as adjuvants to scaling and root planning (SRP) at different phases of periodontal treatment were included. Systematic reviews and studies that evaluated subjects with systemic diseases and those that used subantimicrobial doses of antibiotics were excluded. The initial search identified 1,039 articles, of which seven were selected, and only one met the inclusion criteria. This study showed that subjects taking metronidazole and amoxicillin at the initial phase of treatment exhibited statistically significantly greater reduction in pocket depth and gain in clinical attachment level in initially deep sites (PD≥7 mm) than subjects taking antibiotics after healing (p<0.05). This comparison was conducted 2 months after antibiotic intake, at the healing phase. To date, only one short-term RCT has directly compared different moments of systemic antibiotics administration, as adjuncts to SRP, in the treatment of periodontitis. Although the results of this study suggested some benefits for antibiotics intake during the active phase of therapy, these findings need to be confirmed by larger placebo-controlled randomized clinical trials with longer follow-up periods.

Safety of Bifidobacterium animalis subsp. lactis (B. lactis) strain BB-12-supplemented yogurt in healthy adults on antibiotics: a phase I safety study

PubMed Central

Merenstein, Daniel J; Tan, Tina P; Molokin, Aleksey; Smith, Keisha Herbin; Roberts, Robert F; Shara, Nawar M; Mete, Mihriye; Sanders, Mary Ellen; Solano-Aguilar, Gloria

2015-01-01

Probiotics are live microorganisms that, when administered in sufficient doses, provide health benefits on the host. The United States Food and Drug Administration (FDA) requires phase I safety studies for probiotics when the intended use of the product is as a drug. The purpose of the study was to determine the safety of Bifidobacterium animalis subsp lactis (B. lactis) strain BB-12 (BB-12)-supplemented yogurt when consumed by a generally healthy group of adults who were prescribed a 10-day course of antibiotics for a respiratory infection. Secondary aims were to assess the ability of BB-12 to affect the expression of whole blood immune markers associated with cell activation and inflammatory response. A phase I, double-blinded, randomized controlled study was conducted in compliance with FDA guidelines for an Investigational New Drug (IND). Forty participants were randomly assigned to consume 4 ounces of either BB-12 -supplemented yogurt or non-supplemented control yogurt daily for 10 d. The primary outcome was to assess safety and tolerability, assessed by the number of reported adverse events. A total of 165 non-serious adverse events were reported, with no differences between the control and BB-12 groups. When compared to the control group, B lactis fecal levels were modestly higher in the BB-12-supplemented group. In a small subset of patients, changes in whole blood expression of genes associated with regulation and activation of immune cells were detected in the BB-12-supplemented group. BB-12-supplemented yogurt is safe and well tolerated when consumed by healthy adults concurrently taking antibiotics. This study will form the basis for future randomized clinical trials investigating the potential immunomodulatory effects of BB-12-supplemented yogurt in a variety of disease states. PMID:25569274

Radiation-related quality of life parameters after targeted intraoperative radiotherapy versus whole breast radiotherapy in patients with breast cancer: results from the randomized phase III trial TARGIT-A.

PubMed

Welzel, Grit; Boch, Angela; Sperk, Elena; Hofmann, Frank; Kraus-Tiefenbacher, Uta; Gerhardt, Axel; Suetterlin, Marc; Wenz, Frederik

2013-01-07

Intraoperative radiotherapy (IORT) is a new treatment approach for early stage breast cancer. This study reports on the effects of IORT on radiation-related quality of life (QoL) parameters. Two hundred and thirty women with stage I-III breast cancer (age, 31 to 84 years) were entered into the study. A single-center subgroup of 87 women from the two arms of the randomized phase III trial TARGIT-A (TARGeted Intra-operative radioTherapy versus whole breast radiotherapy for breast cancer) was analyzed. Furthermore, results were compared to non-randomized control groups: n = 90 receiving IORT as a tumor bed boost followed by external beam whole breast radiotherapy (EBRT) outside of TARGIT-A (IORT-boost), and n = 53 treated with EBRT followed by an external-beam boost (EBRT-boost). QoL was collected using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires C30 (QLQ-C30) and BR23 (QLQ-BR23). The mean follow-up period in the TARGIT-A groups was 32 versus 39 months in the non-randomized control groups. Patients receiving IORT alone reported less general pain (21.3 points), breast (7.0 points) and arm (15.1 points) symptoms, and better role functioning (78.7 points) as patients receiving EBRT (40.9; 19.0; 32.8; and 60.5 points, respectively, P < 0.01). Patients receiving IORT alone also had fewer breast symptoms than TARGIT-A patients receiving IORT followed by EBRT for high risk features on final pathology (IORT-EBRT; 7.0 versus 29.7 points, P < 0.01). There were no significant differences between TARGIT-A patients receiving IORT-EBRT compared to non-randomized IORT-boost or EBRT-boost patients and patients receiving EBRT without a boost. In the randomized setting, important radiation-related QoL parameters after IORT were superior to EBRT. Non-randomized comparisons showed equivalent parameters in the IORT-EBRT group and the control groups.

An evaluation of three litter control procedures--trash receptacles, paid workers, and the marked item technique.

PubMed Central

Bacon-Prue, A; Blount, R; Pickering, D; Drabman, R

1980-01-01

This study assessed the effectiveness of three litter control procedures on the grounds of a residential retardation facility. Fifty-seven areas were divided into five groups according to the amount of litter they contained. Daily litter counts were made in one randomly chosen area for four of the groups and weekly litter counts were made from one randomly chosen area from the fifth group. After the baseline period, trash receptacles were placed a high traffic areas on the grounds of the facility. This was followed by the payment of two resident workers for picking up trash. In the next phase, marked pieces of litter were placed on the grounds, and residents voluntarily collected litter and turned it in at a central location. When a marked piece was turned in, that resident received $1.00 and had his or her picture taken and posted. This phase was followed by a return to the trash receptacles phase and then a return to the marked item phase. The results indicated that the marked item procedure was effective in reducing the amount of litter on the campus grounds, but the use of trash receptacles and the payment of resident workers for picking up litter did not noticeably reduce the amount of litter. The results are discussed in terms of the cost effectiveness of the procedures. PMID:6767679

Frequency and management of breakthrough bleeding with continuous use of the transvaginal contraceptive ring: a randomized controlled trial.

PubMed

Sulak, Patricia J; Smith, Virginia; Coffee, Andrea; Witt, Iris; Kuehl, Alicia L; Kuehl, Thomas J

2008-09-01

To assess bleeding patterns with continuous use of the transvaginal contraceptive ring. We did a prospective analysis of daily menstrual flow during a 21/7 cycle followed by 6 months of continuous use and institution of a randomized protocol to manage breakthrough bleeding/spotting. Seventy-four women completed the baseline 21/7 phase and were randomized equally into two groups during the continuous phase. Group 1 was instructed to replace the ring monthly on the same calendar day with no ring-free days. Group 2 was instructed to use the same process, but if breakthrough bleeding/spotting occurred for 5 days or more, they were to remove the ring for 4 days, store it, and then reinsert that ring. Sixty-five women completed the continuous phase with reduced average flow scores in the continuous phase compared with the 21/7 phase (P<.02). Most patients had no to minimal bleeding during continuous use, with group 2 experiencing a statistically greater percentage of days without breakthrough bleeding or spotting (95%) compared with group 1 (89%) (P=.016). Instituting a 4-day hormone-free interval was more (P<.001) effective in resolving breakthrough bleeding/spotting than continuing ring use. A reduction in bleeding occurred during continuous use with replacement of the transvaginal ring compared with baseline 21/7 use. Continuous vaginal ring use resulted in an acceptable bleeding profile in most patients, reduction in flow, reduction in pelvic pain, and a high continuation rate.

The role of the medial caudate nucleus, but not the hippocampus, in a matching-to sample task for a motor response.

PubMed

Kesner, Raymond P; Gilbert, Paul E

2006-04-01

A delayed-match-to-sample task was used to assess memory for motor responses in rats with control, hippocampus, or medial caudate nucleus (MCN) lesions. All testing was conducted on a cheeseboard maze in complete darkness using an infrared camera. A start box was positioned in the centre of the maze facing a randomly determined direction on each trial. On the sample phase, a phosphorescent object was randomly positioned to cover a baited food well in one of five equally spaced positions around the circumference of the maze forming a 180-degree arc 60 cm from the box. The rat had to displace the object to receive food and return to the start box. The box was then rotated to face a different direction. An identical baited phosphorescent object was placed in the same position relative to the start box. A second identical object was positioned to cover a different unbaited well. On the choice phase, the rat must remember the motor response made on the sample phase and make the same motor response on the choice phase to receive a reward. Hippocampus lesioned and control rats improved as a function of increased angle separation used to separate the correct object from the foil (45, 90, 135, and 180 degrees) and matched the performance of controls. However, rats with MCN lesions were impaired across all separations. Results suggest that the MCN, but not the hippocampus, supports working memory and/or a process aimed at reducing interference for motor response selection based on vector angle information.

Selecting promising treatments in randomized Phase II cancer trials with an active control.

PubMed

Cheung, Ying Kuen

2009-01-01

The primary objective of Phase II cancer trials is to evaluate the potential efficacy of a new regimen in terms of its antitumor activity in a given type of cancer. Due to advances in oncology therapeutics and heterogeneity in the patient population, such evaluation can be interpreted objectively only in the presence of a prospective control group of an active standard treatment. This paper deals with the design problem of Phase II selection trials in which several experimental regimens are compared to an active control, with an objective to identify an experimental arm that is more effective than the control or to declare futility if no such treatment exists. Conducting a multi-arm randomized selection trial is a useful strategy to prioritize experimental treatments for further testing when many candidates are available, but the sample size required in such a trial with an active control could raise feasibility concerns. In this study, we extend the sequential probability ratio test for normal observations to the multi-arm selection setting. The proposed methods, allowing frequent interim monitoring, offer high likelihood of early trial termination, and as such enhance enrollment feasibility. The termination and selection criteria have closed form solutions and are easy to compute with respect to any given set of error constraints. The proposed methods are applied to design a selection trial in which combinations of sorafenib and erlotinib are compared to a control group in patients with non-small-cell lung cancer using a continuous endpoint of change in tumor size. The operating characteristics of the proposed methods are compared to that of a single-stage design via simulations: The sample size requirement is reduced substantially and is feasible at an early stage of drug development.

Integrating nutrition and early child-development interventions among infants and preschoolers in rural India.

PubMed

Fernandez-Rao, Sylvia; Hurley, Kristen M; Nair, Krishnapillai Madhavan; Balakrishna, Nagalla; Radhakrishna, Kankipati V; Ravinder, Punjal; Tilton, Nicholas; Harding, Kimberly B; Reinhart, Greg A; Black, Maureen M

2014-01-01

This article describes the development, design, and implementation of an integrated randomized double-masked placebo-controlled trial (Project Grow Smart) that examines how home/preschool fortification with multiple micronutrient powder (MNP) combined with an early child-development intervention affects child development, growth, and micronutrient status among infants and preschoolers in rural India. The 1-year trial has an infant phase (enrollment age: 6-12 months) and a preschool phase (enrollment age: 36-48 months). Infants are individually randomized into one of four groups: placebo, placebo plus early learning, MNP alone, and MNP plus early learning (integrated intervention), conducted through home visits. The preschool phase is a cluster-randomized trial conducted in Anganwadi centers (AWCs), government-run preschools sponsored by the Integrated Child Development System of India. AWCs are randomized into MNP or placebo, with the MNP or placebo mixed into the children's food. The evaluation examines whether the effects of the MNP intervention vary by the quality of the early learning opportunities and communication within the AWCs. Study outcomes include child development, growth, and micronutrient status. Lessons learned during the development, design, and implementation of the integrated trial can be used to guide large-scale policy and programs designed to promote the developmental, educational, and economic potential of children in developing countries. © 2013 New York Academy of Sciences.

Adaptive Randomization of Veliparib-Carboplatin Treatment in Breast Cancer.

PubMed

Rugo, Hope S; Olopade, Olufunmilayo I; DeMichele, Angela; Yau, Christina; van 't Veer, Laura J; Buxton, Meredith B; Hogarth, Michael; Hylton, Nola M; Paoloni, Melissa; Perlmutter, Jane; Symmans, W Fraser; Yee, Douglas; Chien, A Jo; Wallace, Anne M; Kaplan, Henry G; Boughey, Judy C; Haddad, Tufia C; Albain, Kathy S; Liu, Minetta C; Isaacs, Claudine; Khan, Qamar J; Lang, Julie E; Viscusi, Rebecca K; Pusztai, Lajos; Moulder, Stacy L; Chui, Stephen Y; Kemmer, Kathleen A; Elias, Anthony D; Edmiston, Kirsten K; Euhus, David M; Haley, Barbara B; Nanda, Rita; Northfelt, Donald W; Tripathy, Debasish; Wood, William C; Ewing, Cheryl; Schwab, Richard; Lyandres, Julia; Davis, Sarah E; Hirst, Gillian L; Sanil, Ashish; Berry, Donald A; Esserman, Laura J

2016-07-07

The genetic and clinical heterogeneity of breast cancer makes the identification of effective therapies challenging. We designed I-SPY 2, a phase 2, multicenter, adaptively randomized trial to screen multiple experimental regimens in combination with standard neoadjuvant chemotherapy for breast cancer. The goal is to match experimental regimens with responding cancer subtypes. We report results for veliparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, combined with carboplatin. In this ongoing trial, women are eligible for participation if they have stage II or III breast cancer with a tumor 2.5 cm or larger in diameter; cancers are categorized into eight biomarker subtypes on the basis of status with regard to human epidermal growth factor receptor 2 (HER2), hormone receptors, and a 70-gene assay. Patients undergo adaptive randomization within each biomarker subtype to receive regimens that have better performance than the standard therapy. Regimens are evaluated within 10 biomarker signatures (i.e., prospectively defined combinations of biomarker subtypes). Veliparib-carboplatin plus standard therapy was considered for HER2-negative tumors and was therefore evaluated in 3 signatures. The primary end point is pathological complete response. Tumor volume changes measured by magnetic resonance imaging during treatment are used to predict whether a patient will have a pathological complete response. Regimens move on from phase 2 if and when they have a high Bayesian predictive probability of success in a subsequent phase 3 neoadjuvant trial within the biomarker signature in which they performed well. With regard to triple-negative breast cancer, veliparib-carboplatin had an 88% predicted probability of success in a phase 3 trial. A total of 72 patients were randomly assigned to receive veliparib-carboplatin, and 44 patients were concurrently assigned to receive control therapy; at the completion of chemotherapy, the estimated rates of pathological complete response in the triple-negative population were 51% (95% Bayesian probability interval [PI], 36 to 66%) in the veliparib-carboplatin group versus 26% (95% PI, 9 to 43%) in the control group. The toxicity of veliparib-carboplatin was greater than that of the control. The process used in our trial showed that veliparib-carboplatin added to standard therapy resulted in higher rates of pathological complete response than standard therapy alone specifically in triple-negative breast cancer. (Funded by the QuantumLeap Healthcare Collaborative and others; I-SPY 2 TRIAL ClinicalTrials.gov number, NCT01042379.).

Study protocol for a phase II dose evaluation randomized controlled trial of cholecalciferol in critically ill children with vitamin D deficiency (VITdAL-PICU study).

PubMed

McNally, Dayre; Amrein, Karin; O'Hearn, Katharine; Fergusson, Dean; Geier, Pavel; Henderson, Matt; Khamessan, Ali; Lawson, Margaret L; McIntyre, Lauralyn; Redpath, Stephanie; Weiler, Hope A; Menon, Kusum

2017-01-01

Clinical research has recently demonstrated that vitamin D deficiency (VDD) is highly prevalent in the pediatric intensive care unit (PICU) and associated with worse clinical course. Multiple adult ICU trials have suggested that optimization of vitamin D status through high-dose supplementation may reduce mortality and improve other clinically relevant outcomes; however, there have been no trials of rapid normalization in the PICU setting. The objective of this study is to evaluate the safety and efficacy of an enteral weight-based cholecalciferol loading dose regimen in critically ill children with VDD. The VITdAL-PICU pilot study is designed as a multicenter placebo-controlled phase II dose evaluation pilot randomized controlled trial. We aim to randomize 67 VDD critically ill children using a 2:1 randomization schema to receive loading dose enteral cholecalciferol (10,000 IU/kg, maximum of 400,000 IU) or a placebo solution. Participants, caregivers and outcome assessors will be blinded to allocation. Eligibility criteria include ICU patient, aged 37 weeks to 18 years, expected ICU length of stay more than 48 h, anticipated access to bloodwork at 7 days, and VDD (blood total 25 hydroxyvitamin D < 50 nmol/L). The primary objective is to determine whether the dosing protocol normalizes vitamin D status, defined as a blood total 25(OH)D concentration above 75 nmol/L. Secondary objectives include an examination of the safety of the dosing regimen (e.g. hypercalcemia, hypercalciuria, nephrocalcinosis), measures of vitamin D axis function (e.g. calcitriol levels, immune function), and protocol feasibility (eligibility criteria, protocol deviations, blinding). Despite significant observational literature suggesting VDD to be a modifiable risk factor in the PICU setting, there is no robust clinical trial evidence evaluating the benefits of rapid normalization. This phase II clinical trial will evaluate an innovative weight-based dosing regimen intended to rapidly and safely normalize vitamin D levels in critically ill children. Study findings will be used to inform the design of a multicenter phase III trial evaluating the clinical and economic benefits to rapid normalization. Recruitment for this trial was initiated in January 2016 and is expected to continue until November 30, 2017. Clinicaltrials.gov NCT02452762.

Long-acting PEGylated recombinant human growth hormone (Jintrolong) for children with growth hormone deficiency: phase II and phase III multicenter, randomized studies.

PubMed

Luo, Xiaoping; Hou, Ling; Liang, Li; Dong, Guanping; Shen, Shuixian; Zhao, Zhuhui; Gong, Chun Xiu; Li, Yuchuan; Du, Min-Lian; Su, Zhe; Du, Hongwei; Yan, Chaoying

2017-08-01

We assessed the efficacy and safety of a weekly pegylated human growth hormone (PEG-rhGH) (Jintrolong) vs daily rhGH for children with growth hormone deficiency (GHD). Phase II and III, multicenter, open-label, randomized controlled trials. 108 and 343 children with treatment-naive GHD from 6 hospitals in China were enrolled in the phase II and III studies respectively. Patients in the phase II study were randomized 1:1:1 to weekly Jintrolong (0.1 mg/kg/week PEG-rhGH complex), weekly Jintrolong (0.2 mg/kg/week PEG-rhGH complex) or daily rhGH (0.25 mg/kg/week) for 25 weeks. Patients in the phase III study were randomized in a 2:1 ratio to weekly Jintrolong (0.2 mg/kg/week) or daily rhGH (0.25 mg/kg/week) for 25 weeks. The primary endpoint for both studies was height velocity (HV) increase at the end of treatment. Other growth-related parameters, safety and compliance were also monitored. The phase II study established the preliminary efficacy, safety and recommended dose of Jintrolong PEG-rhGH. In the phase III study, we demonstrated significantly greater HV increases in patients receiving Jintrolong treatment (from 2.26 ± 0.87 cm/year to 13.41 ± 3.72 cm/year) vs daily rhGH (from 2.25 ± 0.82 cm/year to 12.55 ± 2.99 cm/year) at the end of treatment ( P  < 0.05). Additionally, significantly greater improvement in the height standard deviation scores was associated with Jintrolong throughout the treatment ( P  < 0.05). Adverse event rates and treatment compliance were comparable between the two groups. Jintrolong PEG-rhGH at a dose of 0.2 mg/kg/week for 25 weeks is effective and safe for GHD treatment and is non-inferior to daily rhGH. © 2017 The authors.

Long-acting PEGylated recombinant human growth hormone (Jintrolong) for children with growth hormone deficiency: phase II and phase III multicenter, randomized studies

PubMed Central

Hou, Ling; Liang, Li; Dong, Guanping; Shen, Shuixian; Zhao, Zhuhui; Gong, Chun Xiu; Li, Yuchuan; Du, Min-lian; Su, Zhe; Du, Hongwei; Yan, Chaoying

2017-01-01

Objective We assessed the efficacy and safety of a weekly pegylated human growth hormone (PEG-rhGH) (Jintrolong) vs daily rhGH for children with growth hormone deficiency (GHD). Design Phase II and III, multicenter, open-label, randomized controlled trials. Methods 108 and 343 children with treatment-naive GHD from 6 hospitals in China were enrolled in the phase II and III studies respectively. Patients in the phase II study were randomized 1:1:1 to weekly Jintrolong (0.1 mg/kg/week PEG-rhGH complex), weekly Jintrolong (0.2 mg/kg/week PEG-rhGH complex) or daily rhGH (0.25 mg/kg/week) for 25 weeks. Patients in the phase III study were randomized in a 2:1 ratio to weekly Jintrolong (0.2 mg/kg/week) or daily rhGH (0.25 mg/kg/week) for 25 weeks. The primary endpoint for both studies was height velocity (HV) increase at the end of treatment. Other growth-related parameters, safety and compliance were also monitored. Results The phase II study established the preliminary efficacy, safety and recommended dose of Jintrolong PEG-rhGH. In the phase III study, we demonstrated significantly greater HV increases in patients receiving Jintrolong treatment (from 2.26 ± 0.87 cm/year to 13.41 ± 3.72 cm/year) vs daily rhGH (from 2.25 ± 0.82 cm/year to 12.55 ± 2.99 cm/year) at the end of treatment (P < 0.05). Additionally, significantly greater improvement in the height standard deviation scores was associated with Jintrolong throughout the treatment (P < 0.05). Adverse event rates and treatment compliance were comparable between the two groups. Conclusion Jintrolong PEG-rhGH at a dose of 0.2 mg/kg/week for 25 weeks is effective and safe for GHD treatment and is non-inferior to daily rhGH. PMID:28566441

A new compound control method for sine-on-random mixed vibration test

NASA Astrophysics Data System (ADS)

Zhang, Buyun; Wang, Ruochen; Zeng, Falin

2017-09-01

Vibration environmental test (VET) is one of the important and effective methods to provide supports for the strength design, reliability and durability test of mechanical products. A new separation control strategy was proposed to apply in multiple-input multiple-output (MIMO) sine on random (SOR) mixed mode vibration test, which is the advanced and intensive test type of VET. As the key problem of the strategy, correlation integral method was applied to separate the mixed signals which included random and sinusoidal components. The feedback control formula of MIMO linear random vibration system was systematically deduced in frequency domain, and Jacobi control algorithm was proposed in view of the elements, such as self-spectrum, coherence, and phase of power spectral density (PSD) matrix. Based on the excessive correction of excitation in sine vibration test, compression factor was introduced to reduce the excitation correction, avoiding the destruction to vibration table or other devices. The two methods were synthesized to be applied in MIMO SOR vibration test system. In the final, verification test system with the vibration of a cantilever beam as the control object was established to verify the reliability and effectiveness of the methods proposed in the paper. The test results show that the exceeding values can be controlled in the tolerance range of references accurately, and the method can supply theory and application supports for mechanical engineering.

Rationale and design of the allogeneiC human mesenchymal stem cells (hMSC) in patients with aging fRAilTy via intravenoUS delivery (CRATUS) study: A phase I/II, randomized, blinded and placebo controlled trial to evaluate the safety and potential efficacy of allogeneic human mesenchymal stem cell infusion in patients with aging frailty.

PubMed

Golpanian, Samuel; DiFede, Darcy L; Pujol, Marietsy V; Lowery, Maureen H; Levis-Dusseau, Silvina; Goldstein, Bradley J; Schulman, Ivonne H; Longsomboon, Bangon; Wolf, Ariel; Khan, Aisha; Heldman, Alan W; Goldschmidt-Clermont, Pascal J; Hare, Joshua M

2016-03-15

Frailty is a syndrome associated with reduced physiological reserves that increases an individual's vulnerability for developing increased morbidity and/or mortality. While most clinical trials have focused on exercise, nutrition, pharmacologic agents, or a multifactorial approach for the prevention and attenuation of frailty, none have studied the use of cell-based therapies. We hypothesize that the application of allogeneic human mesenchymal stem cells (allo-hMSCs) as a therapeutic agent for individuals with frailty is safe and efficacious. The CRATUS trial comprises an initial non-blinded phase I study, followed by a blinded, randomized phase I/II study (with an optional follow-up phase) that will address the safety and pre-specified beneficial effects in patients with the aging frailty syndrome. In the initial phase I protocol, allo-hMSCs will be administered in escalating doses via peripheral intravenous infusion (n=15) to patients allocated to three treatment groups: Group 1 (n=5, 20 million allo-hMSCs), Group 2 (n=5, 100 million allo-hMSCs), and Group 3 (n=5, 200 million allo-hMSCs). Subsequently, in the randomized phase, allo-hMSCs or matched placebo will be administered to patients (n=30) randomly allocated in a 1:1:1 ratio to one of two doses of MSCs versus placebo: Group A (n=10, 100 million allo-hMSCs), Group B (n=10, 200 million allo-hMSCs), and Group C (n=10, placebo). Primary and secondary objectives are, respectively, to demonstrate the safety and efficacy of allo-hMSCs administered in frail older individuals. This study will determine the safety of intravenous infusion of stem cells and compare phenotypic outcomes in patients with aging frailty.

Multi-kW coherent combining of fiber lasers seeded with pseudo random phase modulated light

NASA Astrophysics Data System (ADS)

Flores, Angel; Ehrehreich, Thomas; Holten, Roger; Anderson, Brian; Dajani, Iyad

2016-03-01

We report efficient coherent beam combining of five kilowatt-class fiber amplifiers with a diffractive optical element (DOE). Based on a master oscillator power amplifier (MOPA) configuration, the amplifiers were seeded with pseudo random phase modulated light. Each non-polarization maintaining fiber amplifier was optically path length matched and provides approximately 1.2 kW of near diffraction-limited output power (measured M2<1.1). Consequently, a low power sample of each laser was utilized for active linear polarization control. A low power sample of the combined beam after the DOE provided an error signal for active phase locking which was performed via Locking of Optical Coherence by Single-Detector Electronic-Frequency Tagging (LOCSET). After phase stabilization, the beams were coherently combined via the 1x5 DOE. A total combined output power of 4.9 kW was achieved with 82% combining efficiency and excellent beam quality (M2<1.1). The intrinsic DOE splitter loss was 5%. Similarly, losses due in part to non-ideal polarization, ASE content, uncorrelated wavefront errors, and misalignment errors contributed to the efficiency reduction.

Advanced Collaborative Emissions Study (ACES)

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

Greenbaum, Daniel; Costantini, Maria; Van Erp, Annemoon

2013-12-31

The objective of the Advanced Collaborative Emissions Study (ACES) was to determine before widespread commercial deployment whether or not the new, energy-efficient, heavy duty diesel engines (2007 and 2010 EPA Emissions Standards Compliant) may generate anticipated toxic emissions that could adversely affect the environment and human health. ACES was planned to take place in three phases. In Phase 1, extensive emissions characterization of four production-intent prototype engine and control systems designed to meet 2007 standards for nitrogen oxides (NOx) and particulate matter (PM) was conducted at an existing emissions characterization facility: Southwest Research Institute (SwRI). One of the tested enginesmore » was selected (at random, after careful comparison of results) for health testing in Phase 3. In Phase 2, extensive emission characterization of three production-intent prototype engine and control systems meeting the 2010 standards (including more advanced NOx controls to meet the more stringent 2010 NOx standards) was conducted at the same test facility. In Phase 3, one engine/aftertreatment system selected from Phase 1 was further characterized during health effects studies (at an existing inhalation toxicology laboratory: Lovelace Respiratory Research Institute, [LRRI]) to form the basis of the ACES safety assessment. The Department of Energy (DOE) award provided funding for emissions characterization in Phases 1 and 2 as well as exposure characterization in Phase 3. The main health analyses in Phase 3 were funded separately and are not reported here.« less

[Menstrual prostaglandin and dysmenorrhea: modulation by non-steroidal antiinflammatory drugs].

PubMed

Di Girolamo, G; Gimeno, M A; Faletti, A; de los Santos, A R; Martí, M L; Zmijanovich, R

1999-01-01

The analgesic efficacy and tolerance of lysine clonixinate (LC) as well as LC-induced changes in menstrual prostaglandin levels were studied according to a prospective double-blind randomized crossover design, controlled with ibuprofen (I) and placebo (P). Treatment consisted in 4 consecutive phases: in the first phase, patients refrained from taking medication and during the remaining three phases, they received double-blind fixed doses of 1 tablet of lysine clonixinate 125 mg, I 400 mg or P, q.6 h. at random, three days before onset of menses and during 8 days thereafter. Controls were carried out at each menstrual cycle, assessing pain according to a scale from 0 to 4, onset of premenstrual and intramenstrual symptoms, relief of pain and occurrence of side-effects. During menstruation, patients recorded their assessments of pain in a diary and collected the whole menstrual bleeding during the first three days. The intensity of menstrual pain remained unchanged in controls upon admission (3.16) and during the phase with no treatment (3.04), but was significantly reduced with P (2.4), LC (1.79) and I (1.54). Significantly lower pain intensities compared with placebo were seen with active treatment phases. Forty-two percent of patients treated with P reported premenstrual pain which was significantly reduced to 17% with LC and to 12.5% with I. Active treatment phases revealed 21% of asymptomatic patients during premenstrual and menstrual periods and 71% (LC) and 75% (I) of cases with partial relief of pain. Patients' diaries showed significant pain reductions with LC and I, during the 1st and 2nd days compared with P; such differences were gradually reduced to nil by the 4th day. Levels of menstrual PGs changed according to pain intensity reductions from baseline (P: 29%, (NS); LC: 58% and I: 61%; both were statistically significant, p < 0.01).

Once-Weekly Administration of Sustained-Release Growth Hormone in Korean Prepubertal Children with Idiopathic Short Stature: A Randomized, Controlled Phase II Study.

PubMed

Hwang, Jin Soon; Lee, Hae Sang; Lee, Kee-Hyoung; Yoo, Han-Wook; Lee, Dae-Yeol; Suh, Byung-Kyu; Ko, Cheol Woo; Chung, Woo Yeong; Jin, Dong-Kyu; Shin, Choong Ho; Han, Heon-Seok; Han, Song; Kim, Ho-Seong

2018-06-20

To determine the optimal dose of LB03002, a sustained-release, once-weekly formulation of recombinant human growth hormone (rhGH), and to compare its efficacy and safety with daily rhGH in children with idiopathic short stature (ISS). This multicenter, randomized, open-label, phase II study included GH-naïve, prepubertal children with ISS, randomized to receive daily rhGH 0.37 mg/kg/week (control, n = 16), LB03002 0.5 mg/kg/week (n = 14), or LB03002 0.7 mg/kg/week (n = 16). The primary endpoint was height velocity (HV) change at week 26. At week 26, the least square (LS) means for HV change (cm/year) with control, LB03002 0.5 mg/kg/week, and LB03002 0.7 mg/kg/week were 5.08, 3.65, and 4.38, and the LS means for the change in height standard deviation score were 0.65, 0.49, and 0.58, respectively. The lower bound of the 90% confidence interval for the difference between LB03002 0.7 mg/kg/week and the control in the LS mean for HV change (-1.72) satisfied the noninferiority margin (-1.75). Adverse events were generally mild and short-lived. A once-weekly regimen of LB03002 0.7 mg/kg demonstrated noninferiority to the daily regimen of rhGH 0.37 mg/kg/week in terms of HV increments. LB03002 was well tolerated and its safety profile was comparable with that of daily rhGH. © 2018 S. Karger AG, Basel.

Safety and immunogenicity of inactivated poliovirus vaccine made from Sabin strains: a phase II, randomized, positive-controlled trial.

PubMed

Liao, Guoyang; Li, Rongcheng; Li, Changgui; Sun, Mingbo; Li, Yanping; Chu, Jiayou; Jiang, Shude; Li, Qihan

2012-01-15

The production of Sabin inactivated poliovirus vaccine (IPV) can reduce biosafety requirements in the posteradication/post-oral poliovirus vaccine (OPV) era. We conducted a phase II, randomized, positive-controlled trial to assess the safety and immunogenicity of Sabin IPV. The test groups (A, B, and C) received 3 doses of high, middle, and low D antigen (D Ag) of Sabin IPV at ages 2, 3, and 4 months, respectively. Infants in 2 control groups, group D and group E, received 3 doses of trivalent OPV and conventional IPV (cIPV), respectively, on the same schedule as that of groups A, B, and C. Serum samples were collected before and 30 days after the administration of the third dose. In total, 500 infants were randomly assigned to 5 groups, and 449 infants completed the vaccine series. No serious adverse events were associated with vaccinations. After 3 doses, the seroconversion rates in groups A, B, C, D, and E were 100%, 97.8%, 96.6%, 100%, and 90.1%, respectively, for type 1 poliovirus; 97.7%, 95.7%, 78.7%, 100%, and 90.1%, respectively, for type 2; and 98.8%, 98.9%, 93.3%, 100%, and 97.8%, respectively, for type 3. Sabin IPV has good safety characteristics. The seroconversion rates for type 1 poliovirus (most appropriate concentration, 15 D Ag units [DU]), type 2 (32 DU), and type 3 (45 DU) Sabin IPV were similar to those of the OPV and cIPV control groups. NCT01056705.

Task shifting of frontline community health workers for cardiovascular risk reduction: design and rationale of a cluster randomised controlled trial (DISHA study) in India.

PubMed

Jeemon, Panniyammakal; Narayanan, Gitanjali; Kondal, Dimple; Kahol, Kashvi; Bharadwaj, Ashok; Purty, Anil; Negi, Prakash; Ladhani, Sulaiman; Sanghvi, Jyoti; Singh, Kuldeep; Kapoor, Deksha; Sobti, Nidhi; Lall, Dorothy; Manimunda, Sathyaprakash; Dwivedi, Supriya; Toteja, Gurudyal; Prabhakaran, Dorairaj

2016-03-15

Effective task-shifting interventions targeted at reducing the global cardiovascular disease (CVD) epidemic in low and middle-income countries (LMICs) are urgently needed. DISHA is a cluster randomised controlled trial conducted across 10 sites (5 in phase 1 and 5 in phase 2) in India in 120 clusters. At each site, 12 clusters were randomly selected from a district. A cluster is defined as a small village with 250-300 households and well defined geographical boundaries. They were then randomly allocated to intervention and control clusters in a 1:1 allocation sequence. If any of the intervention and control clusters were <10 km apart, one was dropped and replaced with another randomly selected cluster from the same district. The study included a representative baseline cross-sectional survey, development of a structured intervention model, delivery of intervention for a minimum period of 18 months by trained frontline health workers (mainly Anganwadi workers and ASHA workers) and a post intervention survey in a representative sample. The study staff had no information on intervention allocation until the completion of the baseline survey. In order to ensure comparability of data across sites, the DISHA study follows a common protocol and manual of operation with standardized measurement techniques. Our study is the largest community based cluster randomised trial in low and middle-income country settings designed to test the effectiveness of 'task shifting' interventions involving frontline health workers for cardiovascular risk reduction. CTRI/2013/10/004049 . Registered 7 October 2013.

Ethical Issues for Control-Arm Patients After Revelation of Benefits of Experimental Therapy: A Framework Modeled in Neuroblastoma

PubMed Central

Unguru, Yoram; Joffe, Steven; Fernandez, Conrad V.; Yu, Alice L.

2013-01-01

In 2009, the Children's Oncology Group (COG) phase III randomized controlled trial, ANBL0032, found that adding immunotherapy (Ch14.18) to standard therapy significantly improved outcomes in patients with high-risk neuroblastoma when administered within 110 days after autologous stem-cell transplantation (SCT). After careful deliberation and consultation, the COG Neuroblastoma Committee decided to offer Ch14.18 to prior trial participants who had been randomly assigned to the control arm (no immunotherapy), regardless of the time that had elapsed since SCT. This decision occurred in the context of a limited supply of Ch14.18 and no data regarding its role when administered beyond 110 days. In this article, we analyze the numerous ethical challenges highlighted by the ANBL0032 trial, including the limits of researchers' reciprocity-based obligations to study participants, post-trial access to beneficial therapies, and the balance between scientific knowledge and parental hope. These deliberations may be useful to other researchers when considering their ethical obligations to control-arm participants in the wake of a positive randomized trial. PMID:23295797

Translating basic behavioral and social science research to clinical application: the EVOLVE mixed methods approach.

PubMed

Peterson, Janey C; Czajkowski, Susan; Charlson, Mary E; Link, Alissa R; Wells, Martin T; Isen, Alice M; Mancuso, Carol A; Allegrante, John P; Boutin-Foster, Carla; Ogedegbe, Gbenga; Jobe, Jared B

2013-04-01

To describe a mixed-methods approach to develop and test a basic behavioral science-informed intervention to motivate behavior change in 3 high-risk clinical populations. Our theoretically derived intervention comprised a combination of positive affect and self-affirmation (PA/SA), which we applied to 3 clinical chronic disease populations. We employed a sequential mixed methods model (EVOLVE) to design and test the PA/SA intervention in order to increase physical activity in people with coronary artery disease (post-percutaneous coronary intervention [PCI]) or asthma (ASM) and to improve medication adherence in African Americans with hypertension (HTN). In an initial qualitative phase, we explored participant values and beliefs. We next pilot tested and refined the intervention and then conducted 3 randomized controlled trials with parallel study design. Participants were randomized to combined PA/SA versus an informational control and were followed bimonthly for 12 months, assessing for health behaviors and interval medical events. Over 4.5 years, we enrolled 1,056 participants. Changes were sequentially made to the intervention during the qualitative and pilot phases. The 3 randomized controlled trials enrolled 242 participants who had undergone PCI, 258 with ASM, and 256 with HTN (n = 756). Overall, 45.1% of PA/SA participants versus 33.6% of informational control participants achieved successful behavior change (p = .001). In multivariate analysis, PA/SA intervention remained a significant predictor of achieving behavior change (p < .002, odds ratio = 1.66), 95% CI [1.22, 2.27], controlling for baseline negative affect, comorbidity, gender, race/ethnicity, medical events, smoking, and age. The EVOLVE method is a means by which basic behavioral science research can be translated into efficacious interventions for chronic disease populations.

Immunogenicity and safety assessment of a trivalent, inactivated split influenza vaccine in Korean children: Double-blind, randomized, active-controlled multicenter phase III clinical trial.

PubMed

Han, Seung Beom; Rhim, Jung-Woo; Shin, Hye Jo; Lee, Soo Young; Kim, Hyun-Hee; Kim, Jong-Hyun; Lee, Kyung-Yil; Ma, Sang Hyuk; Park, Joon Soo; Kim, Hwang Min; Kim, Chun Soo; Kim, Dong Ho; Choi, Young Youn; Cha, Sung-Ho; Hong, Young Jin; Kang, Jin Han

2015-01-01

A multicenter, double-blind, randomized, active-control phase III clinical trial was performed to assess the immunogenicity and safety of a trivalent, inactivated split influenza vaccine. Korean children between the ages of 6 months and 18 y were enrolled and randomized into a study (study vaccine) or a control vaccine group (commercially available trivalent, inactivated split influenza vaccine) in a 5:1 ratio. Antibody responses were determined using hemagglutination inhibition assay, and post-vaccination immunogenicity was assessed based on seroconversion and seroprotection rates. For safety assessment, solicited local and systemic adverse events up to 28 d after vaccination and unsolicited adverse events up to 6 months after vaccination were evaluated. Immunogenicity was assessed in 337 and 68 children of the study and control groups. In the study vaccine group, seroconversion rates against influenza A/H1N1, A/H3N2, and B strains were 62.0% (95% CI: 56.8-67.2), 53.4% (95% CI: 48.1-58.7), and 54.9% (95% CI: 48.1-60.2), respectively. The corresponding seroprotection rates were 95.0% (95% CI: 92.6-97.3), 93.8% (95% CI: 91.2-96.4), and 95.3% (95% CI: 93.0-97.5). The lower 95% CI limits of the seroconversion and seroprotection rates were over 40% and 70%, respectively, against all strains. Seroconversion and seroprotection rates were not significantly different between the study and control vaccine groups. Furthermore, the frequencies of adverse events were not significantly different between the 2 vaccine groups, and no serious vaccination-related adverse events were noted. In conclusion, the study vaccine exhibited substantial immunogenicity and safety in Korean children and is expected to be clinically effective.

Randomized controlled trials in children's heart surgery in the 21st century: a systematic review.

PubMed

Drury, Nigel E; Patel, Akshay J; Oswald, Nicola K; Chong, Cher-Rin; Stickley, John; Barron, David J; Jones, Timothy J

2018-04-01

Randomized controlled trials are the gold standard for evaluating health care interventions, yet are uncommon in children's heart surgery. We conducted a systematic review of clinical trials in paediatric cardiac surgery to evaluate the scope and quality of the current international literature. We searched MEDLINE, CENTRAL and LILACS, and manually screened retrieved references and systematic reviews to identify all randomized controlled trials reporting the effect of any intervention on the conduct or outcomes of heart surgery in children published in any language since January 2000; secondary publications and those reporting inseparable adult data were excluded. Two reviewers independently screened studies for eligibility and extracted data; the Cochrane Risk of Bias tool was used to assess for potential biases. We identified 333 trials from 34 countries randomizing 23 902 children. Most were early phase (313, 94.0%), recruiting few patients (median 45, interquartile range 28-82), and only 11 (3.3%) directly evaluated a surgical intervention. One hundred and nine (32.7%) trials calculated a sample size, 52 (15.6%) reported a CONSORT diagram, 51 (15.3%) were publicly registered and 25 (7.5%) had a Data Monitoring Committee. The overall risk of bias was low in 22 (6.6%), high in 69 (20.7%) and unclear in 242 (72.7%). The recent literature in children's heart surgery contains few late-phase clinical trials. Most trials did not conform to the accepted standards of reporting, and the overall risk of bias was low in few studies. There is a need for high-quality, multicentre clinical trials to provide a robust evidence base for contemporary paediatric cardiac surgical practice.

Randomized controlled trials in children’s heart surgery in the 21st century: a systematic review

PubMed Central

Drury, Nigel E; Patel, Akshay J; Oswald, Nicola K; Chong, Cher-Rin; Stickley, John; Barron, David J; Jones, Timothy J

2018-01-01

Abstract OBJECTIVES Randomized controlled trials are the gold standard for evaluating health care interventions, yet are uncommon in children’s heart surgery. We conducted a systematic review of clinical trials in paediatric cardiac surgery to evaluate the scope and quality of the current international literature. METHODS We searched MEDLINE, CENTRAL and LILACS, and manually screened retrieved references and systematic reviews to identify all randomized controlled trials reporting the effect of any intervention on the conduct or outcomes of heart surgery in children published in any language since January 2000; secondary publications and those reporting inseparable adult data were excluded. Two reviewers independently screened studies for eligibility and extracted data; the Cochrane Risk of Bias tool was used to assess for potential biases. RESULTS We identified 333 trials from 34 countries randomizing 23 902 children. Most were early phase (313, 94.0%), recruiting few patients (median 45, interquartile range 28–82), and only 11 (3.3%) directly evaluated a surgical intervention. One hundred and nine (32.7%) trials calculated a sample size, 52 (15.6%) reported a CONSORT diagram, 51 (15.3%) were publicly registered and 25 (7.5%) had a Data Monitoring Committee. The overall risk of bias was low in 22 (6.6%), high in 69 (20.7%) and unclear in 242 (72.7%). CONCLUSIONS The recent literature in children’s heart surgery contains few late-phase clinical trials. Most trials did not conform to the accepted standards of reporting, and the overall risk of bias was low in few studies. There is a need for high-quality, multicentre clinical trials to provide a robust evidence base for contemporary paediatric cardiac surgical practice. PMID:29186478

CR-Calculus and adaptive array theory applied to MIMO random vibration control tests

NASA Astrophysics Data System (ADS)

Musella, U.; Manzato, S.; Peeters, B.; Guillaume, P.

2016-09-01

Performing Multiple-Input Multiple-Output (MIMO) tests to reproduce the vibration environment in a user-defined number of control points of a unit under test is necessary in applications where a realistic environment replication has to be achieved. MIMO tests require vibration control strategies to calculate the required drive signal vector that gives an acceptable replication of the target. This target is a (complex) vector with magnitude and phase information at the control points for MIMO Sine Control tests while in MIMO Random Control tests, in the most general case, the target is a complete spectral density matrix. The idea behind this work is to tailor a MIMO random vibration control approach that can be generalized to other MIMO tests, e.g. MIMO Sine and MIMO Time Waveform Replication. In this work the approach is to use gradient-based procedures over the complex space, applying the so called CR-Calculus and the adaptive array theory. With this approach it is possible to better control the process performances allowing the step-by-step Jacobian Matrix update. The theoretical bases behind the work are followed by an application of the developed method to a two-exciter two-axis system and by performance comparisons with standard methods.

Accuracy and Precision of GPS Carrier-Phase Clock Estimates

DTIC Science & Technology

2001-01-01

International Frequency Control Sym- posium, 5-7 June 1996, Honolulu, Hawaii, USA (IEEE Publication 96CH35935), [19] R. Brown and P. Hwang , 1992...Introduction to Random Signals and Applied Kalman Filtering (John Wiley and Sons, New York). [2O] R. Dach, G. Beutler, U. Hugentobler, S. Schaer, T

Adipose-derived mesenchymal stem cells (AdMSC) for the treatment of secondary-progressive multiple sclerosis: A triple blinded, placebo controlled, randomized phase I/II safety and feasibility study.

PubMed

Fernández, Oscar; Izquierdo, Guillermo; Fernández, Victoria; Leyva, Laura; Reyes, Virginia; Guerrero, Miguel; León, Antonio; Arnaiz, Carlos; Navarro, Guillermo; Páramo, Maria Dolores; Cuesta, Antonio De la; Soria, Bernat; Hmadcha, Abdelkrim; Pozo, David; Fernandez-Montesinos, Rafael; Leal, Maria; Ochotorena, Itziar; Gálvez, Patricia; Geniz, Maria Angeles; Barón, Francisco Javier; Mata, Rosario; Medina, Cristina; Caparrós-Escudero, Carlos; Cardesa, Ana; Cuende, Natividad

2018-01-01

Currently available treatments for secondary progressive multiple sclerosis(SPMS) have limited efficacy and/or safety concerns. Adipose-mesenchymal derived stem cells(AdMSCs) represent a promising option and can be readily obtained using minimally invasive procedures. In this triple-blind, placebo-controlled study, cell samples were obtained from consenting patients by lipectomy and subsequently expanded. Patients were randomized to a single infusion of placebo, low-dose(1x106cells/kg) or high-dose(4x106cells/kg) autologous AdMSC product and followed for 12 months. Safety was monitored recording adverse events, laboratory parameters, vital signs and spirometry. Expanded disability status score (EDSS), magnetic-resonance-imaging, and other measures of possible treatment effects were also recorded. Thirty-four patients underwent lipectomy for AdMSCs collection, were randomized and thirty were infused (11 placebo, 10 low-dose and 9 high-dose); 4 randomized patients were not infused because of karyotype abnormalities in the cell product. Only one serious adverse event was observed in the treatment arms (urinary infection, considered not related to study treatment). No other safety parameters showed changes. Measures of treatment effect showed an inconclusive trend of efficacy. Infusion of autologous AdMSCs is safe and feasible in patients with SPMS. Larger studies and probably treatment at earlier phases would be needed to investigate the potential therapeutic benefit of this technique.

Baricitinib in adult patients with moderate-to-severe atopic dermatitis: a phase 2 parallel, double-blinded, randomized placebo-controlled multiple-dose study.

PubMed

Guttman-Yassky, Emma; Silverberg, Jonathan I; Nemoto, Osamu; Forman, Seth B; Wilke, August; Prescilla, Randy; de la Peña, Amparo; Nunes, Fabio P; Janes, Jonathan; Gamalo, Margaret; Donley, David; Paik, Jim; DeLozier, Amy M; Nickoloff, Brian J; Simpson, Eric L

2018-02-01

Baricitinib, an oral selective inhibitor of Janus kinase (JAK)1 and JAK2, modulates pro-inflammatory cytokine signaling. The efficacy and safety of baricitinib were evaluated in patients with moderate-to-severe atopic dermatitis (AD). In this phase 2, randomized, double-blind, placebo-controlled study, 124 patients with moderate-to-severe AD applied topical corticosteroids (TCS) for 4 weeks before randomization to once daily placebo, baricitinib 2 mg, or baricitinib 4 mg for 16 weeks. Use of TCS was permitted during the study. Primary outcome was the proportion of patients achieving ≥50% reduction in the Eczema Area and Severity Index (EASI-50) compared to placebo. Significantly more baricitinib 4-mg patients achieved EASI-50 compared to placebo (61% vs 37%; P=0.027) at 16 weeks. The proportion of baricitinib 2- and 4-mg patients achieving EASI-50 compared to placebo was significant as early as week 4. Baricitinib also improved pruritus and sleep loss. Treatment-emergent adverse events were reported in 24 (49%) placebo, 17 (46%) baricitinib 2-mg, and 27 (71%) baricitinib 4-mg patients. A TCS standardization period prior to randomization reduced disease severity, limiting the ability to compare results to baricitinib monotherapy. Longer studies are required to confirm baricitinib efficacy and safety in AD patients. Baricitinib used with TCS reduced inflammation and pruritus in patients with moderate-to-severe atopic dermatitis (AD). Copyright © 2018. Published by Elsevier Inc.

Safety and Efficacy of the ACE-Inhibitor Ramipril in Alport Syndrome: The Double-Blind, Randomized, Placebo-Controlled, Multicenter Phase III EARLY PRO-TECT Alport Trial in Pediatric Patients.

PubMed

Gross, Oliver; Friede, Tim; Hilgers, Reinhard; Görlitz, Anke; Gavénis, Karsten; Ahmed, Raees; Dürr, Ulrike

2012-01-01

Introduction. Retrospective observational data show that ACE-inhibitor therapy delays renal failure and improves life expectancy in Alport patients with proteinuria. The EARLY PRO-TECT Alport trial assesses the safety and efficacy of early therapy onset with ramipril in pediatric Alport patients. Methods and analysis. This double-blind, randomized, placebo-controlled, multicenter phase III trial (NCT01485978; EudraCT-number 2010-024300-10) includes 120 pediatric patients aged 24 months to 18 years with early stages of Alport syndrome (isolated hematuria or microalbuminuria). From March 2012, up to 80 patients will be randomized 1:1 to ramipril or placebo. In the event of disease progression during 3-year treatment, patients are unblinded and ramipril is initiated, if applicable. Approximately 40 patients receive open-label ramipril contributing to the safety database. Primary end-points are "time to progression to next disease level" and "incidence of adverse drug events before disease progression." Treatment effect estimates from the randomized comparison and Alport registry data will be combined in supportive analyses to maximize evidence. Conclusion. Without this trial, ACE inhibitors may become standard off-label treatment in Alport syndrome without satisfactory evidence base. The results are expected to be of relevance for therapy of all pediatric patients with kidney disease, and the trial protocol might serve as a model for other rare pediatric glomerulopathies.

Effect of sacrum-perineum heat therapy on active phase labor pain and client satisfaction: a randomized, controlled trial study.

PubMed

Taavoni, Simin; Abdolahian, Somayeh; Haghani, Hamid

2013-09-01

Reduction of labor pain is one of the most important aspects of obstetric care. Heat therapy, typically applied to the woman's back, lower abdomen, groin, and/or perineum during last stage of labor, is an easy pain relief method that does not require highly skilled care. The effectiveness of heat therapy applied to the perineum during the first stage of labor has not been evaluated. This study aimed to evaluate the effectiveness of heat therapy for pain and woman's satisfaction during physiological labor. Sixty primiparous women aged 18-35 years old were randomly assigned to heat therapy and control groups. Pain and satisfaction scores were measured by visual analog scale. The measurements of satisfaction were accomplished after birth. Data were analyzed by using the t-test and chi-square Mean pain scores in the heat therapy group were significantly lower than the control group (P < 0.05). The mean satisfaction score in the heat therapy group was significantly higher than in the control group (P < 0.05). Heat therapy, an inexpensive complementary treatment with low risk, can reduce the intensity of pain and increase mothers' satisfaction with care during the active phase of labor. Wiley Periodicals, Inc.

Directed self-assembly of liquid crystalline blue-phases into ideal single-crystals

NASA Astrophysics Data System (ADS)

Martínez-González, Jose A.; Li, Xiao; Sadati, Monirosadat; Zhou, Ye; Zhang, Rui; Nealey, Paul F.; de Pablo, Juan J.

2017-06-01

Chiral nematic liquid crystals are known to form blue phases--liquid states of matter that exhibit ordered cubic arrangements of topological defects. Blue-phase specimens, however, are generally polycrystalline, consisting of randomly oriented domains that limit their performance in applications. A strategy that relies on nano-patterned substrates is presented here for preparation of stable, macroscopic single-crystal blue-phase materials. Different template designs are conceived to exert control over different planes of the blue-phase lattice orientation with respect to the underlying substrate. Experiments are then used to demonstrate that it is indeed possible to create stable single-crystal blue-phase domains with the desired orientation over large regions. These results provide a potential avenue to fully exploit the electro-optical properties of blue phases, which have been hindered by the existence of grain boundaries.

X-ray light curves of active galactic nuclei are phase incoherent

NASA Technical Reports Server (NTRS)

Krolik, Julian; Done, Chris; Madejski, Grzegorz

1993-01-01

We compute the Fourier phase spectra for the light curves of five low-luminosity active galactic nuclei observed by EXOSAT. There is no statistically significant phase coherence in any of them. This statement is equivalent, subject to a technical caveat, to a demonstration that their fluctuation statistics are Gaussian. Models in which the X-ray output is controlled wholly by a unitary process undergoing a nonlinear limit cycle are therefore ruled out, while models with either a large number of randomly excited independent oscillation modes or nonlinearly interacting spatially dependent oscillations are favored. We also demonstrate how the degree of phase coherence in light curve fluctuations influences the application of causality bounds on internal length scales.

Thermally switchable photonic band-edge to random laser emission in dye-doped cholesteric liquid crystals

NASA Astrophysics Data System (ADS)

Ye, Lihua; Wang, Yan; Feng, Yangyang; Liu, Bo; Gu, Bing; Cui, Yiping; Lu, Yanqing

2018-03-01

By changing the doping concentration of the chiral agent to adjust the relative position of the reflection band of cholesteric liquid crystals and the fluorescence emission spectrum of the dye, photonic band-edge and random lasing were observed, respectively. The reflection band of the cholesteric phase liquid crystal can also be controlled by adjusting the temperature: the reflection band is blue-shifted with increasing temperature, and a reversible switch from photonic band-edge to random lasing is obtained. Furthermore, the laser line width can be thermally adjusted from 1.1 nm (at 27 °C) to 4.6 nm (at 32.1 °C). A thermally tunable polarization state of a random laser from dual cells was observed, broadening the field of application liquid crystal random lasers.

Quenched bond randomness: Superfluidity in porous media and the strong violation of universality

NASA Astrophysics Data System (ADS)

Falicov, Alexis; Berker, A. Nihat

1997-04-01

The effects of quenched bond randomness are most readily studied with superfluidity immersed in a porous medium. A lattice model for3He-4He mixtures and incomplete4He fillings in aerogel yields the signature effect of bond randomness, namely the conversion of symmetry-breaking first-order phase transitions into second-order phase transitions, the λ-line reaching zero temperature, and the elimination of non-symmetry-breaking first-order phase transitions. The model recognizes the importance of the connected nature of aerogel randomness and thereby yields superfluidity at very low4He concentrations, a phase separation entirely within the superfluid phase, and the order-parameter contrast between mixtures and incomplete fillings, all in agreement with experiments. The special properties of the helium mixture/aerogel system are distinctly linked to the aerogel properties of connectivity, randomness, and tenuousness, via the additional study of a regularized “jungle-gym” aerogel. Renormalization-group calculations indicate that a strong violation of the empirical universality principle of critical phenomena occurs under quenched bond randomness. It is argued that helium/aerogel critical properties reflect this violation and further experiments are suggested. Renormalization-group analysis also shows that, adjoiningly to the strong universality violation (which hinges on the occurrence or non-occurrence of asymptotic strong coupling—strong randomness under rescaling), there is a new “hyperuniversality” at phase transitions with asymptotic strong coupling—strong randomness behavior, for example assigning the same critical exponents to random- bond tricriticality and random- field criticality.

Observed Incidence of Uveitis Following Certolizumab Pegol Treatment in Patients With Axial Spondyloarthritis

PubMed Central

Rosenbaum, J. T.; Landewé, R.; Marzo‐Ortega, H.; Sieper, J.; van der Heijde, D.; Davies, O.; Bartz, H.; Hoepken, B.; Nurminen, T.; Deodhar, A.

2016-01-01

Objective Axial spondyloarthritis (axial SpA) is characterized by inflammation of the spine and sacroiliac joints and can also affect extraarticular sites, with the most common manifestation being uveitis. Here we report the incidence of uveitis flares in axial SpA patients from the RAPID‐axSpA trial, including ankylosing spondylitis (AS) and nonradiographic (nr) axial SpA. Methods The RAPID‐axSpA (NCT01087762) trial is double‐blind and placebo‐controlled to week 24, dose‐blind to week 48, and open‐label to week 204. Patients were randomized to certolizumab pegol (CZP) or placebo. Placebo patients entering the dose‐blind phase were re‐randomized to CZP. Uveitis events were recorded on extraarticular manifestation or adverse event forms. Events were analyzed in patients with/without history of uveitis, and rates reported per 100 patient‐years. Results At baseline, 38 of 218 CZP‐randomized patients (17.4%) and 31 of 107 placebo‐randomized patients (29.0%) had past uveitis history. During the 24‐week double‐blind phase, the rate of uveitis flares was lower in CZP (3.0 [95% confidence interval (95% CI) 0.6–8.8] per 100 patient‐years) than in placebo (10.3 [95% CI 2.8–26.3] per 100 patient‐years). All cases observed during the 24‐week double‐blind phase were in patients with a history of uveitis; in these patients, rates were similarly lower for CZP (17.1 [95% CI 3.5–50.1] per 100 patient‐years) than placebo (38.5 [95% CI 10.5–98.5] per 100 patient‐years). Rates of uveitis flares remained low up to week 96 (4.9 [95% CI 3.2–7.4] per 100 patient‐years) and were similar between AS (4.4 [95% CI 2.3–7.7] per 100 patient‐years) and nr‐axial SpA (5.6 [95% CI 2.9–9.8] per 100 patient‐years). Conclusion The rate of uveitis flares was lower for axial SpA patients treated with CZP than placebo during the randomized controlled phase. Incidence of uveitis flares remained low to week 96 and was comparable to rates reported for AS patients receiving other anti–tumor necrosis factor antibodies. PMID:26815944

Observed Incidence of Uveitis Following Certolizumab Pegol Treatment in Patients With Axial Spondyloarthritis.

PubMed

Rudwaleit, M; Rosenbaum, J T; Landewé, R; Marzo-Ortega, H; Sieper, J; van der Heijde, D; Davies, O; Bartz, H; Hoepken, B; Nurminen, T; Deodhar, A

2016-06-01

Axial spondyloarthritis (axial SpA) is characterized by inflammation of the spine and sacroiliac joints and can also affect extraarticular sites, with the most common manifestation being uveitis. Here we report the incidence of uveitis flares in axial SpA patients from the RAPID-axSpA trial, including ankylosing spondylitis (AS) and nonradiographic (nr) axial SpA. The RAPID-axSpA (NCT01087762) trial is double-blind and placebo-controlled to week 24, dose-blind to week 48, and open-label to week 204. Patients were randomized to certolizumab pegol (CZP) or placebo. Placebo patients entering the dose-blind phase were re-randomized to CZP. Uveitis events were recorded on extraarticular manifestation or adverse event forms. Events were analyzed in patients with/without history of uveitis, and rates reported per 100 patient-years. At baseline, 38 of 218 CZP-randomized patients (17.4%) and 31 of 107 placebo-randomized patients (29.0%) had past uveitis history. During the 24-week double-blind phase, the rate of uveitis flares was lower in CZP (3.0 [95% confidence interval (95% CI) 0.6-8.8] per 100 patient-years) than in placebo (10.3 [95% CI 2.8-26.3] per 100 patient-years). All cases observed during the 24-week double-blind phase were in patients with a history of uveitis; in these patients, rates were similarly lower for CZP (17.1 [95% CI 3.5-50.1] per 100 patient-years) than placebo (38.5 [95% CI 10.5-98.5] per 100 patient-years). Rates of uveitis flares remained low up to week 96 (4.9 [95% CI 3.2-7.4] per 100 patient-years) and were similar between AS (4.4 [95% CI 2.3-7.7] per 100 patient-years) and nr-axial SpA (5.6 [95% CI 2.9-9.8] per 100 patient-years). The rate of uveitis flares was lower for axial SpA patients treated with CZP than placebo during the randomized controlled phase. Incidence of uveitis flares remained low to week 96 and was comparable to rates reported for AS patients receiving other anti-tumor necrosis factor antibodies. © 2016, American College of Rheumatology.

Coformulated bictegravir, Emtricitabine (F), tenofovir alafenamide (TAF) after initial treatment with bictegravir or dolutegravir plus F/TAF.

PubMed

Sax, Paul E; Dejesus, Edwin; Crofoot, Gordon; Ward, Douglas; Benson, Paul; Dretler, Robin; Mills, Anthony; Brinson, Cynthia; Wei, Xuelian; Collins, Sean E; Cheng, Andrew

2018-05-22

: A phase 2, randomized, active-controlled study of initial antiretroviral therapy with bictegravir or dolutegravir in combination with emtricitabine and tenofovir alafenamide showed excellent efficacy. After 60 weeks of blinded treatment, participants switched to a single tablet regimen of bictegravir, emtricitabine and tenofovir alafenamide. Switching maintained viral suppression in all participants who chose to remain on the study through at least 12 weeks in the open-label phase, was safe and well tolerated.

The Efficacy and Safety of Shen Guo Lao Nian Granule for Common Cold of Qi-Deficiency Syndrome: Study Protocol for a Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase II Clinical Trial

PubMed Central

Fu, Juanjuan; Ding, Hong; Yang, Haimiao; Huang, Yuhong

2017-01-01

Background Common cold is one of the most frequently occurring illnesses in primary healthcare services and represents considerable disease burden. Common cold of Qi-deficiency syndrome (CCQDS) is an important but less addressed traditional Chinese medicine (TCM) pattern. We designed a protocol to explore the efficacy, safety, and optimal dose of Shen Guo Lao Nian Granule (SGLNG) for treating CCQDS. Methods/Design This is a multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial. A total of 240 eligible patients will be recruited from five centers. Patients are randomly assigned to high-dose group, middle-dose group, low-dose group, or control group in a 1 : 1 : 1 : 1 ratio. All drugs are required to be taken 3 times daily for 5 days with a 5-day follow-up period. Primary outcomes are duration of all symptoms, total score reduction on Jackson's scale, and TCM symptoms scale. Secondary outcomes include every single TCM symptom duration and score reduction, TCM main symptoms disappearance rate, curative effects, and comparison between Jackson's scale and TCM symptom scale. Ethics and Trial Registration This study protocol was approved by the Ethics Committee of Clinical Trials and Biomedicine of West China Hospital of Sichuan University (number IRB-2014-12) and registered with the Chinese Clinical Trial Registry (ChiCTR-IPR-15006349). PMID:29430253

A phase III study evaluating oral glutamine and transforming growth factor-beta 2 on chemotherapy-induced toxicity in patients with digestive neoplasm.

PubMed

Khemissa, Faïza; Mineur, Laurent; Amsellem, Caroline; Assenat, Eric; Ramdani, Mohamed; Bachmann, Patrick; Janiszewski, Chloé; Cristiani, Isabelle; Collin, Fideline; Courraud, Julie; de Forges, Hélène; Dechelotte, Pierre; Senesse, Pierre

2016-03-01

Patients with gastrointestinal (GI) cancer are exposed to cachexia, which is highly correlated with chemotherapy-induced side effects. Research suggests that specific immunonutrients could prevent such toxicities. The primary objective of this phase III study was to evaluate the efficacy of glutamine and transforming growth factor-β2 (TGF-β2) in the prevention of grade 3-4 non-hematological toxicities induced by chemotherapy in patients with GI cancer. We designed a double-blind, randomized, controlled and multicenter trial stratified according to center, type of chemotherapy, presence of cachexia, and age. Patients were randomized to receive either Clinutren Protect(®) (CP) or a control isocaloric diet (without TGF-β2 or glutamine). Between November 2007 and October 2011, 210 patients were enrolled in the study, of which 201 were included in the intention-to-treat analysis. Grade 3-4 non-hematological toxicities were not significantly different between the CP and control groups when evaluated by univariate and multivariate analyses. Likewise, no difference was observed regarding grade 3-4 hematological toxicities or reasons for treatment interruption. This randomized study does not support the hypothesis that oral glutamine and TGF-β2 supplementation is effective to reduce grade 3 or 4 non-hematological toxicities induced by chemotherapy in patients with GI neoplasm. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Iron supplementation and 2-unit red blood cell apheresis: a randomized, double-blind, placebo-controlled study.

PubMed

Radtke, Hartmut; Mayer, Beate; Röcker, Lothar; Salama, Abdulgabar; Kiesewetter, Holger

2004-10-01

The benefits of 2-unit red blood cell (RBC) apheresis are evident, but iron depletion may be a limiting factor in using this technology. Regular iron supplementation may allow a better utilization of this technique. In this study, 260 regular blood donors donated 2-unit RBCs on each of a total of seven visits at intervals of 8 to 10 weeks. The volunteers were randomly assigned to receive 100 mg of iron(II) or placebo daily. Group A received iron capsules after the first three donations, and Group B after the second three donations, respectively. Hemoglobin, serum ferritin, and serum iron were measured before each donation. Mean serum ferritin concentration decreased after each donation in the placebo phase of both treatment groups, but it remained largely constant during the iron phase in Group A, and even increased during the iron phase in Group B. Regular iron supplementation prevents iron depletion in the majority of donors after 2-unit RBC apheresis within an 8- to 10-week period.

The impact of written information and counseling (WOMAN-PRO II Program) on symptom outcomes in women with vulvar neoplasia: A multicenter randomized controlled phase II study.

PubMed

Raphaelis, Silvia; Mayer, Hanna; Ott, Stefan; Mueller, Michael D; Steiner, Enikö; Joura, Elmar; Senn, Beate

2017-07-01

To determine whether written information and/or counseling based on the WOMAN-PRO II Program decreases symptom prevalence in women with vulvar neoplasia by a clinically relevant degree, and to explore the differences between the 2 interventions in symptom prevalence, symptom distress prevalence, and symptom experience. A multicenter randomized controlled parallel-group phase II trial with 2 interventions provided to patients after the initial diagnosis was performed in Austria and Switzerland. Women randomized to written information received a predefined set of leaflets concerning wound care and available healthcare services. Women allocated to counseling were additionally provided with 5 consultations by an Advanced Practice Nurse (APN) between the initial diagnosis and 6months post-surgery that focused on symptom management, utilization of healthcare services, and health-related decision-making. Symptom outcomes were simultaneously measured 5 times to the counseling time points. A total of 49 women with vulvar neoplasia participated in the study. Symptom prevalence decreased in women with counseling by a clinically relevant degree, but not in women with written information. Sporadically, significant differences between the 2 interventions could be observed in individual items, but not in the total scales or subscales of the symptom outcomes. The results indicate that counseling may reduce symptom prevalence in women with vulvar neoplasia by a clinically relevant extent. The observed group differences between the 2 interventions slightly favor counseling over written information. The results justify testing the benefit of counseling thoroughly in a comparative phase III trial. Copyright © 2017 Elsevier Inc. All rights reserved.

Specific Safety Profile of Bevacizumab in Asian Patients With Advanced NSCLC

PubMed Central

Chen, Zhenguang; Zhong, Beilong; Lun, Xueping; Lai, Yingrong; Bella, Amos Ela; Yang, Weilin; Wu, Jiabin

2015-01-01

Abstract Randomized studies have obtained varying findings regarding the benefits and toxicities of bevacizumab in the treatment of nonsmall cell lung cancer (NSCLC). It is unclear whether the discrepancies among trials are due to ethnic/racial differences. We therefore performed a meta-analysis of all published, randomized, controlled clinical trials involving bevacizumab in patients with NSCLC to assess its effectiveness and safety in Asian and non-Asian populations. Results from the phase II JO19907 trial, the phase III AVAiL and ECOG 4599 trials, and the phase IV SAiL trials were used to calculate the benefits and toxicities of bevacizumab in Asian and non-Asian patients. Combined statistical estimates, including hazard ratios and odds ratios, were calculated using fixed-effects and random-effects models. A total of 4308 patients were evaluated. Combining bevacizumab with different chemotherapy regimens resulted in similar objective response rates, overall survival, and progression-free survival in Asian and non-Asian populations. Disease control rates, however, were only reported in Asian populations. The rates of severe bleeding (relative risk [RR], 2.17; P = 0.02) and thromboembolism (RR, 3.65; P < 0.0001) were significantly higher, while the rate of severe proteinuria was significantly lower (RR, 0.43; P < 0.0001), in non-Asian than in Asian populations. The rates of severe hypertension (P = 0.71) and hemoptysis (P = 0.66) were similar in Asian and non-Asian populations. Bevacizumab combined with chemotherapy for first-line NSCLC treatment showed similar benefits in Asian and non-Asian populations, but had specific safety profiles in each. PMID:26091469

Dronabinol for the Treatment of Cannabis Dependence: A Randomized, Double-Blind, Placebo-Controlled Trial

PubMed Central

Levin, Frances R.; Mariani, John J.; Brooks, Daniel J.; Pavlicova, Martina; Cheng, Wendy; Nunes, Edward

2011-01-01

Cannabis dependence is a substantial public health problem. Behavioral treatments have shown promise, but there are no effective medications for cannabis dependence. The purpose of this study was to evaluate the safety and efficacy of dronabinol, a synthetic form of delta-9-tetrahydrocannabinol, a naturally occurring pharmacologically active component of marijuana, in treating cannabis dependence. 156 cannabis-dependent adults were enrolled in a randomized, double-blind, placebo-controlled, 12-week trial. After a 1-week placebo lead-in phase, participants were randomized to receive dronabinol 20 mg twice a day or placebo. Doses were maintained until the end of week 8 and then tapered off over 2 weeks. All participants received weekly motivational enhancement and relapse prevention therapy. Marijuana use was assessed using the timeline followback method. There was no significant difference between treatment groups in the proportion of participants who achieved 2 weeks of abstinence at the end of the maintenance phase (dronabinol: 17.7%; placebo: 15.6%). Although both groups showed a reduction in marijuana use over time, there were no differences between the groups. Treatment retention was significantly higher at the end of the maintenance phase on dronabinol (77%), compared to placebo (61%) (P = .02), and withdrawal symptoms were significantly lower on dronabinol than placebo (P= .02). This is the first trial using an agonist substitution strategy for treatment of cannabis dependence. Dronabinol showed promise, it was well-tolerated, and improved treatment retention and withdrawal symptoms. Future trials might test higher doses, combinations of dronabinol with other medications with complementary mechanisms, or with more potent behavioral interventions. PMID:21310551

Feasibility and Efficacy of the Nintendo Wii Gaming System to Improve Balance Performance Post-Stroke: Protocol of a Phase II Randomized Controlled Trial in an Inpatient Rehabilitation Setting.

PubMed

Bower, Kelly J; Clark, Ross A; McGinley, Jennifer L; Martin, Clarissa L; Miller, Kimberly J

2013-04-01

Balance deficits following stroke are common and debilitating. Commercially available gaming systems, such as the Nintendo(®) (Kyoto, Japan) Wii™, have been widely adopted clinically; however, there is limited evidence supporting their feasibility and efficacy for improving balance performance following stroke. The aim of this trial is to investigate the clinical feasibility and efficacy of using the Nintendo Wii gaming system as an adjunct to standard care to improve balance performance following stroke in an inpatient rehabilitation setting. Thirty participants undergoing inpatient stroke rehabilitation will be recruited into this Phase II, single-blind, randomized controlled trial. Participants will be allocated into a Balance or Upper Limb Group, and both groups will perform activities using the Nintendo Wii in addition to their standard care. Participants will attend three 45-minute sessions per week, for a minimum of 2 and a maximum of 4 weeks. The main focus of the study is to investigate the feasibility of the intervention protocol. This will be evaluated through recruitment, retention, adherence, acceptability, and safety. The Step Test and Functional Reach Test will be the primary efficacy outcomes. Secondary outcomes will include force platform, mobility, and upper limb measures. Assessments will occur at baseline, 2 weeks, and 4 weeks after study entry. To the authors' knowledge, this will be the largest randomized clinical trial to investigate the feasibility and efficacy of the Nintendo Wii gaming system for improving balance performance in a stroke population. The results will inform the design of a Phase III multicenter trial.

Supplemental nicotine preloading for smoking cessation in posttraumatic stress disorder: Results from a randomized controlled trial.

PubMed

Dennis, Paul A; Kimbrel, Nathan A; Dedert, Eric A; Beckham, Jean C; Dennis, Michelle F; Calhoun, Patrick S

2016-08-01

Individuals with posttraumatic stress disorder (PTSD) are more likely to smoke and more likely to relapse following a quit attempt than individuals without PTSD. Thus, there is a significant need to study promising interventions that might improve quit rates for smokers with PTSD. One such intervention, supplemental nicotine patch-preloading, entails the use of nicotine replacement therapy prior to quitting. Objective The objective of this study was to conduct a randomized controlled trial of the efficacy of supplemental nicotine patch-preloading among smokers with PTSD. We hypothesized that, relative to participants in the placebo condition, participants in the nicotine patch-preloading condition would: (1) smoke less and experience reduced craving for cigarettes during the nicotine patch-preloading phase; (2) experience less smoking-associated relief from PTSD symptoms and negative affect during the preloading phase; and (3) exhibit greater latency to lapse, and higher short- and long-term abstinence rates. Sixty-three smokers with PTSD were randomized to either nicotine or placebo patch for three weeks prior to their quit date. Ecological momentary assessment was used to assess craving, smoking, PTSD symptoms, and negative affect during the preloading period. Nicotine patch-preloading failed to reduce smoking or craving during the preloading phase, nor was it associated with less smoking-associated relief from PTSD symptoms and negative affect. Moreover, no differences were observed between the treatment conditions for time to lapse, 6-week abstinence, or 6-month abstinence. The findings from the present research suggest that supplemental nicotine patch-preloading is unlikely to substantially enhance quit rates among smokers with PTSD. Published by Elsevier Ltd.

A randomized phase I study of methanesulfonyl fluoride, an irreversible cholinesterase inhibitor, for the treatment of Alzheimer's disease

PubMed Central

Moss, Donald E; Fariello, Ruggero G; Sahlmann, Jörg; Sumaya, Isabel; Pericle, Federica; Braglia, Enrico

2013-01-01

Aims To ascertain the tolerability profile of single and repeated oral doses of methanesulfonyl fluoride (MSF, SNX-001) in healthy aged subjects, and to determine the degree of erythrocyte acetylcholinesterase (AChE) inhibition induced by MSF after single and repeated oral doses. Methods To calculate properly the kinetics and the duration of AChE inhibition, the effects of MSF were also studied in rodents. These experiments suggested that MSF administered three times per week should provide safe and efficacious AChE inhibition. In a randomized placebo-controlled phase I study, 3.6 mg, 7.2 mg or 10.8 mg MSF were then orally administered to 27 consenting healthy volunteers (aged 50 to 72 years). After a single dose phase and a 1 week wash-out period, the subjects received the same doses three times per week for 2 weeks. Results Twenty-two out of the 27 subjects completed the study. Four patients withdrew due to adverse events (AEs) and one for non-compliance. Erythrocyte AChE was inhibited by a total of 33%, 46%, and 62% after 2 weeks of 3.6 mg, 7.2 mg and 10.8 mg MSF, respectively. No serious AEs occurred. The most frequent AEs were headache (27%), nausea (11%) and diarrhoea (8%). Conclusions MSF proved to be well tolerated even with repeated oral dosing. It is estimated that MSF provided a degree of AChE inhibition that should effectively enhance memory. This molecule deserves to be tested for efficacy in a pilot randomized controlled study in patients with Alzheimer's disease. PMID:23116458

Are Eyes a Mirror of the Soul? What Eye Wrinkles Reveal about a Horse’s Emotional State

PubMed Central

Hintze, Sara; Smith, Samantha; Patt, Antonia; Bachmann, Iris; Würbel, Hanno

2016-01-01

Finding valid indicators of emotional states is one of the biggest challenges in animal welfare science. Here, we investigated in horses whether variation in the expression of eye wrinkles caused by contraction of the inner eyebrow raiser reflects emotional valence. By confronting horses with positive and negative conditions, we aimed to induce positive and negative emotional states, hypothesising that positive emotions would reduce whereas negative emotions would increase eye wrinkle expression. Sixteen horses were individually exposed in a balanced order to two positive (grooming, food anticipation) and two negative conditions (food competition, waving a plastic bag). Each condition lasted for 60 seconds and was preceded by a 60 second control phase. Throughout both phases, pictures of the eyes were taken, and for each horse four pictures per condition and phase were randomly selected. Pictures were scored in random order and by two experimenters blind to condition and phase for six outcome measures: qualitative impression, eyelid shape, markedness of the wrinkles, presence of eye white, number of wrinkles, and the angle between the line through the eyeball and the highest wrinkle. The angle decreased during grooming and increased during food competition compared to control phases, whereas the two phases did not differ during food anticipation and the plastic bag condition. No effects on the other outcome measures were detected. Taken together, we have defined a set of measures to assess eye wrinkle expression reliably, of which one measure was affected by the conditions the horses were exposed to. Variation in eye wrinkle expression might provide valuable information on horse welfare but further validation of specific measures across different conditions is needed. PMID:27732647

Safety Profile of Biologic Drugs in the Therapy of Ulcerative Colitis: A Systematic Review and Network Meta-Analysis.

PubMed

Moćko, Paweł; Kawalec, Paweł; Pilc, Andrzej

2016-08-01

We compared the safety profile of biologic drugs in patients with moderately to severely active ulcerative colitis (UC). A systematic literature search was performed using Medline (PubMed), Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases through February 9, 2016. We included randomized controlled trials (RCTs) that compared the safety of biologic drugs (infliximab, adalimumab, golimumab, and vedolizumab) with one another or with placebo in patients with UC. Two reviewers independently conducted the search and selection of studies and rated the risk of bias in each trial. The network meta-analysis (NMA) was conducted for an induction phase (6-8 weeks) and maintenance phase (52-54 weeks) with a Bayesian hierarchical random effects model in Aggregate Data Drug Information System (ADDIS) software. The PROSPERO registration number was CRD42016032607. Seven RCTs were included in the systematic review with NMA. In the case of the induction phase, the NMA could be conducted for the assessment of the relative safety profile of adalimumab, golimumab, and vedolizumab, and in the case of the maintenance phase of infliximab, adalimumab, golimumab, and vedolizumab. The methodological quality of the included RCTs was evaluated as low risk of bias, but high risk of bias in the case of attrition bias (incomplete outcome data) according to the Cochrane criteria. No significant differences were found in the rate of adverse events in patients treated with the reviewed biologics. Vedolizumab was most likely to have the most favorable safety profile in the induction phase as was infliximab for the maintenance phase. The assessment of the relative safety profile revealed no significant differences between the biologic drugs. Further studies are needed to confirm our findings including head-to-head comparisons between the analyzed biologics. © 2016 Pharmacotherapy Publications, Inc.

Web-Based Tailored Intervention for Preparation of Parents and Children for Outpatient Surgery (WebTIPS): Formative Evaluation and Randomized Controlled Trial

PubMed Central

Fortier, Michelle A.; Bunzli, Elizabeth; Walthall, Jessica; Olshansky, Ellen; Saadat, Haleh; Santistevan, Ricci; Mayes, Linda; Kain, Zeev N.

2015-01-01

Background The purpose of this two-phase project was to conduct formative evaluation and test the preliminary efficacy of a newly developed web-based, tailored behavioral preparation program (WebTIPS) for children undergoing outpatient surgery and their parents Methods Phase I enrolled 13 children aged 2–7 years undergoing outpatient elective surgery and their parents for formative evaluation of WebTIPS. Parent participation focus groups which are common in qualitative research and are a method of asking research participants about their perceptions and attitudes regarding a product or concept. In phase II, children age 2–7 years in two medical centers were randomly assigned to receive the WebTIPS program (n = 38) compared to children receiving standard of care (n = 44). The primary outcome of phase II was child and parent preoperative anxiety. Results In phase I, parents reported WebTIPS to be both helpful (p < 0.001) and easy to use (p < 0.001). In phase II, children in the WebTIPS group (36.2 ± 14.1) were less anxious than children in the standard of care group (46.0 ± 19.0) at entrance to the operating room (p = 0.02; Cohen’s d = 0.59) and introduction of the anesthesia mask (43.5 ± 21.7 vs. 57.0 ± 21.2, respectively, p = 0.01; Cohen’s d = 0.63). Parents in the WebTIPS group (32.1 ± 7.4) also experienced less anxiety compared to parents in the control group (36.8 ± 7.1) in the preoperative holding area (p = 0.004; Cohen’s d = 0.65). Conclusions WebTIPS was well received by parents and children and led to reductions in preoperative anxiety. PMID:25790213

Nd:YAG pulsed-wave laser as support therapy in the treatment of teno-desmopathies of athlete horses: a clinical and experimental trial

NASA Astrophysics Data System (ADS)

Fortuna, Damiano; Rossi, Giacomo; Paolini, Cesare; Magi, Alberto; Losani, Fabrizio; Fallaci, Simone; Pacini, Franco; Porciani, Chiara; Sandler, Anna; Dalla Torre, Riccarda; Pinna, Stefania; Venturini, Antonio

2002-10-01

The ultrasonic evolution of tendinous repair envisages the recovery of ecogenicity: "reparative phase", followed by the realignment of the collagen fibres: "rehabilitative phase". The primary objective was to verify the safety and efficacy of Nd:YAG pulsed wave on teno- desmopathies of horses. Secondary to shorten "reparative phase" for to provide more time for "rehabilitative phase". The study has been divided into two investigations: experimental and clinical. In the experimental investigation, on 3 meat horses, the safety and tolerance of a power laser (35 W/cm2, 25 J/cm2) was investigated. The clinical investigation was performed on 79 sport horses through randomized double-blind. All subjects (Controls and Treated) received, on the subskin above the tendon lesion, the same local infiltration of immunostimulant. The results indicates that the High Intensity Laser Therapy (HILT) is safe and tolerated. It is able of reducing, in significative way, the "reparative phase", with a lower percentage of relapse (20% Treated and 40% Controls), but it is not able to reduce the time of the "rehabilitative phase".

Working With Parents to Prevent Childhood Obesity: Protocol for a Primary Care-Based eHealth Study.

PubMed

Avis, Jillian Ls; Cave, Andrew L; Donaldson, Stephanie; Ellendt, Carol; Holt, Nicholas L; Jelinski, Susan; Martz, Patricia; Maximova, Katerina; Padwal, Raj; Wild, T Cameron; Ball, Geoff Dc

2015-03-25

Parents play a central role in preventing childhood obesity. There is a need for innovative, scalable, and evidence-based interventions designed to enhance parents' motivation to support and sustain healthy lifestyle behaviors in their children, which can facilitate obesity prevention. (1) Develop an online screening, brief intervention, and referral to treatment (SBIRT) eHealth tool to enhance parents' concern for, and motivation to, support children's healthy lifestyle behaviors, (2) refine the SBIRT eHealth tool by assessing end-user acceptability, satisfaction, and usability through focus groups, and (3) determine feasibility and preliminary effectiveness of the refined SBIRT eHealth tool through a randomized controlled trial. This is a three-phase, multi-method study that includes SBIRT eHealth tool development (Phase I), refinement (Phase II), and testing (Phase III). Phase I: Theoretical underpinnings of the SBIRT tool, entitled the Resource Information Program for Parents on Lifestyle and Education (RIPPLE), will be informed by concepts applied within existing interventions, and content will be based on literature regarding healthy lifestyle behaviors in children. The SBIRT platform will be developed in partnership between our research team and a third-party intervention development company. Phase II: Focus groups with parents, as well as health care professionals, researchers, and trainees in pediatrics (n=30), will explore intervention-related perceptions and preferences. Qualitative data from the focus groups will inform refinements to the aesthetics, content, structure, and function of the SBIRT. Phase III: Parents (n=200) of children-boys and girls, 5 to 17 years old-will be recruited from a primary care pediatric clinic while they await their children's clinical appointment. Parents will be randomly assigned to one of five groups-four intervention groups and one control group-as they complete the SBIRT. The randomization function is built into the tool. Parents will complete the eHealth SBIRT using a tablet that will be connected to the Internet. Subsequently, parents will be contacted via email at 1-month follow-up to assess (1) change in concern for, and motivation to, support children's dietary and physical activity behaviors (primary outcome), and (2) use of online resources and referrals to health services for obesity prevention (secondary outcome). This research was successfully funded and received ethics approval. Development of the SBIRT started in summer 2012, and we expect all study-related activities to be completed by fall 2016. The proposed research is timely and applies a novel, technology-based application designed to enhance parents concern for, and motivation to, support children's healthy lifestyle behaviors and encourage use of online resources and community services for childhood obesity prevention. Overall, this research builds on a foundation of evidence supporting the application of SBIRTs to encourage or "nudge" individuals to make healthy lifestyle choices. Findings from Phase III of this project will directly inform a cluster randomized controlled trial to study the effectiveness of our intervention across multiple primary care-based settings. ClinicalTrials.gov NCT02330588; http://clinicaltrials.gov/ct2/show/NCT02330588 (Archived by WebCite at http://www.webcitation.org/6WyUOeRlr).

Efficacy, Safety, and Dose of Pafuramidine, a New Oral Drug for Treatment of First Stage Sleeping Sickness, in a Phase 2a Clinical Study and Phase 2b Randomized Clinical Studies

PubMed Central

Burri, Christian; Yeramian, Patrick D.; Merolle, Ada; Serge, Kazadi Kyanza; Mpanya, Alain; Lutumba, Pascal; Mesu, Victor Kande Betu Ku; Lubaki, Jean-Pierre Fina; Mpoto, Alfred Mpoo; Thompson, Mark; Munungu, Blaise Fungula; Josenando, Théophilo; Bernhard, Sonja C.; Olson, Carol A.; Blum, Johannes; Tidwell, Richard R.; Pohlig, Gabriele

2016-01-01

Background Sleeping sickness (human African trypanosomiasis [HAT]) is caused by protozoan parasites and characterized by a chronic progressive course, which may last up to several years before death. We conducted two Phase 2 studies to determine the efficacy and safety of oral pafuramidine in African patients with first stage HAT. Methods The Phase 2a study was an open-label, non-controlled, proof-of-concept study where 32 patients were treated with 100 mg of pafuramidine orally twice a day (BID) for 5 days at two trypanosomiasis reference centers (Angola and the Democratic Republic of the Congo [DRC]) between August 2001 and November 2004. The Phase 2b study compared pafuramidine in 41 patients versus standard pentamidine therapy in 40 patients. The Phase 2b study was open-label, parallel-group, controlled, randomized, and conducted at two sites in the DRC between April 2003 and February 2007. The Phase 2b study was then amended to add an open-label sequence (Phase 2b-2), where 30 patients received pafuramidine for 10 days. The primary efficacy endpoint was parasitologic cure at 24 hours (Phase 2a) or 3 months (Phase 2b) after treatment completion. The primary safety outcome was the rate of occurrence of World Health Organization Toxicity Scale Grade 3 or higher adverse events. All subjects provided written informed consent. Findings/Conclusion Pafuramidine for the treatment of first stage HAT was comparable in efficacy to pentamidine after 10 days of dosing. The cure rates 3 months post-treatment were 79% in the 5-day pafuramidine, 100% in the 7-day pentamidine, and 93% in the 10-day pafuramidine groups. In Phase 2b, the percentage of patients with at least 1 treatment-emergent adverse event was notably higher after pentamidine treatment (93%) than pafuramidine treatment for 5 days (25%) and 10 days (57%). These results support continuation of the development program for pafuramidine into Phase 3. PMID:26881924

Efficacy, Safety, and Dose of Pafuramidine, a New Oral Drug for Treatment of First Stage Sleeping Sickness, in a Phase 2a Clinical Study and Phase 2b Randomized Clinical Studies.

PubMed

Burri, Christian; Yeramian, Patrick D; Allen, James L; Merolle, Ada; Serge, Kazadi Kyanza; Mpanya, Alain; Lutumba, Pascal; Mesu, Victor Kande Betu Ku; Bilenge, Constantin Miaka Mia; Lubaki, Jean-Pierre Fina; Mpoto, Alfred Mpoo; Thompson, Mark; Munungu, Blaise Fungula; Manuel, Francisco; Josenando, Théophilo; Bernhard, Sonja C; Olson, Carol A; Blum, Johannes; Tidwell, Richard R; Pohlig, Gabriele

2016-02-01

Sleeping sickness (human African trypanosomiasis [HAT]) is caused by protozoan parasites and characterized by a chronic progressive course, which may last up to several years before death. We conducted two Phase 2 studies to determine the efficacy and safety of oral pafuramidine in African patients with first stage HAT. The Phase 2a study was an open-label, non-controlled, proof-of-concept study where 32 patients were treated with 100 mg of pafuramidine orally twice a day (BID) for 5 days at two trypanosomiasis reference centers (Angola and the Democratic Republic of the Congo [DRC]) between August 2001 and November 2004. The Phase 2b study compared pafuramidine in 41 patients versus standard pentamidine therapy in 40 patients. The Phase 2b study was open-label, parallel-group, controlled, randomized, and conducted at two sites in the DRC between April 2003 and February 2007. The Phase 2b study was then amended to add an open-label sequence (Phase 2b-2), where 30 patients received pafuramidine for 10 days. The primary efficacy endpoint was parasitologic cure at 24 hours (Phase 2a) or 3 months (Phase 2b) after treatment completion. The primary safety outcome was the rate of occurrence of World Health Organization Toxicity Scale Grade 3 or higher adverse events. All subjects provided written informed consent. Pafuramidine for the treatment of first stage HAT was comparable in efficacy to pentamidine after 10 days of dosing. The cure rates 3 months post-treatment were 79% in the 5-day pafuramidine, 100% in the 7-day pentamidine, and 93% in the 10-day pafuramidine groups. In Phase 2b, the percentage of patients with at least 1 treatment-emergent adverse event was notably higher after pentamidine treatment (93%) than pafuramidine treatment for 5 days (25%) and 10 days (57%). These results support continuation of the development program for pafuramidine into Phase 3.

Efficacy of pre-exercise low-level laser therapy on isokinetic muscle performance in individuals with type 2 diabetes mellitus: study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Type 2 diabetes, also known non-insulin-dependent diabetes, is the most prevalent type of the disease and involves defects in the secretion and action of insulin. The aim of the proposed study is to evaluate the efficacy of pre-exercise low-level laser therapy (LLLT) on muscle performance of the quadriceps femoris in individuals with type 2 diabetes. Methods/Design A double-blind, randomized, controlled clinical trial will be carried out in two treatment phases. In the first phase, quadriceps muscle performance will be evaluated using an isokinetic dynamometer and the levels of creatine kinase and lactate dehydrogenase (biochemical markers of muscle damage) will be determined. The participants will then be allocated to four LLLT groups through a randomization process using opaque envelopes: Group A (4 Joules), Group B (6 Joules), Group C (8 Joules) and Group D (0 Joules; placebo). Following the administration of LLLT, the participants will be submitted to an isokinetic eccentric muscle fatigue protocol involving the quadriceps muscle bilaterally. Muscle performance and biochemical markers of muscle damage will be evaluated again immediately after as well as 24 and 48 hours after the experimental protocol. One week after the last evaluation the second phase will begin, during which Groups A, B and C will receive the LLLT protocol that achieved the best muscle performance in phase 1 for a period of 4 weeks. At the end of this period, muscle performance will be evaluated again. The protocol for this study is registered with the World Health Organization under Universal Trial Number U1111-1146-7109. Discussion The purpose of this randomized clinical trial is to evaluate the efficacy of pre-exercise LLLT on the performance of the quadriceps muscle (peak torque, total muscle work, maximum power and fatigue index – normalized by body mass) in individuals with DM-2. The study will support the practice of evidence-based to the use of LLLT in improving muscle performance in Individuals with DM-2. Data will be published after the study is completed. PMID:24716713

Efficacy of pre-exercise low-level laser therapy on isokinetic muscle performance in individuals with type 2 diabetes mellitus: study protocol for a randomized controlled trial.

PubMed

Gomes, Cid André Fidelis de Paula; Leal-Junior, Ernesto Cesar Pinto; Biasotto-Gonzalez, Daniela Aparecida; El-Hage, Yasmin; Politti, Fabiano; Gonzalez, Tabajara de Oliveira; Dibai-Filho, Almir Vieira; de Oliveira, Adriano Rodrigues; Frigero, Marcelo; Antonialli, Fernanda Colella; Vanin, Adriane Aver; de Tarso Camillo de Carvalho, Paulo

2014-04-09

Type 2 diabetes, also known non-insulin-dependent diabetes, is the most prevalent type of the disease and involves defects in the secretion and action of insulin. The aim of the proposed study is to evaluate the efficacy of pre-exercise low-level laser therapy (LLLT) on muscle performance of the quadriceps femoris in individuals with type 2 diabetes. A double-blind, randomized, controlled clinical trial will be carried out in two treatment phases. In the first phase, quadriceps muscle performance will be evaluated using an isokinetic dynamometer and the levels of creatine kinase and lactate dehydrogenase (biochemical markers of muscle damage) will be determined. The participants will then be allocated to four LLLT groups through a randomization process using opaque envelopes: Group A (4 Joules), Group B (6 Joules), Group C (8 Joules) and Group D (0 Joules; placebo). Following the administration of LLLT, the participants will be submitted to an isokinetic eccentric muscle fatigue protocol involving the quadriceps muscle bilaterally. Muscle performance and biochemical markers of muscle damage will be evaluated again immediately after as well as 24 and 48 hours after the experimental protocol. One week after the last evaluation the second phase will begin, during which Groups A, B and C will receive the LLLT protocol that achieved the best muscle performance in phase 1 for a period of 4 weeks. At the end of this period, muscle performance will be evaluated again. The protocol for this study is registered with the World Health Organization under Universal Trial Number U1111-1146-7109. The purpose of this randomized clinical trial is to evaluate the efficacy of pre-exercise LLLT on the performance of the quadriceps muscle (peak torque, total muscle work, maximum power and fatigue index - normalized by body mass) in individuals with DM-2. The study will support the practice of evidence-based to the use of LLLT in improving muscle performance in Individuals with DM-2. Data will be published after the study is completed.

Ultrasound enhanced thrombolysis: Clinical evidence

NASA Astrophysics Data System (ADS)

Alexandrov, Andrei V.

2005-04-01

Phase II CLOTBUST randomized clinical trial (Houston, Barcelona, Edmonton, Calgary) evaluated patients with acute ischemic stroke due to intracranial occlusion and treated with intravenous tissue plasminogen activator (TPA) within 3 h of symptom onset. Randomization: monitoring with pulsed wave 2 MHz transcranial Doppler (TCD) (Target) or placebo monitoring (Control). Safety: symptomatic bleeding to the brain (sICH). Primary end-point: complete recanalization on TCD or dramatic clinical recovery by the total NIHSS score <3, or improvement by >10 NIHSS points within 2 hours after TPA bolus. All projected 126 patients were randomized 1:1 to target (median NIHSS 16) or control (NIHSS 17). sICH: 4.8% Target, 4.8% Controls. Primary end-point was achieved by 31 (49%, Target) versus 19 (30%, Control), p<0.03. At 3 months, 22 (42% Target) and 14 (29% Control) patients achieved favorable outcomes. Continuous TCD monitoring of intracranial occlusion safely augments TPA-induced arterial recanalization, and 2 MHz diagnostic ultrasound has a positive biological activity that aids systemic thrombolytic therapy. For the first time in clinical medicine, the CLOTBUST trial provides the evidence that ultrasound enhances thrombolytic activity of a drug in humans thereby confirming intense multi-disciplinary experimental research conducted worldwide for the past 30 years.

Moving Beyond Conventional Clinical Trial End Points in Treatment-refractory Metastatic Colorectal Cancer: A Composite Quality-of-life and Symptom Control End Point.

PubMed

Gong, Jun; Wu, Daniel; Chuang, Jeremy; Tuli, Richard; Simard, John; Hendifar, Andrew

2017-11-01

This review highlights the evidence supporting symptom control and quality-of-life (QOL) measures as predictors of survival in treatment-refractory metastatic colorectal cancer (mCRC) and describes a composite symptom control and QOL end point recently reported in a Phase III trial that may serve as a more reasonable end point of efficacy in this population. A literature search was conducted using MEDLINE to identify clinical studies (including case series and observational, retrospective, and prospective studies) that reported the predictive value of QOL measures for survival in mCRC. The search was limited by the following key words: quality of life, survival, and colorectal cancer. We then performed a second search limited to studies of randomized and Phase III design in mCRC to identify studies that used QOL assessments as their primary end points. A manual search was also performed to include additional studies of potential relevance. There is increasing evidence to support that symptom control and QOL measures are predictors of survival in treatment-refractory mCRC and can serve as an alternative but equally as important end point to survival in this population. A recent large, randomized Phase III trial using a composite primary end point of lean body mass, pain, anorexia, and fatigue reported the feasibility in evaluating benefit in mCRC beyond conventional clinical trial end points. Future studies in treatment-refractory mCRC may be better served by evaluating improvement in symptom control and QOL, which may otherwise serve as the best predictor of survival in last-line treatment settings. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Transcranial direct current stimulation (tDCS) for idiopathic Parkinson's disease.

PubMed

Elsner, Bernhard; Kugler, Joachim; Pohl, Marcus; Mehrholz, Jan

2016-07-18

Idiopathic Parkinson's disease (IPD) is a neurodegenerative disorder, with the severity of the disability usually increasing with disease duration. IPD affects patients' health-related quality of life, disability, and impairment. Current rehabilitation approaches have limited effectiveness in improving outcomes in patients with IPD, but a possible adjunct to rehabilitation might be non-invasive brain stimulation by transcranial direct current stimulation (tDCS) to modulate cortical excitability, and hence to improve these outcomes in IPD. To assess the effectiveness of tDCS in improving motor and non-motor symptoms in people with IPD. We searched the following databases (until February 2016): the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library ; 2016 , Issue 2), MEDLINE, EMBASE, CINAHL, AMED, Science Citation Index, the Physiotherapy Evidence Database (PEDro), Rehabdata, and Inspec. In an effort to identify further published, unpublished, and ongoing trials, we searched trial registers and reference lists, handsearched conference proceedings, and contacted authors and equipment manufacturers. We included only randomised controlled trials (RCTs) and randomised controlled cross-over trials that compared tDCS versus control in patients with IPD for improving health-related quality of life , disability, and impairment. Two review authors independently assessed trial quality (JM and MP) and extracted data (BE and JM). If necessary, we contacted study authors to ask for additional information. We collected information on dropouts and adverse events from the trial reports. We included six trials with a total of 137 participants. We found two studies with 45 participants examining the effects of tDCS compared to control (sham tDCS) on our primary outcome measure, impairment, as measured by the Unified Parkinson's Disease Rating Scale (UPDRS). There was very low quality evidence for no effect of tDCS on change in global UPDRS score ( mean difference (MD) -7.10 %, 95% confidence interval (CI -19.18 to 4.97; P = 0.25, I² = 21%, random-effects model). However, there was evidence of an effect on UPDRS part III motor subsection score at the end of the intervention phase (MD -14.43%, 95% CI -24.68 to -4.18; P = 0.006, I² = 2%, random-effects model; very low quality evidence). One study with 25 participants measured the reduction in off and on time with dyskinesia, but there was no evidence of an effect (MD 0.10 hours, 95% CI -0.14 to 0.34; P = 0.41, I² = 0%, random-effects model; and MD 0.00 hours, 95% CI -0.12 to 0.12; P = 1, I² = 0%, random- effects model, respectively; very low quality evidence).Two trials with a total of 41 participants measured gait speed using measures of timed gait at the end of the intervention phase, revealing no evidence of an effect ( standardised mean difference (SMD) 0.50, 95% CI -0.17 to 1.18; P = 0.14, I² = 11%, random-effects model; very low quality evidence). Another secondary outcome was health-related quality of life and we found one study with 25 participants reporting on the physical health and mental health aspects of health-related quality of life (MD 1.00 SF-12 score, 95% CI -5.20 to 7.20; I² = 0%, inverse variance method with random-effects model; very low quality evidence; and MD 1.60 SF-12 score, 95% CI -5.08 to 8.28; I² = 0%, inverse variance method with random-effects model; very low quality evidence, respectively). We found no study examining the effects of tDCS for improving activities of daily living. In two of six studies, dropouts , adverse events, or deaths occurring during the intervention phase were reported. There was insufficient evidence that dropouts , adverse effects, or deaths were higher with intervention (risk difference (RD) 0.04, 95% CI -0.05 to 0.12; P = 0.40, I² = 0%, random-effects model; very low quality evidence).We found one trial with a total of 16 participants examining the effects of tDCS plus movement therapy compared to control (sham tDCS) plus movement therapy on our secondary outcome, gait speed at the end of the intervention phase, revealing no evidence of an effect (MD 0.05 m/s, 95% CI -0.15 to 0.25; inverse variance method with random-effects model; very low quality evidence). We found no evidence of an effect regarding differences in dropouts and adverse effects between intervention and control groups (RD 0.00, 95% CI -0.21 to 0.21; Mantel-Haenszel method with random-effects model; very low quality evidence). There is insufficient evidence to determine the effects of tDCS for reducing off time ( when the symptoms are not controlled by the medication) and on time with dyskinesia ( time that symptoms are controlled but the person still experiences involuntary muscle movements ) , and for improving health- related quality of life, disability, and impairment in patients with IPD. Evidence of very low quality indicates no difference in dropouts and adverse events between tDCS and control groups.

Effect of Bacillus amyloliquefaciens-based Direct-fed Microbial on Performance, Nutrient Utilization, Intestinal Morphology and Cecal Microflora in Broiler Chickens

PubMed Central

Lei, Xinjian; Piao, Xiangshu; Ru, Yingjun; Zhang, Hongyu; Péron, Alexandre; Zhang, Huifang

2015-01-01

The present study was conducted to evaluate the effect of the dietary supplementation of Bacillus amyloliquefaciens-based direct-fed microbial (DFM) on growth performance, nutrient utilization, intestinal morphology and cecal microflora in broiler chickens. A total of two hundred and eighty eight 1-d-old Arbor Acres male broilers were randomly allocated to one of four experimental treatments in a completely randomized design. Each treatment was fed to eight replicate cages, with nine birds per cage. Dietary treatments were composed of an antibiotic-free basal diet (control), and the basal diet supplemented with either 15 mg/kg of virginiamycin as antibiotic growth promoter (AGP), 30 mg/kg of Bacillus amyloliquefaciens-based DFM (DFM 30) or 60 mg/kg of Bacillus amyloliquefaciens-based DFM (DFM 60). Experimental diets were fed in two phases: starter (d 1 to 21) and finisher (d 22 to 42). Growth performance, nutrient utilization, morphological parameters of the small intestine and cecal microbial populations were measured at the end of the starter (d 21) and finisher (d 42) phases. During the starter phase, DFM and virginiamycin supplementation improved the feed conversion ratio (FCR; p<0.01) compared with the control group. For the finisher phase and the overall experiment (d 1 to 42) broilers fed diets with the DFM had better body weight gain (BWG) and FCR than that of control (p<0.05). Supplementation of virginiamycin and DFM significantly increased the total tract apparent digestibility of crude protein (CP), dry matter (DM) and gross energy during both starter and finisher phases (p<0.05) compared with the control group. On d 21, villus height, crypt depth and villus height to crypt depth ratio of duodenum, jejunum, and ileum were significantly increased for the birds fed with the DFM diets as compared with the control group (p<0.05). The DFM 30, DFM 60, and AGP groups decreased the Escherichia coli population in cecum at d 21 and d 42 compared with control group (p<0.01). In addition, the population of Lactobacillus was increased in DFM 30 and DFM 60 groups as compared with control and AGP groups (p<0.01). It can be concluded that Bacillus amyloliquefaciens-based DFM could be an alternative to the use of AGPs in broilers diets based on plant protein. PMID:25557820

Effect of dance labor on the management of active phase labor pain & clients' satisfaction: a randomized controlled trial study.

PubMed

Abdolahian, Somayeh; Ghavi, Fatemeh; Abdollahifard, Sareh; Sheikhan, Fatemeh

2014-03-30

There are a wide variety of non- pharmacologic pain relief techniques for labor which include pelvic movement, upright position, back massage and partner support during the first stage of labor. The effectiveness of dance labor- which is a combination of these techniques- has not been evaluated. This study aimed to evaluate the effectiveness of dance labor in pain reduction and woman's satisfaction during the first stage of labor. 60 primiparous women aged 18-35 years old were randomly assigned to dance labor and control groups. In the dance labor group, women were instructed to do standing upright with pelvic tilt and rock their hips back and forth or around in a circle while their partner massaged their back and sacrum for a minimum of 30 minutes. In the control group, the participants received usual care during physiologic labor. Pain and satisfaction scores were measured by Visual Analogue Scale. Data were analyzed by using the t. test and Chi-square. Mean pain score in the dance labor group was significantly lower than the control group (P < 0.05). The mean satisfaction score in the dance labor group was significantly higher than in the control group (P < 0.05). Dance labor which is a complementary treatment with low risk can reduce the intensity of pain and increase mothers, satisfaction with care during the active phase of labor.

Efficacy and tolerability of transdermal granisetron for the control of chemotherapy-induced nausea and vomiting associated with moderately and highly emetogenic multi-day chemotherapy: a randomized, double-blind, phase III study.

PubMed

Boccia, Ralph V; Gordan, Lucio N; Clark, Gemma; Howell, Julian D; Grunberg, Steven M

2011-10-01

A novel transdermal formulation of granisetron (the granisetron transdermal delivery system (GTDS)) has been developed to deliver granisetron continuously over 7 days. This double-blind, phase III, non-inferiority study compared the efficacy and tolerability of the GTDS to daily oral granisetron for the control of chemotherapy-induced nausea and vomiting (CINV). Six hundred forty-one patients were randomized to oral (2 mg/day, 3-5 days) or transdermal granisetron (one GTDS patch, 7 days), before receiving multi-day chemotherapy. The primary endpoint was complete control of CINV (no vomiting/retching, no more than mild nausea, no rescue medication) from chemotherapy initiation until 24 h after final administration. The prespecified non-inferiority margin was 15%. Five hundred eighty-two patients were included in the per protocol analysis. The GTDS displayed non-inferiority to oral granisetron: complete control was achieved by 60% of patients in the GTDS group, and 65% in the oral granisetron group (treatment difference, -5%; 95% confidence interval, -13-3). Both treatments were well tolerated, the most common adverse event being constipation. The GTDS provides effective, well-tolerated control of CINV associated with moderately or highly emetogenic multi-day chemotherapy. It offers a convenient alternative route for delivering granisetron for up to 7 days that is as effective as oral granisetron.

Effect of endometrial biopsy on intrauterine insemination outcome in controlled ovarian stimulation cycle.

PubMed

Wadhwa, Leena; Pritam, Amrita; Gupta, Taru; Gupta, Sangeeta; Arora, Sarika; Chandoke, Rajkumar

2015-01-01

The objective was to evaluate the effect of endometrial biopsy (EB) on intrauterine insemination (IUI) outcome in controlled ovarian stimulation (COS) cycle. Prospective randomized control study. Tertiary care center. A total of 251 subjects were enrolled in the study. Subjects undergoing COS with IUI were randomly allocated into three groups. Group A: EB was taken between D19 and 24 of the spontaneous menstrual cycles that precedes the fertility treatment and IUI, which was done in next cycle (n = 86). Group B: EB was taken before D6 of the menstrual cycle, and fertility treatment and IUI was done in the same cycle (n = 90). Group C: (control group) no EB in previous 3 cycle (n = 75). Clinical pregnancy rate (CPR). Clinical pregnancy rate was 19.77%, 31.11%, and 9.3% for Group A, Group B, and Group C, respectively. The results show a highly significant value for the paired t-test of intervention Group B and control Group C of the cases (P = 0.000957). CPR was maximum after first cycle of ovulation induction and IUI following EB scratch in both Groups A and in Group B (P < 0.001). Endometrial biopsy done in early follicular phase in the same cycle of stimulation with IUI gives better CPR as compared with EB done in the luteal phase of the previous cycle.

Effect of Alternate Nostril Breathing Exercise on Experimentally Induced Anxiety in Healthy Volunteers Using the Simulated Public Speaking Model: A Randomized Controlled Pilot Study.

PubMed

Kamath, Ashwin; Urval, Rathnakar P; Shenoy, Ashok K

2017-01-01

A randomized controlled pilot study was carried out to determine the effect of a 15-minute practice of ANB exercise on experimentally induced anxiety using the simulated public speaking model in yoga-naïve healthy young adults. Thirty consenting medical students were equally divided into test and control groups. The test group performed alternate nostril breathing exercise for 15 minutes, while the control group sat in a quiet room before participating in the simulated public speaking test (SPST). Visual Analog Mood Scale and Self-Statements during Public Speaking scale were used to measure the mood state at different phases of the SPST. The psychometric scores of both groups were comparable at baseline. Repeated-measures ANOVA showed a significant effect of phase ( p < 0.05), but group and gender did not have statistically significant influence on the mean anxiety scores. However, the test group showed a trend towards lower mean scores for the anxiety factor when compared with the control group. Considering the limitations of this pilot study and the trend seen towards lower anxiety in the test group, alternate nostril breathing may have potential anxiolytic effect in acute stressful situations. A study with larger sample size is therefore warranted. This trial is registered with CTRI/2014/03/004460.

Effect of Alternate Nostril Breathing Exercise on Experimentally Induced Anxiety in Healthy Volunteers Using the Simulated Public Speaking Model: A Randomized Controlled Pilot Study

PubMed Central

Urval, Rathnakar P.; Shenoy, Ashok K.

2017-01-01

A randomized controlled pilot study was carried out to determine the effect of a 15-minute practice of ANB exercise on experimentally induced anxiety using the simulated public speaking model in yoga-naïve healthy young adults. Thirty consenting medical students were equally divided into test and control groups. The test group performed alternate nostril breathing exercise for 15 minutes, while the control group sat in a quiet room before participating in the simulated public speaking test (SPST). Visual Analog Mood Scale and Self-Statements during Public Speaking scale were used to measure the mood state at different phases of the SPST. The psychometric scores of both groups were comparable at baseline. Repeated-measures ANOVA showed a significant effect of phase (p < 0.05), but group and gender did not have statistically significant influence on the mean anxiety scores. However, the test group showed a trend towards lower mean scores for the anxiety factor when compared with the control group. Considering the limitations of this pilot study and the trend seen towards lower anxiety in the test group, alternate nostril breathing may have potential anxiolytic effect in acute stressful situations. A study with larger sample size is therefore warranted. This trial is registered with CTRI/2014/03/004460. PMID:29159176

Engineering the Flow of Liquid Two-Phase Systems by Passive Noise Control

NASA Astrophysics Data System (ADS)

Zhang, Zeyi; Kong, Tiantian; Zhou, Chunmei; Wang, Liqiu

2018-02-01

We investigate a passive noise-control approach to engineering the two-phase flow in a microfluidic coflow system. The presence or absence of the jet breakup is studied for two immiscible oil phases, in a straight microchannel (referred to as the J device in the main text), an expansion microchannel (the W device) and a microchannel with the expansion-contraction geometry (the S device), respectively. We show that the jet breaks into droplets, in the jetting regime and the dripping regime (also referred to as the widening-jetting regime) for the straight channel and expansion channel, respectively, while a stable long jet does not break for the expansion-contraction geometry. As the inner phase passes the expansion-contraction functional unit, the random noise on the interface is significantly reduced and the hydrodynamic instability is suppressed, for a range of experimental parameters including flow rates, device geometry, liquid viscosity, and interfacial tension. We further present scale-up devices with multiple noise-control units and achieve decimeter-long yet stable jets. Our simple, effective, and robust noise-control approach can benefit microfluidic applications such as microfiber fabrication, interface chemical reaction, and on-chip distance transportation.

Two biomarker-directed randomized trials in European and Chinese patients with nonsmall-cell lung cancer: the BRCA1-RAP80 Expression Customization (BREC) studies.

PubMed

Moran, T; Wei, J; Cobo, M; Qian, X; Domine, M; Zou, Z; Bover, I; Wang, L; Provencio, M; Yu, L; Chaib, I; You, C; Massuti, B; Song, Y; Vergnenegre, A; Lu, H; Lopez-Vivanco, G; Hu, W; Robinet, G; Yan, J; Insa, A; Xu, X; Majem, M; Chen, X; de Las Peñas, R; Karachaliou, N; Sala, M A; Wu, Q; Isla, D; Zhou, Y; Baize, N; Zhang, F; Garde, J; Germonpre, P; Rauh, S; ALHusaini, H; Sanchez-Ronco, M; Drozdowskyj, A; Sanchez, J J; Camps, C; Liu, B; Rosell, R

2014-11-01

In a Spanish Lung Cancer Group (SLCG) phase II trial, the combination of BRCA1 and receptor-associated protein 80 (RAP80) expression was significantly associated with outcome in Caucasian patients with nonsmall-cell lung cancer (NSCLC). The SLCG therefore undertook an industry-independent collaborative randomized phase III trial comparing nonselected cisplatin-based chemotherapy with therapy customized according to BRCA1/RAP80 expression. An analogous randomized phase II trial was carried out in China under the auspices of the SLCG to evaluate the effect of BRCA1/RAP80 expression in Asian patients. Eligibility criteria included stage IIIB-IV NSCLC and sufficient tumor specimen for molecular analysis. Randomization to the control or experimental arm was 1 : 1 in the SLCG trial and 1 : 3 in the Chinese trial. In both trials, patients in the control arm received docetaxel/cisplatin; in the experimental arm, patients with low RAP80 expression received gemcitabine/cisplatin, those with intermediate/high RAP80 expression and low/intermediate BRCA1 expression received docetaxel/cisplatin, and those with intermediate/high RAP80 expression and high BRCA1 expression received docetaxel alone. The primary end point was progression-free survival (PFS). Two hundred and seventy-nine patients in the SLCG trial and 124 in the Chinese trial were assessable for PFS. PFS in the control and experimental arms in the SLCG trial was 5.49 and 4.38 months, respectively [log rank P = 0.07; hazard ratio (HR) 1.28; P = 0.03]. In the Chinese trial, PFS was 4.74 and 3.78 months, respectively (log rank P = 0.82; HR 0.95; P = 0.82). Accrual was prematurely closed on the SLCG trial due to the absence of clinical benefit in the experimental over the control arm. However, the BREC studies provide proof of concept that an international, nonindustry, biomarker-directed trial is feasible. Thanks to the groundwork laid by these studies, we expect that ongoing further research on alternative biomarkers to elucidate DNA repair mechanisms will help define novel therapeutic approaches. NCT00617656/GECP-BREC and ChiCTR-TRC-12001860/BREC-CHINA. © The Author 2014. 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.

Boson expansions based on the random phase approximation representation

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

Pedrocchi, V.G.; Tamura, T.

1984-04-01

A new boson expansion theory based on the random phase approximation is presented. The boson expansions are derived here directly in the random phase approximation representation with the help of a technique that combines the use of the Usui operator with that of a new bosonization procedure, called the term-by-term bosonization method. The present boson expansion theory is constructed by retaining a single collective quadrupole random phase approximation component, a truncation that allows for a perturbative treatment of the whole problem. Both Hermitian, as well as non-Hermitian boson expansions, valid for even nuclei, are obtained.

Phase control and fast start-up of a magnetron using modulation of an addressable faceted cathode

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

Browning, J., E-mail: JimBrowning@BoiseState.edu; Fernandez-Gutierrez, S.; Lin, M. C.

The use of an addressable, faceted cathode has been proposed as a method of modulating current injection in a magnetron to improve performance and control phase. To implement the controllable electron emission, five-sided and ten-sided faceted planar cathodes employing gated field emitters are considered as these emitters could be fabricated on flat substrates. For demonstration, the conformal finite-difference time-domain particle-in-cell simulation, as implemented in VORPAL, has been used to model a ten-cavity, rising sun magnetron using the modulated current sources and benchmarked against a typical continuous current source. For the modulated, ten-sided faceted cathode case, the electrons are injected frommore » three emitter elements on each of the ten facets. Each emitter is turned ON and OFF in sequence at the oscillating frequency with five emitters ON at one time to drive the five electron spokes of the π-mode. The emitter duty cycle is then 1/6th the Radio-Frequency (RF) period. Simulations show a fast start-up time as low as 35 ns for the modulated case compared to 100 ns for the continuous current cases. Analysis of the RF phase using the electron spoke locations and the RF magnetic field components shows that the phase is controlled for the modulated case while it is random, as typical, for the continuous current case. Active phase control during oscillation was demonstrated by shifting the phase of the electron injection 180° after oscillations started. The 180° phase shift time was approximately 25 RF cycles.« less

Molecular Interaction Control in Diblock Copolymer Blends and Multiblock Copolymers with Opposite Phase Behaviors

NASA Astrophysics Data System (ADS)

Cho, Junhan

2014-03-01

Here we show how to control molecular interactions via mixing AB and AC diblock copolymers, where one copolymer exhibits upper order-disorder transition and the other does lower disorder-order transition. Linear ABC triblock copolymers possessing both barotropic and baroplastic pairs are also taken into account. A recently developed random-phase approximation (RPA) theory and the self-consistent field theory (SCFT) for general compressible mixtures are used to analyze stability criteria and morphologies for the given systems. It is demonstrated that the copolymer systems can yield a variety of phase behaviors in their temperature and pressure dependence upon proper mixing conditions and compositions, which is caused by the delicate force fields generated in the systems. We acknowledge the financial support from National Research Foundation of Korea and Center for Photofunctional Energy Materials.

Design of state-feedback controllers including sensitivity reduction, with applications to precision pointing

NASA Technical Reports Server (NTRS)

Hadass, Z.

1974-01-01

The design procedure of feedback controllers was described and the considerations for the selection of the design parameters were given. The frequency domain properties of single-input single-output systems using state feedback controllers are analyzed, and desirable phase and gain margin properties are demonstrated. Special consideration is given to the design of controllers for tracking systems, especially those designed to track polynomial commands. As an example, a controller was designed for a tracking telescope with a polynomial tracking requirement and some special features such as actuator saturation and multiple measurements, one of which is sampled. The resulting system has a tracking performance comparing favorably with a much more complicated digital aided tracker. The parameter sensitivity reduction was treated by considering the variable parameters as random variables. A performance index is defined as a weighted sum of the state and control convariances that sum from both the random system disturbances and the parameter uncertainties, and is minimized numerically by adjusting a set of free parameters.

Perception of Therapeutic Qi, a Nonmechanical, Nonpsychological Factor in Acupuncture That Originates from the Therapist.

PubMed

Hochstrasser, Raphael J; Endler, P Christian; Klein, Sabine D

2015-08-01

So far, most research attempts to explain the mechanism of the action of acupuncture have focused mostly on mechanically-triggered active factors and have produced inconclusive findings. In this study, we investigate whether acupuncture might also involve nonmechanical, nonpsychological active factors originating in the therapist. In 30 individuals, an acupuncture needle was inserted in the acupoint PC6 using a special device without touching the needle. A second device was used to fix the needle rigidly in place, excluding any mechanical transmission of movement from the handle to the needle's tip. Each participant was exposed in random order to a control and a stimulation phase. During the stimulation phase, the free needle's end was held by the therapist to allow the transmission of Qi; during the control phase, it was left untouched. Participants' subjective sensations during the stimulation phase and the control phase were recorded using a questionnaire. Twenty-two of 28 (79%; p = 0.003) test participants believed that they had received stimulation when it had actually been performed, and 26 (93%; p < 0.001) sensed differences between the two experimental phases. Thus, participants were able to sense the transmission of therapeutic Qi in the absence of mechanical or psychological factors. Copyright © 2015. Published by Elsevier B.V.

Yoga vs. physical therapy vs. education for chronic low back pain in predominantly minority populations: study protocol for a randomized controlled trial.

PubMed

Saper, Robert B; Sherman, Karen J; Delitto, Anthony; Herman, Patricia M; Stevans, Joel; Paris, Ruth; Keosaian, Julia E; Cerrada, Christian J; Lemaster, Chelsey M; Faulkner, Carol; Breuer, Maya; Weinberg, Janice

2014-02-26

Chronic low back pain causes substantial morbidity and cost to society while disproportionately impacting low-income and minority adults. Several randomized controlled trials show yoga is an effective treatment. However, the comparative effectiveness of yoga and physical therapy, a common mainstream treatment for chronic low back pain, is unknown. This is a randomized controlled trial for 320 predominantly low-income minority adults with chronic low back pain, comparing yoga, physical therapy, and education. Inclusion criteria are adults 18-64 years old with non-specific low back pain lasting ≥ 12 weeks and a self-reported average pain intensity of ≥ 4 on a 0-10 scale. Recruitment takes place at Boston Medical Center, an urban academic safety-net hospital and seven federally qualified community health centers located in diverse neighborhoods. The 52-week study has an initial 12-week Treatment Phase where participants are randomized in a 2:2:1 ratio into i) a standardized weekly hatha yoga class supplemented by home practice; ii) a standardized evidence-based exercise therapy protocol adapted from the Treatment Based Classification method, individually delivered by a physical therapist and supplemented by home practice; and iii) education delivered through a self-care book. Co-primary outcome measures are 12-week pain intensity measured on an 11-point numerical rating scale and back-specific function measured using the modified Roland Morris Disability Questionnaire. In the subsequent 40-week Maintenance Phase, yoga participants are re-randomized in a 1:1 ratio to either structured maintenance yoga classes or home practice only. Physical therapy participants are similarly re-randomized to either five booster sessions or home practice only. Education participants continue to follow recommendations of educational materials. We will also assess cost effectiveness from the perspectives of the individual, insurers, and society using claims databases, electronic medical records, self-report cost data, and study records. Qualitative data from interviews will add subjective detail to complement quantitative data. This trial is registered in ClinicalTrials.gov, with the ID number: NCT01343927.

Yoga vs. physical therapy vs. education for chronic low back pain in predominantly minority populations: study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Chronic low back pain causes substantial morbidity and cost to society while disproportionately impacting low-income and minority adults. Several randomized controlled trials show yoga is an effective treatment. However, the comparative effectiveness of yoga and physical therapy, a common mainstream treatment for chronic low back pain, is unknown. Methods/Design This is a randomized controlled trial for 320 predominantly low-income minority adults with chronic low back pain, comparing yoga, physical therapy, and education. Inclusion criteria are adults 18–64 years old with non-specific low back pain lasting ≥12 weeks and a self-reported average pain intensity of ≥4 on a 0–10 scale. Recruitment takes place at Boston Medical Center, an urban academic safety-net hospital and seven federally qualified community health centers located in diverse neighborhoods. The 52-week study has an initial 12-week Treatment Phase where participants are randomized in a 2:2:1 ratio into i) a standardized weekly hatha yoga class supplemented by home practice; ii) a standardized evidence-based exercise therapy protocol adapted from the Treatment Based Classification method, individually delivered by a physical therapist and supplemented by home practice; and iii) education delivered through a self-care book. Co-primary outcome measures are 12-week pain intensity measured on an 11-point numerical rating scale and back-specific function measured using the modified Roland Morris Disability Questionnaire. In the subsequent 40-week Maintenance Phase, yoga participants are re-randomized in a 1:1 ratio to either structured maintenance yoga classes or home practice only. Physical therapy participants are similarly re-randomized to either five booster sessions or home practice only. Education participants continue to follow recommendations of educational materials. We will also assess cost effectiveness from the perspectives of the individual, insurers, and society using claims databases, electronic medical records, self-report cost data, and study records. Qualitative data from interviews will add subjective detail to complement quantitative data. Trial registration This trial is registered in ClinicalTrials.gov, with the ID number: NCT01343927. PMID:24568299

Developmental contributions to macronutrient selection: a randomized controlled trial in adult survivors of malnutrition

PubMed Central

Campbell, Claudia P.; Raubenheimer, David; Badaloo, Asha V.; Gluckman, Peter D.; Martinez, Claudia; Gosby, Alison; Simpson, Stephen J.; Osmond, Clive; Boyne, Michael S.

2016-01-01

Abstract Background and objectives: Birthweight differences between kwashiorkor and marasmus suggest that intrauterine factors influence the development of these syndromes of malnutrition and may modulate risk of obesity through dietary intake. We tested the hypotheses that the target protein intake in adulthood is associated with birthweight, and that protein leveraging to maintain this target protein intake would influence energy intake (EI) and body weight in adult survivors of malnutrition. Methodology: Sixty-three adult survivors of marasmus and kwashiorkor could freely compose a diet from foods containing 10, 15 and 25 percentage energy from protein (percentage of energy derived from protein (PEP); Phase 1) for 3 days. Participants were then randomized in Phase 2 (5 days) to diets with PEP fixed at 10%, 15% or 25%. Results: Self-selected PEP was similar in both groups. In the groups combined, selected PEP was 14.7, which differed significantly (P < 0.0001) from the null expectation (16.7%) of no selection. Self-selected PEP was inversely related to birthweight, the effect disappearing after adjusting for sex and current body weight. In Phase 2, PEP correlated inversely with EI (P = 0.002) and weight change from Phase 1 to 2 (P = 0.002). Protein intake increased with increasing PEP, but to a lesser extent than energy increased with decreasing PEP. Conclusions and implications: Macronutrient intakes were not independently related to birthweight or diagnosis. In a free-choice situation (Phase 1), subjects selected a dietary PEP significantly lower than random. Lower PEP diets induce increased energy and decreased protein intake, and are associated with weight gain. PMID:26817484

HealtheSteps™ Study Protocol: a pragmatic randomized controlled trial promoting active living and healthy lifestyles in at-risk Canadian adults delivered in primary care and community-based clinics.

PubMed

Gill, Dawn P; Blunt, Wendy; Bartol, Cassandra; Pulford, Roseanne W; De Cruz, Ashleigh; Simmavong, P Karen; Gavarkovs, Adam; Newhouse, Ian; Pearson, Erin; Ostenfeldt, Bayley; Law, Barbi; Karvinen, Kristina; Moffit, Pertice; Jones, Gareth; Watson, Cori; Zou, Guangyong; Petrella, Robert J

2017-02-07

Physical inactivity is one of the leading causes of chronic disease in Canadian adults. With less than 50% of Canadian adults reaching the recommended amount of daily physical activity, there is an urgent need for effective programs targeting this risk factor. HealtheSteps™ is a healthy lifestyle prescription program, developed from an extensive research base to address risk factors for chronic disease such as physical inactivity, sedentary behaviour and poor eating habits. HealtheSteps™ participants are provided with in-person lifestyle coaching and access to eHealth technologies delivered in community-based primary care clinics and health care organizations. To determine the effectiveness of Healthesteps™, we will conduct a 6-month pragmatic randomized controlled trial with integrated process and economic evaluations of HealtheSteps™ in 5 clinic settings in Southwestern Ontario. 110 participants will be individually randomized (1:1; stratified by site) to either the intervention (HealtheSteps™ program) or comparator (Wait-list control). There are 3 phases of the HealtheSteps™ program, lasting 6 months each. The active phase consists of bi-monthly in-person coaching with access to a full suite of eHealth technology supports. During the maintenance phase I, the in-person coaching will be removed, but participants will still have access to the full suite of eHealth technology supports. In the final stage, maintenance phase II, access to the full suite of eHealth technology supports is removed and participants only have access to publicly available resources and tools. This trial aims to determine the effectiveness of the program in increasing physical activity levels and improving other health behaviours and indicators, the acceptability of the HealtheSteps™ program, and the direct cost for each person participating in the program as well as the costs associated with delivering the program at the different community sites. These results will inform future optimization and scaling up of the program into additional community-based primary care sites. NCT02413385 (Clinicaltrials.gov). Date Registered: April 6, 2015.

Ultra-fast quantum randomness generation by accelerated phase diffusion in a pulsed laser diode.

PubMed

Abellán, C; Amaya, W; Jofre, M; Curty, M; Acín, A; Capmany, J; Pruneri, V; Mitchell, M W

2014-01-27

We demonstrate a high bit-rate quantum random number generator by interferometric detection of phase diffusion in a gain-switched DFB laser diode. Gain switching at few-GHz frequencies produces a train of bright pulses with nearly equal amplitudes and random phases. An unbalanced Mach-Zehnder interferometer is used to interfere subsequent pulses and thereby generate strong random-amplitude pulses, which are detected and digitized to produce a high-rate random bit string. Using established models of semiconductor laser field dynamics, we predict a regime of high visibility interference and nearly complete vacuum-fluctuation-induced phase diffusion between pulses. These are confirmed by measurement of pulse power statistics at the output of the interferometer. Using a 5.825 GHz excitation rate and 14-bit digitization, we observe 43 Gbps quantum randomness generation.

The effects of physical therapy with neuromuscular electrical stimulation in patients with septic shock

PubMed Central

Lago, Alessandra Fabiane; de Oliveira, Anamaria Siriani; de Souza, Hugo Celso Dutra; da Silva, João Santana; Basile-Filho, Anibal; Gastaldi, Ada Clarice

2018-01-01

Abstract Introduction: Septic shock is a potentially fatal organ dysfunction caused by an imbalance of the host response to infection. The changes in microcirculation during sepsis can be explained by the alterations in the endothelial barrier function. Endothelial progenitor cells (EPCs) are a potential recovery index of endothelial function and it an increase in response to neuromuscular electrical stimulation (NMES) was demonstrated. Therefore, the objective of this study is to investigate the effects of NMES in patients with septic shock. Methods and analysis: It is a study protocol for a randomized cross-over design in an intensive care unit of a tertiary University hospital. Thirty-one patients aged 18 to 65 years. The study will be divided in 2 phases: the phase one will be held in the first 72 hours of septic shock and the phase two after 3 days of first assessment. Patients will be randomly selected to the intervention protocol (decubitus position with the limbs raised and NMES) and control protocol (decubitus position with the limbs raised without NMES). After this procedure, the patients will be allocated in group 1 (intervention and control protocol) or group 2 (control and intervention protocol) with a wash-out period of 4 to 6 hours between them. The main outcome is mobilization of EPCs. The secondary outcome is metabolic and hemodynamic data. A linear mixed model will be used for analysis of dependent variables and estimated values of the mean of the differences of each effect. PMID:29419665

High Dose Atorvastatin Decreases Cellular Markers of Immune Activation Without Affecting HIV-1 RNA Levels: Results of a Double-Blind Randomized Placebo Controlled Clinical Trial

DTIC Science & Technology

2011-02-15

M A J O R A R T I C L E High Dose Atorvastatin Decreases Cellular Markers of Immune Activation without Affecting HIV-1 RNA Levels: Results of a... atorvastatin on HIV-1 RNA (primary objective) and cellular markers of immune activation (secondary objective). HIV-infected individuals not receiving...antiretroviral therapy were randomized to receive either 8 weeks of atorvastatin (80 mg) or placebo daily. After a 4–6 week washout phase, participants

Effect of Phase-Breaking Events on Electron Transport in Mesoscopic and Nanodevices

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

Meunier, Vincent; Mintmire, John W; Thushari, Jayasekera

2008-01-01

Existing ballistic models for electron transport in mesoscopic and nanoscale systems break down as the size of the device becomes longer than the phase coherence length of electrons in the system. Krstic et al. experimentally observed that the current in single-wall carbon nanotube systems can be regarded as a combination of a coherent part and a noncoherent part. In this article, we discuss the use of Buettiker phase-breaking technique to address partially coherent electron transport, generalize that to a multichannel problem, and then study the effect of phase-breaking events on the electron transport in two-terminal graphene nanoribbon devices. We alsomore » investigate the difference between the pure-phase randomization and phase/momentum randomization boundary conditions. While momentum randomization adds an extra resistance caused by backward scattering, pure-phase randomization smooths the conductance oscillations because of interference.« less

Clinical studies of the effectiveness and safety of antivenoms.

PubMed

Williams, David J; Habib, Abdulrazaq G; Warrell, David A

2018-05-07

In the 1890s, hyperimmune sera proved effective in animals against challenge by the snake venom against which they had been raised. They were first used, apparently successfully, in a human patient in about 1895. Since then, antivenoms have become accepted as the only reliable specific treatment for snake-bite envenoming. Despite decades of accumulated clinical experience and a number of published randomized comparative and observational studies, the clinical effectiveness and safety of some antivenoms remain open to question, due to a lack of robust randomized controlled trial data. Antivenoms in some poorly regulated markets may have high rates of potentially fatal adverse effects and their use must be balanced by demonstrable effectiveness. Even those manufactured to strict regulatory requirements may pose a rare risk of severe adverse reactions. Most antivenoms currently marketed around the world were registered without first being studied clinically. There is increasing pressure to subject antivenoms, even those that are long-established, to the same protocols of rigorous pre-clinical and clinical assessment that are standard regulatory requirements for other drugs. Conventional clinical testing progresses through Phases I, II, III to IV. Most authorities consider antivenoms too dangerous to be used in Phase I studies in healthy volunteers. An alternative method for preliminary estimation of safety, dose-finding and effectiveness, is proposed - the "3 + 3" dose escalation or de-escalation design, in volunteer patients, as used in oncology to test cytotoxic drugs. Antivenoms are so widely used and well trusted, that there are few ethical justifications for placebo controls. However, placebo might be ethically justified if there were no proven effective treatment and or if withholding or delaying treatment posed acceptably negligible risks to the participants. Antivenom trials are most urgently needed in low-to middle-income countries where there are many practical, logistical and funding challenges. Basic requirements for clinical trials include identification of the biting species of snake in every case; the use of objective, clinically-relevant endpoints, such as restoration of blood coagulability; definition of inclusion, exclusion and withdrawal criteria; assurance of antivenom safety; ethical considerations; inclusion of one or more control (comparator) groups; and analysis based on intention to treat. The highest quality evidence comes from Phase II and larger Phase III studies that have been designed as statistically powerful, randomized, controlled trials (RCTs), ideally with blinding of patients and investigators to avoid bias. Because of the challenges to carrying out clinical trials of antivenoms, Phase IV trials (post-marketing surveillance) are potentially more important and useful than for most other drugs. Copyright © 2018 Elsevier Ltd. All rights reserved.

Quenched bond randomness: Superfluidity in porous media and the strong violation of universality

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

Falicov, A.; Berker, A.N.

1997-04-01

The effects of quenched bond randomness are most readily studied with superfluidity immersed in a porous medium. A lattice model for {sup 3}He-{sup 4}He mixtures and incomplete {sup 4}He fillings in aerogel yields the signature effect of bond randomness, namely the conversion of symmetry-breaking first-order phase transitions into second-order phase transitions, the A-line reaching zero temperature, and the elimination of non-symmetry-breaking first-order phase transitions. The model recognizes the importance of the connected nature of aerogel randomness and thereby yields superfluidity at very low {sup 4}He concentrations, a phase separation entirely within the superfluid phase, and the order-parameter contrast between mixturesmore » and incomplete fillings, all in agreement with experiments. The special properties of the helium mixture/aerogel system are distinctly linked to the aerogel properties of connectivity, randomness, and tenuousness, via the additional study of a regularized {open_quote}jungle-gym{close_quotes} aerogel. Renormalization-group calculations indicate that a strong violation of the empirical universality principle of critical phenomena occurs under quenched bond randomness. It is argued that helium/aerogel critical properties reflect this violation and further experiments are suggested. Renormalization-group analysis also shows that, adjoiningly to the strong universality violation (which hinges on the occurrence or non-occurrence of asymptotic strong coupling-strong randomness under resealing), there is a new {open_quotes}hyperuniversality{close_quotes} at phase transitions with asymptotic strong coupling-strong randomness behavior, for example assigning the same critical exponents to random-bond tricriticality and random-field criticality.« less

Transdermal granisetron versus palonosetron for prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: a multicenter, randomized, open-label, cross-over, active-controlled, and phase IV study.

PubMed

Seol, Young Mi; Kim, Hyo Jeong; Choi, Young Jin; Lee, Eun Mi; Kim, Yang Soo; Oh, Sung Yong; Koh, Su Jin; Baek, Jin Ho; Lee, Won Sik; Joo, Young Don; Lee, Hyun Gi; Yun, Eun Young; Chung, Joo Seop

2016-02-01

Palonosetron is the second-generation 5-hydroxytryptamine 3 receptor antagonist (5-HT3RA) that has shown better efficacy than the first-generation 5-HT3RA for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy (MEC). Granisetron transdermal delivery system (GTDS), a novel transdermal formulation, was developed to deliver granisetron continuously over 7 days. This study compared the efficacy and tolerability of the GTDS to palonosetron for the control of CINV following MEC. A total of 196 patients were randomized to GP or PG group. In this multicenter, randomized, open-label, cross-over, active-controlled, Phase IV study, GP group was assigned to receive transdermal granisetron (one GTDS patch, 7 days) in the first chemotherapy cycle, palonosetron (iv 0.25 mg/day, 1 days) in the second chemotherapy cycle before receiving MEC, and PG group was assigned to receive palonosetron in the first cycle and GTDS in the second cycle. Primary endpoint was the percentage of chemotherapy cycles achieving complete response (CR; defined as no emetic episodes and no rescue medication use) during the acute phase (0-24 h in post-chemotherapy; non-inferiority comparison with palonosetron). Total 333 cycles (165 in GTDS and 168 in palonosetron) were included in the per protocol analysis. The GTDS cycles showed non-inferiority to palonosetron cycles during the acute phase: CR was achieved by 124 (75.2 %) patients in the GTDS cycles and 134 (79.8 %) patients in the palonosetron cycles (treatment difference, -4.6 %; 95 % confidence interval, -13.6-4.4). There was no significant difference in CR rate during acute phase after the end of the first and second chemotherapy cycle between GP and PG group (p = 0.405, p = 0.074). Patients' satisfaction, assessed using Functional Living Index-Emesis (FLI-E), GTDS cycle were higher than those of palonosetron cycle in GP group (FLI-E score; median 1549.5 in GTDS cycle, median 1670.0 in palonosetron cycle). Both treatments were well tolerated and safe. Transdermal granisetron is a good alternative therapeutic option to palonosetron for preventing CINV after MEC.

Prevention of Chronic Kidney Disease and Subsequent Effect on Mortality: A Systematic Review and Meta-Analysis

PubMed Central

Khan, Usman A.; Garg, Amit X.; Parikh, Chirag R.; Coca, Steven G.

2013-01-01

Objectives To perform a systematic review of randomized controlled trials to determine whether prevention or slowing of progression of chronic kidney disease would translate into improved mortality, and if so, the attributable risk due to CKD itself on mortality. Background CKD is associated with increased mortality. This association is largely based on evidence from the observational studies and evidence from randomized controlled trials is lacking. Methods We searched Ovid, Medline and Embase for RCTs in which an intervention was given to prevent or slow the progression of CKD and mortality was reported as primary, secondary or adverse outcomes were eligible and selected. For the first phase, pooled relative risks for renal endpoints were assessed. For the second phase, we assessed the effect on mortality in trials of interventions that definitively reduced CKD endpoints. Results Among 52 studies selected in first phase, only renin-angiotensin-aldosterone-system blockade vs. placebo (n = 18 trials, 32,557 participants) met the efficacy criteria for further analysis in the second phase by reducing renal endpoints 15 to 27% compared to placebo. There was no difference in all-cause mortality (RR 0.99, 95% CI 0.92 to 1.08) or CV death (RR 0.97, 95% CI 0.78 to 1.21) between the treatment and control groups in these trials. There was sufficient statistical power to detect a 9% relative risk reduction in all-cause mortality and a 14% relative risk reduction in cardiovascular mortality. Conclusions Firm evidence is lacking that prevention of CKD translates into reductions in mortality. Larger trials with longer follow-up time are needed to determine the benefit of CKD prevention on survival. PMID:24009665

The effect of tooth brushing and flossing sequence on interdental plaque reduction and fluoride retention: A randomized controlled clinical trial.

PubMed

Mazhari, Fatemeh; Boskabady, Marzie; Moeintaghavi, Amir; Habibi, Atieh

2018-05-09

Mechanical plaque control methods such as brushing and flossing are highly recommended to remove dental plaque. The aim of this study is to evaluate the efficacy of the sequence of brushing and flossing on reducing interdental plaque and increasing fluoride retention in that area. This randomized controlled crossover trial was conducted on 25 dental students. After prophylaxis, they were asked to discontinue all forms of oral hygiene for 48 hours. The study was performed in two phases with two-week washout intervals. In one phase, they first brushed, then flossed (sequence 1: brush-floss group). In the other phase they initially used dental floss then brushed (sequence 2: floss-brush group). At each phase, dental plaque (using the Rustogi Modified Navy Plaque Index) and fluoride concentrations (using a fluoride ion specific electrode) were measured before and after flossing and brushing, and the dental plaque reduction and fluoride increase were compared between the two groups using the mixed model test. A significance level of 5% was selected. In the floss-brush group interdental and whole plaque was reduced significantly more than the brush-floss group (p = 0.001, p = 0.009 respectively). However, marginal plaque did not show any statistically significant difference between the two groups (p = 0.2). Fluoride concentrations in interdental plaque were significantly higher in the floss-brush group than the other group (p = 0.027). The results showed that flossing followed by brushing is preferred to brushing then flossing in order to reduce interdental plaque and increase fluoride concentration in interdental plaque. This article is protected by copyright. All rights reserved. © 2018 American Academy of Periodontology.

Laser-phased-array beam steering based on crystal fiber

NASA Astrophysics Data System (ADS)

Yang, Deng-cai; Zhao, Si-si; Wang, Da-yong; Wang, Zhi-yong; Zhang, Xiao-fei

2011-06-01

Laser-phased-array system provides an elegant means for achieving the inertial-free, high-resolution, rapid and random beam steering. In laser-phased-array system, phase controlling is the most important factor that impacts the system performance. A novel scheme is provided in this paper, the beam steering is accomplished by using crystal fiber array, the difference length between adjacent fiber is fixed. The phase difference between adjacent fiber decides the direction of the output beam. When the wavelength of the input fiber laser is tuned, the phase difference between the adjacent elements has changed. Therefore, the laser beam direction has changed and the beam steering has been accomplished. In this article, based on the proposed scheme, the steering angle of the laser beam is calculated and analyzed theoretically. Moreover, the far-field steering beam quality is discussed.

Validation of the phase II feasibility study in a palliative care setting: gastrografin in malignant bowel obstruction.

PubMed

Lee, Cindy; Vather, Ryash; O'Callaghan, Anne; Robinson, Jackie; McLeod, Briar; Findlay, Michael; Bissett, Ian

2013-12-01

Malignant bowel obstruction (MBO) is common in patients with advanced cancer. To perform a phase II study to assess the feasibility of conducting a phase III trial investigating the therapeutic value of gastrografin in MBO. Randomized double-blinded placebo-controlled feasibility study. Participants received 100 mL of either gastrografin or placebo. Over 8 months, 57 patients were screened and 9 enrolled (15.8% recruitment rate). Of the 9 enrolled, 4 received gastrografin (with 2 completing assessment) and 5 received placebo (with 4 completing assessment). It is not feasible to conduct a phase III trial using the same study protocol. This study validates the use of the phase II feasibility study to assess protocol viability in a palliative population prior to embarking on a larger trial.

Encrypted holographic data storage based on orthogonal-phase-code multiplexing.

PubMed

Heanue, J F; Bashaw, M C; Hesselink, L

1995-09-10

We describe an encrypted holographic data-storage system that combines orthogonal-phase-code multiplexing with a random-phase key. The system offers the security advantages of random-phase coding but retains the low cross-talk performance and the minimum code storage requirements typical in an orthogonal-phase-code-multiplexing system.

A short course of cardiac rehabilitation program is highly cost effective in improving long-term quality of life in patients with recent myocardial infarction or percutaneous coronary intervention.

PubMed

Yu, Cheuk-Man; Lau, Chu-Pak; Chau, June; McGhee, Sarah; Kong, Shun-Ling; Cheung, Bernard Man-Yung; Li, Leonard Sheung-Wai

2004-12-01

To evaluate the long-term effect of a cardiac rehabilitation and prevention program (CRPP) on quality of life (QOL) and its cost effectiveness. Prospective, randomized controlled trial. University-affiliated outpatient cardiac rehabilitation and prevention center. A total of 269 patients (76% men; mean age, 64+/-11 y) with recent acute myocardial infarction (AMI; n=193) or after elective percutaneous coronary intervention (PCI; n=76) were randomized in a ratio of 2 to 1. Patients received either CRPP (an 8-wk exercise and education class in phase 2) or conventional therapy without exercise program (control group). They were followed until they had completed all 4 phases of the program (ie, 2 y). QOL assessments, by using the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and Symptoms Questionnaire, were performed at the end of each phase. Direct health care cost was calculated, whereas cost utility was estimated as money spent (in US dollars) per quality-adjusted life-year (QALY) gained. In the CRPP group, 6 of the 8 SF-36 dimensions improved significantly by phase 2 and were maintained throughout the study period. Patients were less anxious and depressed, and felt more relaxed and contented. In the control group, none of the SF-36 dimensions were improved by phase 2, and bodily pain was increased. In phase 4, only 4 dimensions were improved. Symptoms were unchanged except for increased hostility score. There was a significant gain in net time trade-off in the CRPP group after phase 2. The direct health care expenses in the CRPP and control groups were 15,292 dollars and 15,707 dollars per patient, respectively. Therefore, the cost utility calculated was 640 dollars saved per QALY gained. Savings attributable to CRPP were primarily explained by the lower rate (13% vs 26% of patients, chi2 test=3.9, P <.05) and cost of subsequent PCI (P =.01). In an era of managing patients with coronary heart disease, a short-course CRPP was highly cost effective in providing better QOL to patients with recent AMI or after elective PCI. In addition, the improvement of QOL was quick and sustained for at least 2 years after CRPP.

Effect of lullaby and classical music on physiologic stability of hospitalized preterm infants: a randomized trial.

PubMed

Amini, E; Rafiei, P; Zarei, K; Gohari, M; Hamidi, M

2013-01-01

Music is considered a subset of developmental supportive care. It may act as a suitable auditory stimulant in preterm infants. Also, it may reduce stress responses in autonomic, motor and state systems. To assess and compare the influence of lullaby and classical music on physiologic parameters. This is a randomized clinical trial with cross-over design. A total of 25 stable preterm infants with birth weight of 1000-2500 grams were studied for six consecutive days. Each infant was exposed to three phases: lullaby music, classical music, and no music (control) for two days each. The sequence of these phases was assigned randomly to each subject. Babies were continuously monitored for heart rate, respiratory rate, and oxygen saturation and changes between phases were analyzed. Lullaby reduced heart rate (p < 0.001) and respiratory rate (p = 0.004). These effects extended in the period after the exposure (p < .001 and p = 0.001, respectively). Classical music reduced heart rate (p = 0.018). The effects of classical music disappeared once the music stopped. Oxygen saturation did not change during intervention. Music can affect vital signs of preterm infants; this effect can possibly be related to the reduction of stress during hospitalization. The implications of these findings on clinical and developmental outcomes need further study.

Rate of Imagery in Mental Practice: An Experimental Investigation.

ERIC Educational Resources Information Center

Andre, John C.; Means, John R.

This study examined the effects of mental practice (MP), slow motion mental practice (SMMP), and attention placebo control (APC) on the performance of the putting throw in Frisbee disc golf. Subjects were randomly assigned to the three groups and participated in a pre-treatment performance session, a five session treatment phase, and a…

Efficacy and Safety of Dexmethylphenidate Extended-Release Capsules in Children with Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Greenhill, Laurence L.; Muniz, Rafael; Ball, Roberta R.; Levine, Alan; Pestreich, Linda; Jiang, Hai

2006-01-01

Objective: The efficacy and safety of dexmethylphenidate extended release (d-MPH-ER) was compared to placebo in pediatric patients with attention-deficit/hyperactivity disorder (ADHD). Method: This multicenter, randomized, double-blind, placebo-controlled, parallel-group, two-phase study included 97 patients (ages 6-17 years) with…

A randomized clinical trial in preterm infants on the effects of a home-based early intervention with the 'CareToy System'

PubMed Central

Sgandurra, Giuseppina; Lorentzen, Jakob; Inguaggiato, Emanuela; Bartalena, Laura; Beani, Elena; Cecchi, Francesca; Dario, Paolo; Giampietri, Matteo; Greisen, Gorm; Herskind, Anna; Nielsen, Jens Bo; Rossi, Giuseppe; Cioni, Giovanni

2017-01-01

CareToy system is an innovative tele-rehabilitative tool, useful in providing intensive, individualized, home-based, family-centred Early Intervention (EI) in infants. Our aim was to evaluate, through a Randomized Clinical Trial (RCT) study, the effects of CareToy intervention on early motor and visual development in preterm infants. 41 preterm infants (range age: 3.0–5.9 months of corrected age) were enrolled and randomized into two groups, CareToy and Standard Care. 19 infants randomized in CareToy group performed a 4-week CareToy program, while 22 allocated to control group completed 4 weeks of Standard Care. Infant Motor Profile (IMP) was primary outcome measure, Alberta Infant Motor Scale (AIMS) and Teller Acuity Cards were secondary ones. Assessments were carried out at baseline (T0) and at the end of CareToy training or Standard Care period (T1). T1 was the primary endpoint. After RCT phase, 17 infants from control group carried out a 4-week CareToy program, while 18 infants from the CareToy group continued with Standard Care. At the end of this phase, infants were re-assessed at T2. In RCT phase, delta IMP total score and variation and performance sub-domains were significantly higher (P<0.050) in CareToy group if compared to Standard Care group. Similar results were found for Teller Acuity Cards, while no differences between groups were found for AIMS. No differences were found in any outcome measure results (T2-T0), between infants who started CareToy training before or after one month of standard care. This RCT study confirms the results of a previous pilot study, indicating that CareToy system can provide effective home-based EI. Trial Registration: This trial has been registered at www.clinicaltrials.gov (Identifier NCT01990183). PMID:28328946

A Randomized, Placebo Controlled, Double Masked Phase IB Study Evaluating the Safety and Antiviral Activity of Aprepitant, a Neurokinin-1 Receptor Antagonist in HIV-1 Infected Adults

PubMed Central

Tebas, Pablo; Tuluc, Florin; Barrett, Jeffrey S.; Wagner, Wayne; Kim, Deborah; Zhao, Huaquing; Gonin, René; Korelitz, James; Douglas, Steven D.

2011-01-01

Background Neurokinin-1 receptor (NK1R) antagonists have anti-HIV activity in monocyte-derived macrophages, decrease CCR5 expression and improve natural killer cell function ex vivo. Aprepitant is a NK1R antagonist approved by FDA as an antiemetic. Methods We conducted a phase IB randomized, placebo controlled, double masked study to evaluate the safety, antiviral activity, pharmacokinetics and immune-modulatory effects of aprepitant in HIV-infected adults not receiving antiretroviral therapy, with CD4+ cell count ≥350 cells/mm3 and plasma viral load ≥2,000 copies/ml. Subjects were stratified by viral load (< vs. ≥20,000 copies/ml) and randomized within each stratum to receive aprepitant at 125 mg QD(Low), or 250 mg QD(High), or placebo(PL) for 14 days, and followed for 42 days. Results Thirty subjects were randomized and 27 completed treatment (9, 8, 10 subjects in 125 (Low), 250 (High), and PL groups). 63% were male; 37% white; mean (SD) age 43 (9.3) years. Geometric mean baseline viral load (copies/ml) for Low, High, and PL was 15,709, 33,013, and 19,450, respectively. Mean (95%CI) change in log10 viral load at day 14 for Low, High, and PL was −0.02(−0.24,+0.20), −0.05(−0.21,+0.10), and +0.04(−0.08,+0.16), respectively. The number of subjects with AEs was 4(44.4%), 5(62.5%), and 1(10%) for Low, High, and PL. No Grade 4 AEs occurred. Conclusions Adverse events of aprepitant were more common in the treated groups. At the dose used in this two-week phase IB study, aprepitant showed biological activity, but no significant antiviral activity. Trial Registration ClinicalTrials.gov NCT00428519 PMID:21931661

Randomized Phase II, Double-Blind, Placebo-Controlled Study of Exemestane With or Without Entinostat in Postmenopausal Women With Locally Recurrent or Metastatic Estrogen Receptor-Positive Breast Cancer Progressing on Treatment With a Nonsteroidal Aromatase Inhibitor

PubMed Central

Yardley, Denise A.; Ismail-Khan, Roohi R.; Melichar, Bohuslav; Lichinitser, Mikhail; Munster, Pamela N.; Klein, Pamela M.; Cruickshank, Scott; Miller, Kathy D.; Lee, Min J.; Trepel, Jane B

2013-01-01

Purpose Entinostat is an oral isoform selective histone deacetylase inhibitor that targets resistance to hormonal therapies in estrogen receptor–positive (ER+) breast cancer. This randomized, placebo-controlled, phase II study evaluated entinostat combined with the aromatase inhibitor exemestane versus exemestane alone. Patients and Methods Postmenopausal women with ER+ advanced breast cancer progressing on a nonsteroidal aromatase inhibitor were randomly assigned to exemestane 25 mg daily plus entinostat 5 mg once per week (EE) or exemestane plus placebo (EP). The primary end point was progression-free survival (PFS). Blood was collected in a subset of patients for evaluation of protein lysine acetylation as a biomarker of entinostat activity. Results One hundred thirty patients were randomly assigned (EE group, n = 64; EP group, n = 66). Based on intent-to-treat analysis, treatment with EE improved median PFS to 4.3 months versus 2.3 months with EP (hazard ratio [HR], 0.73; 95% CI, 0.50 to 1.07; one-sided P = .055; two-sided P = .11 [predefined significance level of .10, one-sided]). Median overall survival was an exploratory end point and improved to 28.1 months with EE versus 19.8 months with EP (HR, 0.59; 95% CI, 0.36 to 0.97; P = .036). Fatigue and neutropenia were the most frequent grade 3/4 toxicities. Treatment discontinuation because of adverse events was higher in the EE group versus the EP group (11% v 2%). Protein lysine hyperacetylation in the EE biomarker subset was associated with prolonged PFS. Conclusion Entinostat added to exemestane is generally well tolerated and demonstrated activity in patients with ER+ advanced breast cancer in this signal-finding phase II study. Acetylation changes may provide an opportunity to maximize clinical benefit with entinostat. Plans for a confirmatory study are underway. PMID:23650416

Optical encrypted holographic memory using triple random phase-encoded multiplexing in photorefractive LiNbO3:Fe crystal

NASA Astrophysics Data System (ADS)

Tang, Li-Chuan; Hu, Guang W.; Russell, Kendra L.; Chang, Chen S.; Chang, Chi Ching

2000-10-01

We propose a new holographic memory scheme based on random phase-encoded multiplexing in a photorefractive LiNbO3:Fe crystal. Experimental results show that rotating a diffuser placed as a random phase modulator in the path of the reference beam provides a simple yet effective method of increasing the holographic storage capabilities of the crystal. Combining this rotational multiplexing with angular multiplexing offers further advantages. Storage capabilities can be optimized by using a post-image random phase plate in the path of the object beam. The technique is applied to a triple phase-encoded optical security system that takes advantage of the high angular selectivity of the angular-rotational multiplexing components.

Effects of massage therapy and presence of attendant on pain, anxiety and satisfaction during labor.

PubMed

Mortazavi, Seyedeh Hamideh; Khaki, Siavash; Moradi, Rayhaneh; Heidari, Kazem; Vasegh Rahimparvar, Seyedeh Fatemeh

2012-07-01

To investigate the effects of massage and presenting an attendant on pain, anxiety and satisfaction during labor to clarify some aspects of using an alternative complementary strategy. 120 primiparous women with term pregnancy were divided into massage, attendant and control groups randomly. Massage group received firm and rhythmic massage during labor in three phases. After 30 min massage at each stage, pain, anxiety and satisfaction levels were evaluated. Self-reported present pain intensity scale was used to measure the labor pain. Anxiety and satisfaction were measured with the standard visual analog scale. Massage group had lower pain state in second and third phases (p < 0.05) in comparison with attendant group but reversely, the level of anxiety was lower in attendant group in second and third phases (p < 0.05) and satisfaction was higher in massage group in all four phases (p < 0.001). The massage group had lower pain and anxiety state in three phases in comparison with control group (p < 0.05). Data analysis of satisfaction level showed higher values in four phases in massage group compared with control (p < 0.001) and comparison of attendant and control groups showed higher satisfaction in attendant group in phases 2, 3 and 4 as well (p < 0.001). Duration of active phase was lower in massage group (p < 0.001). Findings suggest that massage is an effective alternative intervention, decreasing pain and anxiety during labor and increasing the level of satisfaction. Also, the supportive role of presenting an attendant can positively influence the level of anxiety and satisfaction.

Dietary intakes associated with successful weight loss and maintenance during the Weight Loss Maintenance Trial

PubMed Central

Champagne, Catherine M.; Broyles, Stephanie T; Moran, Laura D.; Cash, Katherine C.; Levy, Erma J.; Lin, Pao-Hwa; Batch, Bryan C.; Lien, Lillian F.; Funk, Kristine L.; Dalcin, Arlene; Loria, Catherine; Myers, Valerie H.

2011-01-01

Background Dietary components effective in weight maintenance efforts have not been adequately identified. Objective To determine impact of changes in dietary consumption on weight loss and maintenance during the Weight Loss Maintenance (WLM) clinical trial. Design WLM was a randomized controlled trial. Successful weight loss participants who completed Phase I of the trial and lost 4kg were randomized to one of three maintenance intervention arms in Phase II and followed for an additional 30 months. Participants/setting The multicenter trial was conducted from 2003–2007. This substudy included 828 successful weight loss participants. Methods Dietary Measures The Block Food Frequency Questionnaire (FFQ) was used to assess nutrient intake levels and food group servings. Carbohydrates, proteins, fats, dietary fiber and fruit/vegetable and dairy servings were utilized as predictor variables. Data collection The FFQ was collected on all participants at study entry (beginning of Phase I). Those randomized to Phase II completed the FFQ at three additional time points; randomization (beginning of Phase II), 12 and 30 months. Intervention The main intervention focused on long term maintenance of weight loss using the Dietary Approaches to Hypertension (DASH) diet. This substudy examined whether changes to specific dietary variables were associated with weight loss and maintenance. Statistical analyses performed Linear regression models that adjusted for change in total energy examined the relationship between changes in dietary intake and weight for each time period. Site, age, race, sex, and a race-sex interaction were included as covariates. Results Participants who substituted protein for fat lost, on average, 0.33 kg per 6-months during Phase I (p<0.0001) and 0.07 kg per 6-months during Phase II (p<0.0001) per 1% increase in protein. Increased intake of fruits and vegetables was associated with weight loss in Phases I and II: 0.29 kg per 6-months (p<0.0001) and 0.04 kg per 6-months (p=0.0062), respectively, per 1-serving increase. Substitution of carbohydrates for fat and protein for carbohydrates were associated with weight loss during both phases. Increasing dairy intake was associated with significant weight loss during Phase II (−0.17 kg per 6-months per 1-serving increase, p=0.0002), but not in Phase I. Dietary fiber revealed no significant findings. Conclusion Increasing fruits, vegetables, and low-fat dairy may help achieve weight loss and maintenance. PMID:22117658

Random phase detection in multidimensional NMR.

PubMed

Maciejewski, Mark W; Fenwick, Matthew; Schuyler, Adam D; Stern, Alan S; Gorbatyuk, Vitaliy; Hoch, Jeffrey C

2011-10-04

Despite advances in resolution accompanying the development of high-field superconducting magnets, biomolecular applications of NMR require multiple dimensions in order to resolve individual resonances, and the achievable resolution is typically limited by practical constraints on measuring time. In addition to the need for measuring long evolution times to obtain high resolution, the need to distinguish the sign of the frequency constrains the ability to shorten measuring times. Sign discrimination is typically accomplished by sampling the signal with two different receiver phases or by selecting a reference frequency outside the range of frequencies spanned by the signal and then sampling at a higher rate. In the parametrically sampled (indirect) time dimensions of multidimensional NMR experiments, either method imposes an additional factor of 2 sampling burden for each dimension. We demonstrate that by using a single detector phase at each time sample point, but randomly altering the phase for different points, the sign ambiguity that attends fixed single-phase detection is resolved. Random phase detection enables a reduction in experiment time by a factor of 2 for each indirect dimension, amounting to a factor of 8 for a four-dimensional experiment, albeit at the cost of introducing sampling artifacts. Alternatively, for fixed measuring time, random phase detection can be used to double resolution in each indirect dimension. Random phase detection is complementary to nonuniform sampling methods, and their combination offers the potential for additional benefits. In addition to applications in biomolecular NMR, random phase detection could be useful in magnetic resonance imaging and other signal processing contexts.

Stability and dynamical properties of material flow systems on random networks

NASA Astrophysics Data System (ADS)

Anand, K.; Galla, T.

2009-04-01

The theory of complex networks and of disordered systems is used to study the stability and dynamical properties of a simple model of material flow networks defined on random graphs. In particular we address instabilities that are characteristic of flow networks in economic, ecological and biological systems. Based on results from random matrix theory, we work out the phase diagram of such systems defined on extensively connected random graphs, and study in detail how the choice of control policies and the network structure affects stability. We also present results for more complex topologies of the underlying graph, focussing on finitely connected Erdös-Réyni graphs, Small-World Networks and Barabási-Albert scale-free networks. Results indicate that variability of input-output matrix elements, and random structures of the underlying graph tend to make the system less stable, while fast price dynamics or strong responsiveness to stock accumulation promote stability.

Controlling Light Transmission Through Highly Scattering Media Using Semi-Definite Programming as a Phase Retrieval Computation Method.

PubMed

N'Gom, Moussa; Lien, Miao-Bin; Estakhri, Nooshin M; Norris, Theodore B; Michielssen, Eric; Nadakuditi, Raj Rao

2017-05-31

Complex Semi-Definite Programming (SDP) is introduced as a novel approach to phase retrieval enabled control of monochromatic light transmission through highly scattering media. In a simple optical setup, a spatial light modulator is used to generate a random sequence of phase-modulated wavefronts, and the resulting intensity speckle patterns in the transmitted light are acquired on a camera. The SDP algorithm allows computation of the complex transmission matrix of the system from this sequence of intensity-only measurements, without need for a reference beam. Once the transmission matrix is determined, optimal wavefronts are computed that focus the incident beam to any position or sequence of positions on the far side of the scattering medium, without the need for any subsequent measurements or wavefront shaping iterations. The number of measurements required and the degree of enhancement of the intensity at focus is determined by the number of pixels controlled by the spatial light modulator.

Polynomial Method for PLL Controller Optimization†

PubMed Central

Wang, Ta-Chung; Lall, Sanjay; Chiou, Tsung-Yu

2011-01-01

The Phase-Locked Loop (PLL) is a key component of modern electronic communication and control systems. PLL is designed to extract signals from transmission channels. It plays an important role in systems where it is required to estimate the phase of a received signal, such as carrier tracking from global positioning system satellites. In order to robustly provide centimeter-level accuracy, it is crucial for the PLL to estimate the instantaneous phase of an incoming signal which is usually buried in random noise or some type of interference. This paper presents an approach that utilizes the recent development in the semi-definite programming and sum-of-squares field. A Lyapunov function will be searched as the certificate of the pull-in range of the PLL system. Moreover, a polynomial design procedure is proposed to further refine the controller parameters for system response away from the equilibrium point. Several simulation results as well as an experiment result are provided to show the effectiveness of this approach. PMID:22163973

Phase Transition Control for High Performance Ruddlesden-Popper Perovskite Solar Cells.

PubMed

Zhang, Xu; Munir, Rahim; Xu, Zhuo; Liu, Yucheng; Tsai, Hsinhan; Nie, Wanyi; Li, Jianbo; Niu, Tianqi; Smilgies, Detlef-M; Kanatzidis, Mercouri G; Mohite, Aditya D; Zhao, Kui; Amassian, Aram; Liu, Shengzhong Frank

2018-05-01

Ruddlesden-Popper reduced-dimensional hybrid perovskite (RDP) semiconductors have attracted significant attention recently due to their promising stability and excellent optoelectronic properties. Here, the RDP crystallization mechanism in real time from liquid precursors to the solid film is investigated, and how the phase transition kinetics influences phase purity, quantum well orientation, and photovoltaic performance is revealed. An important template-induced nucleation and growth of the desired (BA) 2 (MA) 3 Pb 4 I 13 phase, which is achieved only via direct crystallization without formation of intermediate phases, is observed. As such, the thermodynamically preferred perpendicular crystal orientation and high phase purity are obtained. At low temperature, the formation of intermediate phases, including PbI 2 crystals and solvate complexes, slows down intercalation of ions and increases nucleation barrier, leading to formation of multiple RDP phases and orientation randomness. These insights enable to obtain high quality (BA) 2 (MA) 3 Pb 4 I 13 films with preferentially perpendicular quantum well orientation, high phase purity, smooth film surface, and improved optoelectronic properties. The resulting devices exhibit high power conversion efficiency of 12.17%. This work should help guide the perovskite community to better control Ruddlesden-Popper perovskite structure and further improve optoelectronic and solar cell devices. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Twelve-Month Efficacy and Safety Data for the "Stress Incontinence Control, Efficacy and Safety Study": A Phase III, Multicenter, Prospective, Randomized, Controlled Study Treating Female Stress Urinary Incontinence Using the Vesair Intravesical Balloon.

PubMed

Winkler, Harvey; Jacoby, Karny; Kalota, Susan; Snyder, Jeffrey; Cline, Kevin; Robertson, Kaiser; Kahan, Randall; Green, Lonny; McCammon, Kurt; Rovner, Eric; Rardin, Charles

The "Stress Incontinence Control, Efficacy and Safety Study" (SUCCESS) is a phase III study of the Vesair Balloon in women with stress urinary incontinence who had failed conservative therapy, and either failed surgery, were not candidates for surgery, or chose not to have surgery. The safety and efficacy of the balloon at 12 months is reported for those participants in the treatment arm who elected to continue with the SUCCESS trial beyond the primary end point at 3 months. The SUCCESS trial is a multicenter, prospective, single-blinded, randomized, sham-controlled study. Participants were randomized on a 2.33:1 basis to either Vesair Balloon placement or placebo. The primary efficacy end point was a composite of both a greater than 50% reduction from baseline on 1-hour provocative pad weight test and an at least 10-point improvement in symptoms on the Incontinence Quality of Life questionnaire assessed at the 3-month study visit. Patients in the treatment arm who opted to continue in the trial were followed up prospectively up to 12 months. A total of 221 participants were randomized, including 157 in the treatment arm and 64 in the control arm. Sixty-seven participants in the treatment arm (42.7% of participants enrolled) were evaluated at 12 months, with 56.3% achieving the composite end point and 78.7% having greater than 50% reduction in pad weight from baseline in a per-protocol analysis. In an intent-to-treat analysis treating all participants who did not continue with the balloon as failures, 24% of the participants achieved the composite end point and 33.6% had a greater than 50% reduction in pad weight from baseline. Treatment-related adverse events in this group included dysuria (40.1%), gross hematuria (36.9%), and urinary tract infection (26.1%). In this phase III trial, symptom relief was maintained for those participants who continued therapy for 12 months. The balloon was found to be safe with no device- or procedure-related serious adverse events reported. Additional studies are warranted to determine which patient populations are more tolerant of the balloon and to assess the efficacy and safety of its longer-term use. Additional screening methods, including screening patients for balloon tolerability, are warranted to reduce participant withdrawals.

Random sequences generation through optical measurements by phase-shifting interferometry

NASA Astrophysics Data System (ADS)

François, M.; Grosges, T.; Barchiesi, D.; Erra, R.; Cornet, A.

2012-04-01

The development of new techniques for producing random sequences with a high level of security is a challenging topic of research in modern cryptographics. The proposed method is based on the measurement by phase-shifting interferometry of the speckle signals of the interaction between light and structures. We show how the combination of amplitude and phase distributions (maps) under a numerical process can produce random sequences. The produced sequences satisfy all the statistical requirements of randomness and can be used in cryptographic schemes.

Effects of a tailored lifestyle self-management intervention (TALENT) study on weight reduction: a randomized controlled trial.

PubMed

Melchart, Dieter; Löw, Peter; Wühr, Erich; Kehl, Victoria; Weidenhammer, Wolfgang

2017-01-01

Overweight and obesity are globally increasing risk factors for diseases in the context of metabolic syndrome. A randomized controlled trial was conducted to investigate whether there are any existing differences between two lifestyle intervention strategies with respect to weight reduction after 1 year. A total of 166 subjects with a body mass index of 28-35 kg/m 2 were enrolled in this trial at seven study centers; 109 were randomly allocated to the intervention group (comprehensive lifestyle modification program: web-based Individual Health Management [IHM]) with 3-month reduction phase plus 9-month maintenance phase, and 57 were allocated to the control group (written information with advice for healthy food habits: usual care [UC]). Body weight, waist circumference, blood pressure, laboratory findings, and bioimpedance analysis used to determine body composition were measured at baseline and after 3, 6, 9, and 12 months. The primary outcome parameter was body weight at month 12 compared to baseline. With respect to baseline status there were no statistically significant differences between the groups. Based on the intent-to-treat population, body weight showed a mean decrease of 8.7 kg (SD 6.1) in the intervention group (IHM) and 4.2 kg (SD 5) in the control group (UC) at month 12. This statistically significant difference ( P <0.001) was confirmed by various sensitivity analyses. Body mass index, waist circumference, high-density lipid cholesterol, body fat, and the ratio of fat and body cell mass improved to a significantly higher degree in the IHM group. IHM proved to be superior to UC in weight reduction after 1 year. With a mean loss of about 10% of the baseline weight, a clinically high relevant risk reduction for cardio-metabolic diseases is achievable.

Rationale and design of a randomized controlled, clinical trial investigating a comprehensive exercise stimulus for improving mobility disability outcomes in persons with multiple sclerosis.

PubMed

Motl, Robert W; Pilutti, Lara A; Sandroff, Brian M; Klaren, Rachel; Balantrapu, Swathi; McAuley, Edward; Sosnoff, Jacob J; Fernhall, Bo

2013-05-01

This randomized controlled trial (RCT) examines the effect of a comprehensive exercise training stimulus on physiological function and mobility disability (i.e., problems walking) in individuals with multiple sclerosis (MS) who have walking impairment. This trial will recruit 30 persons with MS across central Illinois who have an Expanded Disability Status Scale score between 4.0 and 6.0, and those persons will be randomized into either the intervention or control arm of the study; the participants will not be blinded regarding group assignment. The intervention will incorporate equal amounts of aerobic, resistance, and balance modes of training delivered 3 times/week with a gradual progression of duration and intensity across a 6-month period. The control will involve stretching along with minimal muscle strengthening stimuli and will be delivered on the same frequency and duration. The primary outcomes will be clinical, kinematic, patient-rated, and physiological measures of mobility disability. The secondary outcomes will be measures of physiological function including aerobic capacity, muscle strength, and balance. This study will lay the foundation for the design of a subsequent Phase II or Phase III RCT by (a) providing effect sizes that can be included in a power analysis for sample size estimation and (b) investigating whether aerobic capacity, muscle strength, and balance are possible factors associated with the beneficial effect of exercise training on walking outcomes. Taken as a whole, the proposed study and our subsequent research agenda has the potential for advancing the management of mobility disability using exercise training in the 2nd stage of MS. Copyright © 2013 Elsevier Inc. All rights reserved.

Daily laxative therapy reduces organ dysfunction in mechanically ventilated patients: a phase II randomized controlled trial.

PubMed

de Azevedo, Rodrigo Palacio; Freitas, Flávio Geraldo Resende; Ferreira, Elaine Maria; Pontes de Azevedo, Luciano Cesar; Machado, Flávia Ribeiro

2015-09-16

Constipation is a common problem in intensive care units. We assessed the efficacy and safety of laxative therapy aiming to promote daily defecation in reducing organ dysfunction in mechanically ventilated patients. We conducted a prospective, randomized, controlled, nonblinded phase II clinical trial at two general intensive care units. Patients expected to remain ventilated for over 3 days were randomly assigned to daily defecation or control groups. The intervention group received lactulose and enemas to produce 1-2 defecations per day. In the control group, absence of defecation was tolerated up to 5 days. Primary outcome was the change in Sequential Organ Failure Assessment (SOFA) score between the date of enrollment and intensive care unit discharge, death or day 14. We included 88 patients. Patients in the treatment group had a higher number of defecations per day (1.3 ± 0.42 versus 0.7 ± 0.56, p < 0.0001) and lower percentage of days without defecation (33.1 ± 15.7% versus 62.3 ± 24.5%, p < 0.0001). Patients in the intervention group had a greater reduction in SOFA score (-4.0 (-6.0 to 0) versus -1.0 (-4.0 to 1.0), p = 0.036) with no difference in mortality rates or in survival time. Adverse events were more frequent in the treatment group (4.5 (3.0-8.0) versus 3.0 (1.0-5.7), p = 0.016), including more days with diarrhea (2.0 (1.0-4.0) versus 1.0 (0-2.0) days, p < 0.0001). Serious adverse events were rare and did not significantly differ between groups. Laxative therapy improved daily defecation in ventilated patients and was associated with a greater reduction in SOFA score. Clinical Trials.gov NCT01607060, registered 24 May 2012.

CrowdPhase: crowdsourcing the phase problem

PubMed Central

Jorda, Julien; Sawaya, Michael R.; Yeates, Todd O.

2014-01-01

The human mind innately excels at some complex tasks that are difficult to solve using computers alone. For complex problems amenable to parallelization, strategies can be developed to exploit human intelligence in a collective form: such approaches are sometimes referred to as ‘crowdsourcing’. Here, a first attempt at a crowdsourced approach for low-resolution ab initio phasing in macromolecular crystallography is proposed. A collaborative online game named CrowdPhase was designed, which relies on a human-powered genetic algorithm, where players control the selection mechanism during the evolutionary process. The algorithm starts from a population of ‘individuals’, each with a random genetic makeup, in this case a map prepared from a random set of phases, and tries to cause the population to evolve towards individuals with better phases based on Darwinian survival of the fittest. Players apply their pattern-recognition capabilities to evaluate the electron-density maps generated from these sets of phases and to select the fittest individuals. A user-friendly interface, a training stage and a competitive scoring system foster a network of well trained players who can guide the genetic algorithm towards better solutions from generation to generation via gameplay. CrowdPhase was applied to two synthetic low-resolution phasing puzzles and it was shown that players could successfully obtain phase sets in the 30° phase error range and corresponding molecular envelopes showing agreement with the low-resolution models. The successful preliminary studies suggest that with further development the crowdsourcing approach could fill a gap in current crystallographic methods by making it possible to extract meaningful information in cases where limited resolution might otherwise prevent initial phasing. PMID:24914965

Cost-effectiveness of strategies to market and train primary health care physicians in brief intervention techniques for hazardous alcohol use.

PubMed

Gomel, M K; Wutzke, S E; Hardcastle, D M; Lapsley, H; Reznik, R B

1998-07-01

The cost-effectiveness of strategies to market and train primary care physicians in brief intervention for hazardous alcohol consumption was examined. Physicians were randomly assigned to one of three marketing strategies designed to promote the "uptake" of a brief intervention package for hazardous and harmful alcohol consumption. The strategies were direct mail, tele-marketing, or academic detailing. One hundred and twenty-seven of those physicians who requested the package during the marketing phase (phase 1) and who also agreed to participate in the training and support phase of the project (phase 2) were matched into one of three training and support conditions: training and no support, training and minimal support, training and maximal support. An additional 34 physicians were randomly selected and assigned to a control condition. The ultimate aim of training and support was to maximise physician screening and counselling rates. Tele-marketing was found to be more cost-effective than academic detailing and direct mail in promoting the uptake of the package. For the training and support phase costs and effects increased with the level of support, hence the issue to be considered is whether the additional cost incurred in moving from one strategy to another is warranted given the increase in the level of outcome.

Dose-response effects of aerobic exercise on estrogen among women at high risk for breast cancer: a randomized controlled trial.

PubMed

Schmitz, Kathryn H; Williams, Nancy I; Kontos, Despina; Domchek, Susan; Morales, Knashawn H; Hwang, Wei-Ting; Grant, Lorita L; DiGiovanni, Laura; Salvatore, Domenick; Fenderson, Desire'; Schnall, Mitchell; Galantino, Mary Lou; Stopfer, Jill; Kurzer, Mindy S; Wu, Shandong; Adelman, Jessica; Brown, Justin C; Good, Jerene

2015-11-01

Medical and surgical interventions for elevated breast cancer risk (e.g., BRCA1/2 mutation, family history) focus on reducing estrogen exposure. Women at elevated risk may be interested in less aggressive approaches to risk reduction. For example, exercise might reduce estrogen, yet has fewer serious side effects and less negative impact than surgery or hormonal medications. Randomized controlled trial. Increased risk defined by risk prediction models or BRCA mutation status. Eligibility: Age 18-50, eumenorrheic, non-smokers, and body mass index (BMI) between 21 and 50 kg/m(2). 139 were randomized. Treadmill exercise: 150 or 300 min/week, five menstrual cycles. Control group maintained exercise <75 min/week. Area under curve (AUC) for urinary estrogen. Secondary measures: urinary progesterone, quantitative digitized breast dynamic contrast-enhanced magnetic resonance imaging background parenchymal enhancement. Mean age 34 years, mean BMI 26.8 kg/m(2). A linear dose-response relationship was observed such that every 100 min of exercise is associated with 3.6 % lower follicular phase estrogen AUC (linear trend test, p = 0.03). No changes in luteal phase estrogen or progesterone levels. There was also a dose-response effect noted: for every 100 min of exercise, there was a 9.7 % decrease in background parenchymal enhancement as measured by imaging (linear trend test, p = 0.009). Linear dose-response effect observed to reduce follicular phase estrogen exposure measured via urine and hormone sensitive breast tissue as measured by imaging. Future research should explore maintenance of effects and extent to which findings are repeatable in lower risk women. Given the high benefit to risk ratio, clinicians can inform young women at increased risk that exercise may blunt estrogen exposure while considering whether to try other preventive therapies.

Critical periods after stroke study: translating animal stroke recovery experiments into a clinical trial

PubMed Central

Dromerick, Alexander W.; Edwardson, Matthew A.; Edwards, Dorothy F.; Giannetti, Margot L.; Barth, Jessica; Brady, Kathaleen P.; Chan, Evan; Tan, Ming T.; Tamboli, Irfan; Chia, Ruth; Orquiza, Michael; Padilla, Robert M.; Cheema, Amrita K.; Mapstone, Mark E.; Fiandaca, Massimo S.; Federoff, Howard J.; Newport, Elissa L.

2015-01-01

Introduction: Seven hundred ninety-five thousand Americans will have a stroke this year, and half will have a chronic hemiparesis. Substantial animal literature suggests that the mammalian brain has much potential to recover from acute injury using mechanisms of neuroplasticity, and that these mechanisms can be accessed using training paradigms and neurotransmitter manipulation. However, most of these findings have not been tested or confirmed in the rehabilitation setting, in large part because of the challenges in translating a conceptually straightforward laboratory experiment into a meaningful and rigorous clinical trial in humans. Through presentation of methods for a Phase II trial, we discuss these issues and describe our approach. Methods: In rodents there is compelling evidence for timing effects in rehabilitation; motor training delivered at certain times after stroke may be more effective than the same training delivered earlier or later, suggesting that there is a critical or sensitive period for strongest rehabilitation training effects. If analogous critical/sensitive periods can be identified after human stroke, then existing clinical resources can be better utilized to promote recovery. The Critical Periods after Stroke Study (CPASS) is a phase II randomized, controlled trial designed to explore whether such a sensitive period exists. We will randomize 64 persons to receive an additional 20 h of upper extremity therapy either immediately upon rehab admission, 2–3 months after stroke onset, 6 months after onset, or to an observation-only control group. The primary outcome measure will be the Action Research Arm Test (ARAT) at 1 year. Blood will be drawn at up to 3 time points for later biomarker studies. Conclusion: CPASS is an example of the translation of rodent motor recovery experiments into the clinical setting; data obtained from this single site randomized controlled trial will be used to finalize the design of a Phase III trial. PMID:25972803

APF530 versus ondansetron, each in a guideline-recommended three-drug regimen, for the prevention of chemotherapy-induced nausea and vomiting due to anthracycline plus cyclophosphamide–based highly emetogenic chemotherapy regimens: a post hoc subgroup analysis of the Phase III randomized MAGIC trial

PubMed Central

Schnadig, Ian D; Agajanian, Richy; Dakhil, Christopher; Gabrail, Nashat; Vacirca, Jeffrey; Taylor, Charles; Wilks, Sharon; Braun, Eduardo; Mosier, Michael C; Geller, Robert B; Schwartzberg, Lee; Vogelzang, Nicholas

2017-01-01

Background APF530, a novel extended-release granisetron injection, was superior to ondansetron in a guideline-recommended three-drug regimen in preventing delayed-phase chemotherapy-induced nausea and vomiting (CINV) among patients receiving highly emetogenic chemotherapy (HEC) in the double-blind Phase III Modified Absorption of Granisetron In the prevention of CINV (MAGIC) trial. Patients and methods This MAGIC post hoc analysis evaluated CINV prevention efficacy and safety of APF530 versus ondansetron, each with fosaprepitant and dexamethasone, in patient subgroup receiving an anthracycline plus cyclophosphamide (AC) regimen. Patients were randomized 1:1 to APF530 500 mg subcutaneously (granisetron 10 mg) or ondansetron 0.15 mg/kg intravenously (IV) (≤16 mg); stratification was by planned cisplatin ≥50 mg/m2 (yes/no). Patients were to receive fosaprepitant 150 mg IV and dexamethasone 12 mg IV on day 1, then dexamethasone 8 mg orally once daily on day 2 and twice daily on days 3 and 4. Patients were mostly younger females (APF530 arm, mean age 54.1 years, female, 99.3%; ondansetron arm, 53.8 years, female 98.3%). The primary end point was delayed-phase (>24–120 hours) complete response (CR). Results APF530 versus ondansetron regimens achieved numerically better CINV control in delayed and overall (0–120 hours) phases for CR, complete control, total response, rescue medication use, and proportion with no nausea. APF530 trends are consistent with the overall population, although not statistically superior given the underpowered AC subgroup analysis. The APF530 regimen in this population was generally well tolerated, with safety comparable to that of the overall population. Conclusion APF530 plus fosaprepitant and dexamethasone effectively prevented CINV among patients receiving AC-based HEC, a large subgroup in whom CINV control has traditionally been challenging. PMID:28579832

Additive effect of rikkunshito, an herbal medicine, on chemotherapy-induced nausea, vomiting, and anorexia in uterine cervical or corpus cancer patients treated with cisplatin and paclitaxel: results of a randomized phase II study (JORTC KMP-02).

PubMed

Ohnishi, Shunsuke; Watari, Hidemichi; Kanno, Maki; Ohba, Yoko; Takeuchi, Satoshi; Miyaji, Tempei; Oyamada, Shunsuke; Nomura, Eiji; Kato, Hidenori; Sugiyama, Toru; Asaka, Masahiro; Sakuragi, Noriaki; Yamaguchi, Takuhiro; Uezono, Yasuhito; Iwase, Satoru

2017-09-01

Rikkunshito, an herbal medicine, is widely prescribed in Japan for the treatment of anorexia and functional dyspepsia, and has been reported to recover reductions in food intake caused by cisplatin. We investigated whether rikkunshito could improve chemotherapy-induced nausea and vomiting (CINV) and anorexia in patients treated with cisplatin. Patients with uterine cervical or corpus cancer who were to receive cisplatin (50 mg/m² day 1) and paclitaxel (135 mg/m² day 0) as first-line chemotherapy were randomly assigned to the rikkunshito group receiving oral administration on days 0-13 with standard antiemetics, or the control group receiving antiemetics only. The primary endpoint was the rate of complete control (CC: no emesis, no rescue medication, and no significant nausea) in the overall phase (0-120 hours). Two-tailed p<0.20 was considered significant in the planned analysis. The CC rate in the overall phase was significantly higher in the rikkunshito group than in the control group (57.9% vs. 35.3%, p=0.175), as were the secondary endpoints: the CC rate in the delayed phase (24-120 hours), and the complete response (CR) rates (no emesis and no rescue medication) in the overall and delayed phases (63.2% vs. 35.3%, p=0.095; 84.2% vs. 52.9%, p=0.042; 84.2% vs. 52.9%, p=0.042, respectively), and time to treatment failure (p=0.059). Appetite assessed by visual analogue scale (VAS) appeared to be superior in the rikkunshito group from day 2 through day 6. Rikkunshito provided additive effect for the prevention of CINV and anorexia. Copyright © 2017. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology

Differential benefits of amoxicillin-metronidazole in different phases of periodontal therapy in a randomized controlled crossover clinical trial.

PubMed

Mombelli, Andrea; Almaghlouth, Adnan; Cionca, Norbert; Courvoisier, Delphine S; Giannopoulou, Catherine

2015-03-01

The specific advantage of administering systemic antibiotics during initial, non-surgical therapy or in the context of periodontal surgery is unclear. This study assesses the differential outcomes of periodontal therapy supplemented with amoxicillin-metronidazole during either the non-surgical or the surgical treatment phase. This is a single-center, randomized placebo-controlled crossover clinical trial with a 1-year follow-up. Eighty participants with Aggregatibacter actinomycetemcomitans-associated moderate to advanced periodontitis were randomized into two treatment groups: group A, antibiotics (500 mg metronidazole plus 375 mg amoxicillin three times per day for 7 days) during the first, non-surgical phase of periodontal therapy (T1) and placebo during the second, surgical phase (T2); and group B, placebo during T1 and antibiotics during T2. The number of sites with probing depth (PD) >4 mm and bleeding on probing (BOP) per patient was the primary outcome. A total of 11,212 sites were clinically monitored on 1,870 teeth. T1 with antibiotics decreased the number of sites with PD >4 mm and BOP per patient significantly more than without (group A: from 34.5 to 5.7, 84%; group B: from 28.7 to 8.7, 70%; P <0.01). Twenty patients treated with antibiotics, but only eight treated with placebo, achieved a 10-fold reduction of diseased sites (P = 0.007). Consequently, fewer patients of group A needed additional therapy, the mean number of surgical interventions was lower, and treatment time in T2 was shorter. Six months after T2, the mean number of residual pockets (group A: 2.8 ± 5.2; group B: 2.2 ± 5.0) was not significantly different and was sustained over 12 months in both groups. Giving the antibiotics during T1 or T2 yielded similar long-term outcomes, but antibiotics in T1 resolved the disease quicker and thus reduced the need for additional surgical intervention.

Three-dimensional image authentication scheme using sparse phase information in double random phase encoded integral imaging.

PubMed

Yi, Faliu; Jeoung, Yousun; Moon, Inkyu

2017-05-20

In recent years, many studies have focused on authentication of two-dimensional (2D) images using double random phase encryption techniques. However, there has been little research on three-dimensional (3D) imaging systems, such as integral imaging, for 3D image authentication. We propose a 3D image authentication scheme based on a double random phase integral imaging method. All of the 2D elemental images captured through integral imaging are encrypted with a double random phase encoding algorithm and only partial phase information is reserved. All the amplitude and other miscellaneous phase information in the encrypted elemental images is discarded. Nevertheless, we demonstrate that 3D images from integral imaging can be authenticated at different depths using a nonlinear correlation method. The proposed 3D image authentication algorithm can provide enhanced information security because the decrypted 2D elemental images from the sparse phase cannot be easily observed by the naked eye. Additionally, using sparse phase images without any amplitude information can greatly reduce data storage costs and aid in image compression and data transmission.

A long-term self-managed handwriting intervention for people with Parkinson's disease: results from the control group of a phase II randomized controlled trial.

PubMed

Collett, Johnny; Franssen, Marloes; Winward, Charlotte; Izadi, Hooshang; Meaney, Andy; Mahmoud, Wala; Bogdanovic, Marko; Tims, Martin; Wade, Derick; Dawes, Helen

2017-12-01

To report on the control group of a trial primarily designed to investigate exercise for improving mobility in people with Parkinson's disease (pwP). The control group undertook a handwriting intervention to control for attention and time spent practising a specific activity. Secondary analysis of a two-arm parallel phase II randomized controlled trial with blind assessment. Community. PwP able to walk ⩾100 m and with no contraindication to exercise were recruited from the Thames Valley, UK, and randomized (1:1) to exercise or handwriting, via a concealed computer-generated list. Handwriting was undertaken at home and exercise in community facilities; both were delivered through workbooks with monthly support visits and involved practice for 1 hour, twice weekly, over a period of six months. Handwriting was assessed, at baseline, 3, 6 and 12 months, using a pangram giving writing speed, amplitude (area) and progressive reduction in amplitude (ratio). The Movement Disorder Society (MDS)-Unified Parkinson's Disease Rating Scale (UPDRS) item 2.7 measured self-reported handwriting deficits. In all, 105 pwP were recruited (analysed: n  = 51 handwriting, n  = 54 exercise). A total of 40 pwP adhered to the handwriting programme, most completing ⩾1 session/week. Moderate effects were found for amplitude (total area: d = 0.32; 95% confidence interval (CI): -0.11 to 0.7; P = 0.13) in favour of handwriting over a period of12 months; effects for writing speed and ratio parameters were small ≤0.11. Self-reported handwriting difficulties also favoured handwriting (UPDRS 2.7: odds ratio (OR) = 0.55; 95% CI: 0.34 to 0.91; P = 0.02). No adverse effects were reported. PwP generally adhere to self-directed home handwriting which may provide benefit with minimal risk. Encouraging effects were found in writing amplitude and, moreover, perceived ability.

Pediatric endurance and limb strengthening (PEDALS) for children with cerebral palsy using stationary cycling: a randomized controlled trial.

PubMed

Fowler, Eileen G; Knutson, Loretta M; Demuth, Sharon K; Siebert, Kara L; Simms, Victoria D; Sugi, Mia H; Souza, Richard B; Karim, Roksana; Azen, Stanley P

2010-03-01

Effective interventions to improve and maintain strength (force-generating capacity) and endurance are needed for children with cerebral palsy (CP). This study was performed to examine the effects of a stationary cycling intervention on muscle strength, locomotor endurance, preferred walking speed, and gross motor function in children with spastic diplegic CP. This was a phase I randomized controlled trial with single blinding. The interventions were performed in community-based outpatient physical therapy clinics. Outcome assessments were performed in university laboratories. Sixty-two ambulatory children aged 7 to 18 years with spastic diplegic CP and Gross Motor Function Classification System levels I to III participated in this study. Participants were randomly assigned to cycling or control (no-intervention) groups. Thirty intervention sessions occurred over 12 weeks. Primary outcomes were peak knee extensor and flexor moments, the 600-Yard Walk-Run Test, the Thirty-Second Walk Test, and the Gross Motor Function Measure sections D and E (GMFM-66). Significant baseline-postintervention improvements were found for the 600-Yard Walk-Run Test, the GMFM-66, peak knee extensor moments at 120 degrees /s, and peak knee flexor moments at 30 degrees /s for the cycling group. Improved peak knee flexor moments at 120 degrees/s were found for the control group only, although not all participants could complete this speed of testing. Significant differences between the cycling and control groups based on change scores were not found for any outcomes. Limitations Heterogeneity of the patient population and intrasubject variability were limitations of the study. Significant improvements in locomotor endurance, gross motor function, and some measures of strength were found for the cycling group but not the control group, providing preliminary support for this intervention. As statistical differences were not found in baseline-postintervention change scores between the 2 groups; the results did not demonstrate that stationary cycling was more effective than no intervention. The results of this phase I study provide guidance for future research.

A statistical model of false negative and false positive detection of phase singularities.

PubMed

Jacquemet, Vincent

2017-10-01

The complexity of cardiac fibrillation dynamics can be assessed by analyzing the distribution of phase singularities (PSs) observed using mapping systems. Interelectrode distance, however, limits the accuracy of PS detection. To investigate in a theoretical framework the PS false negative and false positive rates in relation to the characteristics of the mapping system and fibrillation dynamics, we propose a statistical model of phase maps with controllable number and locations of PSs. In this model, phase maps are generated from randomly distributed PSs with physiologically-plausible directions of rotation. Noise and distortion of the phase are added. PSs are detected using topological charge contour integrals on regular grids of varying resolutions. Over 100 × 10 6 realizations of the random field process are used to estimate average false negative and false positive rates using a Monte-Carlo approach. The false detection rates are shown to depend on the average distance between neighboring PSs expressed in units of interelectrode distance, following approximately a power law with exponents in the range of 1.14 to 2 for false negatives and around 2.8 for false positives. In the presence of noise or distortion of phase, false detection rates at high resolution tend to a non-zero noise-dependent lower bound. This model provides an easy-to-implement tool for benchmarking PS detection algorithms over a broad range of configurations with multiple PSs.

Effectiveness of deep versus moderate muscle relaxation during laparoscopic donor nephrectomy in enhancing postoperative recovery: study protocol for a randomized controlled study.

PubMed

Bruintjes, Moira H D; Braat, Andries E; Dahan, Albert; Scheffer, Gert-Jan; Hilbrands, Luuk B; d'Ancona, Frank C H; Donders, Rogier A R T; van Laarhoven, Cornelis J H M; Warlé, Michiel C

2017-03-04

Postoperative recovery after live donor nephrectomy is largely determined by the consequences of postoperative pain and analgesia consumptions. The use of deep neuromuscular blockade has been shown to reduce postoperative pain scores after laparoscopic surgery. In this study, we will investigate whether deep neuromuscular blockade also improves the early quality of recovery after live donor nephrectomy. The RELAX-study is a phase IV, multicenter, double-blinded, randomized controlled trial, in which 96 patients, scheduled for living donor nephrectomy, will be randomized into two groups: one with deep and one with moderate neuromuscular blockade. Deep neuromuscular blockade is defined as a post-tetanic count of 1-2. Our primary outcome measurement will be the Quality of Recovery-40 questionnaire (overall score) at 24 h after extubation. This study is, to our knowledge, the first randomized study to assess the effectiveness of deep neuromuscular blockade during laparoscopic donor nephrectomy in enhancing postoperative recovery. The study findings may also be applicable for other laparoscopic procedures. clinicaltrials.gov, NCT02838134 . Registered on 29 June 2016.

Prevention of nosocomial infections in critically ill patients with lactoferrin (PREVAIL study): study protocol for a randomized controlled trial.

PubMed

Muscedere, John; Maslove, David; Boyd, John Gordon; O'Callaghan, Nicole; Lamontagne, Francois; Reynolds, Steven; Albert, Martin; Hall, Rick; McGolrick, Danielle; Jiang, Xuran; Day, Andrew G

2016-09-29

Nosocomial infections remain an important source of morbidity, mortality, and increased health care costs in hospitalized patients. This is particularly problematic in intensive care units (ICUs) because of increased patient vulnerability due to the underlying severity of illness and increased susceptibility from utilization of invasive therapeutic and monitoring devices. Lactoferrin (LF) and the products of its breakdown have multiple biological effects, which make its utilization of interest for the prevention of nosocomial infections in the critically ill. This is a phase II randomized, multicenter, double-blinded trial to determine the effect of LF on antibiotic-free days in mechanically ventilated, critically ill, adult patients in the ICU. Eligible, consenting patients will be randomized to receive either LF or placebo. The treating clinician will remain blinded to allocation during the study; blinding will be maintained by using opaque syringes and containers. The primary outcome will be antibiotic-free days, defined as the number of days alive and free of antibiotics 28 days after randomization. Secondary outcomes will include: antibiotic utilization, adjudicated diagnosis of nosocomial infection (longer than 72 h of admission to ICU), hospital and ICU length of stay, change in organ function after randomization, hospital and 90-day mortality, incidence of tracheal colonization, changes in gastrointestinal permeability, and immune function. Outcomes to inform the conduct of a larger definitive trial will also be evaluated, including feasibility as determined by recruitment rates and protocol adherence. The results from this study are expected to provide insight into a potential novel therapeutic use for LF in critically ill adult patients. Further, analysis of study outcomes will inform a future, large-scale phase III randomized controlled trial powered on clinically important outcomes related to the use of LF. The trial was registered at www.ClinicalTrials.gov on 18 November 2013. NCT01996579 .

Experimental analysis of pressure controlled atomization process (PCAP) coatings for replacement of hard chromium plating

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

Tierney, J.C.; Glovan, R.J.; Witt, S.J.

1995-12-31

A four-phase experimental design was utilized to evaluate the abrasive wear and corrosion protection characteristics of VERSAlloy 50 coatings applied to AISI 4130 steel sheet. The coatings were applied with the Pressure Controlled Atomization Process (PCAP), a new thermal spray process being developed for the United States Air Force to replace hard chromium plating. Phase 1 of the design consisted of an evaluation of deposit profiles that were sprayed at five different standoff distances. Profile measurements yielded standard deviations ({sigma}) of the plume at each of the spray distances. Phase 2 consisted of a completely randomized series of eight spraymore » tests in which the track gap or distance between consecutive spray passes was varied by amounts of 0.5{sigma}, 1{sigma}, 2{sigma}, and 3{sigma}. The sprayed test coupons were then evaluated for corrosion protection, abrasive wear resistance, microhardness, and porosity. Results from Phase 2 were used to determine the best track gap or overlap for Phase 3 and Phase 4 testing. Phase 3 consisted of 22-run central composite design. The test coupons were evaluated the same as in Phase 2. Statistical analysis of Phase 3 data revealed that the optimal system operating parameters produced coatings that would either provide superior corrosion protection or resistance to abrasive wear. Phase 4 consisted of four spray tests to validate the results obtained in Phase 3. Phase 4 test coupons were again evaluated with the same analysis as in Phases 2 and 3. The validation tests indicated that PCAP system operating parameters could be controlled to produce VERSAlloy 50 coatings with superior corrosion protection or resistance to abrasive wear.« less

Cannabis for dyskinesia in Parkinson disease: a randomized double-blind crossover study.

PubMed

Carroll, C B; Bain, P G; Teare, L; Liu, X; Joint, C; Wroath, C; Parkin, S G; Fox, P; Wright, D; Hobart, J; Zajicek, J P

2004-10-12

The long-term treatment of Parkinson disease (PD) may be complicated by the development of levodopa-induced dyskinesia. Clinical and animal model data support the view that modulation of cannabinoid function may exert an antidyskinetic effect. The authors conducted a randomized, double-blind, placebo-controlled crossover trial to examine the hypothesis that cannabis may have a beneficial effect on dyskinesia in PD. A 4-week dose escalation study was performed to assess the safety and tolerability of cannabis in six PD patients with levodopa-induced dyskinesia. Then a randomized placebo-controlled crossover study (RCT) was performed, in which 19 PD patients were randomized to receive oral cannabis extract followed by placebo or vice versa. Each treatment phase lasted for 4 weeks with an intervening 2-week washout phase. The primary outcome measure was a change in Unified Parkinson's Disease Rating Scale (UPDRS) (items 32 to 34) dyskinesia score. Secondary outcome measures included the Rush scale, Bain scale, tablet arm drawing task, and total UPDRS score following a levodopa challenge, as well as patient-completed measures of a dyskinesia activities of daily living (ADL) scale, the PDQ-39, on-off diaries, and a range of category rating scales. Seventeen patients completed the RCT. Cannabis was well tolerated, and had no pro- or antiparkinsonian action. There was no evidence for a treatment effect on levodopa-induced dyskinesia as assessed by the UPDRS, or any of the secondary outcome measures. Orally administered cannabis extract resulted in no objective or subjective improvement in dyskinesias or parkinsonism.

Cognitive Analytic Therapy for Bipolar Disorder: A Pilot Randomized Controlled Trial.

PubMed

Evans, Mark; Kellett, Stephen; Heyland, Simon; Hall, Jo; Majid, Shazmin

2017-01-01

The evidence base for treatment of bipolar affective disorder (BD) demands the evaluation of new psychotherapies in order to broaden patient choice. This study reports on the feasibility, safety, helpfulness and effectiveness of cognitive analytic therapy (CAT). In a pilot randomized controlled trial, BD patients in remission were randomized to either receiving 24 sessions of CAT (n = 9) or treatment as usual (n = 9) and were assessed in terms of symptoms, functioning and service usage over time. In the CAT arm no adverse events occurred, 8/9 completed treatment, 5/8 attended all 24 sessions and 2/8 were categorized as recovered. The most common helpful event during CAT was recognition of patterns in mood variability, with helpfulness themes changing according to phase of therapy. No major differences were found when comparing the arms over time in terms of service usage or psychometric outcomes. The study suggests that conducting further research into the effectiveness of CAT in treating BD is warranted and guidance regarding future trials is provided. Copyright © 2016 John Wiley & Sons, Ltd. Treating BD with CAT appears feasible and safe. Retaining fidelity to the reformulation, recognition and revision structure of CAT appears useful. Participants stated that across the phases of CAT, focussing on patterns of mood variability was consistently helpful. Copyright © 2016 John Wiley & Sons, Ltd.

Signature of phase singularities in diffusive regimes in disordered waveguide lattices: interplay and qualitative analysis

NASA Astrophysics Data System (ADS)

Ghosh, Somnath

2018-05-01

Co-existence and interplay between mesoscopic light dynamics with singular optics in spatially random but temporally coherent disordered waveguide lattices is reported. Two CW light beams of 1.55 micron operating wavelength are launched as inputs to 1D waveguide lattices with controllable weak disorder in refractive index profile. Direct observation of phase singularities in the speckle pattern along the length is numerically demonstrated. Quantitative analysis of onset of such singular behavior and diffusive wave propagation is analyzed for the first time.

Clustering and Phase Transitions on a Neutral Landscape

NASA Astrophysics Data System (ADS)

Scott, Adam; King, Dawn; Maric, Nevena; Bahar, Sonya

2012-02-01

The problem of speciation and species aggregation on a neutral landscape, subject to random mutational fluctuations rather than selective drive, has been a focus of research since the seminal work of Kimura on genetic drift. These ideas have received increased attention due to the more recent development of a neutral ecological theory by Hubbell. De Aguiar et al. recently demonstrated, in a computational model, that speciation can occur under neutral conditions; this study bears some comparison with more mathematical studies of clustering on neutral landscapes in the context of branching and annihilating random walks. Here, we show that clustering can occur on a neutral landscape where the dimensions specify the simulated organisms' phenotypes. Unlike the De Aguiar et al. model, we simulate sympatric speciation: the organisms cluster phenotypically, but are not spatially separated. Moreover, we find that clustering occurs not only in the case of assortative mating, but also in the case of asexual fission. Clustering is not observed in a control case where organisms can mate randomly. We find that the population size and the number of clusters undergo phase-transition-like behavior as the maximum mutation size is varied.

Strong Shock Propagating Over A Random Bed of Spherical Particles

NASA Astrophysics Data System (ADS)

Mehta, Yash; Salari, Kambiz; Jackson, Thomas L.; Balachandar, S.; Thakur, Siddharth

2017-11-01

The study of shock interaction with particles has been largely motivated because of its wide-ranging applications. The complex interaction between the compressible flow features, such as shock wave and expansion fan, and the dispersed phase makes this multi-phase flow very difficult to predict and control. In this talk we will be presenting results on fully resolved inviscid simulations of shock interaction with random bed of particles. One of the fascinating observations from these simulations are the flow field fluctuations due to the presence of randomly distributed particles. Rigorous averaging (Favre averaging) of the governing equations results in Reynolds stress like term, which can be classified as pseudo turbulence in this case. We have computed this ``Reynolds stress'' term along with individual fluctuations and the turbulent kinetic energy. Average pressure was also computed to characterize the strength of the transmitted and the reflected waves. This work was supported by the U.S. Department of Energy, National Nuclear Security Administration, Advanced Simulation and Computing Program, as a Cooperative Agreement under the Predictive Science Academic Alliance Program.

Study in Parkinson Disease of Exercise (SPARX): Translating high-intensity exercise from animals to humans

PubMed Central

Moore, Charity G.; Schenkman, Margaret; Kohrt, Wendy M.; Delitto, Anthony; Hall, Deborah A.; Corcos, Daniel

2013-01-01

A burgeoning literature suggests that exercise has a therapeutic benefit in persons with Parkinson disease (PD) and in animal models of PD, especially when animals exercise at high intensity. If exercise is to be prescribed as “first-line” or “add-on” therapy in patients with PD, we must demonstrate its efficacy and dose-response effects through testing phases similar to those used in the testing of pharmacologic agents. The SPARX Trial is a multicenter, randomized, controlled, single-blinded, Phase II study that we designed to test the feasibility of using high-intensity exercise to modify symptoms of PD and to simultaneously test the nonfutility of achieving a prespecified change in patients’ motor scores on the Unified Parkinson Disease Rating Scale (UPDRS). The trial began in May 2102 and is in the process of screening, enrolling, and randomly assigning 126 patients with early-stage PD to 1 of 3 groups: usual care (wait-listed controls), moderate-intensity exercise (4 days/week at 60%–65% maximal heart rate [HRmax]), or high-intensity exercise (4 days/week at 80%–85% HRmax). At 6-month follow-up, the trial is randomly reassigning usual care participants to a moderate-intensity or high-intensity exercise group for the remaining 6 months. The goals of the Phase II trial are to determine if participants can exercise at moderate and high intensities; to determine if either exercise yields benefits consistent with meaningful clinical change (nonfutility); and to document safety and attrition. The advantage of using a non-futility approach allows us to efficiently determine if moderate- or high-intensity exercise warrants further large-scale investigation in PD. PMID:23770108

Protocol and recruitment results from a randomized controlled trial comparing group phone-based versus newsletter interventions for weight loss maintenance among rural breast cancer survivors.

PubMed

Befort, Christie A; Klemp, Jennifer R; Fabian, Carol; Perri, Michael G; Sullivan, Debra K; Schmitz, Kathryn H; Diaz, Francisco J; Shireman, Theresa

2014-03-01

Obesity is a risk factor for breast cancer recurrence and death. Women who reside in rural areas have higher obesity prevalence and suffer from breast cancer treatment-related disparities compared to urban women. The objective of this 5-year randomized controlled trial is to compare methods for delivering extended care for weight loss maintenance among rural breast cancer survivors. Group phone-based counseling via conference calls addresses access barriers, is more cost-effective than individual phone counseling, and provides group support which may be ideal for rural breast cancer survivors who are more likely to have unmet support needs. Women (n=210) diagnosed with Stage 0 to III breast cancer in the past 10 years who are ≥ 3 months out from initial cancer treatments, have a BMI 27-45 kg/m(2), and have physician clearance were enrolled from multiple cancer centers. During Phase I (months 0 to 6), all women receive a behavioral weight loss intervention delivered through group phone sessions. Women who successfully lose 5% of weight enter Phase II (months 6 to 18) and are randomized to one of two extended care arms: continued group phone-based treatment or a mail-based newsletter. During Phase III, no contact is made (months 18 to 24). The primary outcome is weight loss maintenance from 6 to 18 months. Secondary outcomes include quality of life, serum biomarkers, and cost-effectiveness. This study will provide essential information on how to reach rural survivors in future efforts to establish weight loss support for breast cancer survivors as a standard of care. Copyright © 2014 Elsevier Inc. All rights reserved.

Supplemental nicotine preloading for smoking cessation in posttraumatic stress disorder: Results from a randomized controlled trial

PubMed Central

Dennis, Paul A.; Kimbrel, Nathan A.; Dedert, Eric A.; Beckham, Jean C.; Dennis, Michelle F.; Calhoun, Patrick S.

2016-01-01

Background Individuals with posttraumatic stress disorder (PTSD) are more likely to smoke and more likely to relapse following a quit attempt than individuals without PTSD. Thus, there is a significant need to study promising interventions that might improve quit rates for smokers with PTSD. One such intervention, supplemental nicotine patch-preloading, entails the use of nicotine replacement therapy prior to quitting. Objective The objective of this study was to conduct a randomized controlled trial of the efficacy of supplemental nicotine patch-preloading among smokers with PTSD. We hypothesized that, relative to participants in the placebo condition, participants in the nicotine patch-preloading condition would: (1) smoke less and experience reduced craving for cigarettes during the nicotine patch-preloading phase; (2) experience less smoking-associated relief from PTSD symptoms and negative affect during the preloading phase; and (3) exhibit greater latency to lapse, and higher short- and long-term abstinence rates. Methods Sixty-three smokers with PTSD were randomized to either nicotine or placebo patch for three weeks prior to their quit date. Ecological momentary assessment was used to assess craving, smoking, PTSD symptoms, and negative affect during the preloading period. Results Nicotine patch-preloading failed to reduce smoking or craving during the preloading phase, nor was it associated with less smoking-associated relief from PTSD symptoms and negative affect. Moreover, no differences were observed between the treatment conditions for time to lapse, 6-week abstinence, or 6-month abstinence. Conclusions The findings from the present research suggest that supplemental nicotine patch-preloading is unlikely to substantially enhance quit rates among smokers with PTSD. PMID:27046670

Phase II double-blind placebo-controlled randomized study of armodafinil for brain radiation-induced fatigue

PubMed Central

Page, Brandi R.; Shaw, Edward G.; Lu, Lingyi; Bryant, David; Grisell, David; Lesser, Glenn J.; Monitto, Drew C.; Naughton, Michelle J.; Rapp, Stephen R.; Savona, Steven R.; Shah, Sunjay; Case, Doug; Chan, Michael D.

2015-01-01

Background Common acute-term side effects of brain radiotherapy (RT) include fatigue, drowsiness, decreased physical functioning, and decreased quality of life (QOL). We hypothesized that armodafinil (a wakefulness-promoting drug known to reduce fatigue and increase cognitive function in breast cancer patients receiving chemotherapy) would result in reduced fatigue and sleepiness for patients receiving brain RT. Methods A phase II, multi-institutional, placebo-controlled randomized trial assessed feasibility of armodafinil 150 mg/day in participants receiving brain RT, from whom we obtained estimates of variability for fatigue, sleepiness, QOL, cognitive function, and treatment effect. Results From September 20, 2010, to October 20, 2012, 54 participants enrolled with 80% retention and 94% self-reported compliance. There were no grade 4–5 toxicities, and the incidence of grade 2–3 toxicities was similar between treatment arms, the most common of which were anxiety and nausea (15%), headaches (19%), and insomnia (20%). There were no statistically significant differences in end-RT or 4 week post-RT outcomes between armodafinil and placebo in any outcomes (Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue, Brief Fatigue Inventory, Epworth Sleepiness Scale, FACT-Brain, and FACIT-cognitive function). However, in participants with more baseline fatigue, those treated with armodafinil did better than those who received the placebo on the end-RT assessments for several outcomes. Conclusion Armodafinil 150 mg/day was well tolerated in primary brain tumor patients undergoing RT with good compliance. While there was no overall significant effect on fatigue, those with greater baseline fatigue experienced improved QOL and reduced fatigue when using armodafinil. These data suggest that a prospective, phase III randomized trial is warranted for patients with greater baseline fatigue. PMID:25972454

Trial design and rationale for APOLLO, a Phase 3, placebo-controlled study of patisiran in patients with hereditary ATTR amyloidosis with polyneuropathy.

PubMed

Adams, David; Suhr, Ole B; Dyck, Peter J; Litchy, William J; Leahy, Raina G; Chen, Jihong; Gollob, Jared; Coelho, Teresa

2017-09-11

Patisiran is an investigational RNA interference (RNAi) therapeutic in development for the treatment of hereditary ATTR (hATTR) amyloidosis, a progressive disease associated with significant disability, morbidity, and mortality. Here we describe the rationale and design of the Phase 3 APOLLO study, a randomized, double-blind, placebo-controlled, global study to evaluate the efficacy and safety of patisiran in patients with hATTR amyloidosis with polyneuropathy. Eligible patients are 18-85 years old with hATTR amyloidosis, investigator-estimated survival of ≥2 years, Neuropathy Impairment Score (NIS) of 5-130, and polyneuropathy disability score ≤IIIb. Patients are randomized 2:1 to receive either intravenous patisiran 0.3 mg/kg or placebo once every 3 weeks. The primary objective is to determine the efficacy of patisiran at 18 months based on the difference in the change in modified NIS+7 (a composite measure of motor strength, sensation, reflexes, nerve conduction, and autonomic function) between the patisiran and placebo groups. Secondary objectives are to evaluate the effect of patisiran on Norfolk-Diabetic Neuropathy quality of life questionnaire score, nutritional status (as evaluated by modified body mass index), motor function (as measured by NIS-weakness and timed 10-m walk test), and autonomic symptoms (as measured by the Composite Autonomic Symptom Score-31 questionnaire). Exploratory objectives include assessment of cardiac function and pathologic evaluation to assess nerve fiber innervation and amyloid burden. Safety of patisiran will be assessed throughout the study. APOLLO represents the largest randomized, Phase 3 study to date in patients with hATTR amyloidosis, with endpoints that capture the multisystemic nature of this disease. This trial is registered at clinicaltrials.gov ( NCT01960348 ); October 9, 2013.

WR279,396, a Third Generation Aminoglycoside Ointment for the Treatment of Leishmania major Cutaneous Leishmaniasis: A Phase 2, Randomized, Double Blind, Placebo Controlled Study

PubMed Central

Morizot, Gloria; Ben Massoud, Nathalie; Zâatour, Amor; Ben Alaya, Nissaf; Haj Hamida, Nabil Bel; Ahmadi, Zaher El; Downs, Matthew T.; Smith, Philip L.; Dellagi, Koussay; Grögl, Max

2009-01-01

Background Cutaneous leishmaniasis (CL) is a disfiguring disease that confronts clinicians with a quandary: leave patients untreated or engage in a complex or toxic treatment. Topical treatment of CL offers a practical and safe option. Accordingly, the treatment of CL with WR279,396, a formulation of paromomycin and gentamicin in a hydrophilic base, was investigated in a phase 2 clinical study in Tunisia and France. Methods A phase 2, randomized, double blind, vehicle-controlled study was conducted to assess the safety and efficacy of topical WR279,396 when applied twice a day for 20 days as treatment for parasitologically confirmed CL. The study protocol established the primary efficacy end point as complete clinical response (CCR) defined as 50% or greater reduction in the ulceration size of an index lesion by day 50 (D50) followed by complete re-epithelialization by D100, and no relapse through D180. Results Ninety-two subjects were randomized. Leishmania major was identified in 66 of 68 isolates typed (97%). In the intent-to-treat population, 47 of 50 WR279,396 treated participants (94%) met the definition of CCR, compared with 30 of 42 vehicle-placebo participants (71%) [p = 0.0045]. Erythema occurred in 30% and 24% of participants receiving WR279,396 and placebo, respectively [p = 0.64]. There was no clinical or laboratory evidence of systemic toxicity. Conclusion Application of WR279,396 for 20 days was found to be safe and effective in treating L. major CL, and offers great potential as a new, simple, easily applicable, and inexpensive topical therapy for this neglected disease. Trial Registration ClinicalTrials.gov NCT00703924 PMID:19415122

Testing the Model: A Phase 1/11 Randomized Double Blind Placebo Control Trial of Targeted Therapeutics: Liposomal Glutathione and Curcumin

DTIC Science & Technology

2016-10-01

Can non- specific cellular immunity protect HIV-infected persons with very low CD4 counts? Presented at Conference on Integrating Psychology and...Under Review. 50. Nierenberg B, Cooper S, Feuer SJ, Broderick G. Applying Network Medicine to Chronic Illness: A Model for Integrating Psychology ...function in these subjects as compared to GW era sedentary healthy controls. We applied an integrative systems- based approach rooted in computational

Testing the Model: A Phase 1/11 Randomized Double Blind Placebo Control Trial of Targeted Therapeutics: Liposomal Glutathione and Curcumin

DTIC Science & Technology

2017-10-01

HIV-infected persons with very low CD4 counts? Presented at Conference on Integrating Psychology and Medicine, Waheki Island, Auckland, NZ, 10-12th...SJ, Broderick G. Applying Network Medicine to Chronic Illness: A Model for Integrating Psychology into Routine Care. Amer Psych, 2015. Under review...function in these subjects as compared to GW era sedentary healthy controls. We applied an integrative systems- based approach rooted in

Effects of music therapy on labour pain and anxiety in Taiwanese first-time mothers.

PubMed

Liu, Yu-Hsiang; Chang, Mei-Yueh; Chen, Chung-Hey

2010-04-01

The purpose of the study was to investigate the effects of music on pain reaction and anxiety during labour. Music therapy has been used on clinical medicine. Only few scientific studies validate the value on labour women. Randomised controlled trial. Sixty primiparas expected to have a normal spontaneous delivery were randomly assigned to either the experimental group (n = 30) or the control group (n = 30). The experimental group received routine care and music therapy, whereas the control group received routine care only. A self-report visual analogue scale for pain and a nurse-rated present behavioural intensity were used to measure labour pain. Anxiety was measured with a visual analogue scale for anxiety and finger temperature. Pain and anxiety between groups were compared during the latent phase (2-4 cm cervical dilation) and active phase (5-7 cm) separately. Our results revealed that compared with the control group, the experimental group had significantly lower pain, anxiety and a higher finger temperature during the latent phase of labour. However, no significant differences were found between the two groups on all outcome measures during the active phase. This study provides evidence for the use of music as an empirically based intervention of women for labour pain and anxiety during the latent phase of labour. The findings support that music listening is an acceptable and non-medical coping strategy for labouring women. Especially, apply in reducing the pain and anxiety for women who are at the early phase of labour.

Effects of Relaxing Music on Mental Fatigue Induced by a Continuous Performance Task: Behavioral and ERPs Evidence.

PubMed

Guo, Wei; Ren, Jie; Wang, Biye; Zhu, Qin

2015-01-01

The purpose of this study was to investigate whether listening to relaxing music would help reduce mental fatigue and to maintain performance after a continuous performance task. The experiment involved two fatigue evaluation phases carried out before and after a fatigue inducing phase. A 1-hour AX-continuous performance test was used to induce mental fatigue in the fatigue-inducing phase, and participants' subjective evaluation on the mental fatigue, as well as their neurobehavioral performance in a Go/NoGo task, were measured before and after the fatigue-inducing phase. A total of 36 undergraduate students (18-22 years) participated in the study and were randomly assigned to the music group and control group. The music group performed the fatigue-inducing task while listening to relaxing music, and the control group performed the same task without any music. Our results revealed that after the fatigue-inducing phase, (a) the music group demonstrated significantly less mental fatigue than control group, (b) reaction time significantly increased for the control group but not for the music group, (c) larger Go-P3 and NoGo-P3 amplitudes were observed in the music group, although larger NoGo-N2 amplitudes were detected for both groups. These results combined to suggest that listening to relaxing music alleviated the mental fatigue associated with performing an enduring cognitive-motor task.

Clinical feasibility of the Nintendo Wii™ for balance training post-stroke: a phase II randomized controlled trial in an inpatient setting.

PubMed

Bower, Kelly J; Clark, Ross A; McGinley, Jennifer L; Martin, Clarissa L; Miller, Kimberly J

2014-09-01

To investigate the feasibility and potential efficacy of the Nintendo Wii™ for balance rehabilitation after stroke. Phase II, single-blind, randomized controlled trial. Inpatient rehabilitation facility. Thirty adults (mean age 63.6 (14.7) years) undergoing inpatient rehabilitation who were less than three months post-stroke and able to stand unsupported. Participants were allocated to a Balance Group, using the 'Wii Fit Plus' in standing, or Upper Limb Group, using the 'Wii Sports/Sports Resort' in sitting. Both groups undertook three 45 minute sessions per week over two to four weeks in addition to standard care. The primary focus was feasibility, addressed by recruitment, retention, adherence, acceptability and safety. Efficacy was evaluated by balance, mobility and upper limb outcomes. Twenty-one percent of individuals screened were recruited and 86% (n = 30) of eligible people agreed to participate. Study retention and session adherence was 90% and > 99%, respectively, at two weeks; dropping to 70% and 87% at four weeks due to early discharge. All participants reported enjoying the sessions and most felt they were beneficial. No major adverse events occurred. Wii use by the Balance Group was associated with trends for improved balance, with significantly greater improvement in outcomes including the Step Test and Wii Balance Board-derived centre of pressure scores. The Upper Limb Group had larger, non-significant changes in arm function. A Wii-based approach appears feasible and promising for post-stroke balance rehabilitation. A larger randomized controlled trial is recommended to further investigate efficacy. © The Author(s) 2014.

Automatic alternative phase-shift mask CAD layout tool for gate shrinkage of embedded DRAM in logic below 0.18 μm

NASA Astrophysics Data System (ADS)

Ohnuma, Hidetoshi; Kawahira, Hiroichi

1998-09-01

An automatic alternative phase shift mask (PSM) pattern layout tool has been newly developed. This tool is dedicated for embedded DRAM in logic device to shrink gate line width with improving line width controllability in lithography process with a design rule below 0.18 micrometers by the KrF excimer laser exposure. The tool can crete Levenson type PSM used being coupled with a binary mask adopting a double exposure method for positive photo resist. By using graphs, this tool automatically creates alternative PSM patterns. Moreover, it does not give any phase conflicts. By adopting it to actual embedded DRAM in logic cells, we have provided 0.16 micrometers gate resist patterns at both random logic and DRAM areas. The patterns were fabricated using two masks with the double exposure method. Gate line width has been well controlled under a practical exposure-focus window.

Quasi-experimental designs in practice-based research settings: design and implementation considerations.

PubMed

Handley, Margaret A; Schillinger, Dean; Shiboski, Stephen

2011-01-01

Although randomized controlled trials are often a gold standard for determining intervention effects, in the area of practice-based research (PBR), there are many situations in which individual randomization is not possible. Alternative approaches to evaluating interventions have received increased attention, particularly those that can retain elements of randomization such that they can be considered "controlled" trials. Methodological design elements and practical implementation considerations for two quasi-experimental design approaches that have considerable promise in PBR settings--the stepped-wedge design, and a variant of this design, a wait-list cross-over design, are presented along with a case study from a recent PBR intervention for patients with diabetes. PBR-relevant design features include: creation of a cohort over time that collects control data but allows all participants (clusters or patients) to receive the intervention; staggered introduction of clusters; multiple data collection points; and one-way cross-over into the intervention arm. Practical considerations include: randomization versus stratification, training run in phases; and extended time period for overall study completion. Several design features of practice based research studies can be adapted to local circumstances yet retain elements to improve methodological rigor. Studies that utilize these methods, such as the stepped-wedge design and the wait-list cross-over design, can increase the evidence base for controlled studies conducted within the complex environment of PBR.

Optical information authentication using compressed double-random-phase-encoded images and quick-response codes.

PubMed

Wang, Xiaogang; Chen, Wen; Chen, Xudong

2015-03-09

In this paper, we develop a new optical information authentication system based on compressed double-random-phase-encoded images and quick-response (QR) codes, where the parameters of optical lightwave are used as keys for optical decryption and the QR code is a key for verification. An input image attached with QR code is first optically encoded in a simplified double random phase encoding (DRPE) scheme without using interferometric setup. From the single encoded intensity pattern recorded by a CCD camera, a compressed double-random-phase-encoded image, i.e., the sparse phase distribution used for optical decryption, is generated by using an iterative phase retrieval technique with QR code. We compare this technique to the other two methods proposed in literature, i.e., Fresnel domain information authentication based on the classical DRPE with holographic technique and information authentication based on DRPE and phase retrieval algorithm. Simulation results show that QR codes are effective on improving the security and data sparsity of optical information encryption and authentication system.

Efficacy of Healing meditation in reducing anxiety of individuals at the phase of weight loss maintenance: A randomized blinded clinical trial.

PubMed

Sampaio, Cynthia Vieira Sanches; Lima, Manuela Garcia; Ladeia, Ana Marice

2016-12-01

To verify the efficacy of Healing Meditation in reducing anxiety levels in individuals on a weight loss maintenance program. A randomized, controlled, evaluator-blinded clinical trial, conducted between January and October 2014, with a follow-up of 12 weeks. A weight loss secondary care facility in Salvador, Brazil., of 41 patients at the weight maintenance phase (Mean initial BMI 33.6±4.7kg/m 2 , who had attained a mean BMI of 24.5±1.6kg/m 2 in a median period of 7 months). An 8-week Healing Meditation program (n=20), consisting of a 1h weekly meeting, or for a control group on the waiting list (n=21), in addition to the standard clinical program. Total anxiety was measured by the Hamilton Anxiety Scale (HAM-A), before and after the intervention. Secondary analyses included comparison of the effect of meditation on the somatic and psychic components of the scale. Through an intention to treat analysis, we detected a difference in the mean variation between the intervention and control groups in the total anxiety scores of 7.7 (95% CI 6.3-9.2; Cohen's d=3.41). Means and standard deviations for pre and post intervention anxiety scores were 15.5 (3.4) and 7.8 (2.0) for the intervention group and 14.8 (3.4) and 14.9 (3.4) for the control. Healing meditation significantly reduced the anxiety of obese individuals, in the phase of weight maintenance, suggesting this to be an effective auxiliary resource for weight loss maintenance. Copyright © 2016 Elsevier Ltd. All rights reserved.

Efficacy and safety of rolapitant for prevention of chemotherapy-induced nausea and vomiting over multiple cycles of moderately or highly emetogenic chemotherapy.

PubMed

Rapoport, Bernardo; Schwartzberg, Lee; Chasen, Martin; Powers, Dan; Arora, Sujata; Navari, Rudolph; Schnadig, Ian

2016-04-01

Rolapitant, a novel neurokinin-1 receptor antagonist (RA), was shown to protect against delayed chemotherapy-induced nausea and vomiting (CINV) during the first cycle of moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC) in randomized, double-blind trials. This analysis explored the efficacy and safety of rolapitant in preventing CINV over multiple cycles of MEC or HEC. Patients in one phase III MEC, one phase II HEC, and two phase III HEC clinical trials were randomized to receive oral rolapitant (180 mg) or placebo in combination with a 5-hydroxytryptamine type 3 RA and dexamethasone. Regardless of response in cycle 1, patients could continue the same antiemetic treatment for up to six cycles. On days 6-8 of each subsequent chemotherapy cycle, patients reported the incidence of emesis and/or nausea interfering with normal daily life. Post hoc analyses of pooled safety and efficacy data from the four trials were performed for cycles 2-6. Significantly more patients receiving rolapitant than control reported no emesis or interfering nausea (combined measure) in cycles 2 (p = 0.006), 3 (p < 0.001), 4 (p = 0.001), and 5 (p = 0.021). Over cycles 1-6, time-to-first emesis was significantly longer with rolapitant than with control (p < 0.001). The incidence of treatment-related adverse events during cycles 2-6 was similar in rolapitant (5.5%) and control (6.8%) arms. No cumulative toxicity was observed. Over multiple cycles of MEC or HEC, rolapitant provided superior CINV protection and reduced emesis and nausea interfering with daily life compared with control and remained well tolerated. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

The effects of the dopamine agonist rotigotine on hemispatial neglect following stroke.

PubMed

Gorgoraptis, Nikos; Mah, Yee-Haur; Machner, Bjoern; Singh-Curry, Victoria; Malhotra, Paresh; Hadji-Michael, Maria; Cohen, David; Simister, Robert; Nair, Ajoy; Kulinskaya, Elena; Ward, Nick; Greenwood, Richard; Husain, Masud

2012-08-01

Hemispatial neglect following right-hemisphere stroke is a common and disabling disorder, for which there is currently no effective pharmacological treatment. Dopamine agonists have been shown to play a role in selective attention and working memory, two core cognitive components of neglect. Here, we investigated whether the dopamine agonist rotigotine would have a beneficial effect on hemispatial neglect in stroke patients. A double-blind, randomized, placebo-controlled ABA design was used, in which each patient was assessed for 20 testing sessions, in three phases: pretreatment (Phase A1), on transdermal rotigotine for 7-11 days (Phase B) and post-treatment (Phase A2), with the exact duration of each phase randomized within limits. Outcome measures included performance on cancellation (visual search), line bisection, visual working memory, selective attention and sustained attention tasks, as well as measures of motor control. Sixteen right-hemisphere stroke patients were recruited, all of whom completed the trial. Performance on the Mesulam shape cancellation task improved significantly while on rotigotine, with the number of targets found on the left side increasing by 12.8% (P = 0.012) on treatment and spatial bias reducing by 8.1% (P = 0.016). This improvement in visual search was associated with an enhancement in selective attention but not on our measures of working memory or sustained attention. The positive effect of rotigotine on visual search was not associated with the degree of preservation of prefrontal cortex and occurred even in patients with significant prefrontal involvement. Rotigotine was not associated with any significant improvement in motor performance. This proof-of-concept study suggests a beneficial role of dopaminergic modulation on visual search and selective attention in patients with hemispatial neglect following stroke.

The effects of the dopamine agonist rotigotine on hemispatial neglect following stroke

PubMed Central

Gorgoraptis, Nikos; Mah, Yee-Haur; Machner, Bjoern; Singh-Curry, Victoria; Malhotra, Paresh; Hadji-Michael, Maria; Cohen, David; Simister, Robert; Nair, Ajoy; Kulinskaya, Elena; Ward, Nick; Greenwood, Richard

2012-01-01

Hemispatial neglect following right-hemisphere stroke is a common and disabling disorder, for which there is currently no effective pharmacological treatment. Dopamine agonists have been shown to play a role in selective attention and working memory, two core cognitive components of neglect. Here, we investigated whether the dopamine agonist rotigotine would have a beneficial effect on hemispatial neglect in stroke patients. A double-blind, randomized, placebo-controlled ABA design was used, in which each patient was assessed for 20 testing sessions, in three phases: pretreatment (Phase A1), on transdermal rotigotine for 7–11 days (Phase B) and post-treatment (Phase A2), with the exact duration of each phase randomized within limits. Outcome measures included performance on cancellation (visual search), line bisection, visual working memory, selective attention and sustained attention tasks, as well as measures of motor control. Sixteen right-hemisphere stroke patients were recruited, all of whom completed the trial. Performance on the Mesulam shape cancellation task improved significantly while on rotigotine, with the number of targets found on the left side increasing by 12.8% (P = 0.012) on treatment and spatial bias reducing by 8.1% (P = 0.016). This improvement in visual search was associated with an enhancement in selective attention but not on our measures of working memory or sustained attention. The positive effect of rotigotine on visual search was not associated with the degree of preservation of prefrontal cortex and occurred even in patients with significant prefrontal involvement. Rotigotine was not associated with any significant improvement in motor performance. This proof-of-concept study suggests a beneficial role of dopaminergic modulation on visual search and selective attention in patients with hemispatial neglect following stroke. PMID:22761293

Analysis and experimental demonstration of conformal adaptive phase-locked fiber array for laser communications and beam projection applications

NASA Astrophysics Data System (ADS)

Liu, Ling

The primary goal of this research is the analysis, development, and experimental demonstration of an adaptive phase-locked fiber array system for free-space optical communications and laser beam projection applications. To our knowledge, the developed adaptive phase-locked system composed of three fiber collimators (subapertures) with tip-tilt wavefront phase control at each subaperture represents the first reported fiber array system that implements both phase-locking control and adaptive wavefront tip-tilt control capabilities. This research has also resulted in the following innovations: (a) The first experimental demonstration of a phase-locked fiber array with tip-tilt wave-front aberration compensation at each fiber collimator; (b) Development and demonstration of the fastest currently reported stochastic parallel gradient descent (SPGD) system capable of operation at 180,000 iterations per second; (c) The first experimental demonstration of a laser communication link based on a phase-locked fiber array; (d) The first successful experimental demonstration of turbulence and jitter-induced phase distortion compensation in a phase-locked fiber array optical system; (e) The first demonstration of laser beam projection onto an extended target with a randomly rough surface using a conformal adaptive fiber array system. Fiber array optical systems, the subject of this study, can overcome some of the draw-backs of conventional monolithic large-aperture transmitter/receiver optical systems that are usually heavy, bulky, and expensive. The primary experimental challenges in the development of the adaptive phased-locked fiber-array included precise (<5 microrad) alignment of the fiber collimators and development of fast (100kHz-class) phase-locking and wavefront tip-tilt control systems. The precise alignment of the fiber collimator array is achieved through a specially developed initial coarse alignment tool based on high precision piezoelectric picomotors and a dynamic fine alignment mechanism implemented with specially designed and manufactured piezoelectric fiber positioners. Phase-locking of the fiber collimators is performed by controlling the phases of the output beams (beamlets) using integrated polarization-maintaining (PM) fiber-coupled LiNbO3 phase shifters. The developed phase-locking controllers are based on either the SPGD algorithm or the multi-dithering technique. Subaperture wavefront phase tip-tilt control is realized using piezoelectric fiber positioners that are controlled using a computer-based SPGD controller. Both coherent (phase-locked) and incoherent beam combining in the fiber array system are analyzed theoretically and experimentally. Two special fiber-based beam-combining testbeds have been built to demonstrate the technical feasibility of phase-locking compensation prior to free-space operation. In addition, the reciprocity of counter-propagating beams in a phase-locked fiber array system has been investigated. Coherent beam combining in a phase-locking system with wavefront phase tip-tilt compensation at each subaperture is successfully demonstrated when laboratory-simulated turbulence and wavefront jitters are present in the propagation path of the beamlets. In addition, coherent beam combining with a non-cooperative extended target in the control loop is successfully demonstrated.

[Vitex agnus castus extract in the treatment of luteal phase defects due to latent hyperprolactinemia. Results of a randomized placebo-controlled double-blind study].

PubMed

Milewicz, A; Gejdel, E; Sworen, H; Sienkiewicz, K; Jedrzejak, J; Teucher, T; Schmitz, H

1993-07-01

The efficacy of a Vitex agnus castus preparation (Strotan capsules) was investigated in a randomized double blind study vs. placebo. This clinical study involved 52 women with luteal phase defects due to latent hyperprolactinaemia. The daily dose was one capsule (20 mg) Vitex agnus castus preparation and placebo, respectively. Aim of the study was to prove whether the elevated pituitary prolactin reserve can be reduced and deficits in luteal phase length and luteal phase progesterone synthesis be normalized. Blood for hormonal analysis was taken at days 5-8 and day 20 of the menstrual cycle before and after three month of therapy. Latent hyperprolactinaemia was analysed by monitoring the prolactin release 15 and 30 min after i.v. injection of 200 micrograms TRH. 37 complete case reports (placebo: n = 20, verum: n = 17) after 3 month of therapy were statistically evaluated. The prolactin release was reduced after 3 months, shortened luteal phases were normalised and deficits in the luteal progesterone synthesis were eliminated. These changes were significant and occurred only in the verum group. All other hormonal parameters did not change with the exception of 17 beta-estradiol which rouse up in the luteal phase in patients receiving verum. Side effects were not seen, two women treated with the Vitex agnus castus preparation got pregnant. The tested preparation is thought to be an efficient medication in the treatment of luteal phase defects due to latent hyperprolactinaemia.

Design of bifunctional metasurface based on independent control of transmission and reflection.

PubMed

Zhuang, Yaqiang; Wang, Guangming; Cai, Tong; Zhang, Qingfeng

2018-02-05

Multifunctional metasurface integrating different functions can significantly save the occupied space, although most of bifunctional metasurfaces reported to date only control the wave in either reflection or transmission regime. In this paper, we propose a scheme that allows one to independently control the reflection and transmission wavefront under orthogonal polarizations. For demonstration, we design a bifunctional metasurface that simultaneously realizes a diffusion reflection and a focusing transmission. The diffusion reflection is realized using a random phase distribution, which was implemented by randomly arranging two basic coding unit cells with the aid of an ergodic algorithm. Meanwhile, the hyperbolic phase distribution was designed to realize the focusing functionality in the transmission regime. To further show the potential applications, a high-gain lens antenna was designed by assembling the proposed metasurface with a proper feed. Both simulation and measurement results have been carried out, and the agreement between the two results demonstrates the validity of the performance as expected. The backward scattering can be reduced more than 5 dB within 6.4-10 GHz compared with the metallic plate. Moreover, the lens antenna has a gain of 20 dB (with around 13 dB enhancement in comparison with the bare feeding antenna) and an efficiency of 32.5%.

Role of phase synchronisation in turbulence

NASA Astrophysics Data System (ADS)

Moradi, Sara; Teaca, Bogdan; Anderson, Johan

2017-11-01

The role of the phase dynamics in turbulence is investigated. As a demonstration of the importance of the phase dynamics, a simplified system is used, namely the one-dimensional Burgers equation, which is evolved numerically. The system is forced via a known external force, with two components that are added into the evolution equations of the amplitudes and the phase of the Fourier modes, separately. In this way, we are able to control the impact of the force on the dynamics of the phases. In the absence of the direct forcing in the phase equation, it is observed that the phases are not stochastic as assumed in the Random Phase Approximation (RPA) models, and in contrast, the non-linear couplings result in intermittent locking of the phases to ± π/2. The impact of the force, applied purely on the phases, is to increase the occurrence of the phase locking events in which the phases of the modes in a wide k range are now locked to ± π/2, leading to a change in the dynamics of both phases and amplitudes, with a significant localization of the real space flow structures.

Directed Self-Assembly of Liquid Crystalline Blue-Phases into Ideal Single-Crystals

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

Martinez-Gonzalez, Jose A.; Li, Xiao; Sadati, Monirosadat

Chiral nematic liquid crystals are known to form blue phases—liquid states of matter that exhibit ordered cubic arrangements of topological defects. Blue-phase specimens, however, are generally polycrystalline, consisting of randomly oriented domains that limit their performance in applications. A strategy that relies on nano-patterned substrates is presented here for preparation of stable, macroscopic single-crystal blue-phase materials. Different template designs are conceived to exert control over different planes of the blue-phase lattice orientation with respect to the underlying substrate. Experiments are then used to demonstrate that it is indeed possible to create stable single-crystal blue-phase domains with the desired orientation overmore » large regions. Lastly, these results provide a potential avenue to fully exploit the electro-optical properties of blue phases, which have been hindered by the existence of grain boundaries.« less

Control of the orientation and photoinduced phase transitions of macrocyclic azobenzene.

PubMed

Uchida, Emi; Sakaki, Kouji; Nakamura, Yumiko; Azumi, Reiko; Hirai, Yuki; Akiyama, Haruhisa; Yoshida, Masaru; Norikane, Yasuo

2013-12-16

Photoinduced phase transitions caused by photochromic reactions bring about a change in the state of matter at constant temperature. Herein, we report the photoinduced phase transitions of crystals of a photoresponsive macrocyclic compound bearing two azobenzene groups (1) at room temperature on irradiation with UV (365 nm) and visible (436 nm) light. The trans/trans isomer undergoes photoinduced phase transitions (crystal-isotropic phase-crystal) on UV light irradiation. The photochemically generated crystal exhibited reversible phase transitions between the crystal and the mesophase on UV and visible light irradiation. The molecular order of the randomly oriented crystals could be increased by irradiating with linearly polarized visible light, and the value of the order parameter was determined to be -0.84. Heating enhances the thermal cis-to-trans isomerization and subsequent cooling returned crystals of the trans/trans isomer. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Directed Self-Assembly of Liquid Crystalline Blue-Phases into Ideal Single-Crystals

DOE PAGES

Martinez-Gonzalez, Jose A.; Li, Xiao; Sadati, Monirosadat; ...

2017-06-16

Chiral nematic liquid crystals are known to form blue phases—liquid states of matter that exhibit ordered cubic arrangements of topological defects. Blue-phase specimens, however, are generally polycrystalline, consisting of randomly oriented domains that limit their performance in applications. A strategy that relies on nano-patterned substrates is presented here for preparation of stable, macroscopic single-crystal blue-phase materials. Different template designs are conceived to exert control over different planes of the blue-phase lattice orientation with respect to the underlying substrate. Experiments are then used to demonstrate that it is indeed possible to create stable single-crystal blue-phase domains with the desired orientation overmore » large regions. Lastly, these results provide a potential avenue to fully exploit the electro-optical properties of blue phases, which have been hindered by the existence of grain boundaries.« less

Recognizing and managing a deteriorating patient: a randomized controlled trial investigating the effectiveness of clinical simulation in improving clinical performance in undergraduate nursing students.

PubMed

Stayt, Louise Caroline; Merriman, Clair; Ricketts, Barry; Morton, Sean; Simpson, Trevor

2015-11-01

To report the results of a randomized controlled trial which explored the effectiveness of clinical simulation in improving the clinical performance of recognizing and managing an adult deteriorating patient in hospital. There is evidence that final year undergraduate nurses may lack knowledge, clinical skills and situation awareness required to manage a deteriorating patient competently. The effectiveness of clinical simulation as a strategy to teach the skills required to recognize and manage the early signs of deterioration needs to be evaluated. This study was a two centre phase II single, randomized, controlled trial with single blinded assessments. Data were collected in July 2013. Ninety-eight first year nursing students were randomized either into a control group, where they received a traditional lecture, or an intervention group where they received simulation. Participants completed a pre- and postintervention objective structured clinical examination. General Perceived Self Efficacy and Self-Reported Competency scores were measured before and after the intervention. Student satisfaction with teaching was also surveyed. The intervention group performed significantly better in the post-objective structured clinical examination. There was no significant difference in the postintervention General Perceived Self Efficacy and Self-Reported Competency scores between the control and intervention group. The intervention group was significantly more satisfied with their teaching method. Simulation-based education may be an effective educational strategy to teach nurses the skills to effectively recognize and manage a deteriorating patient. © 2015 John Wiley & Sons Ltd.

The hepatocyte phase of Gd-EOB-DTPA-enhanced MRI in the evaluation of hepatic fibrosis and early liver cirrhosis in a rat model: an experimental study.

PubMed

Ma, Chunmei; Liu, Ailian; Wang, Yuanyuan; Geng, Xiaoling; Hao, Li; Song, Qingwei; Sun, Bo; Wang, Heqing; Zhao, Gang

2014-07-17

To evaluate the hepatocyte phase of Gd-EOB-DTPA-enhanced MRI in the early diagnosis of hepatic fibrosis and cirrhosis and assessment of liver function in a rat model. In 2 groups of SD rats, liver fibrosis was induced in experimental animals by repetitive carbon tetrachloride injections, while the control group received saline injections. Five experimental rats and 2 control rats were randomly selected at weeks 4, 8, 12. One week after carbon tetrachloride administration, MRI (FIRM T1WI) scan was performed. Gd-EOB-DTPA (0.08mL) was injected into the rat's tail vein and hepatocyte phase images were obtained after 20min. The pre-enhanced phase and hepatocyte phase signal intensities (SI) were measured, and the relative contrast enhancement index (RCEI) was calculated. ANOVA analysis (LSD) of RCEI values in controls (n=6), hepatic fibrosis (n=7), and histopathologically-determined early cirrhosis group (n=6) was performed. RECI values showed a decreasing trend in the control group, hepatic fibrosis and early cirrhosis groups (1.11±0.43, 0.96±0.22, and 0.57±0.33, respectively). While the difference between the control and early cirrhosis groups was statistically significant (p=0.013), there was no significant difference in the hepatic fibrosis group vs the control (p=0.416) and the hepatic fibrosis group vs the early cirrhosis group (p=0.054). Hepatocyte phase RCEI values obtained with Gd-EOB-DTPA-enhanced MRI scan indicate liver injury in hepatic fibrosis and early cirrhosis. RCEI values are helpful for early diagnosis of liver cirrhosis. Copyright © 2014 Elsevier Inc. All rights reserved.

Efficacy and Safety of Immediate-Release Methylphenidate Treatment for Preschoolers with ADHD

ERIC Educational Resources Information Center

Greenhill, Laurence; Kollins, Scott; Abikoff, Howard; McCracken, James; Riddle, Mark; Swanson, James; McGough, James; Wigal, Sharon; Wigal, Tim; Vitiello, Benedetto; Skrobala, Anne; Posner, Kelly; Ghuman, Jaswinder; Cunningham, Charles; Davies, Mark; Chuang, Shirley; Cooper, Tom

2006-01-01

Objective: The Preschool ADHD Treatment Study (PATS) was a NIMH-funded, six-center, randomized, controlled trial to determine the efficacy and safety of immediate-release methylphenidate (MPH-IR), given t.i.d. to children ages 3 to 5.5 years with attention-deficit/hyperactivity disorder (ADHD). Method: The 8-phase, 70-week PATS protocol included…

Effect of Two Different Methods of Initiating Atomoxetine on the Adverse Event Profile of Atomoxetine

ERIC Educational Resources Information Center

Greenhill, Laurence L.; Newcorn, Jeffrey H.; Gao, Haitao; Feldman, Peter D.

2007-01-01

Objective: To compare the effects of two different methods for initiating atomoxetine in terms of the incidence of early adverse events. Method: Data on atomoxetine treatment-emergent adverse events in youths, ages 6 to 18 years, were analyzed from five randomized, double-blind, placebo-controlled, acute-phase studies. Two studies involve…

Threshold-based epidemic dynamics in systems with memory

NASA Astrophysics Data System (ADS)

Bodych, Marcin; Ganguly, Niloy; Krueger, Tyll; Mukherjee, Animesh; Siegmund-Schultze, Rainer; Sikdar, Sandipan

2016-11-01

In this article we analyze an epidemic dynamics model (SI) where we assume that there are k susceptible states, that is a node would require multiple (k) contacts before it gets infected. In specific, we provide a theoretical framework for studying diffusion rate in complete graphs and d-regular trees with extensions to dense random graphs. We observe that irrespective of the topology, the diffusion process could be divided into two distinct phases: i) the initial phase, where the diffusion process is slow, followed by ii) the residual phase where the diffusion rate increases manifold. In fact, the initial phase acts as an indicator for the total diffusion time in dense graphs. The most remarkable lesson from this investigation is that such a diffusion process could be controlled and even contained if acted upon within its initial phase.

Working With Parents to Prevent Childhood Obesity: Protocol for a Primary Care-Based eHealth Study

PubMed Central

Avis, Jillian LS; Cave, Andrew L; Donaldson, Stephanie; Ellendt, Carol; Holt, Nicholas L; Jelinski, Susan; Martz, Patricia; Maximova, Katerina; Padwal, Raj; Wild, T Cameron

2015-01-01

Background Parents play a central role in preventing childhood obesity. There is a need for innovative, scalable, and evidence-based interventions designed to enhance parents’ motivation to support and sustain healthy lifestyle behaviors in their children, which can facilitate obesity prevention. Objective (1) Develop an online screening, brief intervention, and referral to treatment (SBIRT) eHealth tool to enhance parents’ concern for, and motivation to, support children’s healthy lifestyle behaviors, (2) refine the SBIRT eHealth tool by assessing end-user acceptability, satisfaction, and usability through focus groups, and (3) determine feasibility and preliminary effectiveness of the refined SBIRT eHealth tool through a randomized controlled trial. Methods This is a three-phase, multi-method study that includes SBIRT eHealth tool development (Phase I), refinement (Phase II), and testing (Phase III). Phase I: Theoretical underpinnings of the SBIRT tool, entitled the Resource Information Program for Parents on Lifestyle and Education (RIPPLE), will be informed by concepts applied within existing interventions, and content will be based on literature regarding healthy lifestyle behaviors in children. The SBIRT platform will be developed in partnership between our research team and a third-party intervention development company. Phase II: Focus groups with parents, as well as health care professionals, researchers, and trainees in pediatrics (n=30), will explore intervention-related perceptions and preferences. Qualitative data from the focus groups will inform refinements to the aesthetics, content, structure, and function of the SBIRT. Phase III: Parents (n=200) of children—boys and girls, 5 to 17 years old—will be recruited from a primary care pediatric clinic while they await their children’s clinical appointment. Parents will be randomly assigned to one of five groups—four intervention groups and one control group—as they complete the SBIRT. The randomization function is built into the tool. Parents will complete the eHealth SBIRT using a tablet that will be connected to the Internet. Subsequently, parents will be contacted via email at 1-month follow-up to assess (1) change in concern for, and motivation to, support children’s dietary and physical activity behaviors (primary outcome), and (2) use of online resources and referrals to health services for obesity prevention (secondary outcome). Results This research was successfully funded and received ethics approval. Development of the SBIRT started in summer 2012, and we expect all study-related activities to be completed by fall 2016. Conclusions The proposed research is timely and applies a novel, technology-based application designed to enhance parents concern for, and motivation to, support children’s healthy lifestyle behaviors and encourage use of online resources and community services for childhood obesity prevention. Overall, this research builds on a foundation of evidence supporting the application of SBIRTs to encourage or “nudge” individuals to make healthy lifestyle choices. Findings from Phase III of this project will directly inform a cluster randomized controlled trial to study the effectiveness of our intervention across multiple primary care-based settings. Trial Registration ClinicalTrials.gov NCT02330588; http://clinicaltrials.gov/ct2/show/NCT02330588 (Archived by WebCite at http://www.webcitation.org/6WyUOeRlr). PMID:25831265

Detecting phase transitions in a neural network and its application to classification of syndromes in traditional Chinese medicine

NASA Astrophysics Data System (ADS)

Chen, J.; Xi, G.; Wang, W.

2008-02-01

Detecting phase transitions in neural networks (determined or random) presents a challenging subject for phase transitions play a key role in human brain activity. In this paper, we detect numerically phase transitions in two types of random neural network(RNN) under proper parameters.

Lifestyle intervention reduces body weight and improves cardiometabolic risk factors in worksites.

PubMed

Salinardi, Taylor C; Batra, Payal; Roberts, Susan B; Urban, Lorien E; Robinson, Lisa M; Pittas, Anastassios G; Lichtenstein, Alice H; Deckersbach, Thilo; Saltzman, Edward; Das, Sai Krupa

2013-04-01

Worksites are potentially effective locations for obesity control because they provide opportunities for group intervention and social support. Studies are needed to identify effective interventions in these settings. We examined the effects of a multicomponent lifestyle intervention on weight loss and prevention of regain in 4 worksites (2 intervention and 2 control sites). Overweight and obese employees (n = 133) enrolled in this pilot worksite-randomized controlled trial with a 0-6-mo weight-loss phase and a 6-12-mo structured weight-maintenance phase. The intervention combined recommendations to consume a reduced-energy, low-glycemic load, high-fiber diet with behavioral change education. Outcome measurements included changes in body weight and cardiometabolic risk factors. The mean ± SEM weight loss was substantial in intervention participants, whereas control subjects gained weight (-8.0 ± 0.7 compared with +0.9 ± 0.5 kg, respectively; P < 0.001), and 89% of participants completed the weight-loss phase. Intervention effects were not significant at the 0.05 level but would have been at the 0.10 level (P = 0.08) in a mixed model in which the worksite nested within group was a random factor. There were also significant improvements in cardiometabolic risk factors in intervention compared with control subjects regarding fasting total cholesterol, glucose, systolic blood pressure, and diastolic blood pressure (P ≤ 0.02 for each). No significant weight regain was observed in participants who enrolled in the structured weight-maintenance program (0.5 ± 0.7 kg; P = 0.65), and overweight and obese employees in intervention worksites who were not enrolled in the weight-loss program lost weight compared with subjects in control worksites (-1.3 ± 0.5 compared with +0.7 ± 0.2 kg, respectively; P = 0.02). Worksites can be effective for achieving clinically important reductions in body weight and improved cardiometabolic risk factors. This trial was registered at clinicaltrials.gov as NCT01470222.

Effect of Dance Labor on the Management of Active Phase Labor Pain & Clients’ Satisfaction: A Randomized Controlled Trial Study

PubMed Central

Abdolahian, Somayeh; Ghavi, Fatemeh; Abdollahifard, Sareh; Sheikhan, Fatemeh

2014-01-01

Background: There are a wide variety of non- pharmacologic pain relief techniques for labor which include pelvic movement, upright position, back massage and partner support during the first stage of labor. The effectiveness of dance labor- which is a combination of these techniques- has not been evaluated. Aim: This study aimed to evaluate the effectiveness of dance labor in pain reduction and woman’s satisfaction during the first stage of labor. Methods: 60 primiparous women aged 18-35 years old were randomly assigned to dance labor and control groups. In the dance labor group, women were instructed to do standing upright with pelvic tilt and rock their hips back and forth or around in a circle while their partner massaged their back and sacrum for a minimum of 30 minutes. In the control group, the participants received usual care during physiologic labor. Pain and satisfaction scores were measured by Visual Analogue Scale. Data were analyzed by using the t. test and Chi-square. Findings: Mean pain score in the dance labor group was significantly lower than the control group (P < 0.05). The mean satisfaction score in the dance labor group was significantly higher than in the control group (P < 0.05). Conclusion: Dance labor which is a complementary treatment with low risk can reduce the intensity of pain and increase mothers, satisfaction with care during the active phase of labor. PMID:24762366

Effect of endometrial biopsy on intrauterine insemination outcome in controlled ovarian stimulation cycle

PubMed Central

Wadhwa, Leena; Pritam, Amrita; Gupta, Taru; Gupta, Sangeeta; Arora, Sarika; Chandoke, Rajkumar

2015-01-01

OBJECTIVE: The objective was to evaluate the effect of endometrial biopsy (EB) on intrauterine insemination (IUI) outcome in controlled ovarian stimulation (COS) cycle. DESIGN: Prospective randomized control study. SETTING: Tertiary care center. MATERIALS AND METHODS: A total of 251 subjects were enrolled in the study. Subjects undergoing COS with IUI were randomly allocated into three groups. Group A: EB was taken between D19 and 24 of the spontaneous menstrual cycles that precedes the fertility treatment and IUI, which was done in next cycle (n = 86). Group B: EB was taken before D6 of the menstrual cycle, and fertility treatment and IUI was done in the same cycle (n = 90). Group C: (control group) no EB in previous 3 cycle (n = 75). MAIN OUTCOME MEASURE: Clinical pregnancy rate (CPR). RESULTS: Clinical pregnancy rate was 19.77%, 31.11%, and 9.3% for Group A, Group B, and Group C, respectively. The results show a highly significant value for the paired t-test of intervention Group B and control Group C of the cases (P = 0.000957). CPR was maximum after first cycle of ovulation induction and IUI following EB scratch in both Groups A and in Group B (P < 0.001). CONCLUSIONS: Endometrial biopsy done in early follicular phase in the same cycle of stimulation with IUI gives better CPR as compared with EB done in the luteal phase of the previous cycle. PMID:26538858

Methods of pushing during vaginal delivery and pelvic floor and perineal outcomes: a review.

PubMed

de Tayrac, Renaud; Letouzey, Vincent

2016-12-01

Over the past 20 years, several randomized studies have compared Valsalva and spontaneous pushing techniques during vaginal delivery. This review summarizes current medical knowledge concerning their maternal and fetal consequences, focusing on pelvic and perineal outcomes. We selected nine randomized controlled trials comparing Valsalva and spontaneous pushing, and a secondary analysis of a randomized controlled trial comparing different methods of perineal protection. Two trials showed that spontaneous pushing reduces the risk of perineal tears, but no firm conclusions can be drawn given the heterogeneity and inconsistent results of these studies. Conflicting results have been reported regarding the duration of the second stage of labor. Pushing technique does not seem to affect episiotomy, instrumental delivery or cesarean rates. Maternal satisfaction seems to be better after spontaneous pushing. Spontaneous pushing appears to have no adverse effects on neonatal well being, and one study showed a significant improvement in prenatal fetal parameters during the expulsive phase. Valsalva and spontaneous pushing techniques currently appear comparable in terms of duration, pelvic floor, perineal, and neonatal outcomes. In the absence of strong evidence in favor of either technique, the decision should be guided by patient preference and the clinical situation. Additional, well-designed randomized controlled trials are required.

A double-blind, crossover, randomized comparison of granisetron and ramosetron for the prevention of acute and delayed cisplatin-induced emesis in patients with gastrointestinal cancer: is patient preference a better primary endpoint?

PubMed

Koizumi, Wasaburo; Tanabe, Satoshi; Nagaba, Shizuka; Higuchi, Katsuhiko; Nakayama, Norisuke; Saigenji, Katsunori; Nonaka, Miwa; Yago, Kazuo

2003-12-01

Serotonin receptor antagonists are recommended by the American Society of Clinical Oncology for the prevention of acute and delayed chemotherapy-induced emesis. However, the most effective agent in this class of antiemetic drugs for preventing emesis has not been clearly defined. We therefore performed a double-blind, crossover, randomized, controlled trial comparing the efficacy of granisetron and ramosetron, using patient preference as the primary endpoint. Thirty patients receiving two courses of combined chemotherapy (including > or =60 mg/m(2) cisplatin) for gastric or esophageal cancer were randomly assigned to the granisetron-ramosetron group (treatment phase 1: granisetron, 3 mg; treatment phase 2: ramosetron, 0.3 mg) or the ramosetron-granisetron group (treatment phase 1: ramosetron, 0.3 mg; treatment phase 2: granisetron, 3 mg). All patients received methylprednisolone sodium, 250 mg i.v., during each treatment phase. The efficacy of granisetron and ramosetron was similar in terms of the suppression of emesis and appetite status. However, the majority of patients (19/30, 63.3%) expressed a preference for granisetron, as compared with 9 patients (30.0%) who preferred ramosetron; 2 patients (6.7%) had no preference (chi(2) test: p = 0.008; Fisher's exact test: p = 0.015). (1) A significant proportion of patients prefer granisetron over ramosetron for the prevention of chemotherapy-induced emesis. (2) Granisetron and ramosetron possess similar effectiveness for the suppression of emesis. (3) The variable of 'patient preference' should be accepted as a primary endpoint of antiemetic drug efficacy. Copyright 2003 S. Karger AG, Basel

Developmental contributions to macronutrient selection: a randomized controlled trial in adult survivors of malnutrition.

PubMed

Campbell, Claudia P; Raubenheimer, David; Badaloo, Asha V; Gluckman, Peter D; Martinez, Claudia; Gosby, Alison; Simpson, Stephen J; Osmond, Clive; Boyne, Michael S; Forrester, Terrence E

2016-01-01

Birthweight differences between kwashiorkor and marasmus suggest that intrauterine factors influence the development of these syndromes of malnutrition and may modulate risk of obesity through dietary intake. We tested the hypotheses that the target protein intake in adulthood is associated with birthweight, and that protein leveraging to maintain this target protein intake would influence energy intake (EI) and body weight in adult survivors of malnutrition. Sixty-three adult survivors of marasmus and kwashiorkor could freely compose a diet from foods containing 10, 15 and 25 percentage energy from protein (percentage of energy derived from protein (PEP); Phase 1) for 3 days. Participants were then randomized in Phase 2 (5 days) to diets with PEP fixed at 10%, 15% or 25%. Self-selected PEP was similar in both groups. In the groups combined, selected PEP was 14.7, which differed significantly (P < 0.0001) from the null expectation (16.7%) of no selection. Self-selected PEP was inversely related to birthweight, the effect disappearing after adjusting for sex and current body weight. In Phase 2, PEP correlated inversely with EI (P = 0.002) and weight change from Phase 1 to 2 (P = 0.002). Protein intake increased with increasing PEP, but to a lesser extent than energy increased with decreasing PEP. Macronutrient intakes were not independently related to birthweight or diagnosis. In a free-choice situation (Phase 1), subjects selected a dietary PEP significantly lower than random. Lower PEP diets induce increased energy and decreased protein intake, and are associated with weight gain. © The Author(s) 2015. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.

Method and apparatus for pulse width modulation control of an AC induction motor

DOEpatents

Geppert, Steven; Slicker, James M.

1984-01-01

An inverter is connected between a source of DC power and a three-phase AC induction motor, and a micro-processor-based circuit controls the inverter using pulse width modulation techniques. In the disclosed method of pulse width modulation, both edges of each pulse of a carrier pulse train are equally modulated by a time proportional to sin .THETA., where .THETA. is the angular displacement of the pulse center at the motor stator frequency from a fixed reference point on the carrier waveform. The carrier waveform frequency is a multiple of the motor stator frequency. The modulated pulse train is then applied to each of the motor phase inputs with respective phase shifts of 120.degree. at the stator frequency. Switching control commands of electronic switches in the inverter are stored in a random access memory (RAM) and the locations of the RAM are successively read out in a cyclic manner, each bit of a given RAM location controlling a respective phase input of the motor. The DC power source preferably comprises rechargeable batteries and all but one of the electronic switches in the inverter can be disabled, the remaining electronic switch being part of a "flyback" DC-DC converter circuit for recharging the battery.

Method and apparatus for pulse width modulation control of an AC induction motor

NASA Technical Reports Server (NTRS)

Geppert, Steven (Inventor); Slicker, James M. (Inventor)

1984-01-01

An inverter is connected between a source of DC power and a three-phase AC induction motor, and a micro-processor-based circuit controls the inverter using pulse width modulation techniques. In the disclosed method of pulse width modulation, both edges of each pulse of a carrier pulse train are equally modulated by a time proportional to sin .THETA., where .THETA. is the angular displacement of the pulse center at the motor stator frequency from a fixed reference point on the carrier waveform. The carrier waveform frequency is a multiple of the motor stator frequency. The modulated pulse train is then applied to each of the motor phase inputs with respective phase shifts of 120.degree. at the stator frequency. Switching control commands of electronic switches in the inverter are stored in a random access memory (RAM) and the locations of the RAM are successively read out in a cyclic manner, each bit of a given RAM location controlling a respective phase input of the motor. The DC power source preferably comprises rechargeable batteries and all but one of the electronic switches in the inverter can be disabled, the remaining electronic switch being part of a flyback DC-DC converter circuit for recharging the battery.

Time-resolved dynamics of granular matter by random laser emission

NASA Astrophysics Data System (ADS)

Folli, Viola; Ghofraniha, Neda; Puglisi, Andrea; Leuzzi, Luca; Conti, Claudio

2013-07-01

Because of the huge commercial importance of granular systems, the second-most used material in industry after water, intersecting the industry in multiple trades, like pharmacy and agriculture, fundamental research on grain-like materials has received an increasing amount of attention in the last decades. In photonics, the applications of granular materials have been only marginally investigated. We report the first phase-diagram of a granular as obtained by laser emission. The dynamics of vertically-oscillated granular in a liquid solution in a three-dimensional container is investigated by employing its random laser emission. The granular motion is function of the frequency and amplitude of the mechanical solicitation, we show how the laser emission allows to distinguish two phases in the granular and analyze its spectral distribution. This constitutes a fundamental step in the field of granulars and gives a clear evidence of the possible control on light-matter interaction achievable in grain-like system.

A Locust Phase Change Model with Multiple Switching States and Random Perturbation

NASA Astrophysics Data System (ADS)

Xiang, Changcheng; Tang, Sanyi; Cheke, Robert A.; Qin, Wenjie

2016-12-01

Insects such as locusts and some moths can transform from a solitarious phase when they remain in loose populations and a gregarious phase, when they may swarm. Therefore, the key to effective management of outbreaks of species such as the desert locust Schistocercagregaria is early detection of when they are in the threshold state between the two phases, followed by timely control of their hopper stages before they fledge because the control of flying adult swarms is costly and often ineffective. Definitions of gregarization thresholds should assist preventive control measures and avoid treatment of areas that might not lead to gregarization. In order to better understand the effects of the threshold density which represents the gregarization threshold on the outbreak of a locust population, we developed a model of a discrete switching system. The proposed model allows us to address: (1) How frequently switching occurs from solitarious to gregarious phases and vice versa; (2) When do stable switching transients occur, the existence of which indicate that solutions with larger amplitudes can switch to a stable attractor with a value less than the switching threshold density?; and (3) How does random perturbation influence the switching pattern? Our results show that both subsystems have refuge equilibrium points, outbreak equilibrium points and bistable equilibria. Further, the outbreak equilibrium points and bistable equilibria can coexist for a wide range of parameters and can switch from one to another. This type of switching is sensitive to the intrinsic growth rate and the initial values of the locust population, and may result in locust population outbreaks and phase switching once a small perturbation occurs. Moreover, the simulation results indicate that the switching transient patterns become identical after some generations, suggesting that the evolving process of the perturbation system is not related to the initial value after some fixed number of generations for the same stochastic processes. However, the switching frequency and outbreak patterns can be significantly affected by the intensity of noise and the intrinsic growth rate of the locust population.

Elagolix treatment for endometriosis-associated pain: results from a phase 2, randomized, double-blind, placebo-controlled study.

PubMed

Diamond, Michael P; Carr, Bruce; Dmowski, W Paul; Koltun, William; O'Brien, Chris; Jiang, Ping; Burke, Joshua; Jimenez, Roland; Garner, Elizabeth; Chwalisz, Kristof

2014-03-01

This Phase 2 study evaluated the safety and efficacy of elagolix for treating endometriosis-associated pain. A total of 155 women with laparoscopically confirmed endometriosis were randomized to placebo, elagolix 150 mg, or elagolix 250 mg once daily for 12 weeks. Placebo patients were rerandomized to elagolix and elagolix patients continued their dosing assignment for 12 additional weeks; the primary efficacy measure was changed from baseline in the monthly mean numerical rating scale for pain at week 12. Monthly mean (standard error of the mean) reductions were greater with elagolix versus placebo (-1.19 ± 0.18, -1.25 ± 0.18, and -0.88 ± 0.18 for elagolix 150 mg, 250 mg, and placebo, respectively); differences were not statistically significant. Monthly mean dysmenorrhea and nonmenstrual pelvic pain scores were reduced with elagolix, with significant differences for dysmenorrhea at weeks 8 and 12 versus placebo (P < .05). Minimal bone mineral density changes were observed with elagolix treatment. In women with endometriosis-associated pain, elagolix demonstrated an acceptable efficacy and safety profile in this Phase 2 study.

Effectiveness and safety of valsartan in children aged 6 to 16 years with hypertension.

PubMed

Wells, Thomas; Blumer, Jeffrey; Meyers, Kevin E C; Neto, Jose P R; Meneses, Rejane; Litwin, Mieczysław; Vande Walle, Johan; Solar-Yohay, Susan; Shi, Victor; Han, Guangyang

2011-05-01

The effectiveness and safety of valsartan have not been assessed in hypertensive children. Therefore, hypertensive patients aged 6 to 16 years (n=261) were randomized to receive weight-stratified low- (10/20 mg), medium- (40/80 mg), or high-dose (80/160 mg) valsartan for 2 weeks. After 2 weeks, patients were randomized to a 2-week placebo-controlled withdrawal phase. Dose-dependent reductions in sitting systolic blood pressure (SSBP) and sitting diastolic blood pressure (SDBP) were observed after 2 weeks (low dose, -7.9/-4.6 mm Hg; medium dose, -9.6/-5.8 mm Hg; high dose, -11.5/-7.4 mm Hg [P<.0001 for all groups]). During the withdrawal phase, SSBP and SDBP were both lower in the pooled valsartan group than in the pooled placebo group (SSBP, -2.7 mm Hg [P=.0368]; SDBP, -3.0 mm Hg [P=.0047]). Similar efficacy was observed in all subgroups. Valsartan was well tolerated and headache was the most commonly observed adverse event during both the double-blind and 52-week open-label phases. © 2011 Wiley Periodicals, Inc.

Comparing the Effects of Aromatherapy With Rose Oils and Warm Foot Bath on Anxiety in the First Stage of Labor in Nulliparous Women

PubMed Central

Kheirkhah, Massomeh; Vali Pour, Nassimeh Setayesh; Nisani, Leila; Haghani, Hamid

2014-01-01

Background: Anxiety is the most common emotional response in women during delivery, which can be accompanied with adverse effects on fetus and mother. Objectives: This study was conducted to compare the effects of aromatherapy with rose oil and warm foot bath on anxiety in the active phase of labor in nulliparous women in Tehran, Iran. Patients and Methods: This clinical trial study was performed after obtaining informed written consent on 120 primigravida women randomly assigned into three groups. The experimental group 1 received a 10-minute inhalation and footbath with oil rose. The experimental group 2 received a 10-minute warm water footbath. Both interventions were applied at the onset of active and transitional phases. Control group, received routine care in labor. Anxiety was assessed using visual analogous scale (VASA) at onset of active and transitional phases before and after the intervention. Statistical comparison was performed using SPSS software version 16 and P < 0.05 was considered significant. Results: Anxiety scores in the intervention groups in active phase after intervention were significantly lower than the control group (P < 0.001). Anxiety scores before and after intervention in intervention groups in transitional phase was significantly lower than the control group (P < 0.001). Conclusions: Using aromatherapy and footbath reduces anxiety in active phase in nulliparous women. PMID:25593713

Pulse width modulation inverter with battery charger

DOEpatents

Slicker, James M.

1985-01-01

An inverter is connected between a source of DC power and a three-phase AC induction motor, and a microprocessor-based circuit controls the inverter using pulse width modulation techniques. In the disclosed method of pulse width modulation, both edges of each pulse of a carrier pulse train are equally modulated by a time proportional to sin .theta., where .theta. is the angular displacement of the pulse center at the motor stator frequency from a fixed reference point on the carrier waveform. The carrier waveform frequency is a multiple of the motor stator frequency. The modulated pulse train is then applied to each of the motor phase inputs with respective phase shifts of 120.degree. at the stator frequency. Switching control commands for electronic switches in the inverter are stored in a random access memory (RAM) and the locations of the RAM are successively read out in a cyclic manner, each bit of a given RAM location controlling a respective phase input of the motor. The DC power source preferably comprises rechargeable batteries and all but one of the electronic switches in the inverter can be disabled, the remaining electronic switch being part of a "flyback" DC-DC converter circuit for recharging the battery.

Pulse width modulation inverter with battery charger

NASA Technical Reports Server (NTRS)

Slicker, James M. (Inventor)

1985-01-01

An inverter is connected between a source of DC power and a three-phase AC induction motor, and a microprocessor-based circuit controls the inverter using pulse width modulation techniques. In the disclosed method of pulse width modulation, both edges of each pulse of a carrier pulse train are equally modulated by a time proportional to sin .theta., where .theta. is the angular displacement of the pulse center at the motor stator frequency from a fixed reference point on the carrier waveform. The carrier waveform frequency is a multiple of the motor stator frequency. The modulated pulse train is then applied to each of the motor phase inputs with respective phase shifts of 120.degree. at the stator frequency. Switching control commands for electronic switches in the inverter are stored in a random access memory (RAM) and the locations of the RAM are successively read out in a cyclic manner, each bit of a given RAM location controlling a respective phase input of the motor. The DC power source preferably comprises rechargeable batteries and all but one of the electronic switches in the inverter can be disabled, the remaining electronic switch being part of a flyback DC-DC converter circuit for recharging the battery.

Active phase compensation system for fiber optic holography

NASA Technical Reports Server (NTRS)

Mercer, Carolyn R.; Beheim, Glenn

1988-01-01

Fiber optic delivery systems promise to extend the application of holography to severe environments by simplifying test configurations and permitting the laser to be remotely placed in a more benign location. However, the introduction of optical fiber leads to phase stability problems. Environmental effects cause the pathlengths of the fibers to change randomly, preventing the formation of stationary interference patterns which are required for holography. An active phase control system has been designed and used with an all-fiber optical system to stabilize the phase difference between light emitted from two fibers, and to step the phase difference by 90 deg without applying any constraints on the placement of the fibers. The accuracy of the phase steps is shown to be better than 0.02 deg., and a stable phase difference can be maintained for 30 min. This system can be applied to both conventional and electro-optic holography, as well as to any system where the maintenance of an accurate phase difference between two coherent beams is required.

Active phase compensation system for fiber optic holography

NASA Technical Reports Server (NTRS)

Mercer, Carolyn R.; Beheim, Glenn

1989-01-01

Fiber optic delivery systems promise to extend the application of holography to severe environments by simplifying test configurations and permitting the laser to be remotely placed in a more benign location. However, the introduction of optical fiber leads to phase stability problems. Environmental effects cause the pathlengths of the fibers to change randomly, preventing the formation of stationary interference patterns which are required for holography. An active phase control system has been designed and used with an all-fiber optical system to stabilize the phase difference between light emitted from two fibers, and to step the phase difference by 90 deg without applying any constraints on the placement of the fibers. The accuracy of the phase steps is shown to be better than 0.02 deg., and a stable phase difference can be maintained for 30 min. This system can be applied to both conventional and electro-optic holography, as well as to any system where the maintenance of an accurate phase difference between two coherent beams is required.

A scheme for synchronizing clocks connected by a packet communication network

NASA Astrophysics Data System (ADS)

dos Santos, R. V.; Monteiro, L. H. A.

2012-07-01

Consider a communication system in which a transmitter equipment sends fixed-size packets of data at a uniform rate to a receiver equipment. Consider also that these equipments are connected by a packet-switched network, which introduces a random delay to each packet. Here we propose an adaptive clock recovery scheme able of synchronizing the frequencies and the phases of these devices, within specified limits of precision. This scheme for achieving frequency and phase synchronization is based on measurements of the packet arrival times at the receiver, which are used to control the dynamics of a digital phase-locked loop. The scheme performance is evaluated via numerical simulations performed by using realistic parameter values.

Dimensionality-strain phase diagram of strontium iridates

NASA Astrophysics Data System (ADS)

Kim, Bongjae; Liu, Peitao; Franchini, Cesare

2017-03-01

The competition between spin-orbit coupling, bandwidth (W ), and electron-electron interaction (U ) makes iridates highly susceptible to small external perturbations, which can trigger the onset of novel types of electronic and magnetic states. Here we employ first principles calculations based on density functional theory and on the constrained random phase approximation to study how dimensionality and strain affect the strength of U and W in (SrIrO3)m/(SrTiO3) superlattices. The result is a phase diagram explaining two different types of controllable magnetic and electronic transitions, spin-flop and insulator-to-metal, connected with the disruption of the Jeff=1 /2 state which cannot be understood within a simplified local picture.

A phase II randomized clinical trial on cerebral near-infrared spectroscopy plus a treatment guideline versus treatment as usual for extremely preterm infants during the first three days of life (SafeBoosC): study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Every year in Europe about 25,000 infants are born extremely preterm. These infants have a 20% mortality rate, and 25% of survivors have severe long-term cerebral impairment. Preventative measures are key to reduce mortality and morbidity in an extremely preterm population. The primary objective of the SafeBoosC phase II trial is to examine if it is possible to stabilize the cerebral oxygenation of extremely preterm infants during the first 72 hours of life through the application of cerebral near-infrared spectroscopy (NIRS) oximetry and implementation of an clinical treatment guideline based on intervention thresholds of cerebral regional tissue saturation rStO2. Methods/Design SafeBoosC is a randomized, blinded, multinational, phase II clinical trial. The inclusion criteria are: neonates born more than 12 weeks preterm; decision to conduct full life support; parental informed consent; and possibility to place the cerebral NIRS oximeter within 3 hours after birth. The infants will be randomized into one of two groups. Both groups will have a cerebral oximeter monitoring device placed within three hours of birth. In the experimental group, the cerebral oxygenation reading will supplement the standard treatment using a predefined treatment guideline. In the control group, the cerebral oxygenation reading will not be visible and the infant will be treated according to the local standards. The primary outcome is the multiplication of the duration and magnitude of rStO2 values outside the target ranges of 55% to 85%, that is, the ‘burden of hypoxia and hyperoxia’ expressed in ‘%hours’. To detect a 50% difference between the experimental and control group in %hours, 166 infants in total must be randomized. Secondary outcomes are mortality at term date, cerebral ultrasound score, and interburst intervals on an amplitude-integrated electroencephalogram at 64 hours of life and explorative outcomes include neurodevelopmental outcome at 2 years corrected age, magnetic resonance imaging at term, blood biomarkers at 6 and 64 hours after birth, and adverse events. Discussion Cerebral oximetry guided interventions have the potential to improve neurodevelopmental outcome in extremely preterm infants. It is a logical first step to test if it is possible to reduce the burden of hypoxia and hyperoxia. Trial registration ClinicalTrial.gov, NCT01590316 PMID:23782447

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

A. Alfonsi; C. Rabiti; D. Mandelli

The Reactor Analysis and Virtual control ENviroment (RAVEN) code is a software tool that acts as the control logic driver and post-processing engine for the newly developed Thermal-Hydraulic code RELAP-7. RAVEN is now a multi-purpose Probabilistic Risk Assessment (PRA) software framework that allows dispatching different functionalities: Derive and actuate the control logic required to simulate the plant control system and operator actions (guided procedures), allowing on-line monitoring/controlling in the Phase Space Perform both Monte-Carlo sampling of random distributed events and Dynamic Event Tree based analysis Facilitate the input/output handling through a Graphical User Interface (GUI) and a post-processing data miningmore » module« less

Evaluation of internal peer-review to train nurses recruiting to a randomized controlled trial--Internal Peer-review for Recruitment Training in Trials (InterPReTiT).

PubMed

Mann, Cindy; Delgado, Debbie; Horwood, Jeremy

2014-04-01

A discussion and qualitative evaluation of the use of peer-review to train nurses and optimize recruitment practice in a randomized controlled trial. Sound recruitment processes are critical to the success of randomized controlled trials. Nurses recruiting to trials must obtain consent for an intervention that is administered for reasons other than anticipated benefit to the patient. This requires not only patients' acquiescence but also evidence that they have weighed the relevant information in reaching their decision. How trial information is explained is vital, but communication and training can be inadequate. A discussion of a new process to train nurses recruiting to a randomized controlled trial. Literature from 1999-2013 about consenting to trials is included. Over 3 months from 2009-2010, recruiting nurses reviewed recruitment interviews recorded during the pilot phase of a single-site randomized controlled trial and noted content, communication style and interactions. They discussed their findings during peer-review meetings, which were audio-recorded and analysed using qualitative methodology. Peer-review can enhance nurses' training in trial recruitment procedures by supporting development of the necessary communication skills, facilitating consistency in information provision and sharing best practice. Nurse-led peer-review can provide a forum to share communication strategies that will elicit and address participant concerns and obtain evidence of participant understanding prior to consent. Comparing practice can improve consistency and accuracy of trial information and facilitate identification of recruitment issues. Internal peer-review was well accepted and promoted team cohesion. Further evaluation is needed. © 2013 John Wiley & Sons Ltd.

Random Forest Application for NEXRAD Radar Data Quality Control

NASA Astrophysics Data System (ADS)

Keem, M.; Seo, B. C.; Krajewski, W. F.

2017-12-01

Identification and elimination of non-meteorological radar echoes (e.g., returns from ground, wind turbines, and biological targets) are the basic data quality control steps before radar data use in quantitative applications (e.g., precipitation estimation). Although WSR-88Ds' recent upgrade to dual-polarization has enhanced this quality control and echo classification, there are still challenges to detect some non-meteorological echoes that show precipitation-like characteristics (e.g., wind turbine or anomalous propagation clutter embedded in rain). With this in mind, a new quality control method using Random Forest is proposed in this study. This classification algorithm is known to produce reliable results with less uncertainty. The method introduces randomness into sampling and feature selections and integrates consequent multiple decision trees. The multidimensional structure of the trees can characterize the statistical interactions of involved multiple features in complex situations. The authors explore the performance of Random Forest method for NEXRAD radar data quality control. Training datasets are selected using several clear cases of precipitation and non-precipitation (but with some non-meteorological echoes). The model is structured using available candidate features (from the NEXRAD data) such as horizontal reflectivity, differential reflectivity, differential phase shift, copolar correlation coefficient, and their horizontal textures (e.g., local standard deviation). The influence of each feature on classification results are quantified by variable importance measures that are automatically estimated by the Random Forest algorithm. Therefore, the number and types of features in the final forest can be examined based on the classification accuracy. The authors demonstrate the capability of the proposed approach using several cases ranging from distinct to complex rain/no-rain events and compare the performance with the existing algorithms (e.g., MRMS). They also discuss operational feasibility based on the observed strength and weakness of the method.

Reactive and anticipatory looking in 6-month-old infants during a visual expectation paradigm.

PubMed

Quan, Jeffry; Bureau, Jean-François; Abdul Malik, Adam B; Wong, Johnny; Rifkin-Graboi, Anne

2017-10-01

This article presents data from 278 six-month-old infants who completed a visual expectation paradigm in which audiovisual stimuli were first presented randomly (random phase), and then in a spatial pattern (pattern phase). Infants' eye gaze behaviour was tracked with a 60 Hz Tobii eye-tracker in order to measure two types of looking behaviour: reactive looking (i.e., latency to shift eye gaze in reaction to the appearance of stimuli) and anticipatory looking (i.e., percentage of time spent looking at the location where the next stimulus is about to appear during the inter-stimulus interval). Data pertaining to missing data and task order effects are presented. Further analyses show that infants' reactive looking was faster in the pattern phase, compared to the random phase, and their anticipatory looking increased from random to pattern phases. Within the pattern phase, infants' reactive looking showed a quadratic trend, with reactive looking time latencies peaking in the middle portion of the phase. Similarly, within the pattern phase, infants' anticipatory looking also showed a quadratic trend, with anticipatory looking peaking during the middle portion of the phase.

Shift-phase code multiplexing technique for holographic memories and optical interconnection

NASA Astrophysics Data System (ADS)

Honma, Satoshi; Muto, Shinzo; Okamoto, Atsushi

2008-03-01

Holographic technologies for optical memories and interconnection devices have been studied actively because of high storage capacity, many wiring patterns and high transmission rate. Among multiplexing techniques such as angular, phase code and wavelength-multiplexing, speckle multiplexing technique have gotten attention due to the simple optical setup having an adjustable random phase filter in only one direction. To keep simple construction and to suppress crosstalk among adjacent page data or wiring patterns for efficient holographic memories and interconnection, we have to consider about optimum randomness of the phase filter. The high randomness causes expanding an illumination area of reference beam on holographic media. On the other hands, the small randomness causes the crosstalk between adjacent hologram data. We have proposed the method of holographic multiplexing, shift-phase code multiplexing with a two-dimensional orthogonal matrix phase filter. A lot of orthogonal phase codes can be produced by shifting the phase filter in one direction. It is able to read and record the individual holograms with low crosstalk. We give the basic experimental result on holographic data multiplexing and consider the phase pattern of the filter to suppress the crosstalk between adjacent holograms sufficiently.

Applying STOPP Guidelines in Primary Care Through Electronic Medical Record Decision Support: Randomized Control Trial Highlighting the Importance of Data Quality.

PubMed

Price, Morgan; Davies, Iryna; Rusk, Raymond; Lesperance, Mary; Weber, Jens

2017-06-15

Potentially Inappropriate Prescriptions (PIPs) are a common cause of morbidity, particularly in the elderly. We sought to understand how the Screening Tool of Older People's Prescriptions (STOPP) prescribing criteria, implemented in a routinely used primary care Electronic Medical Record (EMR), could impact PIP rates in community (non-academic) primary care practices. We conducted a mixed-method, pragmatic, cluster, randomized control trial in research naïve primary care practices. Phase 1: In the randomized controlled trial, 40 fully automated STOPP rules were implemented as EMR alerts during a 16-week intervention period. The control group did not receive the 40 STOPP rules (but received other alerts). Participants were recruited through the OSCAR EMR user group mailing list and in person at user group meetings. Results were assessed by querying EMR data PIPs. EMR data quality probes were included. Phase 2: physicians were invited to participate in 1-hour semi-structured interviews to discuss the results. In the EMR, 40 STOPP rules were successfully implemented. Phase 1: A total of 28 physicians from 8 practices were recruited (16 in intervention and 12 in control groups). The calculated PIP rate was 2.6% (138/5308) (control) and 4.11% (768/18,668) (intervention) at baseline. No change in PIPs was observed through the intervention (P=.80). Data quality probes generally showed low use of problem list and medication list. Phase 2: A total of 5 physicians participated. All the participants felt that they were aware of the alerts but commented on workflow and presentation challenges. The calculated PIP rate was markedly less than the expected rate found in literature (2.6% and 4.0% vs 20% in literature). Data quality probes highlighted issues related to completeness of data in areas of the EMR used for PIP reporting and by the decision support such as problem and medication lists. Users also highlighted areas for better integration of STOPP guidelines with prescribing workflows. Many of the STOPP criteria can be implemented in EMRs using simple logic. However, data quality in EMRs continues to be a challenge and was a limiting step in the effectiveness of the decision support in this study. This is important as decision makers continue to fund implementation and adoption of EMRs with the expectation of the use of advanced tools (such as decision support) without ongoing review of data quality and improvement. Clinicaltrials.gov NCT02130895; https://clinicaltrials.gov/ct2/show/NCT02130895 (Archived by WebCite at http://www.webcitation.org/6qyFigSYT). ©Morgan Price, Iryna Davies, Raymond Rusk, Mary Lesperance, Jens Weber. Originally published in JMIR Medical Informatics (http://medinform.jmir.org), 15.06.2017.

Psychiatric adverse events during treatment with brodalumab: Analysis of psoriasis clinical trials.

PubMed

Lebwohl, Mark G; Papp, Kim A; Marangell, Lauren B; Koo, John; Blauvelt, Andrew; Gooderham, Melinda; Wu, Jashin J; Rastogi, Shipra; Harris, Susan; Pillai, Radhakrishnan; Israel, Robert J

2018-01-01

Individuals with psoriasis are at increased risk for psychiatric comorbidities, including suicidal ideation and behavior (SIB). To distinguish between the underlying risk and potential for treatment-induced psychiatric adverse events in patients with psoriasis being treated with brodalumab, a fully human anti-interleukin 17 receptor A monoclonal antibody. Data were evaluated from a placebo-controlled, phase 2 clinical trial; the open-label, long-term extension of the phase 2 clinical trial; and three phase 3, randomized, double-blind, controlled clinical trials (AMAGINE-1, AMAGINE-2, and AMAGINE-3) and their open-label, long-term extensions of patients with moderate-to-severe psoriasis. The analysis included 4464 patients with 9161.8 patient-years of brodalumab exposure. The follow-up time-adjusted incidence rates of SIB events were comparable between the brodalumab and ustekinumab groups throughout the 52-week controlled phases (0.20 vs 0.60 per 100 patient-years). In the brodalumab group, 4 completed suicides were reported, 1 of which was later adjudicated as indeterminate; all patients had underlying psychiatric disorders or stressors. There was no comparator arm past week 52. Controlled study periods were not powered to detect differences in rare events such as suicide. Comparison with controls and the timing of events do not indicate a causal relationship between SIB and brodalumab treatment. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

HPTN 068: A Randomized Control Trial of a Conditional Cash Transfer to Reduce HIV Infection in Young Women in South Africa-Study Design and Baseline Results.

PubMed

Pettifor, Audrey; MacPhail, Catherine; Selin, Amanda; Gómez-Olivé, F Xavier; Rosenberg, Molly; Wagner, Ryan G; Mabuza, Wonderful; Hughes, James P; Suchindran, Chirayath; Piwowar-Manning, Estelle; Wang, Jing; Twine, Rhian; Daniel, Tamu; Andrew, Philip; Laeyendecker, Oliver; Agyei, Yaw; Tollman, Stephen; Kahn, Kathleen

2016-09-01

Young women in South Africa are at high risk for HIV infection. Cash transfers offer promise to reduce HIV risk. We present the design and baseline results from HPTN 068, a phase III, individually randomized trial to assess the effect of a conditional cash transfer on HIV acquisition among South African young women. A total of 2533 young women were randomized to receive a monthly cash transfer conditional on school attendance or to a control group. A number of individual-, partner-, household- and school-level factors were associated with HIV and HSV-2 infection. After adjusting for age, all levels were associated with an increased odds of HIV infection with partner-level factors conveying the strongest association (aOR 3.05 95 % CI 1.84-5.06). Interventions like cash transfers that address structural factors such as schooling and poverty have the potential to reduce HIV risk in young women in South Africa.

Lack of significant anti-inflammatory activity with clindamycin in the treatment of rosacea: results of 2 randomized, vehicle-controlled trials.

PubMed

Martel, Philippe; Jarratt, Michael; Weiss, Jonathan; Carlavan, Isabelle

2017-07-01

Rosacea is a chronic inflammatory skin disease of the face. The objective of the studies described here was to evaluate the efficacy of clindamycin in the treatment of rosacea. Two multicenter, randomized, vehicle-controlled, phase 2 studies were conducted in participants with moderate to severe rosacea. Study A was a 12-week dose-comparison, 5-arm, parallel group comparison of clindamycin cream 1% or vehicle once or twice daily and clindamycin cream 0.3% once daily. Study B was a 2-arm comparison of twice daily clindamycin gel 1% versus vehicle gel. A total of 629 participants (study A, N=416; study B, N=213) were randomized. The results of these studies indicated that clindamycin cream 0.3% and 1% and clindamycin gel 1% were no more effective than the vehicle in the treatment of moderate to severe rosacea, suggesting clindamycin has no intrinsic anti-inflammatory activity in rosacea.

Vaccination With Patient-Specific Tumor-Derived Antigen in First Remission Improves Disease-Free Survival in Follicular Lymphoma

PubMed Central

Schuster, Stephen J.; Neelapu, Sattva S.; Gause, Barry L.; Janik, John E.; Muggia, Franco M.; Gockerman, Jon P.; Winter, Jane N.; Flowers, Christopher R.; Nikcevich, Daniel A.; Sotomayor, Eduardo M.; McGaughey, Dean S.; Jaffe, Elaine S.; Chong, Elise A.; Reynolds, Craig W.; Berry, Donald A.; Santos, Carlos F.; Popa, Mihaela A.; McCord, Amy M.; Kwak, Larry W.

2011-01-01

Purpose Vaccination with hybridoma-derived autologous tumor immunoglobulin (Ig) idiotype (Id) conjugated to keyhole limpet hemocyanin (KLH) and administered with granulocyte-monocyte colony-stimulating factor (GM-CSF) induces follicular lymphoma (FL) –specific immune responses. To determine the clinical benefit of this vaccine, we conducted a double-blind multicenter controlled phase III trial. Patients and Methods Treatment-naive patients with advanced stage FL achieving complete response (CR) or CR unconfirmed (CRu) after chemotherapy were randomly assigned two to one to receive either Id vaccine (Id-KLH + GM-CSF) or control (KLH + GM-CSF). Primary efficacy end points were disease-free survival (DFS) for all randomly assigned patients and DFS for randomly assigned patients receiving at least one dose of Id vaccine or control. Results Of 234 patients enrolled, 177 (81%) achieved CR/CRu after chemotherapy and were randomly assigned. For 177 randomly assigned patients, including 60 patients not vaccinated because of relapse (n = 55) or other reasons (n = 5), median DFS between Id-vaccine and control arms was 23.0 versus 20.6 months, respectively (hazard ratio [HR], 0.81; 95% CI, 0.56 to 1.16; P = .256). For 117 patients who received Id vaccine (n = 76) or control (n = 41), median DFS after randomization was 44.2 months for Id-vaccine arm versus 30.6 months for control arm (HR, 0.62; 95% CI, 0.39 to 0.99; P = .047) at median follow-up of 56.6 months (range, 12.6 to 89.3 months). In an unplanned subgroup analysis, median DFS was significantly prolonged for patients receiving IgM-Id (52.9 v 28.7 months; P = .001) but not IgG-Id vaccine (35.1 v 32.4 months; P = .807) compared with isotype-matched control-treated patients. Conclusion Vaccination with patient-specific hybridoma-derived Id vaccine after chemotherapy-induced CR/CRu may prolong DFS in patients with FL. Vaccine isotype may affect clinical outcome and explain differing results between this and other controlled Id-vaccine trials. PMID:21632504

Development and effectiveness of a mobile phone application conducting health behavioral intervention among men who have sex with men, a randomized controlled trial: study protocol.

PubMed

Yan, Jin; Zhang, Aidi; Zhou, Liang; Huang, Zhulin; Zhang, Pan; Yang, Guoli

2017-04-24

Behavioral intervention is a key approach to HIV prevention among men who have sex with men (MSM). Widespread use of mobile phones provide us with novel opportunities to decrease HIV infection and transmission of MSM. The objective of the study was to design and develop a mobile phone application (app) aims to conduct behavioral intervention to MSM and to evaluate the efficacy of the app-based intervention compared to usual care, to analyze cost-effectiveness and mechanism of the intervention. This study involves 2 phases, phase 1 use qualitative method and phase 2 is a randomized controlled trial lasting for 18 months, they will be conducted in Chagnsha, Hunan Province, China. Phase 1 is to design and develop the app, procedures including retrieval of domestic apps related to prevention and treatment about HIV and sexually transmitted diseases (HIV/STDs), personal interviews with MSM about preferences and functional needs of the HIV prevention app, multidisciplinary experts focused group discussions of the app, software engineers' development and users test of the app will be performed. In phase 2, we will recruit 800 MSM by cooperating with the local center of disease control and prevention and nongovernmental organizations, and divide them into intervention and control group evenly. Intervention group participants will receive app-based HIV prevention. Control group participants will be provided with usual care including HIV/STDs knowledge brochure and free voluntary counseling services. Data will be collected at baseline, 6, 12 and 18 months since subject's participation. Effectiveness of the intervention includes HIV/STDs infection rates, adherence to regularly HIV testing, sexual risk behavior, consistent condom use and relative risk of HIV infection. Cost-effectiveness will be analyzed by decision-analytic modeling, and mechanism analysis of this app-based intervention will be performed by path analysis. This will be the first study of its kind in China to develop an app and implement app-based HIV prevention intervention among MSM. It is of great potential to determine whether app-based intervention is a cost-effective way to decrease HIV infection among MSM and explore intervention mechanism with an accurate method. Chinese Clinical Trial Register ( ChiCTR-IOR-15006724 ). Registered 10 July 2015.

CrowdPhase: crowdsourcing the phase problem

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

Jorda, Julien; Sawaya, Michael R.; Yeates, Todd O., E-mail: yeates@mbi.ucla.edu

The idea of attacking the phase problem by crowdsourcing is introduced. Using an interactive, multi-player, web-based system, participants work simultaneously to select phase sets that correspond to better electron-density maps in order to solve low-resolution phasing problems. The human mind innately excels at some complex tasks that are difficult to solve using computers alone. For complex problems amenable to parallelization, strategies can be developed to exploit human intelligence in a collective form: such approaches are sometimes referred to as ‘crowdsourcing’. Here, a first attempt at a crowdsourced approach for low-resolution ab initio phasing in macromolecular crystallography is proposed. A collaborativemore » online game named CrowdPhase was designed, which relies on a human-powered genetic algorithm, where players control the selection mechanism during the evolutionary process. The algorithm starts from a population of ‘individuals’, each with a random genetic makeup, in this case a map prepared from a random set of phases, and tries to cause the population to evolve towards individuals with better phases based on Darwinian survival of the fittest. Players apply their pattern-recognition capabilities to evaluate the electron-density maps generated from these sets of phases and to select the fittest individuals. A user-friendly interface, a training stage and a competitive scoring system foster a network of well trained players who can guide the genetic algorithm towards better solutions from generation to generation via gameplay. CrowdPhase was applied to two synthetic low-resolution phasing puzzles and it was shown that players could successfully obtain phase sets in the 30° phase error range and corresponding molecular envelopes showing agreement with the low-resolution models. The successful preliminary studies suggest that with further development the crowdsourcing approach could fill a gap in current crystallographic methods by making it possible to extract meaningful information in cases where limited resolution might otherwise prevent initial phasing.« less

Symmetry breaking in tensor models

NASA Astrophysics Data System (ADS)

Benedetti, Dario; Gurau, Razvan

2015-11-01

In this paper we analyze a quartic tensor model with one interaction for a tensor of arbitrary rank. This model has a critical point where a continuous limit of infinitely refined random geometries is reached. We show that the critical point corresponds to a phase transition in the tensor model associated to a breaking of the unitary symmetry. We analyze the model in the two phases and prove that, in a double scaling limit, the symmetric phase corresponds to a theory of infinitely refined random surfaces, while the broken phase corresponds to a theory of infinitely refined random nodal surfaces. At leading order in the double scaling limit planar surfaces dominate in the symmetric phase, and planar nodal surfaces dominate in the broken phase.

Flexible and polarization-controllable diffusion metasurface with optical transparency

NASA Astrophysics Data System (ADS)

Zhuang, Yaqiang; Wang, Guangming; Liang, Jiangang; Cai, Tong; Guo, Wenlong; Zhang, Qingfeng

2017-11-01

In this paper, a novel coding metasurface is proposed to realize polarization-controllable diffusion scattering. The anisotropic Jerusalem-cross unit cell is employed as the basic coding element due to its polarization-dependent phase response. The isotropic random coding sequence is firstly designed to obtain diffusion scattering, and the anisotropic random coding sequence is subsequently realized by adding different periodic coding sequences to the original isotropic one along different directions. For demonstration, we designed and fabricated a flexible polarization-controllable diffusion metasurface (PCDM) with both chessboard diffusion and hedge diffusion under different polarizations. The specular scattering reduction performance of the anisotropic metasurface is better than the isotropic one because the scattered energies are redirected away from the specular reflection direction. For potential applications, the flexible PCDM wrapped around a cylinder structure is investigated and tested for polarization-controllable diffusion scattering. The numerical and experimental results coincide well, indicating anisotropic low scatterings with comparable performances. This paper provides an alternative approach for designing high-performance, flexible, low-scattering platforms.

Efficacy and safety of saxagliptin compared with acarbose in Chinese patients with type 2 diabetes mellitus uncontrolled on metformin monotherapy: Results of a Phase IV open-label randomized controlled study (the SMART study).

PubMed

Du, Jin; Liang, Li; Fang, Hui; Xu, Fengmei; Li, Wei; Shen, Liya; Wang, Xueying; Xu, Chun; Bian, Fang; Mu, Yiming

2017-11-01

To investigate the efficacy, safety and tolerability of saxagliptin compared with acarbose in Chinese patients with type 2 diabetes mellitus inadequately controlled with metformin monotherapy. SMART was a 24-week, multicentre, randomized, parallel-group, open-label Phase IV study conducted at 35 sites in China (September 24, 2014 to September 29, 2015). The primary outcome was absolute change from baseline in HbA1c at Week 24. Secondary outcomes assessed at Week 24 included the proportion of patients achieving HbA1c < 7.0%, the proportion of patients with gastrointestinal adverse events (GI AEs), and the proportion of patients achieving HbA1c < 7.0% without GI AEs. Safety and tolerability were also assessed in all patients who received ≥1 dose of study medication. Four-hundred and eighty-eight patients were randomized (1:1) to saxagliptin or acarbose via a central randomization system (interactive voice/web response system); 241 and 244 patients received saxagliptin and acarbose, respectively, and 238 and 243 of these had ≥1 pre- and ≥1 post-baseline efficacy values recorded. Saxagliptin was non-inferior to acarbose for glycaemic control [Week 24 HbA1c change: -0.82% and -0.78%, respectively; difference (95% confidence interval): -0.04 (-0.22, 0.13)%], with similar proportions of patients in both treatment groups achieving HbA1c < 7.0%. However, fewer GI AEs were reported with saxagliptin compared with acarbose, and a greater number of patients who received saxagliptin achieved HbA1c < 7.0% without GI AEs compared with those receiving acarbose. Both therapies had similar efficacy profiles. However, saxagliptin was associated with fewer GI AEs, suggesting it might be preferential for clinical practice. NCT02243176, clinicaltrials.gov. © 2017 John Wiley & Sons Ltd.

Mavoglurant in fragile X syndrome: Results of two randomized, double-blind, placebo-controlled trials.

PubMed

Berry-Kravis, Elizabeth; Des Portes, Vincent; Hagerman, Randi; Jacquemont, Sébastien; Charles, Perrine; Visootsak, Jeannie; Brinkman, Marc; Rerat, Karin; Koumaras, Barbara; Zhu, Liansheng; Barth, Gottfried Maria; Jaecklin, Thomas; Apostol, George; von Raison, Florian

2016-01-13

Fragile X syndrome (FXS), the most common cause of inherited intellectual disability and autistic spectrum disorder, is typically caused by transcriptional silencing of the X-linked FMR1 gene. Work in animal models has described altered synaptic plasticity, a result of the up-regulation of metabotropic glutamate receptor 5 (mGluR5)-mediated signaling, as a putative downstream effect. Post hoc analysis of a randomized, placebo-controlled, crossover phase 2 trial suggested that the selective mGluR5 antagonist mavoglurant improved behavioral symptoms in FXS patients with completely methylated FMR1 genes. We present the results of two phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group studies of mavoglurant in FXS, designed to confirm this result in adults (n = 175, aged 18 to 45 years) and adolescents (n = 139, aged 12 to 17 years). In both trials, participants were stratified by methylation status and randomized to receive mavoglurant (25, 50, or 100 mg twice daily) or placebo over 12 weeks. Neither of the studies achieved the primary efficacy end point of improvement on behavioral symptoms measured by the Aberrant Behavior Checklist-Community Edition using the FXS-specific algorithm (ABC-C(FX)) after 12 weeks of treatment with mavoglurant. The safety and tolerability profile of mavoglurant was as previously described, with few adverse events. Therefore, under the conditions of our study, we could not confirm the mGluR theory of FXS nor the ability of the methylation state of the FMR1 promoter to predict mavoglurant efficacy. Preclinical results suggest that future clinical trials might profitably explore initiating treatment in a younger population with longer treatment duration and longer placebo run-ins and identifying new markers to better assess behavioral and cognitive benefits. Copyright © 2016, American Association for the Advancement of Science.

Placebo effects in a multiple sclerosis spasticity enriched clinical trial with the oromucosal cannabinoid spray (THC/CBD): dimension and possible causes.

PubMed

Di Marzo, Vincenzo; Centonze, Diego

2015-03-01

Regulatory authorities admit clinical studies with an initial enrichment phase to select patients that respond to treatment before randomization (Enriched Design Studies; EDSs). The trial period aims to prevent long-term drug exposure risks in patients with limited chances of improvement while optimizing costs. In EDSs for symptom control therapies providing early improvements and without a wash-out period, it is difficult to show further improvements and thus large therapeutic gains versus placebo. Moreover, in trials with cannabinoids, the therapeutic gains can be further biased in the postenrichment randomized phase because of carryover and other effects. The aims of the present review article are to examine the placebo effects in the enrichment and postenrichment phases of an EDS with Δ(9) -tetrahydrocannabinol and cannabidiol (THC/CBD) oromucosal spray in patients with multiple sclerosis (MS) spasticity and to discuss the possible causes of maintained efficacy after randomization in the placebo-allocated patients. The overall mean therapeutic gain of THC/CBD spray over placebo in resistant MS spasticity after 16 weeks can be estimated as a ~1.27-point improvement on the spasticity 0-10 Numerical Rating Scale (NRS; ~-20.1% of the baseline NRS score). We conclude that careful interpretation of the results of EDSs is required, especially when cannabinoid-based medications are being investigated. © 2014 John Wiley & Sons Ltd.

Tapentadol immediate-release for acute postbunionectomy pain: a phase 3, randomized, double-blind, placebo-controlled, parallel-group study in Taiwan.

PubMed

Chen, Yeung-Jen; Chiang, Chao-Ching; Huang, Peng-Ju; Huang, Jason; Karcher, Keith; Li, Honglan

2015-11-01

To evaluate the efficacy and safety of tapentadol immediate-release (IR) for treating acute pain following orthopedic bunionectomy surgery in a Taiwanese population. This was a phase 3, randomized, double-blind, placebo-controlled, parallel-group bridging study in which Taiwanese patients (N = 60) with moderate-to-severe pain following bunionectomy were randomized (1:1:1) to receive tapentadol IR 50 or 75 mg or placebo orally every 4-6 hours over a 72 hour period. The primary endpoint was the sum of pain intensity difference over 48 hours (SPID48), analyzed using analysis of variance. Out of 60 patients randomized (mainly women [96.7%]; median age 44 years), 41 (68.3%) completed the treatment. Mean SPID48 values were significantly higher for tapentadol IR (p ≤ 0.006: 50 mg, p ≤ 0.004: 75 mg) compared with placebo. Between-group differences in LS means of SPID48 (vs. placebo) were tapentadol IR 50 mg: 105.6 (95% CI: 32.0; 179.2); tapentadol IR 75 mg: 126.6 (95% CI: 49.5; 203.7). Secondary endpoints including SPID at 12, 24, and 72 hours, time to first use of rescue medication, cumulative distribution of responder rates, total pain relief and sum of total pain relief and sum of pain intensity difference at 12, 24, 48, and 72 hours, and patient global impression of change showed numerically better results supporting that tapentadol IR (50 and 75 mg) was more efficacious than placebo in relieving acute pain. The most frequent treatment emergent adverse events reported in ≥ 10% patients in either group were dizziness, nausea, and vomiting. A limitation of this study may possibly include more controlled patient monitoring through 4-6 hour dosing intervals, which reflects optimal conditions and thus may not approximate real-world clinical practice. However, all treatment groups would be equally affected by such bias of frequent monitoring, if any, since it was a randomized and double-blind study. Tapentadol IR treatment significantly relieved acute postoperative pain and was well tolerated in a Taiwanese population. ClinicalTrials.gov identifier: NCT01813890.

Experimental demonstration of an active phase randomization and monitor module for quantum key distribution

NASA Astrophysics Data System (ADS)

Sun, Shi-Hai; Liang, Lin-Mei

2012-08-01

Phase randomization is a very important assumption in the BB84 quantum key distribution (QKD) system with weak coherent source; otherwise, eavesdropper may spy the final key. In this Letter, a stable and monitored active phase randomization scheme for the one-way and two-way QKD system is proposed and demonstrated in experiments. Furthermore, our scheme gives an easy way for Alice to monitor the degree of randomization in experiments. Therefore, we expect our scheme to become a standard part in future QKD systems due to its secure significance and feasibility.

A study protocol of a three-group randomized feasibility trial of an online yoga intervention for mothers after stillbirth (The Mindful Health Study).

PubMed

Huberty, Jennifer; Matthews, Jeni; Leiferman, Jenn; Cacciatore, Joanne; Gold, Katherine J

2018-01-01

In the USA, stillbirth (in utero fetal death ≥20 weeks gestation) is a major public health issue. Women who experience stillbirth, compared to women with live birth, have a nearly sevenfold increased risk of a positive screen for post-traumatic stress disorder (PTSD) and a fourfold increased risk of depressive symptoms. Because the majority of women who have experienced the death of their baby become pregnant within 12-18 months and the lack of intervention studies conducted within this population, novel approaches targeting physical and mental health, specific to the needs of this population, are critical. Evidence suggests that yoga is efficacious, safe, acceptable, and cost-effective for improving mental health in a variety of populations, including pregnant and postpartum women. To date, there are no known studies examining online-streaming yoga as a strategy to help mothers cope with PTSD symptoms after stillbirth. The present study is a two-phase randomized controlled trial. Phase 1 will involve (1) an iterative design process to develop the online yoga prescription for phase 2 and (2) qualitative interviews to identify cultural barriers to recruitment in non-Caucasian women (i.e., predominately Hispanic and/or African American) who have experienced stillbirth ( N  = 5). Phase 2 is a three-group randomized feasibility trial with assessments at baseline, and at 12 and 20 weeks post-intervention. Ninety women who have experienced a stillbirth within 6 weeks to 24 months will be randomized into one of the following three arms for 12 weeks: (1) intervention low dose (LD) = 60 min/week online-streaming yoga ( n  = 30), (2) intervention moderate dose (MD) = 150 min/week online-streaming yoga ( n  = 30), or (3) stretch and tone control (STC) group = 60 min/week of stretching/toning exercises ( n  = 30). This study will explore the feasibility and acceptability of a 12-week, home-based, online-streamed yoga intervention, with varying doses among mothers after a stillbirth. If feasible, the findings from this study will inform a full-scale trial to determine the effectiveness of home-based online-streamed yoga to improve PTSD. Long-term, health care providers could use online yoga as a non-pharmaceutical, inexpensive resource for stillbirth aftercare. NCT02925481.

Active control: an investigation method for combustion instabilities

NASA Astrophysics Data System (ADS)

Poinsot, T.; Yip, B.; Veynante, D.; Trouvé, A.; Samaniego, J. M.; Candel, S.

1992-07-01

Closed-loop active control methods and their application to combustion instabilities are discussed. In these methods the instability development is impeded with a feedback control loop: the signal provided by a sensor monitoring the flame or pressure oscillations is processed and sent back to actuators mounted on the combustor or on the feeding system. Different active control systems tested on a non-premixed multiple-flame turbulent combustor are described. These systems can suppress all unstable plane modes of oscillation (i.e. low frequency modes). The active instability control (AIC) also constitutes an original and powerful technique for studies of mechanisms leading to instability or resulting from the instability. Two basic applications of this kind are described. In the first case the flame is initially controlled with AIC, the feedback loop is then switched off and the growth of the instability is analysed through high speed Schlieren cinematography and simultaneous sound pressure and reaction rate measurements. Three phases are identified during th growth of the oscillations: (1) a linear phase where acoustic waves induce a flapping motion of the flame sheets without interaction between sheets, (2) a modulation phase, where flame sheets interact randomly and (3) a nonlinear phase where the flame sheets are broken and a limit cycle is reached. In the second case we investigate different types of flame extinctions associated with combustion instability. It is shown that pressure oscillations may lead to partial or total extinctions. Extinctions occur in various forms but usually follow a rapid growth of pressure oscillations. The flame is extinguished during the modulation phase observed in the initiation experiments. In these studies devoted to transient instability phenomena, the control system constitutes a unique investigation tool because it is difficult to obtain the same information by other means. Implications for modelling and prediction of combustion instabilities are discussed.

Procedural and Physical Interventions for Vaccine Injections: Systematic Review of Randomized Controlled Trials and Quasi-Randomized Controlled Trials.

PubMed

Taddio, Anna; Shah, Vibhuti; McMurtry, C Meghan; MacDonald, Noni E; Ipp, Moshe; Riddell, Rebecca Pillai; Noel, Melanie; Chambers, Christine T

2015-10-01

This systematic review evaluated the effectiveness of physical and procedural interventions for reducing pain and related outcomes during vaccination. Databases were searched using a broad search strategy to identify relevant randomized and quasi-randomized controlled trials. Data were extracted according to procedure phase (preprocedure, acute, recovery, and combinations of these) and pooled using established methods. A total of 31 studies were included. Acute infant distress was diminished during intramuscular injection without aspiration (n=313): standardized mean difference (SMD) -0.82 (95% confidence interval [CI]: -1.18, -0.46). Injecting the most painful vaccine last during vaccinations reduced acute infant distress (n=196): SMD -0.69 (95% CI: -0.98, -0.4). Simultaneous injections reduced acute infant distress compared with sequential injections (n=172): SMD -0.56 (95% CI: -0.87, -0.25). There was no benefit of simultaneous injections in children. Less infant distress during the acute and recovery phases combined occurred with vastus lateralis (vs. deltoid) injections (n=185): SMD -0.70 (95% CI: -1.00, -0.41). Skin-to-skin contact in neonates (n=736) reduced acute distress: SMD -0.65 (95% CI: -1.05, -0.25). Holding infants reduced acute distress after removal of the data from 1 methodologically diverse study (n=107): SMD -1.25 (95% CI: -2.05, -0.46). Holding after vaccination (n=417) reduced infant distress during the acute and recovery phases combined: SMD -0.65 (95% CI: -1.08, -0.22). Self-reported fear was reduced for children positioned upright (n=107): SMD -0.39 (95% CI: -0.77, -0.01). Non-nutritive sucking (n=186) reduced acute distress in infants: SMD -1.88 (95% CI: -2.57, -1.18). Manual tactile stimulation did not reduce pain across the lifespan. An external vibrating device and cold reduced pain in children (n=145): SMD -1.23 (95% CI: -1.58, -0.87). There was no benefit of warming the vaccine in adults. Muscle tension was beneficial in selected indices of fainting in adolescents and adults. Interventions with evidence of benefit in select populations include: no aspiration, injecting most painful vaccine last, simultaneous injections, vastus lateralis injection, positioning interventions, non-nutritive sucking, external vibrating device with cold, and muscle tension.

The random field Blume-Capel model revisited

NASA Astrophysics Data System (ADS)

Santos, P. V.; da Costa, F. A.; de Araújo, J. M.

2018-04-01

We have revisited the mean-field treatment for the Blume-Capel model under the presence of a discrete random magnetic field as introduced by Kaufman and Kanner (1990). The magnetic field (H) versus temperature (T) phase diagrams for given values of the crystal field D were recovered in accordance to Kaufman and Kanner original work. However, our main goal in the present work was to investigate the distinct structures of the crystal field versus temperature phase diagrams as the random magnetic field is varied because similar models have presented reentrant phenomenon due to randomness. Following previous works we have classified the distinct phase diagrams according to five different topologies. The topological structure of the phase diagrams is maintained for both H - T and D - T cases. Although the phase diagrams exhibit a richness of multicritical phenomena we did not found any reentrant effect as have been seen in similar models.

Deterministic matrices matching the compressed sensing phase transitions of Gaussian random matrices

PubMed Central

Monajemi, Hatef; Jafarpour, Sina; Gavish, Matan; Donoho, David L.; Ambikasaran, Sivaram; Bacallado, Sergio; Bharadia, Dinesh; Chen, Yuxin; Choi, Young; Chowdhury, Mainak; Chowdhury, Soham; Damle, Anil; Fithian, Will; Goetz, Georges; Grosenick, Logan; Gross, Sam; Hills, Gage; Hornstein, Michael; Lakkam, Milinda; Lee, Jason; Li, Jian; Liu, Linxi; Sing-Long, Carlos; Marx, Mike; Mittal, Akshay; Monajemi, Hatef; No, Albert; Omrani, Reza; Pekelis, Leonid; Qin, Junjie; Raines, Kevin; Ryu, Ernest; Saxe, Andrew; Shi, Dai; Siilats, Keith; Strauss, David; Tang, Gary; Wang, Chaojun; Zhou, Zoey; Zhu, Zhen

2013-01-01

In compressed sensing, one takes samples of an N-dimensional vector using an matrix A, obtaining undersampled measurements . For random matrices with independent standard Gaussian entries, it is known that, when is k-sparse, there is a precisely determined phase transition: for a certain region in the (,)-phase diagram, convex optimization typically finds the sparsest solution, whereas outside that region, it typically fails. It has been shown empirically that the same property—with the same phase transition location—holds for a wide range of non-Gaussian random matrix ensembles. We report extensive experiments showing that the Gaussian phase transition also describes numerous deterministic matrices, including Spikes and Sines, Spikes and Noiselets, Paley Frames, Delsarte-Goethals Frames, Chirp Sensing Matrices, and Grassmannian Frames. Namely, for each of these deterministic matrices in turn, for a typical k-sparse object, we observe that convex optimization is successful over a region of the phase diagram that coincides with the region known for Gaussian random matrices. Our experiments considered coefficients constrained to for four different sets , and the results establish our finding for each of the four associated phase transitions. PMID:23277588

Intensive Blood-Pressure Control in Hypertensive Chronic Kidney Disease

PubMed Central

Appel, Lawrence J.; Wright, Jackson T.; Greene, Tom; Agodoa, Lawrence Y.; Astor, Brad C.; Bakris, George L.; Cleveland, William H.; Charleston, Jeanne; Contreras, Gabriel; Faulkner, Marquetta L.; Gabbai, Francis B.; Gassman, Jennifer J.; Hebert, Lee A.; Jamerson, Kenneth A.; Kopple, Joel D.; Kusek, John W.; Lash, James P.; Lea, Janice P.; Lewis, Julia B.; Lipkowitz, Michael S.; Massry, Shaul G.; Miller, Edgar R.; Norris, Keith; Phillips, Robert A.; Pogue, Velvie A.; Randall, Otelio S.; Rostand, Stephen G.; Smogorzewski, Miroslaw J.; Toto, Robert D.; Wang, Xuelei

2013-01-01

BACKGROUND In observational studies, the relationship between blood pressure and end-stage renal disease (ESRD) is direct and progressive. The burden of hypertension-related chronic kidney disease and ESRD is especially high among black patients. Yet few trials have tested whether intensive blood-pressure control retards the progression of chronic kidney disease among black patients. METHODS We randomly assigned 1094 black patients with hypertensive chronic kidney disease to receive either intensive or standard blood-pressure control. After completing the trial phase, patients were invited to enroll in a cohort phase in which the blood-pressure target was less than 130/80 mm Hg. The primary clinical outcome in the cohort phase was the progression of chronic kidney disease, which was defined as a doubling of the serum creatinine level, a diagnosis of ESRD, or death. Follow-up ranged from 8.8 to 12.2 years. RESULTS During the trial phase, the mean blood pressure was 130/78 mm Hg in the intensive-control group and 141/86 mm Hg in the standard-control group. During the cohort phase, corresponding mean blood pressures were 131/78 mm Hg and 134/78 mm Hg. In both phases, there was no significant between-group difference in the risk of the primary outcome (hazard ratio in the intensive-control group, 0.91; P = 0.27). However, the effects differed according to the baseline level of proteinuria (P = 0.02 for interaction), with a potential benefit in patients with a protein-to-creatinine ratio of more than 0.22 (hazard ratio, 0.73; P = 0.01). CONCLUSIONS In overall analyses, intensive blood-pressure control had no effect on kidney disease progression. However, there may be differential effects of intensive blood-pressure control in patients with and those without baseline proteinuria. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center on Minority Health and Health Disparities, and others.) PMID:20818902

Efficacy of prophylactic antibiotic administration for breast cancer surgery in overweight or obese patients: a randomized controlled trial.

PubMed

Gulluoglu, Bahadir M; Guler, Sertac Ata; Ugurlu, M Umit; Culha, Gulcan

2013-01-01

To assess the impact of prophylactic antibiotics on the prevention of surgical site infection (SSI) and the cost-effectiveness of this prophylaxis for breast cancer surgery in overweight or obese women. SSI is higher than expected after breast surgery. Obesity was found to be one of the risk factors. The trial was designed as a phase IV randomized, controlled, parallel-group efficacy trial. It was conducted at a tertiary university hospital. Overweight or obese women with clinically early-stage breast cancer who had been assigned to undergo surgery were eligible. Patients were randomly allocated to either a prophylaxis or a control group by using a computer-generated list. The prophylaxis group received 1 g ampicillin-sulbactam intravenously at anesthesia. The control group received no intervention. Patients and observers were blinded to the assignments. The primary outcome was the comparison of SSI incidences of the 2 groups. Patients were monitored for 30 days. A total of 369 patients were included in final analysis, out of which 187 were allocated for prophylaxis and 182 were randomly assigned to the control group. Analysis was done according to the intention-to-treat principle. Prophylaxis significantly reduced the SSI rate (4.8%) in the prophylaxis group when compared with that in the control group [13.7%; relative risk (RR) 0.35; 95% CI: 0.17-0.73]. No adverse reaction was observed. The mean SSI-related cost (20.26 USD) was found to be significantly higher in the control group when compared with that (8.48 USD) in the prophylaxis group. Antibiotic prophylaxis significantly decreased SSI incidence after elective surgery and was shown to be cost-effective in obese breast cancer patients. ClinicalTrials.gov Identifier: NCT00356148.

Phase transformation changes in thermocycled nickel-titanium orthodontic wires.

PubMed

Berzins, David W; Roberts, Howard W

2010-07-01

In the oral environment, orthodontic wires will be subject to thermal fluctuations. The purpose of this study was to investigate the effect of thermocycling on nickel-titanium (NiTi) wire phase transformations. Straight segments from single 27 and 35 degrees C copper NiTi (Ormco), Sentalloy (GAC), and Nitinol Heat Activated (3M Unitek) archwires were sectioned into 5mm segments (n=20). A control group consisted of five randomly selected non-thermocycled segments. The remaining segments were thermocycled between 5 and 55 degrees C with five randomly selected segments analyzed with differential scanning calorimetry (DSC; -100<-->150 degrees C at 10 degrees C/min) after 1000, 5000, and 10,000 cycles. Thermal peaks were evaluated with results analyzed via ANOVA (alpha=0.05). Nitinol HA and Sentalloy did not demonstrate qualitative or quantitative phase transformation behavior differences. Significant differences were observed in some of the copper NiTi transformation temperatures, as well as the heating enthalpy with the 27 degrees C copper NiTi wires (p<0.05). Qualitatively, with increased thermocycling the extent of R-phase in the heating peaks decreased in the 35 degrees C copper NiTi, and an austenite to martensite peak shoulder developed during cooling in the 27 degrees C copper NiTi. Repeated temperature fluctuations may contribute to qualitative and quantitative phase transformation changes in some NiTi wires. Copyright 2010 Academy of Dental Materials. All rights reserved.

Lubiprostone: in constipation-predominant irritable bowel syndrome.

PubMed

Carter, Natalie J; Scott, Lesley J

2009-06-18

Lubiprostone is an oral bicyclic fatty acid that selectively activates type 2 chloride channels in the apical membrane of human gastrointestinal epithelial cells, thereby increasing chloride-rich fluid secretion. Although the mechanism is unclear, this may then decrease intestinal transit time, allowing the passage of stool and alleviating symptoms of constipation. Oral lubiprostone was effective in the treatment of patients with constipation-predominant irritable bowel syndrome (IBS-C) in large (n = 193-583) phase II (dose-finding) and phase III randomized, double-blind, placebo-controlled, multicentre trials. The number of patients with IBS-C demonstrating an overall response to treatment (primary endpoint) in the two phase III trials was significantly greater in patients receiving lubiprostone 8 microg twice daily for 3 months than in those receiving placebo. In addition, a randomized, 4-week withdrawal period at the end of one of the phase III trials demonstrated that discontinuation of lubiprostone was not associated with rebound of IBS symptoms. Lubiprostone was generally well tolerated in clinical trials, with the majority of adverse events being of mild to moderate severity. In patients with IBS-C who received lubiprostone 8 microg twice daily, nausea was the most frequently occurring adverse event that was considered possibly or probably treatment related. No serious treatment-related adverse events were reported in a 36-week open-label extension to the phase III trials.

Optimized random phase only holograms.

PubMed

Zea, Alejandro Velez; Barrera Ramirez, John Fredy; Torroba, Roberto

2018-02-15

We propose a simple and efficient technique capable of generating Fourier phase only holograms with a reconstruction quality similar to the results obtained with the Gerchberg-Saxton (G-S) algorithm. Our proposal is to use the traditional G-S algorithm to optimize a random phase pattern for the resolution, pixel size, and target size of the general optical system without any specific amplitude data. This produces an optimized random phase (ORAP), which is used for fast generation of phase only holograms of arbitrary amplitude targets. This ORAP needs to be generated only once for a given optical system, avoiding the need for costly iterative algorithms for each new target. We show numerical and experimental results confirming the validity of the proposal.

Templated Sphere Phase Liquid Crystals for Tunable Random Lasing

PubMed Central

Chen, Ziping; Hu, Dechun; Chen, Xingwu; Zeng, Deren; Lee, Yungjui; Chen, Xiaoxian; Lu, Jiangang

2017-01-01

A sphere phase liquid crystal (SPLC) composed of three-dimensional twist structures with disclinations among them exists between isotropic phase and blue phase in a very narrow temperature range, about several degrees centigrade. A low concentration polymer template is applied to improve the thermal stability of SPLCs and broadens the temperature range to more than 448 K. By template processing, a wavelength tunable random lasing is demonstrated with dye doped SPLC. With different polymer concentrations, the reconstructed SPLC random lasing may achieve more than 40 nm wavelength continuous shifting by electric field modulation. PMID:29140283

EffectS of non-nutritive sWeetened beverages on appetITe during aCtive weigHt loss (SWITCH): Protocol for a randomized, controlled trial assessing the effects of non-nutritive sweetened beverages compared to water during a 12-week weight loss period and a follow up weight maintenance period.

PubMed

Masic, U; Harrold, J A; Christiansen, P; Cuthbertson, D J; Hardman, C A; Robinson, E; Halford, J C G

2017-02-01

Acute and medium-term intervention studies suggest that non-nutritive sweeteners (NNS) are beneficial for weight loss, however there is limited human data on the long-term effects of consuming NNS on weight loss, maintenance, and appetite. Further research is therefore required to elucidate the prolonged impact of NNS consumption on these outcome measures. A randomized parallel groups design will be used to assess whether regular NNS beverage intake is equivalent to a water control in promoting weight loss over 12-weeks (weekly weight loss sessions; Phase I), then supporting weight maintenance over 40-weeks (monthly sessions; Phase II) and subsequently independent weight maintenance over 52-weeks (Phase III) in 432 participants. A subset of these participants (n=116) will complete laboratory-based appetite probe days (15 sessions; 3 sessions each at baseline, at the start of phase I and the end of each phase). A separate subset (n=50) will complete body composition scans (DXA) at baseline and at the end of each phase. All participants will regularly be weighed and will complete questionnaires and cognitive tasks to assess changes in body weight and appetitive behaviours. Measures of physical activity and biochemical markers will also be taken. The trial will assess the efficacy of NNS beverages compared to water during a behavioural weight loss and maintenance programme. We aim to understand whether the impact of NNS on weight, dietary adherence and well-being are beneficial or transient and effects on prolonged successful weight loss and weight maintenance through sustained changes in appetite and eating behaviour. Clinical Trials: NCT02591134; registered: 23.10.2015. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Time-resolved two-window measurement of Wigner functions for coherent backscatter from a turbid medium

NASA Astrophysics Data System (ADS)

Reil, Frank; Thomas, John E.

2002-05-01

For the first time we are able to observe the time-resolved Wigner function of enhanced backscatter from a random medium using a novel two-window technique. This technique enables us to directly verify the phase-conjugating properties of random media. An incident divergent beam displays a convergent enhanced backscatter cone. We measure the joint position and momentum (x, p) distributions of the light field as a function of propagation time in the medium. The two-window technique allows us to independently control the resolutions for position and momentum, thereby surpassing the uncertainty limit associated with Fourier transform pairs. By using a low-coherence light source in a heterodyne detection scheme, we observe enhanced backscattering resolved by path length in the random medium, providing information about the evolution of optical coherence as a function of penetration depth in the random medium.

Personality Disorder Patients' Perspectives on the Introduction of Imagery within Schema Therapy: A Qualitative Study of Patients' Experiences

ERIC Educational Resources Information Center

ten Napel-Schutz, Marieke C.; Abma, Tineke A.; Bamelis, Lotte; Arntz, Arnoud

2011-01-01

A qualitative study was done on patients' perspectives on the first phases of imagery work in the context of schema therapy (ST) for personality disorders. Patients participated in a multi-center randomized controlled study of the effectiveness of ST. Patients' experiences and opinions were collected with semistructured in-depth interviews at the…

Safety and preliminary immunogenicity of Cuban pneumococcal conjugate vaccine candidate in healthy children: a randomized phase I clinical trial.

PubMed

Dotres, Carlos P; Puga, Rinaldo; Ricardo, Yariset; Broño, Carmen R; Paredes, Beatriz; Echemendía, Vladimir; Rosell, Sandra; González, Nadezhda; García-Rivera, Dagmar; Valdés, Yury; Goldblatt, David; Vérez-Bencomo, Vicente

2014-09-15

A new heptavalent conjugate vaccine (PCV7-TT) is under development in Cuba. PCV7-TT contains 2 μg of serotypes 1, 5, 14, 18C, 19F, 23F and 4 μg of 6B, each one conjugated to tetanus toxoid (TT). This vaccine was designed with the serotypes that cause most invasive pneumococcal diseases (IPD) worldwide. In the present study, we investigated the safety and explored the immunogenicity of PCV7-TT during a controlled, randomized and double blind clinical trial phase I in 4-5-year-old children. PCV7-TT was well tolerated and as safe as Synflorix used as control vaccine. Following a single-dose vaccination, all individual serotypes included in PCV7-TT induced statistically significant increase of IgG GMC and OPA GMT. These are the first clinical results of PCV7-TT in children and they pave the way toward next clinical trials in children and infants. This clinical trial was published in the Cuban Public Register of Clinical Trials with code RPCEC00000173. Copyright © 2014 Elsevier Ltd. All rights reserved.

The effect of newly induced mutations on the fitness of genotypes and populations of yeast (Saccharomyces cerevisiae).

PubMed

Orthen, E; Lange, P; Wöhrmann, K

1984-12-01

This paper analyses the fate of artificially induced mutations and their importance to the fitness of populations of the yeast, Saccharomyces cerevisiae, an increasingly important model organism in population genetics. Diploid strains, treated with UV and EMS, were cultured asexually for approximately 540 generations and under conditions where the asexual growth was interrupted by a sexual phase. Growth rates of 100 randomly sampled diploid clones were estimated at the beginning and at the end of the experiment. After the induction of sporulation the growth rates of 100 randomly sampled spores were measured. UV and EMS treatment decreases the average growth rate of the clones significantly but increases the variability in comparison to the untreated control. After selection over approximately 540 generations, variability in growth rates was reduced to that of the untreated control. No increase in mean population fitness was observed. However, the results show that after selection there still exists a large amount of hidden genetic variability in the populations which is revealed when the clones are cultivated in environments other than those in which selection took place. A sexual phase increased the reduction of the induced variability.

Contrast and autoshaping in multiple schedules varying reinforcer rate and duration.

PubMed

Hamilton, B E; Silberberg, A

1978-07-01

Thirteen master pigeons were exposed to multiple schedules in which reinforcement frequency (Experiment I) or duration (Experiment II) was varied. In Phases 1 and 3 of Experiment I, the values of the first and second components' random-interval schedules were 33 and 99 seconds, respectively. In Phase 2, these values were 99 seconds for both components. In Experiment II, a random-interval 33-second schedule was associated with each component. During Phases 1 and 3, the first and second components had hopper durations of 7.5 and 2.5 seconds respectively. During Phase 2, both components' hopper durations were 2.5 seconds. In each experiment, positive contrast obtained for about half the master subjects. The rest showed a rate increase in both components (positive induction). Each master subject's key colors and reinforcers were synchronously presented on a response-independent basis to a yoked control. Richer component key-pecking occurred during each experiment's Phases 1 and 3 among half these subjects. However, none responded during the contrast condition (unchanged component of each experiment's Phase 2). From this it is inferred that autoshaping did not contribute to the contrast and induction findings among master birds. Little evidence of local contrast (highest rate at beginning of richer component) was found in any subject. These data show that (a) contrast can occur independently from autoshaping, (b) contrast assays during equal-valued components may produce induction, (c) local contrast in multiple schedules often does not occur, and (d) differential hopper durations can produce autoshaping and contrast.

A randomized, double-blinded, placebo-controlled phase II trial of recombinant human leukemia inhibitory factor (rhuLIF, emfilermin, AM424) to prevent chemotherapy-induced peripheral neuropathy.

PubMed

Davis, Ian D; Kiers, Lynette; MacGregor, Lachlan; Quinn, Michael; Arezzo, Joseph; Green, Michael; Rosenthal, Mark; Chia, Michael; Michael, Michael; Bartley, Peter; Harrison, Leonie; Daly, Michael

2005-03-01

To determine whether recombinant human leukemia inhibitory factor (rhuLIF, AM424, emfilermin) can prevent or ameliorate the development of chemotherapy-induced peripheral neuropathy (CIPN) after treatment with carboplatin (AUC 6) and paclitaxel (175 mg/m(2) over 3 hours). Randomized double-blind placebo-controlled phase II clinical trial. Eligible patients had solid tumors for which treatment with carboplatin/paclitaxel was appropriate. The primary end point was a standardized composite peripheral nerve electrophysiology (CPNE) score, based on nerve velocities and amplitudes, measured at baseline and after four cycles of chemotherapy. Secondary efficacy end points included CPNE score at last cycle and at exit evaluation, vibration perception threshold, H-reflex latency, symptom scores, and quantitative assessment of neurologic signs. Study drug was given s.c. daily for 7 days starting the day before chemotherapy. Patients were randomized to receive low-dose rhuLIF (2 microg/kg), high-dose rhuLIF (4 microg/kg), or placebo. Patients (n = 117) were randomized across seven neurology test centers. Thirty-six patients received low dose rhuLIF (2 microg/kg), 39 received high dose rhuLIF (4 microg/kg) and 42 received placebo. rhuLIF was well tolerated with 95% compliance and no adverse effects on quality of life. No differences between groups in CPNE or any of the individual neurologic testing variables were observed between baseline and cycle 4 or by the secondary efficacy variables. rhuLIF is not effective in preventing CIPN caused by carboplatin and paclitaxel. CPNE is a reliable and valid tool that was sensitive to the onset and progression of CIPN.

Efficacy and safety of bilastine in Japanese patients with chronic spontaneous urticaria: A multicenter, randomized, double-blind, placebo-controlled, parallel-group phase II/III study.

PubMed

Hide, Michihiro; Yagami, Akiko; Togawa, Michinori; Saito, Akihiro; Furue, Masutaka

2017-04-01

Bilastine, a novel non-sedating second-generation H 1 -antihistamine, has been widely used in the treatment of allergic rhinoconjunctivitis and urticaria with a recommended dose of 20 mg once daily in most European countries since 2010. We evaluated its efficacy and safety in Japanese patients with chronic spontaneous urticaria (CSU). We conducted a multicenter, randomized, double-blind, placebo-controlled phase II/III study (trial registration No. JapicCTI-142574). Patients (age, 18-74 years) were randomly assigned to receive bilastine 20 mg, 10 mg or placebo once daily for 2 weeks. The primary efficacy endpoint was the change from baseline (Day -3 to 0) in total symptom score (TSS) at 2 weeks (Day 8-14), consisting of the itch and rash scores. A total of 304 patients were randomly allocated to bilastine 20 mg (101 patients), bilastine 10 mg (100 patients), and placebo (103 patients). The changes in TSS at 2 weeks were significantly decreased by bilastine 20 mg than did placebo (p < 0.001), demonstrating the superiority of bilastine 20 mg. Bilastine 10 mg also showed a significant difference from placebo (p < 0.001). The TSS changes for the bilastine showed significant improvement from Day 1, and were maintained during the treatment period. The Dermatology Life Quality Index scores were also improved in bilastine than in placebo. The bilastine treatments were safe and well tolerated. Two-week treatment with bilastine (20 or 10 mg) once daily was effective and tolerable in Japanese patients with CSU, demonstrating an early onset of action. Copyright © 2016 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

Evidence for single-dose protection by the bivalent HPV vaccine-Review of the Costa Rica HPV vaccine trial and future research studies.

PubMed

Kreimer, Aimée R; Herrero, Rolando; Sampson, Joshua N; Porras, Carolina; Lowy, Douglas R; Schiller, John T; Schiffman, Mark; Rodriguez, Ana Cecilia; Chanock, Stephen; Jimenez, Silvia; Schussler, John; Gail, Mitchell H; Safaeian, Mahboobeh; Kemp, Troy J; Cortes, Bernal; Pinto, Ligia A; Hildesheim, Allan; Gonzalez, Paula

2018-01-20

The Costa Rica Vaccine Trial (CVT), a phase III randomized clinical trial, provided the initial data that one dose of the HPV vaccine could provide durable protection against HPV infection. Although the study design was to administer all participants three doses of HPV or control vaccine, 20% of women did not receive the three-dose regimens, mostly due to involuntary reasons unrelated to vaccination. In 2011, we reported that a single dose of the bivalent HPV vaccine could be as efficacious as three doses of the vaccine using the endpoint of persistent HPV infection accumulated over the first four years of the trial; findings independently confirmed in the GSK-sponsored PATRICIA trial. Antibody levels after one dose, although lower than levels elicited by three doses, were 9-times higher than levels elicited by natural infection. Importantly, levels remained essentially constant over at least seven years, suggesting that the observed protection provided by a single dose might be durable. Much work has been done to assure these non-randomized findings are valid. Yet, the group of recipients who received one dose of the bivalent HPV vaccine in the CVT and PATRICIA trials was small and not randomly selected nor blinded to the number of doses received. The next phase of research is to conduct a formal randomized, controlled trial to evaluate the protection afforded by a single dose of HPV vaccine. Complementary studies are in progress to bridge our findings to other populations, and to further document the long-term durability of antibody response following a single dose. Published by Elsevier Ltd.

Preliminary evidence that cinnamon improves menstrual cyclicity in women with polycystic ovary syndrome: a randomized controlled trial.

PubMed

Kort, Daniel H; Lobo, Roger A

2014-11-01

To determine the effect of cinnamon on menstrual cyclicity and metabolic dysfunction in women with polycystic ovary syndrome (PCOS). In a prospective, placebo controlled, double-blinded randomized trial, 45 women with PCOS were randomized (1:1) to receive cinnamon supplements (1.5 g/d) or placebo for 6 months. Menstrual cyclicity (average cycles/month) during the 6 months study period was compared between the 2 groups using the Mann-Whitney U test. Changes in menstrual cyclicity and insulin resistance between baseline and the 6 month study period were compared between the 2 groups using Wilcoxon signed rank tests. The 45 women were randomized, 26 women completed 3 months of the study, and 17 women completed the entire 6 months of the study. During the 6 month intervention, menstrual cycles were more frequent in patients taking cinnamon compared with patients taking placebo (median, 0.75; interquartile range, 0.5-0.83 vs median, 0.25; interquartile range, 0-0.54; P = .0085; Mann Whitney U). In patients taking cinnamon, menstrual cyclicity improved from baseline (+ 0.23 cycles/month 95% confidence interval, 0.099-0.36), yet did not improve for women taking placebo. (P = .0076, Wilcoxon signed rank). Samples (n = 5) of serum from the luteal phase in different patients within the cinnamon group were thawed and ovulatory progesterone levels (>3 ng/mL) confirmed. Luteal phase progesterone levels (>3 ng/mL, n = 5) confirmed ovulatory menses. Measures of insulin resistance or serum androgen levels did not change for either group. These preliminary data suggest that cinnamon supplementation improves menstrual cyclicity and may be an effective treatment option for some women with PCOS. Copyright © 2014 Elsevier Inc. All rights reserved.

The Role of Salivary Neuropeptides in Pediatrics: Potential Biomarkers for Integrated Therapies.

PubMed

Gershan, Lynn A; Durham, Paul L; Skidmore, Jaci; Shimizu, Joshua; Cady, Ryan J; Sheng, Xiaoming; Maloney, Christopher G

2015-08-01

Objective measures of symptom response to integrated complementary approaches in pediatrics are evolving. The purpose of this study was to document the concentration range of salivary neuropeptides in healthy controls and in children with cancer, to explore correlations between serum and salivary measurements for Calcitonin Gene-Related Peptide (CGRP) and Vasoactive Intestinal Polypeptide (VIP), and to determine whether there is a change in these salivary neuropeptide levels in response to integrated mind-body therapies. A non-randomized pragmatic study with three phases: Phase 1- Healthy Control Saliva-10 healthy controls provided saliva samples; Phase 2- Cancer Diagnosis Serum-Saliva- 16 mixed-type cancer patients provided blood and saliva samples; Phase 3- Acute Lymphocytic Leukemia (ALL) Saliva Intervention- 12 patients with ALL provided pre- and post-complementary intervention saliva samples. 20-minutes of structured touch or scripted relaxation breathing were administered to patients in Phase 3; Phase 1 and 2 patients did not receive this intervention. cortisol, CGRP, VIP, State/Trait Anxiety Scale, visual analogue scale, vital signs. Salivary CGRP and VIP were similar for children in Phases 1 and 2. There was a correlation between serum and salivary VIP in the mixed cancer group, though not between serum and salivary CGRP. In Phase 3 children, following a complementary intervention, salivary CGRP, heart rate, and systolic blood pressure decreased. These data provide evidence of a decrease in sympathetic output after integrative/complementary therapy intervention in children with cancer. The study underscores the potential role of salivary neuropeptides as non-invasive biomarkers for integrated therapies in pediatrics.

The Role of Salivary Neuropeptides in Pediatrics: Potential Biomarkers for Integrated Therapies

PubMed Central

Gershan, Lynn A; Durham, Paul L; Skidmore, Jaci; Shimizu, Joshua; Cady, Ryan J; Sheng, Xiaoming; Maloney, Christopher G

2015-01-01

Introduction Objective measures of symptom response to integrated complementary approaches in pediatrics are evolving. The purpose of this study was to document the concentration range of salivary neuropeptides in healthy controls and in children with cancer, to explore correlations between serum and salivary measurements for Calcitonin Gene-Related Peptide (CGRP) and Vasoactive Intestinal Polypeptide (VIP), and to determine whether there is a change in these salivary neuropeptide levels in response to integrated mind-body therapies. Methods A non-randomized pragmatic study with three phases: Phase 1- Healthy Control Saliva-10 healthy controls provided saliva samples; Phase 2- Cancer Diagnosis Serum-Saliva- 16 mixed-type cancer patients provided blood and saliva samples; Phase 3- Acute Lymphocytic Leukemia (ALL) Saliva Intervention- 12 patients with ALL provided pre- and post-complementary intervention saliva samples. Interventions 20-minutes of structured touch or scripted relaxation breathing were administered to patients in Phase 3; Phase 1 and 2 patients did not receive this intervention. Outcome Measures cortisol, CGRP, VIP, State/Trait Anxiety Scale, visual analogue scale, vital signs. Results Salivary CGRP and VIP were similar for children in Phases 1 and 2. There was a correlation between serum and salivary VIP in the mixed cancer group, though not between serum and salivary CGRP. In Phase 3 children, following a complementary intervention, salivary CGRP, heart rate, and systolic blood pressure decreased. Discussion/Conclusions These data provide evidence of a decrease in sympathetic output after integrative/complementary therapy intervention in children with cancer. The study underscores the potential role of salivary neuropeptides as non-invasive biomarkers for integrated therapies in pediatrics. PMID:26388958

Efficacious and safe management of moderate to severe scalp seborrhoeic dermatitis using clobetasol propionate shampoo 0·05% combined with ketoconazole shampoo 2%: a randomized, controlled study.

PubMed

Ortonne, J-P; Nikkels, A F; Reich, K; Ponce Olivera, R M; Lee, J H; Kerrouche, N; Sidou, F; Faergemann, J

2011-07-01

Topical antifungals and corticosteroids are the mainstay of treatment for seborrhoeic dermatitis. The short-contact clobetasol propionate 0·05% shampoo (CP) is an efficacious and safe once-daily treatment for scalp psoriasis. To evaluate the efficacy and safety of CP alone and combined with ketoconazole shampoo 2% (KC) in the treatment of moderate to severe scalp seborrhoeic dermatitis. This randomized and investigator-blinded study consisted of three phases, each lasting 4 weeks. During the treatment phase, subjects were randomized to receive KC twice weekly (K2), CP twice weekly (C2), CP twice weekly alternating with KC twice weekly (C2 + K2) or CP four times weekly alternating with KC twice weekly (C4+K2). All subjects received KC once weekly during the maintenance phase and were untreated during the follow-up phase. At the end of the treatment phase, all three CP-containing regimens were significantly more efficacious than K2 in decreasing the overall disease severity (P < 0·05). Both combination regimens were also significantly more efficacious than K2 in decreasing each individual sign of the disease (P < 0·05). While the C2 and C4 + K2 groups experienced slight worsening during the maintenance phase, the efficacy of C2 + K2 was sustained and remained the highest among all groups. All regimens were well tolerated without inducing any skin atrophy. Similarly low incidences of telangiectasia, burning and adverse events were observed among the four groups. The combination therapy of twice-weekly CP alternating with twice-weekly KC provided significantly greater efficacy than KC alone and a sustained effect in the treatment of moderate to severe scalp seborrhoeic dermatitis. © 2011 The Authors. BJD © 2011 British Association of Dermatologists 2011.

Phase II prospective randomized trial of weight loss prior to radical prostatectomy.

PubMed

Henning, Susanne M; Galet, Colette; Gollapudi, Kiran; Byrd, Joshua B; Liang, Pei; Li, Zhaoping; Grogan, Tristan; Elashoff, David; Magyar, Clara E; Said, Jonathan; Cohen, Pinchas; Aronson, William J

2017-12-04

Obesity is associated with poorly differentiated and advanced prostate cancer and increased mortality. In preclinical models, caloric restriction delays prostate cancer progression and prolongs survival. We sought to determine if weight loss (WL) in men with prostate cancer prior to radical prostatectomy affects tumor apoptosis and proliferation, and if WL effects other metabolic biomarkers. In this Phase II prospective trial, overweight and obese men scheduled for radical prostatectomy were randomized to a 5-8 week WL program consisting of standard structured energy-restricted meal plans (1200-1500 Kcal/day) and physical activity or to a control group. The primary endpoint was apoptotic index in the radical prostatectomy malignant epithelium. Secondary endpoints were proliferation (Ki67) in the radical prostatectomy tissue, body weight, body mass index (BMI), waist to hip ratio, body composition, and serum PSA, insulin, triglyceride, cholesterol, testosterone, estradiol, leptin, adiponectin, interleukin 6, interleukin 8, insulin-like growth factor 1, and IGF binding protein 1. In total 23 patients were randomized to the WL intervention and 21 patients to the control group. Subjects in the intervention group had significantly more weight loss (WL:-3.7 ± 0.5 kg; Control:-1.6 ± 0.5 kg; p = 0.007) than the control group and total fat mass was significantly reduced (WL:-2.1 ± 0.4; Control: 0.1 ± 0.3; p = 0.015). There was no significant difference in apoptotic or proliferation index between the groups. Among the other biomarkers, triglyceride, and insulin levels were significantly decreased in the WL compared with the control group. In summary, this short-term WL program prior to radical prostatectomy resulted in significantly more WL in the intervention vs. the control group and was accompanied by significant reductions in body fat mass, circulating triglycerides, and insulin. However, no significant changes were observed in malignant epithelium apoptosis or proliferation. Future studies should consider a longer term or more intensive weight loss intervention.

Sequential Phase 1 and Phase 2 randomized, controlled trials of the safety, immunogenicity and efficacy of combined pre-erythrocytic vaccine antigens RTS,S and TRAP formulated with AS02 Adjuvant System in healthy, malaria naïve adults.

PubMed

Kester, Kent E; Gray Heppner, D; Moris, Philippe; Ofori-Anyinam, Opokua; Krzych, Urszula; Tornieporth, Nadia; McKinney, Denise; Delchambre, Martine; Ockenhouse, Christian F; Voss, Gerald; Holland, Carolyn; Beckey, Jolie Palensky; Ballou, W Ripley; Cohen, Joe

2014-11-20

In an attempt to improve the efficacy of the candidate malaria vaccine RTS,S/AS02, two studies were conducted in 1999 in healthy volunteers of RTS,S/AS02 in combination with recombinant Plasmodium falciparum thrombospondin-related anonymous protein (TRAP). In a Phase 1 safety and immunogenicity study, volunteers were randomized to receive TRAP/AS02 (N=10), RTS,S/AS02 (N=10), or RTS,S+TRAP/AS02 (N=20) at 0, 1 and 6-months. In a Phase 2 challenge study, subjects were randomized to receive either RTS,S+TRAP/AS02 (N=25) or TRAP/AS02 (N=10) at 0 and 1-month, or to a challenge control group (N=8). In both studies, the combination vaccine had an acceptable safety profile and was acceptably tolerated. Antigen-specific antibodies, lymphoproliferative responses, and IFN-γ production by ELISPOT assay elicited with the combination vaccine were qualitatively similar to those generated by the single component vaccines. However, post-dose 2 anti-CS antibodies in the RTS,S+TRAP/AS02 vaccine recipients were lower than in the RTS,S/AS02 vaccine recipients. After challenge, 10 of 11 RTS,S+TRAP/AS02 vaccinees, 5 of 5 TRAP/AS02 vaccinees, and 8 of 8 infectivity controls developed parasitemia, with median pre-patent periods of 13.0, 11.0, and 12.0 days, respectively. The absence of any prevention or delay of parasitemia by TRAP/AS02 suggests no apparent added value of TRAP/AS02 as a candidate vaccine. The absence of significant protection or delay of parasitemia in the 11 RTS,S+TRAP/AS02 vaccine recipients contrasts with previous 2 dose studies of RTS,S/AS02. The small sample size did not permit identifying statistically significant differences between the study arms. However, we speculate, within the constraints of the challenge study, that the presence of the TRAP antigen may have interfered with the vaccine efficacy previously observed with this regimen of RTS,S/AS02, and that any future TRAP-based vaccines should consider employing alternative vaccine platforms. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

A Phase II/III randomized controlled trial comparing perioperative versus postoperative chemotherapy with mFOLFOX6 for lower rectal cancer with suspected lateral pelvic node metastasis: Japan Clinical Oncology Group Study JCOG1310 (PRECIOUS study).

PubMed

Ohue, Masayuki; Iwasa, Satoru; Kanemitsu, Yukihide; Hamaguchi, Tetsuya; Shiozawa, Manabu; Ito, Masaaki; Yasui, Masayoshi; Katayama, Hiroshi; Mizusawa, Junki; Shimada, Yasuhiro

2017-01-01

A randomized phase II/III trial was started in May 2015 comparing perioperative versus postoperative chemotherapy with modified infusional fluorouracil and folinic acid with oxaliplatin for lower rectal cancer patients with suspected lateral pelvic node metastasis. The standard arm is total mesorectal excision or tumor-specific mesorectal excision with lateral pelvic node dissection (LND) followed by postoperative chemotherapy (modified infusional fluorouracil and folinic acid with oxaliplatin; 12 cycles). The experimental (perioperative chemotherapy) arm is six courses of modified infusional fluorouracil and folinic acid with oxaliplatin before and six courses after total mesorectal excision with lateral pelvic node dissection. The aim of this trial is to confirm the superiority of perioperative chemotherapy. A total of 330 patients will be enrolled over 7 years. The primary endpoint in Phase II part is proportion of R0 resection and that in Phase III part is overall survival. Secondary endpoints are progression-free survival, local progression-free survival, etc. This trial has been registered in the UMIN Clinical Trials Registry as UMIN000017603 [http://www.umin.ac.jp/ctr/index-j.htm]. © The Author 2016. Published by Oxford University Press.

Phase 2 Placebo-Controlled Trial of Two Vaccines to Prevent Ebola in Liberia.

PubMed

Kennedy, Stephen B; Bolay, Fatorma; Kieh, Mark; Grandits, Greg; Badio, Moses; Ballou, Ripley; Eckes, Risa; Feinberg, Mark; Follmann, Dean; Grund, Birgit; Gupta, Swati; Hensley, Lisa; Higgs, Elizabeth; Janosko, Krisztina; Johnson, Melvin; Kateh, Francis; Logue, James; Marchand, Jonathan; Monath, Thomas; Nason, Martha; Nyenswah, Tolbert; Roman, François; Stavale, Eric; Wolfson, Julian; Neaton, James D; Lane, H Clifford

2017-10-12

The safety and efficacy of vaccines to prevent Ebola virus disease (EVD) were unknown when the incidence of EVD was peaking in Liberia. We initiated a randomized, placebo-controlled, phase 3 trial of the chimpanzee adenovirus 3 vaccine (ChAd3-EBO-Z) and the recombinant vesicular stomatitis virus vaccine (rVSV∆G-ZEBOV-GP) in Liberia. A phase 2 subtrial was embedded to evaluate safety and immunogenicity. Because the incidence of EVD declined in Liberia, the phase 2 component was expanded and the phase 3 component was eliminated. A total of 1500 adults underwent randomization and were followed for 12 months. The median age of the participants was 30 years; 36.6% of the participants were women. During the week after the administration of vaccine or placebo, adverse events occurred significantly more often with the active vaccines than with placebo; these events included injection-site reactions (in 28.5% of the patients in the ChAd3-EBO-Z group and 30.9% of those in the rVSV∆G-ZEBOV-GP group, as compared with 6.8% of those in the placebo group), headache (in 25.1% and 31.9%, vs. 16.9%), muscle pain (in 22.3% and 26.9%, vs. 13.3%), feverishness (in 23.9% and 30.5%, vs. 9.0%), and fatigue (in 14.0% and 15.4%, vs. 8.8%) (P<0.001 for all comparisons); these differences were not seen at 1 month. Serious adverse events within 12 months after injection were seen in 40 participants (8.0%) in the ChAd3-EBO-Z group, in 47 (9.4%) in the rVSV∆G-ZEBOV-GP group, and in 59 (11.8%) in the placebo group. By 1 month, an antibody response developed in 70.8% of the participants in the ChAd3-EBO-Z group and in 83.7% of those in the rVSV∆G-ZEBOV-GP group, as compared with 2.8% of those in the placebo group (P<0.001 for both comparisons). At 12 months, antibody responses in participants in the ChAd3-EBO-Z group (63.5%) and in those in the rVSV∆G-ZEBOV-GP group (79.5%) remained significantly greater than in those in the placebo group (6.8%, P<0.001 for both comparisons). A randomized, placebo-controlled phase 2 trial of two vaccines that was rapidly initiated and completed in Liberia showed the capability of conducting rigorous research during an outbreak. By 1 month after vaccination, the vaccines had elicited immune responses that were largely maintained through 12 months. (Funded by the National Institutes of Allergy and Infectious Diseases and the Liberian Ministry of Health; PREVAIL I ClinicalTrials.gov number, NCT02344407 .).

Effects of adjunctive treatment with aripiprazole on body weight and clinical efficacy in schizophrenia patients treated with clozapine: a randomized, double-blind, placebo-controlled trial.

PubMed

Fleischhacker, W Wolfgang; Heikkinen, Martti E; Olié, Jean-Pierre; Landsberg, Wally; Dewaele, Patricia; McQuade, Robert D; Loze, Jean-Yves; Hennicken, Delphine; Kerselaers, Wendy

2010-09-01

Clozapine is associated with significant weight gain and metabolic disturbances. This multicentre, randomized study comprised a double-blind, placebo-controlled treatment phase of 16 wk, and an open-label extension phase of 12 wk. Outpatients who met DSM-IV-TR criteria for schizophrenia, who were not optimally controlled while on stable dosage of clozapine for > or =3 months and had experienced weight gain of > or =2.5 kg while taking clozapine, were randomized (n=207) to aripiprazole at 5-15 mg/d or placebo, in addition to a stable dose of clozapine. The primary endpoint was mean change from baseline in body weight at week 16 (last observation carried forward). Secondary endpoints included clinical efficacy, body mass index (BMI) and waist circumference. A statistically significant difference in weight loss was reported for aripiprazole vs. placebo (-2.53 kg vs. -0.38 kg, respectively, difference=-2.15 kg, p<0.001). Aripiprazole-treated patients also showed BMI (median reduction 0.8 kg/m(2)) and waist circumference reduction (median reduction 2.0 cm) vs. placebo (no change in either parameter, p<0.001 and p=0.001, respectively). Aripiprazole-treated patients had significantly greater reductions in total and low-density lipoprotein (LDL) cholesterol. There were no significant differences in Positive and Negative Syndrome Scale total score changes between groups but Clinical Global Impression Improvement and Investigator's Assessment Questionnaire scores favoured aripiprazole over placebo. Safety and tolerability were generally comparable between groups. Combining aripiprazole and clozapine resulted in significant weight, BMI and fasting cholesterol benefits to patients suboptimally treated with clozapine. Improvements may reduce metabolic risk factors associated with clozapine treatment.

Efficacy and safety of Gantong Granules in the treatment of common cold with wind-heat syndrome: study protocol for a randomized controlled trial.

PubMed

Min, Jie; Li, Xiao-qiang; She, Bin; Chen, Yan; Mao, Bing

2015-05-19

Although the common cold is generally mild and self-limiting, it is a leading cause of consultations with doctors and missed days from school and work. In light of its favorable effects of relieving symptoms and minimal side-effects, Traditional Chinese Medicine (TCM) has been widely used to treat the common cold. However, there is a lack of robust evidence to support the clinical utility of such a treatment. This study is designed to evaluate the efficacy and safety of Gantong Granules compared with placebo in patients with the common cold with wind-heat syndrome (CCWHS). This is a multicenter, phase IIb, double-blind, placebo-controlled and randomized clinical trial. A total of 240 patients will be recruited, from 5 centers across China and randomly assigned to the high-dose group, medium-dose group, low-dose group or placebo control group in a 1:1:1:1 ratio. All subjects will receive the treatment for 3 to 5 days, followed by a 7-day follow-up period. The primary outcome is the duration of all symptoms. Secondary outcomes include the duration of primary symptoms and each symptom, time to fever relief and time to fever clearance, change in TCM symptom score, and change in Symptom and Sign Score. This trial will provide high-quality evidence on the efficacy and safety of Gantong Granules in treating CCWHS, and help to optimize the dose selection for a phase III clinical trial. The registration number is ChiCTR-TRC-14004255 , which was assigned by the Chinese Clinical Trial Registry on 12 February 2014.

Phase 2a, randomized, double-blind, placebo-controlled, multicenter, parallel-group study of a H4 R-antagonist (JNJ-39758979) in Japanese adults with moderate atopic dermatitis.

PubMed

Murata, Yoko; Song, Michael; Kikuchi, Hisayuki; Hisamichi, Katsuya; Xu, Xie L; Greenspan, Andrew; Kato, Mai; Chiou, Chiun-Fang; Kato, Takeshi; Guzzo, Cynthia; Thurmond, Robin L; Ohtsuki, Mamitaro; Furue, Masutaka

2015-02-01

This trial was conducted to evaluate the safety and efficacy of the H4 R-antagonist JNJ-39758979 in adult Japanese patients with moderate atopic dermatitis (AD). Eligible patients were randomly assigned to JNJ-39758979 300 mg, 100 mg or placebo once daily for 6 weeks in this phase 2a, double-blind, multicenter, placebo-controlled study. Primary efficacy was assessed via week-6 Eczema Area and Severity Index (EASI) scores. Secondary efficacy assessments included Investigator's Global Assessment (IGA) and patient-reported outcome (PRO) pruritus assessments (Pruritus Categorical Response Scale [PCRS], Pruritus Numeric Rating Scales [PNRS], Pruritus Interference Numeric Rating Scale [PINRS] and Subject's Global Impressions of Change in Pruritus [SGICP]). Eighty-eight of 105 planned patients were randomized before the study was stopped and unblinded for safety reasons. The study did not meet the primary end-point. However, numerical improvements (i.e. decreases) in median EASI were observed with JNJ-39758979 100 mg (-3.7) and 300 mg (-3.0) versus placebo (-1.3) at week 6. Nominally significant improvements across PRO PCRS, PNRS and SGICP assessments were consistently observed, particularly with JNJ-39758979 300 mg. Safety, including adverse events (AE), was comparable between JNJ-39758979 and placebo with the exception of two patients (both receiving JNJ-39758979 300 mg) with serious AE of neutropenia, leading to premature study discontinuation. No deaths were reported. Except for neutropenia, no clinically relevant changes in laboratory values were observed. Although not conclusive, findings suggest H4 R-antagonism may be beneficial for AD, particularly in controlling pruritus. JNJ-39758979 appears to be associated with drug-induced agranulocytosis, likely an off-target effect. © 2014 Japanese Dermatological Association.

Randomized, Double-Blind, Placebo- and Active Comparator-Controlled Crossover Study Evaluating the Abuse Potential of the Antiepileptic Drug Lacosamide in Healthy Recreational Drug Users.

PubMed

Schoedel, Kerri A; Andreas, Jens-Otto; Doty, Pamela; Eckhardt, Klaus; Sellers, Edward M

2017-12-01

This phase 1, randomized, double-blind, placebo- and active comparator-controlled crossover study assessed the abuse potential of the antiepileptic drug, lacosamide. After a qualification phase, 38 healthy, recreational central nervous system-depressant users were randomized to treatment sequences comprising single oral therapeutic (200 mg) and supratherapeutic (800 mg) doses of lacosamide, alprazolam (1.5 and 3 mg), and placebo. Subjective effects were assessed for 24 hours following each dose using a range of scales, with a 5- to 9-day washout between treatments. Mean subjective effects for 200 mg lacosamide were statistically similar to placebo and significantly lower than with alprazolam for most end points. Lacosamide 800 mg elicited transient, statistically significant positive effects compared with placebo, but also persistent Bad Drug Effects including statistically greater maximum effect (Emax) scores for Nausea and Dysphoria compared with other treatments (P < 0.0002). Consistent with this, the 800 mg lacosamide dose showed a significantly lower "at this moment" Drug Liking visual analog scale (VAS) Emax compared with 3 mg alprazolam, but was not different from 1.5 mg alprazolam (73.1/100, 85.4/100, and 78.9/100, respectively, where 50 is neutral). Overall Drug Liking VAS and Take Drug Again VAS Emax for 800 mg lacosamide were not significantly different from placebo and were lower than those for both alprazolam doses (P < 0.0001). These results suggest that in recreational central nervous system-depressant users, lacosamide has detectable abuse-related subjective effects, but a relatively low potential for abuse compared with alprazolam. These findings contributed toward placement of lacosamide into Schedule V of the US Controlled Substances Act.

Immunogenicity and safety of an E. coli-produced bivalent human papillomavirus (type 16 and 18) vaccine: A randomized controlled phase 2 clinical trial.

PubMed

Wu, Ting; Hu, Yue-Mei; Li, Juan; Chu, Kai; Huang, Shou-Jie; Zhao, Hui; Wang, Zhong-Ze; Yang, Chang-Lin; Jiang, Han-Min; Wang, Yi-Jun; Lin, Zhi-Jie; Pan, Hui-Rong; Sheng, Wei; Wei, Fei-Xue; Li, Shao-Wei; Wang, Ying; Zhu, Feng-Cai; Li, Chang-Gui; Zhang, Jun; Xia, Ning-Shao

2015-07-31

This study aimed to investigate the dosage, immunogenicity and safety profile of a novel human papillomavirus (HPV) types 16 and 18 bivalent vaccine produced by E. coli. This randomized, double-blinded, controlled phase 2 trial enrolled women aged 18-25 years in China. Totally 1600 eligible participants were randomized to receive 90μg, 60μg, or 30μg of the recombinant HPV 16/18 bivalent vaccine or the control hepatitis B vaccine on a 0, 1 and 6 month schedule. The designated doses are the combined micrograms of HPV16 and 18 VLPs with dose ratio of 2:1. The immunogenicity of the vaccines was assessed by measuring anti-HPV 16 and 18 neutralizing antibodies and total IgG antibodies. Safety of the vaccine was assessed. All but one of the seronegative participants who received 3 doses of the HPV vaccines seroconverted at month 7 for anti-HPV 16/18 neutralizing antibodies and IgG antibodies. For HPV 16, the geometric mean titers (GMTs) of the neutralizing antibodies were similar between the 60μg (GMT=10,548) and 90μg (GMT=12,505) HPV vaccine groups and were significantly higher than those in the 30μg (GMT=7596) group. For HPV 18, the GMTs of the neutralizing antibodies were similar among the 3 groups. The HPV vaccine was well tolerated. No vaccine-associated serious adverse events were identified. The prokaryotic-expressed HPV vaccine is safe and immunogenic in women aged 18-25 years. The 60μg dosage formulation was selected for further investigation for efficacy. NCT01356823. Copyright © 2015 Elsevier Ltd. All rights reserved.

[A multicenter, randomized, controlled, phase Ⅳ clinical study of PEG-rhG-CSF for preventing chemotherapy induced neutropenia in patients with breast cancer].

PubMed

Jiang, Z F; Xu, F R; Fan, J; Li, B J; Gao, J N; Hu, J W; Wang, X J; Zhang, Y Q; Wang, J H; Li, F; Liu, Q; Liu, Y H; Wang, S; Wang, Y S; Ouyang, Q C; Hu, B; Sun, G P; Zhang, Y; Zang, A M; Fan, P Z; Wu, C P; Liu, J; Zhang, H W; Wang, W; Hu, X C; Tang, L L; Zhang, J; Bao, Y Y; Geng, C Z; Sun, Q; Zhang, F; Yin, Y M; Jiang, H C; An, Y H

2018-04-24

Objective: To explore the efficacy and safety of polyethylene glycal recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patiens with breast cancer. Methods: There were two parts in the present phase Ⅳ clinical study. One was a randomized, controlled clinical study. Patients in this study received PEG-rhG-CSF or rhG-CSF in the first cycle and followed with both PEG-rhG-CSF in the rest of 3 cycles. The other one was a single arm study. Patients who developed Ⅲ/Ⅳ grade neutropenia in the screening cycle received PEG-rhG-CSF in the rest of 3 cycles chemotherapy. Results: In the first cycle of randomized, controlled study, the incidence of Ⅳ grade neutropenia are 31.48% and 35.58% respectively in PEG-rhG-CSF and rhG-CSF group, with no statistically significant differences ( P =0.527 6). The duration of Ⅳ grade neutropenia respectively are 2.22±1.58 and 3.00±1.59 days, with a statistically significant difference ( P =0.016 6). In the single arm study, the incidence of Ⅳ grade neutropenia was 57.76% in screening cycle. And the incidence decreased to 16.35%, 10%, and 8.57% in the followed 3 cycle after the use of PEG-rhG-CSF. The incidence of adverse effects was 5.06%, and the major adverse effect was bone pain which with an incidence of 2.8%. Conclusion: The fixed 6mg dose of PEG-rhG-CSF can effectively prevent neutropenia in patients with breast cancer in multicycle chemotherapy and it has a low incidence of adverse events and mild adverse reaction.

Effect of Guava in Blood Glucose and Lipid Profile in Healthy Human Subjects: A Randomized Controlled Study

PubMed Central

Rakavi, R; Mangaraj, Manaswini

2016-01-01

Introduction The fruit of Psidium guajava (P.guajava) is known to contain free sugars yet the fruit juice showed hypoglycaemic effect. Hypoglycaemic activity of guava leaves has been well documented but not for guava fruit. Aim So we aimed to evaluate the effect of ripe guava (with peel and without peel) fruit supplementation on blood glucose and lipid profile in healthy human subjects. Materials and Methods Randomized Controlled study undertaken in: 1) Baseline; 2) 6 weeks supplementation phase. Forty five healthy MBBS students were included and randomly enrolled into Group A, Group B and Group C. In Baseline phase: Fasting Plasma Glucose (FPG) and serum lipid profile was done in all 3 groups. Group A were supplemented with 400g of ripe guava with peel and group B without peel, for 6 weeks. Rest 15 treated as control i.e., Group C. Result Supplementation of ripe guava fruit with peel reduced BMI as well as blood pressure (p<0.05) in group A, whereas the FPG, Total cholesterol, Triglycerides were found significantly increased (p<0.05). Group B registered a significant fall (p<0.05) in BMI as well as blood pressure. Fall in FPG level after guava pulp supplementation was not significant. Serum Total cholesterol, Triglycerides and Low Density Lipoprotein Cholesterol (LDLc) levels decreased significantly (p<0.05) indicating that guava pulp without peel may have a favourable effect on lipid levels and blood sugar as well. Conclusion Guava fruit without peel is more effective in lowering blood sugar as well as serum total cholesterol, triglycerides and LDLc. It increases HDLc levels also. PMID:27790420

Impact of Virgin Olive Oil and Phenol-Enriched Virgin Olive Oils on the HDL Proteome in Hypercholesterolemic Subjects: A Double Blind, Randomized, Controlled, Cross-Over Clinical Trial (VOHF Study)

PubMed Central

Pedret, Anna; Catalán, Úrsula; Fernández-Castillejo, Sara; Farràs, Marta; Valls, Rosa-M; Rubió, Laura; Canela, Núria; Aragonés, Gerard; Romeu, Marta; Castañer, Olga; de la Torre, Rafael; Covas, Maria-Isabel; Fitó, Montse; Motilva, Maria-José; Solà, Rosa

2015-01-01

The effects of olive oil phenolic compounds (PCs) on HDL proteome, with respect to new aspects of cardioprotective properties, are still unknown. The aim of this study was to assess the impact on the HDL protein cargo of the intake of virgin olive oil (VOO) and two functional VOOs, enriched with their own PCs (FVOO) or complemented with thyme PCs (FVOOT), in hypercholesterolemic subjects. Eligible volunteers were recruited from the IMIM-Hospital del Mar Medical Research Institute (Spain) from April 2012 to September 2012. Thirty-three hypercholesterolemic participants (total cholesterol >200mg/dL; 19 men and 14 women; aged 35 to 80 years) were randomized in the double-blind, controlled, cross-over VOHF clinical trial. The subjects received for 3 weeks 25 mL/day of: VOO, FVOO, or FVOOT. Using a quantitative proteomics approach, 127 HDL-associated proteins were identified. Among these, 15 were commonly differently expressed after the three VOO interventions compared to baseline, with specific changes observed for each intervention. The 15 common proteins were mainly involved in the following pathways: LXR/RXR activation, acute phase response, and atherosclerosis. The three VOOs were well tolerated by all participants. Consumption of VOO, or phenol-enriched VOOs, has an impact on the HDL proteome in a cardioprotective mode by up-regulating proteins related to cholesterol homeostasis, protection against oxidation and blood coagulation while down-regulating proteins implicated in acute-phase response, lipid transport, and immune response. The common observed protein expression modifications after the three VOOs indicate a major matrix effect. Trial Registration International Standard Randomized Controlled Trials ISRCTN77500181. PMID:26061039

Impact of Virgin Olive Oil and Phenol-Enriched Virgin Olive Oils on the HDL Proteome in Hypercholesterolemic Subjects: A Double Blind, Randomized, Controlled, Cross-Over Clinical Trial (VOHF Study).

PubMed

Pedret, Anna; Catalán, Úrsula; Fernández-Castillejo, Sara; Farràs, Marta; Valls, Rosa-M; Rubió, Laura; Canela, Núria; Aragonés, Gerard; Romeu, Marta; Castañer, Olga; de la Torre, Rafael; Covas, Maria-Isabel; Fitó, Montse; Motilva, Maria-José; Solà, Rosa

2015-01-01

The effects of olive oil phenolic compounds (PCs) on HDL proteome, with respect to new aspects of cardioprotective properties, are still unknown. The aim of this study was to assess the impact on the HDL protein cargo of the intake of virgin olive oil (VOO) and two functional VOOs, enriched with their own PCs (FVOO) or complemented with thyme PCs (FVOOT), in hypercholesterolemic subjects. Eligible volunteers were recruited from the IMIM-Hospital del Mar Medical Research Institute (Spain) from April 2012 to September 2012. Thirty-three hypercholesterolemic participants (total cholesterol >200 mg/dL; 19 men and 14 women; aged 35 to 80 years) were randomized in the double-blind, controlled, cross-over VOHF clinical trial. The subjects received for 3 weeks 25 mL/day of: VOO, FVOO, or FVOOT. Using a quantitative proteomics approach, 127 HDL-associated proteins were identified. Among these, 15 were commonly differently expressed after the three VOO interventions compared to baseline, with specific changes observed for each intervention. The 15 common proteins were mainly involved in the following pathways: LXR/RXR activation, acute phase response, and atherosclerosis. The three VOOs were well tolerated by all participants. Consumption of VOO, or phenol-enriched VOOs, has an impact on the HDL proteome in a cardioprotective mode by up-regulating proteins related to cholesterol homeostasis, protection against oxidation and blood coagulation while down-regulating proteins implicated in acute-phase response, lipid transport, and immune response. The common observed protein expression modifications after the three VOOs indicate a major matrix effect. International Standard Randomized Controlled Trials ISRCTN77500181.

Hockey Fans in Training: A Pilot Pragmatic Randomized Controlled Trial.

PubMed

Petrella, Robert J; Gill, Dawn P; Zou, Guangyong; DE Cruz, Ashleigh; Riggin, Brendan; Bartol, Cassandra; Danylchuk, Karen; Hunt, Kate; Wyke, Sally; Gray, Cindy M; Bunn, Christopher; Zwarenstein, Merrick

2017-12-01

Hockey Fans in Training (Hockey FIT) is a gender-sensitized weight loss and healthy lifestyle program. We investigated 1) feasibility of recruiting and retaining overweight and obese men into a pilot pragmatic randomized controlled trial and 2) potential for Hockey FIT to lead to weight loss and improvements in other outcomes at 12 wk and 12 months. Male fans of two ice hockey teams (35-65 yr; body mass index ≥28 kg·m) located in Ontario (Canada) were randomized to intervention (Hockey FIT) or comparator (wait-list control). Hockey FIT includes a 12-wk active phase (weekly, coach-led group meetings including provision of dietary information, practice of behavior change techniques, and safe exercise sessions plus incremental pedometer walking) and a 40-wk minimally supported phase (smartphone app for sustaining physical activity, private online social network, standardized e-mails, booster session/reunion). Measurement at baseline and 12 wk (both groups) and 12 months (intervention group only) included clinical outcomes (e.g., weight) and self-reported physical activity, diet, and self-rated health. Eighty men were recruited in 4 wk; trial retention was >80% at 12 wk and >75% at 12 months. At 12 wk, the intervention group lost 3.6 kg (95% confidence interval, -5.26 to -1.90 kg) more than the comparator group (P < 0.001) and maintained this weight loss to 12 months. The intervention group also demonstrated greater improvements in other clinical measures, physical activity, diet, and self-rated health at 12 wk; most sustained to 12 months. Results suggest feasible recruitment/retention of overweight and obese men in the Hockey FIT program. Results provide evidence for the potential effectiveness of Hockey FIT for weight loss and improved health in at-risk men and, thus, evidence to proceed with a definitive trial.

Contingency management for college student smokers: The role of drinking as a moderator and mediator of smoking abstinence during treatment.

PubMed

Cassidy, Rachel N; Jackson, Kristina M; Rohsenow, Damaris J; Tidey, Jennifer W; Tevyaw, Tracy O' L; Barnett, Nancy P; Monti, Peter M; Miller, Mollie E; Colby, Suzanne M

2018-05-01

Contingency management (CM) is effective for promoting smoking abstinence; however, moderators and mediators of CM treatment efficacy in young adult populations are under-explored. We leveraged fine-grained data from a large randomized controlled trial: 1) to determine whether early attainment of sustained abstinence mediated the effect of treatment on abstinence; 2) to test whether heavy drinking moderated the effect of treatment on abstinence; and 3) to test a serial mediation model of the effects of drinking during early treatment on sustained smoking abstinence. College student smokers (N=110) were randomized to receive either CM treatment or noncontingent reinforcement (NR) over a 21-day treatment period. All participants received $5 for providing twice-daily breath carbon monoxide (CO) samples. In CM, additional money was provided for samples that indicated smoking reduction (Initial Phase; first 7days), and for samples ≤5ppm (Abstinence Phase; following 14days). CM treatment led to greater sustained abstinence relative to NR. Longer sustained abstinence in the Initial Phase partially mediated the effect of treatment on sustained abstinence in the Abstinence Phase. Heavier pretreatment drinkers had shorter periods of sustained abstinence in the Abstinence Phase; this effect was greater in CM. A serial mediation model determined that increased drinking during the Initial Phase led to decreased sustained abstinence, which then led to decreased sustained abstinence in the Abstinence Phase. These data provide a greater understanding of how heavy drinking and early sustained abstinence may affect success during treatment in young adults undergoing contingency management treatment for smoking. Copyright © 2018. Published by Elsevier Ltd.

The effect of mortality salience on women's judgments of male faces.

PubMed

Vaughn, James E; Bradley, Kristopher I; Byrd-Craven, Jennifer; Kennison, Shelia M

2010-08-30

Previous research has shown that individuals who are reminded of their death exhibited a greater desire for offspring than those who were not reminded of their death. The present research investigated whether being reminded of mortality affects mate selection behaviors, such as facial preference judgments. Prior research has shown that women prefer more masculine faces when they are at the high versus low fertility phase of their menstrual cycles. We report an experiment in which women were tested either at their high or fertility phase. They were randomly assigned to either a mortality salience (MS) or control condition and then asked to judge faces ranging from extreme masculine to extreme feminine. The results showed that women's choice of the attractive male face was determined by an interaction between fertility phase and condition. In control conditions, high fertility phase women preferred a significantly more masculine face than women who were in a lower fertility phase of their menstrual cycles. In MS conditions, high fertility phase women preferred a significantly less masculine (i.e., more average) face than women who were in a low fertility phase. The results indicate that biological processes, such as fertility phase, involved in mate selection are sensitive to current environmental factors, such as death reminders. This sensitivity may serve as an adaptive compromise when choosing a mate in potentially adverse environmental conditions.

Clinical evaluation of seven anticalculus dentifrice formulations.

PubMed

Scruggs, R R; Stewart, P W; Samuels, M S; Stamm, J W

1991-01-01

One hundred ninety-two subjects completed a clinical trial to determine the effects of seven dentifrice formulations on calculus inhibition. The double-blind study involved a ten-day control phase and a ten-day experimental phase. For the control phase, subjects were evaluated for calculus present, received a prophylaxis and had pre-weighed mylar strips attached to the lingual surfaces of the mandibular incisors to harvest mineral deposits. Subjects were then assigned the placebo dentifrice for unsupervised twice-daily use and were required to report once a day for a supervised mouthrinse using a 1:3 dilution of the dentrifice. The experimental phase was identical except that subjects were allocated the experimental dentifices using a stratified random assignment based on age, gender and the initial presence of calculus. Simple linear regression analyses of the dry and ash log weights obtained from the strips were performed. The results showed no statistically significant differences among the test products; however, two formulations containing zinc citrate showed some calculus inhibition-potential suggesting that further research and development of such products may be warranted.

Effect of Kangfuxin Solution on Chemo/Radiotherapy-Induced Mucositis in Nasopharyngeal Carcinoma Patients: A Multicenter, Prospective Randomized Phase III Clinical Study

PubMed Central

Luo, Yangkun; Feng, Mei; Fan, Zixuan; Zhu, Xiaodong; Jin, Feng; Li, Rongqing; Wu, Jingbo; Yang, Xia; Jiang, Qinghua; Bai, Hongfang; Huang, Yecai; Lang, Jinyi

2016-01-01

Objective. To evaluate the efficacy and safety of Kangfuxin Solution, a pure Chinese herbal medicine, on mucositis induced by chemoradiotherapy in nasopharyngeal carcinoma patients. Methods. A randomized, parallel-group, multicenter clinical study was performed. A total of 240 patients were randomized to receive either Kangfuxin Solution (test group) or compound borax gargle (control group) during chemoradiotherapy. Oral mucositis, upper gastrointestinal mucositis, and oral pain were evaluated by Common Terminology Criteria for Adverse Events (CTCAE) v3.0 and the Verbal Rating Scale (VRS). Results. Of 240 patients enrolled, 215 were eligible for efficacy analysis. Compared with the control group, the incidence and severity of oral mucositis in the test group were significantly reduced (P = 0.01). The time to different grade of oral mucositis occurrence (grade 1, 2, or 3) was longer in test group (P < 0.01), and the accumulated radiation dose was also higher in test group comparing to the control group (P < 0.05). The test group showed lower incidence of oral pain and gastrointestinal mucositis than the control group (P < 0.01). No significant adverse events were observed. Conclusion. Kangfuxin Solution demonstrated its superiority to compound borax gargle on mucositis induced by chemoradiotherapy. Its safety is acceptable for clinical application. PMID:27375766

A phase II randomized trial of Observation versus stereotactic ablative RadiatIon for OLigometastatic prostate CancEr (ORIOLE).

PubMed

Radwan, Noura; Phillips, Ryan; Ross, Ashley; Rowe, Steven P; Gorin, Michael A; Antonarakis, Emmanuel S; Deville, Curtiland; Greco, Stephen; Denmeade, Samuel; Paller, Channing; Song, Daniel Y; Diehn, Maximilian; Wang, Hao; Carducci, Michael; Pienta, Kenneth J; Pomper, Martin G; DeWeese, Theodore L; Dicker, Adam; Eisenberger, Mario; Tran, Phuoc T

2017-06-29

We describe a randomized, non-blinded Phase II interventional study to assess the safety and efficacy of stereotactic ablative radiotherapy (SABR) for hormone-sensitive oligometastatic prostate adenocarcinoma, and to describe the biology of the oligometastatic state using immunologic, cellular, molecular, and functional imaging correlates. 54 men with oligometastatic prostate adenocarcinoma will be accrued. The primary clinical endpoint will be progression at 6 months from randomization with the hypothesis that SABR to all metastases will forestall progression by disrupting the metastatic process. Secondary clinical endpoints will include local control at 6 months post-SABR, toxicity and quality of life, and androgen deprivation therapy (ADT)-free survival (ADT-FS). Further fundamental analysis of the oligometastatic state with be achieved through correlation with investigational 18 F-DCFPyL PET/CT imaging and measurement of circulating tumor cells, circulating tumor DNA, and circulating T-cell receptor repertoires, facilitating an unprecedented opportunity to characterize, in isolation, the effects of SABR on the dynamics of and immunologic response to oligometastatic disease. Patients will be randomized 2:1 to SABR or observation with minimization to balance assignment by primary intervention, prior hormonal therapy, and PSA doubling time. Progression after 6 months will be compared using Fisher's exact test. Hazard ratios and Kaplan-Meier estimates of progression free survival (PFS), ADT free survival (ADT-FS), time to locoregional progression (TTLP) and time to distant progression (TTDP) will be calculated based on an intention-to-treat. Local control will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Withdrawal from the study prior to 6 months will be counted as progression. Adverse events will be summarized by type and grade. Quality of life pre- and post- SABR will be measured by Brief Pain Inventory. The ORIOLE trial is the first randomized, non-blinded Phase II interventional study in the North America evaluating the safety and efficacy of SABR in oligometastatic hormone-sensitive prostate cancer. Leading-edge laboratory and imaging correlates will provide unique insight into the effects of SABR on the oligometastatic state. ClinicalTrials.gov Identifier: NCT02680587. URL of Registry: https://clinicaltrials.gov/show/NCT02680587 Date of Registration: 02/08/2016. Date of First Participant Enrollment: 05/23/2016.

The Phosphate Binder Ferric Citrate and Mineral Metabolism and Inflammatory Markers in Maintenance Dialysis Patients: Results From Prespecified Analyses of a Randomized Clinical Trial

PubMed Central

Van Buren, Peter N.; Lewis, Julia B.; Dwyer, Jamie P.; Greene, Tom; Middleton, John; Sika, Mohammed; Umanath, Kausik; Abraham, Josephine D.; Arfeen, Shahabul S.; Bowline, Isai G.; Chernin, Gil; Fadem, Stephen Z.; Goral, Simin; Koury, Mark; Sinsakul, Marvin V.; Weiner, Daniel E.

2016-01-01

Background Phosphate binders are the cornerstone of hyperphosphatemia management in dialysis patients. Ferric citrate is an iron-based oral phosphate binder that effectively lowers serum phosphorus levels. Study Design 52-week, open-label, phase 3, randomized, controlled trial for safety-profile assessment. Setting & Participants Maintenance dialysis patients with serum phosphorus levels ≥6.0 mg/dL after washout of prior phosphate binders. Intervention 2:1 randomization to ferric citrate or active control (sevelamer carbonate and/or calcium acetate). Outcomes Changes in mineral bone disease, protein-energy wasting/inflammation, and occurrence of adverse events after 1 year. Measurements Serum calcium, intact parathyroid hormone, phosphorus, aluminum, white blood cell count, percentage of lymphocytes, serum urea nitrogen, and bicarbonate. Results There were 292 participants randomly assigned to ferric citrate, and 149, to active control. Groups were well matched. For mean changes from baseline, phosphorus levels decreased similarly in the ferric citrate and active control groups (−2.04 ± 1.99 [SD] vs −2.18 ± 2.25 mg/dL, respectively; P = 0.9); serum calcium levels increased similarly in the ferric citrate and active control groups (0.22 ± 0.90 vs 0.31 ± 0.95 mg/dL; P = 0.2). Hypercalcemia occurred in 4 participants receiving calcium acetate. Parathyroid hormone levels decreased similarly in the ferric citrate and active control groups (−167.1 ± 399.8 vs −152.7 ± 392.1 pg/mL; P = 0.8). Serum albumin, bicarbonate, serum urea nitrogen, white blood cell count and percentage of lymphocytes, and aluminum values were similar between ferric citrate and active control. Total and low-density lipoprotein cholesterol levels were lower in participants receiving sevelamer than those receiving ferric citrate and calcium acetate. Fewer participants randomly assigned to ferric citrate had serious adverse events compared with active control. Limitations Open-label study, few peritoneal dialysis patients. Conclusions Ferric citrate was associated with similar phosphorus control compared to active control, with similar effects on markers of bone and mineral metabolism in dialysis patients. There was no evidence of protein-energy wasting/inflammation or aluminum toxicity, and fewer participants randomly assigned to ferric citrate had serious adverse events. Ferric citrate is an effective phosphate binder with a safety profile comparable to sevelamer and calcium acetate. PMID:25958079

Speeding up image quality improvement in random phase-free holograms using ringing artifact characteristics.

PubMed

Nagahama, Yuki; Shimobaba, Tomoyoshi; Kakue, Takashi; Masuda, Nobuyuki; Ito, Tomoyoshi

2017-05-01

A holographic projector utilizes holography techniques. However, there are several barriers to realizing holographic projections. One is deterioration of hologram image quality caused by speckle noise and ringing artifacts. The combination of the random phase-free method and the Gerchberg-Saxton (GS) algorithm has improved the image quality of holograms. However, the GS algorithm requires significant computation time. We propose faster methods for image quality improvement of random phase-free holograms using the characteristics of ringing artifacts.

Promoting state health department evidence-based cancer and chronic disease prevention: a multi-phase dissemination study with a cluster randomized trial component

PubMed Central

2013-01-01

Background Cancer and other chronic diseases reduce quality and length of life and productivity, and represent a significant financial burden to society. Evidence-based public health approaches to prevent cancer and other chronic diseases have been identified in recent decades and have the potential for high impact. Yet, barriers to implement prevention approaches persist as a result of multiple factors including lack of organizational support, limited resources, competing emerging priorities and crises, and limited skill among the public health workforce. The purpose of this study is to learn how best to promote the adoption of evidence based public health practice related to chronic disease prevention. Methods/design This paper describes the methods for a multi-phase dissemination study with a cluster randomized trial component that will evaluate the dissemination of public health knowledge about evidence-based prevention of cancer and other chronic diseases. Phase one involves development of measures of practitioner views on and organizational supports for evidence-based public health and data collection using a national online survey involving state health department chronic disease practitioners. In phase two, a cluster randomized trial design will be conducted to test receptivity and usefulness of dissemination strategies directed toward state health department chronic disease practitioners to enhance capacity and organizational support for evidence-based chronic disease prevention. Twelve state health department chronic disease units will be randomly selected and assigned to intervention or control. State health department staff and the university-based study team will jointly identify, refine, and select dissemination strategies within intervention units. Intervention (dissemination) strategies may include multi-day in-person training workshops, electronic information exchange modalities, and remote technical assistance. Evaluation methods include pre-post surveys, structured qualitative phone interviews, and abstraction of state-level chronic disease prevention program plans and progress reports. Trial registration clinicaltrials.gov: NCT01978054. PMID:24330729

Self-duality and phase structure of the 4D random-plaquette Z2 gauge model

NASA Astrophysics Data System (ADS)

Arakawa, Gaku; Ichinose, Ikuo; Matsui, Tetsuo; Takeda, Koujin

2005-03-01

In the present paper, we shall study the 4-dimensional Z lattice gauge model with a random gauge coupling; the random-plaquette gauge model (RPGM). The random gauge coupling at each plaquette takes the value J with the probability 1-p and - J with p. This model exhibits a confinement-Higgs phase transition. We numerically obtain a phase boundary curve in the (p-T)-plane where T is the "temperature" measured in unit of J/k. This model plays an important role in estimating the accuracy threshold of a quantum memory of a toric code. In this paper, we are mainly interested in its "self-duality" aspect, and the relationship with the random-bond Ising model (RBIM) in 2-dimensions. The "self-duality" argument can be applied both for RPGM and RBIM, giving the same duality equations, hence predicting the same phase boundary. The phase boundary curve obtained by our numerical simulation almost coincides with this predicted phase boundary at the high-temperature region. The phase transition is of first order for relatively small values of p<0.08, but becomes of second order for larger p. The value of p at the intersection of the phase boundary curve and the Nishimori line is regarded as the accuracy threshold of errors in a toric quantum memory. It is estimated as p=0.110±0.002, which is very close to the value conjectured by Takeda and Nishimori through the "self-duality" argument.

Prebiopsy Multiparametric Magnetic Resonance Imaging for Prostate Cancer Diagnosis in Biopsy-naive Men with Suspected Prostate Cancer Based on Elevated Prostate-specific Antigen Values: Results from a Randomized Prospective Blinded Controlled Trial.

PubMed

Tonttila, Panu P; Lantto, Juha; Pääkkö, Eija; Piippo, Ulla; Kauppila, Saila; Lammentausta, Eveliina; Ohtonen, Pasi; Vaarala, Markku H

2016-03-01

Multiparametric magnetic resonance imaging (MP-MRI) may improve the detection of clinically significant prostate cancer (PCa). To compare MP-MRI transrectal ultrasound (TRUS)-fusion targeted biopsy with routine TRUS-guided random biopsy for overall and clinically significant PCa detection among patients with suspected PCa based on prostate-specific antigen (PSA) values. This institutional review board-approved, single-center, prospective, randomized controlled trial (April 2011 to December 2014) included 130 biopsy-naive patients referred for prostate biopsy based on PSA values (PSA <20 ng/ml or free-to-total PSA ratio ≤0.15 and PSA <10 ng/ml). Patients were randomized 1:1 to the MP-MRI or control group. Patients in the MP-MRI group underwent prebiopsy MP-MRI followed by 10- to 12-core TRUS-guided random biopsy and cognitive MRI/TRUS fusion targeted biopsy. The control group underwent TRUS-guided random biopsy alone. MP-MRI 3-T phased-array surface coil. The primary outcome was the number of patients with biopsy-proven PCa in the MP-MRI and control groups. Secondary outcome measures included the number of positive prostate biopsies and the proportion of clinically significant PCa in the MP-MRI and control groups. Between-group analyses were performed. Overall, 53 and 60 patients were evaluable in the MP-MRI and control groups, respectively. The overall PCa detection rate and the clinically significant cancer detection rate were similar between the MP-MRI and control groups, respectively (64% [34 of 53] vs 57% [34 of 60]; 7.5% difference [95% confidence interval (CI), -10 to 25], p=0.5, and 55% [29 of 53] vs 45% [27 of 60]; 9.7% difference [95% CI, -8.5 to 27], p=0.8). The PCa detection rate was higher than assumed during the planning of this single-center trial. MP-MRI/TRUS-fusion targeted biopsy did not improve PCa detection rate compared with TRUS-guided biopsy alone in patients with suspected PCa based on PSA values. In this randomized clinical trial, additional prostate magnetic resonance imaging (MRI) before prostate biopsy appeared to offer similar diagnostic accuracy compared with routine transrectal ultrasound-guided random biopsy in the diagnosis of prostate cancer. Similar numbers of cancers were detected with and without MRI. ClinicalTrials.gov identifier: NCT01357512. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Color image encryption based on gyrator transform and Arnold transform

NASA Astrophysics Data System (ADS)

Sui, Liansheng; Gao, Bo

2013-06-01

A color image encryption scheme using gyrator transform and Arnold transform is proposed, which has two security levels. In the first level, the color image is separated into three components: red, green and blue, which are normalized and scrambled using the Arnold transform. The green component is combined with the first random phase mask and transformed to an interim using the gyrator transform. The first random phase mask is generated with the sum of the blue component and a logistic map. Similarly, the red component is combined with the second random phase mask and transformed to three-channel-related data. The second random phase mask is generated with the sum of the phase of the interim and an asymmetrical tent map. In the second level, the three-channel-related data are scrambled again and combined with the third random phase mask generated with the sum of the previous chaotic maps, and then encrypted into a gray scale ciphertext. The encryption result has stationary white noise distribution and camouflage property to some extent. In the process of encryption and decryption, the rotation angle of gyrator transform, the iterative numbers of Arnold transform, the parameters of the chaotic map and generated accompanied phase function serve as encryption keys, and hence enhance the security of the system. Simulation results and security analysis are presented to confirm the security, validity and feasibility of the proposed scheme.

Computational wavelength resolution for in-line lensless holography: phase-coded diffraction patterns and wavefront group-sparsity

NASA Astrophysics Data System (ADS)

Katkovnik, Vladimir; Shevkunov, Igor; Petrov, Nikolay V.; Egiazarian, Karen

2017-06-01

In-line lensless holography is considered with a random phase modulation at the object plane. The forward wavefront propagation is modelled using the Fourier transform with the angular spectrum transfer function. The multiple intensities (holograms) recorded by the sensor are random due to the random phase modulation and noisy with Poissonian noise distribution. It is shown by computational experiments that high-accuracy reconstructions can be achieved with resolution going up to the two thirds of the wavelength. With respect to the sensor pixel size it is a super-resolution with a factor of 32. The algorithm designed for optimal superresolution phase/amplitude reconstruction from Poissonian data is based on the general methodology developed for phase retrieval with a pixel-wise resolution in V. Katkovnik, "Phase retrieval from noisy data based on sparse approximation of object phase and amplitude", http://www.cs.tut.fi/ lasip/DDT/index3.html.

Inflammatory response, growth, and thyroid hormone concentrations are affected by long-term boron supplementation in gilts.

PubMed

Armstrong, T A; Spears, J W; Lloyd, K E

2001-06-01

An experiment was conducted to determine the long-term effects of dietary boron (B) on growth performance, immune function, and plasma and serum characteristics in gilts. Fifty weanling gilts were allotted to 10 pens based on weaning weight and litter origin. Pens were randomly assigned to receive one of two dietary treatments. Treatments consisted of a basal diet low in B (control) and the basal diet supplemented with 5 mg B/kg diet as sodium borate. Gilts remained on their respective experimental diets and with their penmates throughout the nursery, growing, and finishing phases. The B concentration of the basal diet was 0.98, 2.1, and 2.2 mg/kg diet during the nursery, growing, and finishing phases, respectively. At the end of each production phase, animals were weighed and feed consumption was determined to assess growth performance variables. In addition, blood samples were obtained from three randomly selected gilts per pen at the completion of each phase. Boron had no affect (P > 0.58) on growth performance during the nursery phase, but gilts receiving supplemental B had increased (P < 0.05) ADG at the end of the finishing phase and over the entire growing-finishing period. Serum concentrations of triiodothyronine (T3) tended (P < 0.07) to be reduced by dietary B at the end of the nursery phase, but serum thyroxine (T4) was not affected (P = 0.46) by B. At the completion of the growing phase, supplemental B decreased (P < 0.05) the concentrations of T3 and T4 in the serum. In addition, serum concentrations of total cholesterol and the activity of alkaline phosphatase were increased (P < 0.05) by dietary B at the end of the growing phase. Serum concentrations of urea N tended (P < 0.09) to be increased by B at the end of the growing phase. Beginning at d 95 of the experimental period, measures of immune function were assessed in randomly selected gilts. Boron decreased (P < 0.05) the inflammatory response to an intradermal injection of phytohemagglutinin. Boron did not affect (P > 0.30) the blastogenic response of isolated lymphocytes to mitogen stimulation or the humoral immune response against a sheep red blood cell suspension. Results indicate that B may affect serum thyroid hormone concentrations, the inflammatory response, and growth in pigs.

A double-blind randomized discontinuation phase II study of sorafenib (BAY 43-9006) in previously treated non-small cell lung cancer patients: Eastern Cooperative Oncology Group study E2501

PubMed Central

Wakelee, Heather A.; Lee, Ju-Whei; Hanna, Nasser H.; Traynor, Anne M.; Carbone, David P.; Schiller, Joan H.

2012-01-01

Introduction Sorafenib is a raf kinase and angiogenesis inhibitor with activity in multiple cancers. This phase II study in heavily pretreated non-small cell lung cancer (NSCLC) patients (≥ two prior therapies) utilized a randomized discontinuation design. Methods Patients received 400 mg of sorafenib orally twice daily for two cycles (two months) (Step 1). Responding patients on Step 1 continued on sorafenib; progressing patients went off study, and patients with stable disease were randomized to placebo or sorafenib (Step 2), with crossover from placebo allowed upon progression. The primary endpoint of this study was the proportion of patients having stable or responding disease two months after randomization. Results : There were 299 patients evaluated for Step 1 with 81 eligible patients randomized on Step 2 who received sorafenib (n=50) or placebo (n=31). The two-month disease control rates following randomization were 54% and 23% for patients initially receiving sorafenib and placebo respectively, p=0.005. The hazard ratio for progression on Step 2 was 0.51 (95% CI 0.30, 0.87, p=0.014) favoring sorafenib. A trend in favor of overall survival with sorafenib was also observed (13.7 versus 9.0 months from time of randomization), HR 0.67 (95% CI 0.40-1.11), p=0.117. A dispensing error occurred which resulted in unblinding of some patients, but not before completion of the 8 week initial step 2 therapy. Toxicities were manageable and as expected. Conclusions : The results of this randomized discontinuation trial suggest that sorafenib has single agent activity in a heavily pretreated, enriched patient population with advanced NSCLC. These results support further investigation with sorafenib as a single agent in larger, randomized studies in NSCLC. PMID:22982658

Effect of Terbinafine on Theophylline Pharmacokinetics in Healthy Volunteers

PubMed Central

Trépanier, Eric F.; Nafziger, Anne N.; Amsden, Guy W.

1998-01-01

Twelve healthy volunteers were enrolled in an open-label, randomized, crossover study. Subjects received single doses of theophylline (5 mg/kg) with and without multiple-dose terbinafine, and 11 blood samples were collected over 24 h. The study phases were separated by a 4-week washout period. Theophylline serum data were modeled via noncompartmental analysis. When the control phase (i.e., no terbinafine) was compared to the treatment phase (terbinafine), theophylline exposure (the area under the serum concentration-time curve from time zero to infinity) increased by 16% (P = 0.03), oral clearance decreased by 14% (P = 0.04), and half-life increased by 24% (P = 0.002). No significant changes in other theophylline pharmacokinetic parameters were evident. PMID:9517954

Motions and functional performance after supervised physical therapy program versus home-based program after arthroscopic anterior shoulder stabilization: a randomized clinical trial.

PubMed

Ismail, M M; El Shorbagy, K M

2014-01-01

To compare the effects of a standardized supervised physical therapy versus a controlled home-based programs on the rate of shoulder motion and functional recovery after arthroscopic anterior shoulder stabilization. Twenty-seven patients (18-35years) underwent arthroscopic anterior shoulder stabilization. Patients were randomized into two groups. A supervised group (n=14) received a rehabilitation program, 3 sessions/week for 24 weeks and a controlled home treated group (n=13) who followed a home-based program for same period. Range of motion (ROM) of the shoulder was assessed 4 times after each phase of rehabilitation and function was assessed after the 3rd and 4th phase of rehabilitation. Both groups achieved a significant progressive increase in all shoulder motions throughout the study period. Patients in the supervised group achieved 92.6% and 94.2% of the contralateral side in abduction and forward elevation respectively. The controlled home-based group achieved 87.1% and 94.7% of abduction and forward elevation respectively. For external rotation, the percentage ROM achieved was 81.1% for the supervised group and 76.4% for the controlled home-based group. For function assessment, the two groups showed a significant improvement. However, the two groups were not significantly different from each other in all measured variables. A controlled home-based physical therapy program is as effective as a supervised program in increasing shoulder range of motion and function after arthroscopic anterior shoulder stabilization. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Immunogenicity and safety of tetravalent dengue vaccine in 2-11 year-olds previously vaccinated against yellow fever: randomized, controlled, phase II study in Piura, Peru.

PubMed

Lanata, Claudio F; Andrade, Teresa; Gil, Ana I; Terrones, Cynthia; Valladolid, Omar; Zambrano, Betzana; Saville, Melanie; Crevat, Denis

2012-09-07

In a randomized, placebo-controlled, monocenter, observer blinded study conducted in an area where dengue is endemic, we assessed the safety and immunogenicity of a recombinant, live, attenuated, tetravalent dengue vaccine candidate (CYD-TDV) in 2-11 year-olds with varying levels of pre-existing yellow-fever immunity due to vaccination 1-7 years previously. 199 children received 3 injections of CYD-TDV (months 0, 6 and 12) and 99 received placebo (months 0 and 6) or pneumococcal polysaccharide vaccine (month 12). One month after the third dengue vaccination, serotype specific neutralizing antibody GMTs were in the range of 178-190 (1/dil) (versus 16.7-38.1 in the control group), a 10-20 fold-increase from baseline, and 94% of vaccines were seropositive to all four serotypes (versus 39% in the control group). There were no vaccine-related SAEs. The observed reactogenicity profile was consistent with phase I studies, with severity grade 1-2 injection site pain, headache, malaise and fever most frequently reported and no increase after subsequent vaccinations. Virologically confirmed dengue cases were seen after completion of the 3 doses: 1 in the CYD-TDV group (N=199), and 3 in the control group (N=99). A 3-dose regimen of CYD-TDV had a good safety profile in 2-11 year olds with a history of YF vaccination and elicited robust antibody responses that were balanced against the four serotypes. Copyright © 2012 Elsevier Ltd. All rights reserved.

A class of optimum digital phase locked loops for the DSN advanced receiver

NASA Technical Reports Server (NTRS)

Hurd, W. J.; Kumar, R.

1985-01-01

A class of optimum digital filters for digital phase locked loop of the deep space network advanced receiver is discussed. The filter minimizes a weighted combination of the variance of the random component of the phase error and the sum square of the deterministic dynamic component of phase error at the output of the numerically controlled oscillator (NCO). By varying the weighting coefficient over a suitable range of values, a wide set of filters are obtained such that, for any specified value of the equivalent loop-noise bandwidth, there corresponds a unique filter in this class. This filter thus has the property of having the best transient response over all possible filters of the same bandwidth and type. The optimum filters are also evaluated in terms of their gain margin for stability and their steady-state error performance.

Attosecond control of electronic processes by intense light fields.

PubMed

Baltuska, A; Udem, Th; Uiberacker, M; Hentschel, M; Goulielmakis, E; Gohle, Ch; Holzwarth, R; Yakovlev, V S; Scrinzi, A; Hänsch, T W; Krausz, F

2003-02-06

The amplitude and frequency of laser light can be routinely measured and controlled on a femtosecond (10(-15) s) timescale. However, in pulses comprising just a few wave cycles, the amplitude envelope and carrier frequency are not sufficient to characterize and control laser radiation, because evolution of the light field is also influenced by a shift of the carrier wave with respect to the pulse peak. This so-called carrier-envelope phase has been predicted and observed to affect strong-field phenomena, but random shot-to-shot shifts have prevented the reproducible guiding of atomic processes using the electric field of light. Here we report the generation of intense, few-cycle laser pulses with a stable carrier envelope phase that permit the triggering and steering of microscopic motion with an ultimate precision limited only by quantum mechanical uncertainty. Using these reproducible light waveforms, we create light-induced atomic currents in ionized matter; the motion of the electronic wave packets can be controlled on timescales shorter than 250 attoseconds (250 x 10(-18) s). This enables us to control the attosecond temporal structure of coherent soft X-ray emission produced by the atomic currents--these X-ray photons provide a sensitive and intuitive tool for determining the carrier-envelope phase.

Phase 1b randomized trial and follow-up study in Uganda of the blood-stage malaria vaccine candidate BK-SE36.

PubMed

Palacpac, Nirianne Marie Q; Ntege, Edward; Yeka, Adoke; Balikagala, Betty; Suzuki, Nahoko; Shirai, Hiroki; Yagi, Masanori; Ito, Kazuya; Fukushima, Wakaba; Hirota, Yoshio; Nsereko, Christopher; Okada, Takuya; Kanoi, Bernard N; Tetsutani, Kohhei; Arisue, Nobuko; Itagaki, Sawako; Tougan, Takahiro; Ishii, Ken J; Ueda, Shigeharu; Egwang, Thomas G; Horii, Toshihiro

2013-01-01

Up to now a malaria vaccine remains elusive. The Plasmodium falciparum serine repeat antigen-5 formulated with aluminum hydroxyl gel (BK-SE36) is a blood-stage malaria vaccine candidate that has undergone phase 1a trial in malaria-naive Japanese adults. We have now assessed the safety and immunogenicity of BK-SE36 in a malaria endemic area in Northern Uganda. We performed a two-stage, randomized, single-blinded, placebo-controlled phase 1b trial (Current Controlled trials ISRCTN71619711). A computer-generated sequence randomized healthy subjects for 2 subcutaneous injections at 21-day intervals in Stage1 (21-40 year-olds) to 1-mL BK-SE36 (BKSE1.0) (n = 36) or saline (n = 20) and in Stage2 (6-20 year-olds) to BKSE1.0 (n = 33), 0.5-mL BK-SE36 (BKSE0.5) (n = 33), or saline (n = 18). Subjects and laboratory personnel were blinded. Safety and antibody responses 21-days post-second vaccination (Day42) were assessed. Post-trial, to compare the risk of malaria episodes 130-365 days post-second vaccination, Stage2 subjects were age-matched to 50 control individuals. Nearly all subjects who received BK-SE36 had induration (Stage1, n = 33, 92%; Stage2, n = 63, 96%) as a local adverse event. No serious adverse event related to BK-SE36 was reported. Pre-existing anti-SE36 antibody titers negatively correlated with vaccination-induced antibody response. At Day42, change in antibody titers was significant for seronegative adults (1.95-fold higher than baseline [95% CI, 1.56-2.43], p = 0.004) and 6-10 year-olds (5.71-fold [95% CI, 2.38-13.72], p = 0.002) vaccinated with BKSE1.0. Immunogenicity response to BKSE0.5 was low and not significant (1.55-fold [95% CI, 1.24-1.94], p = 0.75). In the ancillary analysis, cumulative incidence of first malaria episodes with ≥5000 parasites/µL was 7 cases/33 subjects in BKSE1.0 and 10 cases/33 subjects in BKSE0.5 vs. 29 cases/66 subjects in the control group. Risk ratio for BKSE1.0 was 0.48 (95% CI, 0.24-0.98; p = 0.04). BK-SE36 is safe and immunogenic. The promising potential of BK-SE36, observed in the follow-up study, warrants a double-blind phase 1/2b trial in children under 5 years. Controlled-Trials.com ISRCTN71619711.

Improved leukemia-free survival after postconsolidation immunotherapy with histamine dihydrochloride and interleukin-2 in acute myeloid leukemia: results of a randomized phase 3 trial.

PubMed

Brune, Mats; Castaigne, Sylvie; Catalano, John; Gehlsen, Kurt; Ho, Anthony D; Hofmann, Wolf-Karsten; Hogge, Donna E; Nilsson, Bo; Or, Reuven; Romero, Ana I; Rowe, Jacob M; Simonsson, Bengt; Spearing, Ruth; Stadtmauer, Edward A; Szer, Jeff; Wallhult, Elisabeth; Hellstrand, Kristoffer

2006-07-01

The primary objective of this phase 3 study was to determine whether postconsolidation immunotherapy with interleukin-2 (IL-2) and histamine dihydrochloride (HDC) improved the leukemia-free survival (LFS) of adult patients with acute myeloid leukemia (AML) in complete remission (CR). Three hundred twenty patients with AML (median age, 57 years; range, 18-84 years) were stratified by CR1 or subsequent CR (CR > 1) and randomly assigned to treatment with HDC/IL-2 or no treatment (control). Treatment comprised 10 21-day cycles with IL-2 (16 400 U/kg) plus HDC (0.5 mg); both compounds were administered by subcutaneous injection twice daily. Study arms were balanced for age, sex, previous treatment, leukemic karyotypes, time from CR to inclusion, and frequency of secondary leukemia. Three years after enrollment of the last patient, treatment with HDC/IL-2 was found to improve LFS over control in the study population (CR1 + CR > 1, n = 320; P < .01, log-rank test). For patients in CR1 (n = 261), treatment significantly improved LFS (P = .01) with 3-year LFS estimates of 40% (HDC/IL-2) compared with 26% (control). Side effects were typically mild to moderate. These results indicate that HDC/IL-2 treatment offers an efficacious and tolerable treatment for patients with AML in remission.

Efficacy of S-flurbiprofen plaster in knee osteoarthritis treatment: Results from a phase III, randomized, active-controlled, adequate, and well-controlled trial.

PubMed

Yataba, Ikuko; Otsuka, Noboru; Matsushita, Isao; Matsumoto, Hideo; Hoshino, Yuichi

2017-01-01

S-flurbiprofen plaster (SFPP) is a novel non-steroidal anti-inflammatory drug (NSAID) patch, intended for topical treatment for musculoskeletal diseases. This trial was conducted to examine the effectiveness of SFPP using active comparator, flurbiprofen (FP) patch, on knee osteoarthritis (OA) symptoms. This was a phase III, multi-center, randomized, adequate, and well-controlled trial, both investigators and patients were blinded to the assigned treatment. Enrolled 633 knee OA patients were treated with either SFPP or FP patch for two weeks. The primary endpoint was improvement in knee pain on rising from the chair as assessed by visual analogue scale (rVAS). Safety was evaluated through adverse events (AEs). The change in rVAS was 40.9 mm in SFPP group and 30.6 mm in FP patch group (p < 0.001). The incidence of drug-related AEs at the application site was 9.5% (32 AEs, 29 mild and 3 moderate) in SFPP and 1.6% in FP patch (p < 0.001). Withdrawals due to AE were five in SFPP and one in FP patch. The superiority of SFPP in efficacy was demonstrated. Most of AEs were mild and few AEs led to treatment discontinuation. Therefore, SFPP provides an additional option for knee OA therapy.

Spatial Distribution of Phase Singularities in Optical Random Vector Waves.

PubMed

De Angelis, L; Alpeggiani, F; Di Falco, A; Kuipers, L

2016-08-26

Phase singularities are dislocations widely studied in optical fields as well as in other areas of physics. With experiment and theory we show that the vectorial nature of light affects the spatial distribution of phase singularities in random light fields. While in scalar random waves phase singularities exhibit spatial distributions reminiscent of particles in isotropic liquids, in vector fields their distribution for the different vector components becomes anisotropic due to the direct relation between propagation and field direction. By incorporating this relation in the theory for scalar fields by Berry and Dennis [Proc. R. Soc. A 456, 2059 (2000)], we quantitatively describe our experiments.

Acceptance of internet-based hearing healthcare among adults who fail a hearing screening.

PubMed

Rothpletz, Ann M; Moore, Ashley N; Preminger, Jill E

2016-09-01

This study measured help-seeking readiness and acceptance of existing internet-based hearing healthcare (IHHC) websites among a group of older adults who failed a hearing screening (Phase 1). It also explored the effects of brief training on participants' acceptance of IHHC (Phase 2). Twenty-seven adults (age 55+) who failed a hearing screening participated. During Phase 1 participants were administered the University of Rhode Island Change Assessment (URICA) and patient technology acceptance model (PTAM) Questionnaire. During Phase 2 participants were randomly assigned to a training or control group. Training group participants attended an instructional class on existing IHHC websites. The control group received no training. The PTAM questionnaire was re-administered to both groups 4-6 weeks following the initial assessment. The majority of participants were either considering or preparing to do something about their hearing loss, and were generally accepting of IHHC websites (Phase 1). The participants who underwent brief IHHC training reported increases in hearing healthcare knowledge and slight improvements in computer self-efficacy (Phase 2). Older adults who fail hearing screenings may be good candidates for IHHC. The incorporation of a simple user-interface and short-term training may optimize the usability of future IHHC programs for this population.

Blocking carbohydrate absorption and weight loss: a clinical trial using Phase 2 brand proprietary fractionated white bean extract.

PubMed

Udani, Jay; Hardy, Mary; Madsen, Damian C

2004-03-01

Phase 2' starch neutralizer brand bean extract product ("Phase 2") is a water-extract of a common white bean (Phaseolus vulgaris) that has been shown in vitro to inhibit the digestive enzyme alpha-amylase. Inhibiting this enzyme may prevent the digestion of complex carbohydrates, thus decreasing the number of carbohydrate calories absorbed and potentially promoting weight loss. Fifty obese adults were screened to participate in a randomized, double-blind, placebo-controlled study evaluating the effects of treatment with Phase 2 versus placebo on weight loss. Participants were randomized to receive either 1500 mg Phase 2 or an identical placebo twice daily with meals. The active study period was eight weeks. Thirty-nine subjects completed the initial screening process and 27 subjects completed the study. The results after eight weeks demonstrated the Phase 2 group lost an average of 3.79 lbs (average of 0.47 lb per week) compared with the placebo group, which lost an average of 1.65 lbs (average of 0.21 lb per week), representing a difference of 129 percent (p=0.35). Triglyceride levels in the Phase 2 group were reduced an average of 26.3 mg/dL, more than three times greater a reduction than observed in the placebo group (8.2 mg/dL) (p=0.07). No adverse events during the study were attributed to the study medication. Clinical trends were identified for weight loss and a decrease in triglycerides, although statistical significance was not reached. Phase 2 shows potential promise as an adjunct therapy in the treatment of obesity and hypertriglyceridemia and further studies with larger numbers of subjects are warranted to conclusively demonstrate effectiveness.

Psychological Interventions for Vaccine Injections in Young Children 0 to 3 Years

PubMed Central

Pillai Riddell, Rebecca; Taddio, Anna; McMurtry, C. Meghan; Chambers, Christine; Shah, Vibhuti; Noel, Melanie

2015-01-01

Background: This systematic review evaluated the effectiveness of distraction for reducing infant distress during vaccinations in young children aged 0 to 3 years. Design/Methods: Database searches identified relevant randomized and quasi-randomized controlled trials. Three separate clinical questions related to variants of the psychological strategy of distraction (directed video; directed toy; nondirected toy) were pursued. Distress was identified as the critical outcome to assess the benefits of distraction and extracted from relevant trials. Distress was analyzed by phase of procedure (distress preprocedure; distress acute; distress recovery; idiosyncratic phases based on some or all of the 3 aforementioned phases). Results: Ten studies were included in the review. Significant results are presented herein. For directed video distraction, moderate quality evidence suggested that distress was lowered in the treatment group standardized mean difference (SMD −0.68 lower [95% confidence interval (CI), −1.04 to −0.32]) for the acute+recovery phase as well as the preprocedure phase (SMD −0.49 lower [95% CI, −7.6 to −0.22]). For directed toy distraction, the analysis of low-quality evidence for a combined preprocedure+acute+recovery phase of distress (analysis n=81), suggested that distress was lowered in the treatment group (SMD −0.47 lower [95% CI, −0.91 to −0.02]). An effect for nondirected toy distraction was also seen, analyzing very–low-quality evidence, for the acute distress phase (n=290; SMD −0.93 lower [95% CI, −1.86 to 0.00]). Conclusion: Generally low-quality to very–low-quality evidence suggests that there may be an effect of directed (toy and video) and nondirected toy distraction for children aged 0 to 3 years, for certain phases of the vaccination. PMID:26201014

Endometrial Injury May Increase the Pregnancy Rate in Patients Undergoing Intrauterine Insemination: An Interventional Randomized Clinical Trial.

PubMed

Bahaa Eldin, Ahmed M; Abdelmaabud, Karim H; Laban, Mohamed; Hassanin, Alaa S; Tharwat, Ahmed A; Aly, Tarek R; Elbohoty, Ahmed E; Elsayed, Helmy M; Ibrahim, Ahmed M; Ibrahim, Mohammed E; Sabaa, Haitham M; Abdelrazik, Azza A; Abdelhady, Ibrahim

2016-10-01

This study aimed to investigate the effect of endometrial injury using Pipelle catheter in the follicular phase (cycle day 5, 6, or 7) of the stimulation cycle on pregnancy rates in patients undergoing intrauterine insemination. This prospective randomized controlled study was carried out in the Assisted Reproductive Technology Unit of Ain Shams University Maternity Hospital, Cairo, Egypt, from July 1, 2013 to August 31, 2015. Three hundred sixty women, 20 to 35 years of age, with patent fallopian tubes, mild male factor infertility, or unexplained infertility were recruited. Participants were allocated randomly into 2 groups: experimental arm and control arm. Women in the experimental arm underwent endometrial biopsy using a Pipelle catheter on day 5, 6, or 7 of the stimulation cycle combined with intrauterine insemination. Women in the control group underwent intrauterine insemination with no endometrial biopsy done. The primary outcomes were the clinical and chemical pregnancy rates. Data of 344 participants were statistically analyzed. The chemical pregnancy rate was 23.66% in the experimental arm and 10.85% in the control arm (P = .002). The clinical pregnancy rate was 18.93% in the experimental arm and 7.42% in the control arm (P = .003). Endometrial injury using a Pipelle catheter in the stimulation cycle may improve pregnancy rates in women undergoing intrauterine insemination. © The Author(s) 2016.

[Urinary leukotrience E(4) level in children with asthma].

PubMed

He, Mei-Juan; Chen, Qiang; Liu, Jian-Mei

2009-11-01

Cysteinyl leukotriene (CysLTs) plays an important role in airway inflammation and remodeling in asthma. Measurement of urinary leukotriene E(4) (LTE(4)) is a sensitive and noninvasive method of assaying total body CysLTs level. This study aimed to evaluate the clinical significance of urinary leukotriene E(4) (LTE(4)) in childhood asthma. Sixty children with acute asthma were randomly divided into montelukast (leukotriene receptor antagonist) treatment and conventional treatment groups (n = 30 each). Urinary LTE(4) levels were measured using ELISA and the airway resistance Rint was assessed by the lung function instrument at the acute and the convalescence phases. Twenty healthy children were used as the control group. Urinary LTE(4) levels in asthmatic children at the acute and the convalescence phases were significantly higher than those in the control group (p<0.01). The urinary LTE(4) levels at the convalescence phase were significantly reduced compared with those at the acute phase in asthmatic children (p<0.01). More significantly decreased urinary LTE(4) levels were noted in the montelukast treatment group than the conventional treatment group at the convalescence phase (p<0.01). In the acute phase, there was no correlation between urinary LTE4 level and Rint in asthmatic children. Urinary LTE(4) level is significantly increased in children with acute asthma. Urinary LTE(4) is a useful marker for the diagnosis of asthma and can be as a predictor of asthma control and marker of susceptibility to treatment with leukotriene receptor antagonists.

The design and conduct of Keep It Off: An online randomized trial of financial incentives for weight-loss maintenance.

PubMed

Shaw, Pamela A; Yancy, William S; Wesby, Lisa; Ulrich, Victoria; Troxel, Andrea B; Huffman, David; Foster, Gary D; Volpp, Kevin

2017-02-01

Background Obesity continues to be a serious public health challenge. Rates are increasing worldwide, with nearly 70% of the US adults overweight or obese, leading to increased clinical and economic burden. While successful approaches for achieving weight loss have been identified, techniques for long-term maintenance of initial weight loss have largely been unsuccessful. Financial incentive interventions have been shown in several settings to be successful in motivating participants to adopt healthy behaviors. Purpose Keep It Off is a three-arm randomized controlled trial that compares the efficacy of a lottery-based incentive, traditional direct payment incentive, and control of daily feedback without any incentive for weight-loss maintenance. This design allows comparison of a traditional direct payment incentive with one based on behavioral economic principles that consider the underlying psychology of decision-making. Methods Participants were randomized in a 2:1 ratio for each active arm relative to control, with a targeted 188 participants in total. Eligible participants were those aged 30-80 who lost at least 11 lb (5 kg) during the first 4 months of participation in Weight Watchers, a national weight-loss program, with whom we partnered. The interventions lasted 6 months (Phase I); participants were followed for an additional 6 months without intervention (Phase II). The primary outcome is weight change from baseline to the end of Phase I, with the change at the end of Phase II a key secondary endpoint. Keep It Off is a pragmatic trial that recruited, consented, enrolled, and followed patients electronically. Participants were provided a wireless weight scale that electronically transmitted daily self-monitored weights. Weights were verified every 3 months at a Weight Watchers center local to the participant and electronically transmitted. Results Using the study web-based platform, we integrated recruitment, enrollment, and follow-up procedures into a digital platform that required little staff effort to implement and manage. We randomized 191 participants in less than 1 year. We describe the design of Keep It Off and implementation of enrollment. Lessons Learned We demonstrated that our pragmatic design was successful in rapid accrual of participants in a trial of interventions to maintain weight loss. Limitations Despite the nationwide reach of Weight Watchers, the generalizability of study findings may be limited by the characteristics of its members. The interventions under study are appropriate for settings where an entity, such as an employer or health insurance company, could offer them as a benefit. Conclusions Keep It Off was implemented and conducted with minimal staff effort. This study has the potential to identify a practical and effective weight-loss maintenance strategy.

Preladenant as an Adjunctive Therapy With Levodopa in Parkinson Disease: Two Randomized Clinical Trials and Lessons Learned.

PubMed

Hauser, Robert A; Stocchi, Fabrizio; Rascol, Olivier; Huyck, Susan B; Capece, Rachel; Ho, Tony W; Sklar, Peter; Lines, Christopher; Michelson, David; Hewitt, David

2015-12-01

Preladenant is an adenosine 2A receptor antagonist that reduced "off" time in a placebo-controlled phase 2b trial in patients with Parkinson disease (PD). We sought to confirm its efficacy in phase 3 trials. To evaluate preladenant as an adjunct to levodopa in patients with PD and motor fluctuations. Two 12-week, phase 3, randomized, placebo-controlled, double-blind trials performed from July 15, 2010, to April 16, 2013. The setting included neurology clinics, clinical research centers, and hospitals in the Americas, the European Union, Eastern Europe, India, and South Africa. Participants included patients with moderate to severe PD taking levodopa who were experiencing motor fluctuations. In trial 1, a total of 778 eligible patients were randomized to the addition of preladenant (2 mg, 5 mg, or 10 mg twice daily), placebo, or rasagiline mesylate (1 mg/d) in a 1:1:1:1:1 ratio. In trial 2, a total of 476 eligible patients were randomized to the addition of preladenant (2 mg or 5 mg twice daily) or placebo in a 1:1:1 ratio. The primary outcome measure was change in off time from baseline to week 12. In trial 1, neither preladenant nor rasagiline was superior to placebo in reducing off time from baseline to week 12. The differences vs placebo were -0.10 hour (95% CI, -0.69 to 0.46 hour) for preladenant 2 mg twice daily, -0.20 hour (95% CI, -0.75 to 0.41 hour) for preladenant 5 mg twice daily, -0.00 hour (95% CI, -0.62 to 0.53 hour) for preladenant 10 mg twice daily, and -0.30 hour (95% CI, -0.90 to 0.26 hour) for rasagiline mesylate 1 mg/d. In trial 2, preladenant was not superior to placebo in reducing off time from baseline to week 12. The differences vs placebo were -0.20 hour (95% CI, -0.72 to 0.35 hour) for preladenant 2 mg twice daily and -0.30 hour (95% CI, -0.86 to 0.21 hour) for preladenant 5 mg twice daily. Preladenant was well tolerated, with the most common adverse event that showed an increase over placebo in both trials being constipation (6%-8% for preladenant vs 1%-3% for placebo). In these phase 3 trials, preladenant did not significantly reduce off time compared with placebo. That the active control rasagiline also failed to demonstrate a significant reduction in off time suggests that issues of study design or conduct may have affected these trials. clinicaltrials.gov Identifier: NCT01155466 and NCT01227265.

Design of a cluster-randomized trial of electronic health record-based tools to address overweight and obesity in primary care.

PubMed

Baer, Heather J; Wee, Christina C; DeVito, Katerina; Orav, E John; Frolkis, Joseph P; Williams, Deborah H; Wright, Adam; Bates, David W

2015-08-01

Primary care providers often fail to identify patients who are overweight or obese or discuss weight management with them. Electronic health record-based tools may help providers with the assessment and management of overweight and obesity. We describe the design of a trial to examine the effectiveness of electronic health record-based tools for the assessment and management of overweight and obesity among adult primary care patients, as well as the challenges we encountered. We developed several new features within the electronic health record used by primary care practices affiliated with Brigham and Women's Hospital in Boston, MA. These features included (1) reminders to measure height and weight, (2) an alert asking providers to add overweight or obesity to the problem list, (3) reminders with tailored management recommendations, and (4) a Weight Management screen. We then conducted a pragmatic, cluster-randomized controlled trial in 12 primary care practices. We randomized 23 clinical teams ("clinics") within the practices to the intervention group (n = 11) or the control group (n = 12). The new features were activated only for clinics in the intervention group. The intervention was implemented in two phases: the height and weight reminders went live on 15 December 2011 (Phase 1), and all of the other features went live on 11 June 2012 (Phase 2). Study enrollment went from December 2011 through December 2012, and follow-up ended in December 2013. The primary outcomes were 6-month and 12-month weight change among adult patients with body mass index ≥25 who had a visit at one of the primary care clinics during Phase 2. Secondary outcome measures included the proportion of patients with a recorded body mass index in the electronic health record, the proportion of patients with body mass index ≥25 who had a diagnosis of overweight or obesity on the electronic health record problem list, and the proportion of patients with body mass index ≥25 who had a follow-up appointment about their weight or were prescribed weight loss medication. We encountered challenges in our development of an intervention within the existing structure of an electronic health record. For example, although we decided to randomize clinics within primary care practices, this decision may have introduced contamination and led to some imbalance of patient characteristics between the intervention and control practices. Using the electronic health record as the primary data source reduced the cost of the study, but not all desired data were recorded for every participant. Despite the challenges, this study should provide valuable information about the effectiveness of electronic health record-based tools for addressing overweight and obesity in primary care. © The Author(s) 2015.

The design and conduct of Keep It Off: An online randomized trial of financial incentives for weight loss maintenance

PubMed Central

Shaw, Pamela A; Yancy, William S; Wesby, Lisa; Ulrich, Victoria; Troxel, Andrea B; Huffman, David; Foster, Gary D; Volpp, Kevin

2016-01-01

Background Obesity continues to be a serious public health challenge. Rates are increasing worldwide, with nearly 70% of US adults overweight or obese, leading to increased clinical and economic burden. While successful approaches for achieving weight loss have been identified, techniques for long-term maintenance of initial weight loss have largely been unsuccessful. Financial incentive interventions have been shown in several settings to be successful in motivating participants to adopt healthy behaviors. Purpose Keep It Off is a three-arm randomized controlled trial that compares the efficacy of a lottery-based incentive, traditional direct payment incentive, and control of daily feedback without any incentive, for weight loss maintenance. This design allows comparison of a traditional direct payment incentive with one based on behavioral economic principles that consider the underlying psychology of decision-making. Methods Participants were randomized in a 2:1 ratio for each active arm relative to control, with a targeted 188 participants total. Eligible participants were those aged 30–80 who lost at least 11 pounds (lb, 5 kilograms (kg)) during the first 4 months of participation in Weight Watchers, a national weight loss program, with whom we partnered. The interventions lasted 6 months (Phase I); participants were followed for 6 additional months without intervention (Phase II). The primary outcome is weight change from baseline to the end of Phase I, with the change at the end of Phase II a key secondary endpoint. Keep It Off is a pragmatic trial that recruited, consented, enrolled and followed patients electronically. Participants were provided a wireless weight scale that electronically transmitted daily self-monitored weights. Weights were verified every 3 months at a Weight Watchers center local to the participant and electronically transmitted. Results Using the study web-based platform, we integrated recruitment, enrollment and follow-up procedures into a digital platform that required little staff effort to implement and manage. We randomized 191 participants in less than one year. We describe the design of Keep It Off and implementation of enrollment. Lessons Learned We demonstrated that our pragmatic design was successful in rapid accrual of participants in a trial of interventions to maintain weight loss. Limitations Despite the nationwide reach of Weight Watchers, the generalizability of study findings may be limited by the characteristics of its members. The interventions under study are appropriate for settings where an entity, such as an employer or health insurance company, could offer them as a benefit. Conclusions Keep It Off was implemented and conducted with minimal staff effort. This study has the potential to identify a practical and effective weight loss maintenance strategy. PMID:27646508

Phase-retrieval attack free cryptosystem based on cylindrical asymmetric diffraction and double-random phase encoding

NASA Astrophysics Data System (ADS)

Wang, Jun; Li, Xiaowei; Hu, Yuhen; Wang, Qiong-Hua

2018-03-01

A phase-retrieval attack free cryptosystem based on the cylindrical asymmetric diffraction and double-random phase encoding (DRPE) is proposed. The plaintext is abstract as a cylinder, while the observed diffraction and holographic surfaces are concentric cylinders. Therefore, the plaintext can be encrypted through a two-step asymmetric diffraction process with double pseudo random phase masks located on the object surface and the first diffraction surface. After inverse diffraction from a holographic surface to an object surface, the plaintext can be reconstructed using a decryption process. Since the diffraction propagated from the inner cylinder to the outer cylinder is different from that of the reversed direction, the proposed cryptosystem is asymmetric and hence is free of phase-retrieval attack. Numerical simulation results demonstrate the flexibility and effectiveness of the proposed cryptosystem.

Simulation study on characteristics of long-range interaction in randomly asymmetric exclusion process

NASA Astrophysics Data System (ADS)

Zhao, Shi-Bo; Liu, Ming-Zhe; Yang, Lan-Ying

2015-04-01

In this paper we investigate the dynamics of an asymmetric exclusion process on a one-dimensional lattice with long-range hopping and random update via Monte Carlo simulations theoretically. Particles in the model will firstly try to hop over successive unoccupied sites with a probability q, which is different from previous exclusion process models. The probability q may represent the random access of particles. Numerical simulations for stationary particle currents, density profiles, and phase diagrams are obtained. There are three possible stationary phases: the low density (LD) phase, high density (HD) phase, and maximal current (MC) in the system, respectively. Interestingly, bulk density in the LD phase tends to zero, while the MC phase is governed by α, β, and q. The HD phase is nearly the same as the normal TASEP, determined by exit rate β. Theoretical analysis is in good agreement with simulation results. The proposed model may provide a better understanding of random interaction dynamics in complex systems. Project supported by the National Natural Science Foundation of China (Grant Nos. 41274109 and 11104022), the Fund for Sichuan Youth Science and Technology Innovation Research Team (Grant No. 2011JTD0013), and the Creative Team Program of Chengdu University of Technology.

Effects of Random Circuit Fabrication Errors on Small Signal Gain and on Output Phase In a Traveling Wave Tube

NASA Astrophysics Data System (ADS)

Rittersdorf, I. M.; Antonsen, T. M., Jr.; Chernin, D.; Lau, Y. Y.

2011-10-01

Random fabrication errors may have detrimental effects on the performance of traveling-wave tubes (TWTs) of all types. A new scaling law for the modification in the average small signal gain and in the output phase is derived from the third order ordinary differential equation that governs the forward wave interaction in a TWT in the presence of random error that is distributed along the axis of the tube. Analytical results compare favorably with numerical results, in both gain and phase modifications as a result of random error in the phase velocity of the slow wave circuit. Results on the effect of the reverse-propagating circuit mode will be reported. This work supported by AFOSR, ONR, L-3 Communications Electron Devices, and Northrop Grumman Corporation.

A 12-week randomized clinical trial investigating the potential for sucralose to affect glucose homeostasis.

PubMed

Grotz, V Lee; Pi-Sunyer, Xavier; Porte, Daniel; Roberts, Ashley; Richard Trout, J

2017-08-01

The discovery of gut sweet taste receptors has led to speculations that non-nutritive sweeteners, including sucralose, may affect glucose control. A double-blind, parallel, randomized clinical trial, reported here and previously submitted to regulatory agencies, helps to clarify the role of sucralose in this regard. This was primarily an out-patient study, with 4-week screening, 12-week test, and 4-week follow-up phases. Normoglycemic male volunteers (47) consumed ∼333.3 mg encapsulated sucralose or placebo 3x/day at mealtimes. HbA1c, fasting glucose, insulin, and C-peptide were measured weekly. OGTTs were conducted in-clinic overnight, following overnight fasting twice during screening phase, twice during test phase, and once at follow-up. Throughout the study, glucose, insulin, C-peptide and HbA1c levels were within normal range. No statistically significant differences between sucralose and placebo groups in change from baseline for fasting glucose, insulin, C-peptide and HbA1c, no clinically meaningful differences in time to peak levels or return towards basal levels in OGTTs, and no treatment group differences in mean glucose, insulin, or C-peptide AUC change from baseline were observed. The results of other relevant clinical trials and studies of gastrointestinal sweet taste receptors are compared to these findings. The collective evidence supports that sucralose has no effect on glycemic control. Copyright © 2017 Heartland Food Products Group. Published by Elsevier Inc. All rights reserved.

The Aspirin Regimens in Essential Thrombocythemia (ARES) phase II randomized trial design: Implementation of the serum thromboxane B2 assay as an evaluation tool of different aspirin dosing regimens in the clinical setting.

PubMed

De Stefano, Valerio; Rocca, Bianca; Tosetto, Alberto; Soldati, Denise; Petrucci, Giovanna; Beggiato, Eloise; Bertozzi, Irene; Betti, Silvia; Carli, Giuseppe; Carpenedo, Monica; Cattaneo, Daniele; Cavalca, Viviana; Dragani, Alfredo; Elli, Elena; Finazzi, Guido; Iurlo, Alessandra; Lanzarone, Giuseppe; Lissandrini, Laura; Palandri, Francesca; Paoli, Chiara; Rambaldi, Alessandro; Ranalli, Paola; Randi, Maria Luigia; Ricco, Alessandra; Rossi, Elena; Ruggeri, Marco; Specchia, Giorgina; Timillero, Andrea; Turnu, Linda; Vianelli, Nicola; Vannucchi, Alessandro M; Rodeghiero, Francesco; Patrono, Carlo

2018-06-01

Once-daily (od), low-dose aspirin (75-100 mg) is recommended to reduce the thrombotic risk of patients with essential thrombocytemia (ET). This practice is based on data extrapolated from other high-risk patients and an aspirin trial in polycythemia vera, with the assumption of similar aspirin pharmacodynamics in the two settings. However, the pharmacodynamics of low-dose aspirin is impaired in ET, reflecting accelerated renewal of platelet cyclooxygenase (COX)-1. ARES is a parallel-arm, placebo-controlled, randomized, dose-finding, phase II trial enrolling 300 ET patients to address two main questions. First, whether twice or three times 100 mg aspirin daily dosing is superior to the standard od regimen in inhibiting platelet thromboxane (TX)A 2 production, without inhibiting vascular prostacyclin biosynthesis. Second, whether long-term persistence of superior biochemical efficacy can be safely maintained with multiple vs. single dosing aspirin regimen. Considering that the primary study end point is serum TXB 2 , a surrogate biomarker of clinical efficacy, a preliminary exercise of reproducibility and validation of this biomarker across all the 11 participating centers was implemented. The results of this preliminary phase demonstrate the importance of controlling reproducibility of biomarkers in multicenter trials and the feasibility of using serum TXB 2 as a reliable end point for dose-finding studies of novel aspirin regimens.

SkQ1 Ophthalmic Solution for Dry Eye Treatment: Results of a Phase 2 Safety and Efficacy Clinical Study in the Environment and During Challenge in the Controlled Adverse Environment Model.

PubMed

Petrov, Anton; Perekhvatova, Natalia; Skulachev, Maxim; Stein, Linda; Ousler, George

2016-01-01

This Phase 2 clinical trial assessed the efficacy and safety of the novel antioxidative, renewable compound SkQ1 for topical treatment of dry eye signs and symptoms. In a single-center, randomized, double-masked, placebo-controlled, 29-day study, 91 subjects with mild to moderate dry eye instilled the study drug twice daily and recorded dry eye symptoms daily. Subjects were randomized 1:1:1 into one of three ophthalmic solution treatment groups: SkQ1 1.55 µg/mL, SkQ1 0.155 µg/mL, or 0.0 µg/mL (placebo). Subjects were exposed to a controlled adverse environment chamber at 3 of the 4 study visits (Day -7, Day 1, and Day 29). Investigator assessments occurred at all study visits. SkQ1 was safe and efficacious in treating dry eye signs and symptoms. Statistically significant improvements with SkQ1 compared to placebo occurred for the dry eye signs of corneal fluorescein staining and lissamine green staining in the central region and lid margin redness, and for the dry eye symptoms of ocular discomfort, dryness, and grittiness. In addition, SkQ1 demonstrated greater efficacy compared to placebo, although the differences were not statistically significant, for corneal fluorescein staining in other regions and/or time points (total staining score, central region, corneal sum score, and temporal region), lissamine green staining for the central and nasal regions, and blink rate scores. This Phase 2 study indicated that SkQ1 is safe and efficacious for the treatment of dry eye signs and symptoms and supported previous study results. Clinicaltrials.gov identifier: NCT02121301. Miotech S.A.

The effects of control of thermal balance on vascular stability in hemodialysis patients: results of the European randomized clinical trial.

PubMed

Maggiore, Quirino; Pizzarelli, Francesco; Santoro, Antonio; Panzetta, Giovanni; Bonforte, Giuseppe; Hannedouche, Thierry; Alvarez de Lara, Maria Antonia; Tsouras, Ioannis; Loureiro, Alfredo; Ponce, Pedro; Sulkovà, Sylvie; Van Roost, Guido; Brink, Hans; Kwan, Jonathan T C

2002-08-01

Many reports note that the use of cool dialysate has a protective effect on blood pressure during hemodialysis (HD) treatments. However, formal clinical trials in which dialysate temperature is tailored to the body temperature of appropriately selected hypotension-prone patients are lacking. We investigated the effect of thermal control of dialysate on hemodynamic stability in hypotension-prone patients selected from 27 centers in nine European countries. Patients were eligible for the study if they had symptomatic hypotensive episodes in 25% or more of their HD sessions, assessed during a prospective screening phase over 1 month. The study is designed as a randomized crossover trial with two phases and two treatment arms, each phase lasting 4 weeks. We used a device allowing the regulation of thermal balance (Blood Temperature Monitor; Fresenius Medical Care, Bad Homberg, Germany), by which we compared a procedure aimed at preventing any transfer of thermal energy between dialysate and extracorporeal blood (thermoneutral dialysis) with a procedure aimed at keeping body temperature unchanged (isothermic dialysis). One hundred sixteen HD patients were enrolled, and 95 patients completed the study. During thermoneutral dialysis (energy flow rate: DeltaE = -0.22 +/- 0.29 kJ/kg x h), 6 of 12 treatments (median) were complicated by hypotension, whereas during isothermic dialysis (energy flow rate: DeltaE = -0.90 +/- 0.35 kJ/kg x h), the median decreased to 3 of 12 treatments (P < 0.001). Systolic and diastolic blood pressures and heart rate were more stable during the latter procedure. Isothermic dialysis was well tolerated by patients. Results show that active control of body temperature can significantly improve intradialytic tolerance in hypotension-prone patients. Copyright 2002 by the National Kidney Foundation, Inc.

A phase I/II randomized, controlled, clinical trial for assessment of the efficacy and safety of β-D-mannuronic acid in rheumatoid arthritis patients.

PubMed

Ahmadi, Hossein; Jamshidi, Ahmad Reza; Gharibdoost, Farhad; Mahmoudi, Mahdi; Rastkari, Noushin; Mostafaei, Shayan; Fattahi, Mohammad Javad; Vojdanian, Mahdi; Cuzzocrea, Salvatore; Rehm, Bernd H A; Matsuo, Hidenori; Hosseini, Mostafa; Aghazadeh, Zahra; Mortazavi-Jahromi, Seyed Shahabeddin; Mirshafiey, Abbas

2018-06-01

Following the potent efficacy of β-D-mannuronic acid (M2000) in phase I/II trial in ankylosing spondylitis patients, the present clinical trial was conducted to evaluate the efficacy, safety, and tolerability of this novel drug in rheumatoid arthritis (RA) patients who had inadequate response to conventional therapy. The study was a 12-week randomized, controlled, phase I/II clinical trial with two treatment arms: M2000 and conventional treatment. Patients who had RA according to the modified American College of Rheumatology (ACR) criteria, with active disease at baseline also inadequate response to conventional therapy, were enrolled in this study. M2000 was administrated at a dose of two capsules (500 mg) per day orally during a period of 12 weeks. The primary endpoint was the proportion of patients fulfilling the ACR 20% improvement criteria after 12 weeks of M2000 therapy. Moreover, the patients were also followed up for safety. There were no statistically significant differences between treatment and conventional groups at baseline characteristics. The ACR20 response rate was significantly higher among M2000-treated patients than conventional-treated control, so that 74% of patients in treatment group showed an ACR20 response after 12 weeks of M2000 therapy (74 versus 16%; P = 0.011). 10% of M2000-treated patients and 57.1% of conventional-treated patient's adverse events occurred during this study. Treatment with M2000 in combination with conventional therapy showed a significantly superior efficacy along with a high safety profile compared to conventional-treated patients. Thereby, M2000 might be suggested as a suitable option in the treatment of RA.

The RAndomized Placebo Phase Study Of Rilonacept in the Treatment of Systemic Juvenile Idiopathic Arthritis (RAPPORT)

PubMed Central

Ilowite, Norman T.; Prather, Kristi; Lokhnygina, Yuliya; Schanberg, Laura E.; Elder, Melissa; Milojevic, Diana; Verbsky, James W.; Spalding, Steven J.; Kimura, Yukiko; Imundo, Lisa F.; Punaro, Marilynn G.; Sherry, David D.; Tarvin, Stacey E.; Zemel, Lawrence S.; Birmingham, James D.; Gottlieb, Beth S.; Miller, Michael L.; O'Neil, Kathleen; Ruth, Natasha M.; Wallace, Carol A.; Singer, Nora G.; Sandborg, Christy I.

2015-01-01

Background Interleukin-1 plays a pivotal role in in the pathogenesis of systemic juvenile idiopathic arthritis (sJIA). We assessed the efficacy and safety of rilonacept (IL-1 trap), an IL-1 inhibitor, in a randomized, double-blind, placebo-controlled trial. Methods An initial 4-week double-blind placebo phase was incorporated into a 24-week randomized multi-center design, followed by an open label phase. We randomized 71 children with at least 2 active joints 1:1 to 2 arms of the study. Patients in the rilonacept arm received rilonacept (4.4mg/kg loading dose followed by 2.2mg/kg weekly, subcutaneously) from day 0; patients in the placebo arm received placebo for 4 weeks followed by a loading dose of rilonacept at week 4 followed by weekly maintenance doses. The primary endpoint was time to response, using adapted JIA ACR30 response criteria coupled with absence of fever and taper of systemic corticosteroids using pre-specified criteria. Results Time to response was shorter in the rilonacept arm than in the placebo arm (Chi-square 7.235, P=.007). Secondary analysis showed 20/35 (57%) of patients in the rilonacept arm responded at week 4 compared to 9/33 (27%) in the placebo arm (P=.016) using the same response criteria. Exacerbation of sJIA (4) was the most common SAE. More patients in the rilonacept arm had elevated liver transaminases, including more than three times the upper limits of normal, as compared to those in the placebo arm. Adverse events were similar in the two arms of the study. Conclusions Rilonacept was generally well tolerated and demonstrated efficacy in active sJIA. PMID:24839206

Randomized phase II study comparing gemcitabine plus dacarbazine versus dacarbazine alone in patients with previously treated soft tissue sarcoma: a Spanish Group for Research on Sarcomas study.

PubMed

García-Del-Muro, Xavier; López-Pousa, Antonio; Maurel, Joan; Martín, Javier; Martínez-Trufero, Javier; Casado, Antonio; Gómez-España, Auxiliadora; Fra, Joaquín; Cruz, Josefina; Poveda, Andrés; Meana, Andrés; Pericay, Carlos; Cubedo, Ricardo; Rubió, Jordi; De Juan, Ana; Laínez, Nuria; Carrasco, Juan Antonio; de Andrés, Raquel; Buesa, José M

2011-06-20

To assess the activity and toxicity of the combination of gemcitabine plus dacarbazine (DTIC) in patients with advanced soft tissue sarcoma (STS) in a randomized, multicenter, phase II study using DTIC alone as a control arm. Patients with previously treated advanced STS were randomly assigned to receive either fixed-dose rate gemcitabine (10 mg/m2/min) at 1800 mg/m2 followed by DTIC at 500 mg/m2 every 2 weeks, or DTIC alone at 1200 mg/m2 every 3 weeks. The primary end point of the study was progression-free rate (PFR) at 3 months. From November 2005 to September 2008, 113 patients were included. PFR at 3 months was 56% for gemcitabine plus DTIC versus 37% for DTIC alone (P = .001). Median progression-free survival was 4.2 months versus 2 months (hazard ratio [HR], 0.58; 95% CI, 0.39 to 0.86; P = .005), and median overall survival was 16.8 months versus 8.2 months (HR, 0.56; 95% CI, 0.36 to 0.90; P = .014); both favored the arm of gemcitabine plus DTIC. Gemcitabine plus DTIC was also associated with a higher objective response or higher stable disease rate than was DTIC alone (49% v 25%; P = .009). Severe toxicities were uncommon, and treatment discontinuation for toxicity was rare. Granulocytopenia was the more common serious adverse event, but febrile neutropenia was uncommon. Asthenia, emesis, and stomatitis were the most frequent nonhematologic effects. The combination of gemcitabine and DTIC is active and well tolerated in patients with STS, providing in this phase II randomized trial superior progression-free survival and overall survival than DTIC alone. This regimen constitutes a valuable therapeutic alternative for these patients.

A Phase 3, Randomized, Double-Blind, Multicenter Study To Evaluate the Safety and Efficacy of Intravenous Iclaprim versus Vancomycin for Treatment of Acute Bacterial Skin and Skin Structure Infections Suspected or Confirmed To Be Due to Gram-Positive Pathogens (REVIVE-2 Study).

PubMed

Holland, Thomas L; O'Riordan, William; McManus, Alison; Shin, Elliot; Borghei, Ali; File, Thomas M; Wilcox, Mark H; Torres, Antoni; Dryden, Matthew; Lodise, Thomas; Oguri, Toyoko; Corey, G Ralph; McLeroth, Patrick; Shukla, Rajesh; Huang, David B

2018-05-01

Iclaprim is a novel diaminopyrimidine antibiotic that may be an effective and safe treatment for serious skin infections. The safety and effectiveness of iclaprim were assessed in a global phase 3, double-blind, randomized, active-controlled trial. Six hundred thirteen adults with acute bacterial skin and skin structure infections (ABSSSIs) suspected or confirmed to be due to Gram-positive pathogens were randomized to iclaprim (80 mg) or vancomycin (15 mg/kg of body weight), both of which were administered intravenously every 12 h for 5 to 14 days. The primary endpoint was a ≥20% reduction in lesion size compared with that at the baseline at 48 to 72 h after the start of administration of study drug in the intent-to-treat population. Among patients randomized to iclaprim, 78.3% (231 of 295) met this primary endpoint, whereas 76.7% (234 of 305) of those receiving vancomycin met this primary endpoint (difference, 1.58%; 95% confidence interval, -5.10% to 8.26%). This met the prespecified 10% noninferiority margin. Iclaprim was well tolerated, with most adverse events being categorized as mild. In conclusion, iclaprim was noninferior to vancomycin in this phase 3 clinical trial for the treatment of acute bacterial skin and skin structure infections. On the basis of these results, iclaprim may be an efficacious and safe treatment for skin infections suspected or confirmed to be due to Gram-positive pathogens. (This trial has been registered at ClinicalTrials.gov under identifier NCT02607618.). Copyright © 2018 American Society for Microbiology.

Phase Transitions on Random Lattices: How Random is Topological Disorder?

NASA Astrophysics Data System (ADS)

Barghathi, Hatem; Vojta, Thomas

2015-03-01

We study the effects of topological (connectivity) disorder on phase transitions. We identify a broad class of random lattices whose disorder fluctuations decay much faster with increasing length scale than those of generic random systems, yielding a wandering exponent of ω = (d - 1) / (2 d) in d dimensions. The stability of clean critical points is thus governed by the criterion (d + 1) ν > 2 rather than the usual Harris criterion dν > 2 , making topological disorder less relevant than generic randomness. The Imry-Ma criterion is also modified, allowing first-order transitions to survive in all dimensions d > 1 . These results explain a host of puzzling violations of the original criteria for equilibrium and nonequilibrium phase transitions on random lattices. We discuss applications, and we illustrate our theory by computer simulations of random Voronoi and other lattices. This work was supported by the NSF under Grant Nos. DMR-1205803 and PHYS-1066293. We acknowledge the hospitality of the Aspen Center for Physics.

The phototoxic and photoallergy potential of clindamycin phosphate 1.2%/ tretinoin 0.025% gel for facial acne: results of two single-center, evaluator-blinded, randomized, vehicle-controlled phase 1 studies in healthy volunteers.

PubMed

Murray, John; Potts, Aaron

2014-01-01

A fixed-dose combination of clindamycin phosphate 1.2% and tretinoin 0.025% gel (VELTIN® (clindamycin phosphate and tretinoin) 1.2%/0.025% Gel [VELTIN]) (clindamycin/tretinoin gel) is currently available for the once-daily topical treatment of acne. Two-phase I studies were conducted to evaluate the phototoxic and photoallergic potential of clindamycin/tretinoin gel. Study 1 (phototoxic) (n=37) and Study 2 (photoallergic) (n=58) were single-center, evaluator-blinded, randomized, vehicle-controlled, phase 1 studies conducted in healthy volunteers. In Study 1, clindamycin/tretinoin gel patches, vehicle gel patches and blank patches (no gel) were applied concurrently for 24 hours to naïve sites. After patch removal, sites were irradiated with 16 joules/cm2 of ultraviolet A light (UVA) then 0.75 minimal erythema dose (MED) of UVA/ultraviolet B light (UVB), the same irradiation protocol followed by 15 joules/cm2 of visible light (VIS), or served as non-irradiated controls. Study 2 examined the effect of repeated drug exposure and involved an induction period (6 repeat phases at the same body sites during which clindamycin/tretinoin gel and vehicle gel patches were applied for 24 hours, removed and sites irradiated with UVB +/- VIS), followed by a rest period (10 to 17 days), then a challenge period that used the protocol described for Study 1. In both studies, inflammatory responses and other cutaneous effects were evaluated at 1, 24, 48, and 72 hours after patch removal. No subject experienced any adverse events in Study 1 (phototoxic). One subject in Study 2 (photoallergic) experienced AEs (diffuse erythema; mild application site irritation at one each of UV/VIS-irradiated clindamycin/tretinoin gel and vehicle gel patch sites) considered definitely related to study product that resulted in discontinuation from the study. Data from Study 1 and the challenge phase from Study 2 showed most subjects had no visible inflammatory reaction to clindamycin/tretinoin gel after irradiation. Clindamycin/tretinoin gel has a favorable safety profile following UV/visible irradiation and a low potential for phototoxicity and photoallergenicity.

Efficacy of Lisdexamfetamine in Adults With Moderate to Severe Binge-Eating Disorder: A Randomized Clinical Trial.

PubMed

Hudson, James I; McElroy, Susan L; Ferreira-Cornwell, M Celeste; Radewonuk, Jana; Gasior, Maria

2017-09-01

The ability of pharmacotherapies to prevent relapse and maintain efficacy with long-term treatment in psychiatric conditions is important. To assess lisdexamfetamine dimesylate maintenance of efficacy in adults with moderate to severe binge-eating disorder. A multinational, phase 3, double-blind, placebo-controlled, randomized withdrawal study including 418 participants was conducted at 49 clinical research study sites from January 27, 2014, to April 8, 2015. Eligible adults met DSM-IV-R binge-eating disorder criteria and had moderate to severe binge eating disorder (≥3 binge-eating days per week for 14 days before open-label baseline; Clinical Global Impressions-Severity [CGI-S] scores ≥4 [moderate severity] at screening and open-label baseline). Following a 12-week, open-label phase (dose optimization, 4 weeks [lisdexamfetamine dimesylate, 50 or 70 mg]; dose maintenance, 8 weeks), lisdexamfetamine responders (≤1 binge eating day per week for 4 consecutive weeks and CGI-S scores ≤2 at week 12) were randomized to placebo or continued lisdexamfetamine during a 26-week, double-blind, randomized withdrawal phase. Lisdexamfetamine administration. The primary outcome variable, time to relapse (≥2 binge-eating days per week for 2 consecutive weeks and ≥2-point CGI-S score increases from randomized withdrawal baseline), was analyzed using a log-rank test (primary analysis); the analysis was stratified for dichotomized 4-week cessation status. Safety assessments included treatment-emergent adverse events. Of the 418 participants enrolled in the open-label phase of the study, 411 (358 [87.1%] women; mean [SD] age, 38.3 [10.4] years) were included in the safety analysis set. Of 275 randomized lisdexamfetamine responders (placebo, n = 138; lisdexamfetamine, n = 137), the observed proportions of participants meeting relapse criteria were 3.7% (5 of 136) for lisdexamfetamine and 32.1% (42 of 131) for placebo. Lisdexamfetamine demonstrated superiority over placebo on the log-rank test (χ21, 40.37; P < .001) for time to relapse; the hazard ratio, based on a Cox proportional hazards model for lisdexamfetamine vs placebo, was 0.09 (95% CI, 0.04-0.23). The treatment-emergent adverse events observed were generally consistent with the known profile of lisdexamfetamine. Risk of binge-eating relapse over 6 months was lower in participants continuing lisdexamfetamine than in those randomized to placebo. The hazard for relapse was lower with lisdexamfetamine than placebo. clinicaltrials.gov Identifier: NCT02009163.

COMPARE CPM-RMI Trial: Intramyocardial Transplantation of Autologous Bone Marrow-Derived CD133+ Cells and MNCs during CABG in Patients with Recent MI: A Phase II/III, Multicenter, Placebo-Controlled, Randomized, Double-Blind Clinical Trial.

PubMed

Naseri, Mohammad Hassan; Madani, Hoda; Ahmadi Tafti, Seyed Hossein; Moshkani Farahani, Maryam; Kazemi Saleh, Davood; Hosseinnejad, Hossein; Hosseini, Saeid; Hekmat, Sepideh; Hossein Ahmadi, Zargham; Dehghani, Majid; Saadat, Alireza; Mardpour, Soura; Hosseini, Seyedeh Esmat; Esmaeilzadeh, Maryam; Sadeghian, Hakimeh; Bahoush, Gholamreza; Bassi, Ali; Amin, Ahmad; Fazeli, Roghayeh; Sharafi, Yaser; Arab, Leila; Movahhed, Mansour; Davaran, Saeid; Ramezanzadeh, Narges; Kouhkan, Azam; Hezavehei, Ali; Namiri, Mehrnaz; Kashfi, Fahimeh; Akhlaghi, Ali; Sotoodehnejadnematalahi, Fattah; Vosough Dizaji, Ahmad; Gourabi, Hamid; Syedi, Naeema; Shahverdi, Abdol Hosein; Baharvand, Hossein; Aghdami, Nasser

2018-10-01

This article published in Cell J (Yakhteh), Vol 20, No 2, Jul-Sep 2018, on pages 267-277, four affiliations (1, 4, 5, and 10) were changed based on authors request. Copyright© by Royan Institute. All rights reserved.

Feeding fat from distillers dried grains with solubles to dairy heifers: III. Effects on long-term reproductive and lactation performance

USDA-ARS?s Scientific Manuscript database

During the prepubertal growth phase, 33 Holstein heifers (133 ± 18 d old) were used in a 24-week randomized complete block design. Treatments included: 1) a control diet (CON) containing ground corn (15.9% of DM) and soybean products (17.9%); 2) a low-fat diet (LFDG) formulated with 21.9% fat-extrac...

Enteric-coated, pH-dependent peppermint oil capsules for the treatment of irritable bowel syndrome in children.

PubMed

Kline, R M; Kline, J J; Di Palma J; Barbero, G J

2001-01-01

In a randomized, double-blind controlled trial, 42 children with irritable bowel syndrome (IBS) were given pH-dependent, enteric-coated peppermint oil capsules or placebo. After 2 weeks, 75% of those receiving peppermint oil had reduced severity of pain associated with IBS. Peppermint oil may be used as a therapeutic agent during the symptomatic phase of IBS.

Post-Exercise Protein Trial: Interactions between Diet and Exercise (PEPTIDE): study protocol for randomized controlled trial.

PubMed

Alghannam, Abdullah F; Tsintzas, Kostas; Thompson, Dylan; Bilzon, James; Betts, James A

2014-11-24

Performing regular exercise is known to manifest a number of health benefits that mainly relate to cardiovascular and muscular adaptations to allow for greater oxygen extraction and utilization. There is increasing evidence that nutrient intake can affect the adaptive response to a single exercise bout, and that protein feeding is important to facilitate this process. Thus, the exercise-nutrient interaction may potentially lead to a greater response to training. The role of post-exercise protein ingestion in enhancing the effects of running-based endurance exercise training relative to energy-matched carbohydrate intervention remains to be established. Additionally, the influence of immediate versus overnight protein ingestion in mediating these training effects is currently unknown. The current protocol aims to establish whether post-exercise nutrient intake and timing would influence the magnitude of improvements during a prescribed endurance training program. The project involves two phases with each involving two treatment arms applied in a randomized investigator-participant double-blind parallel group design. For each treatment, participants will be required to undergo six weeks of running-based endurance training. Immediately post-exercise, participants will be prescribed solutions providing 0.4 grams per kilogram of body mass (g · kg(-1)) of whey protein hydrolysate plus 0.4 g · kg(-1) sucrose, relative to an isocaloric sucrose control (0.8 g · kg(-1); Phase I). In Phase II, identical protein supplements will be provided (0.4 + 0.4 g · kg(-1) · h(-1) of whey protein hydrolysate and sucrose, respectively), with the timing of ingestion manipulated to compare immediate versus overnight recovery feedings. Anthropometric, expired gas, venous blood and muscle biopsy samples will be obtained at baseline and following the six-week training period. By investigating the role of nutrition in enhancing the effects of endurance exercise training, we will provide novel insight regarding nutrient-exercise interactions and the potential to help and develop effective methods to maximize health or performance outcomes in response to regular exercise. Current Controlled Trials registration number: ISRCTN27312291 (date assigned: 4 December 2013). The first participant was randomized on 11 December 2013.

Empagliflozin as adjunct to insulin in Japanese participants with type 1 diabetes: Results of a 4-week, double-blind, randomized, placebo-controlled phase 2 trial.

PubMed

Shimada, Akira; Hanafusa, Toshiaki; Yasui, Atsutaka; Lee, Ganghyuck; Taneda, Yusuke; Sarashina, Akiko; Shiki, Kosuke; George, Jyothis; Soleymanlou, Nima; Marquard, Jan

2018-05-15

This phase 2, double-blind, randomized, placebo-controlled trial (ClinicalTrials.gov NCT02702011) with 4 sites in Japan investigated the pharmacodynamics (PD), pharmacokinetics (PK) and safety profile of empagliflozin in Japanese participants with type 1 diabetes mellitus (T1DM) as adjunctive therapy to insulin. Participants using multiple daily injections of insulin for ≥12 months, with HbA1c of 7.5%-10.0%, entered a 2-week, open-label, placebo run-in period, followed by a 4-week, double-blind period during which participants were randomized 1:1:1:1 to receive empagliflozin 2.5 mg (n = 13), empagliflozin 10 mg (n = 12), empagliflozin 25 mg (n = 12) or placebo (n = 11). The primary objective was to assess the effect of empagliflozin vs placebo on urinary glucose excretion (UGE) after 7 days of treatment. PD: Empagliflozin resulted in a dose-dependent significant increase in 24-hour UGE compared with placebo (UGE placebo-corrected mean [95% confidence interval] change from baseline: 2.5 mg, 65.10 [43.29, 86.90] g/24 h; 10 mg, 81.19 [58.80, 103.58] g/24 h; 25 mg, 98.11 [75.91, 120.31] g/24 h). After 4 weeks of treatment, UGE increase was associated with improved glycaemic control, reduced body weight and decreased insulin needs. Empagliflozin treatment also resulted in dose-dependent increases in serum ketone bodies and free fatty acids. PK: Plasma empagliflozin levels increased in a dose-dependent manner and peaked at 1.5 hours. In this short study, empagliflozin was well tolerated, with no increase in rate of hypoglycaemia and no diabetic ketoacidosis events reported. Based on this short-duration phase 2 study, the PK/PD profile of empagliflozin in Japanese participants with T1DM is comparable to that of non-Japanese participants. © 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Progesterone for Luteal Phase Support in In Vitro Fertilization: Comparison of Vaginal and Rectal Pessaries to Vaginal Capsules: A Randomized Controlled Study

PubMed Central

Khrouf, Mohamed; Slimani, Soufiene; Khrouf, Myriam Razgallah; Braham, Marouen; Bouyahia, Maha; Berjeb, Khadija Kacem; Chaabane, Hanene Elloumi; Merdassi, Ghaya; Kaffel, Aida Zahaf; Zhioua, Amel; Zhioua, Fethi

2016-01-01

BACKGROUND In IVF, Luteal phase support is usually performed using vaginal progesterone. A part of patients using this route reports being uncomfortable with this route. We tried to study whether the rectal route could be an effective alternative and associated with less discomfort. PATIENTS AND METHODS A prospective randomized controlled study. All patient were eligible for IVF treatment for infertility. After oocyte pickup, 186 patients were allocated to one the following protocols for luteal phase support: (i) rectal pessaries group: natural progesterone pessaries administered rectally 200 mg three times a day, (ii) vaginal pessaries group: natural progesterone pessaries administered vaginally 200 mg three times a day), and (iii) vaginal capsules group: natural micronized progesterone capsules administered vaginally 200 mg three times a day. On the day of pregnancy test, patients were asked to fill in a questionnaire conducted by an investigator in order to assess the tolerability and side effects of the LPS treatment taken. The primary endpoint was the occurrence of perineal irritation. RESULTS Fifty eight patients were assigned to the rectal pessaries group, 68 patients to the vaginal pessaries group, and 60 patients to the vaginal capsules group. All patients adhered to their allocated treatment. Implantation and clinical pregnancy rates per transfer did not differ between the three groups. Perineal irritation, which was our primary endpoint, was the same for all the three groups (respectively 1.7 % versus 5.9 % versus 11.7%). Regarding the other side effects, more patients experienced constipation and flatulence with the rectal route, whereas more patients reported vaginal discharge in the vaginal capsules group. CONCLUSION Rectal administration for luteal phase support is effective and well accepted alternative to vaginal route. PMID:28096703

Progesterone for Luteal Phase Support in In Vitro Fertilization: Comparison of Vaginal and Rectal Pessaries to Vaginal Capsules: A Randomized Controlled Study.

PubMed

Khrouf, Mohamed; Slimani, Soufiene; Khrouf, Myriam Razgallah; Braham, Marouen; Bouyahia, Maha; Berjeb, Khadija Kacem; Chaabane, Hanene Elloumi; Merdassi, Ghaya; Kaffel, Aida Zahaf; Zhioua, Amel; Zhioua, Fethi

2016-01-01

In IVF, Luteal phase support is usually performed using vaginal progesterone. A part of patients using this route reports being uncomfortable with this route. We tried to study whether the rectal route could be an effective alternative and associated with less discomfort. A prospective randomized controlled study. All patient were eligible for IVF treatment for infertility. After oocyte pickup, 186 patients were allocated to one the following protocols for luteal phase support: (i) rectal pessaries group: natural progesterone pessaries administered rectally 200 mg three times a day, (ii) vaginal pessaries group: natural progesterone pessaries administered vaginally 200 mg three times a day), and (iii) vaginal capsules group: natural micronized progesterone capsules administered vaginally 200 mg three times a day. On the day of pregnancy test, patients were asked to fill in a questionnaire conducted by an investigator in order to assess the tolerability and side effects of the LPS treatment taken. The primary endpoint was the occurrence of perineal irritation. Fifty eight patients were assigned to the rectal pessaries group, 68 patients to the vaginal pessaries group, and 60 patients to the vaginal capsules group. All patients adhered to their allocated treatment. Implantation and clinical pregnancy rates per transfer did not differ between the three groups. Perineal irritation, which was our primary endpoint, was the same for all the three groups (respectively 1.7 % versus 5.9 % versus 11.7%). Regarding the other side effects, more patients experienced constipation and flatulence with the rectal route, whereas more patients reported vaginal discharge in the vaginal capsules group. Rectal administration for luteal phase support is effective and well accepted alternative to vaginal route.

A randomized controlled trial to evaluate the effectiveness of a cognitive behavioural group approach to improve patient adherence to peritoneal dialysis fluid restrictions: a pilot study.

PubMed

Hare, Jennifer; Clark-Carter, David; Forshaw, Mark

2014-03-01

Peritoneal dialysis (PD) requires patients to take an active role in their adherence to fluid restrictions. Although fluid non-adherence had been identified among this patient group, no specific interventions have been researched or published with in the PD population. The current study sought to investigate whether an applied cognitive behavioural therapy (CBT-based intervention) used among haemodialysis patients would improve fluid adherence among PD patients; utilizing clinical indicators used in practice. Fifteen PD patients identified as fluid non-adherent were randomly assigned to an intervention group (IG) or a deferred-entry control group (CG). The study ran for a total of 21 weeks, with five data collection points; at baseline, post-intervention and at three follow-up points; providing a RCT phase and a combined longitudinal analysis phase. The content of the group intervention encompassed educational, cognitive and behavioural components, aimed to assist patients' self-management of fluid. No significant differences in weight (kg) reduction were found in either phase and undesirable changes in blood pressure (BP) were observed. However, in the longitudinal phase, a statistically significant difference in oedematous status was observed at 6-week follow-up; which may be indicative of fluid adherence. Positive and significant differences were observed in the desired direction for measures of psychological well-being, quality of life and health beliefs; areas correlated with enhanced fluid adherence in other research. This study reveals encouraging and significant changes in predictors of fluid adherence. Although there were no significant changes in weight as a crude clinical measure of fluid intake, significant reductions in oedematous status were observed as a consequence of this CBT-based group intervention.

Saw Palmetto for Symptom Management During Radiation Therapy for Prostate Cancer.

PubMed

Wyatt, Gwen K; Sikorskii, Alla; Safikhani, Abolfazl; McVary, Kevin T; Herman, James

2016-06-01

Lower urinary tract symptoms (LUTSs) affect 75%-80% of men undergoing radiation therapy (RT) for prostate cancer. To determine the safety, maximum tolerated dose (MTD), and preliminary efficacy of Serenoa repens commonly known as saw palmetto (SP) for management of LUTS during RT for prostate cancer. The dose finding phase used the time-to-event continual reassessment method to evaluate safety of three doses (320, 640, and 960 mg) of SP. Dose-limiting toxicities were assessed for 22 weeks using the Common Terminology Criteria for Adverse Events for nausea, gastritis, and anorexia. The exploratory randomized controlled trial phase assessed preliminary efficacy of the MTD against placebo. The primary outcome of LUTS was measured over 22 weeks using the International Prostate Symptom Score. Additional longitudinal assessments included quality of life measured with the Functional Assessment of Cancer Therapy-Prostate. The dose finding phase was completed by 27 men who reported no dose-limiting toxicities and with 20 participants at the MTD of 960 mg daily. The exploratory randomized controlled trial phase included 21 men, and no statistically significant differences in the International Prostate Symptom Score were observed. The prostate-specific concerns score of the Functional Assessment of Cancer Therapy-Prostate improved in the SP group (P = 0.03). Of 11 men in the placebo group, two received physician-prescribed medications to manage LUTS compared with none of the 10 men in the SP group. SP at 960 mg may be a safe herbal supplement, but its efficacy in managing LUTS during RT needs further investigation. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.