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

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.

Comparative Evaluation of Neem Mouthwash on Plaque and Gingivitis: A Double-blind Crossover Study.

PubMed

Jalaluddin, Md; Rajasekaran, U B; Paul, Sam; Dhanya, R S; Sudeep, C B; Adarsh, V J

2017-07-01

The present study aimed at evaluating the impact of neem-containing mouthwash on plaque and gingivitis. This randomized, double-blinded, crossover clinical trial included 40 participants aged 18 to 35 years with washout period of 1 week between the crossover phases. A total of 20 participants, each randomly allocated into groups I and II, wherein in the first phase, group I was provided with 0.2% chlorhexidine gluconate and group II with 2% neem mouthwash. After the scores were recorded, 1-week time period was given to the participants to carry over the effects of the mouthwashes and then the second phase of the test was performed. The participants were instructed to use the other mouthwash through the second test phase. There was a slight reduction of plaque level in the first phase as well as in the second phase. When comparison was made between the groups, no statistically significant difference was seen. Both the groups showed reduction in the gingival index (GI) scores in the first phase, and there was a statistically significant difference in both groups at baseline and after intervention (0.005 and 0.01 respectively). In the second phase, GI scores were reduced in both groups, but there was a statistically significant difference between the groups only at baseline scores (0.01). In the present study, it has been concluded that neem mouthwash can be used as an alternative to chlorhexidine mouthwash based on the reduced scores in both the groups. Using neem mouthwash in maintaining oral hygiene might have a better impact in prevention as well as pervasiveness of oral diseases as it is cost-effective and easily available.

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.

Timing of Adjuvant Surgical Oophorectomy in the Menstrual Cycle and Disease-Free and Overall Survival in Premenopausal Women With Operable Breast Cancer

PubMed Central

Laudico, Adriano V.; Van Dinh, Nguyen; Allred, D. Craig; Uy, Gemma B.; Quang, Le Hong; Salvador, Jonathan Disraeli S.; Siguan, Stephen Sixto S.; Mirasol-Lumague, Maria Rica; Tung, Nguyen Dinh; Benjaafar, Noureddine; Navarro, Narciso S.; Quy, Tran Tu; De La Peña, Arturo S.; Dofitas, Rodney B.; Bisquera, Orlino C.; Linh, Nguyen Dieu; To, Ta Van; Young, Gregory S.; Hade, Erinn M.; Jarjoura, David

2015-01-01

Background: For women with hormone receptor–positive, operable breast cancer, surgical oophorectomy plus tamoxifen is an effective adjuvant therapy. We conducted a phase III randomized clinical trial to test the hypothesis that oophorectomy surgery performed during the luteal phase of the menstrual cycle was associated with better outcomes. Methods: Seven hundred forty premenopausal women entered a clinical trial in which those women estimated not to be in the luteal phase of their menstrual cycle for the next one to six days (n = 509) were randomly assigned to receive treatment with surgical oophorectomy either delayed to be during a five-day window in the history-estimated midluteal phase of the menstrual cycles, or in the next one to six days. Women who were estimated to be in the luteal phase of the menstrual cycle for the next one to six days (n = 231) were excluded from random assignment and received immediate surgical treatments. All patients began tamoxifen within 6 days of surgery and continued this for 5 years. Kaplan-Meier methods, the log-rank test, and multivariable Cox regression models were used to assess differences in five-year disease-free survival (DFS) between the groups. All statistical tests were two-sided. Results: The randomized midluteal phase surgery group had a five-year DFS of 64%, compared with 71% for the immediate surgery random assignment group (hazard ratio [HR] = 1.24, 95% confidence interval [CI] = 0.91 to 1.68, P = .18). Multivariable Cox regression models, which included important prognostic variables, gave similar results (aHR = 1.28, 95% CI = 0.94 to 1.76, P = .12). For overall survival, the univariate hazard ratio was 1.33 (95% CI = 0.94 to 1.89, P = .11) and the multivariable aHR was 1.43 (95% CI = 1.00 to 2.06, P = .05). Better DFS for follicular phase surgery, which was unanticipated, proved consistent across multiple exploratory analyses. Conclusions: The hypothesized benefit of adjuvant luteal phase oophorectomy was not shown in this large trial. PMID:25794890

Comparing Weight Loss-Maintenance Outcomes of a Worksite-Based Lifestyle Program Delivered via DVD and Face-to-Face: A Randomized Trial.

PubMed

Ing, Claire Townsend; Miyamoto, Robin E S; Fang, Rui; Antonio, Mapuana; Paloma, Diane; Braun, Kathryn L; Kaholokula, Joseph Keawe'aimoku

2018-03-01

Native Hawaiians and other Pacific Islanders have high rates of overweight and obesity compared with other ethnic groups in Hawai'i. Effective weight loss and weight loss-maintenance programs are needed to address obesity and obesity-related health inequities for this group. Compare the effectiveness of a 9-month, worksite-based, weight loss-maintenance intervention delivered via DVD versus face-to-face in continued weight reduction and weight loss maintenance beyond the initial weight loss phase. We tested DVD versus face-to-face delivery of the PILI@Work Program's 9-month, weight loss-maintenance phase in Native Hawaiian-serving organizations. After completing the 3-month weight loss phase, participants ( n = 217) were randomized to receive the weight loss-maintenance phase delivered via trained peer facilitators or DVDs. Participant assessments at randomization and postintervention included weight, height, blood pressure, physical functioning, exercise frequency, and fat intake. Eighty-three face-to-face participants were retained at 12 months (74.1%) compared with 73 DVD participants (69.5%). There was no significant difference between groups in weight loss or weight loss maintenance. The number of lessons attended in Phase 1 of the intervention (β = 0.358, p = .022) and baseline systolic blood pressure (β = -0.038, p = .048) predicted percent weight loss at 12 months. Weight loss maintenance was similar across groups. This suggests that low-cost delivery methods for worksite-based interventions targeting at-risk populations can help address obesity and obesity-related disparities. Additionally, attendance during the weight loss phase and lower baseline systolic blood pressure predicted greater percent weight loss during the weight loss-maintenance phase, suggesting that early engagement and initial physical functioning improve long-term weight loss outcomes.

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.

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.

Effects of inhalational anaesthesia with low tidal volume ventilation on end-tidal sevoflurane and carbon dioxide concentrations: prospective randomized study.

PubMed

de la Matta-Martín, M; López-Herrera, D; Luis-Navarro, J C; López-Romero, J L

2014-02-01

We investigated how ventilation with low tidal volumes affects the pharmacokinetics of sevoflurane uptake during the first minutes of inhaled anaesthesia. Forty-eight patients scheduled for lung resection were randomly assigned to three groups. Patients in group 1, 2 and 3 received 3% sevoflurane for 3 min via face mask and controlled ventilation with a tidal volume of 2.2, 8 and 12 ml kg(-1), respectively (Phase 1). After tracheal intubation (Phase 2), 3% sevoflurane was supplied for 2 min using a tidal volume of 8 ml kg(-1) (Phase 3). End-tidal sevoflurane concentrations were significantly higher in group 1 at the end of phase 1 and lower at the end of phase 2 than in the other groups as follows: median of 2.5%, 2.2% and 2.3% in phase 1 for groups 1, 2 and 3, respectively (P<0.001); and 1.7%, 2.1% and 2.0% in phase 2, respectively (P<0.001). End-tidal carbon dioxide values in group 1 were significantly lower at the end of phase 1 and higher at the end of phase 2 than in the other groups as follows: median of 16.5, 31 and 29.5 mm Hg in phase 1 for groups 1, 2 and 3, respectively (P<0.001); and 46.2, 36 and 33.5 mm Hg in phase 2, respectively (P<0.001). When sevoflurane is administered with tidal volume approximating the airway dead space volume, end-tidal sevoflurane and end-tidal carbon dioxide may not correctly reflect the concentration of these gases in the alveoli, leading to misinterpretation of expired gas data. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

A Randomized Phase II Dose-Response Exercise Trial among Colon Cancer Survivors: Purpose, Study Design, Methods, and Recruitment Results

PubMed Central

Brown, Justin C.; Troxel, Andrea B.; Ky, Bonnie; Damjanov, Nevena; Zemel, Babette S.; Rickels, Michael R.; Rhim, Andrew D.; Rustgi, Anil K.; Courneya, Kerry S.; Schmitz, Kathryn H.

2016-01-01

Background Observational studies indicate that higher volumes of physical activity are associated with improved disease outcomes among colon cancer survivors. The aim of this report is to describe the purpose, study design, methods, and recruitment results of the COURAGE trial, a National Cancer Institute (NCI) sponsored, phase II, randomized, dose-response exercise trial among colon cancer survivors. Methods/Results The primary objective of the COURAGE trial is to quantify the feasibility, safety, and physiologic effects of low-dose (150 min·wk−1) and high-dose (300 min·wk−1) moderate-intensity aerobic exercise compared to usual-care control group over six months. The exercise groups are provided with in-home treadmills and heart rate monitors. Between January and July 2015, 1,433 letters were mailed using a population-based state cancer registry; 126 colon cancer survivors inquired about participation, and 39 were randomized onto the study protocol. Age was associated with inquiry about study participation (P<0.001) and randomization onto the study protocol (P<0.001). No other demographic, clinical, or geographic characteristics were associated with study inquiry or randomization. The final trial participant was randomized in August 2015. Six month endpoint data collection was completed in February 2016. Discussion The recruitment of colon cancer survivors into an exercise trial is feasible. The findings from this trial will inform key design aspects for future phase 2 and phase 3 randomized controlled trials to examine the efficacy of exercise to improve clinical outcomes among colon cancer survivors. PMID:26970181

Routine Sub-hepatic Drainage versus No Drainage after Laparoscopic Cholecystectomy: Open, Randomized, Clinical Trial.

PubMed

Shamim, Muhammad

2013-02-01

Surgeons are still following the old habit of routine subhepatic drainage following laparoscopic cholecystectomy (LC). This study aims to compare the outcome of subhepatic drainage with no drainage after LC. This prospective study was conducted in two phases. Phase I was open, randomized controlled trial (RCT), conducted in Civil Hospital Karachi, from August 2004 to June 2005. Phase II was descriptive case series, conducted in author's practice hospitals of Karachi, from July 2005 to December 2009. In phase I, 170 patients with chronic calculous cholecystitis underwent LC. Patients were divided into two groups, subhepatic drainage (group A: 79 patients) or no drainage (group B: 76 patients). The rest 15 patients were excluded either due to conversion or elective subhepatic drainage. In phase II, 218 consecutive patients were enrolled, who underwent LC with no subhepatic drainage. Duration of operation, character, and amount of drain fluid (if placed), postoperative ultrasound for subhepatic collection, postoperative chest X-ray for the measurement of subdiaphragmatic air, postoperative pain, postoperative nausea/vomiting, duration of hospital stay, and preoperative or postoperative complications were noted and analyzed. Duration of operation and hospital stay was slightly longer in group A patients (P values 0.002 and 0.029, respectively); postoperative pain perception, nausea/vomiting, and postoperative complications were nearly same in both groups (P value 0.064, 0.078, and 0.003, respectively). Subhepatic fluid collection was more in group A (P = 0.002), whereas subdiaphragmatic air collection was more in group B (P = 0.003). Phase II results were nearly similar to group B patients in phase I. Routine subhepatic drainage after LC is not necessary in uncomplicated cases.

Effects of zinc supplementation on subscales of anorexia in children: A randomized controlled trial

PubMed Central

Khademian, Majid; Farhangpajouh, Neda; Shahsanaee, Armindokht; Bahreynian, Maryam; Mirshamsi, Mehran; Kelishadi, Roya

2014-01-01

Objectives: This study aims to assess the effects of zinc supplementation on improving the appetite and its subscales in children. Methods: This study was conducted in 2013 in Isfahan, Iran. It had two phases. At the first step, after validation of the Child Eating Behaviour Questionaire (CEBQ), it was completed for 300 preschool children, who were randomly selected. The second phase was conducted as a randomized controlled trial. Eighty of these children were randomly selected, and were randomly assigned to two groups of equal number receiving zinc (10 mg/day) or placebo for 12 weeks. Results: Overall 77 children completed the trial (39 in the case and 3 in the control group).The results showed that zinc supplement can improve calorie intake in children by affecting some CEBQ subscales like Emotional over Eating and Food Responsible. Conclusion: Zinc supplementation had positive impact in promoting the calorie intake and some subscales of anorexia. PMID:25674110

A Comparative Efficacy of Low-Dose Combined Oral Contraceptives Containing Desogestrel and Drospirenone in Premenstrual Symptoms

PubMed Central

Wichianpitaya, Jirath; Taneepanichskul, Surasak

2013-01-01

Objective. To compare the efficacy of low-dose COC containing desogestrel (DSG) with drospirenone (DRSP) in the changes of premenstrual symptoms. Methods. In an open-label randomized controlled trial, 90 women with premenstrual syndrome who required COC were randomly recruited and allocated equally to receive either 6 cycles of 20 micrograms ethinyl estradiol (EE)/150 micrograms DSG (DSG group) or 20 micrograms EE/3 mg DRSP (DRSP group) in 24/4 extended regimen. Analysis of covariance and repeated analysis of variance were used to determine the difference of mean Women's Health Assessment Questionnaire (WHAQ) scores changes between groups, within group, and in premenstrual, menstrual, and postmenstrual phases. Results. Baseline characteristics and WHAQ scores were comparable. At the ends of the 3rd and the 6th cycles, mean WHAQ scores of all the 3 phases in DRSP group showed significant reduction and were significantly lower than those in DSG group. DSG group showed significant reduction in both premenstrual and menstrual phases after the 6th cycle. Adverse effects were comparable in both groups. In conclusion, low-dose COC containing either DSG or DRSP reduced premenstrual symptoms, but the latter showed greater efficacy and earlier reduction. PMID:23577032

The Effect of Aromatherapy Abdominal Massage on Alleviating Menstrual Pain in Nursing Students: A Prospective Randomized Cross-Over Study

PubMed Central

Marzouk, Tyseer M. F.; El-Nemer, Amina M. R.; Baraka, Hany N.

2013-01-01

Dysmenorrhea is a common cause of sickness absenteeism from both classes and work. This study investigated the effect of aromatherapy massage on a group of nursing students who are suffering of primary dysmenorrhea. A randomized blind clinical trial of crossover design was used. In the first treatment phase, group 1 (n = 48) received aromatherapy abdominal massage once daily for seven days prior to menstruation using the essential oils (cinnamon, clove, rose, and lavender in a base of almond oil). Group 2 (n = 47) received the same intervention but with placebo oil (almond oil). In the second treatment phase, the two groups switched to alternate regimen. Level and duration of pain and the amount of menstrual bleeding were evaluated at the baseline and after each treatment phase. During both treatment phases, the level and duration of menstrual pain and the amount of menstrual bleeding were significantly lower in the aromatherapy group than in the placebo group. These results suggests that aromatherapy is effective in alleviating menstrual pain, its duration and excessive menstrual bleeding. Aromatherapy can be provided as a nonpharmacological pain relief measure and as a part of nursing care given to girls suffering of dysmenorrhea, or excessive menstrual bleeding. PMID:23662151

A randomized trial using motivational interviewing for maintenance of blood pressure improvements in a community-engaged lifestyle intervention: HUB city steps

PubMed Central

Landry, Alicia; Madson, Michael; Thomson, Jessica; Zoellner, Jamie; Connell, Carol; Yadrick, Kathleen

2015-01-01

Little is known about the effective dose of motivational interviewing for maintaining intervention-induced health outcome improvements. The purpose of this study was to compare effects of two doses of motivational interviewing for maintaining blood pressure improvements in a community-engaged lifestyle intervention conducted with African-Americans. Participants were tracked through a 12-month maintenance phase following a 6-month intervention targeting physical activity and diet. For the maintenance phase, participants were randomized to receive a low (4) or high (10) dose of motivational interviewing delivered via telephone by trained research staff. Generalized linear models were used to test for group differences in blood pressure. Blood pressure significantly increased during the maintenance phase. No differences were apparent between randomized groups. Results suggest that 10 or fewer motivational interviewing calls over a 12-month period may be insufficient to maintain post-intervention improvements in blood pressure. Further research is needed to determine optimal strategies for maintaining changes. PMID:26590242

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.

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.

Contribution to More Patient-Friendly ART Treatment: Efficacy of Continuous Low-Dose GnRH Agonist as the Only Luteal Support—Results of a Prospective, Randomized, Comparative Study

PubMed Central

Pirard, Céline; Loumaye, Ernest; Wyns, Christine

2015-01-01

Background. The aim of this pilot study was to evaluate intranasal buserelin for luteal phase support and compare its efficacy with standard vaginal progesterone in IVF/ICSI antagonist cycles. Methods. This is a prospective, randomized, open, parallel group study. Forty patients underwent ovarian hyperstimulation with human menopausal gonadotropin under pituitary inhibition with gonadotropin-releasing hormone antagonist, while ovulation trigger and luteal support were achieved using intranasal GnRH agonist (group A). Twenty patients had their cycle downregulated with buserelin and stimulated with hMG, while ovulation trigger was achieved using 10,000 IU human chorionic gonadotropin with luteal support by intravaginal progesterone (group B). Results. No difference was observed in estradiol levels. Progesterone levels on day 5 were significantly lower in group A. However, significantly higher levels of luteinizing hormone were observed in group A during the entire luteal phase. Pregnancy rates (31.4% versus 22.2%), implantation rates (22% versus 15.4%), and clinical pregnancy rates (25.7% versus 16.7%) were not statistically different between groups, although a trend towards higher rates was observed in group A. No luteal phase lasting less than 10 days was recorded in either group. Conclusion. Intranasal administration of buserelin is effective for providing luteal phase support in IVF/ICSI antagonist protocols. PMID:25945092

A randomized comparison of side effects and patient convenience between Cyclogest suppositories and Endometrin tablets used for luteal phase support in IVF treatment.

PubMed

Ng, Ernest Hung Yu; Chan, Carina Chi Wai; Tang, Oi Shan; Ho, Pak Chung

2007-04-01

This study compared side effects and patient convenience of vaginal progesterone suppositories (Cyclogest) and vaginal progesterone tablets (Endometrin) used for luteal phase support in in vitro fertilization/embryo transfer (IVF/ET) cycles using pituitary downregulation. One hundred and thirty-two infertile patients were randomized on the day of ET by a computer-generated randomization list in sealed envelopes to receive either Cyclogest 400mg or Endometrin 100mg twice daily for 14 days. On days 6 and 16 after ET, they rated side effects and patient convenience into four grades: none, mild, moderate and severe by completing a questionnaire. No significant differences in perineal irritation were found on days 6 and 16 after ET between the two groups, although there was a trend of fewer patients with perineal irritation in the Endometrin group. Significantly more patients in the Endometrin group had difficulty of administration on day 6 after ET. There were no differences in the hormonal profile on day 6 after ET and IVF outcomes between the two groups. There was no difference in perineal irritation after the use of Cyclogest suppositories or Endometrin tablets for luteal phase support although more patients found administration of Endometrin tablets difficult.

Adjunctive Mitomycin C or Amniotic Membrane Transplantation for Ahmed Glaucoma Valve Implantation: A Randomized Clinical Trial.

PubMed

Yazdani, Shahin; Mahboobipour, Hassan; Pakravan, Mohammad; Doozandeh, Azadeh; Ghahari, Elham

2016-05-01

To determine whether adjunctive mitomycin C (MMC) or amniotic membrane transplantation (AMT) improve the outcomes of Ahmed glaucoma valve (AGV) implantation. This double-blind, stratified, 3-armed randomized clinical trial includes 75 eyes of 75 patients aged 7 to 75 years with refractory glaucoma. Eligible subjects underwent stratified block randomization; eyes were first stratified to surgery in the superior or inferior quadrants based on feasibility; in each subgroup, eyes were randomly assigned to the study arms using random blocks: conventional AGV implantation (group A, 25 eyes), AGV with MMC (group B, 25 eyes), and AGV with AMT (group C, 25 eyes). The 3 study groups were comparable regarding baseline characteristics and mean follow-up (P=0.288). A total of 68 patients including 23 eyes in group A, 25 eyes in group B, and 20 eyes group C completed the follow-up period and were analyzed. Intraocular pressure was lower in the MMC group only 3 weeks postoperatively (P=0.04) but comparable at other time intervals. Overall success rate was comparable in the 3 groups at 12 months (P=0.217). The number of eyes requiring medications (P=0.30), time to initiation of medications (P=0.13), and number of medications (P=0.22) were comparable. Hypertensive phase was slightly but insignificantly more common with standard surgery (82%) as compared with MMC-augmented (60%) and AMT-augmented (70%) procedures (P=0.23). Complications were comparable over 1 year (P=0.28). Although adjunctive MMC and AMT were safe during AGV implantation, they did not influence success rates or intraocular pressure outcomes. Complications, including hypertensive phase, were also comparable.

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.

Entanglement dynamics in critical random quantum Ising chain with perturbations

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

Huang, Yichen, E-mail: ychuang@caltech.edu

We simulate the entanglement dynamics in a critical random quantum Ising chain with generic perturbations using the time-evolving block decimation algorithm. Starting from a product state, we observe super-logarithmic growth of entanglement entropy with time. The numerical result is consistent with the analytical prediction of Vosk and Altman using a real-space renormalization group technique. - Highlights: • We study the dynamical quantum phase transition between many-body localized phases. • We simulate the dynamics of a very long random spin chain with matrix product states. • We observe numerically super-logarithmic growth of entanglement entropy with time.

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.

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.

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.

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

Predictors of long-term weight loss in adults with modest initial weight loss, by sex and race.

PubMed

Svetkey, Laura P; Ard, Jamy D; Stevens, Victor J; Loria, Catherine M; Young, Deb Y; Hollis, Jack F; Appel, Lawrence J; Brantley, Phillip J; Kennedy, Betty M; Kumanyika, Shiriki K; Batch, Bryan C; Corsino, Leonor; Lien, Lillian F; Vollmer, William M

2012-09-01

Effective weight management interventions could reduce race-sex disparities in cardiovascular disease (CVD), yet little is known about factors associated with successful weight loss maintenance in race-sex subgroups. In the Weight Loss Maintenance trial (WLM), overweight/obese (BMI 25-45 kg/m(2)) adults who lost ≥4 kg in a 6-month behavioral weight loss intervention (phase I) were randomized into one of three 30-month maintenance interventions (phase II). To investigate predictors in subgroups, randomized groups were combined for this analysis. Of 1,685 phase I participants, 1,032 (61%) entered phase II, including 12% black men (BM), 26% black women (BW), 25% white men (WM), and 37% white women (WW). Weight change over the 36-month study ranged from -2.3% (95% confidence interval = -3.1 to -1.5%) in BW to -4.5% (95% confidence interval = -5.7 to -4.0%) in WM, the result of differential weight loss during phase I. Within race, men lost significantly more weight than women, but within sex group, weight loss did not differ significantly between races. Although participants regained weight during phase II, regain did not differ by race-sex group, and mean weight at the end of the study was significantly lower than phase I entry weight for each subgroup. In regression models, phase I weight loss predicted overall 36-month weight loss in all race-sex groups. Healthy dietary pattern at entry, improvement in dietary pattern, or both were predictive in three of four race-sex groups. Few other variables other than initial weight loss and dietary pattern were predictive. Future research should identify additional modifiable influences on long-term maintenance after a modest weight loss.

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

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.

Effect of a Quality Improvement Intervention With Daily Round Checklists, Goal Setting, and Clinician Prompting on Mortality of Critically Ill Patients: A Randomized Clinical Trial.

PubMed

Cavalcanti, Alexandre B; Bozza, Fernando Augusto; Machado, Flavia R; Salluh, Jorge I F; Campagnucci, Valquiria Pelisser; Vendramim, Patricia; Guimaraes, Helio Penna; Normilio-Silva, Karina; Damiani, Lucas Petri; Romano, Edson; Carrara, Fernanda; Lubarino Diniz de Souza, Juliana; Silva, Aline Reis; Ramos, Grazielle Viana; Teixeira, Cassiano; Brandão da Silva, Nilton; Chang, Chung-Chou H; Angus, Derek C; Berwanger, Otavio

2016-04-12

The effectiveness of checklists, daily goal assessments, and clinician prompts as quality improvement interventions in intensive care units (ICUs) is uncertain. To determine whether a multifaceted quality improvement intervention reduces the mortality of critically ill adults. This study had 2 phases. Phase 1 was an observational study to assess baseline data on work climate, care processes, and clinical outcomes, conducted between August 2013 and March 2014 in 118 Brazilian ICUs. Phase 2 was a cluster randomized trial conducted between April and November 2014 with the same ICUs. The first 60 admissions of longer than 48 hours per ICU were enrolled in each phase. Intensive care units were randomized to a quality improvement intervention, including a daily checklist and goal setting during multidisciplinary rounds with follow-up clinician prompting for 11 care processes, or to routine care. In-hospital mortality truncated at 60 days (primary outcome) was analyzed using a random-effects logistic regression model, adjusted for patients' severity and the ICU's baseline standardized mortality ratio. Exploratory secondary outcomes included adherence to care processes, safety climate, and clinical events. A total of 6877 patients (mean age, 59.7 years; 3218 [46.8%] women) were enrolled in the baseline (observational) phase and 6761 (mean age, 59.6 years; 3098 [45.8%] women) in the randomized phase, with 3327 patients enrolled in ICUs (n = 59) assigned to the intervention group and 3434 patients in ICUs (n = 59) assigned to routine care. There was no significant difference in in-hospital mortality between the intervention group and the usual care group, with 1096 deaths (32.9%) and 1196 deaths (34.8%), respectively (odds ratio, 1.02; 95% CI, 0.82-1.26; P = .88). Among 20 prespecified secondary outcomes not adjusted for multiple comparisons, 6 were significantly improved in the intervention group (use of low tidal volumes, avoidance of heavy sedation, use of central venous catheters, use of urinary catheters, perception of team work, and perception of patient safety climate), whereas there were no significant differences between the intervention group and the control group for 14 outcomes (ICU mortality, central line-associated bloodstream infection, ventilator-associated pneumonia, urinary tract infection, mean ventilator-free days, mean ICU length of stay, mean hospital length of stay, bed elevation to ≥30°, venous thromboembolism prophylaxis, diet administration, job satisfaction, stress reduction, perception of management, and perception of working conditions). Among critically ill patients treated in ICUs in Brazil, implementation of a multifaceted quality improvement intervention with daily checklists, goal setting, and clinician prompting did not reduce in-hospital mortality. clinicaltrials.gov Identifier: NCT01785966.

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.

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.

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

Survival distributions impact the power of randomized placebo-phase design and parallel groups randomized clinical trials.

PubMed

Abrahamyan, Lusine; Li, Chuan Silvia; Beyene, Joseph; Willan, Andrew R; Feldman, Brian M

2011-03-01

The study evaluated the power of the randomized placebo-phase design (RPPD)-a new design of randomized clinical trials (RCTs), compared with the traditional parallel groups design, assuming various response time distributions. In the RPPD, at some point, all subjects receive the experimental therapy, and the exposure to placebo is for only a short fixed period of time. For the study, an object-oriented simulation program was written in R. The power of the simulated trials was evaluated using six scenarios, where the treatment response times followed the exponential, Weibull, or lognormal distributions. The median response time was assumed to be 355 days for the placebo and 42 days for the experimental drug. Based on the simulation results, the sample size requirements to achieve the same level of power were different under different response time to treatment distributions. The scenario where the response times followed the exponential distribution had the highest sample size requirement. In most scenarios, the parallel groups RCT had higher power compared with the RPPD. The sample size requirement varies depending on the underlying hazard distribution. The RPPD requires more subjects to achieve a similar power to the parallel groups design. Copyright © 2011 Elsevier Inc. All rights reserved.

Randomized controlled dissemination study of community-to-clinic navigation to promote CRC screening: Study design and implications.

PubMed

Larkey, Linda; Szalacha, Laura; Herman, Patricia; Gonzalez, Julie; Menon, Usha

2017-02-01

Regular screening facilitates early diagnosis of colorectal cancer (CRC) and reduction of CRC morbidity and mortality. Screening rates for minorities and low-income populations remain suboptimal. Provider referral for CRC screening is one of the strongest predictors of adherence, but referrals are unlikely among those who have no clinic home (common among poor and minority populations). This group randomized controlled study will test the effectiveness of an evidence based tailored messaging intervention in a community-to-clinic navigation context compared to no navigation. Multicultural, underinsured individuals from community sites will be randomized (by site) to receive CRC screening education only, or education plus navigation. In Phase I, those randomized to education plus navigation will be guided to make a clinic appointment to receive a provider referral for CRC screening. Patients attending clinic appointments will continue to receive navigation until screened (Phase II) regardless of initial arm assignment. We hypothesize that those receiving education plus navigation will be more likely to attend clinic appointments (H1) and show higher rates of screening (H2) compared to those receiving education only. Phase I group assignment will be used as a control variable in analysis of screening follow-through in Phase II. Costs per screening achieved will be evaluated for each condition and the RE-AIM framework will be used to examine dissemination results. The novelty of our study design is the translational dissemination model that will allow us to assess the real-world application of an efficacious intervention previously tested in a randomized controlled trial. Copyright © 2016. Published by Elsevier Inc.

Comprehensive assessment of long-term effects of reducing intake of energy phase 2 (CALERIE Phase 2) screening and recruitment: Methods and results

USDA-ARS?s Scientific Manuscript database

The Comprehensive Assessment of the Long-term Effects of Reducing Intake of Energy Phase 2 (CALERIE) study is a systematic investigation of sustained 25% calorie restriction (CR) in non-obese humans. CALERIE is a multicenter (3 clinical sites, one coordinating center), parallel group, randomized con...

Renormalization-Group Theory Study of Superfluidity and Phase Separation of Helium Mixtures Immersed in Jungle-Gym Aerogel

NASA Astrophysics Data System (ADS)

Lopatnikova, Anna; Berker, A. Nihat

1997-03-01

Superfluidity and phase separation in ^3He-^4He mixtures immersed in jungle-gym (non-random) aerogel are studied by renormalization-group theory.(Phys. Rev. B, in press (1996)) Phase diagrams are calculated for a variety of aerogel concentrations. Superfluidity at very low ^4He concentrations and a depressed tricritical temperature are found at the onset of superfluidity. A superfluid-superfluid phase separation, terminating at an isolated critical point, is found entirely within the superfluid phase. These phenomena, and trends with respect to aerogel concentration, are explained by the connectivity and tenuousness of jungle-gym aerogel.

A randomized trial of microdose leuprolide acetate protocol versus luteal phase ganirelix protocol in predicted poor responders.

PubMed

DiLuigi, Andrea J; Engmann, Lawrence; Schmidt, David W; Benadiva, Claudio A; Nulsen, John C

2011-06-30

We performed a randomized trial to compare IVF outcomes in 54 poor responder patients undergoing a microdose leuprolide acetate (LA) protocol or a GnRH antagonist protocol incorporating a luteal phase E(2) patch and GnRH antagonist in the preceding menstrual cycle. Cancellation rates, number of oocytes retrieved, clinical pregnancy rates (PR), and ongoing PRs were similar between the two groups. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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.

A randomized, phase 1/2 trial of the safety, tolerability, and immunogenicity of bivalent rLP2086 meningococcal B vaccine in healthy infants.

PubMed

Martinon-Torres, Federico; Gimenez-Sanchez, Francisco; Bernaola-Iturbe, Enrique; Diez-Domingo, Javier; Jiang, Qin; Perez, John L

2014-09-08

Neisseria meningitidis serogroup B (MnB) is a major cause of invasive meningococcal disease in infants. A conserved, surface-exposed lipoprotein, LP2086 (a factor H-binding protein [fHBP]), is a promising MnB vaccine target. A bivalent, recombinant vaccine targeting the fHBP (rLP2086) of MnB was developed. This phase 1/2 clinical study was designed to assess the immunogenicity, safety, and tolerability of a 4-dose series of the rLP2086 vaccine at 20-, 60-, 120-, or 200-μg dose levels in vaccine-naive infants when given with routine childhood vaccines. The study was to consist of two phases: a single-blind sentinel phase and an open-label full enrollment phase. During the sentinel phase, randomization of subjects to the next higher dose was delayed pending a 14-day safety review of dose 1 of the preceding dose cohort. The full enrollment phase was to occur after completion of the sentinel phase. Local reactions were generally mild and adverse events infrequent; however, after only 46 infants were randomized into the study, fever rates were 64% and 90% in subjects receiving one 20- or 60-μg rLP2086 dose, respectively. Most fevers were <39.0°C. Only 2 subjects in the 20-μg group and 1 subject in the 60-μg group experienced fevers >39.0°C; no fevers were >40.0°C. Due to these high fever rates, the study was terminated early. No immunogenicity data were collected. This report discusses the safety and acceptability of rLP2086 in infants after one 20- or 60-μg dose. Due to the high fever rate experienced in the 20- and 60-μg groups, rLP2086 in the current formulation may not be acceptable for infants. Copyright © 2014. Published by Elsevier Ltd.

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.

Switching From Reference Adalimumab to SB5 (Adalimumab Biosimilar) in Patients With Rheumatoid Arthritis: Fifty-Two-Week Phase III Randomized Study Results.

PubMed

Weinblatt, Michael E; Baranauskaite, Asta; Dokoupilova, Eva; Zielinska, Agnieszka; Jaworski, Janusz; Racewicz, Artur; Pileckyte, Margarita; Jedrychowicz-Rosiak, Krystyna; Baek, Inyoung; Ghil, Jeehoon

2018-06-01

The 24-week equivalent efficacy and comparable safety results of the biosimilar SB5 and reference adalimumab (ADA) from the phase III randomized study in patients with moderate-to-severe rheumatoid arthritis (RA) have been reported previously. We undertook this transition study to evaluate patients who switched from ADA to SB5 or who continued to receive SB5 or ADA up to 52 weeks. In this phase III study, patients were initially randomized 1:1 to receive SB5 or ADA (40 mg subcutaneously every other week). At 24 weeks, patients receiving ADA were rerandomized 1:1 to continue with ADA (ADA/ADA group) or to switch to SB5 (ADA/SB5 group) up to week 52; patients receiving SB5 continued with SB5 for 52 weeks (SB5 group). Efficacy, safety, and immunogenicity were evaluated up to 52 weeks. The full analysis set population consisted of 542 patients (269 in the SB5 group, 273 in the ADA overall group [patients who were randomized to receive ADA at week 0], 125 in the ADA/SB5 group, and 129 in the ADA/ADA group). The percentages of patients meeting the American College of Rheumatology 20%, 50%, or 70% improvement criteria (achieving an ACR20, ACR50, or ACR70 response) at week 24 were maintained after the transition from ADA to SB5, and these response rates were comparable across treatment groups throughout the study. ACR20 response rates ranged from 73.4% to 78.8% at week 52. Radiographic progression was minimal and comparable across treatment groups. The safety profile and the incidence of antidrug antibodies were comparable across treatment groups after transition. SB5 was well tolerated over 1 year in patients with RA, with efficacy, safety, and immunogenicity comparable to those of ADA. Switching from ADA to SB5 had no treatment-emergent issues such as increased adverse events, increased immunogenicity, or loss of efficacy. © 2018 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

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.

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

R-THP-COP versus R-CHOP in patients younger than 70 years with untreated diffuse large B cell lymphoma: A randomized, open-label, noninferiority phase 3 trial.

PubMed

Hara, Takeshi; Yoshikawa, Takeshi; Goto, Hideko; Sawada, Michio; Yamada, Toshiki; Fukuno, Kenji; Kasahara, Senji; Shibata, Yuhei; Matsumoto, Takuro; Mabuchi, Ryoko; Nakamura, Nobuhiko; Nakamura, Hiroshi; Ninomiya, Soranobu; Kitagawa, Junichi; Kanemura, Nobuhiro; Nannya, Yasuhito; Katsumura, Naoki; Takahashi, Takeshi; Kito, Yusuke; Takami, Tsuyoshi; Miyazaki, Tatsuhiko; Takeuchi, Tamotsu; Shimizu, Masahito; Tsurumi, Hisashi

2018-06-08

Pirarubicin (tetrahydropyranyl adriamycin [THP]) is an anthracyclin with less cardiotoxicity than doxorubicin (DOX). We previously reported the efficacy and safety of R-THP-COP consisting of rituximab (R), THP, cyclophosphamide (CPA), vincristine (VCR), and prednisolone (PSL) for diffuse large B cell lymphoma (DLBCL) in phase 2 studies. Here, we prospectively compared the efficacy and safety of the R-THP-COP and standard R-CHOP regimen (consisting of R, CPA, DOX, VCR, and PSL) in a noninferiority phase 3 trial. This prospective, randomized phase 3 study included patients younger than 70 years of age with previously untreated DLBCL. The regimen consisted of R (day 1), DOX, or THP (day 3), CPA (day 3), VCR (day 3), and PSL for 5 days every 3 weeks for 6 to 8 cycles. Between July 5, 2006 and June 11, 2013, 81 patients were randomly assigned to the treatment groups (R-CHOP group, 40 patients; R-THP-COP group, 41 patients). R-THP-COP was noninferior to R-CHOP, as assessed by the primary endpoint of complete response rate (85% vs 85% respectively). With a median follow-up of 75.2 months, the 5-year overall survival was 87% in the R-CHOP group and 82% in the R-THP-COP group (hazard ratio [HR]: 0.89, 95% confidence interval [CI]: 0.31-2.49; P = .82). The 5-year progression-free survival was 74% in the R-CHOP group and 79% in the R-THP-COP group (HR: 1.37, 95% CI: 0.56-3.55; P = .49). No grade 3 cardiac side effects were observed in either group. No serious late adverse reactions were observed in either group, with the exception of therapy-related acute myeloid leukemia in the R-THP-COP group. These data indicate that R-THP-COP is noninferior to R-CHOP with regard to clinical response, and has an acceptable safety profile. Thus, this regimen may be an alternative therapy to R-CHOP. Copyright © 2018 John Wiley & Sons, Ltd.

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.

Effects of guar gum ingestion on postprandial blood pressure in older adults.

PubMed

Jang, A L; Hwang, S K; Kim, D U

2015-03-01

The aim of this study was to investigate the effects of guar gum on postprandial blood pressure in older people. A randomized, double-blind, placebo-controlled, cross-over design. Community senior centers in B city, South Korea. Twenty-two older female adults aged 67 to 88 with postprandial hypotension. The participants were randomly assigned to guar gum (semi-fluid food with 9 gram) or placebo intervention during the first treatment phase. After a washout period of 1 week, the two interventions were switched to the other in the second treatment phase. Blood pressure was measured during both phases before having a meal and every 15 minutes during 120 minutes after a meal with automated sphygmomanometer. Change in systolic blood pressure (SBP) over time was significantly different between guar gum and placebo groups (F=4.07, p=0.001). Compared with placebo group, guar gum group had significantly low prevalence of postprandial hypotension (PPH) (guar gum group=18.2% vs. placebo group=72.7%; χ² =13.20, p<0.001). It also had significant difference in change of diastolic blood pressure (DBP) over time between guar gum and placebo groups (F=2.49, p=0.027). This findings show that guar gum could be effective on postprandial drops in blood pressure in older female adults.

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

Sustained-Release Methylphenidate in a Randomized Trial of Treatment of Methamphetamine Use Disorder

PubMed Central

Ling, Walter; Chang, Linda; Hillhouse, Maureen; Ang, Alfonso; Striebel, Joan; Jenkins, Jessica; Hernandez, Jasmin; Olaer, Mary; Mooney, Larissa; Reed, Susan; Fukaya, Erin; Kogachi, Shannon; Alicata, Daniel; Holmes, Nataliya; Esagoff, Asher

2014-01-01

Background and aims No effective pharmacotherapy for methamphetamine (MA) use disorder has yet been found. This study evaluated sustained-release methylphenidate (MPH-SR) compared with placebo (PLA) for treatment of MA use disorder in people also undergoing behavioural support and motivational incentives. Design This was a randomized, double-blind, placebo-controlled design with MPH-SR or PLA provided for 10 weeks (active phase) followed by 4 weeks of single-blind PLA. Twice-weekly clinic visits, weekly group counseling (CBT), and motivational incentives (MI) for MA-negative urine drug screens (UDS) were included. Setting Treatment sites were in Los Angeles, California (LA) and Honolulu, Hawaii (HH), USA. Participants 110 MA-dependent (via DSM-IV) participants (LA = 90; HH = 20). Measurements The primary outcome measure is self-reported days of MA use during the last 30 days of the active phase. Included in the current analyses are drug use (UDS and self-report), retention, craving, compliance (dosing, CBT, MI), adverse events, and treatment satisfaction. Findings No difference was found between treatment groups in self-reported days of MA use during the last 30 days of the active phase (p=0.22). In planned secondary outcomes analyses, however, the MPH group had fewer self-reported MA use days from baseline through the active phase compared with the PLA group (p=0.05). The MPH group also had lower craving scores and fewer marijuana-positive UDS than the PLA group in the last 30 days of the active phase. The two groups had similar retention, other drug use, adverse events, and treatment satisfaction. Conclusions Methylphenidate may lead to a reduction in concurrent methamphetamine use when provided as treatment for patients undergoing behavioural support for moderate to severe methamphetamine use disorder but this requires confirmation. PMID:24825486

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.

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

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.

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.

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.

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

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.

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.

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.

Hymenoptera Venom Immunotherapy: Tolerance and Efficacy of an Ultrarush Protocol versus a Rush and a Slow Conventional Protocol

PubMed Central

Patella, Vincenzo; Florio, Giovanni; Giuliano, Ada; Oricchio, Carmine; Spadaro, Giuseppe; Marone, Gianni; Genovese, Arturo

2012-01-01

Background and Objective. Various venom immunotherapy (VIT) protocols are available for Hymenoptera allergy. Although adverse reactions (ADRs) to VIT are widely reported, controlled trials are still needed. We conducted a randomized prospective study to evaluate ADRs and the efficacy of three VIT regimens. Methods. 76 patients with Hymenoptera allergy, aged 16–76 years, were randomized to receive an ultrarush protocol (group A: 27 patients), a rush protocol (group B: 25), or a slow protocol (group C: 24). Aqueous venom extract was used in incremental phase and an adsorbed depot in maintenance phase. ADRs and accidental Hymenoptera stings during VIT were used to evaluate efficacy. Results. During incremental treatment, ADRs occurred in 1.99%, 3.7%, and 3.9% of patients in groups A, B, and C, and in 0.99%, 1.46%, and 2.7%, respectively, during maintenance. ADRs were significantly fewer in group A (incremental + maintenance phase) than in group C (1.29% versus 3.2%; P = 0.013). Reactions to accidental Hymenoptera stings did not differ among groups (1.1%, 1.2%, and 1.1%). Conclusion. Ultrarush was as effective as the rush and slow protocols and was associated with a low incidence of reactions to stings. This study indicates that ultrarush VIT is a valid therapeutic option for Hymenoptera allergy. PMID:22693521

The use of real-time ultrasound imaging for biofeedback of lumbar multifidus muscle contraction in healthy subjects.

PubMed

Van, Khai; Hides, Julie A; Richardson, Carolyn A

2006-12-01

Randomized controlled trial. To determine if the provision of visual biofeedback using real-time ultrasound imaging enhances the ability to activate the multifidus muscle. Increasingly clinicians are using real-time ultrasound as a form of biofeedback when re-educating muscle activation. The effectiveness of this form of biofeedback for the multifidus muscle has not been reported. Healthy subjects were randomly divided into groups that received different forms of biofeedback. All subjects received clinical instruction on how to activate the multifidus muscle isometrically prior to testing and verbal feedback regarding the amount of multifidus contraction, which occurred during 10 repetitions (acquisition phase). In addition, 1 group received visual biofeedback (watched the multifidus muscle contract) using real-time ultrasound imaging. All subjects were reassessed a week later (retention phase). Subjects from both groups improved their voluntary contraction of the multifidus muscle in the acquisition phase (P<.001) and the ability to recruit the multifidus muscle differed between groups (P<.05), with subjects in the group that received visual ultrasound biofeedback achieving greater improvements. In addition, the group that received visual ultrasound biofeedback retained their improvement in performance from week 1 to week 2 (P>.90), whereas the performance of the other group decreased (P<.05). Real-time ultrasound imaging can be used to provide visual biofeedback and improve performance and retention in the ability to activate the multifidus muscle in healthy subjects.

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

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 .).

A Novel Strategy for Continuation ECT in Geriatric Depression: Phase 2 of the PRIDE Study.

PubMed

Kellner, Charles H; Husain, Mustafa M; Knapp, Rebecca G; McCall, W Vaughn; Petrides, Georgios; Rudorfer, Matthew V; Young, Robert C; Sampson, Shirlene; McClintock, Shawn M; Mueller, Martina; Prudic, Joan; Greenberg, Robert M; Weiner, Richard D; Bailine, Samuel H; Rosenquist, Peter B; Raza, Ahmad; Kaliora, Styliani; Latoussakis, Vassilios; Tobias, Kristen G; Briggs, Mimi C; Liebman, Lauren S; Geduldig, Emma T; Teklehaimanot, Abeba A; Dooley, Mary; Lisanby, Sarah H

2016-11-01

The randomized phase (phase 2) of the Prolonging Remission in Depressed Elderly (PRIDE) study evaluated the efficacy and tolerability of continuation ECT plus medication compared with medication alone in depressed geriatric patients after a successful course of ECT (phase 1). PRIDE was a two-phase multisite study. Phase 1 was an acute course of right unilateral ultrabrief pulse ECT, augmented with venlafaxine. Phase 2 compared two randomized treatment arms: a medication only arm (venlafaxine plus lithium, over 24 weeks) and an ECT plus medication arm (four continuation ECT treatments over 1 month, plus additional ECT as needed, using the Symptom-Titrated, Algorithm-Based Longitudinal ECT [STABLE] algorithm, while continuing venlafaxine plus lithium). The intent-to-treat sample comprised 120 remitters from phase 1. The primary efficacy outcome measure was score on the 24-item Hamilton Depression Rating Scale (HAM-D), and the secondary efficacy outcome was score on the Clinical Global Impressions severity scale (CGI-S). Tolerability as measured by neurocognitive performance (reported elsewhere) was assessed using an extensive test battery; global cognitive functioning as assessed by the Mini-Mental State Examination (MMSE) is reported here. Longitudinal mixed-effects repeated-measures modeling was used to compare ECT plus medication and medication alone for efficacy and global cognitive function outcomes. At 24 weeks, the ECT plus medication group had statistically significantly lower HAM-D scores than the medication only group. The difference in adjusted mean HAM-D scores at study end was 4.2 (95% CI=1.6, 6.9). Significantly more patients in the ECT plus medication group were rated "not ill at all" on the CGI-S compared with the medication only group. There was no statistically significant difference between groups in MMSE score. Additional ECT after remission (here operationalized as four continuation ECT treatments followed by further ECT only as needed) was beneficial in sustaining mood improvement for most patients.

Comparison of oral dydrogesterone with vaginal progesteronefor luteal support in IUI cycles: a randomized clinical trial.

PubMed

Khosravi, Donya; Taheripanah, Robabeh; Taheripanah, Anahita; Tarighat Monfared, Vahid; Hosseini-Zijoud, Seyed-Mostafa

2015-07-01

The aim of this study, we have compared the advantages of oral dydrogestrone with vaginal progesterone (cyclogest) for luteal support in intrauterine insemination (IUI) cycles. Progesterone supplementation is the first line treatment when luteal phase deficiency (LPD) can reasonably be assumed. This study was conduct to compare the effect of oral dydrogestrone with vaginal Cyclogest on luteal phase support in the IUI cycles. This prospective, randomized, double blind study was performed in a local infertility center from May 2013 to May 2014. It consisted of 150 infertile women younger than35years old undergoing ovarian stimulation for IUI cycles. They underwent ovarian stimulation with oral dydrogesterone (20 mg) as group A and vaginal cyclogest (400 mg) as group B in preparation for the IUI cycles. Clinical pregnancy and abortion rates, mid luteal progesterone (7daysafter IUI) and patient satisfaction were compared between two groups. The mean serum progesterone levels was significantly higher in group A in comparison with group B (p=0.001). Pregnancy rates in group A was not statistically different in comparison with group B (p =0.58). Abortion rate in two groups was not statistically different (p =0.056) although rate of abortion was higher in group B in comparison with A group. Satisfaction rates were significantly higher in group A compared to group B (p<0.001). We concluded that oral dydrogestrone is effective as vaginal progesterone for luteal-phase support in woman undergoing IUI cycles. Moreover, the mean serum progesterone levels and satisfaction rates in dydrogestrone group were higher than cyclogest group.

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.

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.

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.

Efficacy and safety of rebamipide liquid for chemoradiotherapy-induced oral mucositis in patients with head and neck cancer: a multicenter, randomized, double-blind, placebo-controlled, parallel-group phase II study.

PubMed

Yokota, T; Ogawa, T; Takahashi, S; Okami, K; Fujii, T; Tanaka, K; Iwae, S; Ota, I; Ueda, T; Monden, N; Matsuura, K; Kojima, H; Ueda, S; Sasaki, K; Fujimoto, Y; Hasegawa, Y; Beppu, T; Nishimori, H; Hirano, S; Naka, Y; Matsushima, Y; Fujii, M; Tahara, M

2017-05-05

Recent preclinical and phase I studies have reported that rebamipide decreased the severity of chemoradiotherapy-induced oral mucositis in patients with oral cancer. This placebo-controlled randomized phase II study assessed the clinical benefit of rebamipide in reducing the incidence of severe chemoradiotherapy-induced oral mucositis in patients with head and neck cancer (HNC). Patients aged 20-75 years with HNC who were scheduled to receive chemoradiotherapy were enrolled. Patients were randomized to receive rebamipide 2% liquid, rebamipide 4% liquid, or placebo. The primary endpoint was the incidence of grade ≥ 3 oral mucositis determined by clinical examination and assessed by central review according to the Common Terminology Criteria of Adverse Events version 3.0. Secondary endpoints were the time to onset of grade ≥ 3 oral mucositis and the incidence of functional impairment (grade ≥ 3) based on the evaluation by the Oral Mucositis Evaluation Committee. From April 2014 to August 2015, 97 patients with HNC were enrolled, of whom 94 received treatment. The incidence of grade ≥ 3 oral mucositis was 29% and 25% in the rebamipide 2% and 4% groups, respectively, compared with 39% in the placebo group. The proportion of patients who did not develop grade ≥ 3 oral mucositis by day 50 of treatment was 57.9% in the placebo group, whereas the proportion was 68.0% in the rebamipide 2% group and 71.3% in the rebamipide 4% group. The incidences of adverse events potentially related to the study drug were 16%, 26%, and 13% in the placebo, rebamipide 2%, and rebamipide 4% groups, respectively. There was no significant difference in treatment compliance among the groups. The present phase II study suggests that mouth washing with rebamipide may be effective and safe for patients with HNC receiving chemoradiotherapy, and 4% liquid is the optimal dose of rebamipide. ClinicalTrials.gov under the identifier NCT02085460 (the date of trial registration: March 11, 2014).

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

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.

Treatment with α-Lipoic Acid over 16 Weeks in Type 2 Diabetic Patients with Symptomatic Polyneuropathy Who Responded to Initial 4-Week High-Dose Loading.

PubMed

Garcia-Alcala, Hector; Santos Vichido, Celia Isabel; Islas Macedo, Silverio; Genestier-Tamborero, Christelle Nathalie; Minutti-Palacios, Marissa; Hirales Tamez, Omara; García, Carlos; Ziegler, Dan

2015-01-01

Effective treatment of diabetic sensorimotor polyneuropathy remains a challenge. To assess the efficacy and safety of α-lipoic acid (ALA) over 20 weeks, we conducted a multicenter randomized withdrawal open-label study, in which 45 patients with type 2 diabetes and symptomatic polyneuropathy were initially treated with ALA (600 mg tid) for 4 weeks (phase 1). Subsequently, responders were randomized to receive ALA (600 mg qd; n = 16) or to ALA withdrawal (n = 17) for 16 weeks (phase 2). During phase 1, the Total Symptom Score (TSS) decreased from 8.9 ± 1.8 points to 3.46 ± 2.0 points. During phase 2, TSS improved from 3.7 ± 1.9 points to 2.5 ± 2.5 points in the ALA treated group (p < 0.05) and remained unchanged in the ALA withdrawal group. The use of analgesic rescue medication was higher in the ALA withdrawal group than ALA treated group (p < 0.05). In conclusion, in type 2 diabetic patients with symptomatic polyneuropathy who responded to initial 4-week high-dose (600 mg tid) administration of ALA, subsequent treatment with ALA (600 mg qd) over 16 weeks improved neuropathic symptoms, whereas ALA withdrawal was associated with a higher use of rescue analgesic drugs. This trial is registered with ClinicalTrials.gov Identifier: NCT02439879.

Customizing chemotherapy in non-small cell lung cancer: the promise is still unmet

PubMed Central

2015-01-01

A combination of cytotoxic agents with cis-platin remains the cornerstone of treatment for the vast majority of patients with non-small cell lung cancer (NSCLC). Molecular analysis of the primary may lead better prognostication and eventually in more accurate therapeutic approaches. Data from retrospective analysis of randomized trials as well as large patients’ series have suggested that chemotherapy may be customized upon molecular-genetic analysis of the tumor cells. The Spanish Lung Cancer Group (SLCG) in collaboration with French lung Cancer Group (FLCG) had conduct randomized, phase III, biomarkers-driven trial and supported simultaneously a randomized phase II trial in collaborating centers in China. Despite the evidence from the preclinical data and the results from the retrospective studies, the results of these trials published recently in Annals of Oncology were in favor of ‘standard approach’. The present commentary tries to give some explanation for the disappointing results, provide potential solution for the future trials and explain why the vision of customizing treatment is still alive. PMID:26629440

Validation of computer simulation training for esophagogastroduodenoscopy: Pilot study.

PubMed

Sedlack, Robert E

2007-08-01

Little is known regarding the value of esophagogastroduodenoscopy (EGD) simulators in education. The purpose of the present paper was to validate the use of computer simulation in novice EGD training. In phase 1, expert endoscopists evaluated various aspects of simulation fidelity as compared to live endoscopy. Additionally, computer-recorded performance metrics were assessed by comparing the recorded scores from users of three different experience levels. In phase 2, the transfer of simulation-acquired skills to the clinical setting was assessed in a two-group, randomized pilot study. The setting was a large gastroenterology (GI) Fellowship training program; in phase 1, 21 subjects (seven expert, intermediate and novice endoscopist), made up the three experience groups. In phase 2, eight novice GI fellows were involved in the two-group, randomized portion of the study examining the transfer of simulation skills to the clinical setting. During the initial validation phase, each of the 21 subjects completed two standardized EDG scenarios on a computer simulator and their performance scores were recorded for seven parameters. Following this, staff participants completed a questionnaire evaluating various aspects of the simulator's fidelity. Finally, four novice GI fellows were randomly assigned to receive 6 h of simulator-augmented training (SAT group) in EGD prior to beginning 1 month of patient-based EGD training. The remaining fellows experienced 1 month of patient-based training alone (PBT group). Results of the seven measured performance parameters were compared between three groups of varying experience using a Wilcoxon ranked sum test. The staffs' simulator fidelity survey used a 7-point Likert scale (1, very unrealistic; 4, neutral; 7, very realistic) for each of the parameters examined. During the second phase of this study, supervising staff rated both SAT and PBT fellows' patient-based performance daily. Scoring in each skill was completed using a 7-point Likert scale (1, strongly disagree; 4, neutral; 7, strongly agree). Median scores were compared between groups using the Wilcoxon ranked sum test. Staff evaluations of fidelity found that only two of the parameters examined (anatomy and scope maneuverability) had a significant degree of realism. The remaining areas were felt to be limited in their fidelity. Of the computer-recorded performance scores, only the novice group could be reliably identified from the other two experience groups. In the clinical application phase, the median Patient Discomfort ratings were superior in the PBT group (6; interquartile range [IQR], 5-6) as compared to the SAT group (5; IQR, 4-6; P = 0.015). PBT fellows' ratings were also superior in Sedation, Patient Discomfort, Independence and Competence during various phases of the evaluation. At no point were SAT fellows rated higher than the PBT group in any of the parameters examined. This EGD simulator has limitations to the degree of fidelity and can differentiate only novice endoscopists from other levels of experience. Finally, skills learned during EGD simulation training do not appear to translate well into patient-based endoscopy skills. These findings suggest against a key element of validity for the use of this computer simulator in novice EGD training.

Effects of Lobeglitazone, a Novel Thiazolidinedione, on Bone Mineral Density in Patients with Type 2 Diabetes Mellitus over 52 Weeks

PubMed Central

Lim, Soo; Kim, Kyoung Min; Kim, Sin Gon; Kim, Doo Man; Woo, Jeong-Taek; Chung, Choon Hee; Ko, Kyung Soo; Park, Jeong Hyun; Park, Yongsoo; Kim, Sang Jin; Jang, Hak Chul

2017-01-01

Background The aim of this multicenter, randomized, double-blind study was to examine the effect of lobeglitazone, a novel thiazolidinedione, on the changes in bone mineral density (BMD) in patients with type 2 diabetes mellitus. Methods A 24-week, double-blinded phase was followed by a 28-week, open-label phase, in which the placebo group also started to receive lobeglitazone. A total of 170 patients aged 34 to 76 years were randomly assigned in a 2:1 ratio to receive lobeglitazone 0.5 mg or a matching placebo orally, once daily. BMD was assessed using dual-energy X-ray absorptiometry at week 24 and at the end of the study (week 52). Results During the double-blinded phase, the femur neck BMD showed decreasing patterns in both groups, without statistical significance (−0.85%±0.36% and −0.78%±0.46% in the lobeglitazone and placebo groups, respectively). The treatment difference between the groups was 0.07%, which was also not statistically significant. Further, minimal, nonsignificant decreases were observed in both groups in the total hip BMD compared to values at baseline, and these differences also did not significantly differ between the groups. During the open-label phase, the BMD was further decreased, but not significantly, by −0.32% at the femur neck and by −0.60% at the total hip in the lobeglitazone group, and these changes did not significantly differ compared with the original placebo group switched to lobeglitazone. Conclusion Our results indicate that treatment with lobeglitazone 0.5 mg over 52 weeks showed no detrimental effect on the BMD compared to the placebo. PMID:29086536

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.

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.

Treatment for premenstrual syndrome with Vitex agnus castus: A prospective, randomized, multi-center placebo controlled study in China.

PubMed

He, Zhong; Chen, Rong; Zhou, Yingfang; Geng, Li; Zhang, Zhenyu; Chen, Shuling; Yao, Yanjun; Lu, Junli; Lin, Shouqing

2009-05-20

To investigate the efficacy and safety of VAC BNO 1095 extract in Chinese women suffering from moderate to severe premenstrual syndrome (PMS). Prospective, double-blind, placebo controlled, parallel-group, multi-center clinical trial design was employed. After screening and preparation phase lasting three cycles, Eligible patients were randomly assigned into treatment or placebo groups and had treatment with VAC extract or placebo for up to three cycles. Efficacy was assessed using the Chinese version PMS-diary (PMSD) and PMTS. Two hundred and seventeen women were eligible to enter the treatment phase (TP) and were randomly assigned into the treatment group (108) or the placebo group (109), 208 provided the efficacy data (treatment 104, placebo 104), and 202 completed the treatment phase (treatment 101, placebo 101). The mean total PMSD score decreased from 29.23 at baseline (0 cycle) to 6.41 at the termination (3rd cycle) for the treatment group and from 28.14 at baseline (0 cycle) to 12.64 at the termination (3rd cycle) for the placebo group. The total PMSD score of 3rd cycle was significantly lower than the baseline in both groups (p<0.0001). The difference in the mean scores from the baseline to the 3rd cycle in the treatment group (22.71+/-10.33) was significantly lower than the difference in the placebo group (15.50+/-12.94, p<0.0001). Results of PMTS were similar, the total scores for PMTS were significantly lower between the two groups (p<0.01) and within each group (p<0.01). The score was decreased from 26.17+/-4.79 to 9.92+/-9.01 for the treatment group, and from 27.10+/-4.76 to 14.59+/-10.69 for the placebo group. A placebo effect of 50% was found in the present study. No serious adverse event (SAE) occurred in both groups. Vitex agnus castus (VAC BNO 1095 corresponding to 40mg herbal drug) is a safe, well tolerated and effective drug of the treatment for Chinese women with the moderate to severe PMS.

The quantum-field renormalization group in the problem of a growing phase boundary

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

Antonov, N.V.; Vasil`ev, A.N.

1995-09-01

Within the quantum-field renormalization-group approach we examine the stochastic equation discussed by S.I. Pavlik in describing a randomly growing phase boundary. We show that, in contrast to Pavlik`s assertion, the model is not multiplicatively renormalizable and that its consistent renormalization-group analysis requires introducing an infinite number of counterterms and the respective coupling constants ({open_quotes}charge{close_quotes}). An explicit calculation in the one-loop approximation shows that a two-dimensional surface of renormalization-group points exits in the infinite-dimensional charge space. If the surface contains an infrared stability region, the problem allows for scaling with the nonuniversal critical dimensionalities of the height of the phase boundarymore » and time, {delta}{sub h} and {delta}{sub t}, which satisfy the exact relationship 2 {delta}{sub h}= {delta}{sub t} + d, where d is the dimensionality of the phase boundary. 23 refs., 1 tab.« less

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.

The effect of moxibustion on alleviating menstrual pain in a population of young nursing students: A prospective randomized cross-over pilot study.

PubMed

Gao, Jing; Wang, Qi; Xian, Shaoxiang; Feng, Yue-mei; Cao, Wei-xin; Ye, Jing-yun; Zhang, Qing-qing; Zou, Cai-lian; Wu, Qing-guang; Liu, Si-jun

2015-12-01

To investigate the effect of moxibustion on alleviating menstrual pain and relieving the symptoms of dysmenorrhea in a cohort of young nursing students in China. A randomized double blind clinical trial of crossover design was used. In the two-phase study, a total of 56 nursing students with menstrual pain in Guangzhou University of Chinese Medicine in China was randomly allocated into two groups. In the first treatment phase, the participants in Group A (n=28) received moxibustion therapy from five days before the menstrual period to the onset through a specific heating box in which burning moxa stick was fixed, the participants in Group B (n=28) received the same heating box but with a paper-wrapped stick incense fixed inside (placebo therapy) during the same intervention period. The acupoints Guanyuan(CV4) and Shenque(CV8) were selected for treatment. After the first treatment phase for two menstrual cycles, the intervention was stopped for three menstrual cycles during a wash period. In the second treatment phase, the intervention of two groups were switched. Group A received the placebo therapy and Group B received moxibustion therapy. NRS, VRS, PRI, VAS and BRS-6 were evaluated at the baseline and after each treatment phase. There was no statistically significant difference in age, history of dysmenorrhea, length of menstrual cycle, age at menarche, duration of menstrual flow, PRI score, VAS score, BRS score and RSS score between Group A and Group B (p>0.05). After the first treatment phase, the score of BRS-6 has significant differences between two groups at the first menstrual cycle (p<0.05). At the second menstrual cycle, the score of VAS, BRS-6,sensory of PRI, affective dimension of PR and total score of PRI in Group A were much lower than Group B (p<0.05). NRS and VRS had significant differences between two groups with Wilcoxon Mann-Whitney test after the first treatment phase (p<0.05). The frequency rating of weakness, loss of appetite, diarrhea, and the total score had significant differences between two groups at the first menstrual cycle (p<0.05). And the frequency rating of weakness, backache, facial blemishes, loss of appetite, diarrhea, and the total score had significant differences between two groups at the second menstrual cycle (p<0.05). The severity rating of backaches, loss of appetite, sleeplessness, and the total score had significant differences between two groups after the second menstrual cycle (p<0.05). After three months' wash period, the score of VAS, BRS-6, sensory of PRI, affective of PR, total score of PRI and VRS had significant differences between two groups after the second treatment phase (p<0.01). And the frequency rating of leg aches, dizziness, nervousness and the total score had significant differences between two groups after the second treatment phase (p<0.05). And the severity rating of abdominal pain, weakness, leg aches, dizziness, nervousness and the total score had significant differences between two groups after the second treatment phase (p<0.05). The results suggested that moxibustion therapy with a heating box was effective for alleviating menstrual pain and symptoms of young female university students in China. The effect of moxibustion might not only due to heat stimulation, but also from the burning of moxa stick. Boxing moxibustion could be recommended as a nonpharmacological pain relief intervention for university students for its cost effectiveness, practical design and relative safety, and it is easy for the university students themselves to self-administer at home. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Deposit Contract Method to Deliver Abstinence Reinforcement for Cigarette Smoking

ERIC Educational Resources Information Center

Dallery, Jesse; Meredith, Steven; Glenn, Irene M.

2008-01-01

Eight smokers were randomly assigned to a deposit contract ($50.00) or to a no-deposit group. Using a reversal design, participants could recoup their deposit (deposit group) or earn vouchers (no-deposit group) for smoking reductions and abstinence (breath carbon monoxide [CO] less than or equal to 4 parts per million) during treatment phases.…

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

Long-term safety and efficacy of tofogliflozin as add-on to insulin in patients with type 2 diabetes: Results from a 52-week, multicentre, randomized, double-blind, open-label extension, Phase 4 study in Japan (J-STEP/INS).

PubMed

Terauchi, Yasuo; Tamura, Masahiro; Senda, Masayuki; Gunji, Ryoji; Kaku, Kohei

2018-05-01

To evaluate the long-term safety and efficacy of tofogliflozin as an add-on treatment to insulin over 52 weeks. This 52-week, multicentre, Phase 4 study consisted of a 16-week, randomized, double-blind, placebo-controlled phase and a 36-week open label extension phase (NCT02201004). Japanese patients with type 2 diabetes mellitus, aged 20 to 75 years, with suboptimal glycaemic control (7.5%-10.5%) receiving insulin monotherapy (basal-bolus, bolus, premix [low and high] and basal) or receiving combination therapy with basal insulin and dipeptidyl peptidase-4 inhibitor were eligible for participation. Patients who received tofogliflozin throughout the study (52 weeks) were referred to as the 'tofo-tofo group' and patients who received placebo and tofogliflozin (36 weeks) were referred to as the 'pla-tofo group'. A total of 210 patients received treatment per randomization. Hypoglycaemia was the most common treatment-emergent adverse event (AE) (42.9% in the tofo-tofo group and 29.4% in the pla-tofo group). Patients reported genital infection, urinary tract infection, excessive urination and AEs related to volume depletion (2.1%, 2.1%, 7.1% and 10.0% of patients in the tofo-tofo group, and 0%, 1.5%, 2.9% and 7.4% of patients in the pla-tofo group, respectively). Mean HbA1c and body weight at baseline (mean changes ± standard error from baseline to Week 52) in the tofo-tofo and pla-tofo groups were 8.53% (-0.76% ± 0.077) and 8.40% (-0.73% ± 0.102); 68.84 kg (-1.52 kg ± 0.207) and 72.24 kg (-2.13 kg ± 0.313), respectively. This study demonstrates the safety and efficacy of tofogliflozin as add-on to insulin therapy in type 2 diabetes mellitus patients, offering a new therapeutic solution to diabetes management. © 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Efficacy and safety of pimecrolimus cream 1% in mild-to-moderate chronic hand dermatitis: a randomized, double-blind trial.

PubMed

Hordinsky, Maria; Fleischer, Alan; Rivers, Jason K; Poulin, Yves; Belsito, Donald; Hultsch, Thomas

2010-08-01

Chronic hand dermatitis is common and difficult to treat. Our aim was to assess the efficacy of pimecrolimus cream 1% in mild-to-moderate chronic hand dermatitis. Adult patients (n = 652) were randomized to pimecrolimus 1% or vehicle cream twice daily with overnight occlusion for 6 weeks, followed by a 6-week open-label pimecrolimus treatment. Primary efficacy was 5-point Investigators' Global Assessment of prospectively selected 'target hand' as treatment success (Investigators' Global Assessment 0 or 1) and treatment failure. Pruritus relief was also assessed. Following double-blind phase treatment, target hand treatment success was achieved in 29.8 and 23.2% of the patients in the pimecrolimus and vehicle groups, respectively (p = 0.057). The proportion of patients experiencing pruritus relief was significantly higher in the pimecrolimus group compared to the vehicle group at all time points throughout the double-blind phase. The groups were comparable with respect to treating disease signs. Pruritus relief, however, was significantly greater in the pimecrolimus group. Copyright 2010 S. Karger AG, Basel.

Quiet eye training improves surgical knot tying more than traditional technical training: a randomized controlled study.

PubMed

Causer, Joe; Harvey, Adrian; Snelgrove, Ryan; Arsenault, Gina; Vickers, Joan N

2014-08-01

We examined the effectiveness of technical training (TT) and quiet eye training (QE) on the performance of one-handed square knot tying in surgical residents. Twenty surgical residents were randomly assigned to the 2 groups and completed pretest, training, retention, and transfer tests. Participants wore a mobile eye tracker that simultaneously recorded their gaze and hand movements. Dependent variables were knot tying performance (%), QE duration (%), number of fixations, total movement time (s), and hand movement phase time (s). The QE training group had significantly higher performance scores, a longer QE duration, fewer fixations, faster total knot tying times, and faster movement phase times compared with the TT group. The QE group maintained performance in the transfer test, whereas the TT group significantly decreased performance from retention to transfer. QE training significantly improved learning, retention, and transfer of surgical knot tying compared with a traditional technical approach. Both performance effectiveness (performance outcome) and movement efficiency (hand movement times) were improved using QE modeling, instruction, and feedback. Copyright © 2014 Elsevier Inc. All rights reserved.

Entanglement entropy at infinite-randomness fixed points in higher dimensions.

PubMed

Lin, Yu-Cheng; Iglói, Ferenc; Rieger, Heiko

2007-10-05

The entanglement entropy of the two-dimensional random transverse Ising model is studied with a numerical implementation of the strong-disorder renormalization group. The asymptotic behavior of the entropy per surface area diverges at, and only at, the quantum phase transition that is governed by an infinite-randomness fixed point. Here we identify a double-logarithmic multiplicative correction to the area law for the entanglement entropy. This contrasts with the pure area law valid at the infinite-randomness fixed point in the diluted transverse Ising model in higher dimensions.

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.

Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial

PubMed Central

Kosaka, H; Okamoto, Y; Munesue, T; Yamasue, H; Inohara, K; Fujioka, T; Anme, T; Orisaka, M; Ishitobi, M; Jung, M; Fujisawa, T X; Tanaka, S; Arai, S; Asano, M; Saito, D N; Sadato, N; Tomoda, A; Omori, M; Sato, M; Okazawa, H; Higashida, H; Wada, Y

2016-01-01

Recent studies have suggested that long-term oxytocin administration can alleviate the symptoms of autism spectrum disorder (ASD); however, factors influencing its efficacy are still unclear. We conducted a single-center phase 2, pilot, randomized, double-blind, placebo-controlled, parallel-group, clinical trial in young adults with high-functioning ASD, to determine whether oxytocin dosage and genetic background of the oxytocin receptor affects oxytocin efficacy. This trial consisted of double-blind (12 weeks), open-label (12 weeks) and follow-up phases (8 weeks). To examine dose dependency, 60 participants were randomly assigned to high-dose (32 IU per day) or low-dose intranasal oxytocin (16 IU per day), or placebo groups during the double-blind phase. Next, we measured single-nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR). In the intention-to-treat population, no outcomes were improved after oxytocin administration. However, in male participants, Clinical Global Impression-Improvement (CGI-I) scores in the high-dose group, but not the low-dose group, were significantly higher than in the placebo group. Furthermore, we examined whether oxytocin efficacy, reflected in the CGI-I scores, is influenced by estimated daily dosage and OXTR polymorphisms in male participants. We found that >21 IU per day oxytocin was more effective than ⩽21 IU per day, and that a SNP in OXTR (rs6791619) predicted CGI-I scores for ⩽21 IU per day oxytocin treatment. No severe adverse events occurred. These results suggest that efficacy of long-term oxytocin administration in young men with high-functioning ASD depends on the oxytocin dosage and genetic background of the oxytocin receptor, which contributes to the effectiveness of oxytocin treatment of ASD. PMID:27552585

Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial.

PubMed

Kosaka, H; Okamoto, Y; Munesue, T; Yamasue, H; Inohara, K; Fujioka, T; Anme, T; Orisaka, M; Ishitobi, M; Jung, M; Fujisawa, T X; Tanaka, S; Arai, S; Asano, M; Saito, D N; Sadato, N; Tomoda, A; Omori, M; Sato, M; Okazawa, H; Higashida, H; Wada, Y

2016-08-23

Recent studies have suggested that long-term oxytocin administration can alleviate the symptoms of autism spectrum disorder (ASD); however, factors influencing its efficacy are still unclear. We conducted a single-center phase 2, pilot, randomized, double-blind, placebo-controlled, parallel-group, clinical trial in young adults with high-functioning ASD, to determine whether oxytocin dosage and genetic background of the oxytocin receptor affects oxytocin efficacy. This trial consisted of double-blind (12 weeks), open-label (12 weeks) and follow-up phases (8 weeks). To examine dose dependency, 60 participants were randomly assigned to high-dose (32 IU per day) or low-dose intranasal oxytocin (16 IU per day), or placebo groups during the double-blind phase. Next, we measured single-nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR). In the intention-to-treat population, no outcomes were improved after oxytocin administration. However, in male participants, Clinical Global Impression-Improvement (CGI-I) scores in the high-dose group, but not the low-dose group, were significantly higher than in the placebo group. Furthermore, we examined whether oxytocin efficacy, reflected in the CGI-I scores, is influenced by estimated daily dosage and OXTR polymorphisms in male participants. We found that >21 IU per day oxytocin was more effective than ⩽21 IU per day, and that a SNP in OXTR (rs6791619) predicted CGI-I scores for ⩽21 IU per day oxytocin treatment. No severe adverse events occurred. These results suggest that efficacy of long-term oxytocin administration in young men with high-functioning ASD depends on the oxytocin dosage and genetic background of the oxytocin receptor, which contributes to the effectiveness of oxytocin treatment of ASD.

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.

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

PubMed

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

2016-05-03

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

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.

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.

A Prospective Randomized Trial of Postural Changes vs Passive Supine Lying during the Second Stage of Labor under Epidural Analgesia

PubMed Central

Simarro, María; Espinosa, José Angel; Salinas, Cecilia; Ojea, Ricardo; Salvadores, Paloma; Walker, Carolina; Schneider, José

2017-01-01

There exist very few studies comparing different postures or postural changes during labor in parturients with epidural analgesia. Aim: To disclose whether the intervention of a multidisciplinary nursing team including a physiotherapist during the second stage of labor improves the obstetric outcome in parturients with epidural analgesia. Design: Prospective randomized trial. Setting: University-affiliated hospital. Population: Women undergoing labor with epidural analgesia after a normal gestation. Methods: 150 women were randomized either to actively perform predefined postural changes during the passive phase of the second stage of labor under the guidance of the attending physiotherapist (study group), or to carry out the whole second stage of labor lying in the traditional supine position (control group). Results: There were significantly more eutocic deliveries (p = 0.005) and, conversely, significantly less instrumental deliveries (p < 0.05) and cesarean sections (p < 0.05) in the study group. The total duration of the second stage of labor was significantly shorter (p < 0.01) in the study group. This was at the expense of the passive phase of the second stage of labor (p < 0.01). Significantly less episiotomies were performed in the study group (31.2% vs 17.8%, p < 0.05). Conclusion: The intervention of a physiotherapist during the second stage of labor significantly improved the obstetric outcome. PMID:29099021

Changes in the Precision of a Study from Planning Phase to Implementation Phase: Evidence from the First Wave of Group Randomized Trials Launched by the Institute of Education Sciences

ERIC Educational Resources Information Center

Spybrook, Jessaca; Lininger, Monica; Cullen, Anne

2011-01-01

The purpose of this study is to extend the work of Spybrook and Raudenbush (2009) and examine how the research designs and sample sizes changed from the planning phase to the implementation phase in the first wave of studies funded by IES. The authors examine the impact of the changes in terms of the changes in the precision of the study from the…

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).

Gait analysis following treadmill training with body weight support versus conventional physical therapy: a prospective randomized controlled single blind study.

PubMed

Lucareli, P R; Lima, M O; Lima, F P S; de Almeida, J G; Brech, G C; D'Andréa Greve, J M

2011-09-01

Single-blind randomized, controlled clinical study. To evaluate, using kinematic gait analysis, the results obtained from gait training on a treadmill with body weight support versus those obtained with conventional gait training and physiotherapy. Thirty patients with sequelae from traumatic incomplete spinal cord injuries at least 12 months earlier; patients were able to walk and were classified according to motor function as ASIA (American Spinal Injury Association) impairment scale C or D. Patients were divided randomly into two groups of 15 patients by the drawing of opaque envelopes: group A (weight support) and group B (conventional). After an initial assessment, both groups underwent 30 sessions of gait training. Sessions occurred twice a week, lasted for 30 min each and continued for four months. All of the patients were evaluated by a single blinded examiner using movement analysis to measure angular and linear kinematic gait parameters. Six patients (three from group A and three from group B) were excluded because they attended fewer than 85% of the training sessions. There were no statistically significant differences in intra-group comparisons among the spatial-temporal variables in group B. In group A, the following significant differences in the studied spatial-temporal variables were observed: increases in velocity, distance, cadence, step length, swing phase and gait cycle duration, in addition to a reduction in stance phase. There were also no significant differences in intra-group comparisons among the angular variables in group B. However, group A achieved significant improvements in maximum hip extension and plantar flexion during stance. Gait training with body weight support was more effective than conventional physiotherapy for improving the spatial-temporal and kinematic gait parameters among patients with incomplete spinal cord injuries.

Pulsatile luteinizing hormone patterns in the follicular phase of the menstrual cycle, polycystic ovarian disease (PCOD) and non-PCOD secondary amenorrhea.

PubMed

Burger, C W; Korsen, T; van Kessel, H; van Dop, P A; Caron, F J; Schoemaker, J

1985-12-01

To characterize the oscillations of plasma LH in normally cycling and amenorrheic women, three groups of women were studied: I, normal women during the follicular phase of the cycle (n = 9); II, women with polycystic ovarian disease (PCOD; n = 11); and III, women with non-PCOD secondary amenorrhea (n = 12). Blood samples were obtained at 10-min intervals for 6 h on 2 separate days. A pulse was defined as an increase in LH at least 20% over the preceding lowest value (nadir). Since LHRH release immediately follows the nadir of the LH levels, the nadir interval (NI) was used for analysis. For analysis, the results from 1 day were selected at random from each subject, and from each day, the same number of NIs also were randomly selected. When two NIs from each patient were selected, the median NI was 75 min in group I, 45 min in group II, and 45 min in group III. When three or four NIs were chosen, the median NI was 60 min in group I, 50 min in group II, and 40 min in group III. The differences between the groups were statistically significant. When three NIs were selected, the mean of the corresponding LH amplitudes was 2.8 U/liter in group I, 6.0 U/liter in group II, and 1.5 U/liter in group III. The differences between these groups were statistically significant. Thus, the NI in PCOD patients was shorter than that during the follicular phase of the cycle, but this short NI is not unique for PCOD, since the NI in non-PCOD secondary amenorrhea patients was even smaller. The LH amplitude was higher in PCOD and lower in non-PCOD secondary amenorrhea compared to that during the follicular phase of the cycle. The decrease in NI in PCOD and/or non-PCOD secondary amenorrhea vs. the NI of the follicular phase could be explained by either a higher frequency of LHRH pulses from the hypothalamus or an increased sensitivity of the pituitary leading to a greater response of the pituitary to LHRH pulses.

Comparison of oral dydrogesterone with vaginal progesteronefor luteal support in IUI cycles: a randomized clinical trial

PubMed Central

Khosravi, Donya; Taheripanah, Robabeh; Taheripanah, Anahita; Tarighat Monfared, Vahid; Hosseini-Zijoud, Seyed-Mostafa

2015-01-01

Background: The aim of this study, we have compared the advantages of oral dydrogestrone with vaginal progesterone (cyclogest) for luteal support in intrauterine insemination (IUI) cycles. Progesterone supplementation is the first line treatment when luteal phase deficiency (LPD) can reasonably be assumed. Objective: This study was conduct to compare the effect of oral dydrogestrone with vaginal Cyclogest on luteal phase support in the IUI cycles. Materials and Methods: This prospective, randomized, double blind study was performed in a local infertility center from May 2013 to May 2014. It consisted of 150 infertile women younger than35years old undergoing ovarian stimulation for IUI cycles. They underwent ovarian stimulation with oral dydrogesterone (20 mg) as group A and vaginal cyclogest (400 mg) as group B in preparation for the IUI cycles. Clinical pregnancy and abortion rates, mid luteal progesterone (7daysafter IUI) and patient satisfaction were compared between two groups. Results: The mean serum progesterone levels was significantly higher in group A in comparison with group B (p=0.001). Pregnancy rates in group A was not statistically different in comparison with group B (p =0.58). Abortion rate in two groups was not statistically different (p =0.056) although rate of abortion was higher in group B in comparison with A group. Satisfaction rates were significantly higher in group A compared to group B (p<0.001). Conclusion: We concluded that oral dydrogestrone is effective as vaginal progesterone for luteal-phase support in woman undergoing IUI cycles. Moreover, the mean serum progesterone levels and satisfaction rates in dydrogestrone group were higher than cyclogest group. PMID:26494991

Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial.

PubMed

Oddis, Chester V; Reed, Ann M; Aggarwal, Rohit; Rider, Lisa G; Ascherman, Dana P; Levesque, Marc C; Barohn, Richard J; Feldman, Brian M; Harris-Love, Michael O; Koontz, Diane C; Fertig, Noreen; Kelley, Stephanie S; Pryber, Sherrie L; Miller, Frederick W; Rockette, Howard E

2013-02-01

To assess the safety and efficacy of rituximab in a randomized, double-blind, placebo-phase trial in adult and pediatric myositis patients. Adults with refractory polymyositis (PM) and adults and children with refractory dermatomyositis (DM) were enrolled. Entry criteria included muscle weakness and ≥2 additional abnormal values on core set measures (CSMs) for adults. Juvenile DM patients required ≥3 abnormal CSMs, with or without muscle weakness. Patients were randomized to receive either rituximab early or rituximab late, and glucocorticoid or immunosuppressive therapy was allowed at study entry. The primary end point compared the time to achieve the International Myositis Assessment and Clinical Studies Group preliminary definition of improvement (DOI) between the 2 groups. The secondary end points were the time to achieve ≥20% improvement in muscle strength and the proportions of patients in the early and late rituximab groups achieving the DOI at week 8. Among 200 randomized patients (76 with PM, 76 with DM, and 48 with juvenile DM), 195 showed no difference in the time to achieving the DOI between the rituximab late (n = 102) and rituximab early (n = 93) groups (P = 0.74 by log rank test), with a median time to achieving a DOI of 20.2 weeks and 20.0 weeks, respectively. The secondary end points also did not significantly differ between the 2 treatment groups. However, 161 (83%) of the randomized patients met the DOI, and individual CSMs improved in both groups throughout the 44-week trial. Although there were no significant differences in the 2 treatment arms for the primary and secondary end points, 83% of adult and juvenile myositis patients with refractory disease met the DOI. The role of B cell-depleting therapies in myositis warrants further study, with consideration for a different trial design. Copyright © 2013 by the American College of Rheumatology.

Long-term maintenance therapy for vulvar lichen sclerosus: the results of a randomized study comparing topical vitamin E with an emollient.

PubMed

Virgili, Annarosa; Minghetti, Sara; Borghi, Alessandro; Corazza, Monica

2013-04-01

The chronic and relapsing nature of vulvar lichen sclerosus (VLS) represents a challenge for its long-term management after an effective treatment with topical corticosteroids. To compare the effect of topical vitamin E with that of an emollient in reducing the risk of VLS relapse over a 52-week maintenance treatment. 156 patients with VLS were enrolled in a 12-week active treatment phase on topical 0.1% mometasone furoate ointment once daily. Those who achieved disease remission entered a 52-week maintenance phase in which patients were randomized to apply either an emollient or topical vitamin E once daily. 80 patients entered the maintenance phase. At 52 weeks, for the vitamin E maintenance group, the cumulative crude relapse rate was 27.8% and the cumulative modified crude relapse rate was 55.6%. For the emollient maintenance group, the cumulative crude relapse rate was 22.7% and the cumulative modified crude relapse rate was 50.0%. The median time to relapse was 20 weeks for the vitamin E group and 18.7 weeks for the emollient group. Once VLS has been stabilized with topical corticosteroids, long-term treatment with both vitamin E and emollients may be considered in maintain LS remission.

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.

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.

Phase 2 Placebo-Controlled Trial of Two Vaccines to Prevent Ebola in Liberia

PubMed Central

Kennedy, S.B.; Bolay, F.; Kieh, M.; Grandits, G.; Badio, M.; Ballou, R.; Eckes, R.; Feinberg, M.; Follmann, D.; Grund, B.; Gupta, S.; Hensley, L.; Higgs, E.; Janosko, K.; Johnson, M.; Kateh, F.; Logue, J.; Marchand, J.; Monath, T.; Nason, M.; Nyenswah, T.; Roman, F.; Stavale, E.; Wolfson, J.; Neaton, J.D.; Lane, H.C.

2017-01-01

BACKGROUND The safety and efficacy of vaccines to prevent Ebola virus disease (EVD) were unknown when the incidence of EVD was peaking in Liberia. METHODS 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 (rVSVΔG-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. RESULTS 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 rVSVΔG-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 rVSVΔG-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 rVSVΔG-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 rVSVΔG-ZEBOV-GP group (79.5%) remained significantly greater than in those in the placebo group (6.8%, P<0.001 for both comparisons). CONCLUSIONS 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.) PMID:29020589

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.

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

Comparative Effectiveness of Three Occupational Therapy Sleep Interventions: A Randomized Controlled Study.

PubMed

Gutman, Sharon A; Gregory, Kristin A; Sadlier-Brown, Megan M; Schlissel, Marcy A; Schubert, Allison M; Westover, Lee Ann; Miller, Richard C

2017-01-01

Although sleep intervention is within the domain of occupational therapy, few studies exist supporting practice. Effectiveness of three sleep interventions was compared: Dreampad Pillow®, iRest® meditation, and sleep hygiene. Twenty-nine participants were randomly assigned to the Dreampad Pillow® ( n = 10), iRest® meditation ( n = 9), and sleep hygiene ( n = 10) groups. In Phase 1, all participants used a 7-day sleep hygiene regimen to reduce poor sleep habits. In Phase 2 (14 days), 10 participants used the Dreampad Pillow® and sleep hygiene, nine used the iRest meditation and sleep hygiene, and 10 continued sleep hygiene only. At intervention-end, the iRest meditation group experienced statistically greater time asleep than both the Dreampad Pillow® ( p < .006, d = 1.87) and sleep hygiene groups ( p < .03, d = 1.80). The Dreampad Pillow® group experienced statistically fewer nighttime awakenings than the iRest® meditation ( p < .04, d = -1.53) and sleep hygiene ( p < .004, d = -1.43) groups. No differences were found between groups in perceived sleep quality, length of time needed to fall asleep, and fatigue level next day. This study provides support for sleep interventions within occupational therapy's domain.

Rapid visual grouping and figure-ground processing using temporally structured displays.

PubMed

Cheadle, Samuel; Usher, Marius; Müller, Hermann J

2010-08-23

We examine the time course of visual grouping and figure-ground processing. Figure (contour) and ground (random-texture) elements were flickered with different phases (i.e., contour and background are alternated), requiring the observer to group information within a pre-specified time window. It was found this grouping has a high temporal resolution: less than 20ms for smooth contours, and less than 50ms for line conjunctions with sharp angles. Furthermore, the grouping process takes place without an explicit knowledge of the phase of the elements, and it requires a cumulative build-up of information. The results are discussed in relation to the neural mechanism for visual grouping and figure-ground segregation. Copyright 2010 Elsevier Ltd. All rights reserved.

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

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.

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

Treatment with α-Lipoic Acid over 16 Weeks in Type 2 Diabetic Patients with Symptomatic Polyneuropathy Who Responded to Initial 4-Week High-Dose Loading

PubMed Central

Garcia-Alcala, Hector; Santos Vichido, Celia Isabel; Islas Macedo, Silverio; Genestier-Tamborero, Christelle Nathalie; Minutti-Palacios, Marissa; Hirales Tamez, Omara; García, Carlos; Ziegler, Dan

2015-01-01

Effective treatment of diabetic sensorimotor polyneuropathy remains a challenge. To assess the efficacy and safety of α-lipoic acid (ALA) over 20 weeks, we conducted a multicenter randomized withdrawal open-label study, in which 45 patients with type 2 diabetes and symptomatic polyneuropathy were initially treated with ALA (600 mg tid) for 4 weeks (phase 1). Subsequently, responders were randomized to receive ALA (600 mg qd; n = 16) or to ALA withdrawal (n = 17) for 16 weeks (phase 2). During phase 1, the Total Symptom Score (TSS) decreased from 8.9 ± 1.8 points to 3.46 ± 2.0 points. During phase 2, TSS improved from 3.7 ± 1.9 points to 2.5 ± 2.5 points in the ALA treated group (p < 0.05) and remained unchanged in the ALA withdrawal group. The use of analgesic rescue medication was higher in the ALA withdrawal group than ALA treated group (p < 0.05). In conclusion, in type 2 diabetic patients with symptomatic polyneuropathy who responded to initial 4-week high-dose (600 mg tid) administration of ALA, subsequent treatment with ALA (600 mg qd) over 16 weeks improved neuropathic symptoms, whereas ALA withdrawal was associated with a higher use of rescue analgesic drugs. This trial is registered with ClinicalTrials.gov Identifier: NCT02439879. PMID:26345602

Cognitive-Behavioral Therapy to Prevent Relapse in Pediatric Responders to Pharmacotherapy for Major Depressive Disorder

PubMed Central

Kennard, Betsy D.; Emslie, Graham J.; Mayes, Taryn L.; Nightingale-Teresi, Jeanne; Nakonezny, Paul A.; Hughes, Jennifer L.; Jones, Jessica M.; Tao, Rongrong; Stewart, Sunita M.; Jarrett, Robin B.

2010-01-01

Objective We present results of a feasibility test of a sequential treatment strategy using continuation phase cognitive-behavioral therapy (CBT) to prevent relapse in youths with major depressive disorder (MDD) who have responded to acute phase pharmacotherapy. Method Forty-six youths (ages 11–18 years) who had responded to 12 weeks of treatment with fluoxetine were randomized to receive either 6 months of continued antidepressant medication management (MM) or antidepressant MM plus relapse prevention CBT (MM+CBT). Primary outcome was time to relapse, defined as a Childhood Depression Rating Scale-Revised score of 40 or higher and 2 weeks of symptom worsening or clinical deterioration warranting alteration of treatment to prevent full relapse. Results Cox proportional hazards regression, adjusting for depression severity at randomization and for the hazard of relapsing by age across the trial, revealed that participants in the MM treatment group had a significantly greater risk for relapse than those in the MM+CBT treatment group (hazard ratio = 8.80; 95% confidence interval 1.01–76.89; χ2 = 3.86, p = .049) during 6 months of continuation treatment. In addition, patient satisfaction was significantly higher in the MM+CBT group. No differences were found between the two treatment groups on attrition rate, serious adverse events, and overall global functioning. Conclusions These preliminary results suggest that continuation phase CBT reduces the risk for relapse by eightfold compared with pharmacotherapy responders who received antidepressant medication alone during the 6-month continuation phase. PMID:18978634

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.

Randomized, open-labeled, non-inferiority study between ciclopiroxolamine 1% cream and ketoconazole 2% foaming gel in mild to moderate facial seborrheic dermatitis.

PubMed

Chosidow, O; Maurette, C; Dupuy, P

2003-01-01

Topical ketoconazole (KC) is considered a standard treatment for seborrheic dermatitis. In a placebo-controlled, double-blind clinical study, we demonstrated that antifungal ciclopiroxolamine (CIC) 1% cream was effective in mild to moderate facial seborrheic dermatitis. We report here the results of a randomized, open-labeled clinical study comparing CIC 1% cream and KC 2% foaming gel in patients with mild to moderate facial seborrheic dermatitis, using a non-inferiority trial design. Three hundred and three patients were enrolled, 154 patients in the CIC group and 149 patients in the KC group, and comprised the study population for intent-to-treat (ITT) analysis. The per protocol (PP) population comprised a total of 282 patients, 147 in the CIC group and 135 in the KC group. Patients were randomly allocated to apply either the CIC 1% cream twice a day for 28 days maximum (initial phase), followed by once a day for another 28 days (maintenance phase); or the KC 2% foaming gel twice a week at the initial phase, followed by once a week during the maintenance phase. Test lesions were defined as lesions localized to the nasolabial folds, alae nasi, and/or the eyebrows. The main efficacy parameter (endpoint) was the proportion of patients who presented a complete disappearance of both erythema and scaling on test lesions and pruritus on all lesions at the end of the initial phase (28 days or less). At baseline, both treatment groups were comparable in terms of demographic data and lesional status. At the end of the initial phase, responders were found to be non-inferior with CIC treatment compared with KC treatment in both study populations (ITT population: 37% CIC responders and 34% KC responders; in the PP population: 39 and 36% responders, respectively). The 95% confidence interval limit for differences were -7.99-13.56 in the ITT population, and -8.06-14.5 in the PP population. At the end of the maintenance phase, treatment response to CIC was greater than to KC in both ITT and PP populations (57 and 44% in both populations, respectively, p = 0.03). Local tolerance as well as global acceptability was better with CIC than with KC (p = 0.001, intergroup analysis). CIC 1% administered as a cream demonstrated to be non-inferior to KC 2% foaming gel in mild to moderate facial seborrheic dermatitis. Copyright 2003 S. Karger AG, Basel

Effect of head group orientation on phospholipid assembly

NASA Astrophysics Data System (ADS)

Paul, Tanay; Saha, Jayashree

2017-06-01

The relationship between bilayer stability and lipid head group orientation is reported. In this work, molecular-dynamics simulations are performed to analyze the structure-property relationship of lipid biomembranes, taking into account coarse-grained model lipid interactions. The work explains the molecular scale mechanism of the phase behavior of lipid systems due to ion-lipid or anesthetic-lipid interactions, where reorientations of dipoles play a key role in modifying lipid phases and thereby alter biomembrane function. Our study demonstrates that simple dipolar reorientation is indeed sufficient in tuning a bilayer to a randomly flipped nonbilayer lamellar phase. This study may be used to assess the impact of changes in lipid phase characteristics on biomembrane structure due to the presence of anesthetics and ions.

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.

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.

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.

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.

Potential additional effect of omentectomy on metabolic syndrome, acute-phase reactants, and inflammatory mediators in grade III obese patients undergoing laparoscopic Roux-en-Y gastric bypass: a randomized trial.

PubMed

Herrera, Miguel F; Pantoja, Juan Pablo; Velázquez-Fernández, David; Cabiedes, Javier; Aguilar-Salinas, Carlos; García-García, Eduardo; Rivas, Alfredo; Villeda, Christian; Hernández-Ramírez, Diego F; Dávila, Andrea; Zaraín, Aarón

2010-07-01

To assess the additional effect of sudden visceral fat reduction by omentectomy on metabolic syndrome, acute-phase reactants, and inflammatory mediators in patients with grade III obesity (G-III O) undergoing laparoscopic Roux-en-Y gastric bypass (LRYGB). Twenty-two patients were randomized into two groups, LRYGB alone or with omentectomy. Levels of interleukin-6, C-reactive protein, tumor necrosis factor-alpha, leptin, adiponectin, glucose, total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides, as well as clinical characteristics, were evaluated before surgery and at 1, 3, 6, and 12 months after surgery. Results were compared between groups. Baseline characteristics were comparable in both groups. Mean operative time was significantly higher in the group of patients who underwent omentectomy (P < 0.001). Median weight of the omentum was 795 +/- 341 g. In one patient, a duodenal perforation occurred at the time of omentectomy. BMI, blood pressure, glucose, total cholesterol, LDL, and triglycerides significantly improved in both groups at 1, 3, 6, and 12 months of follow-up when compared with basal values. However, there were no consistent statistically significant differences among the groups in terms of metabolic syndrome components, acute-phase reactants, and inflammatory mediators. Omentectomy does not have an ancillary short-term significant impact on the components of metabolic syndrome and does not induce important changes in the inflammatory mediators in patients undergoing LRYGB. Operative time is more prolonged when omentectomy is performed.

Stimulant abuser groups to engage in 12-step: a multisite trial in the National Institute on Drug Abuse Clinical Trials Network.

PubMed

Donovan, Dennis M; Daley, Dennis C; Brigham, Gregory S; Hodgkins, Candace C; Perl, Harold I; Garrett, Sharon B; Doyle, Suzanne R; Floyd, Anthony S; Knox, Patricia C; Botero, Christopher; Kelly, Thomas M; Killeen, Therese K; Hayes, Carole; Kau'i Baumhofer, Nicole; Kau'ibaumhofer, Nicole; Seamans, Cindy; Zammarelli, Lucy

2013-01-01

The study evaluated the effectiveness of an 8-week combined group plus individual 12-step facilitative intervention on stimulant drug use and 12-step meeting attendance and service. Multisite randomized controlled trial, with assessments at baseline, mid-treatment, end of treatment, and 3- and 6-month post-randomization follow-ups (FUs). Intensive outpatient substance treatment programs. Individuals with stimulant use disorders (n = 471) randomly assigned to treatment as usual (TAU) or TAU into which the Stimulant Abuser Groups to Engage in 12-Step (STAGE-12) intervention was integrated. Urinalysis and self-reports of substance use and 12-step attendance and activities. Group sessions focused on increasing acceptance of 12-step principles; individual sessions incorporated an intensive referral procedure connecting participants to 12-step volunteers. Compared with TAU, STAGE-12 participants had significantly greater odds of self-reported stimulant abstinence during the active 8-week treatment phase; however, among those who had not achieved abstinence during this period, STAGE-12 participants had more days of use. STAGE-12 participants had lower Addiction Severity Index Drug Composite scores at and a significant reduction from baseline to the 3-month FU, attended 12-step meetings on a greater number of days during the early phase of active treatment, engaged in more other types of 12-step activities throughout the active treatment phase and the entire FU period, and had more days of self-reported service at meetings from mid-treatment through the 6-month FU. The present findings are mixed with respect to the impact of integrating the STAGE-12 intervention into intensive outpatient drug treatment compared with TAU on stimulant drug use. However, the results more clearly indicate that individuals in STAGE-12 had higher rates of 12-step meeting attendance and were engaged in more related activities throughout both the active treatment phase and the entire 6-month FU period than did those in TAU. Copyright © 2013 Elsevier Inc. All rights reserved.

The Transitory Phase to the Attainment of Self-Regulatory Skill in Mathematical Problem Solving

ERIC Educational Resources Information Center

Lazakidou, G.; Paraskeva, F.; Retalis, S.

2007-01-01

Three phases of development of self-regulatory skill in the domain of mathematical problem solving were designed to examine students' behaviour and the effects on their problem solving ability. Forty-eight Grade 4 students (10 year olds) participated in this pilot study. The students were randomly assigned to one of three groups, each representing…

Radio Frequency Signal Reception Via Distributed Wirelessly Networked Sensors Under Random Motion

DTIC Science & Technology

2009-09-01

100. Agent position in Pythagoras modeling in first phase level showing individual unit member interaction where each dot is an individual agent...181 Figure 101. Detail position in Pythagoras modeling in second phase showing detail group interaction where each blue dot is a unit...Table 5. Estimated reset time values and associated change percentage from Pythagoras agent motion

Early High-dosage Atorvastatin Treatment Improved Serum Immune-inflammatory Markers and Functional Outcome in Acute Ischemic Strokes Classified as Large Artery Atherosclerotic Stroke: A Randomized Trial.

PubMed

Tuttolomondo, Antonino; Di Raimondo, Domenico; Pecoraro, Rosaria; Maida, Carlo; Arnao, Valentina; Della Corte, Vittoriano; Simonetta, Irene; Corpora, Francesca; Di Bona, Danilo; Maugeri, Rosario; Iacopino, Domenico Gerardo; Pinto, Antonio

2016-03-01

Statins have beneficial effects on cerebral circulation and brain parenchyma during ischemic stroke and reperfusion. The primary hypothesis of this randomized parallel trial was that treatment with 80 mg/day of atorvastatin administered early at admission after acute atherosclerotic ischemic stroke could reduce serum levels of markers of immune-inflammatory activation of the acute phase and that this immune-inflammatory modulation could have a possible effect on prognosis of ischemic stroke evaluated by some outcome indicators. We enrolled 42 patients with acute ischemic stroke classified as large arteries atherosclerosis stroke (LAAS) randomly assigned in a randomized parallel trial to the following groups: Group A, 22 patients treated with atorvastatin 80 mg (once-daily) from admission day until discharge; Group B, 20 patients not treated with atorvastatin 80 mg until discharge, and after discharge, treatment with atorvastatin has been started. At 72 hours and at 7 days after acute ischemic stroke, subjects of group A showed significantly lower plasma levels of tumor necrosis factor-α, interleukin (IL)-6, vascular cell adhesion molecule-1, whereas no significant difference with regard to plasma levels of IL-10, E-Selectin, and P-Selectin was observed between the 2 groups. At 72 hours and 7 days after admission, stroke patients treated with atorvastatin 80 mg in comparison with stroke subjects not treated with atorvastatin showed a significantly lower mean National Institutes of Health Stroke Scale and modified Rankin scores. Our findings provide the first evidence that atorvastatin acutely administered immediately after an atherosclerotic ischemic stroke exerts a lowering effect on immune-inflammatory activation of the acute phase of stroke and that its early use is associated to a better functional and prognostic profile.

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

The spatial frequencies influence the aesthetic judgment of buildings transculturally.

PubMed

Vannucci, Manila; Gori, Simone; Kojima, Haruyuki

2014-01-01

Recent evidence has shown that buildings designed to be high-ranking, according to the Western architectural decorum, have more impact on the minds of their beholders than low-ranking buildings. Here we investigated whether and how the aesthetic judgment for high- and low-ranking buildings was affected by differences in cultural expertise and by power spectrum differences. A group of Italian and Japanese participants performed aesthetic judgment tasks, with line drawings of high- and low-ranking buildings and with their random-phase versions (an image with the exact power spectrum of the original one but non-recognizable anymore). Irrespective of cultural expertise, high-ranking buildings and their relative random-phase versions received higher aesthetic judgments than low-ranking buildings and their random-phase versions. These findings indicate that high- and low-ranking buildings are differentiated for their aesthetic value and they show that low-level visual processes influence the aesthetic judgment based on differences in the stimuli power spectrum, irrespective of the influence of cultural expertise.

Randomized, Double-Blinded, Phase 2 Trial of WR 279,396 (Paromomycin and Gentamicin) for Cutaneous Leishmaniasis in Panama

PubMed Central

Sosa, Néstor; Capitán, Zeuz; Nieto, Javier; Nieto, Melissa; Calzada, José; Paz, Hector; Spadafora, Carmenza; Kreishman-Deitrick, Mara; Kopydlowski, Karen; Ullman, Diane; McCarthy, William F.; Ransom, Janet; Berman, Jonathan; Scott, Charles; Grogl, Max

2013-01-01

In this randomized, double-blinded Phase 2 trial, 30 patients with Leishmania panamensis cutaneous leishmaniasis were randomly allocated (1:1) to receive once daily topical treatment with WR 279,396 (15% paromomycin + 0.5% gentamicin) or Paromomycin Alone (15% paromomycin) for 20 days. The index lesion cure rate after 6 months follow-up was 13 of 15 (87%) for WR 279,396 and 9 of 15 (60%) for Paromomycin Alone (P = 0.099). When all treated lesions were included, the final cure rate for WR 279,398-treated patients was again 87%, but the final cure rate for Paromomycin Alone-treated patients was 8 of 15 (53.3%; P = 0.046). Both creams were well tolerated with mild application site reactions being the most frequent adverse event. The increased final cure rate in the WR 279,396 group in this small Phase 2 study suggests that the combination product may provide greater clinical benefit than paromomycin monotherapy against L. panamensis cutaneous leishmaniasis. PMID:23857024

Effectiveness of Using Incentives to Improve Parolee Admission and Attendance in Community Addiction Treatment

PubMed Central

Prendergast, Michael L.; Hall, Elizabeth A.; Grossman, Jason; Veliz, Robert; Gregorio, Liliana; Warda, Umme S.; Van Unen, Kory; Knight, Chloe

2017-01-01

This study is a randomized effectiveness trial of the use of incentives to improve treatment utilization among parolees in community treatment. In prison, Admission phase parolees were randomized to Admission Incentive (N=31) or Education (N=29). Attendance phase parolees entering community treatment were randomized to Attendance Incentive (N=104) or Education (N=98). There was no main effect for incentives in either study phase. Neither admission to community treatment (Incentive 60%, Education 64%; p =.74), nor intervention completion (Incentive 22%; Education 27%; p =.46) appeared to be impacted. Time-in-treatment was predicted by age, first arrest age, and type of parole status (Cox regression p<.05), but not by treatment group. Providing incentives did not increase the likelihood that parolees enrolled in or stayed in community treatment. In light of this finding, criminal justice practitioners who are considering incentives to increase admission or retention should be aware that they may not produce the desired outcomes. PMID:28331241

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.

Dynamical conductivity at the dirty superconductor-metal quantum phase transition.

PubMed

Del Maestro, Adrian; Rosenow, Bernd; Hoyos, José A; Vojta, Thomas

2010-10-01

We study the transport properties of ultrathin disordered nanowires in the neighborhood of the superconductor-metal quantum phase transition. To this end we combine numerical calculations with analytical strong-disorder renormalization group results. The quantum critical conductivity at zero temperature diverges logarithmically as a function of frequency. In the metallic phase, it obeys activated scaling associated with an infinite-randomness quantum critical point. We extend the scaling theory to higher dimensions and discuss implications for experiments.

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

Phase II randomized trial comparing high-dose IFN-α2b with temozolomide plus cisplatin as systemic adjuvant therapy for resected mucosal melanoma.

PubMed

Lian, Bin; Si, Lu; Cui, Chuanliang; Chi, Zhihong; Sheng, Xinan; Mao, Lili; Li, Siming; Kong, Yan; Tang, Bixia; Guo, Jun

2013-08-15

Mucosal melanoma is rare and associated with extremely poor prognosis. However, standard adjuvant therapy for mucosal melanoma has not been established. We conducted a randomized phase II clinical trial in patients with resected mucosal melanoma to compare the efficacy and safety of high-dose IFN-α2b (HDI) and temozolomide-based chemotherapy as adjuvant therapy. Patients with mucosal melanoma in stage II/III after surgery were randomized into three groups: observation group (group A, surgery alone), HDI group (group B, treated with 15 × 10(6) U/m(2)/d IFN-α2b, followed by 9 × 10(6) U IFN-α2b), and temozolomide (200 mg/m(2)/d) plus cisplatin (75 mg/m(2)) group (group C). The endpoints were relapse-free survival (RFS), overall survival (OS), and toxicities. One hundred and eighty-nine patients were enrolled and finally analyzed. With a median follow-up of 26.8 months, the median RFS was 5.4, 9.4, and 20.8 months for group A, B, and C, respectively. Estimated median OS for group A, B, and C was 21.2, 40.4, and 48.7 months, respectively. Patients treated with temozolomide plus cisplatin showed significant improvements in RFS (P < 0.001) and OS (P < 0.01) than those treated with either HDI or surgery alone. Toxicities were generally mild to moderate. Both temozolomide-based chemotherapy and HDI are effective and safe as adjuvant therapies for resected mucosal melanoma as compared with observation alone. However, HDI tends to be less effective than temozolomide-based chemotherapy for patients with resected mucosal melanoma in respect to RFS. The temozolomide plus cisplatin regimen might be a better choice for patients with resected mucosal melanoma. ©2013 AACR.

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

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.

Lifshitz phase: the microscopic structure of aqueous and ethanol mixtures of 1,n-diols.

PubMed

Požar, Martina; Perera, Aurélien

2017-06-14

We study binary mixtures of ethylene glycol and 1,3-propandiol with water or ethanol using computer simulations. Despite strong hydrogen bonding tendencies between all these molecules, we find that these mixtures are surprisingly homogeneous, in contrast to the strong micro-heterogeneity found in aqueous ethanol mixtures. The aqueous diol mixtures are found to be close to ideal mixtures, with near-ideal Kirkwood-Buff integrals. Ethanol-diol mixtures show weak non-ideality. The origin of this unexpected randomness is due to the fact that the two hydrogen bonding hydroxyl groups of the 1,n-diol are bound by the neutral alkyl bond, which prevents the micro-segregation of the different types of hydroxyl groups. These findings suggest that random disorder can arise in the presence of strong interactions - in contrast to the usual picture of random disorder due to weak interactions between the components. They point to the important role of molecular topology in tuning concentration fluctuations in complex liquids. We propose and justify herein the name of Lifshitz phases to designate such types of disordered systems.

Using financial incentives to promote physical activity in American Indian adolescents: A randomized controlled trial

PubMed Central

Chadwick, Jennifer Q.; Cannady, Tamela K.; Branam, Dannielle E.; Wharton, David F.; Tullier, Mary A.; Thompson, David M.; Copeland, Kenneth C.

2018-01-01

American Indians (AI) have high prevalence of diabetes in youth and may benefit from increasing physical activity as a strategy to improve metabolic health. We tested whether financial incentives would elicit greater frequency and/or duration of exercise in AI youth at high risk for developing diabetes. Overweight/obese AI boys and girls, 11–20 years old, were instructed to exercise on 3 days/week for 48 weeks at a tribal wellness center. The program was divided into three, 16-week-long phases to test different financial incentive strategies. Within each phase participants were randomly assigned to one of two groups that received different payments for exercise. Phase 1 was designed to test whether the size of the incentive would affect exercise frequency. In Phase 1, the number of exercise sessions did not differ between the group receiving a modest fixed-value payment per exercise session and the group receiving enhanced incentives to exercise more frequently (26 ± 3 versus 28 ± 2 sessions, respectively, p = 0.568). In Phase 2, the provision of an enhanced financial incentive to increase exercise duration resulted longer sessions, as the incentivized and standard payment groups exercised 38 ± 2 versus 29 ± 1 minutes per session (p = 0.002), respectively. In Phase 3, the effect of reducing the incentives on maintenance of exercise behaviors was inconclusive due to high participant withdrawal. Aerobic fitness increased 10% during Phase 1 but was unchanged thereafter. Insulin sensitivity and body composition were unchanged during the study. In conclusion, enhanced financial incentives increased the duration of exercise sessions, but had minimal effects on exercise participation. These results indicate that financial incentives hold promise in motivating previously sedentary, overweight/obese adolescents to exercise longer, but motivating them to sustain an exercise program remains the major challenge. Trial Registration: ClinicalTrials.gov NCT01848353. PMID:29856832

Effects of the concurrent use of a reduced dose of propofol with divided supplemental remifentanil and moderate hyperventilation on duration and morphology of electroconvulsive therapy-induced electroencephalographic seizure activity: A randomized controlled trial.

PubMed

Nishikawa, Kohki; Yamakage, Michiaki

2017-02-01

The clinical adequacy of electroconvulsive therapy (ECT) depends on not only seizure duration but also seizure amplitude and postictal suppression. The objective of this study was to evaluate the effects of combination of a reduced dose of propofol and moderate hyperventilation on seizure duration and electrical stimulus requirement for adequate ictal amplitude and postictal suppression. Prospective, randomized, controlled trial. Operating room at a municipal hospital. Sixty ASA physical status I or II patients scheduled to receive a total of >300 ECT treatments. Patients were randomly assigned to have the three interventions: the use of a standard dose (1mg/kg) of propofol and normoventilation (ETCO 2 of 40-45mmHg) (group P/N), the use of a reduced dose (0.5mg/kg) of propofol with divided remifentanil injections and normoventilation (group RP/N), and the use of a reduced dose of propofol with divided remifentanil injections and moderate hyperventilation (ETCO 2 of 30-35mmHg) (group RP/H). Patients in groups RP/N and RP/H received remifentanil 1μg/kg followed by propofol 0.5mg/kg for unconsciousness and thereafter remifentanil 1μg/kg immediately before the electrical stimulus. Patients in group RP/H had significantly longer durations of electroencephalographic (EEG) seizures in the early phase of the ECT course (P<0.05) and lower intensities of electrical stimulus in the late phase of the ECT course (P<0.05) than those in groups P/N and RP/N. A reduced dose of propofol combined with divided supplemental remifentanil under moderate hyperventilation during ECT may contribute to reduced electrical dosage due to the ability of its augmentation of seizure amplitude and postictal suppression in the late phase of the ECT course. Copyright © 2016 Elsevier Inc. All rights reserved.

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 .

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.

Multiphase contrast medium injection for optimization of computed tomographic coronary angiography.

PubMed

Budoff, Matthew Jay; Shinbane, Jerold S; Child, Janis; Carson, Sivi; Chau, Alex; Liu, Stephen H; Mao, SongShou

2006-02-01

Electron beam angiography is a minimally invasive imaging technique. Adequate vascular opacification throughout the study remains a critical issue for image quality. We hypothesized that vascular image opacification and uniformity of vascular enhancement between slices can be improved using multiphase contrast medium injection protocols. We enrolled 244 consecutive patients who were randomized to three different injection protocols: single-phase contrast medium injection (Group 1), dual-phase contrast medium injection with each phase at a different injection rate (Group 2), and a three-phase injection with two phases of contrast medium injection followed by a saline injection phase (Group 3). Parameters measured were aortic opacification based on Hounsfield units and uniformity of aortic enhancement at predetermined slices (locations from top [level 1] to base [level 60]). In Group 1, contrast opacification differed across seven predetermined locations (scan levels: 1st versus 60th, P < .05), demonstrating significant nonuniformity. In Group 2, there was more uniform vascular enhancement, with no significant differences between the first 50 slices (P > .05). In Group 3, there was greater uniformity of vascular enhancement and higher mean Hounsfield units value across all 60 images, from the aortic root to the base of the heart (P < .05). The three-phase injection protocol improved vascular opacification at the base of the heart, as well as uniformity of arterial enhancement throughout the study.

Effects of Teriparatide Retreatment in Osteoporotic Men and Women

PubMed Central

Finkelstein, Joel S.; Wyland, Jason J.; Leder, Benjamin Z.; Burnett-Bowie, Sherri-Ann M.; Lee, Hang; Jüppner, Harald; Neer, Robert M.

2009-01-01

Context: The stimulatory effect of teriparatide on bone mineral density (BMD) and bone turnover is initially exuberant, but then diminishes. Objective: Our objective was to determine whether retreating with teriparatide after a drug-free period can restore the initial exuberant response to teriparatide. Design and Setting: This was a planned extension of a randomized controlled trial conducted in a single university hospital. Patients and Intervention: Subjects previously participated in a 30-month randomized trial comparing the effects of alendronate (group 1), teriparatide (group 2), or both (group 3) on BMD and bone turnover in men and women with low BMD (phase 1). Subjects who completed phase 1 on their assigned therapy entered phase 2 (months 30–42), during which teriparatide was stopped in groups 2 and 3. Teriparatide was administered to all subjects during months 42 to 54 (phase 3). Main Outcome Measures: We compared changes in BMD and markers of bone turnover (serum osteocalcin, N-terminal propeptide of type 1 collagen, and N-telopeptide) between phase 1 and 3 in subjects receiving teriparatide alone. Results: Posterior-anterior and lateral spine BMD increased 12.5 ± 1.5 and 16.9 ± 1.7%, respectively, during the first 12 months of teriparatide administration and 5.2 ± 0.8 and 6.2 ± 1.8%, respectively, during teriparatide retreatment (P < 0.001 and P = 0.001). Increases in osteocalcin (P < 0.001), N-terminal propeptide of type 1 collagen (P < 0.001), and N-telopeptide (P < 0.001) were greater during the first period of teriparatide administration. Conclusion: The response to teriparatide is attenuated when readministered after a 12-month hiatus. PMID:19401368

Omega-3 fatty acid treatment of children with attention-deficit hyperactivity disorder: A randomized, double-blind, placebo-controlled study

PubMed Central

Bélanger, Stacey Ageranioti; Vanasse, Michel; Spahis, Schohraya; Sylvestre, Marie-Pierre; Lippé, Sarah; l’Heureux, François; Ghadirian, Parviz; Vanasse, Catherine-Marie; Levy, Emile

2009-01-01

BACKGROUND: Although several clinical trials have evaluated the impact of n-3 polyunsaturated fatty acid (PUFA) on patients with attention-deficit hyperactivity disorder (ADHD), changes in plasma PUFA composition were not always assessed following n-3 supplementation. Furthermore, no reports are available on the efficacy of n-3 PUFA in Canadian youth with ADHD. OBJECTIVES: To determine fatty acid (FA) composition, and the efficacy and safety of n-3 PUFA supplementation on ADHD clinical symptoms in French Canadian primary school children. PATIENTS AND METHODS: The Strengths and Weaknesses in ADHD and Normal Behaviors (SWAN) and Conners’ questionnaires were used to assess changes in ADHD symptoms in 37 children (only 26 children completed the study from zero to 16 weeks). They were divided into two groups (A and B), and participated in a 16-week, double-blind, one-way, crossover randomized study. In the first phase, group A received the n-3 PUFA supplement and group B received n-6 PUFA (sunflower oil) as a placebo. During the second phase, group B received the active n-3 PUFA supplement that was continued in group A. FA composition and lipid profile were assessed during the phases of the study. RESULTS: FA differences between groups were observed in the 26 patients. Supplementation with n-3 PUFA resulted in significant increases in eicosapentaenoic and docosahexaenoic acids in group A, while group B was enriched with alpha-linolenic, gamma-linolenic and homo-gamma-linolenic acids. The n-3 PUFA supplement was tolerated without any adverse effects. A statistically significant improvement in symptoms was noted based on the parent version of the Conners’ questionnaire from baseline to the end of phase 1, and this amelioration continued from phases 1 to 2, although the latter changes from phases 1 and 2 were not statistically significant in any of the subscales except for the subscale measuring inattention in group B. The improvement was greater in patients from group A in phase 1 and in patients from group B in phase 2. A subgroup of eight patients (four in each group) displayed a statistically significant clinical improvement following the administration of the n-3 PUFA supplement, particularly for the inattention and global Diagnostic and Statistical Manual of Mental Disorders, Fourth edition, total Conners’ subscales. CONCLUSIONS: A subgroup of children with ADHD who used n-3 PUFA supplements achieved and maintained symptom control. The data of the present study also supported n-3 PUFA safety and tolerability, but limited changes were noted in the FA profile in French Canadians with ADHD. PMID:19436468

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

Anal Cancer: An Examination of Radiotherapy Strategies

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

Glynne-Jones, Rob; Lim, Faye

2011-04-01

The Radiation Therapy Oncology Group 9811, ACCORD-03, and ACT II Phase III trials in anal cancer showed no benefit for cisplatin-based induction and maintenance chemotherapy, or radiation dose-escalation >59 Gy. This review examines the efficacy and toxicity of chemoradiation (CRT) in anal cancer, and discusses potential alternative radiotherapy strategies. The evidence for the review was compiled from randomized and nonrandomized trials of radiation therapy and CRT. A total of 103 retrospective/observational studies, 4 Phase I/II studies, 16 Phase II prospective studies, 2 randomized Phase II studies, and 6 Phase III trials of radiotherapy or chemoradiation were identified. There are nomore » meta-analyses based on individual patient data. A 'one-size-fits-all' approach for all stages of anal cancer is inappropriate. Early T1 tumors are probably currently overtreated, whereas T3/T4 lesions might merit escalation of treatment. Intensity-modulated radiotherapy or the integration of biological therapy may play a role in future.« less

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.

Evaluation of the Efficacy and Safety of DA-9601 versus Its New Formulation, DA-5204, in Patients with Gastritis: Phase III, Randomized, Double-Blind, Non-Inferiority Study.

PubMed

Choi, Yoon Jin; Lee, Dong Ho; Choi, Myung Gyu; Lee, Sung Joon; Kim, Sung Kook; Song, Geun Am; Rhee, Poong Lyul; Jung, Hwoon Yong; Kang, Dae Hwan; Lee, Yong Chan; Lee, Si Hyung; Choi, Suck Chei; Shim, Ki Nam; Seol, Sang Yong; Moon, Jeong Seop; Shin, Yong Woon; Kim, Hyun Soo; Lee, Soo Teik; Cho, Jin Woong; Choi, Eun Kwang; Lee, Oh Young; Jang, Jin Seok

2017-11-01

This study compared the efficacy of DA-9601 (Dong-A ST Co., Seoul, Korea) and its new formulation, DA-5204 (Dong-A ST Co.), for treating erosive gastritis. This phase III, randomized, multicenter, double-blind, non-inferiority trial randomly assigned 434 patients with endoscopically proven gastric mucosal erosions into two groups: DA-9601 3 times daily or DA-5,204 twice daily for 2 weeks. The final analysis included 421 patients (DA-5204, 209; DA-9601, 212). The primary endpoint (rate of effective gastric erosion healing) and secondary endpoints (cure rate of endoscopic erosion and gastrointestinal [GI] symptom relief) were assessed using endoscopy after the treatment. Drug-related adverse events (AEs), including GI symptoms, were also compared. At week 2, gastric healing rates with DA-5204 and DA-9601 were 42.1% (88/209) and 42.5% (90/212), respectively. The difference between the groups was -0.4% (95% confidence interval, -9.8% to 9.1%), which was above the non-inferiority margin of -14%. The cure rate of gastric erosion in both groups was 37.3%. The improvement rates of GI symptoms with DA-5204 and DA-9601 were 40.4% and 40.8%, respectively. There were no statistically significant differences between the two groups in both secondary endpoints. AEs were reported in 18 (8.4%) patients in the DA-5204 group and 19 (8.8%) in the DA-9601 group. Rates of AE were not different between the two groups. No serious AE or adverse drug reaction (ADR) occurred. These results demonstrate the non-inferiority of DA-5204 compared to DA-9601. DA-5204 is as effective as DA-9601 in the treatment of erosive gastritis. Registered randomized clinical trial at ClinicalTrials.gov (NCT02282670). © 2017 The Korean Academy of Medical Sciences.

Long‐term safety and efficacy of tofogliflozin as add‐on to insulin in patients with type 2 diabetes: Results from a 52‐week, multicentre, randomized, double‐blind, open‐label extension, Phase 4 study in Japan (J‐STEP/INS)

PubMed Central

Tamura, Masahiro; Senda, Masayuki; Gunji, Ryoji; Kaku, Kohei

2018-01-01

Aims To evaluate the long‐term safety and efficacy of tofogliflozin as an add‐on treatment to insulin over 52 weeks. Materials and methods This 52‐week, multicentre, Phase 4 study consisted of a 16‐week, randomized, double‐blind, placebo‐controlled phase and a 36‐week open label extension phase (NCT02201004). Japanese patients with type 2 diabetes mellitus, aged 20 to 75 years, with suboptimal glycaemic control (7.5%‐10.5%) receiving insulin monotherapy (basal‐bolus, bolus, premix [low and high] and basal) or receiving combination therapy with basal insulin and dipeptidyl peptidase‐4 inhibitor were eligible for participation. Patients who received tofogliflozin throughout the study (52 weeks) were referred to as the ‘tofo‐tofo group’ and patients who received placebo and tofogliflozin (36 weeks) were referred to as the ‘pla‐tofo group’. Results A total of 210 patients received treatment per randomization. Hypoglycaemia was the most common treatment‐emergent adverse event (AE) (42.9% in the tofo‐tofo group and 29.4% in the pla‐tofo group). Patients reported genital infection, urinary tract infection, excessive urination and AEs related to volume depletion (2.1%, 2.1%, 7.1% and 10.0% of patients in the tofo‐tofo group, and 0%, 1.5%, 2.9% and 7.4% of patients in the pla‐tofo group, respectively). Mean HbA1c and body weight at baseline (mean changes ± standard error from baseline to Week 52) in the tofo‐tofo and pla‐tofo groups were 8.53% (−0.76% ± 0.077) and 8.40% (−0.73% ± 0.102); 68.84 kg (−1.52 kg ± 0.207) and 72.24 kg (−2.13 kg ± 0.313), respectively. Conclusions This study demonstrates the safety and efficacy of tofogliflozin as add‐on to insulin therapy in type 2 diabetes mellitus patients, offering a new therapeutic solution to diabetes management. PMID:29316236

The hypocholesterolemic effect of an antacid containing aluminum hydroxide.

PubMed

Sperber, A D; Henkin, Y; Zuili, I; Bearman, J E; Shany, S

1991-12-01

To evaluate the efficacy, safety, and hypocholesterolemic effect of an aluminum hydroxide-containing antacid in hypercholesterolemic individuals. A prospective, randomized, double-masked, placebo-controlled phase of 2 months' duration, followed by an open-design treatment phase of 2 months' duration and a washout phase of 2 months' duration. Family practice clinics of two rural communities (kibbutzim) in Israel. Fifty-six men and women with hypercholesterolemia (type IIa or IIb). Fifty individuals completed the study. After 2 months of dietary modification (low-fat, low-cholesterol diet), the participants were randomized into two matched groups. Group 1 (28 participants) was treated for 2 months with a chewable antacid tablet containing simethicone, magnesium hydroxide, and 113 mg of aluminum hydroxide per tablet, at a dose of two tablets four times daily. Group 2 (22 participants) was given a similar number of placebo tablets for 2 months. During the following 2 months, both groups received the antacid at the above dose. Lipoprotein levels were evaluated at baseline and every 2 months thereafter for 6 months. Compared with pretreatment levels, Group 1 experienced a decrease in low-density lipoprotein cholesterol (LDL-C) of 9.8% after 2 months (p less than 0.001) and 18.5% after 4 months (p less than 0.001). Compared with Group 2, the decrease in LDL-C in Group 1 was 6.2% at the end of the 2-month double-masked, placebo phase. Although the high-density lipoprotein cholesterol (HDL-C) was also reduced in Group 1 at the end of 4 months of therapy (10.2%), the HDL-C/LDL-C ratio increased by 13% during the same interval (p less than 0.05). The treatment was well tolerated, with minimal side effects. An aluminum hydroxide-containing antacid reduces LDL-C in hypercholesterolemic individuals. Although HDL-C was also reduced to a lesser extent, the overall atherogenic index was improved. Further studies should be conducted to evaluate the long-term safety and efficacy of antacids containing aluminum hydroxide in hypercholesterolemic patients.

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.

Dynamical conductivity at the dirty superconductor-metal quantum phase transition

NASA Astrophysics Data System (ADS)

Hoyos, J. A.; Del Maestro, Adrian; Rosenow, Bernd; Vojta, Thomas

2011-03-01

We study the transport properties of ultrathin disordered nanowires in the neighborhood of the superconductor-metal quantum phase transition. To this end we combine numerical calculations with analytical strong-disorder renormalization group results. The quantum critical conductivity at zero temperature diverges logarithmically as a function of frequency. In the metallic phase, it obeys activated scaling associated with an infinite-randomness quantum critical point. We extend the scaling theory to higher dimensions and discuss implications for experiments. Financial support: Fapesp, CNPq, NSF, and Research Corporation.

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.

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

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

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).

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.

Single-phase and two-phase flow properties of mesaverde tight sandstone formation; random-network modeling approach

NASA Astrophysics Data System (ADS)

Bashtani, Farzad; Maini, Brij; Kantzas, Apostolos

2016-08-01

3D random networks are constructed in order to represent the tight Mesaverde formation which is located in north Wyoming, USA. The porous-space is represented by pore bodies of different shapes and sizes which are connected to each other by pore throats of varying length and diameter. Pore bodies are randomly distributed in space and their connectivity varies based on the connectivity number distribution which is used in order to generate the network. Network representations are then validated using publicly available mercury porosimetry experiments. The network modeling software solves the fundamental equations of two-phase immiscible flow incorporating wettability and contact angle variability. Quasi-static displacement is assumed. Single phase macroscopic properties (porosity, permeability) are calculated and whenever possible are compared to experimental data. Using this information drainage and imbibition capillary pressure, and relative permeability curves are predicted and (whenever possible) compared to experimental data. The calculated information is grouped and compared to available literature information on typical behavior of tight formations. Capillary pressure curve for primary drainage process is predicted and compared to experimental mercury porosimetry in order to validate the virtual porous media by history matching. Relative permeability curves are also calculated and presented.

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.

Analytical evaluation of the combined influence of polarization mode dispersion and group velocity dispersion on the bit error rate performance of optical homodyne quadrature phase-shift keying systems

NASA Astrophysics Data System (ADS)

Taher, Kazi Abu; Majumder, Satya Prasad

2017-12-01

A theoretical approach is presented to evaluate the bit error rate (BER) performance of an optical fiber transmission system with quadrature phase-shift keying (QPSK) modulation under the combined influence of polarization mode dispersion (PMD) and group velocity dispersion (GVD) in a single-mode fiber (SMF). The analysis is carried out without and with polarization division multiplexed (PDM) transmission considering a coherent homodyne receiver. The probability density function (pdf) of the random phase fluctuations due to PMD and GVD at the output of the receiver is determined analytically, considering the pdf of differential group delay (DGD) to be Maxwellian distribution and that of GVD to be Gaussian approximation. The exact pdf of the phase fluctuation due to PMD and GVD is also evaluated from its moments using a Monte Carlo simulation technique. Average BER is evaluated by averaging the conditional BER over the pdf of the random phase fluctuation. The BER performance results are evaluated for different system parameters. It is found that PDM-QPSK coherent homodyne system suffers more power penalty than the homodyne QPSK system without PDM. A PDM-QPSK system suffers a penalty of 4.3 dB whereas power penalty of QPSK system is 3.0 dB at a BER of 10-9 for DGD of 0.8 Tb and GVD of 1700 ps/nm. Analytical results are compared with the experimental results reported earlier and found to have good conformity.

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.

Effect of sodium zirconium cyclosilicate on potassium lowering for 28 days among outpatients with hyperkalemia: the HARMONIZE randomized clinical trial.

PubMed

Kosiborod, Mikhail; Rasmussen, Henrik S; Lavin, Philip; Qunibi, Wajeh Y; Spinowitz, Bruce; Packham, David; Roger, Simon D; Yang, Alex; Lerma, Edgar; Singh, Bhupinder

2014-12-03

Hyperkalemia is a common electrolyte abnormality that may be difficult to manage because of a lack of effective therapies. Sodium zirconium cyclosilicate is a nonabsorbed cation exchanger that selectively binds potassium in the intestine. To evaluate the efficacy and safety of zirconium cyclosilicate for 28 days in patients with hyperkalemia. HARMONIZE was a phase 3, multicenter, randomized, double-blind, placebo-controlled trial evaluating zirconium cyclosilicate in outpatients with hyperkalemia (serum potassium ≥5.1 mEq/L) recruited from 44 sites in the United States, Australia, and South Africa (March-August 2014). Patients (n = 258) received 10 g of zirconium cyclosilicate 3 times daily in the initial 48-hour open-label phase. Patients (n = 237) achieving normokalemia (3.5-5.0 mEq/L) were then randomized to receive zirconium cyclosilicate, 5 g (n = 45 patients), 10 g (n = 51), or 15 g (n = 56), or placebo (n = 85) daily for 28 days. The primary end point was mean serum potassium level in each zirconium cyclosilicate group vs placebo during days 8-29 of the randomized phase. In the open-label phase, serum potassium levels declined from 5.6 mEq/L at baseline to 4.5 mEq/L at 48 hours. Median time to normalization was 2.2 hours, with 84% of patients (95% CI, 79%-88%) achieving normokalemia by 24 hours and 98% (95% CI, 96%-99%) by 48 hours. In the randomized phase, serum potassium was significantly lower during days 8-29 with all 3 zirconium cyclosilicate doses vs placebo (4.8 mEq/L [95% CI, 4.6-4.9], 4.5 mEq/L [95% CI, 4.4-4.6], and 4.4 mEq/L [95% CI, 4.3-4.5] for 5 g, 10 g, and 15 g; 5.1 mEq/L [95% CI, 5.0-5.2] for placebo; P < .001 for all comparisons). The proportion of patients with mean potassium <5.1 mEq/L during days 8-29 was significantly higher in all zirconium cyclosilicate groups vs placebo (36/45 [80%], 45/50 [90%], and 51/54 [94%] for the 5-g, 10-g, and 15-g groups, vs 38/82 [46%] with placebo; P < .001 for each dose vs placebo). Adverse events were comparable between zirconium cyclosilicate and placebo, although edema was more common in the 15-g group (edema incidence: 2/85 [2%], 1/45 [2%], 3/51 [6%], and 8/56 [14%] patients in the placebo, 5-g, 10-g, and 15-g groups). Hypokalemia developed in 5/51 (10%) and 6/56 patients (11%) in the 10-g and 15-g zirconium cyclosilicate groups, vs none in the 5-g or placebo groups. Among outpatients with hyperkalemia, open-label sodium zirconium cyclosilicate reduced serum potassium to normal levels within 48 hours; compared with placebo, all 3 doses of zirconium cyclosilicate resulted in lower potassium levels and a higher proportion of patients with normal potassium levels for up to 28 days. Further studies are needed to evaluate the efficacy and safety of zirconium cyclosilicate beyond 4 weeks and to assess long-term clinical outcomes. clinicaltrials.gov Identifier: NCT02088073.

Direct manipulation of physiological arousal in induced anxiety therapy - biofeedback approach.

PubMed

Sappington, A A

1977-10-01

This study investigated the role of physiological arousal in the affect induction phase of Induced Anxiety therapy by using biofeedback to facilitate arousal. Twenty-one college students who were suffering from free-floating anxiety were assigned randomly to one of three groups: (1) a no-treatment control group simply completed the measures before and after therapy; (2) a conventional Induced Anxiety group went through five standard Induced Anxiety sessions; and (3) biofeedback Induced Anxiety group went through a similar procedure except that biofeedback was used in the affect induction phase to facilitate heart rate increase. It was found that the biofeedback procedure did result in a greater heart rate increase during the affect induction phase arousal than did the conventional procedure (.01 level of significance), but did not facilitate subjective emotional arousal. Biofeedback Induced Anxiety resulted in a greater reduction of trait anxiety as measured by the Multiple Affect Adjective Check List than did the no-treatment group or the conventonal Induced Anxiety group. The conventional Induced Anxiety group did not differ significantly from the no-treatment control group.

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.

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

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.

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.

Imiquimod 5% cream for the treatment of actinic keratosis: results from two phase III, randomized, double-blind, parallel group, vehicle-controlled trials.

PubMed

Lebwohl, Mark; Dinehart, Scott; Whiting, David; Lee, Peter K; Tawfik, Naji; Jorizzo, Joseph; Lee, James H; Fox, Terry L

2004-05-01

The immune system plays a critical role in the development and pathogenesis of actinic keratosis (AK). Imiquimod has been shown to stimulate the cutaneous immune response and be effective for the treatment of nonmelanoma skin cancers. Two phase III, randomized, double-blind, vehicle-controlled studies evaluated the efficacy of imiquimod 5% cream compared with vehicle in the treatment of AK lesions on the face and balding scalp. A total of 436 participants at 24 centers in the United States and Canada were randomized to either imiquimod 5% or vehicle cream. Study cream was applied one time per day, 2 days per week for 16 weeks. Clearance of AK lesions was clinically assessed at an 8-week posttreatment visit. The complete clearance rate was 45.1% for the imiquimod group and 3.2% for the vehicle group. The difference in complete clearance rates (imiquimod minus vehicle) was 41.9% with a 95% confidence interval of 34.9% to 49%. The partial (> or =75%) clearance rate was 59.1% for the imiquimod group and 11.8% for the vehicle group. The difference in partial clearance rates (imiquimod minus vehicle) was 47.3% with a 95% confidence interval of 39.5% to 55.1%. The median percent reduction in AK lesions was 83.3% for the imiquimod group and 0% for the vehicle group. Local skin reactions were common. Severe erythema was reported by 17.7% of participants who received imiquimod and 2.3% of participants who received vehicle. Overall, imiquimod was very well tolerated. Imiquimod 5% cream used 2 times per week for 16 weeks is an effective and well-tolerated treatment for AK.

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

A randomized phase II study of combination therapy with S-1, oral leucovorin, and oxaliplatin (SOL) and mFOLFOX6 in patients with previously untreated metastatic colorectal cancer.

PubMed

Yamazaki, Kentaro; Kuwano, Hiroyuki; Ojima, Hitoshi; Otsuji, Toshio; Kato, Takeshi; Shimada, Ken; Hyodo, Ichinosuke; Nishina, Tomohiro; Shirao, Kuniaki; Esaki, Taito; Ohishi, Takashi; Denda, Tadamichi; Takeuchi, Masahiro; Boku, Narikazu

2015-03-01

Biochemical modulation of 5-fluorouracil (5-FU) by leucovorin (LV) enhances antitumor activity. LV is thus often added to 5-FU-based regimens for the treatment of metastatic colorectal cancer (mCRC). A combination of S-1, oxaliplatin, and LV (SOL) was shown to be feasible, effective, and safe in a previous phase I trial. We therefore conducted a randomized phase II trial to evaluate efficacy and safety of SOL compared with mFOLFOX6. Patients with mCRC and no prior chemotherapy were randomly assigned to receive either SOL or mFOLFOX6. SOL consisted of S-1 (40-60 mg bid) plus oral LV (25 mg bid) for 1 week and oxaliplatin (85 mg/m(2)) on day 1, repeated every 2 weeks. Among 107 patients enrolled from July 2008 through July 2009, 105 (56 in the SOL group and 49 in the mFOLFOX6 group) were eligible and evaluated. The median progression-free survival was 9.6 months in the SOL group and 6.9 months in the mFOLFOX6 group [hazard ratio (HR) 0.83, 95 % confidence interval (CI) 0.49-1.40]. The median overall survival was 29.9 and 25.9 months, respectively (HR 0.91, 95 % CI 0.55-1.49). The response rate was 55 % in both groups. Grade 3 or 4 adverse drug reactions were neutropenia (20 % with SOL vs 41 % with mFOLFOX6), sensory neuropathy (20 vs 2.0 %), anorexia (13 vs 7.8 %), fatigue (11 vs 5.9 %), and diarrhea (11 vs 3.9 %). SOL demonstrated promising efficacy and acceptable toxicity as first-line chemotherapy for mCRC. Further studies of SOL combined with molecular target agents are warranted.

KINECT 3: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial of Valbenazine for Tardive Dyskinesia.

PubMed

Hauser, Robert A; Factor, Stewart A; Marder, Stephen R; Knesevich, Mary Ann; Ramirez, Paul M; Jimenez, Roland; Burke, Joshua; Liang, Grace S; O'Brien, Christopher F

2017-05-01

Tardive dyskinesia is a persistent movement disorder induced by dopamine receptor blockers, including antipsychotics. Valbenazine (NBI-98854) is a novel, highly selective vesicular monoamine transporter 2 inhibitor that demonstrated favorable efficacy and tolerability in the treatment of tardive dyskinesia in phase 2 studies. This phase 3 study further evaluated the efficacy, safety, and tolerability of valbenazine as a treatment for tardive dyskinesia. This 6-week, randomized, double-blind, placebo-controlled trial included patients with schizophrenia, schizoaffective disorder, or a mood disorder who had moderate or severe tardive dyskinesia. Participants were randomly assigned in a 1:1:1 ratio to once-daily placebo, valbenazine at 40 mg/day, or valbenazine at 80 mg/day. The primary efficacy endpoint was change from baseline to week 6 in the 80 mg/day group compared with the placebo group on the Abnormal Involuntary Movement Scale (AIMS) dyskinesia score (items 1-7), as assessed by blinded central AIMS video raters. Safety assessments included adverse event monitoring, laboratory tests, ECG, and psychiatric measures. The intent-to-treat population included 225 participants, of whom 205 completed the study. Approximately 65% of participants had schizophrenia or schizoaffective disorder, and 85.5% were receiving concomitant antipsychotics. Least squares mean change from baseline to week 6 in AIMS dyskinesia score was -3.2 for the 80 mg/day group, compared with -0.1 for the placebo group, a significant difference. AIMS dyskinesia score was also reduced in the 40 mg/day group (-1.9 compared with -0.1). The incidence of adverse events was consistent with previous studies. Once-daily valbenazine significantly improved tardive dyskinesia in participants with underlying schizophrenia, schizoaffective disorder, or mood disorder. Valbenazine was generally well tolerated, and psychiatric status remained stable. Longer trials are necessary to understand the long-term effects of valbenazine in patients with tardive dyskinesia.

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

Daily Rifapentine for Treatment of Pulmonary Tuberculosis. A Randomized, Dose-Ranging Trial

PubMed Central

Savic, Radojka M.; Goldberg, Stefan; Stout, Jason E.; Schluger, Neil; Muzanyi, Grace; Johnson, John L.; Nahid, Payam; Hecker, Emily J.; Heilig, Charles M.; Bozeman, Lorna; Feng, Pei-Jean I.; Moro, Ruth N.; MacKenzie, William; Dooley, Kelly E.; Nuermberger, Eric L.; Vernon, Andrew; Weiner, Marc

2015-01-01

Rationale: Rifapentine has potent activity in mouse models of tuberculosis chemotherapy but its optimal dose and exposure in humans are unknown. Objectives: We conducted a randomized, partially blinded dose-ranging study to determine tolerability, safety, and antimicrobial activity of daily rifapentine for pulmonary tuberculosis treatment. Methods: Adults with sputum smear-positive pulmonary tuberculosis were assigned rifapentine 10, 15, or 20 mg/kg or rifampin 10 mg/kg daily for 8 weeks (intensive phase), with isoniazid, pyrazinamide, and ethambutol. The primary tolerability end point was treatment discontinuation. The primary efficacy end point was negative sputum cultures at completion of intensive phase. Measurements and Main Results: A total of 334 participants were enrolled. At completion of intensive phase, cultures on solid media were negative in 81.3% of participants in the rifampin group versus 92.5% (P = 0.097), 89.4% (P = 0.29), and 94.7% (P = 0.049) in the rifapentine 10, 15, and 20 mg/kg groups. Liquid cultures were negative in 56.3% (rifampin group) versus 74.6% (P = 0.042), 69.7% (P = 0.16), and 82.5% (P = 0.004), respectively. Compared with the rifampin group, the proportion negative at the end of intensive phase was higher among rifapentine recipients who had high rifapentine areas under the concentration–time curve. Percentages of participants discontinuing assigned treatment for reasons other than microbiologic ineligibility were similar across groups (rifampin, 8.2%; rifapentine 10, 15, or 20 mg/kg, 3.4, 2.5, and 7.4%, respectively). Conclusions: Daily rifapentine was well-tolerated and safe. High rifapentine exposures were associated with high levels of sputum sterilization at completion of intensive phase. Further studies are warranted to determine if regimens that deliver high rifapentine exposures can shorten treatment duration to less than 6 months. Clinical trial registered with www.clinicaltrials.gov (NCT 00694629). PMID:25489785

Daily rifapentine for treatment of pulmonary tuberculosis. A randomized, dose-ranging trial.

PubMed

Dorman, Susan E; Savic, Radojka M; Goldberg, Stefan; Stout, Jason E; Schluger, Neil; Muzanyi, Grace; Johnson, John L; Nahid, Payam; Hecker, Emily J; Heilig, Charles M; Bozeman, Lorna; Feng, Pei-Jean I; Moro, Ruth N; MacKenzie, William; Dooley, Kelly E; Nuermberger, Eric L; Vernon, Andrew; Weiner, Marc

2015-02-01

Rifapentine has potent activity in mouse models of tuberculosis chemotherapy but its optimal dose and exposure in humans are unknown. We conducted a randomized, partially blinded dose-ranging study to determine tolerability, safety, and antimicrobial activity of daily rifapentine for pulmonary tuberculosis treatment. Adults with sputum smear-positive pulmonary tuberculosis were assigned rifapentine 10, 15, or 20 mg/kg or rifampin 10 mg/kg daily for 8 weeks (intensive phase), with isoniazid, pyrazinamide, and ethambutol. The primary tolerability end point was treatment discontinuation. The primary efficacy end point was negative sputum cultures at completion of intensive phase. A total of 334 participants were enrolled. At completion of intensive phase, cultures on solid media were negative in 81.3% of participants in the rifampin group versus 92.5% (P = 0.097), 89.4% (P = 0.29), and 94.7% (P = 0.049) in the rifapentine 10, 15, and 20 mg/kg groups. Liquid cultures were negative in 56.3% (rifampin group) versus 74.6% (P = 0.042), 69.7% (P = 0.16), and 82.5% (P = 0.004), respectively. Compared with the rifampin group, the proportion negative at the end of intensive phase was higher among rifapentine recipients who had high rifapentine areas under the concentration-time curve. Percentages of participants discontinuing assigned treatment for reasons other than microbiologic ineligibility were similar across groups (rifampin, 8.2%; rifapentine 10, 15, or 20 mg/kg, 3.4, 2.5, and 7.4%, respectively). Daily rifapentine was well-tolerated and safe. High rifapentine exposures were associated with high levels of sputum sterilization at completion of intensive phase. Further studies are warranted to determine if regimens that deliver high rifapentine exposures can shorten treatment duration to less than 6 months. Clinical trial registered with www.clinicaltrials.gov (NCT 00694629).

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

Moms in motion: a group-mediated cognitive-behavioral physical activity intervention.

PubMed

Cramp, Anita G; Brawley, Lawrence R

2006-08-22

When examining the prevalence of physical inactivity by gender and age, women over the age of 25 are at an increased risk for sedentary behavior. Childbearing and motherhood have been explored as one possible explanation for this increased risk. Post natal exercise studies to date demonstrate promising physical and psychological outcomes, however few physical activity interventions have been theory-driven and tailored to post natal exercise initiates. The purpose of this study was to compare the effects of a group-mediated cognitive behavioral intervention based upon social-cognitive theory and group dynamics (GMCB) to a standard care postnatal exercise program (SE). A randomized, two-arm intervention design was used. Fifty-seven post natal women were randomized to one of two conditions: (1) a standard exercise treatment (SE) and (2) a standard exercise treatment plus group-mediated cognitive behavioral intervention (GMCB). Participants in both conditions participated in a four-week intensive phase where participants received standard exercise training. In addition, GMCB participants received self-regulatory behavioral skills training via six group-mediated counseling sessions. Following the intensive phase, participants engaged in a four-week home-based phase of self-structured exercise. Measures of physical activity, barrier efficacy, and proximal outcome expectations were administered and data were analyzed using ANCOVA procedures. ANCOVA of change scores for frequency, minutes, and volume of physical activity revealed significant treatment effects over the intensive and home-based phases (p's < 0.01). In addition, ANCOVA of change in mean barrier efficacy and proximal outcome expectations at the conclusion of the intensive phase demonstrated that GMCB participants increased their initial level of barrier efficacy and outcome expectations while SE participants decreased (p < 0.05). While both exercise programs resulted in improvements to exercise participation, the GMCB intervention produced greater improvement in overall physical activity, barrier efficacy and proximal outcome expectations.

Robot-assisted Versus Laparoscopic Surgery for Rectal Cancer: A Phase II Open Label Prospective Randomized Controlled Trial.

PubMed

Kim, Min Jung; Park, Sung Chan; Park, Ji Won; Chang, Hee Jin; Kim, Dae Yong; Nam, Byung-Ho; Sohn, Dae Kyung; Oh, Jae Hwan

2018-02-01

The phase II randomized controlled trial aimed to compare the outcomes of robot-assisted surgery with those of laparoscopic surgery in the patients with rectal cancer. The feasibility of robot-assisted surgery over laparoscopic surgery for rectal cancer has not been established yet. Between February 21, 2012 and March 11, 2015, patients with rectal cancer (cT1-3NxM0) were enrolled. Patients were randomized 1:1 to either robot-assisted or laparoscopic surgery, and stratified per sex and administration of preoperative chemoradiotherapy. The primary outcome was the quality of total mesorectal excision (TME) specimen. Secondary outcomes were the circumferential and distal resection margins, the number of harvested lymph nodes, morbidity, bowel function recovery, and quality of life. A total of 163 patients were randomly assigned to the robot-assisted (n = 81) and laparoscopic (n = 82) surgery groups, and 139 patients were eligible for the analyses (73 vs 66, respectively). One patient (1.2%) in the robot-assisted group was converted to open surgery. The TME quality did not differ between the robot-assisted and laparoscopic groups (80.3% vs 78.1% complete TME, respectively; 18.2% vs 21.9% nearly complete TME, respectively; P = 0.599). The resection margins, number of harvested lymph nodes, morbidity, and bowel function recovery also were not significantly different. On analyzing quality of life, scores of the European Organization for Research and Treatment of Cancer Quality of Life (EORTC QLQ C30) and EORTC QLQ CR38 were similar in the 2 groups, but in the EORTC QLQ CR 38 questionnaire, sexual function 12 months postoperatively was better in the robot-assisted group than in the laparoscopic group (P = 0.03). Robot-assisted surgery in rectal cancer showed TME quality comparable with that of laparoscopic surgery, and it demonstrated similar postoperative morbidity, bowel function recovery, and quality of life.

Methylene blue prevents surgery-induced peritoneal adhesions but impairs the early phase of anastomotic wound healing

PubMed Central

Dinc, Soykan; Ozaslan, Cihangir; Kuru, Bekir; Karaca, Sefa; Ustun, Huseyin; Alagol, Haluk; Renda, Nurten; Oz, Murat

2006-01-01

Objectives Adhesion formation continues to be an important problem in gastrointestinal surgery. In recent years, methylene blue (MB) has been reported to be an effective agent for preventing peritoneal adhesions. However, its effects on the wound healing process are unknown. In the present study, we investigated the effects of MB on the early and late phases of anastomotic wound healing and on adhesion formation. Methods We randomly categorized 92 rats into 2 groups in bursting pressure measurements and 50 rats into 3 groups in the adhesion model. We divided the animals into saline-treated (n = 46) or MB-treated (n = 46) groups. Bursting pressures of the anastomoses were measured on postoperative days 3 and 7. In biochemical studies, tissue hydroxyproline levels, total nitrite/nitrate levels and nitric oxide synthase activity were measured on postoperative days 3 and 7. In the adhesion model, we randomly categorized rats into sham (n = 10), saline-treated (n = 20) and MB-treated (n = 20) groups, and the formation of intraperitoneal adhesions was scored on postoperative day 14. We compared the measurement of bursting pressure and biochemical measurements of tissue hydroxyproline levels, total nitrite/nitrate levels and nitric oxide synthase activity. Histopathological findings of specimens were presented. Results During the early phase of wound healing (postoperative day 3), bursting pressures, tissue hydroxyproline, total nitrite/nitrate levels and nitric oxide synthase activity in the MB-treated group were significantly lower than those of the saline-treated group. On postoperative day 7, there was no significant difference in these parameters between MB and saline-treated groups. In the adhesion model, MB caused a significant reduction in the formation of peritoneal adhesions. Conclusion MB prevents peritoneal adhesions but causes a significant impairment of anastomotic bursting pressure during the early phase of the wound healing process by its transient inhibitory effect on the nitric oxide pathway. PMID:17152569

A perfect correlate does not a surrogate make

PubMed Central

Baker, Stuart G; Kramer, Barnett S

2003-01-01

Background There is common belief among some medical researchers that if a potential surrogate endpoint is highly correlated with a true endpoint, then a positive (or negative) difference in potential surrogate endpoints between randomization groups would imply a positive (or negative) difference in unobserved true endpoints between randomization groups. We investigate this belief when the potential surrogate and unobserved true endpoints are perfectly correlated within each randomization group. Methods We use a graphical approach. The vertical axis is the unobserved true endpoint and the horizontal axis is the potential surrogate endpoint. Perfect correlation within each randomization group implies that, for each randomization group, potential surrogate and true endpoints are related by a straight line. In this scenario the investigator does not know the slopes or intercepts. We consider a plausible example where the slope of the line is higher for the experimental group than for the control group. Results In our example with unknown lines, a decrease in mean potential surrogate endpoints from control to experimental groups corresponds to an increase in mean true endpoint from control to experimental groups. Thus the potential surrogate endpoints give the wrong inference. Similar results hold for binary potential surrogate and true outcomes (although the notion of correlation does not apply). The potential surrogate endpointwould give the correct inference if either (i) the unknown lines for the two group coincided, which means that the distribution of true endpoint conditional on potential surrogate endpoint does not depend on treatment group, which is called the Prentice Criterion or (ii) if one could accurately predict the lines based on data from prior studies. Conclusion Perfect correlation between potential surrogate and unobserved true outcomes within randomized groups does not guarantee correct inference based on a potential surrogate endpoint. Even in early phase trials, investigators should not base conclusions on potential surrogate endpoints in which the only validation is high correlation with the true endpoint within a group. PMID:12962545

Prospective Randomized Phase II Parallel Study of Vinorelbine Maintenance Therapy versus Best Supportive Care in Advanced Non-Small Cell Lung Cancer.

PubMed

Khosravi, Adnan; Esfahani-Monfared, Zahra; Seifi, Sharareh; Khodadad, Kian

2017-01-01

Maintenance strategy has been used to improve survival in non-small cell lung cancer (NSCLC). We investigated whether switch maintenance therapy with vinorelbine improved progression free survival (PFS) after first-line chemotherapy with gemcitabine plus carboplatin. In this single blind, parallel, phase 2, randomized trial, patients with NSCLC pathology, age >18 years, Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0-2, and advanced stage (IIIB and IV) were treated with up to 6 cycles of gemcitabine 1250 mg/m 2 (day 1 and 8) plus carboplatin AUC 5 (day 1) every 3 weeks. Patients who did not show progression after first-line chemotherapy were randomly assigned to receive switch maintenance with vinorelbine (25 mg/m 2 , day 1, 15) or the best supportive care until disease progression. A total of 100 patients were registered, of whom 34 had a non-progressive response to first-line chemotherapy and randomly received maintenance vinorelbine (n=19) or best supportive care (n=15). The hazard ratio of PFS in the vinorelbine group relative to the best supportive care group was 1.097 (95% confidence interval = 0.479-2.510; P-value =0.827). There was no significant difference between the overall survival for the two groups (P=0.068). Switch maintenance strategies are beneficial, but defining the right candidates for treatment is a problem. Moreover, the trial designs do not always reflect the real-world considerations. Switch maintenance therapy with vinorelbine, though had tolerable toxicity, did not improve PFS in patients with NSCLC. Therefore, other agents should be considered in this setting.

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.

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.

Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors.

PubMed

Weir, Matthew R; Bakris, George L; Bushinsky, David A; Mayo, Martha R; Garza, Dahlia; Stasiv, Yuri; Wittes, Janet; Christ-Schmidt, Heidi; Berman, Lance; Pitt, Bertram

2015-01-15

Hyperkalemia increases the risk of death and limits the use of inhibitors of the renin-angiotensin-aldosterone system (RAAS) in high-risk patients. We assessed the safety and efficacy of patiromer, a nonabsorbed potassium binder, in a multicenter, prospective trial. Patients with chronic kidney disease who were receiving RAAS inhibitors and who had serum potassium levels of 5.1 to less than 6.5 mmol per liter received patiromer (at an initial dose of 4.2 g or 8.4 g twice a day) for 4 weeks (initial treatment phase); the primary efficacy end point was the mean change in the serum potassium level from baseline to week 4. Eligible patients at the end of week 4 (those with a baseline potassium level of 5.5 to <6.5 mmol per liter in whom the level decreased to 3.8 to <5.1 mmol per liter) entered an 8-week randomized withdrawal phase in which they were randomly assigned to continue patiromer or switch to placebo; the primary efficacy end point was the between-group difference in the median change in the serum potassium level over the first 4 weeks of that phase. In the initial treatment phase, among 237 patients receiving patiromer who had at least one potassium measurement at a scheduled visit after day 3, the mean (±SE) change in the serum potassium level was -1.01±0.03 mmol per liter (P<0.001). At week 4, 76% (95% confidence interval, 70 to 81) of the patients had reached the target potassium level (3.8 to <5.1 mmol per liter). Subsequently, 107 patients were randomly assigned to patiromer (55 patients) or placebo (52 patients) for the randomized withdrawal phase. The median increase in the potassium level from baseline of that phase was greater with placebo than with patiromer (P<0.001); a recurrence of hyperkalemia (potassium level, ≥5.5 mmol per liter) occurred in 60% of the patients in the placebo group as compared with 15% in the patiromer group through week 8 (P<0.001). Mild-to-moderate constipation was the most common adverse event (in 11% of the patients); hypokalemia occurred in 3%. In patients with chronic kidney disease who were receiving RAAS inhibitors and who had hyperkalemia, patiromer treatment was associated with a decrease in serum potassium levels and, as compared with placebo, a reduction in the recurrence of hyperkalemia. (Funded by Relypsa; OPAL-HK ClinicalTrials.gov number, NCT01810939.).

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.

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.

Luteal phase support in intrauterine insemination cycles: a prospective randomized study of 300 mg versus 600 mg intravaginal progesterone tablet.

PubMed

Biberoglu, Ebru H; Tanrıkulu, Filiz; Erdem, Mehmet; Erdem, Ahmet; Biberoglu, Kutay Omer

2016-01-01

Vaginal progesterone (P) has been suggested to be used for luteal phase support (LPS) in controlled ovarian stimulation (COH)-intrauterine insemination (IUI) cycles, however, no concensus exists about the best P dose. Therefore, considering the fecundability rate as the primary end point, our main objective was to find the optimal dose of P in COH-IUI cycles, comparing the two groups of women, each of which comprised of 100 women either on 300 mg or 600 mg of intravaginal P tablets, in a prospective randomized study design. The mean age of the women, duration of infertility, basal and day of hCG injection hormone levels in the female and sperm parameters were similar in the two study groups. Also, duration and dose of gonadotropin given, number of follicles, endometrial thickness, the total, ongoing and multiple pregnancy rates were comparable in both groups. We, therefore, claim that 300 mg of intravaginal micronized P should be the maximum dose of LPS in IUI cycles.

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

Pentoxifylline during steroid window phase at induction to remission increases apoptosis in childhood with acute lymphoblastic leukemia.

PubMed

Gonzalez-Ramella, O; Ortiz-Lazareno, P C; Jiménez-López, X; Gallegos-Castorena, S; Hernández-Flores, G; Medina-Barajas, F; Meza-Arroyo, J; Jave-Suárez, L F; Lerma-Díaz, J M; Sánchez-Zubieta, F; Bravo-Cuellar, A

2016-04-01

Pentoxifylline (PTX) has been shown to increase chemotherapy-induced apoptosis. A clinical trial was developed to evaluate the effect of the addition of PTX to the induction steroid window phase in children with acute lymphoblastic leukemia (ALL). Thirty-two children were enrolled on this study. Children with a new diagnosis of ALL were randomly assigned to receive prednisone (PRD) 40 mg/m(2)/day only during the 7-day treatment pre-phase (PRD group, 11 patients) or to receive PRD with PTX (10 mg/kg/day) (PTX group, 11 patients); the control group included children with normal bone marrow (10 patients). Bone marrow aspiration (BMA) was performed at diagnosis (day -7) in all groups, and at day 0 (end of PRD window) for patients with ALL (PRD and PTX groups). Apoptosis was evaluated by flow cytometry (FC) using Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) stains. Statistical analysis was performed using the Mann-Whitney U test. Apoptotic index at day -7 was similar in all groups. However, at day 0 post-treatment, apoptosis was significantly higher in the PTX group than in the PRD group (p < 0.001). There were no serious adverse effects associated with PTX. PTX potentiates blast apoptosis induced by PRD in children with ALL during steroid window phase.

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.

Controlled randomized clinical trial of spirituality integrated psychotherapy, cognitive-behavioral therapy and medication intervention on depressive symptoms and dysfunctional attitudes in patients with dysthymic disorder.

PubMed

Ebrahimi, Amrollah; Neshatdoost, Hamid Taher; Mousavi, Seyed Ghafur; Asadollahi, Ghorban Ali; Nasiri, Hamid

2013-01-01

Due to the controversy over efficacy of cognitive-behavioral therapy for chronic depression, recently, there has been an increasingly tendency toward therapeutic methods based on the cultural and spiritual approaches. The aim of this research was to compare efficacy of spiritual integrated psychotherapy (SIPT) and cognitive-behavioral therapy (CBT) on the intensity of depression symptoms and dysfunctional attitudes of patients with dysthymic disorder. This study had a mixed qualitative and quantitative design. In the first phase, SIPT model was prepared and, in the second phase, a double-blind random clinical trial was performed. Sixty-two patients with dysthymic disorder were selected from several centers include Nour and Alzahra Medical Center, Counseling Centers of Isfahan University of Medical Sciences and Goldis in Isfahan. The participants were randomly assigned to three experimental groups and one control group. The first group received 8 sessions treatment of SIPT, second groups also had 8 sessions of cognitive-behavioral therapy, which was specific to dysthymic disorder and third group were under antidepressant treatment. Beck depression inventory and dysfunctional attitudes scale were used to evaluate all the participants in four measurement stages. The data were analyzed using MANCOVA repeated measure method. The results revealed that SIPT had more efficacy than medication based on both scales (P < 0.01); however, it was not different from CBT. SIPT was more effective on the modification of dysfunctional attitudes compared with CBT and medication (P < 0.05). These findings supported the efficacy of psychotherapy enriched with cultural capacities and religious teachings.

Psychosocial intervention in at-risk adolescents: using event-related potentials to assess changes in decision making and feedback processing.

PubMed

Pincham, H L; Bryce, D; Fonagy, P; Fearon, R M Pasco

2018-05-25

Decision making and feedback processing are two important cognitive processes that are impacted by social context, particularly during adolescence. The current study examined whether a psychosocial intervention could improve psychological wellbeing in at-risk adolescent boys, thereby improving their decision making and feedback processing skills. Two groups of at-risk adolescents were compared: those who were relatively new to a psychosocial intervention, and those who had engaged over a longer time period. Electroencephalography was recorded while the young people participated in a modified version of the Taylor Aggression Paradigm. The late positive potential (LPP) was measured during the decision phase of the task (where participants selected punishments for their opponents). The feedback-related negativity (FRN) and P3 components were measured during the task's outcome phase (where participants received 'win' or 'lose' feedback). Adolescents who were new to the intervention (the minimal-intervention group) were harsher in their punishment selections than those who had been engaged in the program for much longer. The minimal-intervention group also showed an enhanced LPP during the decision phase of the task, which may be indicative of immature decision making in that group. Analysis of the FRN and P3 amplitudes revealed that the minimal-intervention group was physiologically hypo-sensitive to feedback, compared with the extended-intervention group. Overall, these findings suggest that long-term community-based psychosocial intervention programs are beneficial for at-risk adolescents, and that event-related potentials can be employed as biomarkers of therapeutic change. However, because participants were not randomly allocated to treatment groups, alternative explanations cannot be excluded until further randomized controlled trials are undertaken.

A randomized controlled trial of acupuncture and moxibustion to treat Bell's palsy according to different stages: design and protocol.

PubMed

Chen, Xiaoqin; Li, Ying; Zheng, Hui; Hu, Kaming; Zhang, Hongxing; Zhao, Ling; Li, Yan; Liu, Lian; Mang, Lingling; Yu, Shuyuan

2009-07-01

Acupuncture to treat Bell's palsy is one of the most commonly used methods in China. There are a variety of acupuncture treatment options to treat Bell's palsy in clinical practice. Since Bell's palsy has three different path-stages (acute stage, resting stage and restoration stage), so whether acupuncture is effective in the different path-stages and which acupuncture treatment is the best method are major issues in acupuncture clinical trials about Bell's palsy. In this article, we report the design and protocol of a large sample multi-center randomized controlled trial to treat Bell's palsy with acupuncture. There are five acupuncture groups, with four according to different path-stages and one not. In total, 900 patients with Bell's palsy are enrolled in this study. These patients are randomly assigned to receive one of the following four treatment groups according to different path-stages, i.e. 1) staging acupuncture group, 2) staging acupuncture and moxibustion group, 3) staging electro-acupuncture group, 4) staging acupuncture along yangming musculature group or non-staging acupuncture control group. The outcome measurements in this trial are the effect comparison achieved among these five groups in terms of House-Brackmann scale (Global Score and Regional Score), Facial Disability Index scale, Classification scale of Facial Paralysis, and WHOQOL-BREF scale before randomization (baseline phase) and after randomization. The result of this trial will certify the efficacy of using staging acupuncture and moxibustion to treat Bell's palsy, and to approach a best acupuncture treatment among these five different methods for treating Bell's palsy.

Phase behaviors of supramolecular graft copolymers with reversible bonding

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

Zhang, Xu; Wang, Liquan, E-mail: jlin@ecust.edu.cn, E-mail: lq-wang@ecust.edu.cn; Jiang, Tao

2013-11-14

Phase behaviors of supramolecular graft copolymers with reversible bonding interactions were examined by the random-phase approximation and real-space implemented self-consistent field theory. The studied supramolecular graft copolymers consist of two different types of mutually incompatible yet reactive homopolymers, where one homopolymer (backbone) possesses multifunctional groups that allow second homopolymers (grafts) to be placed on. The calculations carried out show that the bonding strength exerts a pronounced effect on the phase behaviors of supramolecular graft copolymers. The length ratio of backbone to graft and the positions of functional groups along the backbone are also of importance to determine the phase behaviors.more » Phase diagrams were constructed at high bonding strength to illustrate this architectural dependence. It was found that the excess unbounded homopolymers swell the phase domains and shift the phase boundaries. The results were finally compared with the available experimental observations, and a well agreement is shown. The present work could, in principle, provide a general understanding of the phase behaviors of supramolecular graft copolymers with reversible bonding.« less

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.

Contextual Interference in Complex Bimanual Skill Learning Leads to Better Skill Persistence

PubMed Central

Pauwels, Lisa; Swinnen, Stephan P.; Beets, Iseult A. M.

2014-01-01

The contextual interference (CI) effect is a robust phenomenon in the (motor) skill learning literature. However, CI has yielded mixed results in complex task learning. The current study addressed whether the CI effect is generalizable to bimanual skill learning, with a focus on the temporal evolution of memory processes. In contrast to previous studies, an extensive training schedule, distributed across multiple days of practice, was provided. Participants practiced three frequency ratios across three practice days following either a blocked or random practice schedule. During the acquisition phase, better overall performance for the blocked practice group was observed, but this difference diminished as practice progressed. At immediate and delayed retention, the random practice group outperformed the blocked practice group, except for the most difficult frequency ratio. Our main finding is that the random practice group showed superior performance persistence over a one week time interval in all three frequency ratios compared to the blocked practice group. This study contributes to our understanding of learning, consolidation and memory of complex motor skills, which helps optimizing training protocols in future studies and rehabilitation settings. PMID:24960171

Adaptive goal setting and financial incentives: a 2 × 2 factorial randomized controlled trial to increase adults' physical activity.

PubMed

Adams, Marc A; Hurley, Jane C; Todd, Michael; Bhuiyan, Nishat; Jarrett, Catherine L; Tucker, Wesley J; Hollingshead, Kevin E; Angadi, Siddhartha S

2017-03-29

Emerging interventions that rely on and harness variability in behavior to adapt to individual performance over time may outperform interventions that prescribe static goals (e.g., 10,000 steps/day). The purpose of this factorial trial was to compare adaptive vs. static goal setting and immediate vs. delayed, non-contingent financial rewards for increasing free-living physical activity (PA). A 4-month 2 × 2 factorial randomized controlled trial tested main effects for goal setting (adaptive vs. static goals) and rewards (immediate vs. delayed) and interactions between factors to increase steps/day as measured by a Fitbit Zip. Moderate-to-vigorous PA (MVPA) minutes/day was examined as a secondary outcome. Participants (N = 96) were mainly female (77%), aged 41 ± 9.5 years, and all were insufficiently active and overweight/obese (mean BMI = 34.1 ± 6.2). Participants across all groups increased by 2389 steps/day on average from baseline to intervention phase (p < .001). Participants receiving static goals showed a stronger increase in steps per day from baseline phase to intervention phase (2630 steps/day) than those receiving adaptive goals (2149 steps/day; difference = 482 steps/day, p = .095). Participants receiving immediate rewards showed stronger improvement (2762 step/day increase) from baseline to intervention phase than those receiving delayed rewards (2016 steps/day increase; difference = 746 steps/day, p = .009). However, the adaptive goals group showed a slower decrease in steps/day from the beginning of the intervention phase to the end of the intervention phase (i.e. less than half the rate) compared to the static goals group (-7.7 steps vs. -18.3 steps each day; difference = 10.7 steps/day, p < .001) resulting in better improvements for the adaptive goals group by study end. Rate of change over the intervention phase did not differ between reward groups. Significant goal phase x goal setting x reward interactions were observed. Adaptive goals outperformed static goals (i.e., 10,000 steps) over a 4-month period. Small immediate rewards outperformed larger, delayed rewards. Adaptive goals with either immediate or delayed rewards should be preferred for promoting PA. ClinicalTrials.gov ID: NCT02053259 registered prospectively on January 31, 2014.

Preparing Brigade Combat Team Soldiers for Mission Readiness Through Research on Intangible Psychological Constructs and Their Applications: Phase 1

DTIC Science & Technology

2014-02-01

were randomly assigned to treatment groups and examined using a pretest , posttest , and follow-up to evaluate the impact of patient interview and...results of the literature review to inform interview and focus group protocol development for follow on data collection. Literature Review The...similar content or overlapped considerably with one another. Accordingly, similar constructs were grouped under meta- construct headings. A total of

Evaluation of the perioperative analgesic efficacy of buprenorphine, compared with butorphanol, in cats.

PubMed

Warne, Leon N; Beths, Thierry; Holm, Merete; Carter, Jennifer E; Bauquier, Sébastien H

2014-07-15

To compare the analgesic effects of buprenorphine and butorphanol in domestic cats. 2-phase positive-controlled randomized masked clinical trial. 39 healthy female cats (10 in phase 1 and 29 in phase 2). Cats admitted for ovariohysterectomy received buprenorphine (4 in phase 1; 14 in phase 2) or butorphanol (6 in phase 1; 15 in phase 2). In phase 1, cats were premedicated with buprenorphine (0.02 mg/kg [0.009 mg/lb], IM) or butorphanol (0.4 mg/kg [0.18 mg/lb], IM), in combination with medetomidine. Anesthesia was induced with propofol (IV) and maintained with isoflurane in oxygen. After extubation, medetomidine was antagonized with atipamezole. A validated multidimensional composite scale was used to assess signs of pain after surgery starting 20 minutes after extubation and continuing for up to 360 minutes, and pain score comparisons were made between the 2 groups. Phase 2 proceeded similar to phase 1 with the following addition: during wound closure, cats from the butorphanol and buprenorphine groups received butorphanol (0.4 mg/kg, IM) or buprenorphine (0.02 mg/kg, IM), respectively. Phase 1 of the study was stopped after 10 cats were ovariohysterectomized because 9 of 10 cats required rescue analgesia at the first evaluation. In phase 2, at the first pain evaluation, pain scores from the buprenorphine group were lower, and all cats from the butorphanol group required rescue analgesia. None of the cats from the buprenorphine group required rescue analgesia at any time. Buprenorphine (0.02 mg/kg, IM) given before surgery and during wound closure provided adequate analgesia for 6 hours following ovariohysterectomy in cats, whereas butorphanol did not.

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.

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.

A phase III randomized, placebo-controlled, double-blind study of misoprostol rectal suppositories to prevent acute radiation proctitis in patients with prostate cancer

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

Hille, Andrea; Schmidberger, Heinz; Hermann, Robert M.

2005-12-01

Purpose: Acute radiation proctitis is the most relevant complication of pelvic radiation and is still mainly treated supportively. Considering the negative impact of acute proctitis symptoms on patients' daily activities and the potential relationship between the severity of acute radiation injury and late damage, misoprostol was tested in the prevention of acute radiation-induced proctitis. Methods and Materials: A total of 100 patients who underwent radiotherapy for prostate cancer were entered into this phase III randomized, placebo-controlled, double-blind study with misoprostol or placebo suppositories. Radiation-induced toxicity was evaluated weekly during radiotherapy using the Common Toxicity Criteria. Results: Between the placebo andmore » the misoprostol groups, no significant differences in proctitis symptoms occurred: 76% of patients in each group had Grade 1 toxicity, and 26% in the placebo group and 36% in the misoprostol group had Grade 2 toxicity. No differences were found in onset or symptom duration. Comparing the peak incidence of patients' toxicity symptoms, significantly more patients experienced rectal bleeding in the misoprostol group (p = 0.03). Conclusion: Misoprostol given as a once-daily suppository did not decrease the incidence and severity of radiation-induced acute proctitis and may increase the incidence of acute bleeding.« less

Effectiveness and cost-effectiveness of a health coaching intervention to improve the lifestyle of patients with knee osteoarthritis: cluster randomized clinical trial.

PubMed

Carmona-Terés, Victoria; Lumillo-Gutiérrez, Iris; Jodar-Fernández, Lina; Rodriguez-Blanco, Teresa; Moix-Queraltó, Joanna; Pujol-Ribera, Enriqueta; Mas, Xavier; Batlle-Gualda, Enrique; Gobbo-Montoya, Milena; Berenguera, Anna

2015-02-25

The prevalence of osteoarthritis and knee osteoarthritis in the Spanish population is estimated at 17% and 10.2%, respectively. The clinical guidelines concur that the first line treatment for knee osteoarthritis should be non-pharmacological and include weight loss, physical activity and self-management of pain. Health Coaching has been defined as an intervention that facilitates the achievement of health improvement goals, the reduction of unhealthy lifestyles, the improvement of self-management for chronic conditions and quality of life enhancement. The aim of this study is to analyze the effectiveness, cost-effectiveness and cost-utility of a health coaching intervention on quality of life, pain, overweight and physical activity in patients from 18 primary care centres of Barcelona with knee osteoarthritis. Methodology from the Medical Research Council on developing complex interventions. Phase 1: Intervention modelling and operationalization through a qualitative, socioconstructivist study using theoretical sampling with 10 in-depth interviews to patients with knee osteoarthritis and 4 discussion groups of 8-12 primary care professionals, evaluated using a sociological discourse analysis. Phase 2: Effectiveness, cost-effectiveness and cost-utility study with a community-based randomized clinical trial. 360 patients with knee osteoarthritis (180 in each group). Randomization unit: Primary Care Centre. Intervention Group: will receive standard care plus 20-hour health coaching and follow-up sessions. will receive standard care. quality of life as measured by the WOMAC index. Data Analyses: will include standardized response mean and multilevel analysis of repeated measures. Economic analysis: based on cost-effectiveness and cost-utility measures. Phase 3: Evaluation of the intervention programme with a qualitative study. Methodology as in Phase 1. If the analyses show the cost-effectiveness and cost-utility of the intervention the results can be incorporated into the clinical guidelines for the management of knee osteoarthritis in primary care. ISRCTN57405925. Registred 20 June 2014.

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

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

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.

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.

[Corifollitropin alfa in women stimulated for the first time in in vitro fertilization programme].

PubMed

Vraná-Mardešićová, N; Vobořil, J; Melicharová, L; Jelínková, L; Vilímová, Š; Mardešić, T

2017-01-01

To compare results after stimulation with corifollitropin alfa (Elonva) in unselected group of women entering for the first time in in vitro fertilization programme (IVF) with results from Phase III randomized trials with selected groups of women. Prospective study. Sanatorium Pronatal, Praha. 40 unselected women with adequat ovarian reserve entering for the first time in IVF programme were stimulated with corifollitropin alfa and GnRH antagonists. Avarage age in the study group was 32,8 years (29-42 years), women younger then 36 and less then 60 kg received Elonva 100 µg , all others (age > 36 let, weight > 60 kg) Elonva 150 µg. Five days after egg retrieval one blastocyst was transferred (single embryo transfer - eSET). Our results were compared with the resuls in higly selected groups of women from Phase III randomized trials. After stimulation with corifollitropin alfa and GnRH antagonists on average 10,6 (9,2 ± 4,2) eggs could be retrieved, among them 7,3 (6,6 ± 3,9) were M II oocytes (68,9%) and fertilisation rate was 84,6%. After first embryo transfer ("fresh" embryos and embryos from "freeze all" cycles) 14 pregnancies were achieved (37,8%), three pregnancies were achieved later from transfer of frozen-thawed embryos (cumulative pregnancy rate 45,9%). There were three abortions. No severe hyperstimulation syndrom occured. Our results in unselected group of women stimulated for the first in an IVF programme with corifollitropin alfa are fully comparable with results published in randomized trials with selected group of patiens. Corifollitropin alfa in combination with daily GnRH antagonist can be successfully used in normal-responder patients stimulated for the first time in an IVF programmeKeywords: corifollitropin alfa, GnRH antagonists, ovarian stimulation, pregnancy.

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

Effect of Antidepressant Switching vs Augmentation on Remission Among Patients With Major Depressive Disorder Unresponsive to Antidepressant Treatment: The VAST-D Randomized Clinical Trial.

PubMed

Mohamed, Somaia; Johnson, Gary R; Chen, Peijun; Hicks, Paul B; Davis, Lori L; Yoon, Jean; Gleason, Theresa C; Vertrees, Julia E; Weingart, Kimberly; Tal, Ilanit; Scrymgeour, Alexandra; Lawrence, David D; Planeta, Beata; Thase, Michael E; Huang, Grant D; Zisook, Sidney; Rao, Sanjai D; Pilkinton, Patricia D; Wilcox, James A; Iranmanesh, Ali; Sapra, Mamta; Jurjus, George; Michalets, James P; Aslam, Muhammed; Beresford, Thomas; Anderson, Keith D; Fernando, Ronald; Ramaswamy, Sriram; Kasckow, John; Westermeyer, Joseph; Yoon, Gihyun; D'Souza, D Cyril; Larson, Gunnar; Anderson, William G; Klatt, Mary; Fareed, Ayman; Thompson, Shabnam I; Carrera, Carlos J; Williams, Solomon S; Juergens, Timothy M; Albers, Lawrence J; Nasdahl, Clifford S; Villarreal, Gerardo; Winston, Julia L; Nogues, Cristobal A; Connolly, K Ryan; Tapp, Andre; Jones, Kari A; Khatkhate, Gauri; Marri, Sheetal; Suppes, Trisha; LaMotte, Joseph; Hurley, Robin; Mayeda, Aimee R; Niculescu, Alexander B; Fischer, Bernard A; Loreck, David J; Rosenlicht, Nicholas; Lieske, Steven; Finkel, Mitchell S; Little, John T

2017-07-11

Less than one-third of patients with major depressive disorder (MDD) achieve remission with their first antidepressant. To determine the relative effectiveness and safety of 3 common alternate treatments for MDD. From December 2012 to May 2015, 1522 patients at 35 US Veterans Health Administration medical centers who were diagnosed with nonpsychotic MDD, unresponsive to at least 1 antidepressant course meeting minimal standards for treatment dose and duration, participated in the study. Patients were randomly assigned (1:1:1) to 1 of 3 treatments and evaluated for up to 36 weeks. Switch to a different antidepressant, bupropion (switch group, n = 511); augment current treatment with bupropion (augment-bupropion group, n = 506); or augment with an atypical antipsychotic, aripiprazole (augment-aripiprazole group, n = 505) for 12 weeks (acute treatment phase) and up to 36 weeks for longer-term follow-up (continuation phase). The primary outcome was remission during the acute treatment phase (16-item Quick Inventory of Depressive Symptomatology-Clinician Rated [QIDS-C16] score ≤5 at 2 consecutive visits). Secondary outcomes included response (≥50% reduction in QIDS-C16 score or improvement on the Clinical Global Impression Improvement scale), relapse, and adverse effects. Among 1522 randomized patients (mean age, 54.4 years; men, 1296 [85.2%]), 1137 (74.7%) completed the acute treatment phase. Remission rates at 12 weeks were 22.3% (n = 114) for the switch group, 26.9% (n = 136)for the augment-bupropion group, and 28.9% (n = 146) for the augment-aripiprazole group. The augment-aripiprazole group exceeded the switch group in remission (relative risk [RR], 1.30 [95% CI, 1.05-1.60]; P = .02), but other remission comparisons were not significant. Response was greater for the augment-aripiprazole group (74.3%) than for either the switch group (62.4%; RR, 1.19 [95% CI, 1.09-1.29]) or the augment-bupropion group (65.6%; RR, 1.13 [95% CI, 1.04-1.23]). No significant treatment differences were observed for relapse. Anxiety was more frequent in the 2 bupropion groups (24.3% in the switch group [n = 124] vs 16.6% in the augment-aripiprazole group [n = 84]; and 22.5% in augment-bupropion group [n = 114]). Adverse effects more frequent in the augment-aripiprazole group included somnolence, akathisia, and weight gain. Among a predominantly male population with major depressive disorder unresponsive to antidepressant treatment, augmentation with aripiprazole resulted in a statistically significant but only modestly increased likelihood of remission during 12 weeks of treatment compared with switching to bupropion monotherapy. Given the small effect size and adverse effects associated with aripiprazole, further analysis including cost-effectiveness is needed to understand the net utility of this approach. clinicaltrials.gov Identifier: NCT01421342.

Pegvaliase for the treatment of phenylketonuria: A pivotal, double-blind randomized discontinuation Phase 3 clinical trial.

PubMed

Harding, Cary O; Amato, R Stephen; Stuy, Mary; Longo, Nicola; Burton, Barbara K; Posner, John; Weng, Haoling H; Merilainen, Markus; Gu, Zhonghua; Jiang, Joy; Vockley, Jerry

2018-05-01

Pegvaliase is a recombinant Anabaena variabilis phenylalanine ammonia lyase (PAL) enzyme under investigation for treatment of adult phenylketonuria (PKU). This manuscript describes results of a randomized discontinuation trial (RDT) designed to evaluate the effects of pegvaliase treatment on blood phenylalanine (Phe) and neuropsychiatric outcomes in adults with PKU. PRISM-2 is a 4-part, Phase 3 study that enrolled adults with PKU receiving pegvaliase treatment (initiated in a prior Phase 2 or Phase 3 study). The RDT, Part 2 of PRISM-2, was an 8-week trial that evaluated change in blood Phe concentrations, neuropsychiatric and neurocognitive measures, and safety outcomes in PRISM-2 participants who had achieved at least a 20% blood Phe reduction from pre-treatment baseline with pegvaliase treatment. Participants were randomized 2:1 to either continue pegvaliase (20 mg/day or 40 mg/day) or switch to matching placebo. The pooled pegvaliase group enrolled 66 participants and each placebo group enrolled 14 participants. The primary endpoint of change in blood Phe concentration from RDT entry to RDT Week 8 was met with clinically meaningful and statistically significant differences between the pegvaliase and placebo groups. Mean (SD) blood Phe at the beginning of the RDT when all participants were receiving pegvaliase was 563.9 μM (504.6) in the group assigned to the 20 mg/day placebo group (n = 14), 508.2 μM (363.7) in those assigned to the 40 mg/day placebo group (n = 14), and 503.9 μM (520.3) in those assigned to continue pegvaliase treatment (n = 58). At Week 8 of the RDT, the least squares mean change (95% confidence interval) in blood Phe was 949.8 μM (760.4 to 1139.1) for the 20 mg/day placebo group and 664.8 μM (465.5 to 864.1) for the 40 mg/day placebo group in comparison to 26.5 μM (-68.3 to 121.3) for the pooled (20 mg/day and 40 mg/day) pegvaliase group (P < 0.0001 for pooled pegvaliase group vs each placebo group). Adverse events (AEs) were usually lower in the pooled placebo group when compared to the pooled pegvaliase group. The most common AEs for the pooled pegvaliase and pooled placebo groups were arthralgia (13.6% and 10.3%, respectively), headache (12.1% and 24.1%), anxiety (10.6% and 6.9%), fatigue (10.6% and 10.3%), and upper respiratory tract infection (1.5% and 17.2%). Mean blood Phe reduction was sustained in the pegvaliase group, while placebo groups had mean blood Phe concentration increase toward pre-treatment baseline levels. Results from this study confirmed the efficacy of pegvaliase in maintaining reduced blood Phe concentrations with a manageable safety profile for most participants. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Curcumin supplementation ameliorated vascular dysfunction and improved antioxidant status in rats fed a high-sucrose, high-fat diet.

PubMed

Tsai, I-Jung; Chen, Chia-Wen; Tsai, Shin-Yu; Wang, Pei-Yuan; Owaga, Eddy; Hsieh, Rong-Hong

2018-01-29

Vascular endothelial dysfunction is a potential risk factor for cardiovascular disease. This study evaluated the effect of curcumin on factors associated with vascular dysfunction using rats fed a high-sucrose, high-fat (HSF) diet. The experiment included 2 animal feeding phases. In the first feeding phase, male Sprague-Dawley rats were randomly divided into 2 groups: the control group (n = 8) was fed a standard diet (AIN-93G) and the HSF group (n = 24) was fed an HSF diet for 8 weeks to induce obesity. In the second feeding phase, lasting 4 weeks, the HSF group was randomly divided into 3 subgroups: the O group (n = 8) continued feeding on the HSF diet, the OA group (n = 8) had the HSF diet replaced with AIN-93G, and the OC group (n = 8) was fed the HSF diet supplemented with curcumin (300 mg/kg body weight daily). After 8 weeks, the HSF diet significantly elevated levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), insulin, homeostatic model assessment insulin resistance (HOMA-IR), low-density lipoprotein cholesterol (LDL-C), homocysteine (Hcy), C-reactive protein (CRP), vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1) but significantly reduced levels of nitric oxide (NO) and high-density lipoprotein cholesterol (HDL-C). After dietary intervention, the OA and OC groups exhibited significantly lower levels of AST, ALT, HOMA-IR, cholesterol, LDL-C, Hcy, CRP, VCAM-1, and ICAM-1 and higher levels of NO and catalase (CAT) activity compared with the O group. Superoxide dismutase, CAT, and glutathione peroxidase activities were increased in the OA group, while CAT levels were enhanced in the OC group. In conclusion, this study showed that curcumin supplementation and diet modification can inhibit HSF diet-induced vascular dysfunction potentially by enhancing NO production and antioxidant enzyme activities, thereby suppressing inflammation and oxidative damage in the vascular endothelium.

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

[The effect of various methods of luteal phase supplementation on serum progesterone level].

PubMed

Jakiel, G; Bokiniec, M; Bakalczuk, S; Jakubczak, A; Mroczkowski, A

1998-12-01

Examined was the effect of luteal phase supplementation on serum progesterone level with the use of two methods: oral administration of 10 mg dydrogesterone twice daily since the detection of corpus luteum till the menstruation and intramuscular HCG administration in the dose 1500 IU every 4 days and 10 mg dydrogesterone twice daily in the same period. A randomized study, controlled by placebo. 56 infertile women, with luteal phase deficiency assessed on the basis of basal body temperature (decrease shortly after the peak the luteal phase shorter than 11 days) and ovulation determined sonographically. Progesterone was evaluated by an EIA method, on the 3rd, 7th and 11th day since the corpus luteum occurred. The peak of progesterone concentration was assessed in the midluteal phase (7th day) in both supplemented groups, significantly higher than in the placebo group, also in group with dydrogesterone and HCG it was higher than in group with dydrogesterone alone. Progesterone concentration decrease on the 11th day after the ovulation to the values comparable with the placebo group. It has been found that both methods increase serum progesterone level in the time of an assumed implantation but they do not affect the premenstrual period if conception is not achieved.

Randomized study of adjunctive belimumab in participants with generalized myasthenia gravis

PubMed Central

Hewett, Karen; Sanders, Donald B.; Grove, Richard A.; Broderick, Christine L.; Rudo, Todd J.; Bassiri, Ashlyn; Zvartau-Hind, Marina

2018-01-01

Objective To investigate the efficacy and safety of belimumab, a fully human immunoglobulin G1λ monoclonal antibody against B-lymphocyte stimulator, in participants with generalized myasthenia gravis (MG) who remained symptomatic despite standard of care (SoC) therapy. Methods Eligible participants with MG were randomized 1:1 to receive IV belimumab 10 mg/kg or placebo in this phase II, placebo-controlled, multicenter, double-blind study (NCT01480596; BEL115123). Participants received SoC therapies throughout the 24-week treatment phase and 12-week follow-up period. The primary efficacy endpoint was mean change from baseline in the Quantitative Myasthenia Gravis (QMG) scale at week 24; safety assessments included the frequency and severity of adverse events (AEs) and serious AEs. Results Forty participants were randomized (placebo n = 22; belimumab n = 18). The mean change in QMG score from baseline at week 24 was not significantly different for belimumab vs placebo (p = 0.256). There were no statistically significant differences between treatment groups for secondary endpoints, including the MG Composite and MG–Activity of Daily Living scores. Acetylcholine receptor antibody levels decreased over time in both treatment groups. No unexpected AEs were identified and occurrence was similar in the belimumab (78%) and placebo (91%) groups. One participant receiving placebo died (severe sepsis) during the treatment phase. Conclusions The primary endpoint was not met for belimumab in participants with generalized MG receiving SoC. There was no significant difference in mean change in the QMG score at week 24 for belimumab vs placebo. The safety profile of belimumab was consistent with previous systemic lupus erythematosus studies. Classification of evidence This study provides Class I evidence that for participants with generalized MG, belimumab did not significantly improve QMG score compared with placebo. PMID:29661905

Step by step: The feasibility of a 16-week workplace lunchtime walking intervention for physically inactive employees.

PubMed

Thøgersen-Ntoumani, Cecilie; Loughren, Elizabeth; Duda, Joan; Fox, Kenneth Richard

2014-09-01

A 16-week lunchtime walking intervention was designed to increase physical activity in physically inactive University employees. The program was delivered and monitored twice over 7 months to examine feasibility across different seasons. Seventy-five participants (n = 69 females, n = 6 males; mean age = 47.68) were randomly allocated into a Winter (February start) or Spring group (May start). Participants were asked to complete 3 weekday lunchtime walks and 2 weekend walks. Weeks 1 to 10 were led by walk leaders (group phase) while the participants self-organized their walks during weeks 11 to 16 (independent phase). Yamax pedometers recorded daily step counts and walk group leaders recorded participant attendance in the group phase. Acceptability was assessed via a satisfaction survey and 2 focus groups with participants. A participant pool representative by ethnicity, but not gender was recruited using a range of strategies. The program demonstrated good retention across both groups (73%). The intervention was acceptable to participants. More steps were accumulated in the group-led versus the independent phase. The intervention is feasible in this workplace setting across different seasonal periods. In the future, researchers should examine if the findings can be replicated in a definitive trial and generalize to other workplace settings.

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.

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.

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…

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.

The Design of Phase II Clinical Trials Testing Cancer Therapeutics: Consensus Recommendations from the Clinical Trial Design Task Force of the National Cancer Institute Investigational Drug Steering Committee

PubMed Central

Seymour, Lesley; Ivy, S. Percy; Sargent, Daniel; Spriggs, David; Baker, Laurence; Rubinstein, Larry; Ratain, Mark J; Le Blanc, Michael; Stewart, David; Crowley, John; Groshen, Susan; Humphrey, Jeffrey S; West, Pamela; Berry, Donald

2010-01-01

The optimal design of phase II studies continues to be the subject of vigorous debate, especially with regards to studies of newer molecularly targeted agents. The observations that many new therapeutics ‘fail’ in definitive phase III studies, coupled with the numbers of new agents to be tested as well as the increasing costs and complexity of clinical trials further emphasizes the critical importance of robust and efficient phase II design. The Clinical Trial Design Task Force(CTD-TF)of the NCI Investigational Drug Steering Committee (IDSC) has published a series of discussion papers on Phase II trial design in Clinical Cancer Research. The IDSC has developed formal recommendations regarding aspects of phase II trial design which are the subject of frequent debate such as endpoints(response vs. progression free survival), randomization(single arm designs vs. randomization), inclusion of biomarkers, biomarker based patient enrichment strategies, and statistical design(e.g. two stage designs vs. multiple-group adaptive designs). While these recommendations in general encourage the use of progression-free survival as the primary endpoint, the use of randomization, the inclusion of biomarkers and the incorporation of newer designs, we acknowledge that objective response as an endpoint, and single arm designs, remain relevant in certain situations. The design of any clinical trial should always be carefully evaluated and justified based on the characteristic specific to the situation. PMID:20215557

Can Radiation Dose Be Reduced and Image Quality Improved With 80-kV and Dual-Phase Scanning of the Lower Extremities With 64-Slice Computed Tomography Angiography?

PubMed

Zhou, Yunfeng; Wang, Juan; Dassarath, Meera; Wang, Minhong; Zhang, Qiang; Xiong, Yuwei; Yuan, Quan

2015-01-01

To prospectively compare the new computed tomographic angiography (CTA) protocol (NCP) using 80-kV and dual-phase scanning with the routine CTA protocol (RCP) using 120-kV and single-phase scanning in patients with peripheral arterial disease. A total of 60 patients were randomized to undergo the NCP (30 patients) or RCP (30 patients) scan. We compared the arterial attenuation values, overriding of the contrast bolus, signal-to-noise ratio, and radiation dose between 2 groups. The occurrence rate of contrast bolus overriding was not statistically significant (P = 0.69). The average arterial attenuation value in the NCP group was significantly higher (P < 0.05) than that in the RCP group. The radiation dose in the RCP group was significantly higher (P < 0.001) than that in the NCP group. The mean signal-to-noise ratio in the NCP group was significantly lower (P < 0.001). Sixty-four-slice CTA with the NCP can significantly reduce the radiation dose and improve the arterial enhancement and calf arteries imaging.

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.

Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial.

PubMed

Breugom, A J; van Gijn, W; Muller, E W; Berglund, Å; van den Broek, C B M; Fokstuen, T; Gelderblom, H; Kapiteijn, E; Leer, J W H; Marijnen, C A M; Martijn, H; Meershoek-Klein Kranenbarg, E; Nagtegaal, I D; Påhlman, L; Punt, C J A; Putter, H; Roodvoets, A G H; Rutten, H J T; Steup, W H; Glimelius, B; van de Velde, C J H

2015-04-01

The discussion on the role of adjuvant chemotherapy for rectal cancer patients treated according to current guidelines is still ongoing. A multicentre, randomized phase III trial, PROCTOR-SCRIPT, was conducted to compare adjuvant chemotherapy with observation for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision (TME). The PROCTOR-SCRIPT trial recruited patients from 52 hospitals. Patients with histologically proven stage II or III rectal adenocarcinoma were randomly assigned (1:1) to observation or adjuvant chemotherapy after preoperative (chemo)radiotherapy and TME. Radiotherapy consisted of 5 × 5 Gy. Chemoradiotherapy consisted of 25 × 1.8-2 Gy combined with 5-FU-based chemotherapy. Adjuvant chemotherapy consisted of 5-FU/LV (PROCTOR) or eight courses capecitabine (SCRIPT). Randomization was based on permuted blocks of six, stratified according to centre, residual tumour, time between last irradiation and surgery, and preoperative treatment. The primary end point was overall survival. Of 470 enrolled patients, 437 were eligible. The trial closed prematurely because of slow patient accrual. Patients were randomly assigned to observation (n = 221) or adjuvant chemotherapy (n = 216). After a median follow-up of 5.0 years, 5-year overall survival was 79.2% in the observation group and 80.4% in the chemotherapy group [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.62-1.39; P = 0.73]. The HR for disease-free survival was 0.80 (95% CI 0.60-1.07; P = 0.13). Five-year cumulative incidence for locoregional recurrences was 7.8% in both groups. Five-year cumulative incidence for distant recurrences was 38.5% and 34.7%, respectively (P = 0.39). The PROCTOR-SCRIPT trial could not demonstrate a significant benefit of adjuvant chemotherapy with fluoropyrimidine monotherapy after preoperative (chemo)radiotherapy and TME on overall survival, disease-free survival, and recurrence rate. However, this trial did not complete planned accrual. Dutch Colorectal Cancer group, CKTO 2003-16, ISRCTN36266738. © 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.

Cuffed endotracheal tubes in children: the effect of the size of the cuffed endotracheal tube on intracuff pressure.

PubMed

Krishna, Senthil G; Hakim, Mumin; Sebastian, Roby; Dellinger, Heather L; Tumin, Dmitry; Tobias, Joseph D

2017-05-01

In children, the size of the cuffed endotracheal tube is based on various age-based formulas. However, such formulas may over or underestimate the size of the cuffed endotracheal tube. There are no data on the impact of different-sized cuffed endotracheal tubes (ETT) on the intracuff pressure in children. The current study measures intracuff pressure with different-sized cuffed ETT. The study was conducted in an in vitro and in vivo phase. For the in vitro phase, 10 cuffed ETT of size 4.0, 4.5, and 5 mm internal diameter (ID) each were randomly placed inside a 1.0 cm ID plastic tube (mimicking the trachea), which was in turn connected to a 1 l test lung. After inflation of the cuff using the air leak test at a continuous positive airway pressure of 20 cmH 2 O, the intracuff pressure was measured. The in vivo phase was conducted in 100 children (4-8 years) and were randomly divided into two groups to receive either a cuffed endotracheal tube based on the Khine formula (Group R) or a cuffed endotracheal tube that was a half-size (0.5 mm ID) smaller (Group S). Following the inflation of the cuff to seal the trachea, the intracuff pressure was measured. In the in vitro phase, the intracuff pressure was 45 ± 6, 23 ± 1, and 14 ± 6 cmH 2 O with size 4.0, 4.5, and 5 mm ID cuffed ETT, respectively (F-test P < 0.001 for difference among three groups). In the in vivo phase, the mean intracuff pressure in Group R was 25 ± 19 cmH 2 O vs 37 ± 35 cmH 2 O in Group S (95% CI of difference: 1, 23; P = 0.039). If the cuffed endotracheal tube is too small, the trachea can still be sealed by inflating the cuff with additional air. However, this transforms the cuff from the intended high-volume, low-pressure cuff to an undesirable high-volume, high-pressure cuff. © 2017 John Wiley & Sons Ltd.

Sustained efficacy of insulin pump therapy compared with multiple daily injections in type 2 diabetes: 12-month data from the OpT2mise randomized trial.

PubMed

Aronson, R; Reznik, Y; Conget, I; Castañeda, J A; Runzis, S; Lee, S W; Cohen, O

2016-05-01

To compare insulin pump therapy and multiple daily injections (MDI) in patients with type 2 diabetes receiving basal and prandial insulin analogues. After a 2-month dose-optimization period, 331 patients with glycated haemoglobin (HbA1c) levels ≥8.0% and ≤12% were randomized to pump therapy or continued MDI for 6 months [randomization phase (RP)]. The MDI group was subsequently switched to pump therapy during a 6-month continuation phase (CP). The primary endpoint was the between-group difference in change in mean HbA1c from baseline to the end of the RP. The mean HbA1c at baseline was 9% in both groups. At the end of the RP, the reduction in HbA1c was significantly greater with pump therapy than with MDI (-1.1 ± 1.2% vs -0.4 ± 1.1%; p < 0.001). The pump therapy group maintained this improvement to 12 months while the MDI group, which was switched to pump therapy, showed a 0.8% reduction: the final HbA1c level was identical in both arms. In the RP, total daily insulin dose (TDD) was 20.4% lower with pump therapy than with MDI and remained stable in the CP. The MDI-pump group showed a 19% decline in TDD, such that by 12 months TDD was equivalent in both groups. There were no differences in weight gain or ketoacidosis between groups. In the CP, one patient in each group experienced severe hypoglycaemia. Pump therapy has a sustained durable effect on glycaemic control in uncontrolled type 2 diabetes. © 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Sustained efficacy of insulin pump therapy compared with multiple daily injections in type 2 diabetes: 12‐month data from the OpT2mise randomized trial

PubMed Central

Reznik, Y.; Conget, I.; Castañeda, J. A.; Runzis, S.; Lee, S. W.; Cohen, O.

2016-01-01

Aims To compare insulin pump therapy and multiple daily injections (MDI) in patients with type 2 diabetes receiving basal and prandial insulin analogues. Methods After a 2‐month dose‐optimization period, 331 patients with glycated haemoglobin (HbA1c) levels ≥8.0% and ≤12% were randomized to pump therapy or continued MDI for 6 months [randomization phase (RP)]. The MDI group was subsequently switched to pump therapy during a 6‐month continuation phase (CP). The primary endpoint was the between‐group difference in change in mean HbA1c from baseline to the end of the RP. Results The mean HbA1c at baseline was 9% in both groups. At the end of the RP, the reduction in HbA1c was significantly greater with pump therapy than with MDI (−1.1 ± 1.2% vs −0.4 ± 1.1%; p < 0.001). The pump therapy group maintained this improvement to 12 months while the MDI group, which was switched to pump therapy, showed a 0.8% reduction: the final HbA1c level was identical in both arms. In the RP, total daily insulin dose (TDD) was 20.4% lower with pump therapy than with MDI and remained stable in the CP. The MDI–pump group showed a 19% decline in TDD, such that by 12 months TDD was equivalent in both groups. There were no differences in weight gain or ketoacidosis between groups. In the CP, one patient in each group experienced severe hypoglycaemia. Conclusions Pump therapy has a sustained durable effect on glycaemic control in uncontrolled type 2 diabetes. PMID:26854123

A crossover study of the combination therapy of metformin and exenatide or biphasic insulin aspart 30 in overweight or obese patients newly diagnosed with type 2 diabetes mellitus

PubMed Central

Quan, Huibiao; Zhang, Huachuan; Wei, Weiping; Fang, Tuanyu; Chen, Daoxiong; Chen, Kaining

2017-01-01

The aim of the present study was to explore the effects of various combinations of exenatide, metformin (MET) and biphasic insulin aspart 30 (BIA30) on type 2 diabetes mellitus (T2DM). Two hundred overweight or obese patients newly diagnosed with T2DM were evenly randomized into two groups: A (twice daily for all: Phase I, 5 µg exenatide + 0.5 g MET for 4 weeks, then 10 µg exenatide + 0.5 g MET for 8 weeks; Phase II, 0.5 g MET for 12 weeks; Phase III, 0.3–0.4 U/kg/day BIA30 + 0.5 g MET for 12 weeks) and B (Phases I, II, III matched the phases III, II and I in group A). In groups A and B a significant decrease and increase, respectively, in glycated hemoglobin (HbAlc) and body mass index (BMI) was noted during Phase I. A 3.2±0.4-kg decrease in body weight in group A and a 2.6±0.3-kg increase in group B was observed. In Phase II, HbAlc was significantly increased in both groups (P<0.05). In Phase III, the BMI was increased in group A and reduced in group B (P<0.05). There was a 3.8±0.4-kg weight decrease in group B and 4.2±0.5-kg increase in group A (P<0.05). The combination of exenatide and MET promoted weight loss, glycemic control, β-cell function index, C peptide and adiponectin levels. These results suggested that the combination of exenatide and MET is better than the combination of BIA and MET for the therapy of overweight or obese patients newly diagnosed with T2DM. PMID:28912879

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).

Treatment of plaque-type psoriasis with oral CF101: data from an exploratory randomized phase 2 clinical trial.

PubMed

David, M; Akerman, L; Ziv, M; Kadurina, M; Gospodinov, D; Pavlotsky, F; Yankova, R; Kouzeva, V; Ramon, M; Silverman, M H; Fishman, P

2012-03-01

CF101 demonstrated a marked anti-inflammatory effect in Phase 2 studies conducted in patients with rheumatoid arthritis and dry eye syndrome. The aim of this study was to evaluate the safety and efficacy of CF101 for the treatment of patients with moderate to severe plaque-type psoriasis. This was a phase 2, multicentre, randomized, double-blind, dose-ranging, placebo-controlled study. Seventy five patients with moderate to severe plaque-type psoriasis were enrolled, randomized and treated with CF101 (1, 2, or 4 mg) or placebo administered orally twice daily for 12 weeks. Safety and change from base line of Psoriasis Area and Severity Index (PASI) score and physician's global assessment (PGA) score over 12 weeks. In the 2 mg CF101-treated group, a progressive improvement in the mean change from baseline in the PASI score vs. placebo throughout the study period was observed, with a statistically significant difference on weeks 8 and 12 (P = 0.047; P = 0.031, respectively). In this group, 35.3% of the patients achieved PASI ≥ 50 response, and 23.5% of the patients achieved a PGA score of 0 or 1. CF101 was safe and well tolerated. CF101 was well tolerated and demonstrated clear evidence of efficacy in patients with moderate to severe plaque psoriasis. © 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.

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.

Creative arts therapy improves quality of life for pediatric brain tumor patients receiving outpatient chemotherapy.

PubMed

Madden, Jennifer R; Mowry, Patricia; Gao, Dexiang; Cullen, Patsy McGuire; Foreman, Nicholas K

2010-01-01

This mixed methods pilot study evaluated the effects of the creative arts therapy (CAT) on the quality of life (QOL) of children receiving chemotherapy. A 2-group, repeated measures randomized design compared CAT with a volunteer's attention (n = 16). Statistical analysis of the randomized controlled phase of the study suggested an improvement in the following areas after the CAT: parent report of child's hurt (P = .03) and parent report of child's nausea (P = .0061). A nonrandomized phase, using a different instrument showed improved mood with statistical significance on the Faces Scale (P < .01), and patients were more excited (P < .05), happier (P < .02), and less nervous (P < .02). Provider focus groups revealed positive experiences. Case studies are included to exemplify the therapeutic process. With heightened interest in complementary therapy for children with cancer, future research with a larger sample size is needed to document the impact of incorporating creative arts into the healing process.

The effectiveness of propolis on gingivitis: a randomized controlled trial.

PubMed

Bretz, Walter A; Paulino, Niraldo; Nör, Jacques E; Moreira, Alexandre

2014-12-01

A randomized, double-blind, controlled clinical trial was conducted to evaluate the effectiveness of a propolis rinse on induced gingivitis by using the co-twin study design. Twenty-one twin pairs (n=42) were enrolled in a gingivitis study with oral hygiene promotion (14 days) and gingivitis induction (21 days). During the gingivitis induction phase, one member of the twin pair was randomly assigned to a 2% typified propolis rinse, and the other was assigned a color-matched 0.05% sodium fluoride plus 0.05% cetylpyridinium chloride rinse (positive control). Patients rinsed twice daily with 20 mL for 30 seconds for 21 days. Gingivitis was measured on days -14 (baseline), 0 (after hygiene phase), and 21 (after no-hygiene phase) by using the Papillary Bleeding Score (PBS) and by standard digital imaging of the gum tissues (G-parameter). The 38 persons who completed the study (age 13-22 years) were well balanced according to PBS at baseline and G-parameter after the initial hygiene phase. After 21 days without oral hygiene, the propolis rinse and positive control rinse groups did not differ significantly for average PBS measurements or G-parameter. Use of a 2% typified propolis rinse was equivalent to a positive control rinse during a 21-day no-hygiene period.

Belatacept-based immunosuppression in de novo liver transplant recipients: 1-year experience from a phase II randomized study.

PubMed

Klintmalm, G B; Feng, S; Lake, J R; Vargas, H E; Wekerle, T; Agnes, S; Brown, K A; Nashan, B; Rostaing, L; Meadows-Shropshire, S; Agarwal, M; Harler, M B; Garcia-Valdecasas, J-C

2014-08-01

This exploratory phase II study evaluated the safety and efficacy of belatacept in de novo adult liver transplant recipients. Patients were randomized (N = 260) to one of the following immunosuppressive regimens: (i) basiliximab + belatacept high dose [HD] + mycophenolate mofetil (MMF), (ii) belatacept HD + MMF, (iii) belatacept low dose [LD] + MMF, (iv) tacrolimus + MMF, or (v) tacrolimus alone. All received corticosteroids. Demographic characteristics were similar among groups. The proportion of patients who met the primary end point (composite of acute rejection, graft loss, death by month 6) was higher in the belatacept groups (42–48%) versus tacrolimus groups (15–38%), with the highest number of deaths and grafts losses in the belatacept LD group. By month 12, the proportion surviving with a functioning graft was higher with tacrolimus + MMF (93%) and lower with belatacept LD (67%) versus other groups (90%: basiliximab + belatacept HD; 83%: belatacept HD; 88%: tacrolimus). Mean calculated GFR was 15–34 mL/min higher in belatacept-treated patients at 1 year. Two cases of posttransplant lymphoproliferative disease and one case of progressive multifocal leukoencephalopathy occurred in belatacept-treated patients. Follow-up beyond month 12 revealed an increase in death and graft loss in another belatacept group (belatacept HD), after which the study was terminated.

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.

Multicenter, randomized, controlled trial of virtual-reality simulator training in acquisition of competency in colonoscopy.

PubMed

Cohen, Jonathan; Cohen, Seth A; Vora, Kinjal C; Xue, Xiaonan; Burdick, J Steven; Bank, Simmy; Bini, Edmund J; Bodenheimer, Henry; Cerulli, Maurice; Gerdes, Hans; Greenwald, David; Gress, Frank; Grosman, Irwin; Hawes, Robert; Mullin, Gerard; Mullen, Gerard; Schnoll-Sussman, Felice; Starpoli, Anthony; Stevens, Peter; Tenner, Scott; Villanueva, Gerald

2006-09-01

The GI Mentor is a virtual reality simulator that uses force feedback technology to create a realistic training experience. To define the benefit of training on the GI Mentor on competency acquisition in colonoscopy. Randomized, controlled, blinded, multicenter trial. Academic medical centers with accredited gastroenterology training programs. First-year GI fellows. Subjects were randomized to receive 10 hours of unsupervised training on the GI Mentor or no simulator experience during the first 8 weeks of fellowship. After this period, both groups began performing real colonoscopies. The first 200 colonoscopies performed by each fellow were graded by proctors to measure technical and cognitive success, and patient comfort level during the procedure. A mixed-effects model comparison between the 2 groups of objective and subjective competency scores and patient discomfort in the performance of real colonoscopies over time. Forty-five fellows were randomized from 16 hospitals over 2 years. Fellows in the simulator group had significantly higher objective competency rates during the first 100 cases. A mixed-effects model demonstrated a higher objective competence overall in the simulator group (P < .0001), with the difference between groups being significantly greater during the first 80 cases performed. The median number of cases needed to reach 90% competency was 160 in both groups. The patient comfort level was similar. Fellows who underwent GI Mentor training performed significantly better during the early phase of real colonoscopy training.

Transdermal buprenorphine in the treatment of chronic pain: results of a phase III, multicenter, randomized, double-blind, placebo-controlled study.

PubMed

Sorge, Jürgen; Sittl, Reinhard

2004-11-01

Buprenorphine, a potent opioid analgesic, has been available in parenteral and oral or sublingual(SL) formulations for >25 years. In 2001, the buprenorphine transdermal delivery system (TES) was introduced at 3 release rates (35, 52.5, and 70 microg/h) for the treatment of chronic cancer and noncancer pain. This study compared the analgesic efficacy and tolerability of buprenorphine TES at a release rate of 35 microg/h with those of buprenorphine SL and placebo in patients with severe or very severe chronic cancer or noncancer pain. This multicenter, double-blind, placebo-controlled, parallel-group trial was 1 of 3 Phase III studies involved in the clinical development of buprenorphine TDS. It comprised a 6-day open-label run-in phase in which patients received buprenorphine SL 0.8 to 1.6 mg/d as needed and a double-blind phase in which patients were randomized to receive 3 sequential patches containing buprenorphine TES 35 microg/h or placebo, each lasting 72 hours. Rescue analgesia consisting of buprenorphine SL 02-mg tablets was available as needed throughout the double-blind phase. The main outcome measures were (1) the number of buprenorphine SL tablets required in addition to buprenorphine TES during the double-blind phase compared with the placebo group and compared with the buprenorphine SL requirement during the run-in phase, and (2) patients' assessments of pain intensity, pain relief, and duration of sleep uninterrupted by pain in the double-blind phase compared with the run-in phase. Adverse events were documented throughout the study. One hundred thirty-seven patients were included in the double-blind phase (90 buprenorphine TES, 47 placebo). The buprenorphine TES group included 47 men and 43 women (mean [SD] age, 56.0 [12.1] years), and the placebo group included 23 men and 24 women (mean age, 55.7 [12.9] years). Forty-five patients had cancer-related pain and 92 had noncancer-related pain. The 2 treatment groups were comparable with respect to sex distribution, age, height, and body weight Patients receiving buprenorphine TES significantly reduced their consumption of buprenorphine SL tablets in the double-blind phase compared with patients receiving placebo (reduction of 0.6 [0.4] mg vs 0.4 [0.4] mg; P = 0.03). The relationship between the buprenorphine SL dose in the run-in phase and the number of buprenorphine SL tablets required in the double-blind phase was dose dependent in the active-treatment group only. Patients' assessments of pain intensity and pain relief suggested better analgesia with buprenorphine TES than with placebo, although the differences did not reach statistical significance. The proportion of patients who reported sleeping for >6 hours uninterrupted by pain in the double-blind phase compared with the run-in phase increased by 6.4% in the buprenorphine TDS group (35.6% vs 292%, respectively), compared with a decrease of 5.9% in the placebo group (40.4% vs 463%); no statistical analysis of sleep duration data was performed. Buprenorphine TDS was well tolerated, with adverse events generally similar to those associated with other opioids. The incidence of systemic adverse events in the double-blind phase was similar in the 2 treatment groups (28.9% buprenorphine TDS, 27.6% placebo), with the most common adverse events being nausea, dizziness, and vomiting. After patch removal, skin reactions (mainly mild or moderate pruritus and erythema) were seen in 35.6% of the buprenorphine TDS group and 25.5% of the placebo group. In the population studied, buprenorphine TDS provided adequate pain relief, as well as improvements in pain intensity and duration of pain-free sleep. It may be considered a therapeutic option for the treatment of moderate to severe chronic pain.

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.

Randomized phase 2 study of GMI-1070 in SCD: reduction in time to resolution of vaso-occlusive events and decreased opioid use

PubMed Central

Wun, Ted; McCavit, Timothy L.; De Castro, Laura M.; Krishnamurti, Lakshmanan; Lanzkron, Sophie; Hsu, Lewis L.; Smith, Wally R.; Rhee, Seungshin; Magnani, John L.; Thackray, Helen

2015-01-01

Treatment of vaso-occlusive crises (VOC) or events in sickle cell disease (SCD) remains limited to symptom relief with opioids. Animal models support the effectiveness of the pan-selectin inhibitor GMI-1070 in reducing selectin-mediated cell adhesion and abrogating VOC. We studied GMI-1070 in a prospective multicenter, randomized, placebo-controlled, double-blind, phase 2 study of 76 SCD patients with VOC. Study drug (GMI-1070 or placebo) was given every 12 hours for up to 15 doses. Other treatment was per institutional standard of care. All subjects reached the composite primary end point of resolution of VOC. Although time to reach the composite primary end point was not statistically different between the groups, clinically meaningful reductions in mean and median times to VOC resolution of 41 and 63 hours (28% and 48%, P = .19 for both) were observed in the active treatment group vs the placebo group. As a secondary end point, GMI-1070 appeared safe in acute vaso-occlusion, and adverse events were not different in the two arms. Also in secondary analyses, mean cumulative IV opioid analgesic use was reduced by 83% with GMI-1070 vs placebo (P = .010). These results support a phase 3 study of GMI-1070 (now rivipansel) for SCD VOC. This trial was registered at www.clinicaltrials.gov as #NCT01119833. PMID:25733584

A long-term, phase 2, multicenter, randomized, open-label, comparative safety study of pomaglumetad methionil (LY2140023 monohydrate) versus atypical antipsychotic standard of care in patients with schizophrenia

PubMed Central

2013-01-01

Background We compared the time to discontinuation due to lack of tolerability over 24 weeks in patients suffering from schizophrenia treated with pomaglumetad methionil (LY2140023 monohydrate, the prodrug of metabotropic glutamate 2/3 receptor agonist, LY404039) or standard of care (SOC: olanzapine, risperidone, or aripiprazole). Methods Study HBBR was a multicenter, randomized, open-label study comparing the long-term safety and tolerability of LY2140023 with SOC for schizophrenia. Patients had moderate symptomatology with prominent negative symptoms and evidence of functional impairment. Those who met entry criteria were randomized to open-label treatment with either LY2140023 (target dose: 40 mg twice daily [BID]; n = 130) or SOC (n = 131). Results There was no statistically significant difference between LY2140023 and SOC for time to discontinuation due to lack of tolerability (primary objective; P = .184). The Kaplan-Meier estimates revealed comparable time to event profiles. Only 27% of LY2140023 and 45% of SOC patients completed the 24-week open-label, active treatment phase. Twenty-seven patients (20.8%) in the LY2140023 group and 15 patients (11.5%) in the SOC group discontinued due to lack of efficacy (P = .044). Twenty-three patients (17.7%) in the LY2140023 group and 19 patients (14.5%) in the SOC group discontinued due to adverse events (physician and subject decision combined, P = .505). The incidence of serious adverse events was comparable between groups. LY2140023-treated patients reported significantly more treatment-emergent adverse events of vomiting, agitation, and dyspepsia, while SOC-treated patients reported significantly more akathisia and weight gain. The incidence of treatment-emergent parkinsonism (P = .011) and akathisia (P = .029) was significantly greater in SOC group. Improvement in PANSS total score over the initial 6 to 8 weeks of treatment was similar between groups, but improvement was significantly greater in the SOC group at 24-week endpoint (P = .004). LY2140023 and SOC groups had comparable negative symptom improvement at 24-week endpoint (P = .444). Conclusion These data provide further evidence that the potential antipsychotic LY2140023 monohydrate, with a glutamatergic mechanism of action, may have a unique tolerability profile characterized by a low association with some adverse events such as extrapyramidal symptoms and weight gain that may characterize currently available dopaminergic antipsychotics. Trials registration A Long-term, Phase 2, Multicenter, Randomized, Open-label, Comparative Safety Study of LY2140023 Versus Atypical Antipsychotic Standard of Care in Patients with DSM-IV-TR Schizophrenia ClinicalTrials.gov identifier: NCT00845026. PMID:23694720

Integrated Cognitive Behavioral Therapy Versus Cognitive Processing Therapy for Adults With Depression, Substance Use Disorder, and Trauma.

PubMed

Haller, Moira; Norman, Sonya B; Cummins, Kevin; Trim, Ryan S; Xu, Xiaomin; Cui, Ruifeng; Allard, Carolyn B; Brown, Sandra A; Tate, Susan R

2016-03-01

The comorbidity of substance use disorder (SUD), depression, and PTSD is common among veterans. Prior research has shown that among veterans with SUD and depression, those with PTSD did not maintain cognitive-behavioral treatment gains as well as those without PTSD. Thus, the current study was designed to evaluate whether adding trauma-focused treatment following an initial group-based integrated cognitive behavioral treatment (ICBT) for SUD and depression improved treatment outcomes. Participants were 123 veterans (89% male) recruited from the VA San Diego Healthcare System. All participants received ICBT in twice weekly, group-delivered sessions for 12 weeks (Phase 1). Participants were then randomized to receive 12 sessions of individual follow-up sessions (Phase 2) utilizing either ICBT or cognitive processing therapy that was modified to integrate SUD treatment (CPT-M). Results indicated that PTSD and depression symptoms slightly improved at the end of Phase 1 group ICBT and further improved through Phase 2 individual treatment (except for participants without PTSD who received CPT-M), with treatment gains maintained one year later. Substance use significantly improved at the end of Phase 1 group ICBT and these improvements were maintained through Phase 2 and the one year follow-up. Participants in the trauma-focused Phase 2 treatment (CPT-M) exhibited similar levels of symptom reduction and maintenance of treatment gains as those in the non-trauma-focused Phase 2 treatment (ICBT). However, there was a slight advantage for Phase 2 CPT-M over Phase 2 ICBT with respect to heavy drinking outcomes for individuals with PTSD. Overall, the combination of group ICBT followed by either CPT-M or ICBT individual therapy appears to be effective for veterans with depression, SUD, and trauma history. Copyright © 2015. Published by Elsevier Inc.

A whey protein-based multi-ingredient nutritional supplement stimulates gains in lean body mass and strength in healthy older men: A randomized controlled trial

PubMed Central

Bell, Kirsten E.; Snijders, Tim; Zulyniak, Michael; Kumbhare, Dinesh; Parise, Gianni; Chabowski, Adrian

2017-01-01

Protein and other compounds can exert anabolic effects on skeletal muscle, particularly in conjunction with exercise. The objective of this study was to evaluate the efficacy of twice daily consumption of a protein-based, multi-ingredient nutritional supplement to increase strength and lean mass independent of, and in combination with, exercise in healthy older men. Forty-nine healthy older men (age: 73 ± 1 years [mean ± SEM]; BMI: 28.5 ± 1.5 kg/m2) were randomly allocated to 20 weeks of twice daily consumption of either a nutritional supplement (SUPP; n = 25; 30 g whey protein, 2.5 g creatine, 500 IU vitamin D, 400 mg calcium, and 1500 mg n-3 PUFA with 700 mg as eicosapentanoic acid and 445 mg as docosahexanoic acid); or a control (n = 24; CON; 22 g of maltodextrin). The study had two phases. Phase 1 was 6 weeks of SUPP or CON alone. Phase 2 was a 12 week continuation of the SUPP/CON but in combination with exercise: SUPP + EX or CON + EX. Isotonic strength (one repetition maximum [1RM]) and lean body mass (LBM) were the primary outcomes. In Phase 1 only the SUPP group gained strength (Σ1RM, SUPP: +14 ± 4 kg, CON: +3 ± 2 kg, P < 0.001) and lean mass (LBM, +1.2 ± 0.3 kg, CON: -0.1 ± 0.2 kg, P < 0.001). Although both groups gained strength during Phase 2, upon completion of the study upper body strength was greater in the SUPP group compared to the CON group (Σ upper body 1RM: 119 ± 4 vs. 109 ± 5 kg, P = 0.039). We conclude that twice daily consumption of a multi-ingredient nutritional supplement increased muscle strength and lean mass in older men. Increases in strength were enhanced further with exercise training. Trial Registration: ClinicalTrials.gov NCT02281331 PMID:28719669

The effect of ubiquinone and combined antioxidant therapy on oxidative stress markers in non-proliferative diabetic retinopathy: A phase IIa, randomized, double-blind, and placebo-controlled study.

PubMed

Rodríguez-Carrizalez, Adolfo Daniel; Castellanos-González, José Alberto; Martínez-Romero, Esaú César; Miller-Arrevillaga, Guillermo; Pacheco-Moisés, Fermín Paul; Román-Pintos, Luis Miguel; Miranda-Díaz, Alejandra Guillermina

2016-07-01

Objective To evaluate the effect of ubiquinone (Coenzyme Q10) and combined antioxidant therapy (CAT) on oxidative stress markers in non-proliferative diabetic retinopathy (NPDR) under clinical management. Study design In a randomized, double-blind, phase IIa, placebo-controlled, clinical trial, three study groups were formed and administered medications as follows: Group 1, Coenzyme Q10; Group 2, CAT; and Group 3, placebo. Methods Serum levels of the products of lipid peroxidation (LPO) and nitrites/nitrates, as markers of oxidative/nitrosative stress, were measured. As antioxidants, the total antioxidant capacity (TAC), catalase activity, and glutathione peroxidase (GPx) activity were measured. Results Baseline serum levels of LPO and nitrites/nitrates were significantly elevated in the three groups vs. healthy group (P < 0.0001), while final levels in the Coenzyme Q10 and CAT groups were decreased vs. normal levels (P < 0.0001). The baseline TAC was consumed in the three groups (P < 0.0001), while final results in the Coenzyme Q10 and CAT groups improved (P < 0.0001). Baseline catalase activity was increased in all groups vs. normal values (P < 0.001), while final levels in the Coenzyme Q10 (P < 0.001) and CAT groups (P < 0.0001) were decreased. GPx behaved similarly to catalase and improved in the final results (P < 0.0001). Discussion Adjunctive antioxidant treatment for 6 months was effective and safe for improving the oxidative stress in NPDR.

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.

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.

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

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.

Opicapone as Adjunct to Levodopa Therapy in Patients With Parkinson Disease and Motor Fluctuations: A Randomized Clinical Trial.

PubMed

Lees, Andrew J; Ferreira, Joaquim; Rascol, Olivier; Poewe, Werner; Rocha, José-Francisco; McCrory, Michelle; Soares-da-Silva, Patricio

2017-02-01

Catechol O-methyltransferase (COMT) inhibitors are an established treatment for end-of-dose motor fluctuations associated with levodopa therapy in patients with Parkinson disease (PD). Current COMT inhibitors carry a high risk for toxic effects to hepatic cells or show moderate improvement. Opicapone was designed to be effective without the adverse effects. To evaluate the efficacy and safety of 25- and 50-mg/d dosages of opicapone compared with placebo as adjunct to levodopa therapy in patients with PD experiencing end-of-dose motor fluctuations. This phase 3 international, multicenter outpatient study evaluated a 25- and a 50-mg/d dosage of opicapone in a randomized, double-blind, 14- to 15-week, placebo-controlled clinical trial, followed by a 1-year open-label phase during which all patients received active treatment with opicapone. Patients with PD who experienced signs of end-of-dose deterioration and had a mean total awake off-time (state of akinesia or decreased mobility) of at least 1.5 hours, not including morning akinesia, were enrolled. Data were collected from March 18, 2011, through June 25, 2013. Data from the evaluable population were analyzed from July 31, 2013, to July 31, 2014. The primary efficacy outcome of the double-blind phase was the change from baseline in absolute off-time vs placebo based on patient diaries. The open-label phase focused on maintenance of treatment effect in off-time. A total of 427 patients (258 men [60.4%] and 169 women [39.6%]; mean [SD] age, 63.1 [8.8] years) were randomized to a 25-mg/d (n = 129) or a 50-mg/d (n = 154) dosage of opicapone or to placebo (n = 144). Of these, 376 patients completed the double-blind phase and entered the open-label phase, of whom 286 completed 1 year of open-label treatment. At the end of the double-blind phase, the least squares mean change (SE) in off-time was -64.5 (14.4) minutes for the placebo group, -101.7 (14.9) minutes for the 25-mg/d opicapone group, and -118.8 (13.8) minutes for the 50-mg/d opicapone group. The adjusted treatment difference vs placebo was significant for the 50-mg/d opicapone group (treatment effect, -54.3 [95% CI, -96.2 to -12.4] minutes; P = .008), but not for the 25-mg/d opicapone group (treatment effect, -37.2 [95% CI, -80.8 to 6.4] minutes; P = .11). The off-time reduction was sustained throughout the open-label phase (-126.3 minutes at 1-year open-label end point). The most common adverse events in the opicapone vs placebo groups were dyskinesia, constipation, and dry mouth. Fifty-one patients (11.9%) discontinued from the study during the double-blind phase. Treatment with a 50-mg once-daily dose of opicapone was associated with a significant reduction in mean daily off-time in levodopa-treated patients with PD and motor fluctuations, and this effect is maintained for at least 1 year. Opicapone was safe and well tolerated. clinicaltrials.gov Identifier: NCT01227655.

Multicenter, randomized, open-label Phase II study comparing S-1 alternate-day oral therapy with the standard daily regimen as a first-line treatment in patients with unresectable advanced pancreatic cancer.

PubMed

Yamaue, Hiroki; Shimizu, Atsushi; Hagiwara, Yasuhiro; Sho, Masayuki; Yanagimoto, Hiroaki; Nakamori, Shoji; Ueno, Hideki; Ishii, Hiroshi; Kitano, Masayuki; Sugimori, Kazuya; Maguchi, Hiroyuki; Ohkawa, Shinichi; Imaoka, Hiroshi; Hashimoto, Daisuke; Ueda, Kazuki; Nebiki, Hiroko; Nagakawa, Tatsuya; Isayama, Hiroyuki; Yokota, Isao; Ohashi, Yasuo; Shirasaka, Tetsuhiko

2017-04-01

Non-inferiority for overall survival (OS) following alternate-day treatment with the oral anticancer drug S-1 compared with standard daily treatment was assessed in Japanese patients with unresectable advanced pancreatic cancer in a multicenter, randomized, phase II study. This trial was registered at the UMIN Clinical Trials Registry (no. 000008604). Chemotherapy-naïve patients with locally advanced or metastatic pancreatic cancer were randomly assigned 2:1 to treatment with alternate-day (twice daily on alternate days from days 1 through 42 of a 42-day cycle) or daily (twice daily on days 1 through 28 of a 42-day cycle) treatment with S-1. The primary endpoint was OS. Secondary endpoints were progression-free survival (PFS), time to treatment failure, response rate, quality of life assessments, and safety. A total of 190 patients were enrolled, of which 185 were included in the final analysis (alternate-day: 121; daily: 64). Median OS was 9.4 for the alternate-day group and 10.4 months for the daily group [hazard ratio (HR), 1.19; 95% credible interval, 0.86 to 1.64], indicating that non-inferiority of alternate-day treatment to daily treatment was not demonstrated. Median PFS was 3.0 for the alternate-day group and 4.2 months for the daily group (HR, 1.65; 95% credible interval, 1.20-2.29). The incidence of anorexia, fatigue, neutrophils, pigmentation, and pneumonitis was lower in alternate-day treatment compared with daily treatment. S-1 for advanced pancreatic cancer should be taken daily as recommended, based on the decreased OS and PFS and marginal improvement in safety observed in the alternate-day group.

Early High-dosage Atorvastatin Treatment Improved Serum Immune-inflammatory Markers and Functional Outcome in Acute Ischemic Strokes Classified as Large Artery Atherosclerotic Stroke

PubMed Central

Tuttolomondo, Antonino; Di Raimondo, Domenico; Pecoraro, Rosaria; Maida, Carlo; Arnao, Valentina; Corte, Vittoriano Della; Simonetta, Irene; Corpora, Francesca; Di Bona, Danilo; Maugeri, Rosario; Iacopino, Domenico Gerardo; Pinto, Antonio

2016-01-01

Abstract Statins have beneficial effects on cerebral circulation and brain parenchyma during ischemic stroke and reperfusion. The primary hypothesis of this randomized parallel trial was that treatment with 80 mg/day of atorvastatin administered early at admission after acute atherosclerotic ischemic stroke could reduce serum levels of markers of immune-inflammatory activation of the acute phase and that this immune-inflammatory modulation could have a possible effect on prognosis of ischemic stroke evaluated by some outcome indicators. We enrolled 42 patients with acute ischemic stroke classified as large arteries atherosclerosis stroke (LAAS) randomly assigned in a randomized parallel trial to the following groups: Group A, 22 patients treated with atorvastatin 80 mg (once-daily) from admission day until discharge; Group B, 20 patients not treated with atorvastatin 80 mg until discharge, and after discharge, treatment with atorvastatin has been started. At 72 hours and at 7 days after acute ischemic stroke, subjects of group A showed significantly lower plasma levels of tumor necrosis factor-α, interleukin (IL)-6, vascular cell adhesion molecule-1, whereas no significant difference with regard to plasma levels of IL-10, E-Selectin, and P-Selectin was observed between the 2 groups. At 72 hours and 7 days after admission, stroke patients treated with atorvastatin 80 mg in comparison with stroke subjects not treated with atorvastatin showed a significantly lower mean National Institutes of Health Stroke Scale and modified Rankin scores. Our findings provide the first evidence that atorvastatin acutely administered immediately after an atherosclerotic ischemic stroke exerts a lowering effect on immune-inflammatory activation of the acute phase of stroke and that its early use is associated to a better functional and prognostic profile. PMID:27043681

Controlled randomized clinical trial of spirituality integrated psychotherapy, cognitive-behavioral therapy and medication intervention on depressive symptoms and dysfunctional attitudes in patients with dysthymic disorder

PubMed Central

Ebrahimi, Amrollah; Neshatdoost, Hamid Taher; Mousavi, Seyed Ghafur; Asadollahi, Ghorban Ali; Nasiri, Hamid

2013-01-01

Background: Due to the controversy over efficacy of cognitive-behavioral therapy for chronic depression, recently, there has been an increasingly tendency toward therapeutic methods based on the cultural and spiritual approaches. The aim of this research was to compare efficacy of spiritual integrated psychotherapy (SIPT) and cognitive-behavioral therapy (CBT) on the intensity of depression symptoms and dysfunctional attitudes of patients with dysthymic disorder. Materials and Methods: This study had a mixed qualitative and quantitative design. In the first phase, SIPT model was prepared and, in the second phase, a double-blind random clinical trial was performed. Sixty-two patients with dysthymic disorder were selected from several centers include Nour and Alzahra Medical Center, Counseling Centers of Isfahan University of Medical Sciences and Goldis in Isfahan. The participants were randomly assigned to three experimental groups and one control group. The first group received 8 sessions treatment of SIPT, second groups also had 8 sessions of cognitive-behavioral therapy, which was specific to dysthymic disorder and third group were under antidepressant treatment. Beck depression inventory and dysfunctional attitudes scale were used to evaluate all the participants in four measurement stages. The data were analyzed using MANCOVA repeated measure method. Results: The results revealed that SIPT had more efficacy than medication based on both scales (P < 0.01); however, it was not different from CBT. SIPT was more effective on the modification of dysfunctional attitudes compared with CBT and medication (P < 0.05). Conclusion: These findings supported the efficacy of psychotherapy enriched with cultural capacities and religious teachings. PMID:24516853

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.

Safety and Immunogenicity of a Tetravalent Dengue Vaccine Candidate in Healthy Children and Adults in Dengue-Endemic Regions: A Randomized, Placebo-Controlled Phase 2 Study.

PubMed

Sirivichayakul, Chukiat; Barranco-Santana, Elizabeth A; Esquilin-Rivera, Inés; Oh, Helen M L; Raanan, Marsha; Sariol, Carlos A; Shek, Lynette P; Simasathien, Sriluck; Smith, Mary Kathryn; Velez, Ivan Dario; Wallace, Derek; Gordon, Gilad S; Stinchcomb, Dan T

2016-05-15

A safe, effective tetravalent dengue vaccine is a global health priority. The safety and immunogenicity of a live attenuated, recombinant tetravalent dengue vaccine candidate (TDV) were evaluated in healthy volunteers from dengue-endemic countries. This multicenter, double-blind, phase 2 study was conducted in Puerto Rico, Colombia, Singapore, and Thailand. During stage I, 148 volunteers aged 1.5-45 years were sequentially enrolled into 4 age-descending groups and randomized at a ratio of 2:1 to receive TDV or placebo. In stage II (group 5), 212 children aged 1.5-11 years were randomized at a ratio of 3:1 to receive TDV or placebo. Participants received a subcutaneous injection of TDV or placebo on days 0 and 90 and were followed for analysis of safety, seropositivity, and neutralizing antibodies to DENV-1-4. Injection site pain, itching, and erythema (mostly mild) were the only solicited adverse events more frequently reported with TDV than with placebo in all age groups. After 2 TDV doses, seropositivity was >95% in all 5 groups for DENV-1-3 and 72.7%-100% for DENV-4; geometric mean titers ranged from 582 to 1187 for DENV-1, from 582 to 1187 for DENV-2, from 196 to 630 for DENV-3, and from 41 to 210 for DENV-4 among the 5 groups. TDV was well tolerated and immunogenic in volunteers aged 1.5-45 years, irrespective of prevaccination dengue exposure. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mailjournals.permissions@oup.com.

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.

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.

Dronabinol and lofexidine for cannabis use disorder: A randomized, double-blind, placebo-controlled trial.

PubMed

Levin, Frances R; Mariani, John J; Pavlicova, Martina; Brooks, Daniel; Glass, Andrew; Mahony, Amy; Nunes, Edward V; Bisaga, Adam; Dakwar, Elias; Carpenter, Kenneth M; Sullivan, Maria A; Choi, Jean C

2016-02-01

Cannabis use disorder is associated with substantial morbidity and, after alcohol, is the most common drug bringing adolescents and adults into treatment. At present, there are no FDA-approved medications for cannabis use disorder. Combined pharmacologic interventions might be particularly useful in mitigating withdrawal symptoms and promoting abstinence. 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, and lofexidine, an alpha-2 agonist, in treating cannabis dependence. One hundred fifty six cannabis-dependent adults were enrolled and following a 1-week placebo lead-in phase 122 were randomized in a double-blind, placebo-controlled, 11-week trial. Participants were randomized to receive dronabinol 20mg three times a day and lofexidine 0.6 mg three times a day or placebo. Medications were maintained until the end of week eight, were then tapered over two weeks and patients were monitored off medications during the last study week. All participants received weekly motivational enhancement and relapse prevention therapy. Marijuana use was assessed using the timeline follow-back method. There was no significant difference between treatment groups in the proportion of participants who achieved 3 weeks of abstinence during the maintenance phase of the trial (27.9% for the medication group and 29.5% for the placebo group), although both groups showed a reduction over time. Based on this treatment study, the combined intervention did not show promise as a treatment for cannabis use disorder. Published by Elsevier Ireland Ltd.

Dental Students' Preference with Regard to Tactile or Visual Determination of Injection Site for an Inferior Alveolar Nerve Block in Children: A Crossover Randomized Clinical Trial.

PubMed

Ramazani, Nahid; Iranmanesh, Seyed Masoud

2016-01-01

Instruction of local anesthesia injection in an important part of dental education curricula. This study was performed to compare dental students' preference with regard to tactile or visual determination of injection site for an inferior alveolar nerve block (IANB) in children. This crossover randomized clinical trial was conducted on dental students of Zahedan Dental School who took the first practical course of pediatric dentistry in the first academic semester of 2013-14 (n=42). They were randomly divided into two groups. During the first phase, group I was instructed to find the needle insertion point for an IANB via tactile method and group II was instructed to do it visually. In the second phase, the groups received instructions for the alternate technique. Both instructions were done using live demonstrations by the same instructor and immediately after instruction the learners practiced an IANB using the taught method. A five-point Likert scale questionnaire was then filled out by the students. The preference score was determined by calculating the mean of item scores. Data were analyzed using Mann-Whitney U and Wilcoxon Singed Rank tests in SPSS 19 at P=0.05 level of significance. Thirty-eight students completed the study. By using the visual method to perform an IANB, students gained a significantly higher mean preference score (P=0.020). There was a significant difference in the preference of male students (P=0.008). Instruction of IANB by visual identification of needle insertion point is more desirable by students.

Perioperative Granulocyte Colony-Stimulating Factor Does Not Prevent Severe Infections in Patients Undergoing Esophagectomy for Esophageal Cancer

PubMed Central

Schaefer, Hartmut; Engert, Andreas; Grass, Guido; Mansmann, Georg; Wassmer, Gernot; Hubel, Kai; Loehlein, Dietrich; Ulrich, Bernward C.; Lippert, Hans; Knoefel, Wolfram T.; Hoelscher, Arnulf H.

2004-01-01

Objective: Esophagectomy for esophageal cancer is associated with substantial postoperative morbidity as a result of infectious complications. In a prior phase II study, granulocyte colony-stimulating factor (G-CSF) was shown to improve leukocyte function and to reduce infection rates after esophagectomy. The aim of the current randomized, placebo-controlled, multicenter phase III trial was to investigate the clinical efficacy of perioperative G-CSF administration in reducing infection and mortality after esophagectomy for esophageal cancer. Patients and Methods: One hundred fifty five patients with resectable esophageal cancer were randomly assigned to perioperative G-CSF at standard doses (77 patients) or placebo (76 patients), administered from 2 days before until day 7 after esophagectomy. The G-CSF and placebo groups were comparable as regards age, gender, risk, cancer stage, frequency of neoadjuvant radiochemotherapy, and type of esophagectomy (transthoracic or transhiatal esophageal resection). Results: Of 155 randomized patients, 153 were eligible for the intention-to-treat analysis. The rate of infection occurring within the first 10 days after esophagectomy was 43.4% (confidence interval 32.8–55.9%) in the placebo and 44.2% (confidence interval 32.1–55.3%) in the G-CSF group (P = 0.927). 30-day mortality amounted to 5.2% in the G-CSF group versus 5.3% in the placebo group (P = 0.985). Similar results were found in the per-protocol analysis. Conclusion: Perioperative administration of G-CSF failed to reduce postoperative morbidity, infection rate, or mortality in patients with esophageal cancer who underwent esophagectomy. PMID:15213620

Dronabinol and Lofexidine for Cannabis Use Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial*

PubMed Central

Levin, Frances R.; Mariani, John J.; Pavlicova, Martina; Brooks, Daniel; Glass, Andrew; Mahony, Amy; Nunes, Edward V.; Bisaga, Adam; Dakwar, Elias; Carpenter, Kenneth M.; Sullivan, Maria A.; Choi, Jean C.

2016-01-01

Background Cannabis use disorder is associated with substantial morbidity and, after alcohol, is the most common drug bringing adolescents and adults into treatment. At present, there are no FDA-approved medications for cannabis use disorder. Combined pharmacologic interventions might be particularly useful in mitigating withdrawal symptoms and promoting abstinence. Objective 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, and lofexidine, an alpha-2 agonist, in treating cannabis dependence. Methods One hundred fifty six cannabis-dependent adults were enrolled and following a 1-week placebo lead-in phase 122 were randomized in a double-blind, placebo-controlled, 11-week trial. Participants were randomized to receive dronabinol 20 mg three times a day and lofexidine 0.6 mg three times a day or placebo. Medications were maintained until the end of week eight, were then tapered over two weeks and patients were monitored off medications during the last study week. All participants received weekly motivational enhancement and relapse prevention therapy. Marijuana use was assessed using the timeline follow-back method. Results There was no significant difference between treatment groups in the proportion of participants who achieved 3 weeks of abstinence during the maintenance phase of the trial (27.9 % for the medication group and 29.5% for the placebo group), although both groups showed a reduction over time. Conclusions Based on this treatment study, the combined intervention did not show promise as a treatment for cannabis use disorder. PMID:26711160

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.

Progress in low-resolution ab initio phasing with CrowdPhase

DOE PAGES

Jorda, Julien; Sawaya, Michael R.; Yeates, Todd O.

2016-03-01

Ab initio phasing by direct computational methods in low-resolution X-ray crystallography is a long-standing challenge. A common approach is to consider it as two subproblems: sampling of phase space and identification of the correct solution. While the former is amenable to a myriad of search algorithms, devising a reliable target function for the latter problem remains an open question. Here, recent developments in CrowdPhase, a collaborative online game powered by a genetic algorithm that evolves an initial population of individuals with random genetic make-up ( i.e. random phases) each expressing a phenotype in the form of an electron-density map, aremore » presented. Success relies on the ability of human players to visually evaluate the quality of these maps and, following a Darwinian survival-of-the-fittest concept, direct the search towards optimal solutions. While an initial study demonstrated the feasibility of the approach, some important crystallographic issues were overlooked for the sake of simplicity. To address these, the new CrowdPhase includes consideration of space-group symmetry, a method for handling missing amplitudes, the use of a map correlation coefficient as a quality metric and a solvent-flattening step. Lastly, performances of this installment are discussed for two low-resolution test cases based on bona fide diffraction data.« less

Progress in low-resolution ab initio phasing with CrowdPhase

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

Jorda, Julien; Sawaya, Michael R.; Yeates, Todd O.

Ab initio phasing by direct computational methods in low-resolution X-ray crystallography is a long-standing challenge. A common approach is to consider it as two subproblems: sampling of phase space and identification of the correct solution. While the former is amenable to a myriad of search algorithms, devising a reliable target function for the latter problem remains an open question. Here, recent developments in CrowdPhase, a collaborative online game powered by a genetic algorithm that evolves an initial population of individuals with random genetic make-up ( i.e. random phases) each expressing a phenotype in the form of an electron-density map, aremore » presented. Success relies on the ability of human players to visually evaluate the quality of these maps and, following a Darwinian survival-of-the-fittest concept, direct the search towards optimal solutions. While an initial study demonstrated the feasibility of the approach, some important crystallographic issues were overlooked for the sake of simplicity. To address these, the new CrowdPhase includes consideration of space-group symmetry, a method for handling missing amplitudes, the use of a map correlation coefficient as a quality metric and a solvent-flattening step. Lastly, performances of this installment are discussed for two low-resolution test cases based on bona fide diffraction data.« less

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 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.

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).

An accelerated dose escalation with a grass pollen allergoid is safe and well-tolerated: a randomized open label phase II trial.

PubMed

Chaker, A M; Al-Kadah, B; Luther, U; Neumann, U; Wagenmann, M

2015-01-01

The number of injections in the dose escalation of subcutaneous immunotherapy (SCIT) is small for some currently used hypoallergenic allergoids, but can still be inconvenient to patients and can impair compliance. The aim of this trial was to compare safety and tolerability of an accelerated to the conventional dose escalation scheme of a grass pollen allergoid. In an open label phase II trial, 122 patients were 1:1 randomized for SCIT using a grass pollen allergoid with an accelerated dose escalation comprising only 4 weekly injections (Group I) or a conventional dose escalation including 7 weekly injections (Group II). Safety determination included the occurrence of local and systemic adverse events. Tolerability was assessed by patients and physicians. Treatment-related adverse events were observed in 22 (36.1 %) patients in Group I and 15 (24.6 %) in Group II. Local reactions were reported by 18 patients in Group I and 11 in Group II. Five Grade 1 systemic reactions (WAO classification) were observed in Group I and 2 in Group II. Grade 2 reactions occurred 3 times in Group I and 2 times in Group II. Tolerability was rated as "good" or "very good" by 53 (86.9 %) patients in Group I and 59 (100 %) in Group II by investigators. Forty-eight patients in Group I (80.0 %) and 54 in Group II (91.5 %) rated tolerability as "good" or "very good". The dose escalation of a grass pollen allergoid can be accelerated with safety and tolerability profiles comparable to the conventional dose escalation.

Effect of self-hypnosis on duration of labor and maternal and neonatal outcomes: a randomized controlled trial.

PubMed

Werner, Anette; Uldbjerg, Niels; Zachariae, Robert; Nohr, Ellen A

2013-07-01

To examine the effect of a brief course in self-hypnosis for childbirth on duration of the labor and other birth outcomes. A randomized, controlled, single-blind trial. Aarhus University Hospital Skejby, Denmark. A total of 1222 healthy nulliparous women. A hypnosis group receiving three 1-h lessons in self-hypnosis with additional audio-recordings to ease childbirth, a relaxation group receiving three 1-h lessons in various relaxation methods and mindfulness with audio-recordings for additional training, and a usual-care group receiving only the usual antenatal care were compared. Duration of labor, birth complications, lactation success, caring for the child, and preferred future mode of delivery. No differences were found across the three groups on duration from arriving at the birth department until the expulsive phase of second stage of labor, the duration of the expulsive phase, or other birth outcomes. Fewer emergency and more elective cesarean sections occurred in the hypnosis group. No difference was seen across the groups for lactation success or caring for the child but fewer women in the hypnosis group preferred a cesarean section in future pregnancies because of fear of childbirth and negative birth experiences. Learning self-hypnosis to ease childbirth taught as a brief course failed to show any effects on duration of childbirth and other birth outcomes. © 2013 The Authors Acta Obstetricia et Gynecologica Scandinavica © 2013 Nordic Federation of Societies of Obstetrics and Gynecology.

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

A phase II randomized double-blind placebo-controlled study of 6-gingerol as an anti-emetic in solid tumor patients receiving moderately to highly emetogenic chemotherapy.

PubMed

Konmun, J; Danwilai, K; Ngamphaiboon, N; Sripanidkulchai, B; Sookprasert, A; Subongkot, S

2017-04-01

6-Gingerol is a natural compound extracted from ginger. Preclinical studies demonstrated that 6-gingerol has an anti-emetic activity by inhibiting neurokinin-1, serotonin, and dopamine receptors. Several clinical trials examined crude ginger powder for preventing chemotherapy-induced nausea and vomiting (CINV), but none of them was conducted with a standardized bioactive compound. Patients who received moderately to highly emetogenic adjuvant chemotherapy were randomized to receive 6-gingerol 10 mg or placebo orally twice daily for 12 weeks. Ondansetron, metoclopramide, and dexamethasone were given to all patients. The primary endpoint was complete response (CR) rate defined as no emesis or rescue treatment at any time. Eighty-eight patients were randomized to receive 6-gingerol (N = 42) or placebo (N = 46). Most patients received highly emetogenic chemotherapy (93%). Overall CR rate was significantly higher in 6-gingerol group as compared with that of the placebo (77 vs. 32%; P < 0.001). The difference in means of appetite score was significant (P = 0.001) and more noticeable over time. Mean FACT-G score indicating quality of life was significantly higher (86.21) in 6-gingerol group at 64 days as compared with that of placebo group (72.36) (P < 0.001). No toxicity related to 6-gingerol was observed. Patients treated with 6-gingerol reported significantly less grade 3 fatigue (2 vs. 20%; P = 0.020). 6-Gingerol significantly improved overall CR rate in CINV, appetite and quality of life in cancer patients receiving adjuvant chemotherapy. A phase III randomized study of 6-gingerol is warranted to confirm these results.

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

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 Effect of Shoulder Plyometric Training on Amortization Time and Upper-Extremity Kinematics.

PubMed

Swanik, Kathleen A; Thomas, Stephen J; Struminger, Aaron H; Bliven, Kellie C Huxel; Kelly, John D; Swanik, Charles B

2016-12-01

Plyometric training is credited with providing benefits in performance and dynamic restraint. However, limited prospective data exist quantifying kinematic adaptations such as amortization time, glenohumeral rotation, and scapulothoracic position, which may underlie the efficacy of plyometric training for upper-extremity rehabilitation or performance enhancement. To measure upper-extremity kinematics and plyometric phase times before and after an 8-wk upper-extremity strength- and plyometric-training program. Randomized pretest-posttest design. Research laboratory. 40 recreationally active men (plyometric group, age 20.43 ± 1.40 y, height 180.00 ± 8.80 cm, weight 73.07 ± 7.21 kg; strength group, age 21.95 ± 3.40 y, height 173.98 ± 11.91 cm, weight 74.79 ± 13.55 kg). Participants were randomly assigned to either a strength-training group or a strength- and plyometric-training group. Each participant performed the assigned training for 8 wk. Dynamic and static glenohumeral and scapular-rotation measurements were taken before and after the training programs. Dynamic measurement of scapular rotation and time spent in each plyometric phase (concentric, eccentric, and amortization) during a ball-toss exercise were recorded while the subjects were fitted with an electromagnetic tracking system. Static measures included scapular upward rotation at 3 different glenohumeral-abduction angles, glenohumeral internal rotation, and glenohumeral external rotation. Posttesting showed that both groups significantly decreased the time spent in the amortization, concentric, and eccentric phases of a ball-toss exercise (P < .01). Both groups also exhibited significantly decreased static external rotation and increased dynamic scapular upward rotation after the training period (P < .01). The only difference between the training protocols was that the plyometric-training group exhibited an increase in internal rotation that was not present in the strength-training group (P < .01). These findings support the use of both upper-extremity plyometrics and strength training for reducing commonly identified upper-extremity-injury risk factors and improving upper-extremity performance.

Effectiveness of Different Bristle Designs of Toothbrushes and Periodontal Status among Fixed Orthodontic Patients: A Double-blind Crossover Design.

PubMed

Naik, Sandhya P; Punathil, Sameer; Shetty, Praveena; Jayanti, Ipsita; Jalaluddin, Md; Avijeeta, Anisha

2018-02-01

The aim of the present study was to evaluate the effectiveness of different bristle designs of toothbrushes and the periodontal status among patients undergoing fixed orthodontic treatment. This randomized controlled trial (RCT) consisted of 45 adolescents (comprising 20 males and 25 females) undergoing fixed orthodontic treatment. The study participants were randomly allocated to three groups, each group being assigned a locally available toothbrush with a particular design of toothbrush bristle. In the first test phase, group I study participants were allocated to toothbrush with flat bristles, group II study subjects were allocated to toothbrush with zigzag bristles, and group III study participants were allocated to toothbrush with crisscross bristles. The study participants were recalled after 4 weeks to check the effectiveness of the allocated toothbrushes. A washout period of 1 week was maintained to ensure that there was no carryover effect of the different bristle designs. In the second test phase, each patient used the opposite toothbrush bristle design (group I: toothbrush with zigzag bristles, group II: toothbrush with crisscross bristles, and group III: toothbrush with flat bristles). Plaque scores were measured using Turesky-Gilmore-Glickman modification of Quigley-Hein plaque index (PI). In both phase 1 and 2 of this RCT, toothbrush with crisscross bristles exhibited maximum plaque reduction among the three different bristle design toothbrushes following 30 days (p = 0.312 ± 0.102 and 0.280 ± 0.110, respectively), which was statistically significant. It was concluded that all the three designs of toothbrushes were effective in removing plaque in patients with fixed orthodontic appliances. But among the three different toothbrushes, toothbrush with crisscross bristles showed the highest mean plaque reduction. Plaque accumulation around the orthodontic brackets and gingival margins is quite common among the fixed orthodontic patients, who encounter difficulty in maintaining good oral hygiene. Specially designed toothbrushes are very essential for effective plaque removal among the patients undergoing fixed orthodontic treatment.

[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.

Effect of sodium lauryl sulfate on recurrent aphthous stomatitis: a randomized controlled clinical trial.

PubMed

Shim, Y J; Choi, J-H; Ahn, H-J; Kwon, J-S

2012-10-01

To compare the effects of sodium lauryl sulfate (SLS)-free and SLS-containing dentifrice in patient with recurrent aphthous stomatitis (RAS). The design of this study was a double-blind crossover trial. The 90 subjects were divided into three groups: group I used SLS-free (a commercially available SLS-free dentifrice) and SLS-A (SLS-free + 1.5% SLS), group II used SLS-A and SLS-B (a commercially available 1.5% SLS-containing dentifrice), and group III used SLS-free and SLS-B. The subjects used one of the two assigned dentifrices for 8 weeks and then the other for the following 8 weeks. The order of the dentifrices used was selected at random, and there was a 2-week washout period between the two phases. The clinical parameters (number of ulcers, number of episodes, duration of ulcers, mean pain score) were compared between the two phases for each group. The number of ulcers and episodes did not differ significantly between SLS-A, SLS-B, and SLS-free. Only duration of ulcers and mean pain score was significantly decreased during the period using SLS-free. Although SLS-free did not reduce the number of ulcers and episodes, it affected the ulcer-healing process and reduces pain in daily lives in patients with RAS. © 2012 John Wiley & Sons A/S.

Conversion from twice-daily tacrolimus to once-daily extended release tacrolimus (LCPT): the phase III randomized MELT trial.

PubMed

Bunnapradist, S; Ciechanowski, K; West-Thielke, P; Mulgaonkar, S; Rostaing, L; Vasudev, B; Budde, K

2013-03-01

Phase III noninferiority trial examining efficacy and safety of converting stable renal transplant recipients from twice-daily tacrolimus to a novel extended-release once-daily tacrolimus formulation (LCPT) with a controlled agglomeration technology. Controls maintained tacrolimus twice daily. The primary efficacy endpoint was proportion of patients with efficacy failures (death, graft failure, locally read biopsy-proven acute rejection [BPAR], or loss to follow-up) within 12 months. Starting LCPT dose was 30% lower (15% for blacks) than preconversion tacrolimus dose; target trough levels were 4-15 ng/mL. A total of 326 patients were randomized; the mITT population (n = 162 each group) was similar demographically in the two groups. Mean daily dose of LCPT was significantly (p < 0.0001) lower than preconversion tacrolimus dose at each visit; mean trough levels between groups were similar. There were four efficacy failures in each group; safety outcomes were similar between groups. Frequency of premature study drug discontinuation was LCPT: 12% versus tacrolimus twice daily: 5% (p = 0.028). LCPT demonstrated noninferiority to tacrolimus twice daily in efficacy failure rates. LCPT may offer a safe and effective alternative for converting patients to a once-daily formulation. Compared to currently available tacrolimus formulation, LCPT requires lower doses to achieve target trough levels. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

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

Does Post-task Declarative Learning Have an Influence on Early Motor Memory Consolidation Over Day? An fMRI Study

PubMed Central

Rothkirch, Inken; Wolff, Stephan; Margraf, Nils G.; Pedersen, Anya; Witt, Karsten

2018-01-01

Previous studies demonstrated the influence of the post-learning period on procedural motor memory consolidation. In an early period after the acquisition, motor skills are vulnerable to modifications during wakefulness. Indeed, specific interventions such as world-list learning within this early phase of motor memory consolidation seem to enhance motor performance as an indicator for successful consolidation. This finding highlights the idea that manipulations of procedural and declarative memory systems during the early phase of memory consolidation over wakefulness may influence off-line consolidation. Using functional magnetic resonance imaging (fMRI) during initial motor sequence learning and motor sequence recall, we indirectly assess the influence of a secondary task taken place in the early phase of memory consolidation. All participants were scanned using fMRI during the learning phase of a serial reaction time task (SRTT) at 8 a.m. Afterwards, they were randomly assigned to one of five conditions. One group performed a declarative verbal, one a declarative nonverbal learning task. Two groups worked on attention tasks. A control group passed a resting condition. Participants stayed awake the whole day and performed the SRTT in the MRI scanner 12 h later at 8 p.m. At the behavioral level, the analysis of the reaction times failed to show a significant group difference. The primary analysis assessing fMRI data based on the contrast (sequence – random) between learning and retrieval also did not show any significant group differences. Therefore, our main analysis do not support the hypothesis that a secondary task influences the retrieval of the SRTT. In a more liberal fMRI analysis, we compared only the sequence blocks of the SRTT from learning to recall. BOLD signal decreased in the ipsilateral cerebellum and the supplementary motor area solely in the verbal learning group. Although our primary analysis failed to show significant changes between our groups, results of the secondary analysis could be an indication for a beneficial effect of the verbal declarative task in the early post-learning phase. A nonverbal learning task did not affect the activation within the motor network. Further studies are needed to replicate this finding and to assess the usefulness of this manipulation. PMID:29755315

Does Post-task Declarative Learning Have an Influence on Early Motor Memory Consolidation Over Day? An fMRI Study.

PubMed

Rothkirch, Inken; Wolff, Stephan; Margraf, Nils G; Pedersen, Anya; Witt, Karsten

2018-01-01

Previous studies demonstrated the influence of the post-learning period on procedural motor memory consolidation. In an early period after the acquisition, motor skills are vulnerable to modifications during wakefulness. Indeed, specific interventions such as world-list learning within this early phase of motor memory consolidation seem to enhance motor performance as an indicator for successful consolidation. This finding highlights the idea that manipulations of procedural and declarative memory systems during the early phase of memory consolidation over wakefulness may influence off-line consolidation. Using functional magnetic resonance imaging (fMRI) during initial motor sequence learning and motor sequence recall, we indirectly assess the influence of a secondary task taken place in the early phase of memory consolidation. All participants were scanned using fMRI during the learning phase of a serial reaction time task (SRTT) at 8 a.m. Afterwards, they were randomly assigned to one of five conditions. One group performed a declarative verbal, one a declarative nonverbal learning task. Two groups worked on attention tasks. A control group passed a resting condition. Participants stayed awake the whole day and performed the SRTT in the MRI scanner 12 h later at 8 p.m. At the behavioral level, the analysis of the reaction times failed to show a significant group difference. The primary analysis assessing fMRI data based on the contrast (sequence - random) between learning and retrieval also did not show any significant group differences. Therefore, our main analysis do not support the hypothesis that a secondary task influences the retrieval of the SRTT. In a more liberal fMRI analysis, we compared only the sequence blocks of the SRTT from learning to recall. BOLD signal decreased in the ipsilateral cerebellum and the supplementary motor area solely in the verbal learning group. Although our primary analysis failed to show significant changes between our groups, results of the secondary analysis could be an indication for a beneficial effect of the verbal declarative task in the early post-learning phase. A nonverbal learning task did not affect the activation within the motor network. Further studies are needed to replicate this finding and to assess the usefulness of this manipulation.

Safety of a quadrivalent meningococcal serogroups A, C, W and Y conjugate vaccine (MenACWY-CRM) administered with routine infant vaccinations: results of an open-label, randomized, phase 3b controlled study in healthy infants.

PubMed

Abdelnour, Arturo; Silas, Peter E; Lamas, Marta Raquel Valdés; Aragón, Carlos Fernándo Grazioso; Chiu, Nan-Chang; Chiu, Cheng-Hsun; Acuña, Teobaldo Herrera; Castrejón, Tirza De León; Izu, Allen; Odrljin, Tatjana; Smolenov, Igor; Hohenboken, Matthew; Dull, Peter M

2014-02-12

The highest risk for invasive meningococcal disease (IMD) is in infants aged <1 year. Quadrivalent meningococcal conjugate vaccination has the potential to prevent IMD caused by serogroups A, C, W and Y. This phase 3b, multinational, open-label, randomized, parallel-group, multicenter study evaluated the safety of a 4-dose series of MenACWY-CRM, a quadrivalent meningococcal conjugate vaccine, concomitantly administered with routine vaccinations to healthy infants. Two-month-old infants were randomized 3:1 to receive MenACWY-CRM with routine vaccines or routine vaccines alone at ages 2, 4, 6 and 12 months. Adverse events (AEs) that were medically attended and serious adverse events (SAEs) were collected from all subjects from enrollment through 18 months of age. In a subset, detailed safety data (local and systemic solicited reactions and all AEs) were collected for 7 days post vaccination. The primary objective was a non-inferiority comparison of the percentages of subjects with ≥1 severe systemic reaction during Days 1-7 after any vaccination of MenACWY-CRM plus routine vaccinations versus routine vaccinations alone (criterion: upper limit of 95% confidence interval [CI] of group difference <6%). A total of 7744 subjects were randomized with 1898 in the detailed safety arm. The percentage of subjects with severe systemic reactions was 16% after MenACWY-CRM plus routine vaccines and 13% after routine vaccines alone (group difference 3.0% (95% CI -0.8, 6.4%). Although the non-inferiority criterion was not met, post hoc analysis controlling for significant center and group-by-center differences revealed that MenACWY-CRM plus routine vaccinations was non-inferior to routine vaccinations alone (group difference -0.1% [95% CI -4.9%, 4.7%]). Rates of solicited AEs, medically attended AEs, and SAEs were similar across groups. In a large multinational safety study, a 4-dose series of MenACWY-CRM concomitantly administered with routine vaccines was clinically acceptable with a similar safety profile to routine vaccines given alone. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effects of SP6 Acupuncture Point Stimulation on Labor Pain and Duration of Labor

PubMed Central

Yesilcicek Calik, Kiymet; Komurcu, Nuran

2014-01-01

Background: Acupressure has been used frequently to improve labor, manage labor pain, and shorten delivery time. However, there has been little research-based evidence to support the positive effects of acupressure in the obstetric area and obstetric nursing. Objectives: The aim of this study was to evaluate the effects of SP6 acupressure on labor pain and delivery time in primigravida women in labor. Patients and Methods: The study was conducted at the Trabzon Maternity Hospital in Turkey. Its design was a randomized controlled clinical trial study using a single-blinded method. One hundred (100) primigravida women in labor were randomly assigned to either the SP6 acupressure (n = 50) or control group (n = 50). Acupressure was practiced 35 times in total on the SP6 point of both legs in the SP6 acupressure group; 15 times (during contraction) when cervical dilation was 2-3 cm, 10 times when cervical dilation was 5-6 cm and 10 times at 9-10 cm dilation, while the women in the control group received standard care. Labor pain was measured five times using a structured questionnaire of a subjective labor pain scale (visual analogue scale-VAS) when dilation was 2-3 cm (VAS 2), 5-6 cm (VAS 3) and 8-9 cm (VAS 4) before and after acupressure was applied to the SP6 point (VAS 1), and finally at the early postpartum period (VAS 5). The duration of labor in both groups was measured with a partograph and the length of delivery time was calculated in two stages: from 3 cm cervical dilation to full cervical dilation, and from full cervical dilation to delivery. Results: There were significant differences between the groups in subjective labor pain scores (except VAS 4) (P < 0.001). The duration of the Phase one (3 cm dilatation to full dilatation) and Phase two (full dilatation to birth) in the acupressure group was shorter than the control group (Phase one, 225 min and 320 min, respectively; Phase two, 15 min and 20 min, respectively; both P < 0.001). Conclusions: It was determined that SP6 acupressure was effective in decreasing pain and duration of labor. PMID:25558386

Meditative music listening to reduce state anxiety in patients during the uptake phase before positron emission tomography (PET) scans

PubMed Central

Lee, Wen-Li; Liu, Shu-Hsin; Chang, Shu-Min

2017-01-01

Objective: This study examines the effects of listening to meditative music on state anxiety and heart rate variability (HRV) of patients during the uptake phase before positron emission tomography (PET) scans. Methods: A two-group randomized experimental design was used. Eligible patients were randomly assigned to either the experimental or control group. All patients received baseline assessments of state anxiety using Spielberger State-Trait Anxiety Inventory (STAI-S) and HRV before receiving an intravenous injection of radiopharmaceutical fluorine-18 fludeoxyglucose in the uptake room. The experimental group (n = 35) listened individually to 30 min of meditative music, integrating Chinese “Chi” and western frequency resonation in the uptake room. The control group (n = 37) lay on bed quietly for 40 min in the uptake room without music. All patients were assessed for their anxiety level and HRV again, before receiving PET scanning as post-test. Results: The results indicated that patients in the experimental group showed a significant reduction in state anxiety and heart rate, and increase on high frequency norm of HRV (p < 0.001). There was a statistically significant reduction on anxiety level (p < 0.001), heart rate (p < 0.001) and high frequency norm (p = 0.001) in the experimental group compared with those of the control group. Conclusion: Listening to meditative music as a non-invasive and cost-effective strategy can help maximize efforts to promote comfort and relaxation for patients awaiting stressful procedures, such as PET scans. Meditative music can be effective in alleviating state anxiety of patients during the uptake phase before PET scans. Advances in knowledge: The study provides scientific evidence of the effects of listening to meditative music for reducing state anxiety in patients during the uptake phase before PET scans. It may have the potential to lower the risk of unwanted false-positive fluorine-18 fludeoxyglucose uptake in normal organs and to further improve image quality and image interpretation. Listening to meditative music is a safe and inexpensive intervention which can be incorporated into routine procedures to reduce anxiety of patients undergoing PET scans. PMID:27897034

Meditative music listening to reduce state anxiety in patients during the uptake phase before positron emission tomography (PET) scans.

PubMed

Lee, Wen-Li; Sung, Huei-Chuan; Liu, Shu-Hsin; Chang, Shu-Min

2017-02-01

This study examines the effects of listening to meditative music on state anxiety and heart rate variability (HRV) of patients during the uptake phase before positron emission tomography (PET) scans. A two-group randomized experimental design was used. Eligible patients were randomly assigned to either the experimental or control group. All patients received baseline assessments of state anxiety using Spielberger State-Trait Anxiety Inventory (STAI-S) and HRV before receiving an intravenous injection of radiopharmaceutical fluorine-18 fludeoxyglucose in the uptake room. The experimental group (n = 35) listened individually to 30 min of meditative music, integrating Chinese "Chi" and western frequency resonation in the uptake room. The control group (n = 37) lay on bed quietly for 40 min in the uptake room without music. All patients were assessed for their anxiety level and HRV again, before receiving PET scanning as post-test. The results indicated that patients in the experimental group showed a significant reduction in state anxiety and heart rate, and increase on high frequency norm of HRV (p < 0.001). There was a statistically significant reduction on anxiety level (p < 0.001), heart rate (p < 0.001) and high frequency norm (p = 0.001) in the experimental group compared with those of the control group. Listening to meditative music as a non-invasive and cost-effective strategy can help maximize efforts to promote comfort and relaxation for patients awaiting stressful procedures, such as PET scans. Meditative music can be effective in alleviating state anxiety of patients during the uptake phase before PET scans. Advances in knowledge: The study provides scientific evidence of the effects of listening to meditative music for reducing state anxiety in patients during the uptake phase before PET scans. It may have the potential to lower the risk of unwanted false-positive fluorine-18 fludeoxyglucose uptake in normal organs and to further improve image quality and image interpretation. Listening to meditative music is a safe and inexpensive intervention which can be incorporated into routine procedures to reduce anxiety of patients undergoing PET scans.

Effects of Bread with Nigella Sativa on Lipid Profiles, Apolipoproteins and Inflammatory Factor in Metabolic Syndrome Patients

PubMed Central

2016-01-01

Nigella sativa (N.sativa) has been used in traditional medicine and many studies have been performed in different communities in order to reveal the effects of it on medical disorders and chronic diseases. The aim of this study was to investigate the effects of bread with N. Sativa on lipid profiles, apolipoproteins, and inflammatory factors in metabolic syndrome (MetS) patients. A randomized, double-blind, cross-over and clinical trial was conducted in 51 MetS patients of both sexes with age group of 20-65 years old in Chaloos, north of Iran. Patients were randomly divided in two groups. In phase 1, intervention group (A, n = 27) received daily a bread with N. sativa and wheat bran and control group (B, n = 24) received the same bread without N. sativa for 2 months. After 2 weeks of wash out period, phase 2 was started with switch the intervention between two groups. Measuring of lipid profiles, apolipoproteins and inflammatory factor was performed for all patients before and after two phases. In this study, treatment, sequence and time effects of intervention were evaluated and revealed that consumption of bread with N. sativa has no significant treatment and time effects on triglyceride (TG), cholesterol (CHOL), low density lipoprotein (LDL), high density lipoprotein (HDL), apolipoprotein (APO)-A, APO-B and high-sensitivity C-reactive protein (p > 0.05). Sequence effect was significant on CHOL, LDL, APO-A, and APO-B (p < 0.05) but was not significant on other parameters (p > 0.05). Consumption of bread with N. sativa has no a significant effect on lipid profiles, apolipoproteins and inflammatory factor in MetS patients. PMID:27152298

Early functional outcome of two different orthotic concepts in ankle sprains: a randomized controlled trial.

PubMed

Best, Raymond; Böhle, Caroline; Schiffer, Thorsten; Petersen, Wolf; Ellermann, Andree; Brueggemann, Gert Peter; Liebau, Christian

2015-07-01

Purpose of the study was the evaluation of the early functional outcome of patients with an acute ankle sprain treated either with a semirigid, variable, phase-adapted modular ankle orthosis or an invariable orthotic reference device. Forty-seven patients with acute ankle sprain grade II or more were included. In addition, 77 healthy controls as a reference were investigated. The injured subjects were treated with one of the two devices by random for 6 weeks. Ankle scores (FAOS, AOFAS) were taken at baseline after injury, 1 and 3 months after injury. Functional performance tests (balance platform, zig zag run, shuttle run, vertical drop jump) were performed at 1 and 3 months after injury. No significant score differences could be found between the two intervention groups except for achieving a preinjury activity level after 3 months only in the modular orthosis group. Postural functional performances (balance test) also showed no significant differences whereas the results of the agility tests revealed small but significant better results in the modular orthosis group in comparison to the invariable orthosis group. Cohen's effect sizes were high. Differences between the two intervention groups were marginal and very small but significant and--regarding Cohen's effect sizes--effective. Especially relating to functional performance, this might be a careful indication that a more effective strategy for promoting a protected, rapid recovery to physical activity after ankle sprains might be achieved by applying a phase-adapted ankle orthosis. Especially in athletic patients, phase-adapted orthosis should be further investigated and considered to ensure fully protected ligament healing as well as to regain early functional recovery.

Combination of robot-assisted and conventional body-weight-supported treadmill training improves gait in persons with multiple sclerosis: a pilot study.

PubMed

Ruiz, Jennifer; Labas, Michele P; Triche, Elizabeth W; Lo, Albert C

2013-12-01

The majority of persons with multiple sclerosis (MS) experience problems with gait, which they characterize as highly disabling impairments that adversely impact their quality of life. Thus, it is crucial to develop effective therapies to improve mobility for these individuals. The purpose of this study was to determine whether combination gait training, using robot-assisted treadmill training followed by conventional body-weight-supported treadmill training within the same session, improved gait and balance in individuals with MS. This study tested combination gait training in 7 persons with MS. The participants were randomized into the immediate therapy group (IT group) or the delayed therapy group (DT group). In phase I of the trial, the IT group received treatment while the DT group served as a concurrent comparison group. In phase II of the trial, the DT group received treatment identical to the treatment received by the IT group in phase I. Outcome measures included the 6-Minute Walk Test (6MWT), the Timed 25-Foot Walk Test, velocity, cadence, and the Functional Reach Test (FRT). Nonparametric statistical techniques were used for analysis. Combination gait training resulted in significantly greater improvements in the 6MWT for the IT group (median change = +59 m) compared with Phase I DT group (median change = -8 m) (P = 0.08) and FRT (median change = +3.3 cm in IT vs -0.8 cm in the DT group phase I; P = 0.03). Significant overall pre-post improvements following combination gait training were found in 6MWT (+32 m; P = 0.02) and FRT (+3.3 cm; P = 0.06) for IT and Phase II DT groups combined. Combination of robot with body-weight-supported treadmill training gait training is feasible and improved 6MWT and FRT distances in persons with MS.Video Abstract available (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A62) for more insights from the authors.

Practical characteristics of adaptive design in phase 2 and 3 clinical trials.

PubMed

Sato, A; Shimura, M; Gosho, M

2018-04-01

Adaptive design methods are expected to be ethical, reflect real medical practice, increase the likelihood of research and development success and reduce the allocation of patients into ineffective treatment groups by the early termination of clinical trials. However, the comprehensive details regarding which types of clinical trials will include adaptive designs remain unclear. We examined the practical characteristics of adaptive design used in clinical trials. We conducted a literature search of adaptive design clinical trials published from 2012 to 2015 using PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, with common search terms related to adaptive design. We systematically assessed the types and characteristics of adaptive designs and disease areas employed in the adaptive design trials. Our survey identified 245 adaptive design clinical trials. The number of trials by the publication year increased from 2012 to 2013 and did not greatly change afterwards. The most frequently used adaptive design was group sequential design (n = 222, 90.6%), especially for neoplasm or cardiovascular disease trials. Among the other types of adaptive design, adaptive dose/treatment group selection (n = 21, 8.6%) and adaptive sample-size adjustment (n = 19, 7.8%) were frequently used. The adaptive randomization (n = 8, 3.3%) and adaptive seamless design (n = 6, 2.4%) were less frequent. Adaptive dose/treatment group selection and adaptive sample-size adjustment were frequently used (up to 23%) in "certain infectious and parasitic diseases," "diseases of nervous system," and "mental and behavioural disorders" in comparison with "neoplasms" (<6.6%). For "mental and behavioural disorders," adaptive randomization was used in two trials of eight trials in total (25%). Group sequential design and adaptive sample-size adjustment were used frequently in phase 3 trials or in trials where study phase was not specified, whereas the other types of adaptive designs were used more in phase 2 trials. Approximately 82% (202 of 245 trials) resulted in early termination at the interim analysis. Among the 202 trials, 132 (54% of 245 trials) had fewer randomized patients than initially planned. This result supports the motive to use adaptive design to make study durations shorter and include a smaller number of subjects. We found that adaptive designs have been applied to clinical trials in various therapeutic areas and interventions. The applications were frequently reported in neoplasm or cardiovascular clinical trials. The adaptive dose/treatment group selection and sample-size adjustment are increasingly common, and these adaptations generally follow the Food and Drug Administration's (FDA's) recommendations. © 2017 John Wiley & Sons Ltd.

Use of papain gel in disabled patients.

PubMed

Carrillo, C M; Tanaka, M H; Cesar, M F; Camargo, M A F; Juliano, Y; Novo, N F

2008-01-01

This study's purpose was to evaluate complete caries removal time (CCR) and patient acceptance of the chemomechanical caries removal agent and papain gel Papacárie in disabled patients. Fifty-one consecutive patients entered a prospective, controlled, randomized, open study. Patients were divided into 2 groups: (1) group 1=28 children 3 to 10 years old with or without visual or hearing impairments, motor disability on upper limbs, and inability to respond to simple orders; and (2) group 2=23 children, without visual or hearing impairments, with motor disability on the upper limbs and the ability to respond to simple orders. CCR time was measured in both groups. Patients' acceptance was assessed only in group 2 by using the visual analogy of face scale. The visual scale was presented in phase A--after the radiography with the child sitting on the dental chair before the beginning of the treatment, phase B--during the treatment, after total removal of the carious tissue and phase C--after the restoration was complete (treatment was finished). The total CCR average time was 8 minutes for each tooth when groups 1 and 2 were considered. Group 2 patients' acceptance in the first treatment was not statistically significant in all stages. Papacárie gel had a completed caries removal time of 8 minutes per tooth and is well accepted by the patients in all phases and in the first and subsequent visits.

A phase 2 randomized trial of ELND005, scyllo-inositol, in mild to moderate Alzheimer disease

PubMed Central

Sperling, R.; Keren, R.; Porsteinsson, A.P.; van Dyck, C.H.; Tariot, P.N.; Gilman, S.; Arnold, D.; Abushakra, S.; Hernandez, C.; Crans, G.; Liang, E.; Quinn, G.; Bairu, M.; Pastrak, A.; Cedarbaum, J.M.

2011-01-01

Objective: This randomized, double-blind, placebo-controlled, dose-ranging phase 2 study explored safety, efficacy, and biomarker effects of ELND005 (an oral amyloid anti-aggregation agent) in mild to moderate Alzheimer disease (AD). Methods: A total of 353 patients were randomized to ELND005 (250, 1,000, or 2,000 mg) or placebo twice daily for 78 weeks. Coprimary endpoints were the Neuropsychological Test Battery (NTB) and Alzheimer's Disease Cooperative Study–Activities of Daily Living (ADCS-ADL) scale. The primary analysis compared 250 mg (n =84) to placebo (n =82) after an imbalance of infections and deaths led to early discontinuation of the 2 higher dose groups. Results: The 250 mg dose demonstrated acceptable safety. The primary efficacy analysis at 78 weeks revealed no significant differences between the treatment groups on the NTB or ADCS-ADL. Brain ventricular volume showed a small but significant increase in the overall 250 mg group (p =0.049). At the 250 mg dose, scyllo-inositol concentrations increased in CSF and brain and CSF Aβx-42 was decreased significantly compared to placebo (p =0.009). Conclusions: Primary clinical efficacy outcomes were not significant. The safety and CSF biomarker results will guide selection of the optimal dose for future studies, which will target earlier stages of AD. Classification of evidence: Due to the small sample sizes, this Class II trial provides insufficient evidence to support or refute a benefit of ELND005. PMID:21917766

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.

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.

Effects of edaravone on muscle atrophy and locomotor function in patients with ischemic stroke: a randomized controlled pilot study.

PubMed

Naritomi, Hiroaki; Moriwaki, Hiroshi; Metoki, Norifumi; Nishimura, Hiroyuki; Higashi, Yasuto; Yamamoto, Yasumasa; Yuasa, Hiroyuki; Oe, Hiroshi; Tanaka, Kortaro; Saito, Kozue; Terayama, Yasuo; Oda, Tadafumi; Tanahashi, Norio; Kondo, Hisao

2010-01-01

Stroke patients with severe leg paralysis are often bedridden in the acute and subacute phase, which increases the risk of disuse muscle atrophy in the chronic phase. The evidence to date indicates that oxidative stress plays an important role in the mechanism of disuse muscle atrophy. Therefore, the aim of this study was to determine if long-term radical scavenger treatment with edaravone following an acute stroke prevents the progression of disuse muscle atrophy and improves leg locomotor function in the chronic phase. This randomized controlled pilot study was conducted at 19 acute stroke and rehabilitation centers across Japan. Forty-seven ischemic stroke patients with at least leg motor weakness admitted within 24 hours of onset were randomly assigned to receive continuous intravenous infusions of edaravone 30 mg twice daily for 3 days (short-term group) or 10-14 days (long-term group). The primary endpoints of the study included the degree of leg disuse muscle atrophy, as measured by the percentage change from baseline in femoral muscle circumference 15 cm above the knee, and the improvement in leg locomotor function, as assessed by the maximum walking speed over 10 m, 3 months after the onset of stroke. Three-month follow-up was completed by a total of 41 patients (21 in the short-term group and 20 in the long-term group). On admission, there was no significant difference in the severity of stroke or the grade of leg paresis between the two treatment groups. The grade of disuse muscle atrophy and incidence of gait impairment 3 weeks after stroke onset were also similar between the short- and long-term groups. However, disuse muscle atrophy of the paretic and non-paretic legs was significantly less severe in the long-term versus the short-term treatment group (3.6 ± 5.9% and 1.5 ± 6.0% vs 8.3 ± 5.2% and 5.7 ± 6.4%; p < 0.01 and p < 0.05) 3 months after stroke onset. Additionally, the maximum walking speed over a distance of 10 m was significantly greater in the long-term group (98 ± 67 vs 54 ± 55 cm/sec; p < 0.05). Edaravone treatment for up to 14 days suppresses the progression of disuse muscle atrophy and improves leg locomotor function to a greater extent than shorter-term treatment in acute stroke patients. This suggests that the management of stroke may be improved with long-term edaravone therapy by providing myoprotective effects that ameliorate functional outcome in the chronic phase.

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.

Early rehabilitation exercise program for inpatients during an acute exacerbation of chronic obstructive pulmonary disease: a randomized controlled trial.

PubMed

Tang, Clarice Y; Blackstock, Felicity C; Clarence, Michael; Taylor, Nicholas F

2012-01-01

To determine whether an early rehabilitation program was safe and feasible for patients during an acute exacerbation of chronic obstructive pulmonary disease (COPD). In this phase 1 randomized controlled trial, patients with an acute exacerbation of COPD admitted to the hospital were randomly allocated to a low-intensity exercise group, a moderate- to high-intensity exercise group, or a control group, who received routine physical therapy. In addition to routine physical therapy, patients in the exercise group had to participate in an exercise program. The program consisted of twice-daily aerobic and resistance exercise sessions. Primary outcomes were the number and classification of adverse events and program adherence. In 174 exercise sessions, there was 1 serious adverse event of arrhythmia in the low-intensity exercise group that resolved within 1 hour. There were 12 other minor adverse events involving 5 patients with no significant differences between groups. Patients completed an average of 80% of their scheduled sessions with no significant between-group differences. The exercise groups improved significantly in walking distance; however, no significant between-group differences were observed. There was preliminary evidence that it was safe and feasible to implement an exercise program for patients during an acute exacerbation of COPD. Additional studies with larger sample sizes are required to accurately evaluate program effectiveness.

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.

Latanoprostene Bunod 0.024% in Subjects With Open-angle Glaucoma or Ocular Hypertension: Pooled Phase 3 Study Findings.

PubMed

Weinreb, Robert N; Liebmann, Jeffrey M; Martin, Keith R; Kaufman, Paul L; Vittitow, Jason L

2018-01-01

To compare the diurnal intraocular pressure (IOP)-lowering effect of latanoprostene bunod (LBN) 0.024% with timolol maleate 0.5% in subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT). Pooled analysis of two phase 3, randomized, multicenter, double-masked, parallel-group, noninferiority trials (APOLLO and LUNAR), each with open-label safety extension phases. Adults with OAG or OHT were randomized 2:1 to double-masked treatment with LBN once daily (qd) or timolol twice daily (bid) for 3 months followed by open-label LBN treatment for 3 (LUNAR) or 9 (APOLLO) months. IOP was measured at 8 AM, 12 PM, and 4 PM at week 2, week 6, and months 3, 6, 9, and 12. Of the 840 subjects randomized, 774 (LBN, n=523; timolol crossover to LBN, n=251) completed the efficacy phase, and 738 completed the safety extension phase. Mean IOP was significantly lower with LBN versus timolol at all 9 evaluation timepoints during the efficacy phase (P<0.001). A significantly greater proportion of LBN-treated subjects attained a mean IOP ≤18 mm Hg and IOP reduction ≥25% from baseline versus timolol-treated subjects (P<0.001). The IOP reduction with LBN was sustained through the safety phase; subjects crossed over from timolol to LBN experienced additional significant IOP lowering (P≤0.009). Both treatments were well tolerated, and there were no safety concerns with long-term LBN treatment. In this pooled analysis of subjects with OAG and OHT, LBN 0.024% qd provided greater IOP-lowering compared with timolol 0.5% bid and maintained lowered IOP through 12 months. LBN demonstrated a safety profile comparable to that of prostaglandin analogs.

Design of a Phase III cluster randomized trial to assess the efficacy and safety of a malaria transmission blocking vaccine.

PubMed

Delrieu, Isabelle; Leboulleux, Didier; Ivinson, Karen; Gessner, Bradford D

2015-03-24

Vaccines interrupting Plasmodium falciparum malaria transmission targeting sexual, sporogonic, or mosquito-stage antigens (SSM-VIMT) are currently under development to reduce malaria transmission. An international group of malaria experts was established to evaluate the feasibility and optimal design of a Phase III cluster randomized trial (CRT) that could support regulatory review and approval of an SSM-VIMT. The consensus design is a CRT with a sentinel population randomly selected from defined inner and buffer zones in each cluster, a cluster size sufficient to assess true vaccine efficacy in the inner zone, and inclusion of ongoing assessment of vaccine impact stratified by distance of residence from the cluster edge. Trials should be conducted first in areas of moderate transmission, where SSM-VIMT impact should be greatest. Sample size estimates suggest that such a trial is feasible, and within the range of previously supported trials of malaria interventions, although substantial issues to implementation exist. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comparison between two forms of vaginally administered progesterone for luteal phase support in assisted reproduction cycles.

PubMed

Geber, Selmo; Moreira, Ana Carolina Ferreira; de Paula, Sálua Oliveira Calil; Sampaio, Marcos

2007-02-01

The use of progesterone for luteal phase support has been demonstrated to be beneficial in assisted reproduction cycles using gonadotrophin-releasing hormone analogues (GnRHa). Two micronized progesterone preparations are available for vaginal administration: capsules and gel. The objective of this study was to compare the efficacy of these two forms for luteal phase support in assisted reproduction cycles. A total of 244 couples undergoing IVF/intracytoplasmic sperm injection cycles were included in the study and were randomly allocated (sealed envelopes) into two groups: group 1 (122) received vaginal capsules of 200 mg of micronized progesterone (Utrogestan), 3 times daily, and group 2 (122) received micronized progesterone in gel (Crinone 8%), once daily. Both groups received progesterone for 13 days beginning day 1 after oocyte retrieval, continuing until the pregnancy test was performed and until 12 weeks of pregnancy. Groups were compared by clinical data and assisted reproduction results and had similar ages and causes of infertility. Although the pregnancy rate was higher for those receiving progesterone gel than capsules (44.26 and 36.06% respectively), this difference was not statistically significant. The study showed that vaginal progesterone gel and capsules used for luteal phase support in assisted reproduction cycles with long protocol GnRHa result in similar pregnancy rates.

Does exercise deprivation increase the tendency towards morphine dependence in rats?

PubMed

Nakhaee, Mohammad Reza; Sheibani, Vahid; Ghahraman Tabrizi, Kourosh; Marefati, Hamid; Bahreinifar, Sareh; Nakhaee, Nouzar

2010-01-01

Exercise deprivation has been concluded to have some negative effectson psychological well-being. This study was conducted to find outwhether exercise deprivation may lead to morphine dependence in rats. Forty male Wistar rats weighing 162 ± 9 g were housed in clear plasticcages in groups of two under standard laboratory conditions. The studyhad two phases. In phase I, the animals were randomly divided intoexercised (E) and unexercised (UE) groups (n = 20 each) and treadmillrunning was performed based on a standard protocol for three weeks. Atthe end of the training period, plasma β-endorphin levels weredetermined in four rats from each group. In phase II, the animals wereprovided with two bottles, one containing tap water and the other 25mg/l morphine sulfate in tap water for a total of 12 weeks. At the end ofthis phase naloxone was injected intraperitoneally to precipitatemorphine withdrawal. THERE WAS NO SIGNIFICANT DIFFERENCE BETWEEN UE AND E GROUPS INMORPHINE CONSUMPTION (MG/KG/WK) [ F(1,14) = 0.2, P = 0.690; time:F(11,154) =18.72, P < 0.001; interaction: F(11,154) = 1.27 , P = 0.245]. Nostatistically significant difference between the two groups of animals wasseen regarding withdrawal signs. The study showed that discontinuation of exercise does not increasethe tendency of morphine dependence in rats.

Treatment Effect of Drug-Coated Balloons Is Durable to 3 Years in the Femoropopliteal Arteries

PubMed Central

Laird, John R.; Tepe, Gunnar; Brodmann, Marianne; Zeller, Thomas; Scheinert, Dierk; Metzger, Christopher; Micari, Antonio; Sachar, Ravish; Jaff, Michael R.; Wang, Hong; Hasenbank, Melissa S.; Krishnan, Prakash

2018-01-01

Background— Randomized controlled trials have reported favorable 1-year outcomes with drug-coated balloons (DCBs) for the treatment of symptomatic peripheral arterial disease when compared with standard percutaneous transluminal angioplasty (PTA). Evidence remains limited on the durability of the treatment effect with DCBs in the longer term. Methods and Results— IN.PACT SFA is a single-blind, randomized trial (Randomized Trial of IN.PACT Admiral Paclitaxel-Coated Percutaneous Transluminal Angioplasty [PTA] Balloon Catheter vs Standard PTA for the Treatment of Atherosclerotic Lesions in the Superficial Femoral Artery [SFA] and/or Proximal Popliteal Artery [PPA]) that enrolled 331 patients with symptomatic (Rutherford 2–4) femoropopliteal lesions up to 18 cm in length. Patients were randomized 2:1 to receive treatment with DCB or PTA. The 36-month assessments included primary patency, freedom from clinically driven target lesion revascularization, major adverse events, and functional outcomes. At 36 months, primary patency remained significantly higher among patients treated with DCB compared with PTA (69.5% versus 45.1%; log rank P<0.001). The rates of clinically driven target lesion revascularization were 15.2% and 31.1% (P=0.002) for the DCB and PTA groups, respectively. Functional outcomes were similarly improved between treatment groups even though subjects in the DCB group required significantly fewer reinterventions versus those in the PTA group (P<0.001 for target lesion revascularization, P=0.001 for target vessel revascularization). There were no device- or procedure-related deaths as adjudicated by an independent Clinical Events Committee. Conclusions— Three-year results demonstrate a durable and superior treatment effect among patients treated with DCB versus standard PTA, with significantly higher primary patency and lower clinically driven target lesion revascularization, resulting in similar functional improvements with reduced need for repeat interventions. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01175850 for IN.PACT SFA phase I in the European Union and NCT01566461 for IN.PACT SFA phase II in the United States. PMID:29326153

Assessing the Eventual Publication of Clinical Trial Abstracts Submitted to a Large Annual Oncology Meeting.

PubMed

Massey, Paul R; Wang, Ruibin; Prasad, Vinay; Bates, Susan E; Fojo, Tito

2016-03-01

Despite the ethical imperative to publish clinical trials when human subjects are involved, such data frequently remain unpublished. The objectives were to tabulate the rate and ascertain factors associated with eventual publication of clinical trial results reported as abstracts in the Proceedings of the American Society of Clinical Oncology (American Society of Clinical Oncology). Abstracts describing clinical trials for patients with breast, lung, colorectal, ovarian, and prostate cancer from 2009 to 2011 were identified by using a comprehensive online database (http://meetinglibrary.asco.org/abstracts). Abstracts included reported results of a treatment or intervention assessed in a discrete, prospective clinical trial. Publication status at 4-6 years was determined by using a standardized search of PubMed. Primary outcomes were the rate of publication for abstracts of randomized and nonrandomized clinical trials. Secondary outcomes included factors influencing the publication of results. A total of 1,075 abstracts describing 378 randomized and 697 nonrandomized clinical trials were evaluated. Across all years, 75% of randomized and 54% of nonrandomized trials were published, with an overall publication rate of 61%. Sample size was a statistically significant predictor of publication for both randomized and nonrandomized trials (odds ratio [OR] per increase of 100 participants = 1.23 [1.11-1.36], p < .001; and 1.64 [1.15-2.34], p = .006, respectively). Among randomized studies, an industry coauthor or involvement of a cooperative group increased the likelihood of publication (OR 2.37, p = .013; and 2.21, p = .01, respectively). Among nonrandomized studies, phase II trials were more likely to be published than phase I (p < .001). Use of an experimental agent was not a predictor of publication in randomized (OR 0.76 [0.38-1.52]; p = .441) or nonrandomized trials (OR 0.89 [0.61-1.29]; p = .532). This is the largest reported study examining why oncology trials are not published. The data show that 4-6 years after appearing as abstracts, 39% of oncology clinical trials remain unpublished. Larger sample size and advanced trial phase were associated with eventual publication; among randomized trials, an industry-affiliated author or a cooperative group increased likelihood of publication. Unfortunately, we found that, despite widespread recognition of the problem and the creation of central data repositories, timely publishing of oncology clinical trials results remains unsatisfactory. ©AlphaMed Press.

Fluoride Varnish Effect on Preventing Dental Caries in a Sample of 3-6 Years Old Children

PubMed Central

Mohammadi, Tayebeh Malek; Hajizamani, Abolghasem; Hajizamani, Hamid Reza; Abolghasemi, Batol

2015-01-01

Background: Early childhood caries is one of the most prevalent chronic diseases of children that affect their life and their family in different aspects. Using different types of fluoride is one of the most effective ways for preventing the disease. Fluoride varnish is a topical fluoride product which could use in the community even by non-professional. This study aimed to assess the effect of fluoride varnish on dental caries in a group of children aged 3-6 years old in Kerman kindergarten during 6 month’s period. Materials and Methods: This community interventional study recruited a sample of volunteer children from 12 kindergartens through a cluster sampling. Kindergarten randomly allocated to test and control group after matching. Dental examination was performed in three phases of the study by a trained dentist using criteria of Intentional Caries Detection and Assessment System. Fluoride varnish was applied for test group in the first phase after dental examination and also 3 and 6 months after this phase. Control group has received varnish product just after 3 and 6 months after the first dental exam. Mean decayed, missed and filled teeth (dmft) were compared between and within groups using T-test. Results: From 476 children who participated in the study 55% were boys and the 6 years group was the most frequent group with 35% (166). Mean dmft difference was significant between Phase 1 and 2 (P = 0.05) in the test group but there was no significant difference between Phase 2 and 3 (P = 0.07). The difference was not significant between Phase 1 and 2 (P = 0.09) but it was significant between Phase 1 and 3 (P = 0.03) in the control group. Conclusion: The study results showed a decrease in mean dmft after applying the fluoride varnish which confirms previous studies. PMID:25709364

Huo-Luo-Xiao-Ling (HLXL)-Dan, a Traditional Chinese Medicine, for patients with osteoarthritis of the knee: a multi-site, randomized, double-blind, placebo-controlled phase II clinical trial.

PubMed

Lao, L; Hochberg, M; Lee, D Y W; Gilpin, A M K; Fong, H H S; Langenberg, P; Chen, K; Li, E K; Tam, L S; Berman, B

2015-12-01

To examine the efficacy and safety of Huo-Luo-Xiao-Ling (HLXL)-Dan, a Traditional Chinese Medicine (TCM), in patients with knee osteoarthritis (OA). A multi-site, randomized, double-blind, placebo-controlled phase II dose-escalation clinical trial was conducted. Eligible patients who fulfilled American College of Rheumatology criteria were randomized to receive either HLXL or placebo. Clinical assessments included measurement of knee pain and function with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), patient global assessment (PGA), and knee pain scores every 2 weeks. A Data and Safety Monitoring Board (DSMB) was established to review the data for ensuring the quality of the trial. In the first stage, 28 participants were randomized to receive either low-dose HLXL-Dan (2400 mg/day) or placebo for 6 weeks. The results showed no statistical difference between the two groups. The study was then re-designed following the recommendation of DSMB. Ninety-two patients were enrolled in the second stage and were randomized to receive either high-dose HLXL-Dan (4000 mg/day for week 1-2, and 5600 mg/day for week 3-8) or placebo for 8 weeks. All outcome assessments showed significant improvements for both groups after 8 weeks but no significant between-group differences. The change (mean ± SD) of WOMAC pain and WOMAC function scores of HLXL and placebo group after 8 weeks were -1.2 ± 1.7 vs -1.4 ± 1.5, and -1.1 ± 1.6 vs -1.3 ± 1.5 respectively. No serious adverse events were reported. Although safe to use, an 8-week treatment of HLXL-Dan was not superior to placebo for reduction in pain or functional improvement in patients with knee OA. Clinicaltrials.gov (NCT00755326). Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Effects of phase proprioceptive training on balance in patients with chronic stroke.

PubMed

Chae, Seung Hun; Kim, You Lim; Lee, Suk Min

2017-05-01

[Purpose] This study aimed to investigate the effect of phase proprioceptive training on balance in patients with chronic stroke. [Subjects and Methods] Participants included 30 patients with stroke who were randomly assigned to the proprioceptive training group (n=15) or control group (n=15). Participants in the proprioceptive training group underwent proprioceptive training and received general physical therapy each for a total of 20 thirty-minute sessions, five times per week, during a period of four weeks; the control group received general physical therapy for a total of 20 sixty-minute sessions, five times per week, during a period of four weeks. [Results] All participants were evaluated with the Berg Balance Scale, Timed Up and Go (TUG) test, and Activities-specific Balance Confidence (ABC) Scale instrument before and after intervention. After training, the differences in BBS, TUG, and ABC scores in the proprioceptive group were significantly greater than those in the control group. [Conclusion] In conclusion, proprioceptive training was effective on balance ability. Therefore, proprioceptive training may be efficient when combining general physical therapy with phase proprioceptive training for patients with impairments of balance. Further research is needed to investigate proprioceptive training methods.

Prevention and treatment of diarrhoea with Saccharomyces boulardii in children with acute lower respiratory tract infections.

PubMed

Shan, L-S; Hou, P; Wang, Z-J; Liu, F-R; Chen, N; Shu, L-H; Zhang, H; Han, X-H; Han, X-X; Cai, X-X; Shang, Y-X; Vandenplas, Y

2013-12-01

The aim of this study was to determine whether Saccharomyces boulardii prevents and treats diarrhoea and antibiotic-associated diarrhoea (AAD) in children. A total of 333 hospitalised children with acute lower respiratory tract infection were enrolled in a 2-phase open randomised controlled trial. During the 1st phase, all children received intravenous antibiotics (AB). They were randomly allocated to group A (S. boulardii 500 mg/day + AB, n=167) or group B (AB alone, n=166) and followed for 2 weeks. Diarrhoea was defined as ≥3 loose/watery stools/day during at least 2 days, occurring during treatment and/or up to 2 weeks after AB therapy had stopped. AAD was considered when diarrhoea was caused by Clostridium difficile or when stool cultures remained negative. In the 2nd phase of the study, group B patients who developed diarrhoea were randomly allocated to two sub-groups: group B1 (S. boulardii + oral rehydration solution (ORS)) and group B2 (ORS alone). Data from 283 patients were available for analysis. Diarrhoea prevalence was lower in group A than in group B (11/139 (7.9%) vs. 42/144 (29.2%); relative risk (RR): 0.27, 95% confidence interval (CI): 0.1-0.5). S. boulardii reduced the risk of AAD (6/139 (4.3%) vs. 28/144 (19.4%); RR: 0.22; 95% CI: 0.1-0.5). When group B patients developed diarrhoea (n=42), S. boulardii treatment during 5 days (group B1) resulted in lower stool frequency (P<0.05) and higher recovery rate (91.3% in group B1 vs. 21.1% in B2; P<0.001). The mean duration of diarrhoea in group B1 was shorter (2.31±0.95 vs. 8.97±1.07 days; P<0.001). No adverse effects related to S. boulardii were observed. S. boulardii appeared to be effective in the prevention and treatment of diarrhoea and AAD in children treated with intravenous antibiotics.

Effects of pistachio nut supplementation on blood glucose in patients with type 2 diabetes: a randomized crossover trial.

PubMed

Parham, Mahmoud; Heidari, Saeide; Khorramirad, Ashraf; Hozoori, Mohammad; Hosseinzadeh, Fatemeh; Bakhtyari, Lida; Vafaeimanesh, Jamshid

2014-01-01

Diabetes is a chronic, potentially debilitating, and often fatal disease. Dietary strategies to reduce postprandial glycemia are important in the prevention and treatment of diabetes. Nuts are rich in mono- and polyunsaturated fatty acids, which may reduce hyperglycemia and improve metabolism. To evaluate the effectiveness of pistachio nut supplementation on glycemic and inflammatory measures in patients with type 2 diabetes. In this double-blind, randomized, placebo-controlled, crossover trial, 48 diabetic patients were equally assigned to groups A and B. Patients in group A received a snack of 25 g pistachio nuts twice a day for 12 weeks and group B received a control meal without nuts. After 12 weeks of intervention, the patients had an 8-week washout. Then the groups were displaced, and group B received the same amount of pistachios for 12 weeks. With respect to the total change in variables over both phases, there was a marked decrease in HbA1c (-0.4%) and fasting blood glucose (FBG) concentrations (-16 mg/dl) in the pistachio group compared with the control group (p ≤ 0.001 for both). There was no overall significant change in BMI, blood pressure, HOMA-IR, and C-reactive protein (CRP) concentrations. Analysis of the two phases separately showed a decrease in FBG by 14 mg/dl and in HbA1c by 0.45% in the treatment group (A) after 12 weeks, while no significant differences were seen in group B (control group). In the second phase, FBG decreased from 151.36 ± 39.22 to 137.28 ± 28.65 mg/dl (-14 mg/dl) and HbA1c decreased from 7.42 ± 0.97 to 7.15 ± 0.68 mg/dl (-0.28%, p = 0.013 and p = 0.033, respectively) in the pistachio group (B). Pistachio consumption reduced systolic blood pressure (p = 0.007), BMI (p = 0.011), and CRP (p = 0.002) in patients from the treatment groups, but not insulin resistance. Dietary consumption of pistachio nuts as a snack has beneficial effects on glycemic control, blood pressure, obesity, and inflammation markers in diabetic patients.

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.

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

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.

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.

Early headgear effect on the eruption pattern of maxillary second molars.

PubMed

Abed, Yossi; Brin, Ilana

2010-07-01

To test the hypothesis that the use of a combination headgear (HG) during the first phase of orthodontic treatment has no effect on the eruption pattern of the maxillary second permanent molars. The records of the patients in a two-phase randomized clinical trial of early Class II treatment were utilized. The HG group comprised 47 patients, and the control (CON) group comprised 52 patients. The mean age of both groups was 9.4 years at the beginning of the clinical trial (T1). Cephalograms and panoramic views obtained at T1 and at the end of 15 months of phase I treatment or observation (T2) were utilized. The vertical and horizontal movements of the first and second upper molars (U6 and U7, respectively) were measured. The beginning of phase II (T3) and the end of phase II (T4) records were visually reviewed for follow-up of the eruption of the U7. The pattern of movement for the distal and vertical displacement of the U6 and U7 was significantly different in the HG and CON groups (P < .001). At the end of phase I, none of the U7 in either group were diagnosed as malposed or suspected for impaction. At the end of phase II, all but one U7 with a possible cystic lesion had erupted. The hypothesis is rejected. Forces exerted by combination headgear to the U6 in phase I have a distalizing effect and a transitory slowing down effect on the eruption of the U7 buds. These latter teeth always erupted except when pathology occurred.

Active versus passive adverse event reporting after pediatric chiropractic manual therapy: study protocol for a cluster randomized controlled trial.

PubMed

Pohlman, Katherine A; Carroll, Linda; Tsuyuki, Ross T; Hartling, Lisa; Vohra, Sunita

2017-12-01

Patient safety performance can be assessed with several systems, including passive and active surveillance. Passive surveillance systems provide opportunity for health care personnel to confidentially and voluntarily report incidents, including adverse events, occurring in their work environment. Active surveillance systems systematically monitor patient encounters to seek detailed information about adverse events that occur in work environments; unlike passive surveillance, active surveillance allows for collection of both numerator (number of adverse events) and denominator (number of patients seen) data. Chiropractic manual therapy is commonly used in both adults and children, yet few studies have been done to evaluate the safety of chiropractic manual therapy for children. In an attempt to evaluate this, this study will compare adverse event reporting in passive versus active surveillance systems after chiropractic manual therapy in the pediatric population. This cluster randomized controlled trial aims to enroll 70 physicians of chiropractic (unit of randomization) to either passive or active surveillance system to report adverse events that occur after treatment for 60 consecutive pediatric (13 years of age and younger) patient visits (unit of analysis). A modified enrollment process with a two-phase consent procedure will be implemented to maintain provider blinding and minimize dropouts. The first phase of consent is for the provider to confirm their interest in a trial investigating the safety of chiropractic manual therapy. The second phase ensures that they understand the specific requirements for the group to which they were randomized. Percentages, incidence estimates, and 95% confidence intervals will be used to describe the count of reported adverse events in each group. The primary outcome will be the number and quality of the adverse event reports in the active versus the passive surveillance group. With 80% power and 5% one-sided significance level, the sample size was calculated to be 35 providers in each group, which includes an 11% lost to follow-up of chiropractors and 20% of patient visits. This study will be the first direct comparison of adverse event reporting using passive versus active surveillance. It is also the largest prospective evaluation of adverse events reported after chiropractic manual therapy in children, identified as a major gap in the academic literature. ClinicalTrials.gov, ID: NCT02268331 . Registered on 10 October 2014.

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

Four-month moxifloxacin-based regimens for drug-sensitive tuberculosis.

PubMed

Gillespie, Stephen H; Crook, Angela M; McHugh, Timothy D; Mendel, Carl M; Meredith, Sarah K; Murray, Stephen R; Pappas, Frances; Phillips, Patrick P J; Nunn, Andrew J

2014-10-23

Early-phase and preclinical studies suggest that moxifloxacin-containing regimens could allow for effective 4-month treatment of uncomplicated, smear-positive pulmonary tuberculosis. We conducted a randomized, double-blind, placebo-controlled, phase 3 trial to test the noninferiority of two moxifloxacin-containing regimens as compared with a control regimen. One group of patients received isoniazid, rifampin, pyrazinamide, and ethambutol for 8 weeks, followed by 18 weeks of isoniazid and rifampin (control group). In the second group, we replaced ethambutol with moxifloxacin for 17 weeks, followed by 9 weeks of placebo (isoniazid group), and in the third group, we replaced isoniazid with moxifloxacin for 17 weeks, followed by 9 weeks of placebo (ethambutol group). The primary end point was treatment failure or relapse within 18 months after randomization. Of the 1931 patients who underwent randomization, in the per-protocol analysis, a favorable outcome was reported in fewer patients in the isoniazid group (85%) and the ethambutol group (80%) than in the control group (92%), for a difference favoring the control group of 6.1 percentage points (97.5% confidence interval [CI], 1.7 to 10.5) versus the isoniazid group and 11.4 percentage points (97.5% CI, 6.7 to 16.1) versus the ethambutol group. Results were consistent in the modified intention-to-treat analysis and all sensitivity analyses. The hazard ratios for the time to culture negativity in both solid and liquid mediums for the isoniazid and ethambutol groups, as compared with the control group, ranged from 1.17 to 1.25, indicating a shorter duration, with the lower bounds of the 95% confidence intervals exceeding 1.00 in all cases. There was no significant difference in the incidence of grade 3 or 4 adverse events, with events reported in 127 patients (19%) in the isoniazid group, 111 (17%) in the ethambutol group, and 123 (19%) in the control group. The two moxifloxacin-containing regimens produced a more rapid initial decline in bacterial load, as compared with the control group. However, noninferiority for these regimens was not shown, which indicates that shortening treatment to 4 months was not effective in this setting. (Funded by the Global Alliance for TB Drug Development and others; REMoxTB ClinicalTrials.gov number, NCT00864383.).

The Effectiveness of Propolis on Gingivitis: A Randomized Controlled Trial

PubMed Central

Paulino, Niraldo; Nör, Jacques E.; Moreira, Alexandre

2014-01-01

Abstract Background: A randomized, double-blind, controlled clinical trial was conducted to evaluate the effectiveness of a propolis rinse on induced gingivitis by using the co-twin study design. Methods: Twenty-one twin pairs (n=42) were enrolled in a gingivitis study with oral hygiene promotion (14 days) and gingivitis induction (21 days). During the gingivitis induction phase, one member of the twin pair was randomly assigned to a 2% typified propolis rinse, and the other was assigned a color-matched 0.05% sodium fluoride plus 0.05% cetylpyridinium chloride rinse (positive control). Patients rinsed twice daily with 20 mL for 30 seconds for 21 days. Gingivitis was measured on days −14 (baseline), 0 (after hygiene phase), and 21 (after no-hygiene phase) by using the Papillary Bleeding Score (PBS) and by standard digital imaging of the gum tissues (G-parameter). Results: The 38 persons who completed the study (age 13–22 years) were well balanced according to PBS at baseline and G-parameter after the initial hygiene phase. After 21 days without oral hygiene, the propolis rinse and positive control rinse groups did not differ significantly for average PBS measurements or G-parameter. Conclusions: Use of a 2% typified propolis rinse was equivalent to a positive control rinse during a 21-day no-hygiene period. PMID:25380344

Safety and immunogenicity of a killed Leishmania (L.) amazonensis vaccine against cutaneous leishmaniasis in Colombia: a randomized controlled trial.

PubMed

Vélez, I D; del Pilar Agudelo, S; Arbelaez, M P; Gilchrist, K; Robledo, S M; Puerta, J A; Zicker, F; Berman, J; Modabber, F

2000-01-01

The safety and immunogenicity of an intramuscular (i.m.) and intradermal (ID) formulation of autoclaved Leishmania (Leishmania) amazonensis vaccine was evaluated in 296 volunteers in a randomized, placebo-controlled, double-blind trial in Colombia. There were 4 vaccination groups: i.m. vaccine, i.m. placebo, ID vaccine, and ID placebo. The ID formulations were mixed with BCG as adjuvant at the time of injection. For each group, 3 vaccinations were given with a 20-day interval between injections, and adverse events were monitored at 20 min, and at 2, 7 and 21 days after each injection. BCG-induced adverse reactions resulted in cancellation of the third vaccine administration in the ID groups. Antibody titres did not differ significantly between the groups. Montenegro skin-test conversion was achieved by 86.4% and 90% of the i.m. vaccine group and by 25% and 5% of the i.m. placebo group 80 days and 1 year after vaccination, respectively. A significant increase in mean Leishmania-antigen lymphocyte proliferation indexes was observed after i.m. vaccine immunization, but not after i.m. placebo immunization, 80 days and 1 year after vaccination. Significant levels of IFN gamma but not IL-10 were observed 1 year after vaccination in the i.m. vaccine group compared to the i.m. placebo group. The good safety profile and evidence of Th1 immune reactions due to i.m. vaccination in this phase-I/II study suggest that a population-based phase-III efficacy trial of the i.m. vaccine should be initiated.

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

PubMed

Tyring, Stephen; Solomon, James A; Staedtler, Gerald; Lott, Jason P; Nkulikiyinka, Richard; Shakery, Kaweh

2016-10-01

Patient-reported treatment outcomes are important for evaluating the impact of drug therapies on patient experience. A randomized, double-blind, vehicle-controlled, parallel-group, multicenter, phase 3 study was conducted in 961 participants to assess patient perception of efficacy, utility, and effect on quality of life (QOL) of an azelaic acid (AzA) 15% foam formulation for the treatment of papulopustular rosacea (PPR). Secondary end points included patient-reported global assessment of treatment response, global assessment of tolerability, and opinion on cosmetic acceptability and practicability of product use. Quality of life assessments included the Dermatology Quality of Life Index (DLQI) and Rosacea Quality of Life Index (RosaQOL). Self-reported global assessment of treatment response favored AzA foam over vehicle foam (P<.001), with 57.2% of the AzA foam group reporting excellent or good improvement versus 44.7% in the vehicle foam group. Tolerability was rated excellent or good in 67.8% of the AzA foam group versus 78.2% of the vehicle foam group. Mean overall DLQI scores at end of treatment (EoT) were improved (P=.018) in favor of the AzA foam group compared with the vehicle foam group. Both treatment groups showed improvements in RosaQOL. Treatment with AzA foam was associated with improved QOL and meaningful reductions in the patient-perceived burden of PPR, which correlates with earlier reported primary end points of this study and supports the inclusion of patient perspectives in studies evaluating the effects of topical dermatologic treatments.

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.

High altitude induced anorexia: effect of changes in leptin and oxidative stress levels.

PubMed

Vats, Praveen; Singh, Vijay Kumar; Singh, Som Nath; Singh, Shashi Bala

2007-01-01

High altitude (HA) exposure usually leads to a significant weight loss in non-acclimatized humans. Anorexia is believed to be the main cause of this body weight loss. Appetite regulatory peptides, i.e. leptin and neuropeptide Y play a key role in food intake and energy homeostasis. Recent studies suggests increased oxidative stress during HA exposure. In present study effect of HA exposure on levels of leptin and NPY was evaluated along with N-acetyl cysteine (NAC) and vitamin E supplementation in relation to food intake and body weight changes. The study was conducted on 30 healthy male volunteers (age 19-29 years). Subjects were divided randomly into three groups of 10 each. Group 1 (placebo) supplemented with 400 mg of calcium gluconate, group 2 and 3 were supplemented with 400 mg of NAC and 400 mg vitamin E, respectively per day. The study was conducted at low altitude (320 m, Phase I), at HA 3600 m (Phase II) and at an altitude of 4580 m (Phase III). On HA exposure significant reduction in plasma leptin levels was observed in all the groups on day 2 (Phase II) along with decrease in food intake and reduction in body weight. Statistically significant increase in blood malondialdehyde (MDA) levels was seen in all the groups on HA exposure (Phase II, Day 2), but the maximum increase was in case of placebo group (65.1%) on day 2 (Phase II) in comparison to low altitude values. The decrease in energy intake was almost same in all the groups indicating that antioxidant supplementation did not provide any protection against HA anorexia. From the study, it may be concluded that leptin and oxidative stress possibly are not the key players for HA anorexia.

Optimal dose selection accounting for patient subpopulations in a randomized Phase II trial to maximize the success probability of a subsequent Phase III trial.

PubMed

Takahashi, Fumihiro; Morita, Satoshi

2018-02-08

Phase II clinical trials are conducted to determine the optimal dose of the study drug for use in Phase III clinical trials while also balancing efficacy and safety. In conducting these trials, it may be important to consider subpopulations of patients grouped by background factors such as drug metabolism and kidney and liver function. Determining the optimal dose, as well as maximizing the effectiveness of the study drug by analyzing patient subpopulations, requires a complex decision-making process. In extreme cases, drug development has to be terminated due to inadequate efficacy or severe toxicity. Such a decision may be based on a particular subpopulation. We propose a Bayesian utility approach (BUART) to randomized Phase II clinical trials which uses a first-order bivariate normal dynamic linear model for efficacy and safety in order to determine the optimal dose and study population in a subsequent Phase III clinical trial. We carried out a simulation study under a wide range of clinical scenarios to evaluate the performance of the proposed method in comparison with a conventional method separately analyzing efficacy and safety in each patient population. The proposed method showed more favorable operating characteristics in determining the optimal population and dose.

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.

Upregulation of Zinc Absorption Matches Increases in Physiologic Requirements for Zinc in Women Consuming High- or Moderate-Phytate Diets during Late Pregnancy and Early Lactation.

PubMed

Hambidge, K Michael; Miller, Leland V; Mazariegos, Manolo; Westcott, Jamie; Solomons, Noel W; Raboy, Victor; Kemp, Jennifer F; Das, Abhik; Goco, Norman; Hartwell, Ty; Wright, Linda; Krebs, Nancy F

2017-06-01

Background: Estimated physiologic requirements (PRs) for zinc increase in late pregnancy and early lactation, but the effect on dietary zinc requirements is uncertain. Objective: The aim of this study was to determine changes in daily fractional absorbed zinc and total absorbed zinc (TAZ) from ad libitum diets of differing phytate contents in relation to physiologic zinc requirements during pregnancy and lactation. Methods: This was a prospective observational study of zinc absorption at 8 (phase 1) and 34 (phase 2) wk of gestation and 2 (phase 3) and 6 (phase 4) mo of lactation. Participants were indigenous Guatemalan women of childbearing age whose major food staple was maize and who had been randomly assigned in a larger study to either of 2 ad libitum feeding groups: low-phytate maize (LP; 1.6 mg/g; n = 14) or control maize (C; 7.1 mg/g; n = 8). Total dietary zinc (milligrams per day, TDZ) and phytate (milligrams per day) were determined from duplicate diets and fractional absorption (FAZ) by dual isotope ratio technique (TAZ = TDZ × FAZ). All variables were examined longitudinally and by group and compared with PRs. TAZ values at later phases were compared with phase 1. Measured TAZ was compared with predicted TAZ for nonpregnant, nonlactating (NPNL) women. Results: TAZ was greater in the LP group than in the C group at all phases. All variables increased from phase 1 to phases 2 and 3 and declined at phase 4. TAZ increased by 1.25 mg/d ( P = 0.045) in the C group and by 0.81 mg/d ( P = 0.058) in the LP group at phase 2. At phase 3, the increases were 2.66 mg/d ( P = 0.002) in the C group and 2.28 mg/d ( P = 0.0004) in the LP group, compared with a 1.37-mg/d increase in PR. Measured TAZ was greater than predicted values in phases 2-4. Conclusions: Upregulation of zinc absorption in late pregnancy and early lactation matches increases in PRs of pregnant and lactating women, regardless of dietary phytate, which has implications for dietary zinc requirements of pregnant and lactating women. © 2017 American Society for Nutrition.

A Comparative Study on the Life-Saving Radioprotective Effects of Vitamins A, E, C and Over-the-Counter Multivitamins.

PubMed

Mortazavi, S M J; Rahimi, S; Mosleh-Shirazi, M A; Arjomandi, M; Soleimani, A; Koohi Hossein-Abadi, O; Haghani, M; Alavi, M

2015-06-01

Oral intake of vitamins which present antioxidant characteristics can protect living organisms against oxidative damage caused by exposure to ionizing radiation. It was previously reported that administration of high levels of vitamin C can lead to increased DNA damage through production of hydroxyl radicals from hydrogen peroxide by the Fenton reaction. However, our early experiments did not confirm this hypothesis. The main goal of this study was to determine if high doses of Vit C can show life-saving radioprotective effects. Phase I: Seventy two male Balb/c mice weighing 20-25g were randomly divided into six groups of 12 animals each. Group I; Vit E for five days, Groups II and III; Vit C and Vit A. Group 4; all three vitamins. Group V; an over-the-counter multivitamin. Group VI; none of the above. Phase II: 120 male BALB/c mice weighing 20-25g were randomly divided into 12 groups of 10 each. Group I; Vit A for five days. Groups II-IV; Vit C 200 mg/kg, 400 mg/kg, 800 mg/kg, respectively. Group V-VII; Vit E at daily doses of 200 iu/kg, 400 iu/kg, 800 iu/kg, respectively. Group VIII and IX; all three vitamins at low and high doses, respectively. Group X; an over-the-counter multivitamin. Group XI; controls group and Group XII; received pure olive oil. All animals (Phases I and II) were exposed to a lethal dose of gamma rays and the survival rates of the animals were monitored and recorded continuously for 16 days after exposure. Phase I: 14 days after irradiation the survival rate for control group was 33.33%, while the survival rates for the 1st to 5th groups were 45.45%, 81.81%, 50%, 57.14%, and 9.09% , respectively. Phase II: The survival rates in the control group and the group that only received pure olive oil, were 50% and 60%, respectively. Survival rate in the animals received Vit C at daily doses of 200 mg/kg, 400 mg/kg, 800 mg/kg, were 90%, 90% and 90%, respectively. Log rank (Mantel-Cox) test showed statistically significant differences between the survival rates in control irradiated mice (no vitamins) and mice received Vit C at daily doses of 200 mg/kg (P=0.042), 400 mg/kg (P=0.042) and 800 mg/kg (P=0.042). Altogether, findings of this study showed that even high doses of Vit C can show life-saving radioprotective effects. The significant radioprotective effect of Vit C at doses used in this study, opens new horizons in developing non-toxic, cost effective, easily available radioprotectors in life-threatening situations such as exposure to lethal doses of ionizing radiation.  The radioprotective effect of Vit A and Vit E seem to be less efficient compared to that of Vit C.

Antisense oligonucleotides targeting apolipoprotein(a) in people with raised lipoprotein(a): two randomised, double-blind, placebo-controlled, dose-ranging trials.

PubMed

Viney, Nicholas J; van Capelleveen, Julian C; Geary, Richard S; Xia, Shuting; Tami, Joseph A; Yu, Rosie Z; Marcovina, Santica M; Hughes, Steven G; Graham, Mark J; Crooke, Rosanne M; Crooke, Stanley T; Witztum, Joseph L; Stroes, Erik S; Tsimikas, Sotirios

2016-11-05

Elevated lipoprotein(a) (Lp[a]) is a highly prevalent (around 20% of people) genetic risk factor for cardiovascular disease and calcific aortic valve stenosis, but no approved specific therapy exists to substantially lower Lp(a) concentrations. We aimed to assess the efficacy, safety, and tolerability of two unique antisense oligonucleotides designed to lower Lp(a) concentrations. We did two randomised, double-blind, placebo-controlled trials. In a phase 2 trial (done in 13 study centres in Canada, the Netherlands, Germany, Denmark, and the UK), we assessed the effect of IONIS-APO(a) Rx , an oligonucleotide targeting apolipoprotein(a). Participants with elevated Lp(a) concentrations (125-437 nmol/L in cohort A; ≥438 nmol/L in cohort B) were randomly assigned (in a 1:1 ratio in cohort A and in a 4:1 ratio in cohort B) with an interactive response system to escalating-dose subcutaneous IONIS-APO(a) Rx (100 mg, 200 mg, and then 300 mg, once a week for 4 weeks each) or injections of saline placebo, once a week, for 12 weeks. Primary endpoints were mean percentage change in fasting plasma Lp(a) concentration at day 85 or 99 in the per-protocol population (participants who received more than six doses of study drug) and safety and tolerability in the safety population. In a phase 1/2a first-in-man trial, we assessed the effect of IONIS-APO(a)-L Rx , a ligand-conjugated antisense oligonucleotide designed to be highly and selectively taken up by hepatocytes, at the BioPharma Services phase 1 unit (Toronto, ON, Canada). Healthy volunteers (Lp[a] ≥75 nmol/L) were randomly assigned to receive a single dose of 10-120 mg IONIS-APO(a)L Rx subcutaneously in an ascending-dose design or placebo (in a 3:1 ratio; single-ascending-dose phase), or multiple doses of 10 mg, 20 mg, or 40 mg IONIS-APO(a)L Rx subcutaneously in an ascending-dose design or placebo (in an 8:2 ratio) at day 1, 3, 5, 8, 15, and 22 (multiple-ascending-dose phase). Primary endpoints were mean percentage change in fasting plasma Lp(a) concentration, safety, and tolerability at day 30 in the single-ascending-dose phase and day 36 in the multiple-ascending-dose phase in participants who were randomised and received at least one dose of study drug. In both trials, the randomised allocation sequence was generated by Ionis Biometrics or external vendor with a permuted-block randomisation method. Participants, investigators, sponsor personnel, and clinical research organisation staff who analysed the data were all masked to the treatment assignments. Both trials are registered with ClinicalTrials.gov, numbers NCT02160899 and NCT02414594. From June 25, 2014, to Nov 18, 2015, we enrolled 64 participants to the phase 2 trial (51 in cohort A and 13 in cohort B). 35 were randomly assigned to IONIS-APO(a) Rx and 29 to placebo. At day 85/99, participants assigned to IONIS-APO(a) Rx had mean Lp(a) reductions of 66·8% (SD 20·6) in cohort A and 71·6% (13·0) in cohort B (both p<0·0001 vs pooled placebo). From April 15, 2015, to Jan 11, 2016, we enrolled 58 healthy volunteers to the phase 1/2a trial of IONIS-APO(a)-L Rx . Of 28 participants in the single-ascending-dose phase, three were randomly assigned to 10 mg, three to 20 mg, three to 40 mg, six to 80 mg, six to 120 mg, and seven to placebo. Of 30 participants in the multiple-ascending-dose phase, eight were randomly assigned to 10 mg, eight to 20 mg, eight to 40 mg, and six to placebo. Significant dose-dependent reductions in mean Lp(a) concentrations were noted in all single-dose IONIS-APO(a)-L Rx groups at day 30. In the multidose groups, IONIS-APO(a)-L Rx resulted in mean reductions in Lp(a) of 66% (SD 21·8) in the 10 mg group, 80% (SD 13·7%) in the 20 mg group, and 92% (6·5) in the 40 mg group (p=0·0007 for all vs placebo) at day 36. Both antisense oligonucleotides were safe. There were two serious adverse events (myocardial infarctions) in the IONIS-APO(a) Rx phase 2 trial, one in the IONIS-APO(a) Rx and one in the placebo group, but neither were thought to be treatment related. 12% of injections with IONIS-APO(a) Rx were associated with injection-site reactions. IONIS-APO(a)-L Rx was associated with no injection-site reactions. IONIS-APO(a)-L Rx is a novel, tolerable, potent therapy to reduce Lp(a) concentrations. IONIS-APO(a)-L Rx might mitigate Lp(a)-mediated cardiovascular risk and is being developed for patients with elevated Lp(a) concentrations with existing cardiovascular disease or calcific aortic valve stenosis. Ionis Pharmaceuticals. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

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.

Comparison of efficacy and tolerance between combination therapy and monotherapy as first-line chemotherapy in elderly patients with advanced gastric cancer: Study protocol for a randomized controlled trial.

PubMed

Lee, Keun-Wook; Zang, Dae Young; Ryu, Min-Hee; Kim, Ki Hyang; Kim, Mi-Jung; Han, Hye Sook; Koh, Sung Ae; Park, Jin Hyun; Kim, Jin Won; Nam, Byung-Ho; Choi, In Sil

2017-12-01

The combination of a fluoropyrimidine [5-fluorouracil (5-FU), capecitabine, or S-1] with a platinum analog (cisplatin or oxaliplatin) is the most widely accepted first-line chemotherapy regimen for metastatic or recurrent advanced gastric cancer (AGC), based on the results of clinical trials. However, there is little evidence to guide chemotherapy for elderly patients with AGC because of under-representation of this age group in clinical trials. Thus, the aim of this study is to determine the optimal chemotherapy regimen for elderly patients with AGC by comparing the efficacies and safeties of combination therapy versus monotherapy as first-line chemotherapy. This study is a randomized, controlled, multicenter, phase III trial. A total of 246 elderly patients (≥70 years old) with metastatic or recurrent AGC who have not received previous palliative chemotherapy will be randomly allocated to a combination therapy group or a monotherapy group. Patients randomized to the combination therapy group will receive fluoropyrimidine plus platinum combination chemotherapy (capecitabine/cisplatin, S-1/cisplatin, capecitabine/oxaliplatin, or 5-FU/oxaliplatin), and those randomized to the monotherapy group will receive fluoropyrimidine monotherapy (capecitabine, S-1, or 5-FU). The primary outcome is the overall survival of patients in each treatment group. The secondary outcomes include progression-free survival, response rate, quality of life, and safety. We are conducting this pragmatic trial to determine whether elderly patients with AGC will obtain the same benefit from chemotherapy as younger patients. We expect that this study will help guide decision-making for the optimal treatment of elderly patients with AGC.

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.

A randomized, blinded, multicenter trial of a gentamicin vancomycin gel (DFA-02) in patients undergoing abdominal surgery.

PubMed

Bennett-Guerrero, Elliott; Berry, Scott M; Bergese, Sergio D; Fleshner, Phillip R; Minkowitz, Harold S; Segura-Vasi, Alvaro M; Itani, Kamal M F; Henderson, Karen W; Rackowski, Felicia P; Aberle, Laura H; Stryjewski, Martin E; Corey, G Ralph; Allenby, Kent S

2017-06-01

SI is a significant medical problem. DFA-02 is an investigational bioresorbable modified release gel consisting of both gentamicin (16.8 mg/mL) and vancomycin (18.8 mg/mL). A Phase 2a study, where the drug was applied during surgical incision closure, suggested safety and tolerability but was not designed to assess its efficacy. In a Phase 2b randomized, blinded trial patients undergoing abdominal, primarily colorectal, surgery were randomized (4:1:1) to one of three study arms: DFA-02, matching placebo gel, or standard of care (SOC) involving irrigation of the wound with normal saline. The DFA-02 and placebo gel groups received up to 20 mL of study drug inserted above the fascia during wound closure, and were treated in a double-blind manner; the SOC group was treated in a single-blind manner. The primary endpoint was SSI (adjudicated centrally by a blinded committee) through postoperative day 30. Overall, 445 subjects (intention-to-treat) were randomized at 35 centers with 425 subjects completing the study and being evaluable. There were 67 SSIs (15.8%): 64.2% superficial, 7.5% deep, and 28.4% organ space. The incidence of SSI was not statistically significantly different between the DFA-02 and the placebo gel/SOC arms combined, 42/287 = 14.6% vs 25/138 = 18.1% (p = 0.36), respectively. Rehospitalization within 30 days was also similar between study groups (DFA-02 28.6%, placebo gel 21.4%, SOC 27.3%). In this multicenter, blinded, randomized trial with central adjudication, the gentamicin/vancomycin gel was not associated with a significant reduction in SSI. Patients undergoing abdominal surgery were randomized to one of three study arms: DFA-02 gel consisting of both gentamicin and vancomycin, matching placebo gel, or standard of care (SOC). Of 425 patients completing the study at 35 sites the gentamicin/vancomycin gel was not associated with a significant reduction in SSI. Copyright © 2016 Elsevier Inc. All rights reserved.

Is the bioreactivity of vitamin-E-modified dialyzer an expression of increased plasmatic vitamin E concentration?

PubMed

Senatore, Massimimo; Nicoletti, A; Rizzuto, G

2002-10-01

The present study was designed to test the biocompatibility of a new vitamin E-modified multilayer membrane compared with highly biocompatible polysulphone dialyzer and acrylonitrile dialyzer. Thirty patients (mean age 53.2 +/- 15.3 SD years; dialytic age 36 +/- 5.6 months) were selected for the study. The study was divided into three periods of 6 months (phases A, B and C). In the first phase (from Jan. 1999 to June 1999) patients undergoing maintenance bicarbonate dialysis were randomly divided into three filter groups composed, respectively, of 10 patients: acrylonitrile group, polysulphone group and vitamin E-coated dialyzer group. In the phase B (from July 1999 to Dec. 1999) and in the phase C (from Jan. 2000 to June 2000), all three groups changed their own dialysis membranes. Vitamin E-coated dialyzer causes significant decreases in beta(2)-microglobulin, ferritin and immunoglobulin G, a normalization of complement C3 and an increase of plasmatic vitamin E compared to other filters. In the VE group homocysteine decreases but not in a significant manner. In addition, this dialyzer seems not to influence lipid pattern and protein-energy malnutrition parameters. These results clearly show a positive effect of this new filter in influencing different biochemical parameters, perhaps saving vitamin E and reducing polymorphonuclear cell activation. Copyright 2002 S. Karger AG, Basel

Modeling and Compensation of Random Drift of MEMS Gyroscopes Based on Least Squares Support Vector Machine Optimized by Chaotic Particle Swarm Optimization.

PubMed

Xing, Haifeng; Hou, Bo; Lin, Zhihui; Guo, Meifeng

2017-10-13

MEMS (Micro Electro Mechanical System) gyroscopes have been widely applied to various fields, but MEMS gyroscope random drift has nonlinear and non-stationary characteristics. It has attracted much attention to model and compensate the random drift because it can improve the precision of inertial devices. This paper has proposed to use wavelet filtering to reduce noise in the original data of MEMS gyroscopes, then reconstruct the random drift data with PSR (phase space reconstruction), and establish the model for the reconstructed data by LSSVM (least squares support vector machine), of which the parameters were optimized using CPSO (chaotic particle swarm optimization). Comparing the effect of modeling the MEMS gyroscope random drift with BP-ANN (back propagation artificial neural network) and the proposed method, the results showed that the latter had a better prediction accuracy. Using the compensation of three groups of MEMS gyroscope random drift data, the standard deviation of three groups of experimental data dropped from 0.00354°/s, 0.00412°/s, and 0.00328°/s to 0.00065°/s, 0.00072°/s and 0.00061°/s, respectively, which demonstrated that the proposed method can reduce the influence of MEMS gyroscope random drift and verified the effectiveness of this method for modeling MEMS gyroscope random drift.

Transdermal granisetron for the prevention of nausea and vomiting following moderately or highly emetogenic chemotherapy in Chinese patients: a randomized, double-blind, phase III study.

PubMed

Yang, Liu-Qing; Sun, Xin-Chen; Qin, Shu-Kui; Chen, Ying-Xia; Zhang, He-Long; Cheng, Ying; Chen, Zhen-Dong; Shi, Jian-Hua; Wu, Qiong; Bai, Yu-Xian; Han, Bao-Hui; Liu, Wei; Ouyang, Xue-Nong; Liu, Ji-Wei; Zhang, Zhi-Hui; Li, Yong-Qiang; Xu, Jian-Ming; Yu, Shi-Ying

2016-12-01

The granisetron transdermal delivery system (GTDS) has been demonstrated effectiveness in the control of chemotherapy-induced nausea and vomiting (CINV) in previous studies. This is the first phase III study to evaluate the efficacy and tolerability of GTDS in patients receiving moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC) in China. A total of 313 patients were randomized into the GTDS group (one transdermal granisetron patch, 7 days) or the oral granisetron group (granisetron oral 2 mg/day, ≥2 days). The primary endpoint was the percentage of patients achieving complete control (CC) from chemotherapy initiation until 24 h after final administration (PEEP). Chi-square test and Fisher's exact test were used for statistical analysis. Two hundred eighty-one patients were included in the per protocol analysis. During PEEP, CC was achieved by 67 (47.52%) patients in the GTDS group and 83 (59.29%) patients in the oral granisetron group. There was no statistical significance between the groups (P=0.0559). However, the difference of the CC percentage mainly occurred on the first day of chemotherapy between the groups. The CC was 70.13% on day 1 in the GTDS group, which was significantly lower than that of 91.03% in the oral granisetron group in the full analysis set. In the following days of chemotherapy, the CC was similar between the groups. In terms of cisplatin-contained regimen and female, there was statistical significance between the groups. Both treatments were well tolerated and safe. The most common adverse event was constipation. GTDS provided effective and well-tolerated control of CINV in Chinese patients, especially to non-cisplatin-contained regimen.

Complementary and alternative therapies to relieve labor pain: A comparative study between music therapy and Hoku point ice massage.

PubMed

Dehcheshmeh, Faranak Safdari; Rafiei, Hossein

2015-11-01

Pain is a common experience for women during labor. In the present study, we compared the effect of two types of non-pharmacological pain relief methods "music therapy" and "Hoku point ice massage" on the severity of labor pain. This prospective, randomized, controlled trial was conducted in Shahrekord, Iran, from September 2013 to June 2014. We randomly assigned 90 primiparous women who expected a normal childbirth into three groups: group "A" received music therapy, group "B" received Hoku point ice massage, and group "C" received usual labor care. At the beginning of the active phase (4 cm cervical dilation) and before and after each intervention (at dilations 4, 6, and 8 cm), the intensities of labor pain were measured using Visual Analogue Scale (VAS). At the beginning of the active phase, the mean VAS scores were 5.58 ± 1.29, 5.42 ± 1.31, and 6.13 ± 1.37 in the women in groups "A," "B," and "C," respectively (P > 0.05). After the intervention, the mean pain scores were significantly lower at all of the time points in groups "A" and "B" than in group "C" women (P < 0.05). Although the pain scores showed a more decreasing trend after the intervention in group "A" than that in group "B," the difference between the two groups was not statistically significant (P > 0.05). Music therapy and Hoku point ice massage are easily available and inexpensive methods and have a similar effect in relieving labor pain. Copyright © 2015 Elsevier Ltd. All rights reserved.

Impact of sleep, screen time, depression and stress on weight change in the intensive weight loss phase of the LIFE study.

PubMed

Elder, C R; Gullion, C M; Funk, K L; Debar, L L; Lindberg, N M; Stevens, V J

2012-01-01

The LIFE study is a two-phase randomized clinical trial comparing two approaches to maintaining weight loss following guided weight loss. Phase I provided a nonrandomized intensive 6-month behavioral weight loss intervention to 472 obese (body mass index 30-50) adult participants. Phase II is the randomized weight loss maintenance portion of the study. This paper focuses on Phase I measures of sleep, screen time, depression and stress. The Phase I intervention consisted of 22 group sessions led over 26 weeks by behavioral counselors. Recommendations included reducing dietary intake by 500 calories per day, adopting the Dietary Approaches to Stop Hypertension (DASH) dietary pattern and increasing physical exercise to at least 180 min per week. Measures reported here are sleep time, insomnia, screen time, depression and stress at entry and post-weight loss intervention follow-up. The mean weight loss for all participants over the intensive Phase I weight loss intervention was 6.3 kg (s.d. 7.1). Sixty percent (N=285) of participants lost at least 4.5 kg (10 lbs) and were randomized into Phase II. Participants (N=472) attended a mean of 73.1% (s.d. 26.7) of sessions, completed 5.1 (s.d. 1.9) daily food records/week, and reported 195.1 min (s.d. 123.1) of exercise per week. Using logistic regression, sleep time (quadratic trend, P=0.030) and lower stress (P=0.024) at entry predicted success in the weight loss program, and lower stress predicted greater weight loss during Phase I (P=0.021). In addition, weight loss was significantly correlated with declines in stress (P=0.048) and depression (P=0.035). Results suggest that clinicians and investigators might consider targeting sleep, depression and stress as part of a behavioral weight loss intervention.

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.

Soy Isoflavone supplementation for breast cancer risk reduction: a randomized phase II trial

PubMed Central

Khan, SA; Chatterton, RT; Michel, N; Bryk, M; Lee, O; Ivancic, D; Heinz, R.; Zalles, CM; Helenowski, I; Jovanovic, B; Franke, A; Bosland, M; Wang, J; Hansen, NM; Bethke, KP; Dew, A; Coomes, M.; Bergan, RC.

2012-01-01

Background Soy isoflavone consumption may protect against breast cancer development. We conducted a Phase IIB trial of soy isoflavone supplementation, to examine its effect on breast epithelial proliferation and other biomarkers in the healthy high risk breast. Methods 126 consented women underwent a random fine needle aspiration (rFNA); those with ≥ 4000 epithelial cells were randomized to a double-blind six-month intervention of mixed soy isoflavones (PTIG-2535) or placebo, followed by repeat rFNA. Cells were examined for Ki-67 labeling index (Ki-67 LI), and atypia. Expression of 28 genes related to proliferation, apoptosis and estrogenic effect was measured using quantitative RT-PCR. Hormone and protein levels were measured in nipple aspirate fluid (NAF). All statistical tests were 2-sided. Results 98 women were evaluable for Ki-67 LI. In 49 treated women, the median Ki-67 LI was 1.18 at entry and 1.12 post-intervention, whereas in 49 placebo subjects it was 0.97 and 0.92 (p for between-group change 0.32). Menopausal stratification yielded similar results between groups, but within premenopausal soy-treated women, Ki-67 LI increased from 1.71 to 2.18 (p=0.04). We saw no treatment effect on cytologic atypia or NAF parameters. There were significant increases in the expression of 14/28 genes within the soy, but not the control group, without significant between-group differences. Plasma genistein values demonstrated excellent compliance. Conclusions A six-month intervention of mixed soy isoflavones in healthy, high risk adult western women did not reduce breast epithelial proliferation, suggesting a lack of efficacy for breast cancer prevention, and a possible adverse effect in premenopausal women. PMID:22307566

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.

Tretinoin Nanogel 0.025% Versus Conventional Gel 0.025% in Patients with Acne Vulgaris: A Randomized, Active Controlled, Multicentre, Parallel Group, Phase IV Clinical Trial

PubMed Central

Chandrashekhar, B S; Anitha, M.; Ruparelia, Mukesh; Vaidya, Pradyumna; Aamir, Riyaz; Shah, Sunil; Thilak, S; Aurangabadkar, Sanjeev; Pal, Sandeep; Saraswat, Abir

2015-01-01

Background: Conventional topical tretinoin formulation is often associated with local adverse events. Nanogel formulation of tretinoin has good physical stability and enables good penetration of tretinoin into the pilo-sebaceous glands. Aim: The present study was conducted to assess the efficacy and safety of a nanogel formulation of tretinoin as compared to its conventional gel formulation in the treatment of acne vulgaris of the face. Materials and Methods: This randomized, active controlled, multicentric, phase IV clinical trial evaluated the treatment of patients with acne vulgaris of the face by the two gel formulations locally applied once daily at night for 12 wk. Acne lesion counts (inflammatory, non-inflammatory & total) and severity grading were carried out on the monthly scheduled visits along with the tolerability assessments. Results: A total of 207 patients were randomized in the study. Reductions in the total (72.9% vs. 65.0%; p = 0.03) and inflammatory (78.1% vs. 66.9%; p = 0.02) acne lesions were reported to be significantly greater with the nanogel formulation as compared to the conventional gel formulation. Local adverse events were significantly less (p = 0.04) in the nanogel group (13.3%) as compared to the conventional gel group (24.7%). Dryness was the most common adverse event reported in both the treatment groups while peeling of skin, burning sensation and photosensitivity were reported in patients using the conventional gel only. Conclusion: In the treatment of acne vulgaris of the face, tretinoin nanogel formulation appears to be more effective and better tolerated than the conventional gel formulation. PMID:25738069

Health-related quality of life, cognitive screening, and functional status in a randomized phase III trial (EF-14) of tumor treating fields with temozolomide compared to temozolomide alone in newly diagnosed glioblastoma.

PubMed

Zhu, Jay-Jiguang; Demireva, Petya; Kanner, Andrew A; Pannullo, Susan; Mehdorn, Maximilian; Avgeropoulos, Nicholas; Salmaggi, Andrea; Silvani, Antonio; Goldlust, Samuel; David, Carlos; Benouaich-Amiel, Alexandra

2017-12-01

We characterized health-related quality of life (HRQoL), cognitive, and functional status in newly diagnosed glioblastoma (GBM) patients receiving Tumor treating fields (TTFields) with temozolomide (TMZ) versus TMZ alone in a planned interim analysis of a randomized phase III trial [NCT00916409], which showed significant improvement in progression-free and overall survival with TTFields/TMZ. After radiotherapy with concomitant TMZ, newly diagnosed GBM patients were randomized (2:1) to TTFields/TMZ (n = 210) or TMZ (n = 105). Interim analysis was performed in 315 patients with ≥18 months of follow-up. HRQoL, a secondary endpoint, was evaluated in per-protocol patient population and expressed as change from baseline (CFB) at 3, 6, and 9 months for each subscale in the EORTC QLQ-C30/BN20. Karnofsky performance scores (KPS) and Mini-Mental State Examination scores (MMSE) were assessed. CFB in HRQoL was balanced in treatment groups at the 12-month time point. Initially, HRQoL improved in patients treated with TTFields/TMZ (CFB3: 24% and CFB6: 13%) versus TMZ (CFB3: -7% and CFB6: -17%), though this difference was no longer evident at the 9-month point. General scales, including physical and social functioning, showed no difference at 9 and 12 months. TTFields/TMZ group reported higher concerns of "itchy skin". KPS over 12 months was just below 90 in both groups. Cognitive status (MMSE) was stable over time. HRQoL, KPS, and MMSE were balanced in both groups over time. There was no preliminary evidence that HRQoL, cognitive, and functional status is adversely affected by the continuous use of TTFields.

Efficacy and Safety of Baricitinib in Japanese Patients with Active Rheumatoid Arthritis Receiving Background Methotrexate Therapy: A 12-week, Double-blind, Randomized Placebo-controlled Study.

PubMed

Tanaka, Yoshiya; Emoto, Kahaku; Cai, Zhihong; Aoki, Takehiro; Schlichting, Douglas; Rooney, Terence; Macias, William

2016-03-01

To evaluate efficacy and safety, baricitinib [Janus kinase (JAK) 1/JAK2 inhibitor] was compared with placebo in Japanese patients with active rheumatoid arthritis (RA) despite background treatment with methotrexate (MTX). This was a phase IIB, double-blind, randomized, placebo-controlled study (clinicaltrials.gov: NCT01469013). Patients had moderate to severe active adult-onset RA despite stable treatment with MTX. Patients (n = 145) were randomized in a 2:1:1:1:1 ratio to placebo or 1 mg, 2 mg, 4 mg, or 8 mg oral baricitinib daily for 12 weeks. The primary analysis compared the combined 4/8-mg dose groups with placebo for the American College of Rheumatology (ACR) 20 response rate at 12 weeks. Other outcomes included additional measures of disease activity, physical function, laboratory abnormalities, and adverse events. A significantly higher proportion of patients in the combined 4/8-mg baricitinib group (37/48, 77%) compared with the placebo group (15/49, 31%) had at least an ACR20 response after 12 weeks of treatment (p < 0.001). Significant improvements in disease activity, remission, and physical function were observed as early as Week 2 of treatment with baricitinib, particularly with daily doses of ≥ 4 mg. Only 1 patient receiving baricitinib discontinued because of an adverse event. Adverse event rates with baricitinib doses ≤ 4 mg daily were similar to placebo, but there was a higher incidence of adverse events and laboratory abnormalities in the 8-mg group. In this phase II study, baricitinib was well tolerated and rapidly improved the signs, symptoms, and physical function of Japanese patients with active RA, supporting continued development of baricitinib (clinicaltrials.gov NCT01469013).

Dental Students’ Preference with Regard to Tactile or Visual Determination of Injection Site for an Inferior Alveolar Nerve Block in Children: A Crossover Randomized Clinical Trial

PubMed Central

Iranmanesh, Seyed Masoud

2016-01-01

Objectives: Instruction of local anesthesia injection in an important part of dental education curricula. This study was performed to compare dental students’ preference with regard to tactile or visual determination of injection site for an inferior alveolar nerve block (IANB) in children. Materials and Methods: This crossover randomized clinical trial was conducted on dental students of Zahedan Dental School who took the first practical course of pediatric dentistry in the first academic semester of 2013–14 (n=42). They were randomly divided into two groups. During the first phase, group I was instructed to find the needle insertion point for an IANB via tactile method and group II was instructed to do it visually. In the second phase, the groups received instructions for the alternate technique. Both instructions were done using live demonstrations by the same instructor and immediately after instruction the learners practiced an IANB using the taught method. A five-point Likert scale questionnaire was then filled out by the students. The preference score was determined by calculating the mean of item scores. Data were analyzed using Mann-Whitney U and Wilcoxon Singed Rank tests in SPSS 19 at P=0.05 level of significance. Results: Thirty-eight students completed the study. By using the visual method to perform an IANB, students gained a significantly higher mean preference score (P=0.020). There was a significant difference in the preference of male students (P=0.008). Conclusions: Instruction of IANB by visual identification of needle insertion point is more desirable by students. PMID:27536327

Practice schedule and acquisition, retention, and transfer of a throwing task in 6-yr.-old children.

PubMed

Granda Vera, Juan; Montilla, Mariano Medina

2003-06-01

Earlier studies have raised questions about the usefulness of variable and random practice in learning motor tasks so this study was designed to investigate the effects of contextual interference in young children, and specifically to evaluate the effectiveness of variable or random practice structure in 6-yr.-old boys and girls. Participants on a variable practice schedule showed better performances than those on a blocked schedule. The differences between the two groups were significant in the acquisition, retention, and transfer phases. These results support the hypothesis that contextual interference enhances skill learning. Because the study involved groups of young children in the setting of their normally scheduled physical education class, the practical applications of the results are evident.

Randomized Phase II Trial of Adjuvant WT -1 Analog Peptide Vaccine in Patients with Malignant Pleural Mesothelioma after Completion of Multimodality Therapy

DTIC Science & Technology

2016-09-01

Interest Group 2016 Meeting Poster discussion at the American Society of Clinical Oncology Annual Meeting 2016 CONCLUSION: The clinical trial is now...Clinical Oncology 2016 Annual Meeting, Chicago, IL, Poster Discussion Presentation, June 4, 2016. APPENDICES: None SUPPORTING DATA: None

Mediators of Telephone-Based Continuing Care for Alcohol and Cocaine Dependence

ERIC Educational Resources Information Center

Mensinger, Janell Lynn; Lynch, Kevin G.; Tenhave, Thomas R.; McKay, James R.

2007-01-01

A previous randomized trial with 224 alcohol and/or cocaine addicts who had completed an initial phase of treatment indicated that 12 weeks of telephone-based continuing care yielded higher abstinence rates over 24 months than did group counseling continuing care. The current study examined mediators of this treatment effect. Results suggested…

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…

Hockey Fans in Training: A Pilot Pragmatic Randomized Controlled Trial

PubMed Central

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

2017-01-01

ABSTRACT Introduction 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. Methods Male fans of two ice hockey teams (35–65 yr; body mass index ≥28 kg·m−2) 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. Results 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. Conclusions 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. PMID:28719494

A randomized, double blind, controlled, multi center study of Ilaparazole in the treatment of reflux esophagitis-Phase III clinical trial.

PubMed

Xue, Yan; Qin, Xianghong; Zhou, Liya; Lin, Sanren; Wang, Ling; Hu, Haitang; Xia, Jielai

2018-05-01

Proton pump inhibitors (PPIs) are the main drugs for the treatment of reflux esophagitis. Phase II clinical trials showed that, compared with Esomeprazole, the new PPI Ilaparazole is great in terms of efficacy for reflux symptoms relief and curling for esophagitis. The aim of this study was to confirm suitable dose of Ilaparazole in the treatment of reflux esophagitis. This study used a randomized, double-blind, parallel positive drug control, multi-center design. A total of 537patients diagnosed as reflux esophagitis by gastroscopy were randomly divided into Ilaparazole group (n = 322, Ilaparazole 10 mg QD) and esomeprazole group (n = 215, Esomeprazole 40 mg QD). The patients in the two groups were treated for 8 weeks. Heartburn and reflux symptoms prior to treatment, and 2, 4 and 8 weeks after the treatment were assessed. Gastroscopy was performed after 4 weeks of treatment. Unhealed patients within 4 weeks underwent gastroscopy again at the end of 8 weeks. A total of 471 cases completed the treatment. In Esomeprazole and Ilaparazole groups. After 8 weeks treatment, the healing rate in Esomeprazole group and Ilaparazole group were 82.79% (94.94%) and 83.54% (92.50%), respectively. The corresponding rate difference [Ilaparazole-esomeprazole] was 0.75% (-2.44%) and the two-sided 95% CI was -5.72 to 7.22 (-6.90 to 2.01). The symptom disappearance rates for FAS (PPS) were 75.81% (82.02%) and 76.71% (80.36%) P = 0.8223 (0.7742). Adverse reactions related to the drugs were: 10.70% and 11.80%, (P = 0.7817). The efficacy and safety of Ilaparazole (10 mg/day) in treating reflux esophagitis was similar to esomeprazole (40 mg/day). Ilaparazole (10 mg/day) can be used in the treatment of esophagitis. The clinical trial registration number of the study is NCT 02860624. Copyright © 2018. Published by Elsevier Inc.

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.

Water-based vs. non-water-based physiotherapy for rehabilitation of postural deformities in Parkinson's disease: a randomized controlled pilot study.

PubMed

Volpe, Daniele; Giantin, Maria Giulia; Manuela, Pilleri; Filippetto, Consuelo; Pelosin, Elisa; Abbruzzese, Giovanni; Antonini, Angelo

2017-08-01

To compare the efficacy of two physiotherapy protocols (water-based vs. non-water-based) on postural deformities of patients with Parkinson's disease. A single blind, randomized controlled pilot study. Inpatient (Rehabilitative Department). A total of 30 patients with idiopathic Parkinson's disease. Participants were randomly assigned to one of two eight-week treatment groups: Water-based ( n = 15) or non-water-based physiotherapy exercises ( n = 15). Changes in the degree of cervical and dorsal flexion and in the angle of lateral inclination of the trunk (evaluated by means of a posturographic system) were used as primary outcomes. Unified Parkinson Disease Rating Scale section III, Time Up and Go Test, Berg Balance Scale, Activities-specific Balance Confidence, Falls Efficacy Scale and the Parkinson's disease quality of life questionnaire (39 items) were the secondary outcomes. All outcomes were assessed at baseline, at the end of training and eight weeks after treatment. Patients were always tested at the time of their optimal antiparkinsonian medication ('on' phase). After the treatment, only Parkinson's disease subjects randomized to water-based treatment showed a significant improvement of trunk posture with a significant reduction of cervical flexion (water-based group: -65.2°; non-water-based group: +1.7°) and dorsal flexion (water-based group: -22.5°; non-water-based group: -6.5°) and lateral inclination of the trunk (water-based group: -2.3°; non-water-based group: +0.3°). Both groups presented significant improvements in the secondary clinical outcomes without between-group differences. Our results show that water-based physiotherapy was effective for improving postural deformities in patients with Parkinson's disease.

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 ).

Dexpramipexole versus placebo for patients with amyotrophic lateral sclerosis (EMPOWER): a randomised, double-blind, phase 3 trial.

PubMed

Cudkowicz, Merit E; van den Berg, Leonard H; Shefner, Jeremy M; Mitsumoto, Hiroshi; Mora, Jesus S; Ludolph, Albert; Hardiman, Orla; Bozik, Michael E; Ingersoll, Evan W; Archibald, Donald; Meyers, Adam L; Dong, Yingwen; Farwell, Wildon R; Kerr, Douglas A

2013-11-01

In a phase 2 study, dexpramipexole (25-150 mg twice daily) was well tolerated for up to 9 months and showed a significant benefit at the high dose in a combined assessment of function and mortality in patients with amyotrophic lateral sclerosis. We aimed to assess efficacy and safety of dexpramipexole in a phase 3 trial of patients with familial or sporadic disease. In our randomised, double-blind, placebo-controlled phase 3 trial (EMPOWER), we enrolled participants aged 18-80 years (with first amyotrophic lateral sclerosis symptom onset 24 months or less before baseline) at 81 academic medical centres in 11 countries. We randomly allocated eligible participants (1:1) with a centralised voice-interactive online system to twice-daily dexpramipexole 150 mg or matched placebo for 12-18 months, stratified by trial site, area of disease onset (bulbar vs other areas), and previous use of riluzole. The primary endpoint was the combined assessment of function and survival (CAFS) score, based on changes in amyotrophic lateral sclerosis functional rating scale-revised (ALSFRS-R) total scores and time to death up to 12 months. We assessed the primary endpoint in all participants who received at least one dose and had at least one post-dose ALSFRS-R measurement or died. We monitored adverse events in all participants. This study is registered with ClinicalTrials.gov, number NCT01281189. Between March 28, 2011, and Sept 30, 2011, we enrolled 943 participants (474 randomly allocated dexpramipexole, 468 randomly allocated placebo, and one withdrew). Least-square mean CAFS scores at 12 months did not differ between participants in the dexpramipexole group (score 441·76, 95% CI 415·43-468·08) and those in the placebo group (438·84, 412·81-464·88; p=0·86). At 12 months, we noted no differences in mean change from baseline in ALSFRS-R total score (-13·34 in the dexpramipexole group vs -13·42 in the placebo group; p=0·90) or time to death (74 [16%] vs 79 [17%]; hazard ratio 1·03 [0·75-1·43]; p=0·84). 37 (8%) participants in the dexpramipexole group developed neutropenia compared with eight (2%) participants in the placebo group, and incidence of other adverse events was similar between groups. Dexpramipexole was generally well tolerated but did not differ from placebo on any prespecified efficacy endpoint measurement. Our trial can inform the design of future clinical research strategies in amyotrophic lateral sclerosis. Biogen Idec. Copyright © 2013 Elsevier Ltd. All rights reserved.

Efficacy and tolerability of fimasartan, a new angiotensin receptor blocker, compared with losartan (50/100 mg): a 12-week, phase III, multicenter, prospective, randomized, double-blind, parallel-group, dose escalation clinical trial with an optional 12-week extension phase in adult Korean patients with mild-to-moderate hypertension.

PubMed

Lee, Sang Eun; Kim, Yong-Jin; Lee, Hae-Young; Yang, Han-Mo; Park, Chang-Gyu; Kim, Jae-Joong; Kim, Soon-Kil; Rhee, Moo-Yong; Oh, Byung-Hee

2012-03-01

Angiotensin receptor blockers (ARBs) is an effective and well tolerated first-line antihypertensive drug. Fimasartan is a newly developed ARB that has not been compared with other ARBs with regard to its efficacy and tolerability. The goal of this study was to determine the noninferiority of fimasartan to losartan with regard to its efficacy and tolerability in adult Korean patients with mild-to-moderate hypertension. This was a randomized, multicenter, double-blind, parallel group, dose escalation, Phase III, noninferiority clinical trial. Patients aged 18 to 70 years with mild-to-moderate hypertension were randomized to receive either fimasartan 60/120 mg daily or losartan 50/100 mg daily with optional titration. Antihypertensive efficacy and tolerability were evaluated for 12 weeks. The primary end point was noninferiority of improvement in mean siDBP from baseline to week 12 for fimasartan compared with losartan. The incidence and severity of adverse events (AEs) and adverse drug reactions (ADRs) were evaluated to assess their tolerability. In addition, some patients whose blood pressure reached goal levels participated in a 24-week extension study for additional assessment of tolerability and efficacy. Five hundred six patients were randomly allocated to receive fimasartan (n = 256) or losartan (n = 250). There was no significant difference in baseline demographic characteristics between the 2 treatment groups (fimasartan-treated group-mean age, 53.96 [8.79] years; mean weight, 70.58 [11.73] kg; male, 68.02%; losartan-treated group-mean age, 53.58 [9.61] years; mean weight, 69.80 [11.08] kg; male, 70.17%). At week 12, siDBP was significantly decreased from baseline in both groups (-11.26 [7.53] mm Hg in the fimasartan group and -8.56 [7.72] mm Hg in the losartan group [P < 0.0001]). The between-group difference was 2.70 mm Hg (P = 0.0002), and the lower limit of the 2-sided 95% CI (1.27 mm Hg) was higher than the prespecified noninferiority margin (-2.5 mm Hg). The incidence of ADRs were 7.84% and 10.40% in the fimasartan and losartan groups, respectively (χ(2) test, P = 0.3181). The efficacy of fimasartan was maintained over 24 weeks, and its tolerability was comparable with losartan in the extension study. In this study with eligible adult Korean patients who had mild-to-moderate hypertension, the reduction of siDBP after 12 weeks of treatment with fimasartan 60/120 mg was noninferior to that of losartan 50/100 mg. By post hoc comparison, between-group differences in siDBP were significant in favor of fimasartan, suggesting superiority to losartan. There was no statistically significant difference in tolerability between the groups. This efficacy and tolerability were maintained throughout the additional 12-week extension study. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

Randomized comparison of next-generation sequencing and array comparative genomic hybridization for preimplantation genetic screening: a pilot study.

PubMed

Yang, Zhihong; Lin, James; Zhang, John; Fong, Wai Ieng; Li, Pei; Zhao, Rong; Liu, Xiaohong; Podevin, William; Kuang, Yanping; Liu, Jiaen

2015-06-23

Recent advances in next-generation sequencing (NGS) have provided new methods for preimplantation genetic screening (PGS) of human embryos from in vitro fertilization (IVF) cycles. However, there is still limited information about clinical applications of NGS in IVF and PGS (IVF-PGS) treatments. The present study aimed to investigate the effects of NGS screening on clinical pregnancy and implantation outcomes for PGS patients in comparison to array comparative genomic hybridization (aCGH) screening. This study was performed in two phases. Phase I study evaluated the accuracy of NGS for aneuploidy screening in comparison to aCGH. Whole-genome amplification (WGA) products (n = 164) derived from previous IVF-PGS cycles (n = 38) were retrospectively analyzed with NGS. The NGS results were then compared with those of aCGH. Phase II study further compared clinical pregnancy and implantation outcomes between NGS and aCGH for IVF-PGS patients. A total of 172 patients at mean age 35.2 ± 3.5 years were randomized into two groups: 1) NGS (Group A): patients (n = 86) had embryos screened with NGS and 2) aCGH (Group B): patients (n = 86) had embryos screened with aCGH. For both groups, blastocysts were vitrified after trophectoderm biopsy. One to two euploid blastocysts were thawed and transferred to individual patients primarily based on the PGS results. Ongoing pregnancy and implantation rates were compared between the two study groups. NGS detected all types of aneuploidies of human blastocysts accurately and provided a 100 % 24-chromosome diagnosis consistency with the highly validated aCGH method. Moreover, NGS screening identified euploid blastocysts for transfer and resulted in similarly high ongoing pregnancy rates for PGS patients compared to aCGH screening (74.7 % vs. 69.2 %, respectively, p >0.05). The observed implantation rates were also comparable between the NGS and aCGH groups (70.5 % vs. 66.2 %, respectively, p >0.05). While NGS screening has been recently introduced to assist IVF patients, this is the first randomized clinical study on the efficiency of NGS for preimplantation genetic screening in comparison to aCGH. With the observed high accuracy of 24-chromosome diagnosis and the resulting high ongoing pregnancy and implantation rates, NGS has demonstrated an efficient, robust high-throughput technology for PGS.

Safety of Russian-backbone seasonal trivalent, live-attenuated influenza vaccine in a phase II randomized placebo-controlled clinical trial among children in urban Bangladesh.

PubMed

Ortiz, Justin R; Goswami, Doli; Lewis, Kristen D C; Sharmeen, Amina Tahia; Ahmed, Moshtaq; Rahman, Mustafizur; Rahman, Mohammed Z; Feser, Jodi; Neuzil, Kathleen M; Brooks, W Abdullah

2015-06-26

Live-attenuated influenza vaccines (LAIVs) have the potential to be affordable, effective, and logistically feasible for immunization of children in low-resource settings. We conducted a phase II, randomized, double-blind, parallel group, placebo-controlled trial on the safety of the Russian-backbone, seasonal trivalent LAIV among children aged 24 through 59 months in Dhaka, Bangladesh in 2012. After vaccination, we monitored participants for six months with weekly home visits and study clinic surveillance for solicited and unsolicited adverse events, protocol-defined wheezing illness (PDWI), and serious adverse events (SAEs), including all cause hospitalizations. Three hundred children were randomized and administered LAIV (n=150) or placebo (n=150). No immediate post-vaccination reactions occurred in either group. Solicited reactions were similar between vaccine and placebo groups during the first 7 days post-vaccination and throughout the entire trial. There were no statistically significant differences in participants experiencing PDWI between LAIV and placebo groups throughout the trial (n=13 vs. n=16, p=0.697). Of 131 children with a history of medical treatment or hospitalization for asthma or wheezing at study entry, 65 received LAIV and 66 received placebo. Among this subset, there was no statistical difference in PDWI occurring throughout the trial between the LAIV or placebo groups (7.7% vs. 19.7%, p=0.074). While there were no related SAEs, LAIV recipients had six unrelated SAEs and placebo recipients had none. These SAEs included three due to traumatic injury and bone fracture, and one each due to accidental overdose of paracetamol, abdominal pain, and acute gastroenteritis. None of the participants with SAEs had laboratory-confirmed influenza, wheezing illness, or other signs of acute respiratory illness at the time of their events. In this randomized, controlled trial among 300 children aged 24 through 59 months in urban Bangladesh, Russian-backbone LAIV was safe and well tolerated. Further evaluation of LAIV safety and efficacy in a larger cohort is warranted. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Investigating the Contextual Interference Effect Using Combination Sports Skills in Open and Closed Skill Environments

PubMed Central

Cheong, Jadeera P.G.; Lay, Brendan; Razman, Rizal

2016-01-01

This study attempted to present conditions that were closer to the real-world setting of team sports. The primary purpose was to examine the effects of blocked, random and game-based training practice schedules on the learning of the field hockey trap, close dribble and push pass that were practiced in combination. The secondary purpose was to investigate the effects of predictability of the environment on the learning of field hockey sport skills according to different practice schedules. A game-based training protocol represented a form of random practice in an unstable environment and was compared against a blocked and a traditional random practice schedule. In general, all groups improved dribble and push accuracy performance during the acquisition phase when assessed in a closed environment. In the retention phase, there were no differences between the three groups. When assessed in an open skills environment, all groups improved their percentage of successful executions for trapping and passing execution, and improved total number of attempts and total number of successful executions for both dribbling and shooting execution. Between-group differences were detected for dribbling execution with the game-based group scoring a higher number of dribbling successes. The CI effect did not emerge when practicing and assessing multiple sport skills in a closed skill environment, even when the skills were practiced in combination. However, when skill assessment was conducted in a real-world situation, there appeared to be some support for the CI effect. Key points The contextual interference effect was not supported when practicing several skills in combination when the sports skills were assessed in a closed skill environment. There appeared to be some support for the contextual interference effect when sports skills were assessed in an open skill environment, which were similar to a real game situation. A game-based training schedule can be used as an alternative practice schedule as it displayed superior learning compared to a blocked practice schedule when assessed by the game performance test (real-world setting). The game-based training schedule also matched the blocked and random practice schedules in the other tests. PMID:26957940

Investigating the Contextual Interference Effect Using Combination Sports Skills in Open and Closed Skill Environments.

PubMed

Cheong, Jadeera P G; Lay, Brendan; Razman, Rizal

2016-03-01

This study attempted to present conditions that were closer to the real-world setting of team sports. The primary purpose was to examine the effects of blocked, random and game-based training practice schedules on the learning of the field hockey trap, close dribble and push pass that were practiced in combination. The secondary purpose was to investigate the effects of predictability of the environment on the learning of field hockey sport skills according to different practice schedules. A game-based training protocol represented a form of random practice in an unstable environment and was compared against a blocked and a traditional random practice schedule. In general, all groups improved dribble and push accuracy performance during the acquisition phase when assessed in a closed environment. In the retention phase, there were no differences between the three groups. When assessed in an open skills environment, all groups improved their percentage of successful executions for trapping and passing execution, and improved total number of attempts and total number of successful executions for both dribbling and shooting execution. Between-group differences were detected for dribbling execution with the game-based group scoring a higher number of dribbling successes. The CI effect did not emerge when practicing and assessing multiple sport skills in a closed skill environment, even when the skills were practiced in combination. However, when skill assessment was conducted in a real-world situation, there appeared to be some support for the CI effect. Key pointsThe contextual interference effect was not supported when practicing several skills in combination when the sports skills were assessed in a closed skill environment.There appeared to be some support for the contextual interference effect when sports skills were assessed in an open skill environment, which were similar to a real game situation.A game-based training schedule can be used as an alternative practice schedule as it displayed superior learning compared to a blocked practice schedule when assessed by the game performance test (real-world setting). The game-based training schedule also matched the blocked and random practice schedules in the other tests.

Postburn itching, pain, and psychological symptoms are reduced with massage therapy.

PubMed

Field, T; Peck, M; Scd; Hernandez-Reif, M; Krugman, S; Burman, I; Ozment-Schenck, L

2000-01-01

Twenty patients with burn injuries were randomly assigned to a massage therapy or a standard treatment control group during the remodeling phase of wound healing. The massage therapy group received a 30-minute massage with cocoa butter to a closed, moderate-sized scar tissue area twice a week for 5 weeks. The massage therapy group reported reduced itching, pain, and anxiety and improved mood immediately after the first and last therapy sessions, and their ratings on these measures improved from the first day to the last day of the study.

Clinical effects of Angelica dahurica dressing on patients with I-II phase pressure sores.

PubMed

Gong, Fen; Niu, Junzhi; Pei, Xing

2016-11-02

Angelica dahurica is a well-known traditional Chinese Medicine (TCM), while little information is available about its effects on pressure sores. We aimed to investigate the clinical effect of Angelica dahurica on patients with I-II phase pressure sores, as well as the underlying mechanism. Patients (n = 98) with phase I and phase II pressure sores were enrolled and randomly assigned to control and treated groups. In addition to holistic nursing, patients in the control group received compound clotrimazole cream, while patients in the treated group received continuous 4 weeks of external application of Angelica dahurica dressing. Therapeutic effect was recorded, along with the levels of interleukin-8 (IL-8), epidermal growth factor (EGF), transforming growth factor (TGF)-β, and vascular endothelial growth factor (VEGF). Besides, HaCaT cells were cultured with different concentrations of Angelica dahurica, and then cell viability, clone formation numbers, cell cycle, and levels of cyclin D1 and cyclin-dependent kinase (CDK) 2 were determined. The total effective rate in the treated group was significantly higher than in the control group. Levels of IL-8, EGF, TGF-β, and VEGF were statistically increased by Angelica dahurica. In addition, the cell viability and clone formation numbers were significantly upregulated by Angelica dahurica in a dose-dependent manner. Also, the percentage of cells in G0/G1 phase, and levels of cyclin D1 and CDK2 were significantly elevated. Our results suggest that Angelica dahurica may provide an effective clinical treatment for I-II phase pressure sores.

A Randomized, Multicenter, Double-blind, Phase III Study to Evaluate the Efficacy on Allergic Rhinitis and Safety of a Combination Therapy of Montelukast and Levocetirizine in Patients With Asthma and Allergic Rhinitis.

PubMed

Kim, Mi-Kyeong; Lee, Sook Young; Park, Hae-Sim; Yoon, Ho Joo; Kim, Sang-Ha; Cho, Young Joo; Yoo, Kwang-Ha; Lee, Soo-Keol; Kim, Hee-Kyoo; Park, Jung-Won; Park, Heung-Woo; Chung, Jin-Hong; Choi, Byoung Whui; Lee, Byung-Jae; Chang, Yoon-Seok; Jo, Eun-Jung; Lee, Sang-Yeub; Cho, You Sook; Jee, Young-Koo; Lee, Jong-Myung; Jung, Jina; Park, Choon-Sik

2018-06-24

The aim of this study was to evaluate the efficacy and safety of a fixed-dose combination of montelukast and levocetirizine in patients with perennial allergic rhinitis with mild to moderate asthma compared with the efficacy and safety of montelukast alone. This study was a 4-week, randomized, multicenter, double-blind, Phase III trial. After a 1-week placebo run-in period, the subjects were randomized to receive montelukast (10mg/day, n = 112) or montelukast (10 mg/day)/levocetirizine (5 mg/day) (n = 116) treatment for 4 weeks. The primary efficacy end point was mean daytime nasal symptom score. Other efficacy end points included mean nighttime nasal symptom score, mean composite symptom score, overall assessment of allergic rhinitis by both subjects and physicians, forced expiratory volume in 1 second (FEV 1 ), forced vital capacity (FVC), FEV 1 /FVC, asthma control test score, and the frequency of rescue medication used during the treatment period. Of 333 patients screened for this study, 228 eligible patients were randomized to treatment. The mean (SD) age of patients was 43.32 (15.02) years, and two thirds of subjects were female (66.67%). The demographic characteristics were similar between the treatment groups. Compared with the montelukast group, the montelukast/levocetirizine group reported significant reductions in mean daytime nasal symptom score (least squares mean [SE] of combination vs montelukast, -0.98 [0.06] vs -0.81 [0.06]; P = 0.045). For all other allergic rhinitis efficacy end points, the montelukast/levocetirizine group showed greater improvement than the montelukast group. Similar results were observed in overall assessment scores and in FEV 1 , FVC, FEV 1 /FVC, and asthma control test score changes from baseline for the 2 treatment groups. Montelukast/levocetirizine was well tolerated, and the safety profile was similar to that observed in the montelukast group. The fixed-dose combination of montelukast and levocetirizine was effective and safe in treating perennial allergic rhinitis in patients with asthma compared with montelukast alone. ClinicalTrials.gov identifier: NCT02552667. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Effect of Ezetimibe on Insulin Secretion in db/db Diabetic Mice

PubMed Central

Zhong, Yong; Wang, Jun; Gu, Ping; Shao, Jiaqing; Lu, Bin; Jiang, Shisen

2012-01-01

Objective. To investigate the effect of ezetimibe on the insulin secretion in db/db mice. Methods. The db/db diabetic mice aged 8 weeks were randomly assigned into 2 groups and intragastrically treated with ezetimibe or placebo for 6 weeks. The age matched db/m mice served as controls. At the end of experiment, glucose tolerance test was performed and then the pancreas was collected for immunohistochemistry. In addition, in vitro perfusion of pancreatic islets was employed for the detection of insulin secretion in the first phase. Results. In the ezetimibe group, the fasting blood glucose was markedly reduced, and the total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were significantly lowered when compared with those in the control group (P < 0.05). At 120 min after glucose tolerance test, the area under curve in the ezetimibe group was significantly smaller than that in the control group (P < 0.05), but the AUCINS0−30 was markedly higher. In vitro perfusion of pancreatic islets revealed the first phase insulin secretion was improved. In addition, the insulin expression in the pancreas in the ezetimibe group was significantly increased as compared to the control group. Conclusion. Ezetimibe can improve glucose tolerance, recover the first phase insulin secretion, and protect the function of β cells in mice. PMID:23118741

Permissive or Trophic Enteral Nutrition and Full Enteral Nutrition Had Similar Effects on Clinical Outcomes in Intensive Care: A Systematic Review of Randomized Clinical Trials.

PubMed

Silva, Camila F A; de Vasconcelos, Simone G; da Silva, Thales A; Silva, Flávia M

2018-01-26

The aim of this study was to systematically review the effect of permissive underfeeding/trophic feeding on the clinical outcomes of critically ill patients. A systematic review of randomized clinical trials to evaluate the mortality, length of stay, and mechanical ventilation duration in patients randomized to either hypocaloric or full-energy enteral nutrition was performed. Data sources included PubMed and Scopus and the reference lists of the articles retrieved. Two independent reviewers participated in all phases of this systematic review as proposed by the Cochrane Handbook, and the review was reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 7 randomized clinical trials that included a total of 1,717 patients were reviewed. Intensive care unit length of stay and mechanical ventilation duration were not statistically different between the intervention and control groups in all randomized clinical trials, and mortality rate was also not different between the groups. In conclusion, hypocaloric enteral nutrition had no significantly different effects on morbidity and mortality in critically ill patients when compared with full-energy nutrition. It is still necessary to determine the safety of this intervention in this group of patients, the optimal amount of energy provided, and the duration of this therapy. © 2018 American Society for Parenteral and Enteral Nutrition.

S-1 and irinotecan plus bevacizumab versus mFOLFOX6 or CapeOX plus bevacizumab as first-line treatment in patients with metastatic colorectal cancer (TRICOLORE): a randomized, open-label, phase III, noninferiority trial.

PubMed

Yamada, Y; Denda, T; Gamoh, M; Iwanaga, I; Yuki, S; Shimodaira, H; Nakamura, M; Yamaguchi, T; Ohori, H; Kobayashi, K; Tsuda, M; Kobayashi, Y; Miyamoto, Y; Kotake, M; Shimada, K; Sato, A; Morita, S; Takahashi, S; Komatsu, Y; Ishioka, C

2018-03-01

Combination therapy with oral fluoropyrimidine and irinotecan has not yet been established as first-line treatment of metastatic colorectal cancer (mCRC). We carried out a randomized, open-label, phase III trial to determine whether S-1 and irinotecan plus bevacizumab is noninferior to mFOLFOX6 or CapeOX plus bevacizumab in terms of progression-free survival (PFS). Patients from 53 institutions who had previously untreated mCRC were randomly assigned (1 : 1) to receive either mFOLFOX6 or CapeOX plus bevacizumab (control group) or S-1 and irinotecan plus bevacizumab (experimental group; a 3-week regimen: intravenous infusions of irinotecan 150 mg/m2 and bevacizumab 7.5 mg/kg on day 1, oral S-1 80 mg/m2 twice daily for 2 weeks, followed by a 1-week rest; or a 4-week regimen: irinotecan 100 mg/m2 and bevacizumab 5 mg/kg on days 1 and 15, S-1 80 mg/m2 twice daily for 2 weeks, followed by a 2-week rest). The primary end point was PFS. The noninferiority margin was 1.25; noninferiority would be established if the upper limit of the 95% confidence interval (CI) for the hazard ratio (HR) of the control group versus the experimental group was less than this margin. Between June 2012 and September 2014, 487 patients underwent randomization. Two hundred and forty-three patients assigned to the control group and 241 assigned to the experimental group were included in the primary analysis. Median PFS was 10.8 months (95% CI 9.6-11.6) in the control group and 14.0 months (95% CI 12.4-15.5) in the experimental group (HR 0.84, 95% CI 0.70-1.02; P < 0.0001 for noninferiority, P = 0.0815 for superiority). One hundred and fifty-seven patients (64.9%) in the control group and 140 (58.6%) in the experimental group had adverse events of grade 3 or higher. S-1 and irinotecan plus bevacizumab is noninferior to mFOLFOX6 or CapeOX plus bevacizumab with respect to PFS as first-line treatment of mCRC and could be a new standard treatment. UMIN000007834.

A randomized control trial to evaluate the importance of pre-training basic laparoscopic psychomotor skills upon the learning curve of laparoscopic intra-corporeal knot tying.

PubMed

Molinas, Carlos Roger; Binda, Maria Mercedes; Sisa, Cesar Manuel; Campo, Rudi

2017-01-01

Training of basic laparoscopic psychomotor skills improves the acquisition of more advanced laparoscopic tasks, such as laparoscopic intra-corporeal knot tying (LICK). This randomized controlled trial was designed to evaluate whether pre-training of basic skills, as laparoscopic camera navigation (LCN), hand-eye coordination (HEC), and bimanual coordination (BMC), and the combination of the three of them, has any beneficial effect upon the learning curve of LICK. The study was carried out in a private center in Asunción, Paraguay, by 80 medical students without any experience in surgery. Four laparoscopic tasks were performed in the ENCILAP model (LCN, HEC, BMC, and LICK). Participants were allocated to 5 groups (G1-G5). The study was structured in 5 phases. In phase 1, they underwent a base-line test ( T 1 ) for all tasks (1 repetition of each task in consecutive order). In phase 2, participants underwent different training programs (30 consecutive repetitions) for basic tasks according to the group they belong to (G1: none; G2: LCN; G3: HEC; G4: BMC; and G5: LCN, HEC, and BMC). In phase 3, they were tested again ( T 2 ) in the same manner than at T 1 . In phase 4, they underwent a standardized training program for LICK (30 consecutive repetitions). In phase 5, they were tested again ( T 3 ) in the same manner than at T 1 and T 2 . At each repetition, scoring was based on the time taken for task completion system. The scores were plotted and non-linear regression models were used to fit the learning curves to one- and two-phase exponential decay models for each participant (individual curves) and for each group (group curves). The LICK group learning curves fitted better to the two-phase exponential decay model. From these curves, the starting points ( Y 0), the point after HEC training/before LICK training ( Y 1), the Plateau, and the rate constants ( K ) were calculated. All groups, except for G4, started from a similar point ( Y 0). At Y 1, G5 scored already better than the others (G1 p  = .004; G2 p  = .04; G3 p  < .0001; G4 NS). Although all groups reached a similar Plateau, G5 has a quicker learning than the others, demonstrated by a higher K (G1 p  < 0.0001; G2 p  < 0.0001; G3 p  < 0.0001; and G4 p  < 0.0001). Our data confirms that training improves laparoscopic skills and demonstrates that pre-training of all basic skills (i.e., LCN, HEC, and BMC) shortens the LICK learning curve.

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

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

The Women's Recovery Group Study: a Stage I trial of women-focused group therapy for substance use disorders versus mixed-gender group drug counseling.

PubMed

Greenfield, Shelly F; Trucco, Elisa M; McHugh, R Kathryn; Lincoln, Melissa; Gallop, Robert J

2007-09-06

The aim of this Stage I Behavioral Development Trial was to develop a manual-based 12-session Women's Recovery Group (WRG) and to pilot test this new treatment in a randomized controlled trial against a mixed-gender Group Drug Counseling (GDC), an effective manual-based treatment for substance use disorders. After initial manual development, two pre-pilot groups of WRG were conducted to determine feasibility and initial acceptability of the treatment among subjects and therapists. In the pilot stage, women were randomized to either WRG or GDC. No significant differences in substance use outcomes were found between WRG and GDC during the 12-week group treatment. However, during the 6-month post-treatment follow-up, WRG members demonstrated a pattern of continued reductions in substance use while GDC women did not. In addition, pilot WRG women with alcohol dependence had significantly greater reductions in average drinks/drinking day than GDC women 6 months post-treatment (p<.03, effect size=0.81). While satisfaction with both groups was high, women were significantly more satisfied with WRG than GDC (p<.009, effect size=1.11). In this study, the newly developed 12-session women-focused WRG was feasible with high satisfaction among participants. It was equally effective as mixed-gender GDC in reducing substance use during the 12-week in-treatment phase, but demonstrated significantly greater improvement in reductions in drug and alcohol use over the post-treatment follow-up phase compared with GDC. A women-focused single-gender group treatment may enhance longer-term clinical outcomes among women with substance use disorders.

Aquatic versus land-based exercises as early functional rehabilitation for elite athletes with acute lower extremity ligament injury: a pilot study.

PubMed

Kim, Eunkuk; Kim, Taegyu; Kang, Hyunyong; Lee, Jongha; Childers, Martin K

2010-08-01

To compare outcomes between aquatic and land-based exercises during early-phase recovery from acute lower extremity ligament injuries in elite athletes. A single-blinded, covariate adaptive randomized, controlled study. National training center for elite athletes. Twenty-two athletes with isolated grade I or II ligament injury in ankles or knees were randomized into either an aquatic or land-based exercise group. Early functional rehabilitation program (ranging, strengthening, proprioceptive training, and functional exercises) was performed in both groups. All exercises were identical except for the training environment. Data were collected at baseline and at 2 and 4 weeks using a visual analog scale (VAS) for pain; static stability (overall stability index [OSI] level 5 and 3); dynamic stability (TCT), and percentage single-limb support time (%SLST). Both groups showed decreases in VAS, OSI 5 and 3, and TCT, with a concomitant increase in %SLST at 2 and 4 weeks (P < .05). No significant differences were detected between the 2 groups in any of the outcome measures. However, the line graphs for VAS, OSI 3, TCT, and %SLST in the aquatic exercise group were steeper than those in the land-based exercise group indicating significant group by time interactions (P < .05). These data indicate that the aquatic exercise group improved more rapidly than the land-based exercise group. For elite athletes with acute ligament sprains in the lower limb, aquatic exercises may provide advantages over standard land-based therapy for rapid return to athletic activities. Consequently, aquatic exercise could be recommended for the initial phase of a rehabilitation program. Copyright © 2010 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Efficacy and Safety of Paliperidone Palmitate 3-Month Formulation for Patients with Schizophrenia: A Randomized, Multicenter, Double-Blind, Noninferiority Study

PubMed Central

Xu, Haiyan; Gopal, Srihari; Nuamah, Isaac; Ravenstijn, Paulien; Janik, Adam; Schotte, Alain; Hough, David; Fleischhacker, Wolfgang W.

2016-01-01

Background: This double-blind, parallel-group, multicenter, phase-3 study was designed to test the noninferiority of paliperidone palmitate 3-month formulation (PP3M) to the currently marketed 1-month formulation (PP1M) in patients (age 18–70 years) with schizophrenia, previously stabilized on PP1M. Methods: After screening (≤3 weeks) and a 17-week, flexible-dosed, open-label phase (PP1M: day 1 [150mg eq. deltoid], day 8 [100mg eq. deltoid.], weeks 5, 9, and 13 [50, 75, 100, or 150mg eq., deltoid/gluteal]), clinically stable patients were randomized (1:1) to PP3M (fixed-dose, 175, 263, 350, or 525mg eq. deltoid/gluteal) or PP1M (fixed-dose, 50, 75, 100, or 150mg eq. deltoid/gluteal) for a 48-week double-blind phase. Results: Overall, 1016/1429 open-label patients entered the double-blind phase (PP3M: n=504; PP1M: n=512) and 842 completed it (including patients with relapse). PP3M was noninferior to PP1M: relapse rates were similar in both groups (PP3M: n=37, 8%; PP1M: n=45, 9%; difference in relapse-free rate: 1.2% [95% CI:-2.7%; 5.1%]) based on Kaplan-Meier estimates (primary efficacy). Secondary endpoint results (changes from double-blind baseline in positive and negative symptom score total and subscale scores, Clinical Global Impression-Severity, and Personal and Social Performance scores) were consistent with primary endpoint results. No clinically relevant differences were observed in pharmacokinetic exposures between PP3M and PP1M. Both groups had similar tolerability profiles; increased weight was the most common treatment-emergent adverse event (double-blind phase; 21% each). No new safety signals were detected. Conclusion: Taken together, PP3M with its 3-month dosing interval is a unique option for relapse prevention in schizophrenia. PMID:26902950

A randomized, double-blind, placebo- controlled study on the anti-haemostatic effects of Curcuma longa, Angelica sinensis and Panax ginseng.

PubMed

Fung, Foon Yin; Wong, Wan Hui; Ang, Seng Kok; Koh, Hwee Ling; Kun, Mei Ching; Lee, Lai Heng; Li, Xiaomei; Ng, Heng Joo; Tan, Chuen Wen; Zhao, Yan; Linn, Yeh Ching

2017-08-15

Herbs with "blood-activating" properties by traditional medicine theory often raise concerns for their possible anti-platelet or anticoagulation effects based on reports from in vitro studies. Such herbs have been implicated for bleeding manifestations based on only anecdotal reports. In particular, the combination of such herbs with anti-platelet agents is often empirically advised against despite lack of good clinical evidence. Here we studied 3 commonly used herbal preparations Curcuma longa, Angelica sinensis and Panax ginseng on their respective anti-platelet and anticoagulation effect, alone and in combination with aspirin. This is a randomized, double-blind, placebo-controlled trial involving 25 healthy volunteers for each herbal preparation. Each subject underwent 3 phases comprising of herbal product alone, aspirin alone and aspirin with herbal product, where each phase lasted for 3 weeks with 2 weeks of washout between phases. PT/APTT, platelet function by light transmission aggregometry and thrombin generation assay by calibrated automated thrombogram were measured at baseline and after each phase. Information on adverse reaction including bleeding manifestations was collected after each phase. On the whole there was no clinically relevant impact on platelet and coagulation function. With the exception of 5 of 24 subjects in the Curcuma longa group, 2 of 24 subjects in the Angelica sinensis group and 1 of 23 subjects in the Panax ginseng group who had an inhibition in arachidonic-acid induced platelet aggregation, there was no effect of these 3 herbals products on platelet aggregation by other agonists. Combination of these herbal products with aspirin respectively did not further aggravate platelet inhibition caused by aspirin. None of the herbs impaired PT/APTT or thrombin generation. There was no significant bleeding manifestation. This study on healthy volunteers provides good evidence on the lack of bleeding risks of Curcuma longa, Angelica sinensis and Panax ginseng either used alone or in combination with aspirin. Copyright © 2017 Elsevier GmbH. All rights reserved.

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.

Effects of an Advanced Sleep Schedule and Morning Short Wavelength Light Exposure on Circadian Phase in Young Adults with Late Sleep Schedules

PubMed Central

Sharkey, Katherine M.; Carskadon, Mary A.; Figueiro, Mariana G.; Zhu, Yong; Rea, Mark S.

2011-01-01

Objective We examined the effects of an advanced sleep/wake schedule and morning short wavelength (blue) light in 25 adults (mean age±SD = 21.8±3 years; 13 women) with late sleep schedules and subclinical features of delayed sleep phase syndrome (DSPD). Methods After a baseline week, participants kept individualized, fixed, advanced 7.5-hour sleep schedules for 6 days. Participants were randomly assigned to groups to receive “blue” (470 nm, ~225 lux, n=12) or “dim” (< 1 lux, n=13) light for one hour after waking each day. Head-worn “Daysimeters” measured light exposure; actigraphs and sleep diaries confirmed schedule compliance. Salivary dim light melatonin onset (DLMO), self-reported sleep, and mood were examined with 2×2 ANOVA. Results After 6 days, both groups showed significant circadian phase advances, but morning blue-light was not associated with larger phase shifts than dim-light exposure. The average DLMO advances (mean±SD) were 1.5±1.1 hours in the dim light group and 1.4±0.7 hours in the blue light group. Conclusions Adherence to a fixed advanced sleep/wake schedule resulted in significant circadian phase shifts in young adults with subclinical DSPD with or without morning blue light exposure. Light/dark exposures associated with fixed early sleep schedules are sufficient to advance circadian phase in young adults. PMID:21704557

Effects of an advanced sleep schedule and morning short wavelength light exposure on circadian phase in young adults with late sleep schedules.

PubMed

Sharkey, Katherine M; Carskadon, Mary A; Figueiro, Mariana G; Zhu, Yong; Rea, Mark S

2011-08-01

We examined the effects of an advanced sleep/wake schedule and morning short wavelength (blue) light in 25 adults (mean age±SD=21.8±3 years; 13 women) with late sleep schedules and subclinical features of delayed sleep phase disorder (DSPD). After a baseline week, participants kept individualized, fixed, advanced 7.5-h sleep schedules for 6days. Participants were randomly assigned to groups to receive "blue" (470nm, ∼225lux, n=12) or "dim" (<1lux, n=13) light for 1h after waking each day. Head-worn "Daysimeters" measured light exposure; actigraphs and sleep diaries confirmed schedule compliance. Salivary dim light melatonin onset (DLMO), self-reported sleep, and mood were examined with 2×2 ANOVA. After 6days, both groups showed significant circadian phase advances, but morning blue light was not associated with larger phase shifts than dim-light exposure. The average DLMO advances (mean±SD) were 1.5±1.1h in the dim light group and 1.4±0.7h in the blue light group. Adherence to a fixed advanced sleep/wake schedule resulted in significant circadian phase shifts in young adults with subclinical DSPD with or without morning blue light exposure. Light/dark exposures associated with fixed early sleep schedules are sufficient to advance circadian phase in young adults. Copyright © 2011 Elsevier B.V. All rights reserved.

Integration of a Community Pharmacy Simulation Program into a Therapeutics Course.

PubMed

Shin, Jaekyu; Tabatabai, Daryush; Boscardin, Christy; Ferrone, Marcus; Brock, Tina

2018-02-01

Objective. To demonstrate the feasibility of integrating the computer simulation, MyDispense, into a therapeutics course and to measure its effects on student perception and learning. Methods. We conducted a prospective study with an experimental phase and an implementation phase. In the first phase, students were randomized to complete a therapeutics case using MyDispense or traditional paper methods in class. In the second phase, all students completed two therapeutic cases using MyDispense in class with the option to complete four additional outside-of-class cases using MyDispense. Students completed pre- and post-tests in class and three surveys. Results. In the experimental phase, mean test scores increased from pre- to post-test for both MyDispense and traditional paper groups, but the difference between the groups was not statistically significant. Students in the traditional paper group reported statistically significant gains in confidence compared to the MyDispense group. In the implementation phase, mean test scores again increased, however, student perception of the use of MyDispense for therapeutics was negative. Completing the optional outside-of-class cases, however, was positively and significantly correlated with the midterm and final examination scores. Conclusion. Implementation of MyDispense in therapeutics may be feasible and has positive effects (eg, correlation with exam scores, capacity for immediate feedback, and potential for effective self-study). With short-term use and in the absence of assessment methods that also require seeking information from patients, students prefer to learn via traditional paper cases.

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.

[Effects of rare earth compounds on human peripheral mononuclear cell telomerase and apoptosis].

PubMed

Yu, Li; Dai, Yu-Cheng; Yuan, Zhao-Kang; Li, Jie

2004-07-01

To study the effects of rare earth exposure on human telomerase and apoptosis of human peripheral mononuclear cells (PBMNs). Rare earth mine lot in Xunwu county, the biggest ion absorptive rare earth mine lot of China, was selected as the study site. Another village of Xunwu county, with comparable geological structure and social environment was selected as the control site. Thirty healthy adults were randomly selected from the study site as exposure group and another 30 healthy adults randomly selected from the control site as control group. The blood content of 15 rare earth elements, including La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu and Y, were determined by inductive coupled plasma-source mass spectrometry (ICP-MS). The total contents of rare earth elements in the blood were calculated. The TRAP and FCM assays were carried out to analyse the telomerase and apoptosis of human PBMNCs respectively. In the exposure group, the concentration of La, Ce, Dy and Y were significantly higher (P<0.001), and Pr, Nd, Sm, Gd and Yb were higher than those in the control group (P<0.05). The total content of rare earth in the blood of exposure group showed significant difference compared with control group (P<0.001). Telomerase activity in PBMNs of the exposure group was higher than that in the control group (P<0.05); there were 11 adults in the exposure group (30 adults) and 5 adults in control group (30 adults) showed positive telomerase activity. The average age of the exposure group was (38.69 +/- 8.02) years-old, while the control group was (40.45 +/- 9.02) years-old (P >0.05). It was found that there was a significant relationship between telomerase activity and the total content of rare earth elements (P <0.01). 3. The proportion of apoptosis was not different between the two groups (P >0.05), but the cells in the S-phase and G2-M phase were increased (P <0.01) in the exposed group. The telomerase activity of PBMNs in the rare earth elements exposed group was higher than that of the control group, and there is no effect on apoptotic rate of PBMNs, but may promote the diploid DNA replication, and increase the percentage of G2/M and S phase cells.

Memantine and constraint-induced aphasia therapy in chronic poststroke aphasia.

PubMed

Berthier, Marcelo L; Green, Cristina; Lara, J Pablo; Higueras, Carolina; Barbancho, Miguel A; Dávila, Guadalupe; Pulvermüller, Friedemann

2009-05-01

We conducted a randomized, double-blind, placebo-controlled, parallel-group study of both memantine and constraint-induced aphasia therapy (CIAT) on chronic poststroke aphasia followed by an open-label extension phase. Patients were randomized to memantine (20 mg/day) or placebo alone during 16 weeks, followed by combined drug treatment with CIAT (weeks 16-18), drug treatment alone (weeks 18-20), and washout (weeks 20-24), and finally, an open-label extension phase of memantine (weeks 24-48). After baseline evaluations, clinical assessments were done at two end points (weeks 16 and 18), and at weeks 20, 24, and 48. Outcome measures were changes in the Western Aphasia Battery-Aphasia Quotient and the Communicative Activity Log. Twenty-eight patients were included, and 27 completed both treatment phases. The memantine group showed significantly better improvement on Western Aphasia Battery-Aphasia Quotient compared with the placebo group while the drug was taken (week 16, p = 0.002; week 18, p = 0.0001; week 20, p = 0.005) and at the washout assessment (p = 0.041). A significant increase in Communicative Activity Log was found in favor of memantine-CIAT relative to placebo-CIAT (week 18, p = 0.040). CIAT treatment led to significant improvement in both groups (p = 0.001), which was even greater under additional memantine treatment (p = 0.038). Beneficial effects of memantine were maintained in the long-term follow-up evaluation, and patients who switched to memantine from placebo experienced a benefit (p = 0.02). Both memantine and CIAT alone improved aphasia severity, but best outcomes were achieved combining memantine with CIAT. Beneficial effects of memantine and CIAT persisted on long-term follow-up.

[The efficacy of the complex medication Phyto-Hypophyson L in female, hormone-related sterility. A randomized, placebo-controlled clinical double-blind study].

PubMed

Bergmann, J; Luft, B; Boehmann, S; Runnebaum, B; Gerhard, I

2000-08-01

In a prospective, randomized, placebo-controlled, double-blind study, the effects of Phyto Hypophyson L (Steierl-Pharma GmbH, Herrsching, Germany), an Agnus castus-containing homeopathic preparation, were investigated in 67 women with fertility disorders. 37 women with oligomenorrhea and 30 women with amenorrhea received 50 drops of Phyto Hypophyson L or placebo 3 times a day over 3 months or 3 cycles. OUTCOME MEASURE AND RESULTS: The outcome measure being spontaneous menstruation, improved concentration of progesterone in the luteal phase, shortening of the cycle, earlier ovulation, and pregnancy was achieved in 38 out of 67 women. It was achieved more often from women with oligomenorrhea in the Phyto Hypophyson L group compared to the placebo group (82 versus 45%, p = 0.021). However, there was no significant effect when viewing the whole group. The baby take-home rate during the therapy and 6 months after the end of the therapy showed a ratio of 6 : 2 (18.7 : 6.4%). This result was not significant. Furthermore, in the oligomenorrhea verum group we observed a significant increase of progesterone during the luteal phase compared to the oligomenorrhea placebo group. Only very few undesirable drug effects were observed. In women with sterility and oligomenorrhea, a treatment with Phyto Hypophyson L can be recommended over a period of 3-6 months. Copyright 2000 S. Karger GmbH, Freiburg

Testing of blood products in a polytrauma model: results of a multi-institutional randomized preclinical trial.

PubMed

Alam, Hasan B; Bice, Leticia M; Butt, Muhammad U; Cho, S David; Dubick, Michael A; Duggan, Michael; Englehart, Michael S; Holcomb, John B; Morris, Melanie S; Prince, M Dale; Schreiber, Martin A; Shults, Christian; Sondeen, Jill L; Tabbara, Malek; Tieu, Brandon H; Underwood, Samantha A

2009-10-01

Trauma-induced coagulopathy, acidosis, and hypothermia form a "lethal triad" that is difficult to treat and is associated with extremely high mortality. This study was performed at three academic centers to evaluate whether resuscitation with blood components could reverse the coagulopathy in a complex polytrauma model. Yorkshire swine (40 +/- 5 kg) were subjected to a three-phase protocol: (a) "Prehospital" phase = femur fracture, hemorrhage (60% blood volume), and 30 minutes shock + infusion of saline (3x shed blood) + induction of hypothermia (33 degrees C); (b) "Early hospital" phase = grade V liver injury; and (c) "Operative" phase= liver packing. After liver packing, the animals (n = 60) were randomized to the following groups: (1) Sham-instrumentation and anesthesia without hemorrhage/injuries, (2) fresh whole blood (FWB), (3) 6% hetastarch (Hextend), (4) fresh frozen plasma/packed RBCs in 1:1 ratio (1:1 FFP/PRBC), and (5) FFP alone. Treatment volumes were equal to the volume of shed blood. Hemodynamic and physiologic parameters and coagulation profile (thrombelastography, prothrombin time, activated partial thromboplastin time, international normalized ratio, and platelets) were monitored during the experiment and for 4 hours posttreatment. At the end of prehospital phase, animals had developed significant acidosis (lactate >5 mmol/L and base deficit >9 mmol/L) and coagulopathy. Posttreatment mortality rates were 85% and 0% for the Hextend and blood component treated groups, respectively (p < 0.05). Hemodynamic parameters and survival rates were similar in groups that were treated with blood products (FWB, FFP, and FFP:PRBC). Animals treated with FFP and Hextend had significant anemia compared with the groups that received red blood cells (FWB and FFP:PRBC). Treatment with FFP and FFP:PRBC corrected the coagulopathy as effectively as FWB, whereas Hextend treatment worsened coagulopathy. In this reproducible model, we have shown that trauma-associated coagulopathy is made worse by hetastarch, but it can be rapidly reversed with the administration of blood components. Impressively, infusion of FFP, even without any red blood cells, can correct the coagulopathy and result in excellent early survival.

Safety and Immunogenicity of an AMA-1 Malaria Vaccine in Malian Adults: Results of a Phase 1 Randomized Controlled Trial

PubMed Central

Thera, Mahamadou A.; Doumbo, Ogobara K.; Coulibaly, Drissa; Diallo, Dapa A.; Kone, Abdoulaye K.; Guindo, Ando B.; Traore, Karim; Dicko, Alassane; Sagara, Issaka; Sissoko, Mahamadou S.; Baby, Mounirou; Sissoko, Mady; Diarra, Issa; Niangaly, Amadou; Dolo, Amagana; Daou, Modibo; Diawara, Sory I.; Heppner, D. Gray; Stewart, V. Ann; Angov, Evelina; Bergmann-Leitner, Elke S.; Lanar, David E.; Dutta, Sheetij; Soisson, Lorraine; Diggs, Carter L.; Leach, Amanda; Owusu, Alex; Dubois, Marie-Claude; Cohen, Joe; Nixon, Jason N.; Gregson, Aric; Takala, Shannon L.; Lyke, Kirsten E.; Plowe, Christopher V.

2008-01-01

Background The objective was to evaluate the safety, reactogenicity and immunogenicity of the AMA-1-based blood-stage malaria vaccine FMP2.1/AS02A in adults exposed to seasonal malaria. Methodology/Principal Findings A phase 1 double blind randomized controlled dose escalation trial was conducted in Bandiagara, Mali, West Africa, a rural town with intense seasonal transmission of Plasmodium falciparum malaria. The malaria vaccine FMP2.1/AS02A is a recombinant protein (FMP2.1) based on apical membrane antigen-1 (AMA-1) from the 3D7 clone of P. falciparum, adjuvanted with AS02A. The comparator vaccine was a cell-culture rabies virus vaccine (RabAvert). Sixty healthy, malaria-experienced adults aged 18–55 y were recruited into 2 cohorts and randomized to receive either a half dose or full dose of the malaria vaccine (FMP2.1 25 µg/AS02A 0.25 mL or FMP2.1 50 µg/AS02A 0.5 mL) or rabies vaccine given in 3 doses at 0, 1 and 2 mo, and were followed for 1 y. Solicited symptoms were assessed for 7 d and unsolicited symptoms for 30 d after each vaccination. Serious adverse events were assessed throughout the study. Titers of anti-AMA-1 antibodies were measured by ELISA and P. falciparum growth inhibition assays were performed on sera collected at pre- and post-vaccination time points. Transient local pain and swelling were common and more frequent in both malaria vaccine dosage groups than in the comparator group. Anti-AMA-1 antibodies increased significantly in both malaria vaccine groups, peaking at nearly 5-fold and more than 6-fold higher than baseline in the half-dose and full-dose groups, respectively. Conclusion/Significance The FMP2.1/AS02A vaccine had a good safety profile, was well-tolerated, and was highly immunogenic in malaria-exposed adults. This malaria vaccine is being evaluated in Phase 1 and 2 trials in children at this site. Trial Registration ClinicalTrials.gov NCT00308061 PMID:18213374

A health insurance company-initiated practice support intervention for optimizing acid-suppressing drug prescriptions in primary care.

PubMed

Smeets, Hugo M; Hoes, Arno W; Zuithoff, Nicolaas P A; van Dijk, Paul C M; van der Lee, Arnold P M; de Wit, Niek J

2011-08-01

A health insurance-initiated programme to improve cost-effectiveness of acid-suppressing drugs (ASDs). To evaluate the effect of two different interventions of general practitioner support in reducing drug prescription. A sequential cluster randomized controlled trial with 90 participating general practitioners in a telephone support (TS) group or practice visit (PV) group. TS group received support in phase-1 (first 6 months), but served as control group in phase-2 (6-12 months period). PV group received no intervention in phase-1, serving as the control group for the TS group, but received support in phase-2. Prescription data were extracted from Agis Health Insurance Database. Outcomes were the proportion of responders to drug reduction and the number of defined daily dose (DDD). Differences in users and DDD were analysed using multilevel regression analysis. At baseline, 3424 patients used ASD chronically (211 DDDs, on average). The difference between TS and control groups among responders was 3.2% [95% confidence interval (CI): 0.8; 5.6] and relative risk was 1.26 (95% CI: 1.06; 1.51). The difference between PV and control groups was not relevant (0.4%, 95% CI: -1.99; 2.79 and relative risk: 1.01, 95% CI: 0.82; 1.20). The difference in DDD per patient was -3.0 (95% CI: -8.9; 2.9) and -5.82 (95% CI: -12.4; 0.73), respectively. This health insurance company-initiated intervention had a moderate effect on ASD prescription. In contrast to TS, PVs did not seem to reduce ASD prescription rates.

Dacomitinib versus erlotinib in patients with advanced-stage, previously treated non-small-cell lung cancer (ARCHER 1009): a randomised, double-blind, phase 3 trial.

PubMed

Ramalingam, Suresh S; Jänne, Pasi A; Mok, Tony; O'Byrne, Kenneth; Boyer, Michael J; Von Pawel, Joachim; Pluzanski, Adam; Shtivelband, Mikhail; Docampo, Lara Iglesias; Bennouna, Jaafar; Zhang, Hui; Liang, Jane Q; Doherty, Jim P; Taylor, Ian; Mather, Cecile B; Goldberg, Zelanna; O'Connell, Joseph; Paz-Ares, Luis

2014-11-01

Dacomitinib is an irreversible pan-EGFR family tyrosine kinase inhibitor. Findings from a phase 2 study in non-small cell lung cancer showed favourable efficacy for dacomitinib compared with erlotinib. We aimed to compare dacomitinib with erlotinib in a phase 3 study. In a randomised, multicentre, double-blind phase 3 trial in 134 centres in 23 countries, we enrolled patients who had locally advanced or metastatic non-small-cell lung cancer, progression after one or two previous regimens of chemotherapy, Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, and presence of measurable disease. We randomly assigned patients in a 1:1 ratio to dacomitinib (45 mg/day) or erlotinib (150 mg/day) with matching placebo. Treatment allocation was masked to the investigator, patient, and study funder. Randomisation was stratified by histology (adenocarcinoma vs non-adenocarcinoma), ethnic origin (Asian vs non-Asian and Indian sub-continent), performance status (0-1 vs 2), and smoking status (never-smoker vs ever-smoker). The coprimary endpoints were progression-free survival per independent review for all randomly assigned patients, and for all randomly assigned patients with KRAS wild-type tumours. The study has completed accrual and is registered with ClinicalTrials.gov, number NCT01360554. Between June 22, 2011, and March 12, 2013, we enrolled 878 patients and randomly assigned 439 to dacomitinib (256 KRAS wild type) and 439 (263 KRAS wild type) to erlotinib. Median progression-free survival was 2·6 months (95% CI 1·9-2·8) in both the dacomitinib group and the erlotinib group (stratified hazard ratio [HR] 0·941, 95% CI 0·802-1·104, one-sided log-rank p=0·229). For patients with wild-type KRAS, median progression-free survival was 2·6 months for dacomitinib (95% CI 1·9-2·9) and erlotinib (95% CI 1·9-3·0; stratified HR 1·022, 95% CI 0·834-1·253, one-sided p=0·587). In patients who received at least one dose of study drug, the most frequent grade 3-4 adverse events were diarrhoea (47 [11%] patients in the dacomitinib group vs ten [2%] patients in the erlotinib group), rash (29 [7%] vs 12 [3%]), and stomatitis (15 [3%] vs two [<1%]). Serious adverse events were reported in 52 (12%) patients receiving dacomitinib and 40 (9%) patients receiving erlotinib. Irreversible EGFR inhibition with dacomitinib was not superior to erlotinib in an unselected patient population with advanced non-small-cell lung cancer or in patients with KRAS wild-type tumours. Further study of irreversible EGFR inhibitors should be restricted to patients with activating EGFR mutations. Pfizer. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effects of virtual reality training using Nintendo Wii and treadmill walking exercise on balance and walking for stroke patients.

PubMed

Bang, Yo-Soon; Son, Kyung Hyun; Kim, Hyun Jin

2016-11-01

[Purpose] The purpose of this study is to investigate the effects of virtual reality training using Nintendo Wii on balance and walking for stroke patients. [Subjects and Methods] Forty stroke patients with stroke were randomly divided into two exercise program groups: virtual reality training (n=20) and treadmill (n=20). The subjects underwent their 40-minute exercise program three times a week for eight weeks. Their balance and walking were measured before and after the complete program. We measured the left/right weight-bearing and the anterior/posterior weight-bearing for balance, as well as stance phase, swing phase, and cadence for walking. [Results] For balance, both groups showed significant differences in the left/right and anterior/posterior weight-bearing, with significant post-program differences between the groups. For walking, there were significant differences in the stance phase, swing phase, and cadence of the virtual reality training group. [Conclusion] The results of this study suggest that virtual reality training providing visual feedback may enable stroke patients to directly adjust their incorrect weight center and shift visually. Virtual reality training may be appropriate for patients who need improved balance and walking ability by inducing their interest for them to perform planned exercises on a consistent basis.

Effects of virtual reality training using Nintendo Wii and treadmill walking exercise on balance and walking for stroke patients

PubMed Central

Bang, Yo-Soon; Son, Kyung Hyun; Kim, Hyun Jin

2016-01-01

[Purpose] The purpose of this study is to investigate the effects of virtual reality training using Nintendo Wii on balance and walking for stroke patients. [Subjects and Methods] Forty stroke patients with stroke were randomly divided into two exercise program groups: virtual reality training (n=20) and treadmill (n=20). The subjects underwent their 40-minute exercise program three times a week for eight weeks. Their balance and walking were measured before and after the complete program. We measured the left/right weight-bearing and the anterior/posterior weight-bearing for balance, as well as stance phase, swing phase, and cadence for walking. [Results] For balance, both groups showed significant differences in the left/right and anterior/posterior weight-bearing, with significant post-program differences between the groups. For walking, there were significant differences in the stance phase, swing phase, and cadence of the virtual reality training group. [Conclusion] The results of this study suggest that virtual reality training providing visual feedback may enable stroke patients to directly adjust their incorrect weight center and shift visually. Virtual reality training may be appropriate for patients who need improved balance and walking ability by inducing their interest for them to perform planned exercises on a consistent basis. PMID:27942130

Community detection in networks with unequal groups.

PubMed

Zhang, Pan; Moore, Cristopher; Newman, M E J

2016-01-01

Recently, a phase transition has been discovered in the network community detection problem below which no algorithm can tell which nodes belong to which communities with success any better than a random guess. This result has, however, so far been limited to the case where the communities have the same size or the same average degree. Here we consider the case where the sizes or average degrees differ. This asymmetry allows us to assign nodes to communities with better-than-random success by examining their local neighborhoods. Using the cavity method, we show that this removes the detectability transition completely for networks with four groups or fewer, while for more than four groups the transition persists up to a critical amount of asymmetry but not beyond. The critical point in the latter case coincides with the point at which local information percolates, causing a global transition from a less-accurate solution to a more-accurate one.

Efficacy and safety of aripiprazole once-monthly in Asian patients with schizophrenia: a multicenter, randomized, double-blind, non-inferiority study versus oral aripiprazole.

PubMed

Ishigooka, Jun; Nakamura, Jun; Fujii, Yasuo; Iwata, Nakao; Kishimoto, Toshifumi; Iyo, Masaomi; Uchimura, Naohisa; Nishimura, Ryoji; Shimizu, Naoaki

2015-02-01

This study was designed to evaluate efficacy and safety of aripiprazole once-monthly (AOM) by verifying non-inferiority of AOM to oral aripiprazole in Asian patients with schizophrenia. The study consisted of a screening phase and three phases: an oral conversion phase (≤12weeks), an oral stabilization phase (≤12weeks) and a 52-week double-blind phase. Patients meeting stabilization criteria for 4weeks during the oral stabilization phase were randomly assigned (1:1) to AOM (400mg) or oral aripiprazole (6-24mg/day). The primary endpoint was Kaplan-Meier estimated rate of non-exacerbation of psychotic symptoms/non-relapse at Week 26. A total of 724 patients were screened, and 502 patients entered the oral stabilization phase. Of 455 patients randomized in the double-blind phase, 228 received AOM and 227 received oral aripiprazole. The non-exacerbation of psychotic symptoms/non-relapse rates at Week 26 were 95.0% (AOM) and 94.7% (oral aripiprazole) and the difference was 0.3% (95% CI: -3.9,4.5), thus non-inferiority of AOM compared to oral aripiprazole with respect to non-exacerbation of psychotic symptoms/non-relapse rate was shown with a margin of -3.9% which is well above the pre-defined non-inferiority limit (-15%). The proportions of patients meeting exacerbation of psychotic symptoms/relapse criteria and stabilization of psychotic symptoms/maintenance criteria were 6.6% and 92.5% in both groups. Discontinuation rates due to all reasons were 25.9% (AOM) and 33.5% (oral aripiprazole). AOM was well tolerated as well as oral aripiprazole. Non-inferiority of AOM to oral aripiprazole was established. AOM is efficacious in maintenance treatment of stabilized schizophrenia, with comparable efficacy and tolerability to oral aripiprazole. JapicCTI-101175. Copyright © 2014 Elsevier B.V. All rights reserved.

Topology and the universe

NASA Astrophysics Data System (ADS)

Gott, J. Richard, III

1998-09-01

Topology may play an important role in cosmology in several different ways. First, Einstein's field equations tell us about the local geometry of the universe but not about its topology. Therefore, the universe may be multiply connected. Inflation predicts that the fluctuations that made clusters and groups of galaxies arose from random quantum fluctuations in the early universe. These should be Gaussian random phase. This can be tested by quantitatively measuring the topology of large-scale structure in the universe using the genus statistic. If the original fluctuations were Gaussian random phase then the structure we see today should have a spongelike topology. A number of studies by our group and others have shown that this is indeed the case. Future tests using the Sloan Digital Sky Survey should be possible. Microwave background fluctuations should also exhibit a characteristic symmetric pattern of hot and cold spots. The COBE data are consistent with this pattern and the MAP and PLANCK satellites should provide a definitive test. If the original inflationary state was metastable then it should decay by making an infinite number of open inflationary bubble universes. This model makes a specific prediction for the power spectrum of fluctuations in the microwave background which can be checked by the MAP and PLANCK satellites. Finally, Gott and Li have proposed how a multiply connected cosmology with an early epoch of closed timelike curves might allow the universe to be its own mother.

What is the ideal dose and power output of low-level laser therapy (810 nm) on muscle performance and post-exercise recovery? Study protocol for a double-blind, randomized, placebo-controlled trial.

PubMed

de Oliveira, Adriano Rodrigues; Vanin, Adriane Aver; De Marchi, Thiago; Antonialli, Fernanda Colella; Grandinetti, Vanessa dos Santos; de Paiva, Paulo Roberto Vicente; Albuquerque Pontes, Gianna Móes; Santos, Larissa Aline; Aleixo Junior, Ivo de Oliveira; de Carvalho, Paulo de Tarso Camillo; Bjordal, Jan Magnus; Leal-Junior, Ernesto Cesar Pinto

2014-02-27

Recent studies involving phototherapy applied prior to exercise have demonstrated positive results regarding the attenuation of muscle fatigue and the expression of biochemical markers associated with recovery. However, a number of factors remain unknown, such as the ideal dose and application parameters, mechanisms of action and long-term effects on muscle recovery. The aims of the proposed project are to evaluate the long-term effects of low-level laser therapy on post-exercise musculoskeletal recovery and identify the best dose andapplication power/irradiation time. A double-blind, randomized, placebo-controlled clinical trial with be conducted. After fulfilling the eligibility criteria, 28 high-performance athletes will be allocated to four groups of seven volunteers each. In phase 1, the laser power will be 200 mW and different doses will be tested: Group A (2 J), Group B (6 J), Group C (10 J) and Group D (0 J). In phase 2, the best dose obtained in phase 1 will be used with the same distribution of the volunteers, but with different powers: Group A (100 mW), Group B (200 mW), Group C (400 mW) and Group D (0 mW). The isokinetic test will be performed based on maximum voluntary contraction prior to the application of the laser and after the eccentric contraction protocol, which will also be performed using the isokinetic dynamometer. The following variables related to physical performance will be analyzed: peak torque/maximum voluntary contraction, delayed onset muscle soreness (algometer), biochemical markers of muscle damage, inflammation and oxidative stress. Our intention, is to determine optimal laser therapy application parameters capable of slowing down the physiological muscle fatigue process, reducing injuries or micro-injuries in skeletal muscle stemming from physical exertion and accelerating post-exercise muscle recovery. We believe that, unlike drug therapy, LLLT has a biphasic dose-response pattern. The protocol for this study is registered with the Protocol Registry System, ClinicalTrials.gov identifier NCT01844271.

Effect of progesterone concentration and duration of proestrus on fertility in beef cattle after fixed-time artificial insemination.

PubMed

Dadarwal, D; Mapletoft, R J; Adams, G P; Pfeifer, L F M; Creelman, C; Singh, J

2013-03-15

The objective was to determine the effect of plasma progesterone concentration and the duration of proestrus during growth of the ovulatory follicle on fertility in beef cattle. Heifers (N = 61) and postpartum cows (N = 79) were assigned randomly to four groups in a two-by-two design involving luteal-phase versus subluteal-phase plasma progesterone concentrations and normal versus short proestrus. To synchronize follicular wave emergence, estradiol-17β was given im during the midluteal phase (Day 0) and concurrently, a once-used controlled intravaginal progesterone-releasing device was placed intravaginally. In the subluteal-phase progesterone groups, a luteolytic dose of PGF(2α) was given on Day 0 and again 12 hours later. In the luteal-phase progesterone groups, PGF(2α) was not given (so as to retain a functional CL). The controlled intravaginal progesterone-releasing device was removed and PGF(2α) was given on Days 7 or 8 in the normal- and short-proestrus groups, respectively. Cattle were given lutropin im 12 or 36 hours later in the short- and normal-proestrus groups, respectively, with AI at 12 hours after lutropin treatment. Transrectal ultrasonography was used to monitor ovarian response during treatments and to diagnose pregnancy 60 days after AI. Cattle (heifers and cows combined) in the subluteal-phase progesterone groups and normal proestrus groups had a larger follicle at the time of AI, and a larger CL that secreted more progesterone 9 days after AI than cattle with luteal-phase progesterone concentrations or those with short proestrus (P < 0.03). There was a higher incidence of ovulation (P < 0.01) the day after AI in heifers (55/61; 90%) than in cows (44/79; 56%). Pregnancy rates ranged from 11% to 54%, and were higher in cattle (heifers and cows combined) in the subluteal-phase progesterone groups and normal proestrus groups than in the luteal-phase progesterone or short proestrus groups, respectively, (P < 0.02). In conclusion, a short proestrous interval reduced pregnancy rate after fixed-time AI in beef cattle. A low progesterone environment during growth of the ovulatory follicle increased the preovulatory follicle size and subsequent CL size and function, and compensated for the effect of a short proestrus on pregnancy rates. Copyright © 2013 Elsevier Inc. All rights reserved.

The 10-year trend of adult diabetes, prediabetes and associated risk factors in Tehran: Phases 1 and 4 of Tehran Lipid and Glucose Study.

PubMed

Mahtab, Niroomand; Farzad, Hadaegh; Mohsen, Bahaeddini; Nakisa, Darvishi

Type 2 diabetes is a global problem with significant morbidity and healthcare costs. In this study, we aimed to determine the 10-year trend of diabetes, prediabetes and their risk factors in the adult urban population of Tehran Lipid and Glucose Study (TLGS). In this cross-sectional study, we included all patients above 20 years of age who were registered in phases 1 and 4 of TLGS. Each phase had a 3-year duration. 4580 patients were recruited in each phase (916 patients in each age-group, including 3772 males and 5145 females). Random cluster sampling was used in phase 1 and convenience sampling was used in phase 4. Diabetes and glucose tolerance status were determined according to the 1991 criteria of the American Diabetes Association. In our five age groups, risk factors were compared, which included physical activity, waist circumference, body mass index, education, smoking, lipid profile and family history. Exclusion criteria were placement of an individual in the same age-group in the two phases and pregnancy. We calculated the prevalence of diabetes and dysglycemia in each age-group. Age-specific prevalence rates were determined. Prevalence of risk factors in the two phases were compared using chi-square test and Student t-test. Mann-Whitney U test was used to analyze the variables with non-normal distribution. In this study, 3976 individuals were recruited in phase 1 (2308 women and 1668 men; female to male ratio 1.38) and 4941 individuals were recruited in phase 4 (2837 women and 2104 men; female to male ratio 1.35). Prevalence of prediabetes in all age groups (except for the 30-39 years age-group) were increased in phase 4 compared to phase 1. Prevalence of known diabetes in all age groups were increased in phase 4 compared to phase 1, yet, the increase was significant only in the 30-39 and 60-69 years age groups (1.8% vs. 0.7% and 19.0% vs. 10.2%, respectively). Newly diagnosed diabetes was decreased in all age groups in phase 4, except for the 60-69 years age-group. The incidence of newly diagnosed diabetes in the 60-69 years age-group was significantly higher in phase 4 compared to the similar age-group of phase 1 (15.2% vs. 11.8%; p<0.001). Physical activity, body mass index, waist circumference (central obesity), general obesity, smoking (except for the 30-39 and 40-49 years age groups), and level of education were significantly higher in phase 4 compared to phase 1. Marriage rates were significantly lower in phase 4 compared to phase 1 across all studied age groups. We observed an increasing trend in the prevalence of diabetes over a 10-year period in TLGS. This is an accordance with estimates ​​in this field and highlights the need for education, prevention, treatment and control of diabetes. We also found increased rates of central and general obesity, smoking and divorce along with decreased marriage rates, which should be considered by the healthcare policymakers and state health officials as significant risk factors of diabetes. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Pregnancy Rate Following Luteal Phase Support in Iranian Women with Polycystic Ovarian Syndrome

PubMed Central

Foroozanfard, Fatemeh; Saberi, Hamidreza; Moraveji, Seyed Alireza; Bazarganipour, Fatemeh

2014-01-01

Background To assess the efficacy of luteal phase support (LPS) using intravaginal progesterone (P) on pregnancy rate in Iranian women with polycystic ovarian syndrome (PCOS) who used a combination for ovulation induction consisting of letrozole or clomi- phene citrate (CC) and human menopausal gonadotropin (HMG). Materials and Methods This was a randomized clinical trial undertaken in a fertility clinic in Kashan, Isfahan Province, Iran. A total of 198 patients completed treatment and follow up. Base on chosen ovulation induction programs, they were divided into two following group: i. CC group (n=98) used a combination consisting of CC (100 mg×5 day) and HMG (150 IU×5 day) and ii. letrozole group (n=100) used a combination consisting of letrozole (5 mg×5 day) and HMG (150 IU×5 day). After human chorionic gonadotropin (hCG) administration (5000 IU), the patients (n=122) who randomly re- ceived intravaginal P (Cyclogest, 400 mg daily) were included in LPS group, while the rest (n=123) were included in non-P cycles group. The outcome was the comparison of chemical pregnancy rate between the groups. Results Our findings showed that LPS was associated with a 10% higher pregnancy rate than in non-P cycles, although this difference did not reach statistical significant (p=0.08). LPS improved pregnancy rate in both CC (4%) and letrozole (6%) groups. In addition, patients who used letrozole for ovulation induction along with intravaginal P showed higher pregnancy rates than CC group. Conclusion Administration of vaginal P for LPS may improve the pregnancy rate in women with PCOS using letrozole or CC in combination with HMG for ovulation induc- tion (Registration Number: IRCT201206072967N4). PMID:25379150

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

In vivo antiplaque efficacy of combined antimicrobial dentifrice and rinse hygiene regimens.

PubMed

White, Donald J; Barker, Matthew L; Klukowska, Malgorzata

2008-06-01

To evaluate using digital plaque image analysis the antiplaque efficacy of oral care regimens including use of antimicrobial toothpaste in combination with antimicrobial mouthrinse. 16 subjects completed the study protocol including: (1) initial treatment phase, all subjects used a standard sodium fluoride dentifrice with 2x/day brushing, (2) second treatment phase, subjects were randomized to two treatment groups: stannous fluoride/sodium hexametaphosphate dentifrice or sodium fluoride triclosan/copolymer dentifrice; (3) third treatment phase, the group using stannous fluoride dentifrice rinsed with alcohol-free cetylpyridinium chloride mouthrinse and the group using triclosan dentifrice rinsed with essential oil mouthrinse. During each phase, plaque levels were assessed in the morning before toothbrushing (AM), post-brushing in the morning (PB) and in the afternoon (PM). Stannous fluoride dentifrice was superior to triclosan dentifrice in plaque growth inhibition between toothbrushing. Both mouthrinses provided additional plaque prevention benefits when used with antimicrobial dentifrices. The cetylpyridinium chloride mouthrinse and stannous fluoride dentifrice regimen was particularly effective, building accretive efficacy over time. Average plaque reductions exceeded 50% vs. sodium fluoride dentifrice alone. Chemotherapeutic dentifrices and rinses increase plaque control used alone and particularly in combination. The stannous fluoride-cetylpyridinium chloride regimen showed the greatest benefits.

Changes in Gait Symmetry After Training on a Treadmill with Biofeedback in Chronic Stroke Patients: A 6-Month Follow-Up from a Randomized Controlled Trial

PubMed Central

Drużbicki, Mariusz; Guzik, Agnieszka; Przysada, Grzegorz; Kwolek, Andrzej; Brzozowska-Magoń, Agnieszka; Sobolewski, Marek

2016-01-01

Background One of the most significant challenges for patients who survive a stroke is relearning basic motor tasks such as walking. The goal of this study was to evaluate whether training on a treadmill with visual biofeedback improves gait symmetry, as well as spatiotemporal and kinematic gait parameters, in stroke patients. Material/Methods Thirty patients in the chronic phase after a stroke were randomly allocated into groups with a rehabilitation program of treadmill training with or without visual biofeedback. The training program lasted 10 days. Spatiotemporal and kinematic gait parameters were evaluated. For all parameters analyzed, a symmetrical index was calculated. Follow-up studies were performed 6 months after completion of the program. Results The symmetrical index had significantly normalized in terms of the step length (p=0.006), stance phase time, and inter-limb ratio in the intervention group. After 6 months, the improvement in the symmetry of the step length had been maintained. In the control group, no statistically significant change was observed in any of the parameters tested. There was no significant difference between the intervention group and the control group on completion of the program or at 6 months following the completion of the program. Conclusions Training on a treadmill has a significant effect on the improvement of spatiotemporal parameters and symmetry of gait in patients with chronic stroke. In the group with the treadmill training using visual biofeedback, no significantly greater improvement was observed. PMID:27941712

Combined Diosmectite and Mesalazine Treatment for Mild-to-Moderate Ulcerative Colitis: A Randomized, Placebo-Controlled Study

PubMed Central

Jiang, Xue-Liang; Wang, Hua-Hong; Cui, Hui-Fei

2015-01-01

Background The relapse rate of ulcerative colitis (UC) is high. The efficacy of combined diosmectite and mesalazine treatment for active mild-to-moderate UC was investigated. Material/Methods A total of 120 patients with UC were enrolled in this randomized, single-blind, placebo-controlled study. Sixty patients were assigned to the Diosmectite group (diosmectite and mesalazine) and 60 were assigned to Placebo group (placebo and mesalazine). In the induction phase, the primary end point was the clinical remission rate at 8 weeks; secondary end points were clinical response, endothelial mucosal healing, Mayo score, erythrocyte sedimentation rate, C-reactive protein levels, and defecation frequency. In the maintenance phase, the primary end point was clinical remission at 52 weeks; secondary end points were clinical response, endothelial mucosal healing, Mayo score, erythrocyte sedimentation rate, and defecation frequency. Results At 8 weeks, the Diosmectite group had a significantly higher clinical remission rate (68.3% vs. 50%) and mucosal healing rate (66.7% vs. 48.3%) compared with the Placebo group. There were no significant differences in clinical response rates, Mayo score, erythrocyte sedimentation rate, C-reactive protein, or defecation frequency. At 52 weeks, the Diosmectite group had a significantly higher clinical remission rate (61.7% vs. 40%) and mucosal healing rate (60% vs. 38.3%) compared with the Placebo group. Defecation frequency was lower, but this was not significant. Conclusions Combined diosmectite and mesalazine treatment successfully induced and maintained the treatment of active mild-to-moderate UC as indicated by higher rates of clinical remission and mucosal healing. PMID:25582578

Early sensory re-education of the hand after peripheral nerve repair based on mirror therapy: a randomized controlled trial.

PubMed

Paula, Mayara H; Barbosa, Rafael I; Marcolino, Alexandre M; Elui, Valéria M C; Rosén, Birgitta; Fonseca, Marisa C R

2016-01-01

Mirror therapy has been used as an alternative stimulus to feed the somatosensory cortex in an attempt to preserve hand cortical representation with better functional results. To analyze the short-term functional outcome of an early re-education program using mirror therapy compared to a late classic sensory program for hand nerve repair. This is a randomized controlled trial. We assessed 20 patients with median and ulnar nerve and flexor tendon repair using the Rosen Score combined with the DASH questionnaire. The early phase group using mirror therapy began on the first postoperative week and lasted 5 months. The control group received classic sensory re-education when the protective sensation threshold was restored. All participants received a patient education booklet and were submitted to the modified Duran protocol for flexor tendon repair. The assessments were performed by the same investigator blinded to the allocated treatment. Mann-Whitney Test and Effect Size using Cohen's d score were used for inter-group comparisons at 3 and 6 months after intervention. The primary outcome (Rosen score) values for the Mirror Therapy group and classic therapy control group after 3 and 6 months were 1.68 (SD=0.5); 1.96 (SD=0.56) and 1.65 (SD=0.52); 1.51 (SD=0.62), respectively. No between-group differences were observed. Although some clinical improvement was observed, mirror therapy was not shown to be more effective than late sensory re-education in an intermediate phase of nerve repair in the hand. Replication is needed to confirm these findings.

Use of virtual reality intervention to improve reaction time in children with cerebral palsy: A randomized controlled trial.

PubMed

Pourazar, Morteza; Mirakhori, Fatemeh; Hemayattalab, Rasool; Bagherzadeh, Fazlolah

2017-09-21

The purpose of this study was to investigate the training effects of Virtual Reality (VR) intervention program on reaction time in children with cerebral palsy. Thirty boys ranging from 7 to 12 years (mean = 11.20; SD = .76) were selected by available sampling method and randomly divided into the experimental and control groups. Simple Reaction Time (SRT) and Discriminative Reaction Time (DRT) were measured at baseline and 1 day after completion of VR intervention. Multivariate analysis of variance (MANOVA) and paired sample t-test were performed to analyze the results. MANOVA test revealed significant effects for group in posttest phase, with lower reaction time in both measures for the experimental group. Based on paired sample t-test results, both RT measures significantly improved in experimental group following the VR intervention program. This paper proposes VR as a promising tool into the rehabilitation process for improving reaction time in children with cerebral palsy.

Quantitative assessment of the effectiveness of phase 1 orthodontic treatment using the American Board of Orthodontics Discrepancy Index.

PubMed

Vasilakou, Nefeli; Araujo, Eustaquio A; Kim, Ki Beom; Oliver, Donald R

2016-12-01

This retrospective study included a sample of 300 randomly selected patients from the archived records of Saint Louis University's graduate orthodontic clinic, St. Louis, Mo, from 1990 to 2012. The objective of this study was to quantify the changes obtained in phase 1 of orthodontic treatment and determine how much improvement, if any, has occurred before the initiation of the second phase. For the purpose of this study, prephase 1 and prephase 2 records of 300 subjects were gathered. All were measured using the American Board of Ortodontics Discrepancy Index (DI), and a score was given for each phase. The difference of the 2 scores indicated the quantitative change of the complexity of the treatment. Paired t tests were used to compare the scores. Additionally, the sample was categorized into 3 groups according to the Angle classifications, and the same statistics were used to identify significant changes between the 2 scores. Analysis of variance was applied to compare the 3 groups and determine which had the most change. Percentages of change were calculated for the significant scores. The total DI score overall and the scores of all 3 groups were significantly reduced from before to after phase 1. Overall, 42% improvement was observed. The Class I group showed 49.3% improvement, the Class II group 34.5% and the Class III group 58.5%. Most components of the DI improved significantly, but a few showed negative changes. Significant reductions of DI scores were observed in the total sample and in all Angle classification groups. This indicates that early treatment reduces the complexity of the malocclusions. Only 2 components of the DI showed statistically significant negative changes. Copyright © 2016 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Switching to nilotinib versus imatinib dose escalation in patients with chronic myeloid leukaemia in chronic phase with suboptimal response to imatinib (LASOR): a randomised, open-label trial.

PubMed

Cortes, Jorge E; De Souza, Carmino Antonio; Ayala, Manuel; Lopez, Jose Luis; Bullorsky, Eduardo; Shah, Sandip; Huang, Xiaojun; Babu, K Govind; Abdulkadyrov, Kudrat; de Oliveira, José Salvador Rodrigues; Shen, Zhi-Xiang; Sacha, Tomasz; Bendit, Israel; Liang, Zhizhou; Owugah, Tina; Szczudlo, Tomasz; Khanna, Sadhvi; Fellague-Chebra, Rafik; le Coutre, Philipp D

2016-12-01

Optimal management of patients with chronic myeloid leukaemia in chronic phase with suboptimal cytogenetic response remains undetermined. This study aimed to investigate the safety and efficacy of switching to nilotinib vs imatinib dose escalation for patients with suboptimal cytogenetic response on imatinib. We did a phase 3, open-label, randomised trial in patients with chronic myeloid leukaemia in chronic phase with suboptimal cytogenetic response to imatinib according to the 2009 European LeukemiaNet criteria, in Latin America, Europe, and Asia (59 hospitals and care centres in 12 countries). Eligible patients were aged 18 years or older with Philadelphia chromosome-positive chronic myeloid leukaemia in chronic phase and Eastern Cooperative Oncology Group performance status of 0-2. Before enrolment, all patients had received 3-18 months of imatinib 400 mg once daily and had a suboptimal cytogenetic response according to 2009 ELN recommendations, established through bone marrow cytogenetics. By use of an interactive response technology using fixed blocks, we randomly assigned patients (1:1) to switch to nilotinib 400 mg twice per day or an escalation of imatinib dose to 600 mg once per day (block size of 4). Investigators and participants were not blinded to study treatment. Crossover was allowed for loss of response or intolerance at any time, or for patients with no complete cytogenetic response at 6 months. The primary endpoint was complete cytogenetic response at 6 months in the intention-to-treat population. Efficacy endpoints were based on the intention-to-treat population, with all patients assessed according to the treatment group to which they were randomised (regardless of crossover); the effect of crossover was assessed in post-hoc analyses, in which responses achieved after crossover were excluded. We present the final results at 24 months' follow-up. This study is registered with ClinicalTrials.gov (NCT00802841). Between July 7, 2009, and Aug 29, 2012, we enrolled 191 patients. 96 patients were randomly assigned to nilotinib and 95 patients were randomly assigned to imatinib. Complete cytogenetic response at 6 months was achieved by 48 of 96 patients in the nilotinib group (50%, 95·18% CI 40-61) and 40 of 95 in the imatinib group (42%, 32-53%; difference 7·9% in favour of nilotinib; 95% CI -6·2 to 22·0, p=0·31). Excluding responses achieved after crossover, 48 (50%) of 96 patients in the nilotinib group and 34 (36%) of 95 patients in the imatinib group achieved complete cytogenic response at 6 months (nominal p=0·058). Grade 3-4 non-haematological adverse events occurring in more than one patient were headache (nilotinib group, n=2 [2%, including 1 after crossover to imatinib]; imatinib group, n=1 [1%]), blast cell crisis (nilotinib group, n=1 [1%]; imatinib group, n=1 [1%]), and QT prolongation (nilotinib group, n=1 [1%]; imatinib group, n=1 [1%, after crossover to nilotinib]). Serious adverse events on assigned treatment were reported in 11 (11%) of 96 patients in the nilotinib group and nine (10%) of 93 patients in the imatinib group. Seven (7%) of 96 patients died in the nilotinib group and five (5%) of 93 patients died in the imatinib group; no deaths were treatment-related. While longer-term analyses are needed to establish whether the clinical benefits observed with switching to nilotinib are associated with improved long-term survival outcomes, our results suggest that patients with suboptimal cytogenetic response are more likely to achieve improved cytogenetic and molecular responses with switching to nilotinib than with imatinib dose escalation, although the difference was not statistically significant when responses achieved after crossover were included. Novartis Pharmaceuticals. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

Two-year efficacy and safety of AIR inhaled insulin in patients with type 1 diabetes: An open-label randomized controlled trial.

PubMed

Garg, Satish K; Mathieu, Chantal; Rais, Nadeem; Gao, Haitao; Tobian, Janet A; Gates, Jeffrey R; Ferguson, Jeffrey A; Webb, David M; Berclaz, Pierre-Yves

2009-09-01

Patients with type 1 diabetes require intensive insulin therapy for optimal glycemic control. AIR((R)) inhaled insulin (system from Eli Lilly and Company, Indianapolis, IN) (AIR is a registered trademark of Alkermes, Inc., Cambridge, MA) may be an efficacious and safe alternative to subcutaneously injected (SC) mealtime insulin. This was a Phase 3, 2-year, randomized, open-label, active-comparator, parallel-group study in 385 patients with type 1 diabetes who were randomly assigned to receive AIR insulin or SC insulin (regular human insulin or insulin lispro) at mealtimes. Both groups received insulin glargine once daily. Efficacy measures included mean change in hemoglobin A1C (A1C) from baseline to end point, eight-point self-monitored blood glucose profiles, and insulin dosage. Safety assessments included hypoglycemic events, pulmonary function tests, adverse events, and insulin antibody levels. In both treatment groups, only 20% of subjects reached the target of A1C <7.0%. A significant A1C difference of 0.44% was seen favoring SC insulin, with no difference between the groups in insulin doses or hypoglycemic events at end point. Patients in both treatment groups experienced progressive decreases in lung function, but larger (reversible) decrements in diffusing capacity of the lung for carbon monoxide (DL(CO)) were associated with AIR insulin treatment. Greater weight gain was seen with SC insulin treatment. The AIR inhaled insulin program was terminated by the sponsor prior to availability of any Phase 3 data for reasons unrelated to safety or efficacy. Despite early termination, this trial provides evidence that AIR insulin was less efficacious in lowering A1C and was associated with a greater decrease in DL(CO) and increased incidence of cough than SC insulin in patients with type 1 diabetes.

Efficacy of vitamins C, E, and their combination for treatment of restless legs syndrome in hemodialysis patients: a randomized, double-blind, placebo-controlled trial.

PubMed

Sagheb, Mohammad Mahdi; Dormanesh, Banafshe; Fallahzadeh, Mohammad Kazem; Akbari, Hamideh; Sohrabi Nazari, Sahar; Heydari, Seyed Taghi; Behzadi, Saeed

2012-05-01

Restless legs syndrome (RLS) is a common disorder in hemodialysis patients that leads to insomnia and impaired quality of life. Because high oxidative stress has been implicated in the pathogenesis of RLS, we sought to evaluate the efficacy of vitamins C and E and their combination in reducing the severity of RLS symptoms in hemodialysis patients in this randomized, double-blind, placebo-controlled, four-arm parallel trial. Sixty stable hemodialysis patients who had all four diagnostic criteria for RLS developed by the International Restless Legs Syndrome Group with no acute illness or history of renal stone were randomly allocated to four fifteen-patient parallel groups to receive vitamin C (200 mg) and vitamin E (400 mg), vitamin C (200 mg) and placebo, vitamin E (400 mg) and placebo, and double placebo daily for eight weeks. International Restless Legs Scale (IRLS) scores were measured for all patients at baseline and at the end of treatment phase. The primary outcome was absolute change in IRLS sum score from baseline to the end of treatment phase. Means of IRLS sum score decreased significantly in the vitamins C and E (10.3 ± 5.3, 95% CI: 7.4-13.3), vitamin C and placebo (10 ± 3.5, 95% CI: 8.1-11.9), and vitamin E and placebo groups (10.1 ± 6, 95% CI: 6.8-13.5) compared with the double placebo group (3.1 ± 3, 95% CI: 1.5-4.8), (P<0.001); however, no differences were observed between these treatment groups. Vitamins C and E and their combination are safe and effective treatments for reducing the severity of RLS in hemodialysis patients over the short-term. Copyright © 2012 Elsevier B.V. All rights reserved.

A randomized, multi-center, open-label, phase III study of once-per-cycle DA-3031, a pegylated G-CSF, in comparison with daily filgrastim in patients receiving TAC chemotherapy for breast cancer.

PubMed

Park, K H; Lee, S; Park, J H; Kang, S Y; Kim, H Y; Park, I H; Park, Y H; Im, Y H; Lee, H J; Park, S; Lee, S I; Jung, K H; Kim, Y S; Seo, Jae Hong

2017-02-01

This multi-center, randomized, phase III study was conducted to demonstrate the non-inferiority of DA-3031 compared with daily filgrastim in patients during the first cycle of chemotherapy for breast cancer in terms of the duration of severe neutropenia (DSN). Seventy-four patients with breast cancer who were receiving combination chemotherapy with docetaxel, doxorubicin, and cyclophosphamide (TAC) were enrolled. All participants were randomized to receive either daily subcutaneous injections of filgrastim 100 μg/m 2 /day for up to 10 days or a single subcutaneous injection of DA-3031 at fixed doses of 6 mg on day 2 of each chemotherapy cycle. The mean duration of grade 4 (G4) neutropenia in cycle 1 was 2.08 ± 0.85 days for the filgrastim group and 2.28 ± 1.14 days for the DA-3031 group. The difference between groups was 0.2 ± 1.10 days (95 % confidence interval (CI) = -0.26, 0.66), which supported non-inferiority. No statistically significant differences were observed in nadir absolute neutrophil count (ANC) (154.34/mm 3 and 161.75/mm 3 for the filgrastim and DA-3031 groups, respectively; P = 0.8414) or in time to ANC recovery (10.03 ± 0.75 and 9.83 ± 1.56 days in the filgrastim and DA-3031 groups, respectively; P = 0.0611) during cycle 1. Serious AEs occurred in six (15.8 %) patients receiving filgrastim and in ten (27.8 %) patients receiving DA-3031; however, none was determined to be related to the study drug. DA-3031 and daily filgrastim are similar in regard to DSN and safety in breast cancer patients receiving TAC chemotherapy.

The Effects of a Sport-Specific Maximal Strength and Conditioning Training on Critical Velocity, Anaerobic Running Distance, and 5-km Race Performance.

PubMed

Karsten, Bettina; Stevens, Liesbeth; Colpus, Mark; Larumbe-Zabala, Eneko; Naclerio, Fernando

2016-01-01

To investigate the effects of a sport-specific maximal 6-wk strength and conditioning program on critical velocity (CV), anaerobic running distance (ARD), and 5-km time-trial performance (TT). 16 moderately trained recreational endurance runners were tested for CV, ARD, and TT performances on 3 separate occasions (baseline, midstudy, and poststudy). Participants were randomly allocated into a strength and conditioning group (S&C; n = 8) and a comparison endurance-training-only group (EO; n = 8). During the first phase of the study (6 wk), the S&C group performed concurrent maximal strength and endurance training, while the EO group performed endurance-only training. After the retest of all variables (midstudy), both groups subsequently, during phase 2, performed another 6 wk of endurance-only training that was followed by poststudy tests. No significant change for CV was identified in either group. The S&C group demonstrated a significant decrease for ARD values after phases 1 and 2 of the study. TT performances were significantly different in the S&C group after the intervention, with a performance improvement of 3.62%. This performance increase returned close to baseline after the 6-wk endurance-only training. Combining a 6-wk resistance-training program with endurance training significantly improves 5-km TT performance. Removing strength training results in some loss of those performance improvements.

Applicability of randomized trials in radiation oncology to standard clinical practice.

PubMed

Apisarnthanarax, Smith; Swisher-McClure, Samuel; Chiu, Wing K; Kimple, Randall J; Harris, Stephen L; Morris, David E; Tepper, Joel E

2013-08-15

Randomized controlled trials (RCTs) are commonly used to inform clinical practice; however, it is unclear how generalizable RCT data are to patients in routine clinical practice. The authors of this report assessed the availability and applicability of randomized evidence guiding medical decisions in a cohort of patients who were evaluated for consideration of definitive management in a radiation oncology clinic. The medical records of consecutive, new patient consultations between January and March 2007 were reviewed. Patient medical decisions were classified as those with (Group 1) or without (Group 2) available, relevant level I evidence (phase 3 RCT) supporting recommended treatments. Group 1 medical decisions were further divided into 3 groups based on the extent of fulfilling eligibility criteria for each RCT: Group 1A included decisions that fulfilled all eligibility criteria; Group 1B, decisions that did not fulfill at least 1 minor eligibility criteria; or Group 1C, decisions that did not fulfill at least 1 major eligibility criteria. Patient and clinical characteristics were tested for correlations with the availability of evidence. Of the 393 evaluable patients, malignancies of the breast (30%), head and neck (18%), and genitourinary system (14%) were the most common presenting primary disease sites. Forty-seven percent of all medical decisions (n = 451) were made without available (36%) or applicable (11%) randomized evidence to inform clinical decision making. Primary tumor diagnosis was significantly associated with the availability of evidence (P < .0001). A significant proportion of medical decisions in an academic radiation oncology clinic were made without available or applicable level I evidence, underscoring the limitations of relying solely on RCTs for the development of evidence-based health care. Copyright © 2013 American Cancer Society.

A randomized, double-blind, placebo-controlled, proof-of-concept trial of creatine monohydrate as adjunctive treatment for bipolar depression.

PubMed

Toniolo, Ricardo Alexandre; Silva, Michelle; Fernandes, Francy de Brito Ferreira; Amaral, José Antonio de Mello Siqueira; Dias, Rodrigo da Silva; Lafer, Beny

2018-02-01

Depressive episodes are a major cause of morbidity and dysfunction in individuals suffering from bipolar disorder. Currently available treatments for this condition have limited efficacy and new therapeutic options are needed. Extensive research in the pathophysiology of bipolar disorder points to the existence of mitochondrial and bioenergetic dysfunction. We hypothesized that creatine monohydrate, a nutraceutical that works as a mitochondrial modulator, would be effective as an adjunctive therapy for bipolar depression. We conducted a double-blind trial in which 35 patients with bipolar disorder type I or II in a depressive episode by DSM-IV criteria and in use of regular medication for the treatment of this phase of the disease were randomly allocated into two adjunctive treatment groups for 6 weeks: creatine monohydrate 6 g daily (N = 17) or placebo (N = 18). Primary efficacy was assessed by the change in the Montgomery-Åsberg Depression Rating Scale (MADRS). We did not find a statistically significant difference in the comparison between groups for the change in score on the MADRS after 6 weeks in an intention-to-treat (ITT) analysis (p = 0.560; Cohen's d = 0.231). However, we found significant superiority of creatine add-on vs. placebo when we considered the remission criterion of a MADRS score ≤ 12 at week 6 analyzing the outcome of the 35 randomized patients on ITT (52.9% remission in the creatine group vs. 11.1% remission in the placebo group) and of the 23 completers (66.7% remission in the creatine group vs. 18.2% remission in the placebo group) (p = 0.012; OR = 9.0 and p = 0.036; OR = 9.0, respectively). Two patients who received creatine switched to hypomania/mania early in the trial. No clinically relevant physical side-effects were reported or observed. This proof-of-concept study, aiming to restore brain bioenergetics using an adjunctive mitochondrial modulator, is not conclusive on the efficacy of creatine add-on for bipolar depression, but suggests that this compound may have a role in the adjunctive treatment of this phase of the illness. Further investigation through randomized controlled trials with larger samples should be conducted to verify the efficacy of creatine supplementation for bipolar depression and also for subsyndromal depressive symptoms.

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

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.

Quality-of-life outcomes from a randomized phase III trial of dose-dense weekly paclitaxel and carboplatin compared with conventional paclitaxel and carboplatin as a first-line treatment for stage II-IV ovarian cancer: Japanese Gynecologic Oncology Group Trial (JGOG3016).

PubMed

Harano, K; Terauchi, F; Katsumata, N; Takahashi, F; Yasuda, M; Takakura, S; Takano, M; Yamamoto, Y; Sugiyama, T

2014-01-01

Dose-dense weekly paclitaxel (Taxol) and carboplatin (dd-TC) improved survival compared with conventional tri-weekly paclitaxel and carboplatin (c-TC) as a first-line chemotherapy for newly diagnosed stage II-IV ovarian cancer in the Japanese Gynecologic Oncology Group 3016 trial. We report the quality-of-life (QoL) results from this trial. A total of 637 patients were randomly assigned to receive c-TC or dd-TC (c-TC, n = 319; dd-TC, n = 312) and were asked to complete a QoL assessment at baseline, just after the third and sixth chemotherapy cycles, and at 12 months after randomization. QoL was assessed using Functional Assessment of Cancer Therapy (FACT)-general (FACT-G), FACT-taxane subscale (FACT-T), and FACT-ovary subscale (FACT-Ov). The overall QoL and that according to each subscale were analyzed using mixed-effects models adjusted for treatment and time. Baseline QoL assessment was completed by 204 out of 319 (63.9%) and 200 out of 312 (64.1%) patients in the c-TC and dd-TC groups, respectively. In these groups, the compliance rates with regard to QoL assessment were 74.5% and 73.0%, respectively, after three chemotherapy cycles; 86.8% and 86.9%, respectively, after six chemotherapy cycles; and 74.2% and 71.6%, respectively, at 12 months after randomization. The overall QoL did not differ significantly between the two treatment groups up to 12 months after randomization (P = 0.46). However, QoL according to the FACT-T subscale was significantly lower in the dd-TC group than in the c-TC group (P = 0.02). dd-TC does not decrease overall QoL compared with c-TC.

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.

Maintenance of Clinical and Radiographic Benefit With Intravenous Golimumab Therapy in Patients With Active Rheumatoid Arthritis Despite Methotrexate Therapy: Week‐112 Efficacy and Safety Results of the Open‐Label Long‐Term Extension of a Phase III, Double‐Blind, Randomized, Placebo‐Controlled Trial

PubMed Central

Mendelsohn, Alan M.; Kim, Lilianne; Xu, Zhenhua; Leu, Jocelyn; Han, Chenglong; Lo, Kim Hung; Westhovens, Rene; Weinblatt, Michael E.

2015-01-01

Objective To evaluate the safety, efficacy, pharmacokinetics, immunogenicity, and radiographic progression through 2 years of treatment with intravenous (IV) golimumab plus methotrexate (MTX) in an open‐label extension of a phase III trial of patients with active rheumatoid arthritis (RA) despite MTX therapy. Methods In the phase III, double‐blind, randomized, placebo‐controlled GO‐FURTHER trial, 592 patients with active RA were randomized (2:1) to intravenous golimumab 2 mg/kg plus MTX (Group 1) or placebo plus MTX (Group 2) at weeks 0 and 4, then every 8 weeks thereafter; placebo patients crossed over to golimumab at week 16 (early escape) or week 24 (crossover). The final golimumab infusion was at week 100. Assessments included American College of Rheumatology 20%, 50%, 70% (ACR20, ACR50, ACR70) response criteria, 28‐joint count disease activity score using the C‐reactive protein level (DAS28‐CRP), physical function and quality of life measures, and changes in the modified Sharp/van der Heijde scores (SHS). Safety was monitored through week 112. Results In total, 486 patients (82.1%) continued treatment through week 100, and 68.1%, 43.8%, and 23.5% had an ACR20/50/70 response, respectively, at week 100. Clinical response and improvements in physical function and quality of life were generally maintained from week 24 through 2 years. Mean change from baseline to week 100 in SHS score was 0.74 in Group 1 and 2.10 in Group 2 (P = 0.005); progression from week 52 to week 100 was clinically insignificant in both groups. A total of 481 patients completed the safety followup through week 112; 79.1% had an adverse event, and 18.2% had a serious adverse event. Conclusion Clinical response to IV golimumab plus MTX was maintained through week 100. Radiographic progression following golimumab treatment was clinically insignificant between week 52 and week 100. No unexpected adverse events occurred through week 112, and the safety profile was consistent with anti–tumor necrosis factor therapy. PMID:25623393

Evaluation of the Efficacy and Safety of the Lercanidipine/Valsartan Combination in Korean Patients With Essential Hypertension Not Adequately Controlled With Lercanidipine Monotherapy: A Randomized, Multicenter, Parallel Design, Phase III Clinical Trial.

PubMed

Na, Sang-Hoon; Lee, Hae-Young; Hong Baek, Sang; Jeon, Hui-Kyung; Kang, Jin-Ho; Kim, Yoon-Nyun; Park, Chang-Gyu; Ryu, Jae-Kean; Rhee, Moo-Yong; Kim, Moo-Hyun; Hong, Taek-Jong; Choi, Dong-Ju; Cho, Seong-Wook; Cha, Dong-Hun; Jeon, Eun-Seok; Kim, Jae-Joong; Shin, Joon-Han; Park, Sung-Ha; Lee, Seung-Hwan; John, Sung-Hee; Shin, Eun-Seok; Kim, Nam-Ho; Lee, Sung-Yun; Kwan, Jun; Jeong, Myung-Ho; Kim, Sang-Wook; Jeong, Jin-Ok; Kim, Dong-Woon; Lee, Nam-Ho; Park, Woo-Jung; Ahn, Jeong-Cheon; Won, Kyung-Heon; Uk Lee, Seung; Cho, Jang-Hyun; Kim, Soon-Kil; Ahn, Taehoon; Hong, Sukkeun; Yoo, Sang-Yong; Kim, Song-Yi; Kim, Byung-Soo; Juhn, Jae-Hyeon; Kim, Sun-Young; Lee, Yu-Jeong; Oh, Byung-Hee

2015-08-01

The objective of this study was to evaluate the efficacy and safety of the lercanidipine/valsartan combination compared with lercanidipine monotherapy in patients with hypertension. Part 1 of this study was the randomized, multicenter, double-blind, parallel group, Phase III, 8-week clinical trial to compare superiority of lercanidipine 10 mg/valsartan 80 mg (L10/V80) and lercanidipine 10 mg/valsartan 160 mg (L10/V160) combinations with lercanidipine 10 mg (L10) monotherapy. At screening, hypertensive patients, whose diastolic blood pressure (DBP) was >90 mm Hg after 4 weeks with L10, were randomized to 3 groups of L10, L10/V80, and L10/V160. The primary end point was the change in the mean sitting DBP from baseline (week 0) after 8 weeks of therapy. Patients who were randomly assigned to L10/V160 and whose mean DBP was still ≥ 90 mm Hg in part 1 were enrolled to the up-titration extension study with lercanidipine 20 mg/valsartan 160 mg (L20/V160) (part 2). Of 772 patients screened, 497 were randomized to 3 groups (166 in the L10 group, 168 in the L10/V80 group, and 163 in the L10/V160 group). Mean (SD) age was 55 (9.9) years, and male patients comprised 69%. The mean (SD) baseline systolic blood pressure (SBP)/DBP were 148.4 (15.1)/94.3 (9.5) mm Hg. No significant differences were found between groups in baseline characteristics except the percentages of previous history of antihypertensive medication. The primary end points, the changes of mean (SD) DBP at week 8 from the baseline were -2.0 (8.8) mm Hg in the L10 group, -6.7 (8.5) mm Hg in L10/V80 group, and -8.1 (8.4) mm Hg in L10/V160 group. The adjusted mean difference between the combination groups and the L10 monotherapy group was -4.6 mm Hg (95% CI, -6.5 to -2.6; P < 0.001) in the L10/V80 group and -5.9 mm Hg (95% CI, -7.9 to -4.0, P < 0.001) in the L10/V160 group, which had significantly greater efficacy in BP lowering. A total of 74 patients were enrolled in the part 2 extension study. Changes of mean (SD) DBP and SBP from week 8 to week 12 and week 16 were -5.6 (7.9)/-8.0 (12.0) mm Hg and -5.5 (7.0)/-8.5 (11.3) mm Hg, respectively. For evaluation of the safety profile, the frequencies of adverse events between groups were also not significantly different. The most frequently reported adverse events were headache (6 cases, 20.7%) in the L10 group, dizziness (8 cases, 16.3%) in L10/V80 group, and nasopharyngitis (3 cases, 9.4%) in L10/V160 group, and the incidences of adverse events were not different between groups. Treatment of L10/V80 or L10/V160 combination therapy resulted in significantly greater BP lowering compared with L10 monotherapy. Moreover, the L20/V160 high dose combination had additional BP lowering effect compared with nonresponders with the L10/V160 combination. ClinicalTrials.gov: NCT01928628. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

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.

Does stage tailoring matter in brief alcohol interventions for job-seekers? A randomized controlled trial.

PubMed

Freyer-Adam, Jennis; Baumann, Sophie; Schnuerer, Inga; Haberecht, Katja; Bischof, Gallus; John, Ulrich; Gaertner, Beate

2014-11-01

To investigate whether or not a stage tailored intervention is more effective than a non-stage tailored intervention of the same intensity in reducing alcohol use among job-seekers with unhealthy alcohol use, and whether initial motivation to change is a moderator of efficacy. A three-group randomized controlled trial with 3-, 6- and 15-month follow-ups. Three job agencies in Germany. A total of 1243 job-seekers with unhealthy alcohol use were randomized to (i) stage tailored intervention based on the transtheoretical model of change (ST), (ii) non-stage tailored intervention based on the theory of planned behaviour (NST) and (iii) assessment only (controls). Participants received feedback letters and manuals at baseline and 3 months later. Piecewise latent growth models were calculated measuring change in 'alcohol use' from baseline to month 3 (active intervention phase) and from months 3 to 15 (post-intervention phase, primary outcome). Motivation to change was included as a 4-point continuous measure. All groups reduced alcohol use from months 0 to 3 (controls: mean = -0.866, NST: mean = -0.883, ST: mean = -0.718, Ps ≤ 0.001). Post-intervention (months 3-15), low-motivated individuals in the ST group showed a greater reduction than those in the control group (β = 0.135, P = 0.039, Cohen's d = 0.42) and in the NST group (β = 0.180, P = 0.009, Cohen's d = 0.55). In contrast, compared to the ST group (β = 0.030, P = 0.361), alcohol use decreased more strongly with higher initial motivation in the NST group (β = -0.118, P = 0.010). Among job-seekers with high levels of alcohol consumption, an intervention tailored to motivational 'stage of change' was more effective than a non-stage tailored intervention for reducing alcohol use 15 months after baseline assessment in participants with low initial motivation to change. © 2014 Society for the Study of Addiction.

Pupil dilation dynamics with an intracameral fixed combination of mydriatics and anesthetic during cataract surgery.

PubMed

Chiambaretta, Frederic; Pleyer, Uwe; Behndig, Anders; Pisella, Pierre-Jean; Mertens, Erik; Limao, Antonio; Fasce, Francesco; Fernandez, Joaquin; Benmoussa, Salah-Eddine; Labetoulle, Marc; Cochener, Beatrice

2018-03-01

To compare the pupil dynamics of an intracameral combination of 2 mydriatics and 1 anesthetic (Mydrane) to a standard topical regimen for cataract surgery. Sixty-two centers in Europe and 6 centers in Algeria. Prospective case series. Pupil size measurements were performed in 2 randomized studies (phase 2 and phase 3) under masked conditions (recorded videography, masked reading center). The outcomes in the phase 2 study supported evaluation of the timeframe to obtain pupil dilation and the phase 3 study provided results on mydriasis stability. Phase 2 and phase 3 comprised 139 patients and 591 patients, respectively. After intracameral combination administration, 95% of the pupil dilation was achieved within a mean of 28.6 seconds ± 4.6 (SD). At the beginning of capsulorhexis creation, the mean pupil diameter was larger than 7.0 mm in both groups. The intraoperative pupil diameter remained stable in the intracameral combination group and decreased in the topical group. The mean change in pupil size just before capsulorhexis to the end of surgery (just before cefuroxime injection) was -0.22 ± 0.72 mm and -1.67 ± 0.98 mm, respectively. No clinically significant change in pupil diameter (change <1.0 mm) occurred in the majority of the intracameral combination group (89.3%) compared with the topical group (26.8%). Intracameral combination of 2 mydriatics and 1 anesthetic is an alternative to topical mydriatics for cataract surgery. The prompt onset of pupil dilation and the stable mydriasis induced by this drug combination improved the intraoperative conditions during crucial steps, such as intraocular lens implantation. Copyright © 2018. Published by Elsevier Inc.

A double-blind randomized controlled pilot trial examining the safety and efficacy of therapeutic touch in premature infants.

PubMed

Whitley, Julie Anne; Rich, Bonnie L

2008-12-01

To explore the hypothesis that nontouch therapy such as therapeutic touch (TT) reduces stress to a clinically important degree and is safe to use in preterm infants. A pilot randomized, double-blind, controlled trial. Two groups of 10 infants were enrolled and randomly assigned to treatment or nontreatment groups. Gestational age was less than 29 weeks. Demographic descriptions of the 2 groups were statistically similar. The observer and staff were blinded to assignment; the TT practitioner was blinded to observed measurements. Each infant received either TT or no therapeutic touch (NTT) for 5 minutes on 3 consecutive days at the same time of day, behind a curtain. Heart period variability (HPV) was measured 5 minutes before, during, and after the treatment phase. Examination of the parameters of oxygen saturation and episodes of apnea demonstrated no increase in adverse events in TT group compared with NTT group. Repeated-measures multivariate analysis of variance on HPV revealed differences in the interaction of group assignment with low-frequency, high-frequency, and low-to-high- frequency ratio interaction (F2,143 = 8.076, P = .000) and for group, day, and low-frequency, high-frequency, and low-to-high-frequency ratio (F2,288 = 3.146, P = .015), and in the posttreatment time period (F1,16 = 6.259, P = .024), reflective of greater parasympathetic activity in TT group. In this pilot trial, HPV showed an increase for the TT group compared with the NTT group. The study reveals no adverse effects of TT in preterm infants.

Effects of Functional Fascial Taping on pain and function in patients with non-specific low back pain: a pilot randomized controlled trial.

PubMed

Chen, Shu-Mei; Alexander, Ron; Lo, Sing Kai; Cook, Jill

2012-10-01

To compare the short-term and medium-term effect of Functional Fascial Taping to placebo taping on pain and function in people with non-specific low back pain. A pilot randomized controlled trial with a 2-week intervention, and 2-, 6- and 12-week follow-up. Individuals with non-specific low back pain recruited from local communities. Forty-three participants with non-specific low back pain for more than 6 weeks were randomized into either Functional Fascial Taping group (n = 21) or placebo group (n = 22). The intervention group was treated with Functional Fascial Taping while the control group was treated with placebo taping. Both groups received four treatments over 2 weeks. Worst and average pain and function were assessed at baseline, after the 2-week intervention, and at 6 and 12 weeks follow-up. The Functional Fascial Taping group demonstrated significantly greater reduction in worst pain compared to placebo group after the 2-week intervention (P = 0.02, effect size = 0.74; 95% confidence interval 0.11-1.34). A higher proportion of participants in Functional Fascial Taping group attained the minimal clinically important difference in worst pain (P = 0.007) and function (P = 0.007) than those in placebo group after the 2-week intervention. There were no significant differences in either group's disability rating or clinically important difference in average pain at any time. Functional Fascial Taping reduced worst pain in patients with non-acute non-specific low back pain during the treatment phase. No medium-term differences in pain or function were observed.

Axitinib dose titration: analyses of exposure, blood pressure and clinical response from a randomized phase II study in metastatic renal cell carcinoma.

PubMed

Rini, B I; Melichar, B; Fishman, M N; Oya, M; Pithavala, Y K; Chen, Y; Bair, A H; Grünwald, V

2015-07-01

In a randomized, double-blind phase II trial in patients with metastatic renal cell carcinoma (mRCC), axitinib versus placebo titration yielded a significantly higher objective response rate. We evaluated pharmacokinetic and blood pressure (BP) data from this study to elucidate relationships among axitinib exposure, BP change, and efficacy. Patients received axitinib 5 mg twice daily during a lead-in period. Patients who met dose-titration criteria were randomized 1:1 to stepwise dose increases with axitinib or placebo. Patients ineligible for randomization continued without dose increases. Serial 6-h and sparse pharmacokinetic sampling were carried out; BP was measured at clinic visits and at home in all patients, and by 24-h ambulatory BP monitoring (ABPM) in a subset of patients. Area under the plasma concentration-time curve from 0 to 24 h throughout the course of treatment (AUCstudy) was higher in patients with complete or partial responses than those with stable or progressive disease in the axitinib-titration arm, but comparable between these groups in the placebo-titration and nonrandomized arms. In the overall population, AUCstudy and efficacy outcomes were not strongly correlated. Mean BP across the population was similar when measured in clinic, at home, or by 24-h ABPM. Weak correlations were observed between axitinib steady-state exposure and diastolic BP. When grouped by change in diastolic BP from baseline, patients in the ≥10 and ≥15 mmHg groups had longer progression-free survival. Optimal axitinib exposure may differ among patients with mRCC. Pharmacokinetic or BP measurements cannot be used exclusively to guide axitinib dosing. Individualization of treatment with vascular endothelial growth factor receptor tyrosine kinase inhibitors, including axitinib, is thus more complex than anticipated and cannot be limited to a single clinical factor. © 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.

[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.

Effects of Pistachio Nut Supplementation on Blood Glucose in Patients with Type 2 Diabetes: A Randomized Crossover Trial

PubMed Central

Parham, Mahmoud; Heidari, Saeide; Khorramirad, Ashraf; Hozoori, Mohammad; Hosseinzadeh, Fatemeh; Bakhtyari, Lida; Vafaeimanesh, Jamshid

2014-01-01

BACKGROUND: Diabetes is a chronic, potentially debilitating, and often fatal disease. Dietary strategies to reduce postprandial glycemia are important in the prevention and treatment of diabetes. Nuts are rich in mono- and polyunsaturated fatty acids, which may reduce hyperglycemia and improve metabolism. OBJECTIVES: To evaluate the effectiveness of pistachio nut supplementation on glycemic and inflammatory measures in patients with type 2 diabetes. METHODS: In this double-blind, randomized, placebo-controlled, crossover trial, 48 diabetic patients were equally assigned to groups A and B. Patients in group A received a snack of 25 g pistachio nuts twice a day for 12 weeks and group B received a control meal without nuts. After 12 weeks of intervention, the patients had an 8-week washout. Then the groups were displaced, and group B received the same amount of pistachios for 12 weeks. RESULTS: With respect to the total change in variables over both phases, there was a marked decrease in HbA1c (-0.4%) and fasting blood glucose (FBG) concentrations (-16 mg/dl) in the pistachio group compared with the control group (p ≤ 0.001 for both). There was no overall significant change in BMI, blood pressure, HOMA-IR, and C-reactive protein (CRP) concentrations. Analysis of the two phases separately showed a decrease in FBG by 14 mg/dl and in HbA1c by 0.45% in the treatment group (A) after 12 weeks, while no significant differences were seen in group B (control group). In the second phase, FBG decreased from 151.36 ± 39.22 to 137.28 ± 28.65 mg/dl (-14 mg/dl) and HbA1c decreased from 7.42 ± 0.97 to 7.15 ± 0.68 mg/dl (-0.28%, p = 0.013 and p = 0.033, respectively) in the pistachio group (B). Pistachio consumption reduced systolic blood pressure (p = 0.007), BMI (p = 0.011), and CRP (p = 0.002) in patients from the treatment groups, but not insulin resistance. CONCLUSIONS: Dietary consumption of pistachio nuts as a snack has beneficial effects on glycemic control, blood pressure, obesity, and inflammation markers in diabetic patients. PMID:25396407

Effects of Budesonide on Cabazitaxel Pharmacokinetics and Cabazitaxel-Induced Diarrhea: A Randomized, Open-Label Multicenter Phase II Study.

PubMed

Nieuweboer, Annemieke J M; de Graan, Anne-Joy M; Hamberg, Paul; Bins, Sander; van Soest, Robert J; van Alphen, Robbert J; Bergman, Andries M; Beeker, Aart; van Halteren, Henk; Ten Tije, Albert J; Zuetenhorst, Hanneke; van der Meer, Nelly; Chitu, Dana; de Wit, Ronald; Mathijssen, Ron H J

2017-04-01

Purpose: Forty-seven percent of patients in the pivotal trial of cabazitaxel reported diarrhea of any grade. Aiming to reduce the incidence of diarrhea, we studied the effects of budesonide on the grade of cabazitaxel-induced diarrhea during the first two treatment cycles. Experimental Design: Between December 2011 and October 2015, 246 metastatic castration-resistant prostate cancer patients were randomized to receive standard-of-care cabazitaxel 25 mg/m 2 every 3 weeks plus prednisone 10 mg/day (group CABA) or same dose/schedule of cabazitaxel with concomitant budesonide 9 mg daily during the first two treatment cycles (group BUD). The occurrence of diarrhea was reported by physicians and by patients in a diary. χ 2 tests were used to compare incidence numbers. An intention-to-treat principle was used. Results: In the phase II trial, 227 patients were evaluable. Grade 2-3 diarrhea occurred in 35 patients (15%) and grade 4 diarrhea was not reported. The incidence of grade 2-3 diarrhea was comparable in both treatment groups: 14 of 113 patients in group CABA (12%) versus 21 of 114 patients in group BUD (18%; P = 0.21). Seven patients were admitted to the hospital with diarrhea ( n = 5 group CABA vs. n = 2 group BUD). PSA response was seen in 30% of patients and was not affected by budesonide coadministration ( P = 0.29). Also, other toxicities were not affected by budesonide coadministration. Conclusions: The incidence of cabazitaxel-induced diarrhea was notably lower than reported in the TROPIC trial and appears manageable in routine clinical practice. Budesonide coadministration did not reduce the incidence or severity of cabazitaxel-induced diarrhea. Clin Cancer Res; 23(7); 1679-83. ©2016 AACR . ©2016 American Association for Cancer Research.

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.

Design, conduct, and analyses of Breast International Group (BIG) 1-98: a randomized, double-blind, phase-III study comparing letrozole and tamoxifen as adjuvant endocrine therapy for postmenopausal women with receptor-positive, early breast cancer.

PubMed

Giobbie-Hurder, Anita; Price, Karen N; Gelber, Richard D

2009-06-01

Aromatase inhibitors provide superior disease control when compared with tamoxifen as adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer. To present the design, history, and analytic challenges of the Breast International Group (BIG) 1-98 trial: an international, multicenter, randomized, double-blind, phase-III study comparing the aromatase inhibitor letrozole with tamoxifen in this clinical setting. From 1998-2003, BIG 1-98 enrolled 8028 women to receive monotherapy with either tamoxifen or letrozole for 5 years, or sequential therapy of 2 years of one agent followed by 3 years of the other. Randomization to one of four treatment groups permitted two complementary analyses to be conducted several years apart. The first, reported in 2005, provided a head-to-head comparison of letrozole versus tamoxifen. Statistical power was increased by an enriched design, which included patients who were assigned sequential treatments until the time of the treatment switch. The second, reported in late 2008, used a conditional landmark approach to test the hypothesis that switching endocrine agents at approximately 2 years from randomization for patients who are disease-free is superior to continuing with the original agent. The 2005 analysis showed the superiority of letrozole compared with tamoxifen. The patients who were assigned tamoxifen alone were unblinded and offered the opportunity to switch to letrozole. Results from other trials increased the clinical relevance about whether or not to start treatment with letrozole or tamoxifen, and analysis plans were expanded to evaluate sequential versus single-agent strategies from randomization. Due to the unblinding of patients assigned tamoxifen alone, analysis of updated data will require ascertainment of the influence of selective crossover from tamoxifen to letrozole. BIG 1-98 is an example of an enriched design, involving complementary analyses addressing different questions several years apart, and subject to evolving analytic plans influenced by new data that emerge over time.

mFOLFOX6 Plus Panitumumab Versus 5-FU/LV Plus Panitumumab After Six Cycles of Frontline mFOLFOX6 Plus Panitumumab: A Randomized Phase II Study of Patients With Unresectable or Advanced/Recurrent, RAS Wild-type Colorectal Carcinoma (SAPPHIRE)-Study Design and Rationale.

PubMed

Nagata, Naoki; Mishima, Hideyuki; Kurosawa, Shuichi; Oba, Koji; Sakamoto, Junichi

2017-06-01

In Japan, oxaliplatin (OXA)/5-fluorouracil (5-FU)/leucovorin (LV)-the mFOLFOX6 regimen-is the most frequently used first-line chemotherapy backbone for metastatic colorectal cancer. However, peripheral nerve disorders caused by OXA during mFOLFOX6 therapy can decrease patients' quality of life. OXA can be safely discontinued from a FOLFOX regimen after 6 cycles during first-line therapy. Also, for patients who discontinue OXA without having experienced peripheral nerve disorders, reintroducing OXA in the later stages of treatment could remain an option. The study is a phase II, multicenter, open-label, parallel-group, randomized, controlled exploratory study comparing the efficacy and safety of mFOLFOX6 plus panitumumab and 5-FU/LV plus panitumumab in patients with chemotherapy-naïve, unresectable, advanced or recurrent colorectal carcinoma of RAS wild-type (SAPPHIRE; ClinicalTrials.gov identifier, NCT02337946). Eligible patients will receive 6 cycles of mFOLFOX6 plus panitumumab combination therapy, followed by 1:1 randomization to either further treatment with mFOLFOX6 plus panitumumab or discontinuation of OXA and treatment with 5-FU/LV plus panitumumab. Up to 100 randomized patients will receive treatment for approximately 12 months or until any of the criteria for treatment discontinuation have been met. The primary endpoint is progression-free survival rate at 9 months after the day of randomization. The secondary endpoints are progression-free survival, overall survival, response rate, and interval to treatment failure. Safety will be evaluated according to the incidence and severity of adverse events, including the incidence of peripheral nerve and skin disorders. Additional endpoints will include maintenance of performance status, continuation of OXA in the mFOLFOX6 plus panitumumab group, and continuation of panitumumab in both groups. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Optimal back-to-front airplane boarding.

PubMed

Bachmat, Eitan; Khachaturov, Vassilii; Kuperman, Ran

2013-06-01

The problem of finding an optimal back-to-front airplane boarding policy is explored, using a mathematical model that is related to the 1+1 polynuclear growth model with concave boundary conditions and to causal sets in gravity. We study all airplane configurations and boarding group sizes. Optimal boarding policies for various airplane configurations are presented. Detailed calculations are provided along with simulations that support the main conclusions of the theory. We show that the effectiveness of back-to-front policies undergoes a phase transition when passing from lightly congested airplanes to heavily congested airplanes. The phase transition also affects the nature of the optimal or near-optimal policies. Under what we consider to be realistic conditions, optimal back-to-front policies lead to a modest 8-12% improvement in boarding time over random (no policy) boarding, using two boarding groups. Having more than two groups is not effective.

Development of Maps of Simple and Complex Cells in the Primary Visual Cortex

PubMed Central

Antolík, Ján; Bednar, James A.

2011-01-01

Hubel and Wiesel (1962) classified primary visual cortex (V1) neurons as either simple, with responses modulated by the spatial phase of a sine grating, or complex, i.e., largely phase invariant. Much progress has been made in understanding how simple-cells develop, and there are now detailed computational models establishing how they can form topographic maps ordered by orientation preference. There are also models of how complex cells can develop using outputs from simple cells with different phase preferences, but no model of how a topographic orientation map of complex cells could be formed based on the actual connectivity patterns found in V1. Addressing this question is important, because the majority of existing developmental models of simple-cell maps group neurons selective to similar spatial phases together, which is contrary to experimental evidence, and makes it difficult to construct complex cells. Overcoming this limitation is not trivial, because mechanisms responsible for map development drive receptive fields (RF) of nearby neurons to be highly correlated, while co-oriented RFs of opposite phases are anti-correlated. In this work, we model V1 as two topographically organized sheets representing cortical layer 4 and 2/3. Only layer 4 receives direct thalamic input. Both sheets are connected with narrow feed-forward and feedback connectivity. Only layer 2/3 contains strong long-range lateral connectivity, in line with current anatomical findings. Initially all weights in the model are random, and each is modified via a Hebbian learning rule. The model develops smooth, matching, orientation preference maps in both sheets. Layer 4 units become simple cells, with phase preference arranged randomly, while those in layer 2/3 are primarily complex cells. To our knowledge this model is the first explaining how simple cells can develop with random phase preference, and how maps of complex cells can develop, using only realistic patterns of connectivity. PMID:21559067

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.

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).

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 effect of four-phase teaching method on midwifery students’ emotional intelligence in managing the childbirth

PubMed Central

Mohamadirizi, Soheila; Fahami, Fariba; Bahadoran, Parvin; Ehsanpour, Soheila

2015-01-01

Background: An active teaching method has been used widely in medical education. The aim of this study was to determine the effectiveness of the four-phase teaching method on midwifery students’ emotional intelligence (EQ) in managing the childbirth. Materials and Methods: This was an experimental study that performed in 2013 in Isfahan University of Medical Sciences. Thirty midwifery students were involved in this study and selected through a random sampling method. The EQ questionnaire (43Q) was completed by both the groups, before and after the education. The collected data were analyzed using SPSS 14, the independent t-test, and the paired t-test. The statistically significant level was considered to be <0.05. Results: The findings of the independent t-test did not show any significant difference between EQ scores of the experimental and the control group before the intervention, whereas a statistically significant difference was observed after the intervention between the scores of two groups (P = 0.009). The paired t-test showed a statistically significant difference in EQ scores in the two groups after the intervention in the four-phase and the control group, respectively, as P = 0.005 and P = 0.018. Furthermore, the rate of self-efficiency has increased in the experimental group and control group as 66% and 13% (P = 0.024), respectively. Conclusion: The four-phase teaching method can increase the EQ levels of midwifery students. Therefore, the conduction of this educational model is recommended as an effective learning method. PMID:26097861

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

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.

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.

Evaluation of the effects of ice massage applied to large intestine 4 (hegu) on postpartum pain during the active phase of labor

PubMed Central

Can, Hafize Ozturk; Saruhan, Aynur

2015-01-01

Background: The uterus continues to contract after childbirth. The pain caused by the contractions of the uterus can be as severe as labor pain. The study was aimed to evaluate the effects of ice massage applied to the large intestine 4 (LI4) on postpartum pain during the active phase of labor. Materials and Methods: The study was designed as a randomized controlled trial with three groups and carried out in two stages. The study sample comprised of 150 pregnant women, who were referred to a maternity hospital. In the experimental group, ice massage was applied to LI4 during four contractions within the active phase of labor. In the placebo group, pressure was applied to LI4 using silicone balloons and the third group was the control group. The Visual Analog Scale (VAS) and The McGill (Melzack) Pain Questionnaire (MPQ) were compared among the experimental, placebo, and control groups. Results: The mothers in the ice application group had the lowest mean VAS score. It was determined that ice massage applied to LI4 during the active phase of labor did not lead to any statistical differences in mothers in the first 24 hours postpartum in terms of the characteristics of the pain with MPQ and VAS. Conclusions: In the study, the perception of pain was tried to be minimized by applying pressure with ice balloons to LI4. However, although the application was determined to have made no difference in the pain intensity, the mothers’ statements in the ice application group suggested that they felt more comfortable than did the mothers in the other groups. PMID:25709702

Efficacy, Safety, and Tolerability of Fulranumab as an Adjunctive Therapy in Patients With Inadequately Controlled, Moderate-to-Severe Chronic Low Back Pain: A Randomized, Double-blind, Placebo-controlled, Dose-ranging, Dose-loading Phase II Study.

PubMed

Sanga, Panna; Polverejan, Elena; Wang, Steven; Kelly, Kathleen M; Thipphawong, John

2016-06-01

Fulranumab is an investigational, fully human recombinant monoclonal antibody (IgG2) that neutralizes the biological actions of human nerve growth factor. Low back pain is a common cause of noncancer chronic pain and represents one of the most significant socioeconomic health-related problems in developed countries. This randomized, double-blind, placebo-controlled study was conducted to evaluate the analgesic effect of fulranumab in patients with moderate-to-severe chronic low back pain. Patients (aged 18-80 years) were randomized to receive subcutaneous injections every 4 weeks in 1 of 5 parallel treatment groups: placebo or fulranumab 1mg (1mgQ4wk), 3mg (3mgQ4wk), 3mg after a 6mg loading dose (6mgLD+3mgQ4wk), or 10mg (10mgQ4wk) every 4 weeks. A total of 385 patients (median age, 53 years; women, 54%) received at least 1 injection of study medication. No statistically significant differences were observed in improvement of pain intensity scores between the fulranumab treatment regimens and the placebo group at week 12 (primary end point; mean [SD], placebo: -2.0 [2.17], 1mgQ4wk: -1.9 [2.14], 3mgQ4wk: -2.2 [1.89], 6mgLD+3mgQ4wk: -2.0 [1.72] and 10mgQ4wk: -2.1 [2.18]). Results for secondary efficacy parameters (change in the Oswestry Disability Index, Brief Pain Inventory-Short Form, and Patient Global Assessment scales) were consistent with the primary outcome. A placebo effect was observed; the overall percentage of patients with treatment-emergent adverse events (TEAEs) was similar between the placebo (76%) and fulranumab treatment groups (77%-90%). Across all phases, the most common TEAEs in at least 10% of patients (combined fulranumab group vs placebo) were arthralgia (15% vs 12%), back pain (15% vs 18%), upper respiratory tract infection (15% vs 8%), paresthesia (14% vs 8%), diarrhea (12% vs 4%), headache (12% vs 8%), hypoesthesia (11% vs 5%), pain in extremity (11% vs 8%), sinusitis (10% vs 5%), and nasopharyngitis (10% vs 9%). Across all phases, neurologic TEAEs were less frequent in the placebo group (14%) versus the fulranumab treatment groups (25%). In the posttreatment phase, 8 patients had joint replacement operations, which were considered a result of normal progression of osteoarthritis. One case in the 10-mg group was determined to be rapid progession of osteoarthritis and was considered to be possibly related to study drug. Fulranumab did not demonstrate efficacy compared with placebo in patients with chronic low back pain but was generally well-tolerated. ClinicalTrials.gov identifier: NCT00973024. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Assessing critical thinking in medical sciences students in two sequential semesters: Does it improve?

PubMed

Athari, Zeinab-Sadat; Sharif, Sayyed-Mostafa; Nasr, Ahmad Reza; Nematbakhsh, Mehdi

2013-01-01

Critical thinking is an important outcome criterion of higher education in any discipline. Medical and paramedical students always encounter with many new problems in clinical settings and medicinal laboratory, and critical thinking is an essential skill in obtaining a better approach for problem solving. We performed a pre-and post-test to evaluate the change of critical thinking skills in medical sciences students who enrolled in Isfahan University of Medical Sciences in Iran during the academic years 2008-2010. In a longitudinal design study, the critical thinking skills were compared in medical sciences students in two sequential semesters using the California Critical Thinking Skills Test. The test is divided into two parts (parts 1 and 2), including 17 items in each part. Based on proportional stratified sampling, a groups of students (group 1, n=159) were selected from the university population, who enrolled in medicine, pharmacy, nursing, and rehabilitation colleges. The students in group 1 were asked to complete the part 1 of the test (phase I). After one semester, another group (group 2, n=138) from the same population was randomly selected, and they were asked to complete the part two (phase II). The students' demographic data also were recorded. The California critical thinking skills test was translated and it validity and reliability were approved before. No significant difference was observed between the two groups in the demographic data. The students critical thinking scores in phase II significantly reduced in comparison with phase 1 (p<0.05). The phase II scores in subdivisions of analysis, inference, inductive reasoning, and deductive reasoning also failed to demonstrate improvement. It seems curriculum reform is necessary to improve the students' critical thinking.

Lunar phases and zodiac signs do not influence quality of radical cystectomy--a statistical analysis of 452 patients with invasive bladder cancer.

PubMed

May, Matthias; Braun, Kay-Patrick; Helke, Christian; Richter, Willi; Vogler, Horst; Hoschke, Bernd; Siegsmund, Michael

2007-01-01

To determine the influence of the lunar phases and the position of the moon in the zodiac on the frequency of complications and the survival of bladder cancer patients after radical cystectomy. It has been postulated that radical cystectomy performed during the waxing moon, or particularly at full moon, or at the zodiac sign Libra is associated with a poorer outcome. We tested this hypothesis by evaluating the progression-free survival, the complication rate and the re-operation rate for 452 consecutive patients after radical cystectomy. In this retrospective review, the dates of surgery were allocated to the lunar phases and the zodiac signs. Based on these classifications, the patients were placed in groups which combined the lunar phase laws and differentiated between evidently unfavorable (full moon or waxing moon and/or the zodiac sign Libra; assigned to group 1) and favorable periods for surgery (new moon or waning moon and other signs of the zodiac apart from Libra; assigned to group 2). The mean follow-up was 49 months (range 0-158 months). A total of 244 patients (54%) were operated during an unfavorable period (group 1) and 208 (46%) patients during the auspicious period (group 2). The mean age, gender and kind of urinary derivation did not differ significantly in the two groups. Pathological tumor stages were evenly distributed according to the lunar phase groups (P = 0.713). We found no significant differences in the perioperative mortality rates, early re-operation rates, early complications, and late complications across the two groups. No significant differences in progression-free survival were observed when timing of cystectomy during the lunar cycle was considered (P = 0.231). Our analysis demonstrated no predictable influence of the lunar phase on survival or complications. Although this was not a prospective randomized trial, the statistical magnitude of the results do not support any recommendations for scheduling patients for radical cystectomy at any particular day of the lunar phase.

Home-based exercise program and fall-risk reduction in older adults with multiple sclerosis: phase 1 randomized controlled trial.

PubMed

Sosnoff, Jacob J; Finlayson, Marcia; McAuley, Edward; Morrison, Steve; Motl, Robert W

2014-03-01

To determine the feasibility, safety, and efficacy of a home-based exercise intervention targeting fall risk in older adults with multiple sclerosis. A randomized controlled pilot trial. A home-based exercise program. Participants were randomly allocated to either a home-based exercise intervention group (n = 13) or a waiting list control group (n = 14). The exercise group completed exercises targeting lower muscle strength and balance three times a week for 12 weeks. The control group continued normal activity. Fall risk (Physiological Profile Assessment scores), balance (Berg Balance Scale), and walking testing prior to and immediately following the 12-week intervention. Each outcome measure was placed in an analysis of covariance with group as the between-subject factor and baseline values as the covariate. Effect sizes were calculated. Twelve participants from the control group and ten from the exercise group completed the study. There were no related adverse events. Fall risk was found to decrease in the exercise group following the intervention (1.1 SD 1.0 vs. 0.6 SD 0.6) while there was an increase in fall risk in the control group (1.9 SD 1.5 vs. 2.2 SD 1.9). Effect sizes for most outcomes were large (η(2) > 0.15). Home-based exercise was found to be feasible, safe, and effective for reducing physiological fall risk in older adults with multiple sclerosis. Our findings support the implementation of a larger trial to reduce fall risk in persons with multiple sclerosis.

Pomaglumetad Methionil (LY2140023 Monohydrate) and Aripiprazole in Patients with Schizophrenia: A Phase 3, Multicenter, Double-Blind Comparison.

PubMed

Adams, David H; Zhang, Lu; Millen, Brian A; Kinon, Bruce J; Gomez, Juan-Carlos

2014-01-01

We tested the hypothesis that long-term treatment with pomaglumetad methionil would demonstrate significantly less weight gain than aripiprazole in patients with schizophrenia. In this 24-week, multicenter, randomized, double-blind, Phase 3 study, 678 schizophrenia patients were randomized to either pomaglumetad methionil (n = 516) or aripiprazole (n = 162). Treatment groups were also compared on efficacy and various safety measures, including serious adverse events (SAEs), discontinuation due to adverse events (AEs), treatment-emergent adverse events (TEAEs), extrapyramidal symptoms (EPS), and suicide-related thoughts and behaviors. The pomaglumetad methionil group showed significantly greater weight loss at Week 24 (Visit 12) compared with the aripiprazole group (-2.8 ± 0.4 versus 0.4 ± 0.6; P < 0.001). However, change in Positive and Negative Syndrome Scale (PANSS) total scores for aripiprazole was significantly greater than for pomaglumetad methionil (-15.58 ± 1.58 versus -12.03 ± 0.99; P = 0.045). The incidences of SAEs (8.2% versus 3.1%; P = 0.032) and discontinuation due to AEs (16.2% versus 8.7%; P = 0.020) were significantly higher for pomaglumetad methionil compared with aripiprazole. No statistically significant differences in the incidence of TEAEs, EPS, or suicidal ideation or behavior were noted between treatment groups. In conclusion, long-term treatment with pomaglumetad methionil resulted in significantly less weight gain than aripiprazole. This trial is registered with ClinicalTrials.gov NCT01328093.

A cluster randomized controlled platform trial comparing group MEmory specificity training (MEST) to group psychoeducation and supportive counselling (PSC) in the treatment of recurrent depression.

PubMed

Werner-Seidler, Aliza; Hitchcock, Caitlin; Bevan, Anna; McKinnon, Anna; Gillard, Julia; Dahm, Theresa; Chadwick, Isobel; Panesar, Inderpal; Breakwell, Lauren; Mueller, Viola; Rodrigues, Evangeline; Rees, Catrin; Gormley, Siobhan; Schweizer, Susanne; Watson, Peter; Raes, Filip; Jobson, Laura; Dalgleish, Tim

2018-06-01

Impaired ability to recall specific autobiographical memories is characteristic of depression, which when reversed, may have therapeutic benefits. This cluster-randomized controlled pilot trial investigated efficacy and aspects of acceptability, and feasibility of MEmory Specificity Training (MEST) relative to Psychoeducation and Supportive Counselling (PSC) for Major Depressive Disorder (N = 62). A key aim of this study was to determine a range of effect size estimates to inform a later phase trial. Assessments were completed at baseline, post-treatment and 3-month follow-up. The cognitive process outcome was memory specificity. The primary clinical outcome was symptoms on the Beck Depression Inventory-II at 3-month follow-up. The MEST group demonstrated greater improvement in memory specificity relative to PSC at post-intervention (d = 0.88) and follow-up (d = 0.74), relative to PSC. Both groups experienced a reduction in depressive symptoms at 3-month follow-up (d = 0.67). However, there was no support for a greater improvement in depressive symptoms at 3 months following MEST relative to PSC (d = -0.04). Although MEST generated changes on memory specificity and improved depressive symptoms, results provide no indication that MEST is superior to PSC in the resolution of self-reported depressive symptoms. Implications for later-phase definitive trials of MEST are discussed. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effectiveness of balance exercises in the acute post-operative phase following total hip and knee arthroplasty: A randomized clinical trial

PubMed Central

Overend, Tom J; Spaulding, Sandi J; Zecevic, Aleksandra; Kramer, John F

2015-01-01

Objectives: To determine the effectiveness of balance exercises in the acute post-operative phase following total hip arthroplasty or total knee arthroplasty. Methods: Patients who had total hip arthroplasty (n = 30) or total knee arthroplasty (n = 33) were seen in their residence 1–2 times per week for 5 weeks. At the first post-operative home visit, patients were randomly assigned to either typical (TE, n = 33) or typical plus balance (TE + B, n = 30) exercise groups. The TE group completed seven typical surgery-specific joint range-of-motion and muscle strengthening exercises, while the TE + B group completed the typical exercises plus three balance exercises. Patients were assessed before and 5 weeks after administering the rehabilitation program using four outcome measures: (1) the Berg Balance Scale, (2) the Timed Up and Go test, (3) the Western Ontario McMaster Universities Osteoarthritis Index, and (4) the Activities-specific Balance Confidence Scale. Results: Post-intervention scores for all four outcome measures were significantly improved (p < 0.01) over baseline scores. Patients who participated in the TE + B group demonstrated significantly greater improvement on the Berg Balance Scale and the Timed Up and Go tests (p < 0.01). Conclusion: Balance exercises added to a typical rehabilitation program resulted in significantly greater improvements in balance and functional mobility compared to typical exercises alone. PMID:26770765

The use of recombinant human LH (lutropin alfa) in the late stimulation phase of assisted reproduction cycles: a double-blind, randomized, prospective study.

PubMed

Tarlatzis, B; Tavmergen, E; Szamatowicz, M; Barash, A; Amit, A; Levitas, E; Shoham, Z

2006-01-01

The effect of recombinant human LH (r-hLH; lutropin alfa) in women undergoing controlled ovarian stimulation with recombinant human FSH (r-hFSH) prior to IVF was investigated. After down-regulation with the GnRH agonist, buserelin, 114 normo-ovulatory women (aged 18-37 years) received r-hFSH alone until the lead follicle reached a diameter of 14 mm. Patients were then randomized in a double-blind fashion to receive r-hFSH in addition to r-hLH, 75 IU s.c., or placebo daily for a maximum of 10 days prior to oocyte retrieval and IVF. The primary end-point was the number of metaphase II oocytes. There were no significant differences between treatment groups for the primary end-point. Serum estradiol concentrations on the day of HCG administration were significantly higher in the group receiving r-hLH plus r-hFSH than in the group receiving r-hFSH alone (P = 0.0001), but there were no significant differences between the groups in dose and duration of r-hFSH treatment required, oocyte maturation, fertilization rate, pregnancy rate and live birth rate. In this patient population, the addition of r-hLH during the late follicular phase of a long GnRH agonist and r-hFSH stimulation cycle provides no further benefit in terms of oocyte maturation or other end-points.

A randomized controlled trial of cognitive behavioral therapy for individuals at clinical high risk of psychosis.

PubMed

Addington, Jean; Epstein, Irvin; Liu, Lu; French, Paul; Boydell, Katherine M; Zipursky, Robert B

2011-01-01

There has been increasing interest in early detection during the prodromal phase of a psychotic disorder. To date a few treatment studies have been published with some promising results for both pharmacological treatments, using second generation antipsychotics, and psychological interventions, mainly cognitive behavioral therapy. The purpose of this study was to determine first if cognitive behavioral therapy (CBT) was more effective in reducing the rates of conversion compared to a supportive therapy and secondly whether those who received CBT had improved symptoms compared to those who received supportive therapy. Fifty-one individuals at clinical high risk of developing psychosis were randomized to CBT or a supportive therapy for up to 6 months. The sample was assessed at 6, 12 and 18 months post baseline on attenuated positive symptoms, negative symptoms, depression, anxiety and social functioning. Conversions to psychosis only occurred in the group who received supportive therapy although the difference was not significant. Both groups improved in attenuated positive symptoms, depression and anxiety and neither improved in social functioning and negative symptoms. There were no differences between the two treatment groups. However, the improvement in attenuated positive symptoms was more rapid for the CBT group. There are limitations of this trial and potential explanations for the lack of differences. However, both the results of this study and the possible explanations have significant implications for early detection and intervention in the pre-psychotic phase and for designing future treatments. Copyright © 2010 Elsevier B.V. All rights reserved.

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.

[Clinical trial of a combination of three drugs in fixed proportions in the treatment of tuberculosis. Groupe de Travail sur la Chimiothérapie de la Tuberculose].

PubMed

Chaulet, P; Boulahbal, F

1995-10-01

The Matiben Chest Clinic at the West Algiers University Teaching Hospital, and 3 outpatient clinics specializing in tuberculosis and lung disease in Algiers. To determine the tolerance and efficacy of a fixed proportion combination of 3 antituberculosis drugs (per tablet: 50 mg isoniazid + 120 mg rifampicin + 300 mg pyrazinamide) given during the first 2 months of a daily 6-month chemotherapy regimen. Random prospective treatment trial comparing a group of 124 patients receiving the triple combination with another group of 126 patients receiving the 3 drugs separately during the initial treatment phase. The continuation phase was identical for the 2 groups. Comparison of tolerance in the first 2 months, and of the failure and relapse rates (respectively at the end of treatment and 24 months after the end of treatment). During the first 2 months side-effects were significantly more common in the group receiving the drugs separately. At the end of treatment and during the following 24 months there were no significant differences in the cumulative rates of observed failures and relapses (2% and 1%). The triple combination studied could replace the separate drugs in the initial treatment phase in countries where the bioavailability of the drugs used has been proven.

Effects of workload preview on task scheduling during simulated instrument flight.

PubMed

Andre, A D; Heers, S T; Cashion, P A

1995-01-01

Our study examined pilot scheduling behavior in the context of simulated instrument flight. Over the course of the flight, pilots flew along specified routes while scheduling and performing several flight-related secondary tasks. The first phase of flight was flown under low-workload conditions, whereas the second phase of flight was flown under high-workload conditions in the form of increased turbulence and a disorganized instrument layout. Six pilots were randomly assigned to each of three workload preview groups. Subjects in the no-preview group were not given preview of the increased-workload conditions. Subjects in the declarative preview group were verbally informed of the nature of the flight workload manipulation but did not receive any practice under the high-workload conditions. Subjects in the procedural preview group received the same instructions as the declarative preview group but also flew half of the practice flight under the high-workload conditions. The results show that workload preview fostered efficient scheduling strategies. Specifically, those pilots with either declarative or procedural preview of future workload demands adopted an efficient strategy of scheduling more of the difficult secondary tasks during the low-workload phase of flight. However, those pilots given a procedural preview showed the greatest benefits in overall flight performance.

Self-administration of intranasal influenza vaccine: Immunogenicity and volunteer acceptance

PubMed Central

Burgess, Timothy H.; Murray, Clinton K.; Bavaro, Mary F.; Landrum, Michael L.; O’Bryan, Thomas A.; Rosas, Jessica G.; Cammarata, Stephanie M.; Martin, Nicholas J.; Ewing, Daniel; Raviprakash, Kanakatte; Mor, Deepika; Zell, Elizabeth R.; Wilkins, Kenneth J.; Millar, Eugene V.

2018-01-01

Background In outbreak settings, mass vaccination strategies could maximize health protection of military personnel. Self-administration of live attenuated influenza vaccine (LAIV) may be a means to vaccinate large numbers of people and achieve deployment readiness while sparing the use of human resources. Methods A phase IV, open-label, randomized controlled trial evaluating the immunogenicity and acceptance of self-administered (SA) LAIV was conducted from 2012 to 2014. SA subjects were randomized to either individual self-administration or self-administration in a group setting. Control randomized subjects received healthcare worker-administered (HCWA) LAIV. Anti-hemagglutinin (HAI) antibody concentrations were measured pre- and post-vaccination. The primary endpoint was immunogenicity non-inferiority between SA and HCWA groups. Subjects were surveyed on preferred administration method. Results A total of 1077 subjects consented and were randomized (529 SA, 548 HCWA). Subject characteristics were very similar between groups, though SA subjects were younger, more likely to be white and on active duty. The per-protocol analysis included 1024 subjects (501 SA, 523 HCWA). Post-vaccination geometric mean titers by vaccine strain and by study group (HCWA vs. SA) were: A/H1N1 (45.8 vs. 48.7, respectively; p = 0.43), A/H3N2 (45.5 vs. 46.4; p = 0.80), B/Yamagata (17.2 vs. 17.8; p = 0.55). Seroresponses to A components were high (∼67%), while seroresponses to B components were lower (∼25%). Seroresponse did not differ by administration method. Baseline preference for administration method was similar between groups, with the majority in each group expressing no preference. At follow-up, the majority (64%) of SA subjects preferred SA vaccine. Conclusions LAIV immunogenicity was similar for HCWA and SA vaccines. SA was well-tolerated and preferred to HCWA among those who performed SA. PMID:26117150

A randomized phase II trial of personalized peptide vaccine plus low dose estramustine phosphate (EMP) versus standard dose EMP in patients with castration resistant prostate cancer.

PubMed

Noguchi, Masanori; Kakuma, Tatsuyuki; Uemura, Hirotsugu; Nasu, Yasutomo; Kumon, Hiromi; Hirao, Yasuhiko; Moriya, Fukuko; Suekane, Shigetaka; Matsuoka, Kei; Komatsu, Nobukazu; Shichijo, Shigeki; Yamada, Akira; Itoh, Kyogo

2010-07-01

Personalized peptide vaccination (PPV) combined with chemotherapy could be a novel approach for many cancer patients. In this randomized study, we evaluated the anti-tumor effect and safety of PPV plus low-dose estramustine phosphate (EMP) as compared to standard-dose EMP for HLA-A2- or -A24-positive patients with castration resistant prostate cancer. Patients were randomized into groups receiving either PPV plus low-dose EMP (280 mg/day) or standard-dose EMP (560 mg/day). After disease progression, patients were switched to the opposite regime. The primary end point was progression-free survival (PFS). We randomly assigned 28 patients to receive PPV plus low-dose EMP and 29 patients to receive standard-dose EMP. Nineteen events in the PPV group and 20 events in the EMP group occurred during the first treatment. Median PFS for the first treatment was 8.5 months in the PPV group and 2.8 months in the EMP group with a hazard ratio (HR) of 0.28 (95% CI, 0.14-0.61; log-rank P = 0.0012), while there was no difference for median PFS for the second treatment. The HR for overall survival was 0.3 (95% CI, 0.1-0.91) in favor of the PPV plus low-dose EMP group (log-rank, P = 0.0328). The PPV plus low-dose EMP was well tolerated without major adverse effects and with increased levels of IgG and cytotoxic-T cell responses to the vaccinated peptides. PPV plus low-dose EMP was associated with an improvement in PSA-based PFS as compared to the standard-dose EMP alone.

Comparative trial of low- and high-dose zonisamide as monotherapy for childhood epilepsy.

PubMed

Eun, So-Hee; Kim, Heung Dong; Eun, Baik-Lin; Lee, In Kyu; Chung, Hee Jung; Kim, Joon Sik; Kang, Hoon-Chul; Lee, Young-Mock; Suh, Eun Sook; Kim, Dong Wook; Eom, Soyong; Lee, Joon Soo; Moon, Han Ku

2011-09-01

To evaluate the effectiveness of zonisamide (ZNS) as monotherapy in children with newly diagnosed epilepsy. This randomized, multicenter trial included a 2-4-week titration and a 24-week maintenance phase after randomization to low-(3-4 mg/kg/day) or high-(6-8 mg/kg/day) dose groups as target maintenance dosages. The primary outcome measure was the seizure-free rate over 6 months, while a secondary measure was the change in cognition and behavior from screening to the end of the maintenance phase. Out of 125 patients enrolled, 90 (49 low-dose and 41 high-dose) completed the study. Forty-one patients (63.1%) in the low-dose group and 34(57.6%) in the high-dose group achieved 6 months' freedom from seizures (p=0.66). After treatment, the picture arrangement subtest improved in the low-dose group (p=0.047) while the vocabulary subtest worsened in the high-dose group (p=0.020). Comparing between the two groups, the vocabulary subtest in the high-dose group was significantly worse than that in the low-dose group (p=0.002). Social competence, somatic complaints, depression/anxiety and delinquent and aggressive behavior in the low-dose group were significantly improved (p<0.05). Moreover, total social competence, somatic complaints, delinquent behavior, externalizing, and total behavior problems were significantly more improved in the low-dose group than the high-dose group (p<0.05). ZNS is an effective monotherapy for newly diagnosed childhood epilepsy. Lower doses of ZNS have a similar efficacy and more beneficial neurocognitive effects compared to higher doses. When prescribing higher doses of ZNS, one must be aware of the possible manifestation of problems associated with language development, such as those affecting vocabulary acquisition. Copyright © 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

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.

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.

Berberine containing quadruple therapy for initial Helicobacter pylori eradication: An open-label randomized phase IV trial.

PubMed

Zhang, Di; Ke, Li; Ni, Zhen; Chen, Yu; Zhang, Lin-Hui; Zhu, Shao-Hua; Li, Chan-Juan; Shang, Lei; Liang, Jie; Shi, Yong-Quan

2017-08-01

Due to increasing antimicrobial resistance, a bismuth-based quadruple regimen has been recommended as an alternative first-line therapy for Helicobacter pylori (H pylori) eradication. However, different results are varied greatly and the availability of bismuth was limited in some countries. We assessed the efficacy and safety of 14-day berberine-containing quadruple therapy as an alternative regimen for H pylori eradication. In a randomized, open-label, non-inferiority, phase IV trial between November 25, 2014, and October 15, 2015, 612 treatment-naive patients were randomly assigned to 14-day berberine-containing (n = 308) or 14-day bismuth-containing (n = 304) quadruple therapy. The primary outcomes were eradication rates determined by the C urea breath test (C-UBT) 28 days after the end of treatment. The secondary outcomes were adverse events and compliance. The baseline demographic data including age, gender, body mass index (BMI), general condition and severity score were not statistically different in both groups. The eradication rates in bismuth and berberine groups were 86.4% (266/308) and 90.1% (274/304) in intention-to-treat (ITT) analysis (P = .149), and 89.6% (266/297) and 91.3% (273/299) in per-protocol (PP) analysis (P = .470), respectively. No statistically significant difference was found in the overall incidence of adverse events between both groups (35.7% vs 28.6%, P = .060). Both regimens achieved the recommended efficacy for H pylori eradication. The berberine-containing quadruple regimen was not inferior to bismuth-containing quadruple regimen and can be recommended as an alternative regimen for H pylori eradication in the local region.

Preliminary efficacy and safety of an oromucosal standardized cannabis extract in chemotherapy-induced nausea and vomiting.

PubMed

Duran, Marta; Pérez, Eulàlia; Abanades, Sergio; Vidal, Xavier; Saura, Cristina; Majem, Margarita; Arriola, Edurne; Rabanal, Manel; Pastor, Antoni; Farré, Magí; Rams, Neus; Laporte, Joan-Ramon; Capellà, Dolors

2010-11-01

Despite progress in anti-emetic treatment, many patients still suffer from chemotherapy-induced nausea and vomiting (CINV). This is a pilot, randomized, double-blind, placebo-controlled phase II clinical trial designed to evaluate the tolerability, preliminary efficacy, and pharmacokinetics of an acute dose titration of a whole-plant cannabis-based medicine (CBM) containing delta-9-tetrahydrocannabinol and cannabidiol, taken in conjunction with standard therapies in the control of CINV. Patients suffering from CINV despite prophylaxis with standard anti-emetic treatment were randomized to CBM or placebo, during the 120 h post-chemotherapy period, added to standard anti-emetic treatment. Tolerability was measured as the number of withdrawals from the study during the titration period because of adverse events (AEs). The endpoint for the preliminary efficacy analysis was the proportion of patients showing complete or partial response. Seven patients were randomized to CBM and nine to placebo. Only one patient in the CBM arm was withdrawn due to AEs. A higher proportion of patients in the CBM group experienced a complete response during the overall observation period [5/7 (71.4%) with CMB vs. 2/9 (22.2%) with placebo, the difference being 49.2% (95% CI 1%, 75%)], due to the delayed period. The incidence of AEs was higher in the CBM group (86% vs. 67%). No serious AEs were reported. The mean daily dose was 4.8 sprays in both groups. Compared with placebo, CBM added to standard antiemetic therapy was well tolerated and provided better protection against delayed CINV. These results should be confirmed in a phase III clinical trial. © 2010 Department of Health, Generalitat of Catalonia. British Journal of Clinical Pharmacology © 2010 The British Pharmacological Society.

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.).

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.

Comparison of different anesthesia techniques during esophagogastroduedenoscopy in children: a randomized trial.

PubMed

Patino, Mario; Glynn, Susan; Soberano, Mark; Putnam, Philip; Hossain, Md Monir; Hoffmann, Clifford; Samuels, Paul; Kibelbek, Michael J; Gunter, Joel

2015-10-01

Esophagogastroduedenoscopy (EGD) in children is usually performed under general anesthesia. Anesthetic goals include minimization of airway complications while maximizing operating room (OR) efficiency. Currently, there is no consensus on which anesthetic technique best meets these goals. We performed a prospective randomized study comparing three different anesthetic techniques. To evaluate the incidence of respiratory complications (primary aim) and institutional efficiency (secondary aim) among three different anesthetic techniques in children undergoing EGD. Subjects received a standardized inhalation induction of anesthesia followed by randomization to one of the three groups: Group intubated, sevoflurane (IS), Group intubated, propofol (IP), and Group native airway, nonintubated, propofol (NA). Respiratory complications included minor desaturation (SpO2 between 94% and 85%), severe desaturation (SpO2 < 85%), apnea, airway obstruction/laryngospasm, aspiration, and/or inadequate anesthesia during the endoscopy. Evaluation of institutional efficiency was determined by examining the time spent during the different phases of care (anesthesia preparation, procedure, OR stay, recovery, and total perioperative care). One hundred and seventy-nine children aged 1-12 years (median 7 years; 4.0, 10.0) were enrolled (Group IS N = 60, Group IP N = 59, Group NA N = 61). The incidence of respiratory complications was higher in the Group NA (0.459) vs Group IS (0.033) or Group IP (0.086) (P < 0.0001). The most commonly observed complications were desaturation, inadequate anesthesia, and apnea. There were no differences in institutional efficiency among the three groups. Respiratory complications were more common in Group NA. The use of native airway with propofol maintenance during EGD does not offer advantages with respect to respiratory complications or institutional efficiency. © 2015 John Wiley & Sons Ltd.

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.

The Efficacy of Propranolol in Retinopathy of Prematurity and its Correlation with the Platelet Mass Index.

PubMed

Korkmaz, Levent; Baştuğ, Osman; Ozdemir, Ahmet; Korkut, Sabriye; Karaca, Cagatay; Akin, Mustafa Ali; Gunes, Tamer; Kurtoglu, Selim; Ozturk, Mehmet Adnan

2017-01-01

Retinopathy of Prematurity (ROP) is a proliferative vitreoretinopathy which is one of the most frequent causes of blindness in children. In an attempt to find a solution to this important problem in preterm children, the search for new, effective treatment modalities with fewer side effects is underway. In our study, which was planned for this reason, we aimed to investigate the effects of propranolol treatment applied to cases of ROP in various stages during the second phase (known as the neovascularization-hypoxia phase) and to determine the correlation of these effects with the platelet mass index (PMI). A total of 171 preterm infants at risk of ROP were selected randomly for inclusion in the study. All of the patients were classified according to their stage of ROP and were divided into control and treatment groups. While the cases in the control group were administered physiological saline solution, those in the treatment group were administered propranolol in the period that corresponded to the second stage of the disease. The thrombocyte and PMI values in the first and second stages of each study group were recorded. A significant difference was found between the control and treatment groups of the stage 2 ROP study subjects. In the stage 2 ROP study group, no significant difference was detected between the control and treatment cases in terms of platelet counts in phase 1 or in the PMI values and the thrombolytic counts in phase 2. On the other hand, in phase 2 of the stage 2 ROP study subjects significant differences were detected between the control and treatment group in terms of PMI values. In the study, it was found in the stage 2 ROP study group that propranolol reduced the need for laser photocoagulation significantly. Also, in parallel to the efficacy of propranolol in this study group, a decrease was observed in PMI values.

Evaluation of a specialized oncology nursing supportive care intervention in newly diagnosed breast and colorectal cancer patients following surgery: a cluster randomized trial.

PubMed

Sussman, Jonathan; Bainbridge, Daryl; Whelan, Timothy J; Brazil, Kevin; Parpia, Sameer; Wiernikowski, Jennifer; Schiff, Susan; Rodin, Gary; Sergeant, Myles; Howell, Doris

2018-05-01

Better coordination of supportive services during the early phases of cancer care has been proposed to improve the care experience of patients. We conducted a randomized trial to test a community-based nurse-led coordination of care intervention in cancer patients. Surgical practices were cluster randomized to a control group involving usual care practices or a standardized nursing intervention consisting of an in-person supportive care assessment with ongoing support to meet identified needs, including linkage to community services. Newly diagnosed breast and colorectal cancer patients within 7 days of cancer surgery were eligible. The primary outcome was the patient-reported outcome (PRO) of continuity of care (CCCQ) measured at 3 weeks. Secondary outcomes included unmet supportive care needs (SCNS), quality of life (EORTC QLQ-C30), health resource utilization, and level of uncertainty with care trajectory (MUIS) at 3 and/or 8 weeks. A total of 121 breast and 72 colorectal patients were randomized through 28 surgical practices. There was a small improvement in the informational domain of continuity of care (difference 0.29 p = 0.05) and a trend to less emergency room use (15.8 vs 7.1%) (p = 0.07). There were no significant differences between groups on unmet need, quality of life, or uncertainty. We did not find substantial gaps in the PROs measured immediately following surgery for breast and colorectal cancer patients. The results of this study support a more targeted approach based on need and inform future research focused on improving navigation during the initial phases of cancer treatment. ClinicalTrials.gov Identifier: NCT00182234. SONICS-Effectiveness of Specialist Oncology Nursing.

52-week results of the phase 3 randomized study comparing SB4 with reference etanercept in patients with active rheumatoid arthritis

PubMed Central

Emery, Paul; Vencovský, Jiří; Sylwestrzak, Anna; Leszczyński, Piotr; Porawska, Wieslawa; Baranauskaite, Asta; Tseluyko, Vira; Zhdan, Vyacheslav M.; Stasiuk, Barbara; Milasiene, Roma; Barrera Rodriguez, Aaron Alejandro; Cheong, Soo Yeon; Ghil, Jeehoon

2017-01-01

Abstract Objective To compare the 52-week efficacy and safety of SB4 [an etanercept biosimilar] with reference etanercept (ETN) in patients with active RA. Methods In a phase 3, randomized, double-blind, multicentre study, patients with moderate to severe RA despite MTX treatment were randomized to receive 50 mg/week of s.c. SB4 or ETN up to week 52. Efficacy assessments included ACR response rates, 28-joint DAS, Simplified and Clinical Disease Activity Indices and changes in the modified total Sharp score (mTSS). Safety and immunogenicity were also evaluated. Results A total of 596 patients were randomized to receive either SB4 (n = 299) or ETN (n = 297) and 505 (84.7%) patients completed 52 weeks of the study. At week 52, the ACR20 response rates in the per-protocol set were comparable between SB4 (80.8%) and ETN (81.5%). All efficacy results were comparable between the two groups and they were maintained up to week 52. Radiographic progression was also comparable and the change from baseline in the mTSS was 0.45 for SB4 and 0.74 for ETN. The safety profile of SB4 was similar to that of ETN and the incidence of anti-drug antibody development up to week 52 was 1.0 and 13.2% in the SB4 and ETN groups, respectively. Conclusion Efficacy including radiographic progression was comparable between SB4 and ETN up to week 52. SB4 was well tolerated and had a similar safety profile to that of ETN. Trial registration number ClinicalTrials.gov NCT01895309, EudraCT 2012-005026-30 PMID:28968793

The mental health of UK Gulf war veterans: phase 2 of a two phase cohort study.

PubMed

Ismail, Khalida; Kent, Kate; Brugha, Traolach; Hotopf, Matthew; Hull, Lisa; Seed, Paul; Palmer, Ian; Reid, Steve; Unwin, Catherine; David, Anthony S; Wessely, Simon

2002-09-14

To examine the prevalence of psychiatric disorders in veterans of the Gulf war with or without unexplained physical disability (a proxy measure of ill health) and in similarly disabled veterans who had not been deployed to the Gulf war (non-Gulf veterans). Two phase cohort study. Current and ex-service UK military personnel. Phase 1 consisted of three randomly selected samples of Gulf veterans, veterans of the 1992-7 Bosnia peacekeeping mission, and UK military personnel not deployed to the Gulf war (Era veterans) who had completed a postal health questionnaire. Phase 2 consisted of randomly selected subsamples from phase 1 of Gulf veterans who reported physical disability (n=111) or who did not report disability (n=98) and of Bosnia (n=54) and Era (n=79) veterans who reported physical disability. Psychiatric disorders assessed by the schedule for clinical assessment in neuropsychiatry and classified by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition. Only 24% (n=27) of the disabled Gulf veterans had a formal psychiatric disorder (depression, anxiety, or alcohol related disorder). The prevalence of psychiatric disorders in non-disabled Gulf veterans was 12%. Disability and psychiatric disorders were weakly associated in the Gulf group when confounding was adjusted for (adjusted odds ratio 2.4, 99% confidence interval 0.8 to 7.2, P=0.04). The prevalence of psychiatric disorders was similar in disabled non-Gulf veterans and disabled Gulf veterans ( 19% v 24%; 1.3, 0.5 to 3.4). All groups had rates for post-traumatic stress disorder of between 1% and 3%. Most disabled Gulf veterans do not have a formal psychiatric disorder. Post-traumatic stress disorder is not higher in Gulf veterans than in other veterans. Psychiatric disorders do not fully explain self reported ill health in Gulf veterans; alternative explanations for persistent ill health in Gulf veterans are needed.

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.

Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and Cardioprotection Among Metabolically Healthy Obese Adults: A Randomized Clinical Trial.

PubMed

Trepanowski, John F; Kroeger, Cynthia M; Barnosky, Adrienne; Klempel, Monica C; Bhutani, Surabhi; Hoddy, Kristin K; Gabel, Kelsey; Freels, Sally; Rigdon, Joseph; Rood, Jennifer; Ravussin, Eric; Varady, Krista A

2017-07-01

Alternate-day fasting has become increasingly popular, yet, to date, no long-term randomized clinical trials have evaluated its efficacy. To compare the effects of alternate-day fasting vs daily calorie restriction on weight loss, weight maintenance, and risk indicators for cardiovascular disease. A single-center randomized clinical trial of obese adults (18 to 64 years of age; mean body mass index, 34) was conducted between October 1, 2011, and January 15, 2015, at an academic institution in Chicago, Illinois. Participants were randomized to 1 of 3 groups for 1 year: alternate-day fasting (25% of energy needs on fast days; 125% of energy needs on alternating "feast days"), calorie restriction (75% of energy needs every day), or a no-intervention control. The trial involved a 6-month weight-loss phase followed by a 6-month weight-maintenance phase. The primary outcome was change in body weight. Secondary outcomes were adherence to the dietary intervention and risk indicators for cardiovascular disease. Among the 100 participants (86 women and 14 men; mean [SD] age, 44 [11] years), the dropout rate was highest in the alternate-day fasting group (13 of 34 [38%]), vs the daily calorie restriction group (10 of 35 [29%]) and control group (8 of 31 [26%]). Mean weight loss was similar for participants in the alternate-day fasting group and those in the daily calorie restriction group at month 6 (-6.8% [95% CI, -9.1% to -4.5%] vs -6.8% [95% CI, -9.1% to -4.6%]) and month 12 (-6.0% [95% CI, -8.5% to -3.6%] vs -5.3% [95% CI, -7.6% to -3.0%]) relative to those in the control group. Participants in the alternate-day fasting group ate more than prescribed on fast days, and less than prescribed on feast days, while those in the daily calorie restriction group generally met their prescribed energy goals. There were no significant differences between the intervention groups in blood pressure, heart rate, triglycerides, fasting glucose, fasting insulin, insulin resistance, C-reactive protein, or homocysteine concentrations at month 6 or 12. Mean high-density lipoprotein cholesterol levels at month 6 significantly increased among the participants in the alternate-day fasting group (6.2 mg/dL [95% CI, 0.1-12.4 mg/dL]), but not at month 12 (1.0 mg/dL [95% CI, -5.9 to 7.8 mg/dL]), relative to those in the daily calorie restriction group. Mean low-density lipoprotein cholesterol levels were significantly elevated by month 12 among the participants in the alternate-day fasting group (11.5 mg/dL [95% CI, 1.9-21.1 mg/dL]) compared with those in the daily calorie restriction group. Alternate-day fasting did not produce superior adherence, weight loss, weight maintenance, or cardioprotection vs daily calorie restriction. clinicaltrials.gov Identifier: NCT00960505.

[The influence of the menstrual cycle on acute and persistent pain after laparoscopic cholecystectomy].

PubMed

Sari, Sinem; Kozanhan, Betul; Egilmez, Ayse Ilksen; Soyder, Aykut; Aydin, Osman Nuri; Galimberti, Fabrizio; Sessler, Daniel; Turan, Alparslan

Fluctuations of female sex hormones during menstrual cycle influence pain perception. Endogenous pain inhibition is impaired in follicular phase of menstrual cycle. We tested the primary hypothesis that the women having surgery during their follicular phase have more acute pain and require higher opioids than those in the luteal phase, and secondarily we tested that women who have surgery during their follicular phase have more incisional pain at 3 month postoperatively. 127 adult females having laparoscopic cholecystectomy were randomized to have surgery during the luteal or follicular phase of their menstrual cycle. Standardized anesthesia and pain management regimen was given to all patients. Pain and analgesic consumption were evaluated in post-anesthesia care unit and every 4h in the first 24h. Adverse effects were questioned every 4h. Time to oral intake and ambulation were recorded. Post-surgical pain, hospital anxiety, depression scale, SF-12 questionnaire were evaluated at 1 and 3 month visits. There was no difference in acute pain scores and analgesic consumption through the 24h period, Visual Analog Scale at 24h was 1.5±1.5cm for follicular group 1.4±1.7cm for luteal group (p=0.57). Persistent postoperative pain was significantly more common one and at three month, with an incidence was 33% and 32% in the patients at follicular phase versus 16% and 12% at luteal phase, respectively. The Visual Analog Scale at one and at three month was 1.6±0.7cm and 1.8±0.8cm for follicular group and 2.7±1.3cm and 2.9±1.7cm in the luteal group (p=0.02), respectively. There were no significant differences between the groups with respect to anxiety and depression, SF-12 scores at either time. Nausea was more common in follicular-phase group (p=0.01) and oral feeding time was shorter in follicular phase (5.9±0.9h) than in luteal phase (6.8±1.9h, p=0.02). Although persistent postoperative pain was significantly more common one and three months after surgery the magnitude of the pain was low. Our results do not support scheduling operations to target particular phases of the menstrual cycle. Copyright © 2017 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Rebamipide (OPC-12759) in the treatment of dry eye: a randomized, double-masked, multicenter, placebo-controlled phase II study.

PubMed

Kinoshita, Shigeru; Awamura, Saki; Oshiden, Kazuhide; Nakamichi, Norihiro; Suzuki, Hiroyuki; Yokoi, Norihiko

2012-12-01

To investigate the dose response for efficacy of 1% and 2% rebamipide ophthalmic suspension compared with placebo in patients with dry eye. A randomized, double-masked, multicenter, placebo-controlled, parallel-group, dose-response phase II study. A total of 308 patients with dry eye. After a 2-week screening period, patients were randomized to receive placebo or 1% rebamipide or 2% rebamipide administered as 1 drop in each eye 4 times daily for 4 weeks. The primary objective end point was change in fluorescein corneal staining (FCS) score from baseline to last observation carried forward (LOCF). Secondary objective end points were lissamine green conjunctival staining (LGCS) score, tear film break-up time (TBUT), and the Schirmer's test. Secondary subjective end points included dry eye-related ocular symptoms (foreign body sensation, dryness, photophobia, eye pain, and blurred vision) score and patients' overall treatment impression score. Rebamipide dose response was observed in FCS, LGCS, and TBUT scores. Both 1% and 2% rebamipide were significantly more effective than the placebo in terms of the change from baseline to LOCF for FCS, LGCS, and TBUT scores. There was no significant difference between the rebamipide and placebo groups from baseline to LOCF in Schirmer's test values, and dose response was not observed. In the predefined dry eye subpopulation with a baseline FCS score of 10 to 15, the mean change from baseline in the 2% rebamipide group was larger than that in the 1% rebamipide group. Change from baseline to LOCF for all 5 dry eye-related ocular symptom scores and patients' overall treatment impression showed significant improvements in the 1% and 2% rebamipide groups compared with the placebo group, except for photophobia in the 1% rebamipide group. No deaths or drug-related serious adverse events occurred in any treatment group. The incidence of ocular abnormalities was similar across the rebamipide and placebo groups. Rebamipide was effective in treating both objective signs and subjective symptoms of dry eye and were well tolerated in this 4-week study. Although 1% and 2% rebamipide were both efficacious, 2% rebamipide may be more effective than 1% rebamipide in some measures. Proprietary or commercial disclosure may be found after the references. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Live attenuated tetravalent (G1-G4) bovine-human reassortant rotavirus vaccine (BRV-TV): Randomized, controlled phase III study in Indian infants.

PubMed

Saluja, Tarun; Palkar, Sonali; Misra, Puneet; Gupta, Madhu; Venugopal, Potula; Sood, Ashwani Kumar; Dhati, Ravi Mandyam; Shetty, Avinash; Dhaded, Sangappa Malappa; Agarkhedkar, Sharad; Choudhury, Amlan; Kumar, Ramesh; Balasubramanian, Sundaram; Babji, Sudhir; Adhikary, Lopa; Dupuy, Martin; Chadha, Sangeet Mohan; Desai, Forum; Kukian, Darshna; Patnaik, Badri Narayan; Dhingra, Mandeep Singh

2017-06-16

Rotavirus remains the leading cause of diarrhoea among children <5years. We assessed immunogenic non-inferiority of a tetravalent bovine-human reassortant rotavirus vaccine (BRV-TV) over the licensed human-bovine pentavalent rotavirus vaccine RV5. Phase III single-blind study (parents blinded) in healthy infants randomized (1:1) to receive three doses of BRV-TV or RV5 at 6-8, 10-12, and 14-16weeks of age. All concomitantly received a licensed diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b conjugate vaccine (DTwP-HepB-Hib) and oral polio vaccine (OPV). Immunogenic non-inferiority was evaluated in terms of the inter-group difference in anti-rotavirus serum IgA seroresponse (primary endpoint), and seroprotection/seroresponse rates to DTwP-HepB-Hib and OPV vaccines. Seroresponse was defined as a ≥4-fold increase in titers from baseline to D28 post-dose 3. Non-inferiority was declared if the difference between groups (based on the lower limit of the 95% confidence interval [CI]) was above -10%. Each subject was evaluated for solicited adverse events 7days and unsolicited & serious adverse events 28days following each dose of vaccination. Of 1195 infants screened, 1182 were randomized (590 to BRV-TV; 592 to RV5). Non-inferiority for rotavirus serum IgA seroresponse was not established: BRV-TV, 47.1% (95%CI: 42.8; 51.5) versus RV5, 61.2% (95%CI: 56.8; 65.5); difference between groups, -14.08% (95%CI: -20.4; -7.98). Serum IgA geometric mean concentrations at D28 post-dose 3 were 28.4 and 50.1U/ml in BRV-TV and RV5 groups, respectively. For all DTwP-HepB-Hib and OPV antigens, seroprotection/seroresponse was elicited in both groups and the -10% non-inferiority criterion between groups was met. There were 16 serious adverse events, 10 in BRV-TV group and 6 in RV5 group; none were classified as vaccine related. Both groups had similar vaccine safety profiles. BRV-TV was immunogenic but did not meet immunogenic non-inferiority criteria to RV5 when administered concomitantly with routine pediatric antigens in infants. Copyright © 2017 Elsevier Ltd. All rights reserved.

A randomized, double-blind, active control, multicenter, dose-finding study of lipegfilgrastim (XM22) in breast cancer patients receiving myelosuppressive therapy.

PubMed

Buchner, Anton; Elsässer, Reiner; Bias, Peter

2014-11-01

This dose-ranging study was conducted to identify the optimal fixed dose of lipegfilgrastim compared with pegfilgrastim 6.0 mg for the provision of neutrophil support during myelosuppressive chemotherapy in patients with breast cancer. A phase 2 study was conducted in which 208 chemotherapy-naive patients were randomized to receive lipegfilgrastim 3.0, 4.5, or 6.0 mg or pegfilgrastim 6.0 mg. Study drugs were administered as a single subcutaneous injection on day 2 of each chemotherapy cycle (doxorubicin/docetaxel on day 1 for four 3-week cycles). The primary outcome measure was duration of severe neutropenia (DSN) in cycle 1. Patients treated with lipegfilgrastim experienced shorter DSN in cycle 1 with higher doses. The mean DSN was 0.76 days in the lipegfilgrastim 6.0-mg group and 0.87 days in the pegfilgrastim 6.0-mg group, with no significant differences between treatment groups. Treatment with lipegfilgrastim 6.0 mg was consistently associated with a higher absolute neutrophil count (ANC) at nadir, shorter ANC recovery time, and a similar safety and tolerability profile compared with pegfilgrastim. This phase 2 study demonstrated that lipegfilgrastim 6.0 mg is the optimal dose for patients with breast cancer and provides neutrophil support that is at least equivalent to the standard 6.0-mg fixed dose of pegfilgrastim.

Are orange lollies effective in preventing nausea and vomiting related to dimethyl sulfoxide? A multicenter randomized trial.

PubMed

Gonella, Silvia; Berchialla, Paola; Bruno, Benedetto; Di Giulio, Paola

2014-09-01

Nausea and vomiting (NV) related to DMSO affect patients undergoing auto-SCT despite antiemetic measures. Orange flavoring may reduce gastrointestinal symptoms. A multicenter, randomized, three-arm, open-label trial in four Italian large bone marrow transplant centers was conducted to assess the effectiveness of orange aroma in preventing NV related to DMSO. Patients were randomized to orange ice lollies, non-citrus ice lollies, and routine treatment (deep breaths) during reinfusion. Data on NV were collected up to 5 days after infusion; 69/98 patients were randomized: 23 to orange, 21 to non-citrus ice lollies, and 25 to routine treatment. Although 48 h after transplantation no differences were observed in controlled nausea (Numerical Rating Scale (NRS) 0-100, ≤25) or vomiting, significantly fewer patients had no episodes of vomiting, no antiemetic rescue therapy, and no nausea (NRS <5) in the deep breath vs lollies groups (P = 0.017). The intensity of nausea over time differed significantly between ice lollies vs routine care (P = 0.001) groups, but not between the orange and non-citrus groups (P = 0.428). The vasoconstrictive action of ice may prevent NV related to DMSO in the acute phase and reduce the need for rescue antiemetic therapy. Ice lollies offer a simple, noninvasive, and economic means for relieving nausea and vomiting related to this preservative.

Effect of Periodontal Therapy With Amoxicillin-Metronidazole on Pharyngeal Carriage of Penicillin- and Erythromycin-Resistant Viridans Streptococci.

PubMed

Mombelli, Andrea; Cionca, Norbert; Almaghlouth, Adnan; Cherkaoui, Abdessalam; Schrenzel, Jacques; Giannopoulou, Catherine

2016-05-01

Previous studies have focused on antibiotic resistance of Gram-negative bacteria before and after periodontal therapy. The purpose of this analysis is to assess changes in resistance patterns of the commensal Gram-positive microbiota. The viridans group streptococci (VGS) have been suggested to serve as reservoirs of resistance genes for more pathogenic streptococci and may be implicated in some non-oral infections. In this randomized clinical trial, 80 patients with periodontitis are distributed randomly into two groups. In group A, patients received 375 mg amoxicillin and 500 mg metronidazole three times per day for 7 days during the non-surgical treatment phase (T1). In group B, the antibiotics were administered during the surgical phase (T2). Resistance of VGS to penicillin and erythromycin was determined by the epsilometer test. At baseline, VGS from 12.5% (group A) and 11.8% (group B) of patients had a minimum inhibitory concentration (MIC) >2 μg/mL to penicillin. Three months after T1, VGS from 15.6% and 16.7% of patients had an MIC >2 μg/mL, respectively. Six months after T2 VGS from 5.9% and 5.9% and 12 months after T2 VGS from 6.1% and 6.3% patients had an MIC >2 μg/mL. There was no effect of therapy with antibiotics, administered either in T1 or T2, on the carriage of penicillin-resistant VGS. Erythromycin resistance was high at baseline and remained unchanged throughout the study. MICs for penicillin and erythromycin were correlated (P <0.05). Amoxicillin plus metronidazole did not significantly affect the resistance pattern of the VGS to penicillin or erythromycin.

Meal replacement with a low-calorie diet formula in weight loss maintenance after weight loss induction with diet alone.

PubMed

Vázquez, C; Montagna, C; Alcaraz, F; Balsa, J A; Zamarrón, I; Arrieta, F; Botella-Carretero, J I

2009-10-01

Weight loss in obesity can reduce morbidity and mortality and benefits persist as long as weight loss is maintained. Weight maintenance is difficult in the long term and new strategies need to be developed to achieve this goal. We aimed to evaluate the efficacy of substituting a low-calorie diet formula for a meal in a weight loss program during the maintenance phase. Randomized paralleled clinical trial including 62 adult patients with at least a 5% weight loss with diet alone for 6 months, randomized to two groups: daily replacement of one meal with a low-calorie diet formula, or dieting alone for another 6 months (weight maintenance phase). Weight maintenance or further weight loss occurred in 83.9% of patients in the intervention group, whereas only in 58.1% in the control group (P=0.025). As a whole, patients in the intervention group lost a further 3.2+/-3.7% of initial weight compared with a 1.3+/-3.6% in the control group (P=0.030). Body fat mass diminished in both groups, with no differences between them (1.6+/-3.5 vs 1.0+/-9.3 kg, respectively, P=0.239), and the same happened with free fat mass (0.9+/-3.3 vs 0.4+/-6.7 kg, respectively, P=0.471). A multivariate logistic regression analysis (R (2)=0.114, P=0.023) retained only the intervention as a predictor of the achievement of weight maintenance with an odds ratio (95% confidence interval) of 3.756 (1.138-12.391). Substitution of a low-calorie diet formula for a meal is an effective measure for weight loss maintenance compared with dieting alone.

Early sensory re-education of the hand after peripheral nerve repair based on mirror therapy: a randomized controlled trial

PubMed Central

Paula, Mayara H.; Barbosa, Rafael I.; Marcolino, Alexandre M.; Elui, Valéria M. C.; Rosén, Birgitta; Fonseca, Marisa C. R.

2016-01-01

BACKGROUND: Mirror therapy has been used as an alternative stimulus to feed the somatosensory cortex in an attempt to preserve hand cortical representation with better functional results. OBJECTIVE: To analyze the short-term functional outcome of an early re-education program using mirror therapy compared to a late classic sensory program for hand nerve repair. METHOD: This is a randomized controlled trial. We assessed 20 patients with median and ulnar nerve and flexor tendon repair using the Rosen Score combined with the DASH questionnaire. The early phase group using mirror therapy began on the first postoperative week and lasted 5 months. The control group received classic sensory re-education when the protective sensation threshold was restored. All participants received a patient education booklet and were submitted to the modified Duran protocol for flexor tendon repair. The assessments were performed by the same investigator blinded to the allocated treatment. Mann-Whitney Test and Effect Size using Cohen's d score were used for inter-group comparisons at 3 and 6 months after intervention. RESULTS: The primary outcome (Rosen score) values for the Mirror Therapy group and classic therapy control group after 3 and 6 months were 1.68 (SD=0.5); 1.96 (SD=0.56) and 1.65 (SD=0.52); 1.51 (SD=0.62), respectively. No between-group differences were observed. CONCLUSION: Although some clinical improvement was observed, mirror therapy was not shown to be more effective than late sensory re-education in an intermediate phase of nerve repair in the hand. Replication is needed to confirm these findings. PMID:26786080