The administration to Indonesians of monosodium L-glutamate in Indonesian foods: an assessment of adverse reactions in a randomized double-blind, crossover, placebo-controlled study.

PubMed

Prawirohardjono, W; Dwiprahasto, I; Astuti, I; Hadiwandowo, S; Kristin, E; Muhammad, M; Kelly, M F

2000-04-01

Monosodium L-glutamate (MSG) has been suggested to cause postprandial symptoms after the ingestion of Chinese or oriental meals. Therefore, we examined whether such symptoms could be elicited in Indonesians ingesting levels of MSG typically found in Indonesian cuisine. Healthy volunteers (n = 52) were treated with capsules of placebo or MSG (1.5 and 3.0 g/person) as part of a standardized Indonesian breakfast. The study used a rigorous, randomized, double-blind, crossover design. The occurrence of symptoms after MSG ingestion did not differ from that after consumption of the placebo.

Native whey induces higher and faster leucinemia than other whey protein supplements and milk: A randomized controlled trial

USDA-ARS?s Scientific Manuscript database

Resistance exercise and protein intake are both strong stimuli for muscle protein synthesis. The potential for a protein to acutely increase muscle protein synthesis seems partly dependent on absorption kinetics and the amino acid composition. The aim of this double-blinded randomized cross-over stu...

Response-Order Effects in Survey Methods: A Randomized Controlled Crossover Study in the Context of Sport Injury Prevention.

PubMed

Chan, Derwin K; Ivarsson, Andreas; Stenling, Andreas; Yang, Sophie X; Chatzisarantis, Nikos L; Hagger, Martin S

2015-12-01

Consistency tendency is characterized by the propensity for participants responding to subsequent items in a survey consistent with their responses to previous items. This method effect might contaminate the results of sport psychology surveys using cross-sectional design. We present a randomized controlled crossover study examining the effect of consistency tendency on the motivational pathway (i.e., autonomy support → autonomous motivation → intention) of self-determination theory in the context of sport injury prevention. Athletes from Sweden (N = 341) responded to the survey printed in either low interitem distance (IID; consistency tendency likely) or high IID (consistency tendency suppressed) on two separate occasions, with a one-week interim period. Participants were randomly allocated into two groups, and they received the survey of different IID at each occasion. Bayesian structural equation modeling showed that low IID condition had stronger parameter estimates than high IID condition, but the differences were not statistically significant.

Crossover ensembles of random matrices and skew-orthogonal polynomials

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

Kumar, Santosh, E-mail: skumar.physics@gmail.com; Pandey, Akhilesh, E-mail: ap0700@mail.jnu.ac.in

2011-08-15

Highlights: > We study crossover ensembles of Jacobi family of random matrices. > We consider correlations for orthogonal-unitary and symplectic-unitary crossovers. > We use the method of skew-orthogonal polynomials and quaternion determinants. > We prove universality of spectral correlations in crossover ensembles. > We discuss applications to quantum conductance and communication theory problems. - Abstract: In a recent paper (S. Kumar, A. Pandey, Phys. Rev. E, 79, 2009, p. 026211) we considered Jacobi family (including Laguerre and Gaussian cases) of random matrix ensembles and reported exact solutions of crossover problems involving time-reversal symmetry breaking. In the present paper we givemore » details of the work. We start with Dyson's Brownian motion description of random matrix ensembles and obtain universal hierarchic relations among the unfolded correlation functions. For arbitrary dimensions we derive the joint probability density (jpd) of eigenvalues for all transitions leading to unitary ensembles as equilibrium ensembles. We focus on the orthogonal-unitary and symplectic-unitary crossovers and give generic expressions for jpd of eigenvalues, two-point kernels and n-level correlation functions. This involves generalization of the theory of skew-orthogonal polynomials to crossover ensembles. We also consider crossovers in the circular ensembles to show the generality of our method. In the large dimensionality limit, correlations in spectra with arbitrary initial density are shown to be universal when expressed in terms of a rescaled symmetry breaking parameter. Applications of our crossover results to communication theory and quantum conductance problems are also briefly discussed.« less

Almond consumption improved glycemic control and lipid profiles in patients with type 2 diabetes mellitus

USDA-ARS?s Scientific Manuscript database

Almond consumption is associated with ameliorations in obesity, hyperlipidemia, hypertension, and hyperglycemia. The hypothesis of this 12-wk randomized crossover clinical trial was that almond consumption would improve glycemic control and decrease risk to cardiovascular disease in 20 Chinese type ...

Omega-3/Omega-6 Fatty Acids for Attention Deficit Hyperactivity Disorder: A Randomized Placebo-Controlled Trial in Children and Adolescents

ERIC Educational Resources Information Center

Johnson, Mats; Ostlund, Sven; Fransson, Gunnar; Kadesjo, Bjorn; Gillberg, Christopher

2009-01-01

Objective: The aim of the study was to assess omega 3/6 fatty acids (eye q) in attention deficit hyperactivity disorder (ADHD). Method: The study included a randomized, 3-month, omega 3/6 placebo-controlled, one-way crossover trial with 75 children and adolescents (8-18 years), followed by 3 months with omega 3/6 for all. Investigator-rated ADHD…

Orange pomace improves postprandial glycemic responses: an acute, randomized, placebo-controlled, double-blind, crossover trial in overweight men

USDA-ARS?s Scientific Manuscript database

Orange pomace (OP), a fiber-rich byproduct of juice production, has the potential for being formulated into a variety of food products. We hypothesized that OP would diminish postprandial glycemic responses to a high carbohydrate/fat breakfast and lunch. We conducted an acute, randomized, placebo-co...

Melatonin improves sleep in children with epilepsy: randomized, double-blind cross-over study

PubMed Central

Jain, Sejal V; Horn, Paul S; Simakajornboon, Narong; Beebe, Dean W; Holland, Katherine; Byars, Anna W; Glauser, Tracy A

2015-01-01

Objective Insomnia, especially maintenance insomnia is widely prevalent in epilepsy. Although melatonin is commonly used, limited data address its efficacy. We performed a randomized, double-blind, placebo-controlled, cross-over study to identify the effects of melatonin on sleep and seizure control in children with epilepsy. Methods Eleven pre-pubertal, developmentally normal children aged 6–11 years with epilepsy were randomized by software algorithm to receive placebo or 9 mg sustained release melatonin for 4 weeks, followed by a 1-week washout and 4-week crossover condition. The pharmacy performed blinding; patients, parents and study staff other than a statistician were blinded. Primary outcomes were sleep onset latency and wakefulness after sleep onset (WASO) measured on polysomnography. Secondary outcomes included seizure frequency, epileptiform spike density per hour of sleep on EEG and reaction time measures on psychomotor vigilance task. Statistical tests appropriate for cross-over designs were used for analysis. Results Data were analyzed from ten subjects who completed the study. Melatonin decreased sleep latency (Mean difference (MD): 11.4 min, p= 0.02) and WASO (MD 22 min, p=0.04) as compared to placebo. No worsening of spike density or seizure frequency was seen. Additionally, Slow-wave sleep duration and REM latency were increased with melatonin and REM sleep duration was decreased. These changes were statistically significant. Worsening of headache was noted in one subject with migraine on melatonin. Conclusion Sustained-release melatonin resulted in statistically significant decreases in sleep latency and WASO. No clear effects on seizures were observed but the study was too small to allow any conclusions to be drawn in this regard. PMID:25862116

Lactobacillus salivarius WB21--containing tablets for the treatment of oral malodor: a double-blind, randomized, placebo-controlled crossover trial.

PubMed

Suzuki, Nao; Yoneda, Masahiro; Tanabe, Kazunari; Fujimoto, Akie; Iha, Kosaku; Seno, Kei; Yamada, Kazuhiko; Iwamoto, Tomoyuki; Masuo, Yosuke; Hirofuji, Takao

2014-04-01

This study evaluated the effect of probiotic intervention using lactobacilli on oral malodor. We conducted a 14-day, double-blind, placebo-controlled, randomized crossover trial of tablets containing Lactobacillus salivarius WB21 (2.0 × 10(9) colony-forming units per day) or placebo taken orally by patients with oral malodor. Organoleptic test scores significantly decreased in both the probiotic and placebo periods compared with the respective baseline scores (P < .001 and P = .002), and no difference was detected between periods. In contrast, the concentration of volatile sulfur compounds (VSCs) (P = .019) and the average probing pocket depth (P = .001) decreased significantly in the probiotic period compared with the placebo period. Bacterial quantitative analysis found significantly lower levels of ubiquitous bacteria (P = .003) and Fusobacterium nucleatum (P = .020) in the probiotic period. These results indicated that daily oral consumption of tablets containing probiotic lactobacilli could help to control oral malodor and malodor-related factors. Copyright © 2014 Elsevier Inc. All rights reserved.

Cannabis for dyskinesia in Parkinson disease: a randomized double-blind crossover study.

PubMed

Carroll, C B; Bain, P G; Teare, L; Liu, X; Joint, C; Wroath, C; Parkin, S G; Fox, P; Wright, D; Hobart, J; Zajicek, J P

2004-10-12

The long-term treatment of Parkinson disease (PD) may be complicated by the development of levodopa-induced dyskinesia. Clinical and animal model data support the view that modulation of cannabinoid function may exert an antidyskinetic effect. The authors conducted a randomized, double-blind, placebo-controlled crossover trial to examine the hypothesis that cannabis may have a beneficial effect on dyskinesia in PD. A 4-week dose escalation study was performed to assess the safety and tolerability of cannabis in six PD patients with levodopa-induced dyskinesia. Then a randomized placebo-controlled crossover study (RCT) was performed, in which 19 PD patients were randomized to receive oral cannabis extract followed by placebo or vice versa. Each treatment phase lasted for 4 weeks with an intervening 2-week washout phase. The primary outcome measure was a change in Unified Parkinson's Disease Rating Scale (UPDRS) (items 32 to 34) dyskinesia score. Secondary outcome measures included the Rush scale, Bain scale, tablet arm drawing task, and total UPDRS score following a levodopa challenge, as well as patient-completed measures of a dyskinesia activities of daily living (ADL) scale, the PDQ-39, on-off diaries, and a range of category rating scales. Seventeen patients completed the RCT. Cannabis was well tolerated, and had no pro- or antiparkinsonian action. There was no evidence for a treatment effect on levodopa-induced dyskinesia as assessed by the UPDRS, or any of the secondary outcome measures. Orally administered cannabis extract resulted in no objective or subjective improvement in dyskinesias or parkinsonism.

Promising effects of oxytocin on social and food-related behaviour in young children with Prader-Willi syndrome: a randomized, double-blind, controlled crossover trial.

PubMed

Kuppens, R J; Donze, S H; Hokken-Koelega, A C S

2016-12-01

Prader-Willi syndrome (PWS) is known for hyperphagia with impaired satiety and a specific behavioural phenotype with stubbornness, temper tantrums, manipulative and controlling behaviour and obsessive-compulsive features. PWS is associated with hypothalamic and oxytocinergic dysfunction. In humans without PWS, intranasal oxytocin administration had positive effects on social and eating behaviour, and weight balance. To evaluate the effects of intranasal oxytocin compared to placebo administration on social behaviour and hyperphagia in children with PWS. Randomized, double-blind, placebo-controlled, crossover study in a PWS Reference Center in the Netherlands. Crossover intervention with twice daily intranasal oxytocin (dose range 24-48 IU/day) and placebo administration, both during 4 weeks, in 25 children with PWS (aged 6 to 14 years). In the total group, no significant effects of oxytocin on social behaviour or hyperphagia were found, but in the 17 children younger than 11 years, parents reported significantly less anger (P = 0·001), sadness (P = 0·005), conflicts (P = 0·010) and food-related behaviour (P = 0·011), and improvement of social behaviour (P = 0·018) during oxytocin treatment compared with placebo. In the eight children older than 11 years, the items happiness (P = 0·039), anger (P = 0·042) and sadness (P = 0·042) were negatively influenced by oxytocin treatment compared to placebo. There were no side effects or adverse events. This randomized, double-blind, placebo-controlled study suggests that intranasal oxytocin administration has beneficial effects on social behaviour and food-related behaviour in children with PWS younger than 11 years of age, but not in those older than 11 years of age. © 2016 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.

Low-dose lisinopril in normotensive men with idiopathic oligospermia and infertility: a 5-year randomized, controlled, crossover pilot study.

PubMed

Mbah, A U; Ndukwu, G O; Ghasi, S I; Shu, E N; Ozoemena, F N; Mbah, J O; Onodugo, O D; Ejim, E C; Eze, M I; Nkwo, P O; Okonkwo, P O

2012-04-01

The outcomes of drug treatment for male infertility remain conjectural, with controversial study results. Our pilot study employed a randomized, placebo-controlled, crossover methodology with intention-to-treat analysis. Thirty-three men with idiopathic oligospermia were randomized to start either daily oral lisinopril 2.5 mg (n = 17) or daily oral placebo (n = 16). Lisinopril was found to cause a normalization of seminal parameters in 53.6% of the participants. Although the mean ejaculate volume was unchanged (P ≥ 0.093), the total sperm cell count and the percentage of motile sperm cells increased (P ≤ 0.03 and P < 0.001, respectively), whereas the percentage of sperm cells with abnormal morphology decreased (P ≤ 0.04). The pregnancy rate was 48.5%, and there was no serious adverse drug event. It is concluded, albeit cautiously, that prolonged treatment with 2.5 mg/day of oral lisinopril may be well tolerated in normotensive men with idiopathic oligospermia, may improve sperm quantity and quality, and may enhance fertility in approximately half of those treated.

Prevention of EP Migratory Contamination in a Cluster Randomized Trial to Increase tPA Use in Stroke (The INSTINCT Trial)

PubMed Central

Weston, Victoria C.; Meurer, William J.; Frederiksen, Shirley M.; Fox, Allison K.; Scott, Phillip A.

2016-01-01

Objectives Cluster randomized trials (CRTs) are increasingly utilized to evaluate quality improvement interventions aimed at healthcare providers. In trials testing emergency department interventions, migration of emergency physicians (EPs) between hospitals is an important concern, as contamination may affect both internal and external validity. We hypothesized that geographically isolating emergency departments would prevent migratory contamination in a CRT designed to increase ED delivery of tPA in stroke (The INSTINCT Trial). Methods INSTINCT was a prospective, cluster randomized, controlled trial. 24 Michigan community hospitals were randomly selected in matched pairs for study. Contamination was defined at the cluster level, with substantial contamination defined a priori as >10% of EPs affected. Non-adherence, total crossover (contamination + non-adherence), migration distance and characteristics were determined. Results 307 emergency physicians were identified at all sites. Overall, 7 (2.3%) changed study sites. 1 moved between control sites, leaving 6 (2.0%) total crossovers. Of these, 2 (0.7%) moved from intervention to control (contamination) and 4 (1.3%) moved from control to intervention (non-adherence). Contamination was observed in 2 of 12 control sites, with 17% and 9% contamination of the total site EP workforce at follow-up, respectively. Average migration distance was 42 miles for all EPs moving in the study and 35 miles for EPs moving from intervention to control sites. Conclusion The mobile nature of emergency physicians should be considered in the design of quality improvement CRTs. Increased reporting of contamination in CRTs is encouraged to clarify thresholds and facilitate CRT design. PMID:25440230

Dietary Protein and Calcium Interact to Influence Calcium Retention: A Controlled Feeding Study

USDA-ARS?s Scientific Manuscript database

Objective: To test the effect of dietary protein on Ca (Ca) retention at low and high Ca intakes. Methods: In a randomized, controlled feeding study with a 2x2 factorial crossover design, healthy post-menopausal women (n=27), consumed either ~675 or ~1510 mg Ca/d, with both low and high protein (pro...

Hyperbaric oxygen therapy can improve post concussion syndrome years after mild traumatic brain injury - randomized prospective trial.

PubMed

Boussi-Gross, Rahav; Golan, Haim; Fishlev, Gregori; Bechor, Yair; Volkov, Olga; Bergan, Jacob; Friedman, Mony; Hoofien, Dan; Shlamkovitch, Nathan; Ben-Jacob, Eshel; Efrati, Shai

2013-01-01

Traumatic brain injury (TBI) is the leading cause of death and disability in the US. Approximately 70-90% of the TBI cases are classified as mild, and up to 25% of them will not recover and suffer chronic neurocognitive impairments. The main pathology in these cases involves diffuse brain injuries, which are hard to detect by anatomical imaging yet noticeable in metabolic imaging. The current study tested the effectiveness of Hyperbaric Oxygen Therapy (HBOT) in improving brain function and quality of life in mTBI patients suffering chronic neurocognitive impairments. The trial population included 56 mTBI patients 1-5 years after injury with prolonged post-concussion syndrome (PCS). The HBOT effect was evaluated by means of prospective, randomized, crossover controlled trial: the patients were randomly assigned to treated or crossover groups. Patients in the treated group were evaluated at baseline and following 40 HBOT sessions; patients in the crossover group were evaluated three times: at baseline, following a 2-month control period of no treatment, and following subsequent 2-months of 40 HBOT sessions. The HBOT protocol included 40 treatment sessions (5 days/week), 60 minutes each, with 100% oxygen at 1.5 ATA. "Mindstreams" was used for cognitive evaluations, quality of life (QOL) was evaluated by the EQ-5D, and changes in brain activity were assessed by SPECT imaging. Significant improvements were demonstrated in cognitive function and QOL in both groups following HBOT but no significant improvement was observed following the control period. SPECT imaging revealed elevated brain activity in good agreement with the cognitive improvements. HBOT can induce neuroplasticity leading to repair of chronically impaired brain functions and improved quality of life in mTBI patients with prolonged PCS at late chronic stage. ClinicalTrials.gov NCT00715052.

Modafinil Improves Real Driving Performance in Patients with Hypersomnia: A Randomized Double-Blind Placebo-Controlled Crossover Clinical Trial

PubMed Central

Philip, Pierre; Chaufton, Cyril; Taillard, Jacques; Capelli, Aurore; Coste, Olivier; Léger, Damien; Moore, Nicholas; Sagaspe, Patricia

2014-01-01

Study Objective: Patients with excessive daytime sleepiness (EDS) are at high risk for driving accidents, and physicians are concerned by the effect of alerting drugs on driving skills of sleepy patients. No study has up to now investigated the effect of modafinil (a reference drug to treat EDS in patients with hypersomnia) on on-road driving performance of patients suffering from central hypersomnia. The objective is to evaluate in patients with central hypersomnia the effect of a wake-promoting drug on real driving performance and to assess the relationship between objective sleepiness and driving performance. Design and Participants: Randomized, crossover, double-blind placebo-controlled trial conducted among 13 patients with narcolepsy and 14 patients with idiopathic hypersomnia. Patients were randomly assigned to receive modafinil (400 mg) or placebo for 5 days prior to the driving test. Each condition was separated by at least 3 weeks of washout. Measurements: Mean number of Inappropriate Line Crossings, Standard Deviation of Lateral Position of the vehicle and mean sleep latency in the Maintenance of Wakefulness Test were assessed. Results: Modafinil reduced the mean number of Inappropriate Line Crossings and Standard Deviation of Lateral Position of the vehicle compared to placebo (F(1,25) = 4.88, P < 0.05 and F(1,25) = 3.87, P = 0.06 tendency). Mean sleep latency at the Maintenance of Wakefulness Test significantly correlated with the mean number of Inappropriate Line Crossings (r = -0.41, P < 0.001). Conclusions: Modafinil improves driving performance in patients with narcolepsy and idiopathic hypersomnia. The Maintenance of Wakefulness Test is a suitable clinical tool to assess fitness to drive in this population. Citation: Philip P; Chaufton C; Taillard J; Capelli A; Coste O; Léger D; Moore N; Sagaspe P. Modafinil improves real driving performance in patients with hypersomnia: a randomized double-blind placebo-controlled crossover clinical trial. SLEEP 2014;37(3):483-487. PMID:24587570

An improved genetic algorithm and its application in the TSP problem

NASA Astrophysics Data System (ADS)

Li, Zheng; Qin, Jinlei

2011-12-01

Concept and research actuality of genetic algorithm are introduced in detail in the paper. Under this condition, the simple genetic algorithm and an improved algorithm are described and applied in an example of TSP problem, where the advantage of genetic algorithm is adequately shown in solving the NP-hard problem. In addition, based on partial matching crossover operator, the crossover operator method is improved into extended crossover operator in order to advance the efficiency when solving the TSP. In the extended crossover method, crossover operator can be performed between random positions of two random individuals, which will not be restricted by the position of chromosome. Finally, the nine-city TSP is solved using the improved genetic algorithm with extended crossover method, the efficiency of whose solution process is much higher, besides, the solving speed of the optimal solution is much faster.

Polydextrose: its impact on short-term food intake and subjective feelings of satiety in males-a randomized controlled cross-over study.

PubMed

Ranawana, Viren; Muller, Adelaide; Henry, C Jeya K

2013-04-01

Polydextrose is a low-calorie highly branched-chain glucose polymer that is poorly digested in the upper gastrointestinal tract and therefore demonstrates fibre-like properties. Fibre has been shown to increase satiety and possibly reduce food intake. Therefore, the objective of the current study was to examine the effects of polydextrose on short-term satiety and energy intake. In a repeated-measures randomized blind cross-over design, 26 healthy males consumed a 400-g fruit smoothie containing 12 g (3 %) of polydextrose, and a buffet lunch 60 min after the smoothie. Motivational ratings for satiety and palatability and lunch energy intake were measured. The effects of the polydextrose-containing smoothie were compared against a polydextrose-free control smoothie. Polydextrose did not significantly alter the taste and palatability of the fruit smoothie. Consuming the polydextrose-containing smoothie resulted in a significantly lower energy intake at lunch (102 kcal less) compared to the control. Polydextrose may be a good fortificant for reducing short-term food intake.

An Herbal Drug, Gongjin-dan, Ameliorates Acute Fatigue Caused by Short-Term Sleep-Deprivation: A Randomized, Double-Blinded, Placebo-Controlled, Crossover Clinical Trial.

PubMed

Son, Mi Ju; Im, Hwi-Jin; Ku, Boncho; Lee, Jun-Hwan; Jung, So Young; Kim, Young-Eun; Lee, Sung Bae; Kim, Jun Young; Son, Chang-Gue

2018-01-01

Introduction: Gongjin-dan (GJD) is an herbal drug commonly used in Korea and China to combat fatigue, but there are only few clinical studies on its effectiveness and experimental studies on its mechanism of action, and no randomized controlled trial of GJD on the efficacy and mechanism of action has been reported. Here, we performed an exploratory study to evaluate both questions regarding GJD use in humans. Methods: A randomized, double-blinded, placebo-controlled, crossover clinical trial was conducted in the Republic of Korea. Healthy male participants were recruited and randomly allocated to groups receiving GJD-placebo or placebo-GJD in sequence. Fatigue was artificially induced by sleep deprivation for 2 nights. The primary outcome was a change in serum cortisol level; levels of biomarkers for stress hormones as well as oxidative stress and immunologic factors were also assessed, and questionnaires on fatigue and sleep quality were conducted. Results: Twelve and 11 participants were assigned to the GJD-placebo and placebo-GJD groups, respectively. Of all 23 participants, depending on crossover design, we analyzed a total of 20 participants for GJD, and 21 for placebo. An increase in serum cortisol appeared to be attenuated by GJD administration ( p = 0.25), but the effect was not statistically significant; a similar pattern was observed in salivary cortisol levels ( p = 0.14). Overall, GJD showed a tendency to reduce fatigue according to the Brief Fatigue Inventory (BFI, p = 0.07) and the Fatigue Severity Scale (FSS, p = 0.13) questionnaires. BFI and FSS scores in the first stage (before the crossover), however, were significantly improved (BFI, p = 0.02; FSS, p = 0.05) after GJD treatment (relative to placebo). GJD also seemed to improve sleep quality as assessed by the Leeds Sleep Evaluation Questionnaire ( p = 0.06), with a significant improvement specifically in the condition "Getting To Sleep" ( p = 0.02). Five participants experienced minor adverse events, but no adverse events were specific to the GJD administration period. Conclusions: This trial produced the first clinical evidence that GJD might have anti-fatigue properties, especially under sleep deprivation; however, the investigation of cortisol-mediated mechanisms requires further larger-scale studies in the future. World Health Organization International Clinical Trials Registry Platform KCT0001681 (http://apps.who.int/trialsearch/Trial2.aspx?TrialID=KCT0001681).

Consumption of high-fat meal containing cheese compared with vegan alternative lowers postprandial C-reactive protein in overweight and obese individuals with metabolic abnormalities: a randomized controlled cross-over study

USDA-ARS?s Scientific Manuscript database

Dietary recommendations suggest decreased consumption of SFA to minimize CVD risk; however, not all foods rich in SFA are equivalent. To evaluate the effects of SFA in a dairy food matrix, as Cheddar cheese, v. SFA from a vegan-alternative test meal on postprandial inflammatory markers, a randomized...

Intervention for phantom limb pain: A randomized single crossover study of mirror therapy.

PubMed

Ramadugu, Shashikumar; Nagabushnam, Satish C; Katuwal, Nagendra; Chatterjee, Kaushik

2017-01-01

Mirror therapy suggested to help relieve phantom limb pain (PLP) by resolving the visual- proprioceptive dissociation in the brain, but studies so far either had shorter follow-up or smaller sample size. In this randomized single crossover trial, 64 amputees with PLP in the age group of 15-75 years of age were distributed into test and control groups by simple randomization method. Of these 28 in control and 32 in test groups, respectively, completed the 4 weeks of mirror therapy and 12 weeks of follow-up assessments. A standardized set of exercises for 15 min/day for 4 and 8 weeks in test and control groups (in the first 4 weeks, the mirror was covered), respectively, was administered under supervision of one of the authors. All were assessed using the visual analog scale and Short-Form McGill Pain Questionnaire on day 0 and at 4, 8, and 12 weeks after therapy. In control group for the initial 4 weeks, the mirror was covered. The assessing author was blinded to the group to which the participants belonged. Significant reduction in PLP was noted in the test group at 4 weeks compared to the control group ( P < 0.0001). Significant reduction was seen in control group also after the switchover and sustained for 12 weeks in both. No harm was reported. Mirror therapy is effective in relieving the intensity, duration, frequency, and overall PLP, and improvement is maintained up to 12 weeks' posttherapy.

Test equality in binary data for a 4 × 4 crossover trial under a Latin-square design.

PubMed

Lui, Kung-Jong; Chang, Kuang-Chao

2016-10-15

When there are four or more treatments under comparison, the use of a crossover design with a complete set of treatment-receipt sequences in binary data is of limited use because of too many treatment-receipt sequences. Thus, we may consider use of a 4 × 4 Latin square to reduce the number of treatment-receipt sequences when comparing three experimental treatments with a control treatment. Under a distribution-free random effects logistic regression model, we develop simple procedures for testing non-equality between any of the three experimental treatments and the control treatment in a crossover trial with dichotomous responses. We further derive interval estimators in closed forms for the relative effect between treatments. To evaluate the performance of these test procedures and interval estimators, we employ Monte Carlo simulation. We use the data taken from a crossover trial using a 4 × 4 Latin-square design for studying four-treatments to illustrate the use of test procedures and interval estimators developed here. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Antioxidants intake and dry eye syndrome: a crossover, placebo-controlled, randomized trial.

PubMed

Drouault-Holowacz, Sophie; Bieuvelet, Séverine; Burckel, André; Rigal, Danièle; Dubray, Claude; Lichon, Jean-Louis; Bringer, Paul; Pilon, Francois; Chiambaretta, Frédéric

2009-01-01

To assess whether an orally administered antioxidant dietary supplement could improve the objective clinical signs and alleviate the subjective symptoms of dry eye syndrome. Twenty-four subjects diagnosed with dry eye syndrome were randomized in a crossover, double-blind, controlled, randomized study to receive a placebo or an antioxidants combination (Oxybiane) for 12 weeks. In all subjects, break-up time (BUT) test, Schirmer test, ocular symptoms (sore eyes, burning, itching, sensation of foreign object in the eye, photophobia, sticky eyes, and redness), visual comfort, and general well-being were evaluated weekly. After 12 weeks of supplementation with Oxybiane, both the BUT scores (27.3%+/-8.4% with Oxybiane versus 3.61%+/-4.3% with the placebo, p=0.017) and the Schirmer scores (26.9%+/-14.2% with Oxybiane versus -4.7%+/-3.4% with the placebo, p=0.037) were significantly increased. A significantly improvement was also observed considering subjective clinical symptoms such as burning (p=0.031), itching (p=0.027), sensation of foreign body in eye (p=0.030), and redness (p=0.043). CONCLUSIONS. Supplementation with oral antioxidants can improve both tear stability and quantity but also subjective clinical signs.

A Feasibility Randomized Controlled Crossover Trial of Home-Based Warm Footbath to Improve Sleep in the Chronic Phase of Traumatic Brain Injury.

PubMed

Chiu, Hsiao-Yean; Lin, En-Yuan; Chiu, Hsiao-Ting; Chen, Pin-Yuan

2017-12-01

Sleep disturbance is a common complaint after traumatic brain injury (TBI). The aim of this study was to examine the effects of a home-based warm footbath intervention on sleep in patients with TBI. This was a randomized controlled crossover study, and 23 adults with TBI were recruited and randomized to receive first a 30-minute, 41°C warm footbath and then a usual care, or vice versa, with each lasting 3 days and separated by a 3-day washout. Sleep efficiency, sleep onset latency (SOL), total sleep time, and wake after sleep onset (WASO) were assessed by actigraphy. We found that home-based warm footbath significantly had a reduced SOL (difference, -5.11 minutes) and a suppressed WASO (difference, -2.57 minutes) compared with those of usual care, but not in sleep efficiency and total sleep time. No adverse effect was reported. This study suggested that home-based warm footbath is practical and effective in relieving post-TBI sleep disturbances, particular in SOL and WASO. Nurses can use home-based warm footbath as an effective intervention for management of sleep disturbances after TBI.

Self-Administered Computer Therapy for Apraxia of Speech: Two-Period Randomized Control Trial With Crossover.

PubMed

Varley, Rosemary; Cowell, Patricia E; Dyson, Lucy; Inglis, Lesley; Roper, Abigail; Whiteside, Sandra P

2016-03-01

There is currently little evidence on effective interventions for poststroke apraxia of speech. We report outcomes of a trial of self-administered computer therapy for apraxia of speech. Effects of speech intervention on naming and repetition of treated and untreated words were compared with those of a visuospatial sham program. The study used a parallel-group, 2-period, crossover design, with participants receiving 2 interventions. Fifty participants with chronic and stable apraxia of speech were randomly allocated to 1 of 2 order conditions: speech-first condition versus sham-first condition. Period 1 design was equivalent to a randomized controlled trial. We report results for this period and profile the effect of the period 2 crossover. Period 1 results revealed significant improvement in naming and repetition only in the speech-first group. The sham-first group displayed improvement in speech production after speech intervention in period 2. Significant improvement of treated words was found in both naming and repetition, with little generalization to structurally similar and dissimilar untreated words. Speech gains were largely maintained after withdrawal of intervention. There was a significant relationship between treatment dose and response. However, average self-administered dose was modest for both groups. Future software design would benefit from incorporation of social and gaming components to boost motivation. Single-word production can be improved in chronic apraxia of speech with behavioral intervention. Self-administered computerized therapy is a promising method for delivering high-intensity speech/language rehabilitation. URL: http://orcid.org/0000-0002-1278-0601. Unique identifier: ISRCTN88245643. © 2016 American Heart Association, Inc.

Increased calcium absorption from synthetic stable amorphous calcium carbonate: Double-blind randomized crossover clinical trial in post-menopausal women

USDA-ARS?s Scientific Manuscript database

Calcium supplementation is a widely recognized strategy for achieving adequate calcium intake. We designed this blinded, randomized, crossover interventional trial to compare the bioavailability of a new stable synthetic amorphous calcium carbonate (ACC) with that of crystalline calcium carbonate (C...

Prevention of emergency physician migratory contamination in a cluster randomized trial to increase tissue plasminogen activator use in stroke (the INSTINCT trial).

PubMed

Weston, Victoria C; Meurer, William J; Frederiksen, Shirley M; Fox, Allison K; Scott, Phillip A

2014-12-01

Cluster randomized trials (CRTs) are increasingly used to evaluate quality improvement interventions aimed at health care providers. In trials testing emergency department (ED) interventions, migration of emergency physicians (EPs) between hospitals is an important concern, as contamination may affect both internal and external validity. We hypothesized that geographically isolating EDs would prevent migratory contamination in a CRT designed to increase ED delivery of tissue plasminogen activator (tPA) in stroke (the INSTINCT trial). INSTINCT was a prospective, cluster randomized, controlled trial. Twenty-four Michigan community hospitals were randomly selected in matched pairs for study. Contamination was defined at the cluster level, with substantial contamination defined a priori as greater than 10% of EPs affected. Nonadherence, total crossover (contamination+nonadherence), migration distance, and characteristics were determined. Three hundred seven EPs were identified at all sites. Overall, 7 (2.3%) changed study sites. One moved between control sites, leaving 6 (2.0%) total crossovers. Of these, 2 (0.7%) moved from intervention to control (contamination); and 4 (1.3%) moved from control to intervention (nonadherence). Contamination was observed in 2 of 12 control sites, with 17% and 9% contamination of the total site EP workforce at follow-up, respectively. Average migration distance was 42 miles for all EPs moving in the study and 35 miles for EPs moving from intervention to control sites. The mobile nature of EPs should be considered in the design of quality improvement CRTs. Increased reporting of contamination in CRTs is encouraged to clarify thresholds and facilitate CRT design. Copyright © 2014 Elsevier Inc. All rights reserved.

Differential effects of estrogen and progestin on apolipoprotein B100 and B48 kinetics in postmenopausal women

USDA-ARS?s Scientific Manuscript database

The distinct effects of the estrogen and progestin components of hormonal therapy on the metabolism of apolipoprotein (apo) B-containing lipoproteins have not been studied. We enrolled eight healthy postmenopausal women in a placebo-controlled, randomized, double-blind, crossover study. Each subject...

Digestive and physiological effects of a wheat bran extract, arabino-xylan-oligosaccharide, in breakfast cereal

USDA-ARS?s Scientific Manuscript database

We assessed whether a wheat bran extract containing arabino-xylan-oligosaccharide (AXOS) elicited a prebiotic effect and influenced other physiologic parameters when consumed in ready-to-eat cereal at two dose levels. This double-blind, randomized, controlled, crossover trial evaluated the effects o...

Right ventricular function during one-lung ventilation: effects of pressure-controlled and volume-controlled ventilation.

PubMed

Al Shehri, Abdullah M; El-Tahan, Mohamed R; Al Metwally, Roshdi; Qutub, Hatem; El Ghoneimy, Yasser F; Regal, Mohamed A; Zien, Haytham

2014-08-01

To test the effects of pressure-controlled (PCV) and volume-controlled (VCV) ventilation during one-lung ventilation (OLV) for thoracic surgery on right ventricular (RV) function. A prospective, randomized, double-blind, controlled, crossover study. A single university hospital. Fourteen pairs of consecutive patients scheduled for elective thoracotomy. Patients were assigned randomly to ventilate the dependent lung with PCV or VCV mode, each in a randomized crossover order using tidal volume of 6 mL/kg, I: E ratio 1: 2.5, positive end-expiratory pressure (PEEP) of 5 cm H2O and respiratory rate adjusted to maintain normocapnia. Intraoperative changes in RV function (systolic and early diastolic tricuspid annular velocity (TAV), end-systolic volume (ESV), end-diastolic volume (EDV) and fractional area changes (FAC)), airway pressures, compliance and oxygenation index were recorded. The use of PCV during OLV resulted in faster systolic (10.1±2.39 vs. 5.8±1.67 cm/s, respectively), diastolic TAV (9.2±1.99 vs. 4.6±1.42 cm/s, respectively) (p<0.001) and compliance and lower ESV, EDV and airway pressures (p<0.05) than during the use of VCV. Oxygenation indices were similar during the use of VCV and PCV. The use of PCV offers more improved RV function than the use of VCV during OLV for open thoracotomy. These results apply specifically to younger patients with good ventricular and pulmonary functions. © 2014 Elsevier Inc. All rights reserved.

The effect of Neuragen PN® on Neuropathic pain: A randomized, double blind, placebo controlled clinical trial

PubMed Central

2010-01-01

Background A double blind, randomized, placebo controlled study to evaluate the safety and efficacy of the naturally derived topical oil, "Neuragen PN®" for the treatment of neuropathic pain. Methods Sixty participants with plantar cutaneous (foot sole) pain due to all cause peripheral neuropathy were recruited from the community. Each subject was randomly assigned to receive one of two treatments (Neuragen PN® or placebo) per week in a crossover design. The primary outcome measure was acute spontaneous pain level as reported on a visual analog scale. Results There was an overall pain reduction for both treatments from pre to post application. As compared to the placebo, Neuragen PN® led to significantly (p < .05) greater pain reduction. Fifty six of sixty subjects (93.3%) receiving Neuragen PN® reported pain reduction within 30 minutes. This reduction within 30 minutes occurred in only twenty one of sixty (35.0%) subjects receiving the placebo. In a break out analysis of the diabetic only subgroup, 94% of subjects in the Neuragen PN® group achieved pain reduction within 30 minutes vs 11.0% of the placebo group. No adverse events were observed. Conclusions This randomized, placebo controlled, clinical trial with crossover design revealed that the naturally derived oil, Neuragen PN®, provided significant relief from neuropathic pain in an all cause neuropathy group. Participants with diabetes within this group experienced similar pain relief. Trial registration ISRCTN registered: ISRCTN13226601 PMID:20487567

Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial.

PubMed

Ross, Stephen; Bossis, Anthony; Guss, Jeffrey; Agin-Liebes, Gabrielle; Malone, Tara; Cohen, Barry; Mennenga, Sarah E; Belser, Alexander; Kalliontzi, Krystallia; Babb, James; Su, Zhe; Corby, Patricia; Schmidt, Brian L

2016-12-01

Clinically significant anxiety and depression are common in patients with cancer, and are associated with poor psychiatric and medical outcomes. Historical and recent research suggests a role for psilocybin to treat cancer-related anxiety and depression. In this double-blind, placebo-controlled, crossover trial, 29 patients with cancer-related anxiety and depression were randomly assigned and received treatment with single-dose psilocybin (0.3 mg/kg) or niacin, both in conjunction with psychotherapy. The primary outcomes were anxiety and depression assessed between groups prior to the crossover at 7 weeks. Prior to the crossover, psilocybin produced immediate, substantial, and sustained improvements in anxiety and depression and led to decreases in cancer-related demoralization and hopelessness, improved spiritual wellbeing, and increased quality of life. At the 6.5-month follow-up, psilocybin was associated with enduring anxiolytic and anti-depressant effects (approximately 60-80% of participants continued with clinically significant reductions in depression or anxiety), sustained benefits in existential distress and quality of life, as well as improved attitudes towards death. The psilocybin-induced mystical experience mediated the therapeutic effect of psilocybin on anxiety and depression. In conjunction with psychotherapy, single moderate-dose psilocybin produced rapid, robust and enduring anxiolytic and anti-depressant effects in patients with cancer-related psychological distress. ClinicalTrials.gov Identifier: NCT00957359. © The Author(s) 2016.

Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial

PubMed Central

Ross, Stephen; Bossis, Anthony; Guss, Jeffrey; Agin-Liebes, Gabrielle; Malone, Tara; Cohen, Barry; Mennenga, Sarah E; Belser, Alexander; Kalliontzi, Krystallia; Babb, James; Su, Zhe; Corby, Patricia; Schmidt, Brian L

2016-01-01

Background: Clinically significant anxiety and depression are common in patients with cancer, and are associated with poor psychiatric and medical outcomes. Historical and recent research suggests a role for psilocybin to treat cancer-related anxiety and depression. Methods: In this double-blind, placebo-controlled, crossover trial, 29 patients with cancer-related anxiety and depression were randomly assigned and received treatment with single-dose psilocybin (0.3 mg/kg) or niacin, both in conjunction with psychotherapy. The primary outcomes were anxiety and depression assessed between groups prior to the crossover at 7 weeks. Results: Prior to the crossover, psilocybin produced immediate, substantial, and sustained improvements in anxiety and depression and led to decreases in cancer-related demoralization and hopelessness, improved spiritual wellbeing, and increased quality of life. At the 6.5-month follow-up, psilocybin was associated with enduring anxiolytic and anti-depressant effects (approximately 60–80% of participants continued with clinically significant reductions in depression or anxiety), sustained benefits in existential distress and quality of life, as well as improved attitudes towards death. The psilocybin-induced mystical experience mediated the therapeutic effect of psilocybin on anxiety and depression. Conclusions: In conjunction with psychotherapy, single moderate-dose psilocybin produced rapid, robust and enduring anxiolytic and anti-depressant effects in patients with cancer-related psychological distress. Trial Registration: ClinicalTrials.gov Identifier: NCT00957359 PMID:27909164

Tic Reduction with Risperidone Versus Pimozide in a Randomized, Double-Blind, Crossover Trial

ERIC Educational Resources Information Center

Gilbert, Donald L.; Batterson, J. Robert; Sethuraman, Gopalan; Sallee, Floyd R.

2004-01-01

Objective: To compare the tic suppression, electrocardiogram (ECG) changes, weight gain, and side effect profiles of pimozide versus risperidone in children and adolescents with tic disorders. Method: This was a randomized, double-blind, crossover (evaluable patient analysis) study. Nineteen children aged 7 to 17 years with Tourette's or chronic…

Low to moderate alcohol consumption on serum vitamin D and other indicators of bone health in postmenopausal women in a controlled feeding study

USDA-ARS?s Scientific Manuscript database

Heavy alcohol drinking adversely affects vitamin D status and bone health. However, data from randomized, placebo-controlled trials (RCTs) on the effects of low to moderate alcohol consumption on vitamin D status and bone health in humans is unavailable. The objective of this cross-over RCT was to e...

Effects of supervised exercise on progression-free survival in lymphoma patients: an exploratory follow-up of the HELP Trial.

PubMed

Courneya, Kerry S; Friedenreich, Christine M; Franco-Villalobos, Conrado; Crawford, Jennifer J; Chua, Neil; Basi, Sanraj; Norris, Mary K; Reiman, Tony

2015-02-01

Few randomized controlled trials in exercise oncology have examined survival outcomes. Here, we report an exploratory follow-up of progression-free survival (PFS) from the Healthy Exercise for Lymphoma Patients (HELP) Trial. The HELP Trial randomized 122 lymphoma patients between 2005 and 2008 to either control (n = 62) or 12 weeks of supervised aerobic exercise (n = 60). PFS events were abstracted from medical records in 2013. In addition to the randomized comparison, we explored the effects of exercise adherence (<80 % vs. ≥80 %) and control group crossover (no vs. yes). After a median follow-up of 61 months (interquartile range 36-67), the adjusted 5-year PFS was 64.8 % for the exercise group compared with 65.0 % for the control group (Hazard ratio [HR] 1.01, 95 % CI 0.51-2.01, p = 0.98). In the secondary analysis, the adjusted 5-year PFS was 59.0 % in the control group without crossover compared with 69.2 % for the control group with crossover (HR 0.68, 95 % CI 0.22-2.06, p = 0.49), 67.7 % for the exercise group with <80 % adherence (HR 0.72, 95 % CI 0.28-1.85, p = 0.50), and 68.4 % for the exercise group with ≥80 % adherence (HR 0.70, 95 % CI 0.32-1.56, p = 0.39). In a post hoc analysis combining the three groups that received supervised exercise, the adjusted 5-year PFS for the supervised exercise groups was 68.5 % compared with 59.0 % for the group that received no supervised exercise (HR 0.70, 95 % CI 0.35-1.39, p = 0.31). This exploratory follow-up of the HELP Trial suggests that supervised aerobic exercise may be associated with improved PFS in lymphoma patients. Larger trials designed to answer this question are needed.

A randomized, controlled trial of bright light therapy for agitated behaviors in dementia patients residing in long-term care.

PubMed

Lyketsos, C G; Lindell Veiel, L; Baker, A; Steele, C

1999-07-01

Agitated behaviors are common in dementia patients residing in chronic care settings. Their occurrence may be associated with lack of adequate exposure to sunlight and with circadian rhythm disturbances. Prior research has suggested that bright light therapy (BLT) may reduce agitated behaviors in dementia patients. The aim of this study was to test the efficacy of BLT in a randomized, controlled, crossover clinical trial. Fifteen patients with dementia and agitated behaviors residing in a chronic care facility were randomized in a crossover design to morning BLT for 1 hour per day or to a control condition with dim light exposure. Patients were treated in either condition for 4 weeks, followed by 1 week on no treatment, prior to being crossed over to the other condition. Eight out of 15 patients completed the entire study. The rest completed at least 2 weeks of study. Patients randomized to the BLT condition exhibited a statistically significant improvement in nocturnal sleep from a mean of 6.4 hours/night to 8.1 hours/night 4 weeks later (p<0.05). The sleep of patients in the control condition did not improve significantly. There were no other significant differences between baseline and follow-up, nor between BLT and control treated patients on the other outcome measures, which included the Behavioral Pathology in Alzheimer Disease scale (Behave-AD) and the Cornell Scale for Depression in Dementia. Patients with dementia in chronic care who exhibit agitated behaviors sleep more hours at night when administered morning BLT. However, BLT does not lead to improvements in agitated behaviors in institutionalized patients with dementia with non-disturbed sleep-wake cycles. Copyright 1999 John Wiley & Sons, Ltd.

Hypnosis and Local Anesthesia for Dental Pain Relief-Alternative or Adjunct Therapy?-A Randomized, Clinical-Experimental Crossover Study.

PubMed

Wolf, Thomas Gerhard; Wolf, Dominik; Callaway, Angelika; Below, Dagna; d'Hoedt, Bernd; Willershausen, Brita; Daubländer, Monika

2016-01-01

This prospective randomized clinical crossover trial was designed to compare hypnosis and local anesthesia for experimental dental pain relief. Pain thresholds of the dental pulp were determined. A targeted standardized pain stimulus was applied and rated on the Visual Analogue Scale (0-10). The pain threshold was lower under hypnosis (58.3 ± 17.3, p < .001), maximal (80.0) under local anesthesia. The pain stimulus was scored higher under hypnosis (3.9 ± 3.8) than with local anesthesia (0.0, p < .001). Local anesthesia was superior to hypnosis and is a safe and effective method for pain relief in dentistry. Hypnosis seems to produce similar effects observed under sedation. It can be used in addition to local anesthesia and in individual cases as an alternative for pain control in dentistry.

Acute Garcinia mangostana (mangosteen) supplementation does not alleviate physical fatigue during exercise: a randomized, double-blind, placebo-controlled, crossover trial.

PubMed

Chang, Chih-Wei; Huang, Tzu-Zung; Chang, Wen-Hsin; Tseng, Yi-Chun; Wu, Yu-Tse; Hsu, Mei-Chich

2016-01-01

The purple mangosteen (Garcinia mangostana), known as the "queen of fruit," is widely consumed and unique not only because of its outstanding appearance and flavor but also its remarkable and diverse pharmacological effects. The aim of the present study is to evaluate the effect of acute mangosteen supplementation on physical fatigue during exercise. A randomized, double-blind, placebo-controlled, crossover study was carried out by 12 healthy adults. The participants were randomly assigned to receive acute oral administration of either 250 mL of the mangosteen-based juice (supplementation treatment; 305 mg of α-mangostin and 278 mg of hydroxycitric acid) or a placebo (control treatment) 1 h before cycle ergometer exercise. Time to exhaustion, heart rate, Borg Rating of Perceived Exertion score, blood biochemical markers (namely ammonia, cortisol, creatine kinase, aspartate aminotransferase, alanine aminotransferase, glucose, and lactate), muscle dynamic stiffness, and Profile of Mood States (POMS) were evaluated and recorded. The results showed all parameters we examined were significantly altered by the exercise challenge, which demonstrated they directly reflected the condition of fatigue. However, there were no differences between the two treatments besides a positive impact on the POMS examination. The occurrence of physical fatigue depends on multiple underlying mechanisms. We concluded that acute mangosteen supplementation had no impact on alleviating physical fatigue during exercise.

Daily Consumption of Virgin Coconut Oil Increases High-Density Lipoprotein Cholesterol Levels in Healthy Volunteers: A Randomized Crossover Trial.

PubMed

Chinwong, Surarong; Chinwong, Dujrudee; Mangklabruks, Ampica

2017-01-01

This open-label, randomized, controlled, crossover trial assessed the effect of daily virgin coconut oil (VCO) consumption on plasma lipoproteins levels and adverse events. The study population was 35 healthy Thai volunteers, aged 18-25. At entry, participants were randomly allocated to receive either (i) 15 mL VCO or (ii) 15 mL 2% carboxymethylcellulose (CMC) solution (as control), twice daily, for 8 weeks. After 8 weeks, participants had an 8-week washout period and then crossed over to take the alternative regimen for 8 weeks. Plasma lipoproteins levels were measured in participants at baseline, week-8, week-16, and week-24 follow-up visits. Results . Of 32 volunteers with complete follow-up (16 males and 16 females), daily VCO intake significantly increased high-density lipoprotein cholesterol by 5.72 mg/dL ( p = 0.001) compared to the control regimen. However, there was no difference in the change in total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels between the two regimens. Mild diarrhea was reported by some volunteers when taking VCO, but no serious adverse events were reported. Conclusion . Daily consumption of 30 mL VCO in young healthy adults significantly increased high-density lipoprotein cholesterol. No major safety issues of taking VCO daily for 8 weeks were reported.

Analgesic Effect of Topical Sodium Diclofenac before Retinal Photocoagulation for Diabetic Retinopathy: A Randomized Double-masked Placebo-controlled Intraindividual Crossover Clinical Trial.

PubMed

Ramezani, Alireza; Entezari, Morteza; Shahbazi, Mohammad Mehdi; Semnani, Yosef; Nikkhah, Homayoun; Yaseri, Mehdi

2017-04-01

To evaluate the analgesic effect of topical sodium diclofenac 0.1% before retinal laser photocoagulation for diabetic retinopathy. Diabetic patients who were candidates for peripheral laser photocoagulation were included in a randomized, placebo-controlled, intraindividual, two-period, and crossover clinical trial. At the first session and based on randomization, one eye received topical sodium diclofenac 0.1% and the other eye received an artificial tear drop (as placebo) three times before laser treatment. At the second session, eyes were given the alternate drug. Patients scored their pain using visual analogue scale (max, 10 cm) at both sessions. Patients and the surgeon were blinded to the drops given. Difference of pain level was the main outcome measure. A total of 200 eyes of 100 patients were enrolled. Both treatments were matched regarding the applied laser. Pain sensation based on visual analogue scale was 5.6 ± 3.0 in the treated group and 5.5 ± 3.0 in the control group. The calculated treatment effect was 0.15 (95% confidence interval, -0.27 to 0.58; p = 0.486). The estimated period effect was 0.24 ( p = 0.530) and the carryover effect was not significant ( p = 0.283). Pretreatment with topical sodium diclofenac 0.1% does not have any analgesic effect during peripheral retinal laser photocoagulation in diabetic patients.

Daily Consumption of Virgin Coconut Oil Increases High-Density Lipoprotein Cholesterol Levels in Healthy Volunteers: A Randomized Crossover Trial

PubMed Central

2017-01-01

This open-label, randomized, controlled, crossover trial assessed the effect of daily virgin coconut oil (VCO) consumption on plasma lipoproteins levels and adverse events. The study population was 35 healthy Thai volunteers, aged 18–25. At entry, participants were randomly allocated to receive either (i) 15 mL VCO or (ii) 15 mL 2% carboxymethylcellulose (CMC) solution (as control), twice daily, for 8 weeks. After 8 weeks, participants had an 8-week washout period and then crossed over to take the alternative regimen for 8 weeks. Plasma lipoproteins levels were measured in participants at baseline, week-8, week-16, and week-24 follow-up visits. Results. Of 32 volunteers with complete follow-up (16 males and 16 females), daily VCO intake significantly increased high-density lipoprotein cholesterol by 5.72 mg/dL (p = 0.001) compared to the control regimen. However, there was no difference in the change in total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels between the two regimens. Mild diarrhea was reported by some volunteers when taking VCO, but no serious adverse events were reported. Conclusion. Daily consumption of 30 mL VCO in young healthy adults significantly increased high-density lipoprotein cholesterol. No major safety issues of taking VCO daily for 8 weeks were reported. PMID:29387131

Intervention for phantom limb pain: A randomized single crossover study of mirror therapy

PubMed Central

Ramadugu, Shashikumar; Nagabushnam, Satish C.; Katuwal, Nagendra; Chatterjee, Kaushik

2017-01-01

Introduction: Mirror therapy suggested to help relieve phantom limb pain (PLP) by resolving the visual- proprioceptive dissociation in the brain, but studies so far either had shorter follow-up or smaller sample size. Materials and Methods: In this randomized single crossover trial, 64 amputees with PLP in the age group of 15–75 years of age were distributed into test and control groups by simple randomization method. Of these 28 in control and 32 in test groups, respectively, completed the 4 weeks of mirror therapy and 12 weeks of follow-up assessments. A standardized set of exercises for 15 min/day for 4 and 8 weeks in test and control groups (in the first 4 weeks, the mirror was covered), respectively, was administered under supervision of one of the authors. All were assessed using the visual analog scale and Short-Form McGill Pain Questionnaire on day 0 and at 4, 8, and 12 weeks after therapy. In control group for the initial 4 weeks, the mirror was covered. The assessing author was blinded to the group to which the participants belonged. Results: Significant reduction in PLP was noted in the test group at 4 weeks compared to the control group (P < 0.0001). Significant reduction was seen in control group also after the switchover and sustained for 12 weeks in both. No harm was reported. Conclusion: Mirror therapy is effective in relieving the intensity, duration, frequency, and overall PLP, and improvement is maintained up to 12 weeks’ posttherapy. PMID:29497188

A Phase III Randomized Clinical Trial of a 0.5% Timolol + 0.2% Brimonidine + 2.0% Dorzolamide Fixed Combination, Preservative-Free Ophthalmic Solution vs. 0.5% Timolol + 0.2% Brimonidine + 2.0% Dorzolamide Fixed Combination in Patients with Controlled Primary Open-Angle Glaucoma.

PubMed

Gómez-Aguayo, Francisco; Paczka, José A; Leñero-Córdova, Rubén; Jiménez-Román, Jesús; Davila-Villarreal, Jaime; Hartleben, Curt; Baiza-Durán, Leopoldo; Olvera-Montaño, Oscar; García-Velez, Francisco; Muñoz-Villegas, Patricia

2018-06-01

The aim of this prospective crossover study was to evaluate the non-inferiority of PRO-122 (a preservative-free fixed combination) compared with 0.5% timolol + 0.2% brimonidine + 2.0% dorzolamide fixed combination (KOF) by evaluating its efficacy, tolerability and safety in subjects with controlled primary open-angle glaucoma (POAG) previously treated with KOF for at least 2 months. In a prospective, crossover, randomized, double-masked multicenter study, patients previously treated with KOF were randomly assigned to receive either PRO-122 or KOF for 30 days. On day 31, the A sequence changed to KOF, while the B sequence received PRO-122. All patients remained in the protocol for 30 additional days for a total of 60 days. The main efficacy endpoint was maintaining the controlled intraocular pressure (IOP). The safety and tolerability of both products were assessed by the presence of adverse events (AEs), ocular findings, a questionnaire on ocular comfort and the VF-14 index. A total of 51 patients participated. After application of PRO-122 twice a day, its efficacy was demonstrated through maintenance of the controlled IOP in patients previously controlled with KOF. The crossover between PRO-122 and KOF and vice versa, after 30 days of use, did not affect IOP control. PRO-122 was shown not to be inferior to KOF in maintaining IOP at control levels. The safety of both drugs is similar, as neither presented drug-related AEs or differences regarding safety issues. The tolerability of the two medications-evaluated by ocular findings, the questionnaire on ocular comfort and the VF-14 index-was also determined to be similar. The controlled IOP in patients with controlled POAG treated with PRO-122 was maintained both in relation to the initial controlled IOP of the study and when compared with KOF in the B sequence. Finally, the treatment with PRO-122 demonstrated similar safety and tolerability to KOF. Laboratorios Sophia, S.A. de C.V. (Zapopan, Jalisco, México). ClinicalTrials.gov identifier: NCT03257813 (registered retrospectively).

No evidence for differential dose effects of hydrocortisone on intrusive memories in female patients with complex post-traumatic stress disorder--a randomized, double-blind, placebo-controlled, crossover study.

PubMed

Ludäscher, Petra; Schmahl, Christian; Feldmann, Robert E; Kleindienst, Nikolaus; Schneider, Miriam; Bohus, Martin

2015-10-01

Post-traumatic stress disorder is characterized by intrusive traumatic memories. Presently, a controversial debate is ongoing regarding whether reduced cortisol secretion in post-traumatic stress disorder promotes an automatic retrieval of trauma-associated memories. Hence, a pharmacological elevation of cortisol was proposed to decrease post-traumatic stress disorder symptoms, particularly intrusions. The present study investigated the impact of two different doses of hydrocortisone on automatic memory retrieval using a randomized, double-blind, placebo-controlled, crossover study in 30 inpatients with post-traumatic stress disorder. All participants were female and received various psychotropic medications. They were randomly assigned to one of two groups within a crossover design: they received either 1 week placebo followed by 1 week hydrocortisone 10/d, followed by 1 week placebo, followed by hydrocortisone 30 mg/d (15 participants) or 1 week hydrocortisone 30 mg/d, followed by 1 week placebo, followed by 1 week hydrocortisone 10 mg/d, followed by 1 week placebo (15 participants). The outcome measures were the frequency and the intensity of intrusions, the overall symptomatology of post-traumatic stress disorder and the general psychopathology. We did not find any differences in the frequency and the intensity of post-traumatic stress disorder-related intrusions between the 10 mg hydrocortisone, the 30 mg hydrocortisone and the placebo condition. All effect sizes for the hydrocortisone condition vs. placebo were very small. Additionally, the overall symptomatology of post-traumatic stress disorder and the general psychopathology did not differ between the hydrocortisone therapies and placebo. Our results do not show any effect of the hydrocortisone administration on intrusions in complex post-traumatic stress disorder. © The Author(s) 2015.

Small Amounts of Gluten in Subjects With Suspected Nonceliac Gluten Sensitivity: A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Trial.

PubMed

Di Sabatino, Antonio; Volta, Umberto; Salvatore, Chiara; Biancheri, Paolo; Caio, Giacomo; De Giorgio, Roberto; Di Stefano, Michele; Corazza, Gino R

2015-09-01

There is debate over the existence of nonceliac gluten sensitivity (NCGS) intestinal and extraintestinal symptoms in response to ingestion of gluten-containing foods by people without celiac disease or wheat allergy. We performed a randomized, double-blind, placebo-controlled, cross-over trial to determine the effects of administration of low doses of gluten to subjects with suspected NCGS. We enrolled 61 adults without celiac disease or a wheat allergy who believed ingestion of gluten-containing food to be the cause of their intestinal and extraintestinal symptoms. Participants were assigned randomly to groups given either 4.375 g/day gluten or rice starch (placebo) for 1 week, each via gastrosoluble capsules. After a 1-week gluten-free diet, participants crossed over to the other group. The primary outcome was the change in overall (intestinal and extraintestinal) symptoms, determined by established scoring systems, between gluten and placebo intake. A secondary outcome was the change in individual symptom scores between gluten vs placebo. According to the per-protocol analysis of data from the 59 patients who completed the trial, intake of gluten significantly increased overall symptoms compared with placebo (P = .034). Abdominal bloating (P = .040) and pain (P = .047), among the intestinal symptoms, and foggy mind (P = .019), depression (P = .020), and aphthous stomatitis (P = .025), among the extraintestinal symptoms, were significantly more severe when subjects received gluten than placebo. In a cross-over trial of subjects with suspected NCGS, the severity of overall symptoms increased significantly during 1 week of intake of small amounts of gluten, compared with placebo. Clinical trial no: ISRCTN72857280. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Efficient assessment of efficacy in post-traumatic peripheral neuropathic pain patients: pregabalin in a randomized, placebo-controlled, crossover study

PubMed Central

Jenkins, Tim M; Smart, Trevor S; Hackman, Frances; Cooke, Carol; Tan, Keith KC

2012-01-01

Background: Detecting the efficacy of novel analgesic agents in neuropathic pain is challenging. There is a critical need for study designs with the desirable characteristics of assay sensitivity, low placebo response, reliable pain recordings, low cost, short duration of exposure to test drug and placebo, and relevant and recruitable population. Methods: We designed a proof-of-concept, double-blind, randomized, placebo-controlled, crossover study in patients with post-traumatic peripheral neuropathic pain (PTNP) to evaluate whether such a study design had the potential to detect efficacious agents. Pregabalin, known to be efficacious in neuropathic pain, was used as the active analgesic. We also assessed physical activity throughout the study. Results: Twenty-five adults (20–70 years of age) with PTNP for ≥3 months entered a screening week and were then randomized to one of the two following treatment sequences: (1) pregabalin followed by placebo or (2) placebo followed by pregabalin. These 2-week treatment periods were separated by a 2-week washout period. Patients on pregabalin treatment received escalating doses to a final dosage of 300 mg/day (days 5–15). In an attempt to minimize placebo response, patients received placebo treatment during the screening week and the 2-week washout period. Average daily pain scores (primary endpoint) were significantly reduced for pregabalin versus placebo, with a mean treatment difference of −0.81 (95% confidence interval: −1.45 to −0.17; P = 0.015). Conclusion: The efficacy of pregabalin was similar to that identified in a large, parallel group trial in PTNP. Therefore, this efficient crossover study design has potential utility for future proof-of-concept studies in neuropathic pain. PMID:22888270

Ruxolitinib reduces JAK2 p.V617F allele burden in patients with polycythemia vera enrolled in the RESPONSE study.

PubMed

Vannucchi, Alessandro Maria; Verstovsek, Srdan; Guglielmelli, Paola; Griesshammer, Martin; Burn, Timothy C; Naim, Ahmad; Paranagama, Dilan; Marker, Mahtab; Gadbaw, Brian; Kiladjian, Jean-Jacques

2017-07-01

In patients with polycythemia vera (PV), an elevated JAK2 p.V617F allele burden is associated with indicators of more severe disease (e.g., leukocytosis, splenomegaly, and increased thrombosis risk); however, correlations between allele burden reductions and clinical benefit in patients with PV have not been extensively evaluated in a randomized trial. This exploratory analysis from the multicenter, open-label, phase 3 Randomized Study of Efficacy and Safety in Polycythemia Vera With JAK Inhibitor INCB018424 Versus Best Supportive Care trial evaluated the long-term effect of ruxolitinib treatment on JAK2 p.V617F allele burden in patients with PV. Evaluable JAK2 p.V617F-positive patients randomized to ruxolitinib (n = 107) or best available therapy (BAT) who crossed over to ruxolitinib at week 32 (n = 97) had consistent JAK2 p.V617F allele burden reductions throughout the study. At all time points measured (up to weeks 208 [ruxolitinib-randomized] and 176 [ruxolitinib crossover]), mean changes from baseline over time in JAK2 p.V617F allele burden ranged from -12.2 to -40.0% (ruxolitinib-randomized) and -6.3 to -17.8% (ruxolitinib crossover). Complete or partial molecular response was observed in 3 patients (ruxolitinib-randomized, n = 2; ruxolitinib crossover, n = 1) and 54 patients (ruxolitinib-randomized, n = 33; ruxolitinib crossover, n = 20; BAT, n = 1), respectively. Among patients treated with interferon as BAT (n = 13), the mean maximal reduction in allele burden from baseline was 25.6% after crossover to ruxolitinib versus 6.6% before crossover. Collectively, the data from this exploratory analysis suggest that ruxolitinib treatment for up to 4 years provides progressive reductions in JAK2 p.V617F allele burden in patients with PV who are resistant to or intolerant of hydroxyurea. The relationship between allele burden changes and clinical outcomes in patients with PV remains unclear.

Comparison of antiemetic efficacy of granisetron and ondansetron in Oriental patients: a randomized crossover study.

PubMed Central

Poon, R. T.; Chow, L. W.

1998-01-01

A double-blind randomized crossover trial was performed to compare the antiemetic efficacy of two 5-HT3 receptor antagonists, granisetron and ondansetron, in Chinese patients receiving adjuvant chemotherapy (cyclophosphamide, methotrexate and 5-fluorouracil) for breast cancer. Twenty patients were randomized to receive chemotherapy with either granisetron on day 1 and ondansetron on day 8 of the first cycle followed by the reverse order in the second cycle, or vice versa. The number of vomiting episodes and the severity of nausea in the first 24 h (acute vomiting/nausea) and the following 7 days (delayed vomiting/nausea) were studied. Acute vomiting was completely prevented in 29 (72.5%) cycles with granisetron and 27 (67.5%) cycles with ondansetron, and treatment failure (>5 vomiting episodes) occurred in two (5%) cycles with each agent (P = NS). Acute nausea was completely controlled in 15 (37.5%) cycles with granisetron and 14 (35%) cycles with ondansetron, whereas severe acute nausea occurred in four (10%) cycles with each agent (P = NS). However, complete response for delayed vomiting was observed in only 21 (52.5%) cycles with granisetron and 22 (55%) cycles with ondansetron (P = NS), and delayed nausea was completely controlled in only 11 (27.5%) and ten (25%) cycles respectively (P = NS). In conclusion, both granisetron and ondansetron are effective in controlling acute nausea and vomiting in Chinese patients, with equivalent antiemetic efficacy. Control of delayed nausea and vomiting is less satisfactory. PMID:9635849

Differential Effects of Methylphenidate on Attentional Functions in Children with Attention-Deficit-Hyperactivity Disorder

ERIC Educational Resources Information Center

Konrad, Kerstin; Gunther, Thomas; Hanisch, Charlotte; Herpertz-Dahlmann, Beate

2004-01-01

Objective: To examine the effects of methylphenidate on different attentional functions and behavior in children with attention-deficit-hyperactivity disorder (ADHD). Method: A total of 60 ADHD children aged between 8 and 12 years completed a randomized, double-blind, placebo-controlled, within-subject crossover trial with two doses of…

Simulated Driving Changes in Young Adults with ADHD Receiving Mixed Amphetamine Salts Extended Release and Atomoxetine

ERIC Educational Resources Information Center

Kay, Gary G.; Michaels, M. Alex; Pakull, Barton

2009-01-01

Background: Psychostimulant treatment may improve simulated driving performance in young adults with attention-deficit/hyperactivity disorder (ADHD). Method: This was a randomized, double-blind, placebo-controlled, crossover study of simulated driving performance with mixed amphetamine salts--extended release (MAS XR) 50 mg/day (Cohort 1) and…

Aged Garlic Extract Improves Adiponectin Levels in Subjects with Metabolic Syndrome: A Double-Blind, Placebo-Controlled, Randomized, Crossover Study

PubMed Central

Gómez-Arbeláez, Diego; Lahera, Vicente; Oubiña, Pilar; Valero-Muñoz, Maria; de las Heras, Natalia; Rodríguez, Yudy; García, Ronald Gerardo; Camacho, Paul Anthony; López-Jaramillo, Patricio

2013-01-01

Background. Garlic (Allium sativum) has been shown to have important benefits in individuals at high cardiovascular risk. The aim of the present study was to evaluate the effects of the administration of aged garlic extract (AGE) on the risk factors that constitute the cluster of metabolic syndrome (MS). Methods and Design. Double-blind, crossover, randomized, placebo-controlled clinical trial to assess the effect of 1.2 g/day of AGE (Kyolic), for 24 weeks of treatment (12 weeks of AGE and 12 weeks of placebo), on subjects with MS. Results. The administration of AGE increased the plasma levels of adiponectin (P = 0.027). No serious side effects associated with the intervention were reported. Conclusion. The present results have shown for the first time that the administration of AGE for 12 weeks increased plasma adiponectin levels in patients with MS. This suggests that AGE might be a useful, novel, nonpharmacological therapeutic intervention to increase adiponectin and to prevent cardiovascular (CV) complications in individuals with MS. PMID:23533302

Hyperbaric Oxygen Therapy Can Improve Post Concussion Syndrome Years after Mild Traumatic Brain Injury - Randomized Prospective Trial

PubMed Central

Fishlev, Gregori; Bechor, Yair; Volkov, Olga; Bergan, Jacob; Friedman, Mony; Hoofien, Dan; Shlamkovitch, Nathan; Ben-Jacob, Eshel; Efrati, Shai

2013-01-01

Background Traumatic brain injury (TBI) is the leading cause of death and disability in the US. Approximately 70-90% of the TBI cases are classified as mild, and up to 25% of them will not recover and suffer chronic neurocognitive impairments. The main pathology in these cases involves diffuse brain injuries, which are hard to detect by anatomical imaging yet noticeable in metabolic imaging. The current study tested the effectiveness of Hyperbaric Oxygen Therapy (HBOT) in improving brain function and quality of life in mTBI patients suffering chronic neurocognitive impairments. Methods and Findings The trial population included 56 mTBI patients 1–5 years after injury with prolonged post-concussion syndrome (PCS). The HBOT effect was evaluated by means of prospective, randomized, crossover controlled trial: the patients were randomly assigned to treated or crossover groups. Patients in the treated group were evaluated at baseline and following 40 HBOT sessions; patients in the crossover group were evaluated three times: at baseline, following a 2-month control period of no treatment, and following subsequent 2-months of 40 HBOT sessions. The HBOT protocol included 40 treatment sessions (5 days/week), 60 minutes each, with 100% oxygen at 1.5 ATA. “Mindstreams” was used for cognitive evaluations, quality of life (QOL) was evaluated by the EQ-5D, and changes in brain activity were assessed by SPECT imaging. Significant improvements were demonstrated in cognitive function and QOL in both groups following HBOT but no significant improvement was observed following the control period. SPECT imaging revealed elevated brain activity in good agreement with the cognitive improvements. Conclusions HBOT can induce neuroplasticity leading to repair of chronically impaired brain functions and improved quality of life in mTBI patients with prolonged PCS at late chronic stage. Trial Registration ClinicalTrials.gov NCT00715052 PMID:24260334

Spin dynamics of random Ising chain in coexisting transverse and longitudinal magnetic fields

NASA Astrophysics Data System (ADS)

Liu, Zhong-Qiang; Jiang, Su-Rong; Kong, Xiang-Mu; Xu, Yu-Liang

2017-05-01

The dynamics of the random Ising spin chain in coexisting transverse and longitudinal magnetic fields is studied by the recursion method. Both the spin autocorrelation function and its spectral density are investigated by numerical calculations. It is found that system's dynamical behaviors depend on the deviation σJ of the random exchange coupling between nearest-neighbor spins and the ratio rlt of the longitudinal and the transverse fields: (i) For rlt = 0, the system undergoes two crossovers from N independent spins precessing about the transverse magnetic field to a collective-mode behavior, and then to a central-peak behavior as σJ increases. (ii) For rlt ≠ 0, the system may exhibit a coexistence behavior of a collective-mode one and a central-peak one. When σJ is small (or large enough), system undergoes a crossover from a coexistence behavior (or a disordered behavior) to a central-peak behavior as rlt increases. (iii) Increasing σJ depresses effects of both the transverse and the longitudinal magnetic fields. (iv) Quantum random Ising chain in coexisting magnetic fields may exhibit under-damping and critical-damping characteristics simultaneously. These results indicate that changing the external magnetic fields may control and manipulate the dynamics of the random Ising chain.

The Effect of Head Massage on the Regulation of the Cardiac Autonomic Nervous System: A Pilot Randomized Crossover Trial.

PubMed

Fazeli, Mir Sohail; Pourrahmat, Mir-Masoud; Liu, Mailan; Guan, Ling; Collet, Jean-Paul

2016-01-01

To evaluate the effect of a single 10-minute session of Chinese head massage on the activity of the cardiac autonomic nervous system via measurement of heart rate variability (HRV). In this pilot randomized crossover trial, each participant received both head massage and the control intervention in a randomized fashion. The study was conducted at Children's & Women's Health Centre of British Columbia between June and November 2014. Ten otherwise healthy adults (6 men and 4 women) were enrolled in this study. The intervention comprised 10 minutes of head massage therapy (HMT) in a seated position compared with a control intervention of sitting quietly on the same chair with eyes closed for an equal amount of time (no HMT). The primary outcome measures were the main parameters of HRV, including total power (TP), high frequency (HF), HF as a normalized unit, pre-ejection period, and heart rate (HR). A single short session (10 minutes) of head massage demonstrated an increase in TP continuing up to 20 minutes after massage and reaching statistical significance at 10 minutes after massage (relative change from baseline, 66% for HMT versus -6.6% for no HMT; p = 0.017). The effect on HF also peaked up to 10 minutes after massage (59.4% for HMT versus 4% for no HMT; p = 0.139). Receiving head massage also decreased HR by more than three-fold compared to the control intervention. This study shows the potential benefits of head massage by modulating the cardiac autonomic nervous system through an increase in the total variability and a shift toward higher parasympathetic nervous system activity. Randomized controlled trials with larger sample size and multiple sessions of massage are needed to substantiate these findings.

Does Mckuer's Law Hold for Heart Rate Control via Biofeedback Display?

NASA Technical Reports Server (NTRS)

Courter, B. J.; Jex, H. R.

1984-01-01

Some persons can control their pulse rate with the aid of a biofeedback display. If the biofeedback display is modified to show the error between a command pulse-rate and the measured rate, a compensatory (error correcting) heart rate tracking control loop can be created. The dynamic response characteristics of this control loop when subjected to step and quasi-random disturbances were measured. The control loop includes a beat-to-beat cardiotachmeter differenced with a forcing function from a quasi-random input generator; the resulting error pulse-rate is displayed as feedback. The subject acts to null the displayed pulse-rate error, thereby closing a compensatory control loop. McRuer's Law should hold for this case. A few subjects already skilled in voluntary pulse-rate control were tested for heart-rate control response. Control-law properties are derived, such as: crossover frequency, stability margins, and closed-loop bandwidth. These are evaluated for a range of forcing functions and for step as well as random disturbances.

Effects of Risperidone on Cognitive-Motor Performance and Motor Movements in Chronically Medicated Children

ERIC Educational Resources Information Center

Aman, Michael G.; Hollway, Jill A.; Leone, Sarah; Masty, Jessica; Lindsay, Ronald; Nash, Patricia; Arnold, L. Eugene

2009-01-01

This study was designed to explore the placebo-controlled effects of risperidone on cognitive-motor processes, dyskinetic movements, and behavior in children receiving maintenance risperidone therapy. Sixteen children aged 4-14 years with disruptive behavior were randomly assigned to drug order in a crossover study of risperidone and placebo for 2…

Time Course of Treatment Effect of OROS[R] Methylphenidate in Children with ADHD

ERIC Educational Resources Information Center

Armstrong, Robert B.; Damaraju, C. V.; Ascher, Steve; Schwarzman, Lesley; O'Neill, James; Starr, H. Lynn

2012-01-01

Objective: The authors evaluated the time course of the treatment effect of Osmotic-Release Oral System methylphenidate (OROS[R] MPH) HCl (Concerta[R], Raritan, NJ) CII in children with ADHD. Method: Data were combined from two double-blind, randomized, placebo-controlled, cross-over, analog classroom studies in children (9-12 years) with ADHD.…

Acute Exercise and Academic Achievement in High School Youth

ERIC Educational Resources Information Center

Harveson, Andrew; Hannon, James; Brusseau, Timothy; Podlog, Les; Chase, Ben; Kang, Kyoung-doo

2018-01-01

The purpose of this study was to compare the acute effects of Aerobic Exercise (AE), Resistance Exercise (RE), and a nonexercise (NE) control on measures of academic achievement (AA) and cognition in 10th grade males and females. This study utilized a randomized crossover design. Tenth grade males and females performed three exercise trials (AE,…

Chronic dietary fiber supplementation with wheat dextrin does not inhibit calcium and magnesium absorption in premenopausal and postmenopausal women

USDA-ARS?s Scientific Manuscript database

This placebo-controlled, randomized, crossover clinical study examined the effect of chronic wheat dextrin intake on calcium and magnesium absorption. Forty premenopausal and post menopausal women (mean +/- SD age 49.9 +/- 9.8 years)consumed wheat dextrin or placebo (15 g/day) for 2 weeks prior to 4...

Evaluation of 5 Hour Energy Drink on the Blood Pressure and Electrocardiograph Parameters on Young Healthy Volunteers: A Randomized, Double Blind, Crossover, Placebo-Controlled Trial (Presentation)

DTIC Science & Technology

2014-02-11

other substances. • There have been reports of atrial fibrillation , Takotsubo cardiomyopathy and sudden cardiac deaths in healthy individuals...baseline cardiac rhythm, history of atrial or ventricular arrhythmia, baseline corrected QT (QTc) interval greater than 440 milliseconds (msec

Respiratory protection during simulated emergency pediatric life support: a randomized, controlled, crossover study.

PubMed

Schumacher, Jan; Gray, Stuart A; Michel, Sophie; Alcock, Roger; Brinker, Andrea

2013-02-01

Emergency pediatric life support (EPLS) of children infected with transmissible respiratory diseases requires adequate respiratory protection for medical first responders. Conventional air-purifying respirators (APR) and modern loose-fitting powered air-purifying respirator-hoods (PAPR-hood) may have a different impact during pediatric resuscitation and therefore require evaluation. This study investigated the influence of APRs and PAPR-hoods during simulated pediatric cardiopulmonary resuscitation. Study design was a randomized, controlled, crossover study. Sixteen paramedics carried out a standardized EPLS scenario inside an ambulance, either unprotected (control) or wearing a conventional APR or a PAPR-hood. Treatment times and wearer comfort were determined and compared. All paramedics completed the treatment objectives of the study arms without adverse events. Study subjects reported that communication, dexterity and mobility were significantly better in the APR group, whereas the heat-build-up was significantly less in the PAPR-hood group. Treatment times compared to the control group did not significantly differ for the APR group but did with the PAPR-hood group (261±12 seconds for the controls, 275±9 seconds for the conventional APR and 286±13 seconds for the PAPR-hood group, P < .05. APRs showed a trend to better treatment times compared to PAPR-hoods during simulated pediatric cardiopulmonary resuscitation. Study participants rated mobility, ease of communication and dexterity with the tight-fitting APR system significantly better compared to the loose-fitting PAPR-hood.

AN INTERVENTION TO ASSIST MEN WHO HAVE SEX WITH MEN DISCLOSE THEIR SEROSTATUS TO CASUAL SEX PARTNERS

PubMed Central

Serovich, Julianne M.; Reed, Sandra; Grafsky, Erika L.; Andrist, David

2009-01-01

This article reports pilot data from a newly developed disclosure intervention and associated measures specifically tailored for disclosure to casual sexual partners. Treatment consisted of a four-session, theoretically driven intervention focusing on the costs and benefits of disclosure. Using a randomized control, crossover design 77 men were randomized into one of three conditions (wait-list control, facilitator only, and computer and facilitator). Results of the study suggest that facilitated administration of the pilot intervention was effective in reducing mean scores on the HIV disclosure behavior and attitude scales and that these reductions were both statistically and practically significant. PMID:19519236

Randomized controlled trial of nettle sting for treatment of base-of-thumb pain.

PubMed Central

Randall, C; Randall, H; Dobbs, F; Hutton, C; Sanders, H

2000-01-01

There are numerous published references to use of nettle sting for arthritis pain but no randomized controlled trials have been reported. We conducted a randomized controlled double-blind crossover study in 27 patients with osteoarthritic pain at the base of the thumb or index finger. Patients applied stinging nettle leaf (Urtica dioica) daily for one week to the painful area. The effect of this treatment was compared with that of placebo, white deadnettle leaf (Lamium album), for one week after a five-week washout period. Observations of pain and disability were recorded for the twelve weeks of the study. After one week's treatment with nettle sting, score reductions on both visual analogue scale (pain) and health assessment questionnaire (disability) were significantly greater than with placebo (P = 0.026 and P = 0.0027). PMID:10911825

Skating crossovers on a motorized flywheel: a preliminary experimental design to test effect on speed and on crossovers.

PubMed

Smith, Aynsley M; Krause, David A; Stuart, Michael J; Montelpare, William J; Sorenson, Matthew C; Link, Andrew A; Gaz, Daniel V; Twardowski, Casey P; Larson, Dirk R; Stuart, Michael B

2013-12-01

Ice hockey requires frequent skater crossovers to execute turns. Our investigation aimed to determine the effectiveness of training crossovers on a motorized, polyethylene high-resistance flywheel. We hypothesized that high school hockey players training on the flywheel would perform as well as their peers training on ice. Participants were 23 male high-school hockey players (age 15-19 years). The study used an experimental prospective design to compare players who trained for 9 sessions on the 22-foot flywheel with players who trained for 9 sessions on a similarly sized on-ice circle. Both groups were compared with control subjects who were randomly selected from the same participant pool as those training on ice. All players were tested before and after their 3-week training regimens, and control subjects were asked to not practice crossovers between testing. Group 1 trained in a hockey training facility housing the flywheel, and group 2 trained in the ice hockey arena where testing occurred. Primary outcome measures tested in both directions were: (a) speed (time in seconds) required to skate crossovers for 3 laps of a marked face-off circle, (b) cadence of skating crossovers on the similarly sized circles, and (c) a repeat interval speed test, which measures anaerobic power. No significant changes were found between groups in on-ice testing before and after training. Among the group 1 players, 7 of 8 believed they benefited from flywheel training. Group 2 players, who trained on ice, did not improve performance significantly over group 1 players. Despite the fact that no significant on-ice changes in performance were observed in objective measures, players who trained on the flywheel subjectively reported that the flywheel is an effective cost-effective alternative to training on ice. This is a relevant finding when placed in context with limited availability of on-ice training.

Coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone improves postprandial endothelial dysfunction in patients with borderline and stage 1 hypertension.

PubMed

Kajikawa, Masato; Maruhashi, Tatsuya; Hidaka, Takayuki; Nakano, Yukiko; Kurisu, Satoshi; Matsumoto, Takeshi; Iwamoto, Yumiko; Kishimoto, Shinji; Matsui, Shogo; Aibara, Yoshiki; Yusoff, Farina Mohamad; Kihara, Yasuki; Chayama, Kazuaki; Goto, Chikara; Noma, Kensuke; Nakashima, Ayumu; Watanabe, Takuya; Tone, Hiroshi; Hibi, Masanobu; Osaki, Noriko; Katsuragi, Yoshihisa; Higashi, Yukihito

2018-01-12

The purpose of this study was to evaluate acute effects of coffee with a high content of chlorogenic acids and different hydroxyhydroquinone contents on postprandial endothelial dysfunction. This was a single-blind, randomized, placebo-controlled, crossover-within-subject clinical trial. A total of 37 patients with borderline or stage 1 hypertension were randomized to two study groups. The participants consumed a test meal with a single intake of the test coffee. Subjects in the Study 1 group were randomized to single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone or coffee with a high content of chlorogenic acids and a high content of hydroxyhydroquinone with crossover. Subjects in the Study 2 group were randomized to single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone or placebo coffee with crossover. Endothelial function assessed by flow-mediated vasodilation and plasma concentration of 8-isoprostanes were measured at baseline and at 1 and 2 h after coffee intake. Compared with baseline values, single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone, but not coffee with a high content of chlorogenic acids and high content of hydroxyhydroquinone or placebo coffee, significantly improved postprandial flow-mediated vasodilation and decreased circulating 8-isoprostane levels. These findings suggest that a single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone is effective for improving postprandial endothelial dysfunction. URL for Clinical Trial: https://upload.umin.ac.jp ; Registration Number for Clinical Trial: UMIN000013283.

Effects of Transcranial Direct Current Stimulation, Transcranial Pulsed Current Stimulation, and Their Combination on Brain Oscillations in Patients with Chronic Visceral Pain: A Pilot Crossover Randomized Controlled Study.

PubMed

Thibaut, Aurore; Russo, Cristina; Hurtado-Puerto, Aura Maria; Morales-Quezada, Jorge Leon; Deitos, Alícia; Petrozza, John Christopher; Freedman, Steven; Fregni, Felipe

2017-01-01

Chronic visceral pain (CVP) syndromes are persistently painful disorders with a remarkable lack of effective treatment options. This study aimed at evaluating the effects of different neuromodulation techniques in patients with CVP on cortical activity, through electreocephalography (EEG) and on pain perception, through clinical tests. A pilot crossover randomized controlled study. Out-patient. Adults with CVP (>3 months). Participants received four interventions in a randomized order: (1) transcranial pulsed current stimulation (tPCS) and active transcranial direct current stimulation (tDCS) combined, (2) tPCS alone, (3) tDCS alone, and (4) sham condition. Resting state quantitative electroencephalography (qEEG) and pain assessments were performed before and after each intervention. Results were compared with a cohort of 47 healthy controls. We enrolled six patients with CVP for a total of 21 visits completed. Compared with healthy participants, patients with CVP showed altered cortical activity characterized by increased power in theta, alpha and beta bands, and a significant reduction in the alpha/beta ratio. Regarding tES, the combination of tDCS with tPCS had no effect on power in any of the bandwidths, nor brain regions. Comparing tPCS with tDCS alone, we found that tPCS induced higher increase in power within the theta and alpha bandwidths. This study confirms that patients with CVP present abnormal EEG-indexed cortical activity compared with healthy controls. Moreover, we showed that combining two types of neurostimulation techniques had no effect, whereas the two interventions, when applied individually, have different neural signatures.

Weighted blankets and sleep in autistic children--a randomized controlled trial.

PubMed

Gringras, Paul; Green, Dido; Wright, Barry; Rush, Carla; Sparrowhawk, Masako; Pratt, Karen; Allgar, Victoria; Hooke, Naomi; Moore, Danielle; Zaiwalla, Zenobia; Wiggs, Luci

2014-08-01

To assess the effectiveness of a weighted-blanket intervention in treating severe sleep problems in children with autism spectrum disorder (ASD). This phase III trial was a randomized, placebo-controlled crossover design. Participants were aged between 5 years and 16 years 10 months, with a confirmed ASD diagnosis and severe sleep problems, refractory to community-based interventions. The interventions were either a commercially available weighted blanket or otherwise identical usual weight blanket (control), introduced at bedtime; each was used for a 2-week period before crossover to the other blanket. Primary outcome was total sleep time (TST) recorded by actigraphy over each 2-week period. Secondary outcomes included actigraphically recorded sleep-onset latency, sleep efficiency, assessments of child behavior, family functioning, and adverse events. Sleep was also measured by using parent-report diaries. Seventy-three children were randomized and analysis conducted on 67 children who completed the study. Using objective measures, the weighted blanket, compared with the control blanket, did not increase TST as measured by actigraphy and adjusted for baseline TST. There were no group differences in any other objective or subjective measure of sleep, including behavioral outcomes. On subjective preference measures, parents and children favored the weighted blanket. The use of a weighted blanket did not help children with ASD sleep for a longer period of time, fall asleep significantly faster, or wake less often. However, the weighted blanket was favored by children and parents, and blankets were well tolerated over this period. Copyright © 2014 by the American Academy of Pediatrics.

Eating marshmallows reduces ileostomy output: a randomized crossover trial.

PubMed

Clarebrough, E; Guest, G; Stupart, D

2015-12-01

Anecdotally, many ostomates believe that eating marshmallows can reduce ileostomy effluent. There is a plausible mechanism for this, as the gelatine contained in marshmallows may thicken small bowel fluid, but there is currently no evidence that this is effective. This was a randomized crossover trial. Adult patients with well-established ileostomies were included. Ileostomy output was measured for 1 week during which three marshmallows were consumed three times daily, and for one control week where marshmallows were not eaten. There was a 2-day washout period. Patients were randomly allocated to whether the control or intervention week occurred first. In addition, a questionnaire was administered regarding patient's subjective experience of their ileostomy function. Thirty-one participants were recruited; 28 completed the study. There was a median reduction in ileostomy output volume of 75 ml per day during the study period (P = 0.0054, 95% confidence interval 23.4-678.3) compared with the control week. Twenty of 28 subjects (71%) experienced a reduction in their ileostomy output, two had no change and six reported an increase. During the study period, participants reported fewer ileostomy bag changes (median five per day vs six in the control period, P = 0.0255). Twenty of 28 (71%) reported that the ileostomy effluent was thicker during the study week (P = 0.023). Overall 19 (68%) participants stated they would use marshmallows in the future if they wanted to reduce or thicken their ileostomy output. Eating marshmallows leads to a small but statistically significant reduction in ileostomy output. Colorectal Disease © 2015 The Association of Coloproctology of Great Britain and Ireland.

Switching patients with acromegaly from octreotide to pasireotide improves biochemical control: crossover extension to a randomized, double-blind, Phase III study.

PubMed

Bronstein, Marcello D; Fleseriu, Maria; Neggers, Sebastian; Colao, Annamaria; Sheppard, Michael; Gu, Feng; Shen, Chiung-Chyi; Gadelha, Mônica; Farrall, Andrew J; Hermosillo Reséndiz, Karina; Ruffin, Matthieu; Chen, YinMiao; Freda, Pamela

2016-04-02

Many patients with acromegaly do not achieve biochemical control with first-generation somatostatin analogues. A large, multicenter, randomized, Phase III core study demonstrated that pasireotide LAR had significantly superior efficacy over octreotide LAR. This analysis explores the efficacy and safety of switching therapeutic arms in inadequately controlled patients during a 12-month crossover extension. Patients with inadequate biochemical control (GH ≥2.5 μg/L and/or IGF-1 > ULN) at end of core study (month 12) were eligible to switch to pasireotide LAR 40 mg/28 days (n = 81) or octreotide LAR 20 mg/28 days (n = 38). One dose escalation to pasireotide LAR 60 mg/28 days or octreotide LAR 30 mg/28 days was permitted, but not mandatory, at month 17 or 20. Twelve months after crossover, 17.3 % of pasireotide LAR and 0 % of octreotide LAR patients achieved GH <2.5 μg/L and normal IGF-1 (main outcome measure); 27.2 and 5.3 % of pasireotide LAR and octreotide LAR patients achieved normal IGF-1, respectively; 44.4 and 23.7 % of pasireotide LAR and octreotide LAR patients achieved GH <2.5 μg/L, respectively. Mean (±SD) tumor volume further decreased from the end of the core study by 25 % (±25) and 18 % (±28); 54.3 % of pasireotide LAR and 42.3 % of octreotide LAR patients achieved significant (≥20 %) tumor volume reduction during the extension. The safety profile of pasireotide LAR was similar to that of octreotide LAR, with the exception of the frequency and degree of hyperglycemia-related adverse events. Pasireotide LAR is a promising treatment option for patients with acromegaly inadequately controlled with the first-generation somatostatin analogue octreotide LAR. clinicaltrials.gov, NCT00600886 . Registered 14 January 2008.

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 Short-Term Fasting on Systemic Cytochrome P450-Mediated Drug Metabolism in Healthy Subjects: A Randomized, Controlled, Crossover Study Using a Cocktail Approach.

PubMed

Lammers, Laureen A; Achterbergh, Roos; van Schaik, Ron H N; Romijn, Johannes A; Mathôt, Ron A A

2017-10-01

Short-term fasting can alter drug exposure but it is unknown whether this is an effect of altered oral bioavailability and/or systemic clearance. Therefore, the aim of our study was to assess the effect of short-term fasting on oral bioavailability and systemic clearance of different drugs. In a randomized, controlled, crossover trial, 12 healthy subjects received a single administration of a cytochrome P450 (CYP) probe cocktail, consisting of caffeine (CYP1A2), metoprolol (CYP2D6), midazolam (CYP3A4), omeprazole (CYP2C19) and warfarin (CYP2C9), on four occasions: an oral (1) and intravenous (2) administration after an overnight fast (control) and an oral (3) and intravenous (4) administration after 36 h of fasting. Pharmacokinetic parameters of the probe drugs were analyzed using the nonlinear mixed-effects modeling software NONMEM. Short-term fasting increased systemic caffeine clearance by 17% (p = 0.04) and metoprolol clearance by 13% (p < 0.01), whereas S-warfarin clearance decreased by 19% (p < 0.01). Fasting did not affect bioavailability. The study demonstrates that short-term fasting alters CYP-mediated drug metabolism in a non-uniform pattern without affecting oral bioavailability.

A randomized, controlled cross-over trial of dermally-applied lavender (Lavandula angustifolia) oil as a treatment of agitated behaviour in dementia.

PubMed

O'Connor, Daniel W; Eppingstall, Barbara; Taffe, John; van der Ploeg, Eva S

2013-11-13

Lavender essential oil shows evidence of sedative properties in neurophysiological and animal studies but clinical trials of its effectiveness as a treatment of agitation in people with dementia have shown mixed results. Study methods have varied widely, however, making comparisons hazardous. To help remedy previous methodological shortcomings, we delivered high grade lavender oil in specified amounts to nursing home residents whose agitated behaviours were recorded objectively. 64 nursing home residents with frequent physically agitated behaviours were entered into a randomized, single-blind cross-over trial of dermally-applied, neurophysiologically active, high purity 30% lavender oil versus an inactive control oil. A blinded observer counted the presence or absence of target behaviours and rated participants' predominant affect during each minute for 30 minutes prior to exposure and for 60 minutes afterwards. Lavender oil did not prove superior to the control oil in reducing the frequency of physically agitated behaviours or in improving participants' affect. Studies of essential oils are constrained by their variable formulations and uncertain pharmacokinetics and so optimal dosing and delivery regimens remain speculative. Notwithstanding this, topically delivered, high strength, pure lavender oil had no discernible effect on affect and behaviour in a well-defined clinical sample. Australian and New Zealand Clinical Trials Registry (ACTRN 12609000569202).

Hyperbaric Oxygen Therapy in the Treatment of Chronic Mild-Moderate Blast-Induced Traumatic Brain Injury Post-Concussion Syndrome (PCS) and Post Traumatic Stress Disorder (PTSD)

DTIC Science & Technology

2017-10-01

a randomized sham- controlled double-blind design with the sham- control group receiving slightly pressurized air at the beginning and end of each... controlled ( non -treatment, non -sham) single-arm crossover single-blind study. The scope of the project is to recruit, enroll, test, treat, re-test and...the P.I. conducted a non - controlled pilot trial of hyperbaric oxygen therapy (HBOT 1.5 atmospheres absolute/60 minutes, twice/day, 40 treatments

Multimodal Cognitive Enhancement Therapy for Patients with Mild Cognitive Impairment and Mild Dementia: A Multi- Center, Randomized, Controlled, Double-Blind, Crossover Trial.

PubMed

Han, Ji Won; Lee, Hyeonggon; Hong, Jong Woo; Kim, Kayoung; Kim, Taehyun; Byun, Hye Jin; Ko, Ji Won; Youn, Jong Chul; Ryu, Seung-Ho; Lee, Nam-Jin; Pae, Chi-Un; Kim, Ki Woong

2017-01-01

We developed and evaluated the effect of Multimodal Cognitive Enhancement Therapy (MCET) consisting of cognitive training, cognitive stimulations, reality orientation, physical therapy, reminiscence therapy, and music therapy in combination in older people with mild cognitive impairment (MCI) or mild dementia. This study was a multi-center, double-blind, randomized, placebo-controlled, two-period cross-over study (two 8-week treatment phases separated by a 4-week wash-out period). Sixty-four participants with MCI or dementia whose Clinical Dementia Rating was 0.5 or 1 were randomized to the MCET group or the mock-therapy (placebo) group. Outcomes were measured at baseline, week 9, and week 21. Fifty-five patients completed the study. Mini-Mental State Examination (effect size = 0.47, p = 0.013) and Alzheimer's Disease Assessment Scale-Cognitive Subscale (effect size = 0.35, p = 0.045) scores were significantly improved in the MCET compared with mock-therapy group. Revised Memory and Behavior Problems Checklist frequency (effect size = 0.38, p = 0.046) and self-rated Quality of Life - Alzheimer's Disease (effect size = 0.39, p = 0.047) scores were significantly improved in the MCET compared with mock-therapy. MCET improved cognition, behavior, and quality of life in people with MCI or mild dementia more effectively than conventional cognitive enhancing activities did.

The effects of intermittent use of the SGLT-2 inhibitor, dapagliflozin, in overweight patients with type 2 diabetes in Japan: a randomized, crossover, controlled clinical trial.

PubMed

Kato, Kanako; Suzuki, Kunihiro; Aoki, Chie; Sagara, Masaaki; Niitani, Takafumi; Wakamatsu, Sho; Yanagi, Kazunori; Aso, Yoshimasa

2017-06-01

This study examined the effects of short-term administration of the sodium glucose cotransporter 2 (SGLT-2) inhibitor, dapagliflozin, on visceral fat area (VFA) in Japanese patients with type 2 diabetes. In this randomized, crossover, controlled clinical trial, overweight patients with type 2 diabetes were randomized to treatment with 5 mg dapagliflozin for the first (n = 27) or second 12-week study period (n = 29). The parameters evaluated at baseline and after 12 and 24 weeks included blood pressure, hemoglobin A1c (HbA1c), body composition, VFA, and subcutaneous fat area (SFA). In both groups, dapagliflozin administration improved the levels of HbA1c, body weight, blood pressure, total fat mass, and VFA. Cessation of dapagliflozin, however, reversed the improvements in HbA1c, blood pressure, body weight, and SFA levels, whereas reductions in VFA and total fat mass levels were somewhat maintained even after 12 weeks without treatment. Dapagliflozin led to decreases in VFA and, consequently, body weight after a short treatment period. However, these effects were largely reversed by the cessation of dapagliflozin, suggesting that this agent should be administered continuously to maintain clinical usefulness in overweight patients with type 2 diabetes.

Dietary nitrate supplementation in COPD: an acute, double-blind, randomized, placebo-controlled, crossover trial.

PubMed

Kerley, Conor P; Cahill, Kathleen; Bolger, Kenneth; McGowan, Aisling; Burke, Conor; Faul, John; Cormican, Liam

2015-01-30

The acute consumption of dietary nitrate has been shown to improve exercise capacity in athletes, healthy adults and subjects with peripheral vascular disease. Many COPD patients have reduced exercise capacity. We hypothesized that acute nitrate consumption might increase incremental shuttle walk test (ISWT) distance in COPD subjects. Eleven COPD subjects were randomly assigned to consume either a high nitrate or a matched, low nitrate beverage in a double-blind, randomized, placebo-controlled, crossover design. ISWT distance was measured both before and 3 h after the beverage and change was recorded. After a 7-day washout, ISWT distances were re-measured before and 3 h after the alternate beverage and changes were recorded. We observed an increase in ISWT distance after consuming the high nitrate juice (25 m) compared with a reduction after the low nitrate juice (14 m) (p < 0.01). This improvement in exercise capacity was associated with significant increases in serum nitrate (p < 0.000005) and nitrite (p < 0.01) levels and a significant lowering of resting blood pressure (<0.05). In patients with stable COPD, the acute consumption of dietary nitrate increased serum nitrate/nitrite levels and exercise capacity and was associated with a decrease in resting blood pressure. Nitrate consumption might alter exercise capacity in COPD patients. Copyright © 2014 Elsevier Inc. All rights reserved.

1% hydrocortisone ointment is an effective treatment of pruritus ani: a pilot randomized controlled crossover trial.

PubMed

Al-Ghnaniem, R; Short, K; Pullen, A; Fuller, L C; Rennie, J A; Leather, A J M

2007-12-01

Pruritus ani (PA) is a common condition which is difficult to treat in the absence of obvious predisposing factors. There is paucity of evidence-based guidelines on the treatment of this condition. We examined whether 1% hydrocortisone ointment is an effective treatment for PA. A pilot randomized, double-blind, placebo-controlled, crossover trial was carried out. Eleven patients consented to take part in the trial and ten completed the study. After a 2-week run-in period, patients with primary PA were randomly allocated to receive 1% hydrocortisone ointment or placebo for 2 weeks followed by the opposite treatment for a further 2-week period. There was a washout period of 2 weeks between treatments. The primary outcome measure was reduction in itch using a visual analogue score (VAS). The secondary outcome measures were improvement in quality of life measured using a validated questionnaire (Dermatology Life Quality Index, DLQI) and improvement in clinical appearance of the perianal skin using the Eczema Area and Severity Index (EASI) score. Treatment with 1% hydrocortisone ointment resulted in a 68% reduction in VAS compared with placebo (P=0.019), a 75% reduction in DLQI score (P=0.067), and 81% reduction in EASI score (P=0.01). A short course of mild steroid ointment is an effective treatment for PA.

Immediate Effects of Core Stabilization Exercise on β-Endorphin and Cortisol Levels Among Patients With Chronic Nonspecific Low Back Pain: A Randomized Crossover Design.

PubMed

Paungmali, Aatit; Joseph, Leonard Henry; Punturee, Khanittha; Sitilertpisan, Patraporn; Pirunsan, Ubon; Uthaikhup, Sureeporn

The main objective of the study was to measure the levels of plasma β-endorphin (PB) and plasma cortisol (PC) under lumbar core stabilization exercise (LCSE), placebo and control conditions in patients with chronic nonspecific low back pain. Twenty-four participants with chronic nonspecific low back pain participated in a randomized, placebo-controlled, crossover design study. There were 3 experimental exercise conditions: control condition (positioning in crook lying and rest), placebo condition (passive cycling in crook lying using automatic cycler), and LCSE on a Pilates device tested with a 48-hour interval between sessions by concealed randomization. A blood sample was collected before and after the exercise conditions. Plasma β-endorphin and PC were measured through enzyme-linked immunosorbent assay and electrochemiluminescence in a Cobas E411 auto analyzer. A significant difference in PB level was identified before and after the LCSE condition (P < .05), whereas no significant differences were noted in control and placebo exercise conditions. Also, the trend of elevation of PB under the LCSE was significantly different compared with the placebo and control conditions (P < .01). In contrast, the PC level remained unchanged in all 3 conditions. The findings of this study indicate that LCSE could possibly influence PB but not PC level among patients with chronic nonspecific low back pain. The mechanism of action of the pain-relieving effect of LCSE might be related to an endogenous opioid mechanism as part of its effects and might not be involved with a stress-induced analgesia mechanism. Copyright © 2018. Published by Elsevier Inc.

Aniracetam tested in chronic psychosyndrome after long-term exposure to organic solvents. A randomized, double-blind, placebo-controlled cross-over study with neuropsychological tests.

PubMed

Somnier, F E; Ostergaard, M S; Boysen, G; Bruhn, P; Mikkelsen, B O

1990-01-01

In order to examine if the nootropic drug, aniracetam, was capable of improving cognitive performance, 44 subjects suffering from chronic psychosyndrome after long-term exposure to organic solvents were included in a randomized, double-blind, placebo-controlled, cross-over study. The treatment periods were 3 months with aniracetam 1 g daily and 3 months with placebo. Neuropsychological tests as well as a physical and neurological examination were performed at entry into the study and after each treatment period, together with an evaluation of the subjects' overall condition. Neither the doctors' nor the subjects' own assessment of the overall condition indicated that the trial medication had had any effect. No significant changes in neuropsychological symptoms were observed. A statistically significant difference in favour of antiracetam was found in only 1 of the 19 neuropsychological test measures, namely a test for constructional ability. However, in another test on visuo-spatial function, a statistically significant result was found in favour of placebo. Thus, aniracetam was found to be ineffective in the treatment of subjects suffering from chronic psychosyndrome after long-term exposure to organic solvents.

A pilot study assessing the effectiveness of a glycerin suppository in controlled colostomy emptying.

PubMed

McClees, Nancy; Mikolaj, Eda L; Carlson, Sharon L; Pryor-McCann, Joan

2004-01-01

The focus of this research was to explore another way for the patient to manage their colostomy. It was hoped that by inserting a glycerin suppository into the colostomy one would be able to evacuate the lower large intestine more effectively and efficiently. To determine if persons with a sigmoid colostomy could obtain fecal continence by instituting a daily self-administered bowel-stimulating suppository. Randomized crossover comparative study comparing usual ostomy emptying practice with emptying with a glycerine suppository to stimulate controlled emptying. Adult males and females with a sigmoid colostomy were studied in their homes. The instruments included a profile questionnaire, a take-home diary, crossover and end-of-study questionnaires, and an exit questionnaire. Subjects were randomized to their usual pouching method or to the experimental suppository method for 14 days each. There was no difference in fecal output, fecal volume, or flatus between the 2 groups. The action of the suppository was affected by its failure to remain in the bowel for an adequate amount of time. Further research is needed to determine if an adjunct device/method to hold the suppository in place would produce successful results.

Effects of SuperUlam on Supporting Concentration and Mood: A Randomized, Double-Blind, Placebo-Controlled Crossover Study.

PubMed

Udani, Jay K

2013-01-01

Background. SuperUlam is a proprietary blend of natural ingredients aimed at supporting brain health. We aimed to evaluate the effect of SuperUlam on attention and mood in healthy adults. Methods. Twenty healthy individuals aged 35-65 were enrolled in this randomized, double-blind, placebo-controlled, crossover study. Study duration was 3 weeks and consisted of 3 visits. Measurement of cognitive function included computer-based testing of reaction time, complex attention, working memory, sustained attention, and executive functioning. Mood testing was performed via the profile of mood states (POMS) survey and the Chalder fatigue scale. Results. Cognitive function testing demonstrated a significant improvement from baseline in executive functioning, cognitive flexibility, reaction time, and working memory in the product group only (P < 0.05). When comparing the study product to placebo, the data demonstrated a significant decrease in tension, depression, and anger (P < 0.05). There was no significant difference between the product and placebo in the other measures of mood, including vigor, fatigue, confusion, and total mood disturbance. No adverse events were reported. Conclusions. Supplementation with SuperUlam is safe to consume with potential benefits to cognitive function and mood.

Effects of SuperUlam on Supporting Concentration and Mood: A Randomized, Double-Blind, Placebo-Controlled Crossover Study

PubMed Central

Udani, Jay K

2013-01-01

Background. SuperUlam is a proprietary blend of natural ingredients aimed at supporting brain health. We aimed to evaluate the effect of SuperUlam on attention and mood in healthy adults. Methods. Twenty healthy individuals aged 35–65 were enrolled in this randomized, double-blind, placebo-controlled, crossover study. Study duration was 3 weeks and consisted of 3 visits. Measurement of cognitive function included computer-based testing of reaction time, complex attention, working memory, sustained attention, and executive functioning. Mood testing was performed via the profile of mood states (POMS) survey and the Chalder fatigue scale. Results. Cognitive function testing demonstrated a significant improvement from baseline in executive functioning, cognitive flexibility, reaction time, and working memory in the product group only (P < 0.05). When comparing the study product to placebo, the data demonstrated a significant decrease in tension, depression, and anger (P < 0.05). There was no significant difference between the product and placebo in the other measures of mood, including vigor, fatigue, confusion, and total mood disturbance. No adverse events were reported. Conclusions. Supplementation with SuperUlam is safe to consume with potential benefits to cognitive function and mood. PMID:24371452

Automatic Molecular Design using Evolutionary Techniques

NASA Technical Reports Server (NTRS)

Globus, Al; Lawton, John; Wipke, Todd; Saini, Subhash (Technical Monitor)

1998-01-01

Molecular nanotechnology is the precise, three-dimensional control of materials and devices at the atomic scale. An important part of nanotechnology is the design of molecules for specific purposes. This paper describes early results using genetic software techniques to automatically design molecules under the control of a fitness function. The fitness function must be capable of determining which of two arbitrary molecules is better for a specific task. The software begins by generating a population of random molecules. The population is then evolved towards greater fitness by randomly combining parts of the better individuals to create new molecules. These new molecules then replace some of the worst molecules in the population. The unique aspect of our approach is that we apply genetic crossover to molecules represented by graphs, i.e., sets of atoms and the bonds that connect them. We present evidence suggesting that crossover alone, operating on graphs, can evolve any possible molecule given an appropriate fitness function and a population containing both rings and chains. Prior work evolved strings or trees that were subsequently processed to generate molecular graphs. In principle, genetic graph software should be able to evolve other graph representable systems such as circuits, transportation networks, metabolic pathways, computer networks, etc.

Increased Erythrocyte Eicosapentaenoic Acid and Docosahexaenoic Acid Are Associated With Improved Attention and Behavior in Children With ADHD in a Randomized Controlled Three-Way Crossover Trial.

PubMed

Milte, Catherine M; Parletta, Natalie; Buckley, Jonathan D; Coates, Alison M; Young, Ross M; Howe, Peter R C

2015-11-01

To investigate effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on attention, literacy, and behavior in children with ADHD. Ninety children were randomized to consume supplements high in EPA, DHA, or linoleic acid (control) for 4 months each in a crossover design. Erythrocyte fatty acids, attention, cognition, literacy, and Conners' Parent Rating Scales (CPRS) were measured at 0, 4, 8, 12 months. Fifty-three children completed the treatment. Outcome measures showed no significant differences between the three treatments. However, in children with blood samples (n = 76-46), increased erythrocyte EPA + DHA was associated with improved spelling (r = .365, p < .001) and attention (r = -.540, p < .001) and reduced oppositional behavior (r = -.301, p < .003), hyperactivity (r = -.310, p < .001), cognitive problems (r = -.326, p < .001), Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) hyperactivity (r = -.270, p = .002) and DSM-IV inattention (r = -.343, p < .001). Increasing erythrocyte DHA and EPA via dietary supplementation may improve behavior, attention, and literacy in children with ADHD. © The Author(s) 2013.

Intravenous immunoglobulin treatment of the complex regional pain syndrome: a randomized trial.

PubMed

Goebel, Andreas; Baranowski, Andrew; Maurer, Konrad; Ghiai, Artemis; McCabe, Candy; Ambler, Gareth

2010-02-02

Treatment of long-standing complex regional pain syndrome (CRPS) is empirical and often of limited efficacy. Preliminary data suggest that the immune system is involved in sustaining this condition and that treatment with low-dose intravenous immunoglobulin (IVIG) may substantially reduce pain in some patients. To evaluate the efficacy of IVIG in patients with longstanding CRPS under randomized, controlled conditions. A randomized, double-blind, placebo-controlled crossover trial. (National Research Registry number: N0263177713; International Standard Randomised Controlled Trial Number Registry: 63918259) University College London Hospitals Pain Management Centre. Persons who had pain intensity greater than 4 on an 11-point (0 to 10) numerical rating scale and had CRPS for 6 to 30 months that was refractory to standard treatment. IVIG, 0.5 g/kg, and normal saline in separate treatments, divided by a washout period of at least 28 days. The primary outcome was pain intensity 6 to 19 days after the initial treatment and the crossover treatment. 13 eligible participants were randomly assigned between November 2005 and May 2008; 12 completed the trial. The average pain intensity was 1.55 units lower after IVIG treatment than after saline (95% CI, 1.29 to 1.82; P < 0.001). In 3 patients, pain intensity after IVIG was less than after saline by 50% or more. No serious adverse reactions were reported. The trial was small, and recruitment bias and chance variation could have influenced results and their interpretation. IVIG, 0.5 g/kg, can reduce pain in refractory CRPS. Studies are required to determine the best immunoglobulin dose, the duration of effect, and when repeated treatments are needed. Association of Anaesthetists of Great Britain and Ireland, University College London Hospitals Charity, and CSL-Behring.

2-Methacryloyloxyethyl phosphorylcholine (MPC)-polymer suppresses an increase of oral bacteria: a single-blind, crossover clinical trial.

PubMed

Fujiwara, Natsumi; Yumoto, Hiromichi; Miyamoto, Koji; Hirota, Katsuhiko; Nakae, Hiromi; Tanaka, Saya; Murakami, Keiji; Kudo, Yasusei; Ozaki, Kazumi; Miyake, Yoichiro

2018-05-16

The biocompatible 2-methacryloyloxyethyl phosphorylcholine (MPC)-polymers, which mimic a biomembrane, reduce protein adsorption and bacterial adhesion and inhibit cell attachment. The aim of this study is to clarify whether MPC-polymer can suppress the bacterial adherence in oral cavity by a crossover design. We also investigated the number of Fusobacterium nucleatum, which is the key bacterium forming dental plaque, in clinical samples. This study was a randomized, placebo-controlled, single-blind, crossover study, with two treatment periods separated by a 2-week washout period. We conducted clinical trial with 20 healthy subjects to evaluate the effect of 5% MPC-polymer mouthwash after 5 h on oral microflora. PBS was used as a control. The bacterial number in the gargling sample before and after intervention was counted by an electronic bacterial counter and a culture method. DNA amounts of total bacteria and F. nucleatum were examined by q-PCR. The numbers of total bacteria and oral streptcocci after 5 h of 5% MPC-polymer treatment significantly decreased, compared to the control group. Moreover, the DNA amounts of total bacteria and F. nucleatum significantly decreased by 5% MPC-polymer mouthwash. We suggest that MPC-polymer coating in the oral cavity may suppress the oral bacterial adherence. MPC-polymer can be a potent compound for the control of oral microflora to prevent oral infection.

Ebselen does not improve oxidative stress and vascular function in patients with diabetes: a randomized, crossover trial.

PubMed

Beckman, Joshua A; Goldfine, Allison B; Leopold, Jane A; Creager, Mark A

2016-12-01

Oxidative stress is a key driver of vascular dysfunction in diabetes mellitus. Ebselen is a glutathione peroxidase mimetic. A single-site, randomized, double-masked, placebo-controlled, crossover trial was carried out in 26 patients with type 1 or type 2 diabetes to evaluate effects of high-dose ebselen (150 mg po twice daily) administration on oxidative stress and endothelium-dependent vasodilation. Treatment periods were in random order of 4 wk duration, with a 4-wk washout between treatments. Measures of oxidative stress included nitrotyrosine, plasma 8-isoprostanes, and the ratio of reduced to oxidized glutathione. Vascular ultrasound of the brachial artery and plethysmographic measurement of blood flow were used to assess flow-mediated and methacholine-induced endothelium-dependent vasodilation of conduit and resistance vessels, respectively. Ebselen administration did not affect parameters of oxidative stress or conduit artery or forearm arteriolar vascular function compared with placebo treatment. There was no difference in outcome by diabetes type. Ebselen, at the dose and duration evaluated, does not improve the oxidative stress profile, nor does it affect endothelium-dependent vasodilation in patients with diabetes mellitus. Copyright © 2016 the American Physiological Society.

Electroacupuncture prevents endothelial dysfunction induced by ischemia-reperfusion injury via a cyclooxygenase-2-dependent mechanism: A randomized controlled crossover trial

PubMed Central

Park, Jimin; Woo, Jong Shin; Leem, Jungtae; Park, Jun Hyeong; Lee, Sanghoon; Chung, Hyemoon; Lee, Jung Myung; Kim, Jin-Bae; Kim, Woo-Shik; Kim, Kwon Sam; Kim, Weon

2017-01-01

Objective Exploring clinically effective methods to reduce ischemia-reperfusion (IR) injury in humans is critical. Several drugs have shown protective effects, but studies using other interventions have been rare. Electroacupuncture (EA) has induced similar protection in several animal studies but no study has investigated how the effects could be translated and reproduced in humans. This study aimed to explore the potential effect and mechanisms of EA in IR-induced endothelial dysfunction in humans. Methods This is a prospective, randomized, crossover, sham-controlled trial consisting of two protocols. Protocol 1 was a crossover study to investigate the effect of EA on IR-induced endothelial dysfunction. Twenty healthy volunteers were randomly assigned to EA or sham EA (sham). Flow mediated dilation (FMD) of the brachial artery (BA), nitroglycerin-mediated endothelial independent dilation, blood pressure before and after IR were measured. In protocol 2, seven volunteers were administered COX-2 inhibitor celecoxib (200 mg orally twice daily) for five days. After consumption, volunteers underwent FMD before and after IR identical to protocol 1. Results In protocol 1, baseline BA diameter, Pre-IR BA diameter and FMD were similar between the two groups (p = NS). After IR, sham group showed significantly blunted FMD (Pre-IR: 11.41 ± 3.10%, Post-IR: 4.49 ± 2.04%, p < 0.001). However, EA protected this blunted FMD (Pre-IR: 10.96 ± 5.30%, Post-IR: 9.47 ± 5.23%, p = NS, p < 0.05 compared with sham EA after IR). In protocol 2, this protective effect was completely abolished by pre-treatment with celecoxib (Pre-IR: 11.05 ± 3.27%; Post-IR: 4.20 ± 1.68%, p = 0.001). Conclusion EA may prevent IR-induced endothelial dysfunction via a COX-2 dependent mechanism. PMID:28591155

The Effects of Aroma Foot Massage on Blood Pressure and Anxiety in Japanese Community-Dwelling Men and Women: A Crossover Randomized Controlled Trial

PubMed Central

Tomooka, Kiyohide; Ohira, Tetsuya; Ogino, Keiki; Tanigawa, Takeshi

2016-01-01

Objectives The aim of this study was to investigate the effects of aroma foot massage on blood pressure, anxiety, and health-related quality of life (QOL) in Japanese community-dwelling men and women using a crossover randomized controlled trial. Methods Fifty-seven eligible participants (5 men and 52 women) aged 27 to 72 were randomly divided into 2 intervention groups (group A: n = 29; group B: n = 28) to participate in aroma foot massages 12 times during the 4-week intervention period. Systolic and diastolic blood pressure (SBP and DBP, respectively), heart rate, state anxiety, and health-related QOL were measured at the baseline, 4-week follow-up, and 8-week follow-up. The effects of the aroma foot massage intervention on these factors and the proportion of participants with anxiety were analyzed using a linear mixed-effect model for a crossover design adjusted for participant and period effects. Furthermore, the relationship between the changes in SBP and state anxiety among participants with relieved anxiety was assessed using a linear regression model. Results Aroma foot massage significantly decreased the mean SBP (p = 0.02), DBP (p = 0.006), and state anxiety (p = 0.003) as well as the proportion of participants with anxiety (p = 0.003). Although it was not statistically significant (p = 0.088), aroma foot massage also increased the score of mental health-related QOL. The change in SBP had a significant and positive correlation with the change in state anxiety (p = 0.01) among participants with relieved anxiety. Conclusion The self-administered aroma foot massage intervention significantly decreased the mean SBP and DBP as well as the state anxiety score, and tended to increase the mental health-related QOL scores. The results suggest that aroma foot massage may be an easy and effective way to improve mental health and blood pressure. Trial Registration University Hospital Medical Information Network 000014260 PMID:27010201

The Effects of Aroma Foot Massage on Blood Pressure and Anxiety in Japanese Community-Dwelling Men and Women: A Crossover Randomized Controlled Trial.

PubMed

Eguchi, Eri; Funakubo, Narumi; Tomooka, Kiyohide; Ohira, Tetsuya; Ogino, Keiki; Tanigawa, Takeshi

2016-01-01

The aim of this study was to investigate the effects of aroma foot massage on blood pressure, anxiety, and health-related quality of life (QOL) in Japanese community-dwelling men and women using a crossover randomized controlled trial. Fifty-seven eligible participants (5 men and 52 women) aged 27 to 72 were randomly divided into 2 intervention groups (group A: n = 29; group B: n = 28) to participate in aroma foot massages 12 times during the 4-week intervention period. Systolic and diastolic blood pressure (SBP and DBP, respectively), heart rate, state anxiety, and health-related QOL were measured at the baseline, 4-week follow-up, and 8-week follow-up. The effects of the aroma foot massage intervention on these factors and the proportion of participants with anxiety were analyzed using a linear mixed-effect model for a crossover design adjusted for participant and period effects. Furthermore, the relationship between the changes in SBP and state anxiety among participants with relieved anxiety was assessed using a linear regression model. Aroma foot massage significantly decreased the mean SBP (p = 0.02), DBP (p = 0.006), and state anxiety (p = 0.003) as well as the proportion of participants with anxiety (p = 0.003). Although it was not statistically significant (p = 0.088), aroma foot massage also increased the score of mental health-related QOL. The change in SBP had a significant and positive correlation with the change in state anxiety (p = 0.01) among participants with relieved anxiety. The self-administered aroma foot massage intervention significantly decreased the mean SBP and DBP as well as the state anxiety score, and tended to increase the mental health-related QOL scores. The results suggest that aroma foot massage may be an easy and effective way to improve mental health and blood pressure. University Hospital Medical Information Network 000014260.

Randomized, Double-Blinded, Placebo-Controlled Crossover Trial of Treating Erectile Dysfunction with Sildenafil After Radiotherapy and Short-Term Androgen Deprivation Therapy: Results of RTOG 0215

PubMed Central

Bruner, Deborah Watkins; James, Jennifer L.; Bryan, Charlene J.; Pisansky, Thomas M.; Rotman, Marvin; Corbett, Thomas; Speight, Joycelyn; Byhardt, Roger; Sandler, Howard; Bentzen, Søren; Kachnic, Lisa; Berk, Lawrence

2013-01-01

Introduction Erectile dysfunction (ED) may be the most commonly observed adverse event (AE) associated with the combination of radiation therapy (RT) and androgen deprivation therapy (ADT). A significant number of men are trying phosphodiesterase type 5 inhibitors (PDE5s) such as sildenafil to treat ED, yet sildenafil studies to date shed little light on the response to ED after ADT. Aim The purpose of this trial was to evaluate sildenafil in the treatment of ED in prostate cancer patients previously treated with external beam RT and neoadjuvant and concurrent ADT. Methods In this randomized, double-blinded crossover trial, eligible patients received RT/ADT for intermediate risk prostate cancer and currently had ED as defined by the International Index of Erectile Function (IIEF). Patients were randomized to 12 weeks of sildenafil or placebo followed by 1 week of no treatment then 12 weeks of the alternative. Treatment differences were evaluated using a marginal model for binary crossover data. Main Outcome Measures The primary end point was improved erectile function, as measured by the IIEF. Results The study accrued 115 patients and 61 (55%) completed all three IIEF assessments. Sildenafil effect was significant (P = 0.009) with a difference in probabilities of erectile response of 0.17 (95% confidence interval: 0.06, 0.29), and 0.21 (0.06, 0.38) for patients receiving ≤120 days of ADT. However, as few as 21% of patients had a treatment-specific response, only improving during sildenafil but not during the placebo phase. Conclusions This is the first controlled trial to suggest a positive sildenafil response for ED treatment in patients previously treated with RT/ADT, however, only a minority of patients responded to treatment. ADT duration may be associated with response and requires further study. The overall low response rate suggests the need for study of additional or preventative strategies for ED after RT/ADT for prostate cancer. PMID:21235716

Efficacy and safety of 10-mg azilsartan compared with 8-mg candesartan cilexetil in Japanese patients with hypertension: a randomized crossover non-inferiority trial.

PubMed

Takahara, Mitsuyoshi; Shiraiwa, Toshihiko; Shindo, Megumi; Arai, Akie; Kusuda, Yuko; Katakami, Naoto; Kaneto, Hideaki; Matsuoka, Taka-Aki; Shimomura, Iichiro

2014-09-01

We investigated whether 10 mg per day of azilsartan, one-half of the normal dosage, would be non-inferior to 8 mg per day of candesartan cilexetil for controlling blood pressure in Japanese patients with hypertension. In this open-label, randomized, crossover trial, 309 hypertensive Japanese adults treated with 8-mg candesartan cilexetil were randomized into two arms and received either 10-mg azilsartan or 8-mg candesartan cilexetil in a crossover manner. The primary efficacy outcome was systolic blood pressure, and the margin of non-inferiority was set to be 2.5 mm Hg. The participants were 67±11 years old, and 180 (58%) were male. The baseline systolic and diastolic blood pressure levels were 127.1±13.2 and 69.7±11.2 mm Hg, respectively. During the study period, the difference in systolic blood pressure between the treatments with 10-mg azilsartan and 8-mg candesartan cilexetil was -1.7 mm Hg, with the two-sided 95% confidence interval (CI) ranged from -3.2 to -0.2 mm Hg. The upper boundary of the 95% CI was below the margin of 2.5 mm Hg, confirming the non-inferiority of 10-mg azilsartan to 8-mg candesartan cilexetil. The difference also reached significance (P=0.037). The corresponding difference in diastolic blood pressure was -1.4 (95% CI: -2.4 to -0.4) mm Hg (P=0.006). Treatment with 10-mg azilsartan was similar to 8-mg candesartan cilexetil in its association with rare adverse events. In conclusion, 10-mg azilsartan was non-inferior to 8-mg candesartan cilexetil for controlling systolic blood pressure in Japanese hypertensive patients already being treated with 8-mg candesartan cilexetil.

Acute changes of hip joint range of motion using selected clinical stretching procedures: A randomized crossover study.

PubMed

Hammer, Adam M; Hammer, Roger L; Lomond, Karen V; O'Connor, Paul

2017-12-01

Hip adductor flexibility and strength is an important component of athletic performance and many activities of daily living. Little research has been done on the acute effects of a single session of stretching on hip abduction range of motion (ROM). The aim of this study was to compare 3 clinical stretching procedures against passive static stretching and control on ROM and peak isometric maximal voluntary contraction (MVC). Using a randomized crossover study design, a total of 40 participants (20 male and 20 female) who had reduced hip adductor muscle length attended a familiarization session and 5 testing sessions on non-consecutive days. Following the warm-up and pre-intervention measures of ROM and MVC, participants were randomly assigned 1 of 3 clinical stretching procedures (modified lunge, multidirectional, and joint mobilization) or a static stretch or control condition. Post-intervention measures of ROM and MVC were taken immediately following completion of the assigned condition. An ANOVA using a repeated measure design with the change score was conducted. All interventions resulted in small but statistically significant (p < 0.05) increases (1.0°-1.7°) in ROM with no inter-condition differences except one. Multidirectional stretching was greater than control (p = 0.031). These data suggest that a single session of stretching has only a minimal effect on acute changes of hip abduction ROM. Although hip abduction is a frontal plane motion, to effectively increase the extensibility of the structures that limit abduction, integrating multi-planar stretches may be indicated. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

The efficacy of music therapy protocols for decreasing pain, anxiety, and muscle tension levels during burn dressing changes: a prospective randomized crossover trial.

PubMed

Tan, Xueli; Yowler, Charles J; Super, Dennis M; Fratianne, Richard B

2010-01-01

The purpose of this study was to explore the efficacy of two music therapy protocols on pain, anxiety, and muscle tension levels during dressing changes in burn patients. Twenty-nine inpatients participated in this prospective, crossover randomized controlled trial. On two consecutive days, patients were randomized to receive music therapy services either on the first or second day of the study. On control days, they received no music. On music days, patients practiced music-based imagery (MBI), a form of music-assisted relaxation with patient-specific mental imagery before and after dressing changes. Also, on music days during dressing changes, the patients engaged in music alternate engagement (MAE), which consisted of active participation in music making. The dependent variables were the patients' subjective ratings of their pain and anxiety levels and the research nurse's objective ratings of their muscle tension levels. Two sets of data were collected before, three sets during, and another two sets after dressing changes. The results showed significant decrease in pain levels before (P < .025), during (P < .05), and after (P < .025) dressing changes on days the patients received music therapy in contrast to control days. Music therapy was also associated with a decrease in anxiety and muscle tension levels during the dressing changes (P < .05) followed by a reduction in muscle tension levels after dressing changes (P < .025). Music therapy significantly decreases the acute procedural pain, anxiety, and muscle tension levels associated with daily burn care.

Patient-centered outcomes comparing digital and conventional implant impression procedures: a randomized crossover trial.

PubMed

Joda, Tim; Brägger, Urs

2016-12-01

The aim of this randomized controlled trial was to compare patient-centered outcomes during digital and conventional implant impressions. In a crossover study design, intraoral scanning (IOS) [test] as well as classical polyether impressions [control] were both performed on 20 patients for single-tooth replacement with implant-supported crowns. The sequential distribution of either starting with the test or the control procedure was randomly selected. Patients' perception and satisfaction on the level of convenience-related factors were assessed with visual analogue scale (VAS) questionnaires. In addition, clinical work time was separately recorded for test and control procedures. Statistical analyses were performed with Wilcoxon signed-rank tests and corrected for multiple testing by the method of Holm. On VAS ranging from 0 to 100, patients scored a mean convenience level of 78.6 (SD ± 14.0) in favor of IOS compared to conventional impressions with 53.6 (SD ± 15.4) [P = 0.0001]. All included patients would prefer the digital workflow if in the future they could choose between the two techniques. Secondary, IOS was significantly faster with 14.8 min (SD ± 2.2) compared to the conventional approach with 17.9 min (SD ± 1.1) [P = 0.0001]. Based on the findings of this investigation, both impression protocols worked successfully for all study participants capturing the 3D implant positions. However, the digital technique emerges as the most preferred one according to patient-centered outcomes and was more time-effective compared to conventional impressions. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Affective responses in mountain hiking—A randomized crossover trial focusing on differences between indoor and outdoor activity

PubMed Central

Einwanger, Jürgen; Hartl, Arnulf; Kopp, Martin

2017-01-01

Introduction Affective responses during physical activity (PA) are important for engagement in PA programs and for adherence to a physically active lifestyle. Little is known about the affective responses to PA bouts lasting longer than 45 minutes. Therefore, the aims of the present study were to analyse acute effects on affective responses of a three-hour outdoor PA intervention (mountain hiking) compared to a sedentary control situation and to an indoor treadmill condition. Methods Using a randomized crossover design, 42 healthy participants were randomly exposed to three different conditions: outdoor mountain hiking, indoor treadmill walking, and sedentary control situation (approximately three hours each). Measures included the Feeling Scale, Felt Arousal Scale and a Mood Survey Scale. Repeated measures ANOVAs were used to analyse differences between the conditions. Results Compared to the control situation, the participants showed a significant increase in affective valence (d = 1.21, p < .001), activation (d = 0.81, p = .004), elation (d = 1.07, p < .001), and calmness (d = 0.84, p = .004), and a significant decrease in fatigue (d = -1.19, p < .001) and anxiety (d = -.79, p < .001) after mountain hiking. Outdoor mountain hiking showed significantly greater positive effects on affective valence, activation, and fatigue compared to indoor treadmill walking. Discussion The results indicate that a three-hour PA intervention (mountain hiking) elicits higher positive and lower negative affective responses compared to a sedentary control situation and to an indoor PA condition. Outdoor mountain hiking can be recommended by health professionals as a form of PA with the potential to positively influence affective responses. Trial registration ClinicalTrials.gov NCT02853760. https://clinicaltrials.gov/. Date of registration: 08/02/2016 (retrospectively registered). Date of enrolment of the first participant to the trial: 05/01/2014. PMID:28520774

Randomized Trial of Hypnosis as a Pain and Symptom Management Strategy in Adults with Sickle Cell Disease

PubMed Central

Wallen, Gwenyth R; Middleton, Kimberly R; Ames, Nancy; Brooks, Alyssa T; Handel, Daniel

2014-01-01

Sickle cell disease (SCD) is the most common genetic disease in African-Americans, characterized by recurrent painful vaso-occlusive crises. Medical therapies for controlling or preventing crises are limited because of efficacy and/or toxicity. This is a randomized, controlled, single-crossover protocol of hypnosis for managing pain in SCD patients. Participants receive hypnosis from a trained hypnosis therapist followed by six weeks of self-hypnosis using digital media. Those in the control arm receive SCD education followed by a six-week waiting period before crossing over to the hypnosis arm of the study. Outcome measures include assessments of pain (frequency, intensity and quality), anxiety, coping strategies, sleep, depression, and health care utilization. To date, there are no published randomized, controlled trials evaluating the efficacy of hypnosis on SCD pain modulation in adults. Self-hypnosis for pain management may be helpful in modulating chronic pain, improving sleep quality, and decreasing use of narcotics in patients with SCD. TRIAL REGISTRATION ClinicalTrials.gov: NCT00393250 PMID:25520557

A Randomized Crossover Trial of Dietary Sodium Restriction in Stage 3–4 CKD

PubMed Central

Padilla, Robin L.; Gillespie, Brenda W.; Heung, Michael; Hummel, Scott L.; Derebail, Vimal Kumar; Pitt, Bertram; Levin, Nathan W.; Zhu, Fansan; Abbas, Samer R.; Liu, Li; Kotanko, Peter; Klemmer, Philip

2017-01-01

Background and objectives Patients with chronic kidney disease (CKD) are often volume expanded and hypertensive. Few controlled studies have assessed the effects of a sodium-restricted diet (SRD) in CKD. Design, setting, participants, & measurements We conducted a randomized crossover trial to evaluate the effect of SRD (target <2 g sodium per day) versus usual diet on hydration status (by bioelectrical impedance spectroscopy) and blood pressure (BP) between May of 2009 and May of 2013. A total of 58 adults with stage 3–4 CKD were enrolled from two academic sites: University of Michigan (n=37) and University of North Carolina at Chapel Hill (n=21); 60% were men, 43% were diabetic, 93% were hypertensive, and mean age was 61 years. Participants followed SRD or usual diet for 4 weeks, followed by a 2-week washout period and a 4-week crossover phase. During the SRD, dieticians provided counseling every 2 weeks, using motivational interviewing techniques. Results Whole-body extracellular volume and calf intracellular volume decreased by 1.02 L (95% confidence interval [95% CI], −1.48 to −0.56; P<0.001) and −0.06 L (95% CI, −0.12 to −0.01; P=0.02), respectively, implying decreased fluid content on the SRD compared with usual diet. Significant reductions in urinary sodium (−57.3 mEq/24 h; 95% CI, −81.8 to −32.9), weight (−2.3 kg; 95% CI, −3.2 to −1.5), and 24-hour systolic BP (−10.8 mmHg; 95% CI, −17.0 to −4.6) were also observed (all P<0.01). Albumin-to-creatinine ratio did not change significantly and mean serum creatinine increased slightly (0.1 mg/dl; 95% CI, −0.01 to 0.2; P=0.06). No period or carryover effects were observed. Results were similar when analyzed from phase 1 only before crossover, although P values were modestly larger because of the loss of power. Conclusions In this randomized crossover trial, implementation of SRD in patients with CKD stage 3–4 resulted in clinically and statistically significant improvement in BP and hydration status. This simple dietary intervention merits a larger trial in CKD to evaluate effects on major clinical outcomes. PMID:28209636

Cranberry (poly)phenol metabolites correlate with improvements in vascular function: A double-blind, randomized, controlled, dose-response, crossover study.

PubMed

Rodriguez-Mateos, Ana; Feliciano, Rodrigo P; Boeres, Albert; Weber, Timon; Dos Santos, Claudia Nunes; Ventura, M Rita; Heiss, Christian

2016-10-01

Cranberries are rich in potentially bioactive (poly)phenols. The aim of this paper was to investigate whether cranberry juice intake can improve vascular function in healthy men in a dose- and time-dependent manner, and to understand which of the circulating (poly)phenol metabolites correlate with vascular effects. A double-blind randomized controlled crossover trial was conducted in ten healthy males. Flow-mediated dilation (FMD), blood pressure, pulse wave velocity and augmentation index were investigated at baseline, 1, 2, 4, 6, and 8 h post-consumption of cranberry juices containing 409, 787, 1238, 1534, and 1910 mg of total cranberry (poly)phenols (TP), and a control drink. Plasma (poly)phenol metabolites were analyzed by UPLC-Q-TOF MS using authentic standards. We observed dose-dependent increases in FMD at 1, 2, 4, 6, and 8 h with a peak at 4 h and maximal effects with juice containing 1238 mg TP. A total of 60 metabolites were quantified in plasma after cranberry consumption. Twelve (poly)phenol metabolites significantly correlated with the increases in FMD, including ferulic and caffeic acid sulfates, quercetin-3-O-ß-D-glucuronide and a γ-valerolactone sulfate. (Poly)phenols in cranberry juice can improve vascular function in healthy males and this is linked to the presence of specific newly identified plasma metabolites. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of Pregabalin on Cardiovascular Responses to Exercise and Postexercise Pain and Fatigue in Fibromyalgia: A Randomized, Double-Blind, Crossover Pilot Study

PubMed Central

White, Andrea T.; Light, Kathleen C.; Bateman, Lucinda; Hughen, Ronald W.; Vanhaitsma, Timothy A.; Light, Alan R.

2015-01-01

Pregabalin, an approved treatment for fibromyalgia (FM), has been shown to decrease sympathetic nervous system (SNS) activity and inhibit sympathetically maintained pain, but its effects on exercise responses have not been reported. Methods. Using a randomized double-blind crossover design, we assessed the effect of 5 weeks of pregabalin (versus placebo) on acute cardiovascular and subjective responses to moderate exercise in 19 FM patients. Blood pressure (BP), heart rate (HR), and ratings of perceived exertion (RPE) during exercise and ratings of pain, physical fatigue, and mental fatigue before, during, and for 48 hours after exercise were compared in patients on pregabalin versus placebo and also versus 18 healthy controls. Results. On placebo, exercise RPE and BP were significantly higher in FM patients than controls (p < 0.04). Pregabalin responders (n = 12, defined by patient satisfaction and symptom changes) had significantly lower exercise BP, HR, and RPE on pregabalin versus placebo (p < 0.03) and no longer differed from controls (p > 0.26). Cardiovascular responses of nonresponders (n = 7) were not altered by pregabalin. In responders, pregabalin improved ratings of fatigue and pain (p < 0.04), but negative effects on pain and fatigue were seen in nonresponders. Conclusions. These preliminary findings suggest that pregabalin may normalize cardiovascular and subjective responses to exercise in many FM patients. PMID:27026828

A randomized, controlled cross-over trial of dermally-applied lavender (Lavandula angustifolia) oil as a treatment of agitated behaviour in dementia

PubMed Central

2013-01-01

Background Lavender essential oil shows evidence of sedative properties in neurophysiological and animal studies but clinical trials of its effectiveness as a treatment of agitation in people with dementia have shown mixed results. Study methods have varied widely, however, making comparisons hazardous. To help remedy previous methodological shortcomings, we delivered high grade lavender oil in specified amounts to nursing home residents whose agitated behaviours were recorded objectively. Methods 64 nursing home residents with frequent physically agitated behaviours were entered into a randomized, single-blind cross-over trial of dermally-applied, neurophysiologically active, high purity 30% lavender oil versus an inactive control oil. A blinded observer counted the presence or absence of target behaviours and rated participants’ predominant affect during each minute for 30 minutes prior to exposure and for 60 minutes afterwards. Results Lavender oil did not prove superior to the control oil in reducing the frequency of physically agitated behaviours or in improving participants’ affect. Conclusions Studies of essential oils are constrained by their variable formulations and uncertain pharmacokinetics and so optimal dosing and delivery regimens remain speculative. Notwithstanding this, topically delivered, high strength, pure lavender oil had no discernible effect on affect and behaviour in a well-defined clinical sample. Trial registration Australian and New Zealand Clinical Trials Registry (ACTRN 12609000569202) PMID:24219098

Randomized Crossover Comparison of Personalized MPC and PID Control Algorithms for the Artificial Pancreas

PubMed Central

Pinsker, Jordan E.; Lee, Joon Bok; Dassau, Eyal; Seborg, Dale E.; Bradley, Paige K.; Gondhalekar, Ravi; Bevier, Wendy C.; Huyett, Lauren; Zisser, Howard C.; Doyle, Francis J.

2016-01-01

OBJECTIVE To evaluate two widely used control algorithms for an artificial pancreas (AP) under nonideal but comparable clinical conditions. RESEARCH DESIGN AND METHODS After a pilot safety and feasibility study (n = 10), closed-loop control (CLC) was evaluated in a randomized, crossover trial of 20 additional adults with type 1 diabetes. Personalized model predictive control (MPC) and proportional integral derivative (PID) algorithms were compared in supervised 27.5-h CLC sessions. Challenges included overnight control after a 65-g dinner, response to a 50-g breakfast, and response to an unannounced 65-g lunch. Boluses of announced dinner and breakfast meals were given at mealtime. The primary outcome was time in glucose range 70–180 mg/dL. RESULTS Mean time in range 70–180 mg/dL was greater for MPC than for PID (74.4 vs. 63.7%, P = 0.020). Mean glucose was also lower for MPC than PID during the entire trial duration (138 vs. 160 mg/dL, P = 0.012) and 5 h after the unannounced 65-g meal (181 vs. 220 mg/dL, P = 0.019). There was no significant difference in time with glucose <70 mg/dL throughout the trial period. CONCLUSIONS This first comprehensive study to compare MPC and PID control for the AP indicates that MPC performed particularly well, achieving nearly 75% time in the target range, including the unannounced meal. Although both forms of CLC provided safe and effective glucose management, MPC performed as well or better than PID in all metrics. PMID:27289127

Efficacy of homeopathically potentized antimony on blood coagulation. A randomized placebo controlled crossover trial.

PubMed

Heusser, Peter; Berger, Sarah; Stutz, Monika; Hüsler, André; Haeberli, André; Wolf, Ursula

2009-02-01

Homeopathically potentized antimony 6x is traditionally used in anthroposophic medicine for an alleged pro-coagulatory effect in bleeding disorders. However, the scientific evidence base is yet insufficient. Results of a previous in vitro study suggested a slight increase of maximal clot firmness (MCF) and a tendency towards a shorter clotting time (CT). The objective of this study was to investigate the pro-coagulatory effects of antimony in vivo, and possible unexpected or adverse events. A randomized placebo controlled double blind crossover study was carried out in 30 healthy volunteers (15 males, 15 females). Each participant received intravenously 10 ml of antimony 6x and placebo in a randomized order at an interval of 1 month. Thrombelastography (TEG) was carried out immediately before and 30 and 60 min after the injection. Statistically significant pro-coagulatory effects were observed 30 min after injection for CT in men (p = 0.0306), and for MCF in men and women combined (p = 0.0476). The effect of antimony was significantly larger on test day 1 than on test day 2, whereas the effect of placebo was similar on both test days. No unexpected adverse or adverse events causally related to antimony were observed. This study adds evidence to the hypothesis that homeopathically potentized antimony may be efficacious in vivo. The consistency of the results with previous in vitro results indicates an effect on MCF and CT. The in vivo application of antimony 6x is safe. Copyright (c) 2009 S. Karger AG, Basel.

Distractive Auditory Stimuli in the Form of Music in Individuals With COPD: A Systematic Review.

PubMed

Lee, Annemarie L; Desveaux, Laura; Goldstein, Roger S; Brooks, Dina

2015-08-01

Music has been used as a distractive auditory stimulus (DAS) in patients with COPD, but its effects are unclear. This systematic review aimed to establish the effect of DAS on exercise capacity, symptoms, and health-related quality of life (HRQOL) under three conditions: (1) during exercise training, (2) during exercise testing, and (3) for symptom management at rest. Randomized controlled or crossover trials as well as cohort studies of DAS during exercise training, during formal exercise testing, and for symptom management among individuals with COPD were identified from a search of seven databases. Two reviewers independently assessed study quality. Weighted mean differences (WMDs) with 95% CIs were calculated using a random-effects model. Thirteen studies (12 of which were randomized controlled or crossover trials) in 415 participants were included. DAS increased exercise capacity when applied over at least 2 months of exercise training (WMD, 98 m; 95% CI, 47-150 m). HRQOL improved only after a training duration of 3 months. Less dyspnea was noted with DAS during exercise training, but this was not consistently observed in short-term exercise testing or as a symptom management strategy at rest. DAS appears to reduce symptoms of dyspnea and fatigue when used during exercise training, with benefits observed in exercise capacity and HRQOL. When applied during exercise testing, the effects on exercise capacity and symptoms and as a strategy for symptom management at rest are inconsistent.

Metformin vs myoinositol: which is better in obese polycystic ovary syndrome patients? A randomized controlled crossover study.

PubMed

Tagliaferri, Valeria; Romualdi, Daniela; Immediata, Valentina; De Cicco, Simona; Di Florio, Christian; Lanzone, Antonio; Guido, Maurizio

2017-05-01

Due to the central role of metabolic abnormalities in the pathophysiology of polycystic ovary syndrome (PCOS), insulin sensitizing agents have been proposed as a feasible treatment option. To investigate which is the more effective between metformin and myoinositol (MYO) on hormonal, clinical and metabolic parameters in obese patients with PCOS. Crossover randomized controlled study. Thirty-four PCOS obese women (age: 25·62 ± 4·7 years; BMI: 32·55 ± 5·67 kg/m 2 ) were randomized to receive metformin (850 mg twice a day) or MYO (1000 mg twice a day) for 6 months. After a 3 month washout, the same subjects received the other compound for the following 6 months. Ultrasonographic pelvic examinations, hirsutism score, anthropometric and menstrual pattern evaluation, hormonal profile assays, oral glucose tolerance test (OGTT) and lipid profile at baseline and after 6 months of treatment were performed. Both metformin and MYO significantly reduced the insulin response to OGTT and improved insulin sensitivity. Metformin significantly decreased body weight and improved menstrual pattern and Ferriman-Gallwey score. Metformin treatment was also associated with a significant decrease in LH and oestradiol levels, androgens and anti-müllerian hormone levels. None of these clinical and hormonal changes were observed during MYO administration. Both treatments improved the glyco-insulinaemic features of obese PCOS patients, but only metformin seems to exert a beneficial effect on the endocrine and clinical features of the syndrome. © 2017 John Wiley & Sons Ltd.

Feasibility and preliminary efficacy of the effects of flavanoid-rich purple grape juice on the vascular health of childhood cancer survivors: a randomized, controlled crossover trial.

PubMed

Blair, Cindy K; Kelly, Aaron S; Steinberger, Julia; Eberly, Lynn E; Napurski, Char; Robien, Kim; Neglia, Joseph P; Mulrooney, Daniel A; Ross, Julie A

2014-12-01

Childhood cancer survivors have an increased risk of developing cardiovascular disease following treatment, yet few interventions have been evaluated to reduce this risk. Purple grape juice (pGJ), a rich source of flavonoids with antioxidant properties, has been shown in adults to reduce oxidative stress and improve endothelial function. We examined the effects of supplementing meals with pGJ on microvascular endothelial function and markers of oxidative stress and inflammation in 24 cancer survivors (ages 10-21 years). In a randomized controlled crossover trial consisting of two, 4 week intervention periods, each preceded by a 4 week washout period, subjects received in random order 6 ounces twice daily of pGJ and clear apple juice (cAJ; similar in calories but lower in flavonoids). Measurements were obtained before and after each supplementation period; change was evaluated using mixed effects ANOVA. pGJ did not improve endothelial function, measured using digital reactive hyperemia, compared with cAJ (mean change: pGJ 0.06, cAJ 0.22; difference of mean change [95% CI]: -0.16 [-0.42 - 0.11], P = 0.25). No significant changes in plasma concentrations of oxidized-LDL, myeloperoxidase, or high sensitivity C-reactive protein were observed. After 4 weeks of daily consumption of flavonoid-rich pGJ, no measurable change in vascular function was observed in these childhood cancer survivors. © 2014 Wiley Periodicals, Inc.

Randomized Crossover Study of the Natural Restorative Environment Intervention to Improve Attention and Mood in Heart Failure.

PubMed

Jung, Miyeon; Jonides, John; Northouse, Laurel; Berman, Marc G; Koelling, Todd M; Pressler, Susan J

In heart failure (HF), attention may be decreased because of lowered cerebral blood flow and increased attentional demands needed for self-care. Guided by the Attention Restoration Theory, the objective was to test the efficacy of the natural restorative environment (NRE) intervention on improving attention and mood among HF patients and healthy adults. A randomized crossover pilot study was conducted among 20 HF patients and an age- and education-matched comparison group of 20 healthy adults to test the efficacy of the NRE intervention compared with an active control intervention. Neuropsychological tests were administered to examine attention, particularly attention span, sustained attention, directed attention, and attention switching, at before and after the intervention. Mood was measured with the Positive and Negative Affect Schedule. No significant differences were found in attention and mood after the NRE intervention compared with the control intervention among the HF patients and the healthy adults. In analyses with HF patients and healthy adults combined (n = 40), significant differences were found. Compared with the control intervention, sustained attention improved after the NRE intervention (P = .001) regardless of the presence of HF. Compared with the healthy adults, HF patients performed significantly worse on attention switching after the control intervention (P = .045). The NRE intervention may be efficacious in improving sustained attention in HF patients. Future studies are needed to enhance the NRE intervention to be more efficacious and tailored for HF patients and test the efficacy in a larger sample of HF patients.

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

PubMed

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

2008-01-01

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

A randomized, double-blind, crossover, placebo-controlled comparative clinical trial of arginine aspartate plus adenosine monophosphate for the intermittent treatment of male erectile dysfunction.

PubMed

Neuzillet, Y; Hupertan, V; Cour, F; Botto, H; Lebret, T

2013-03-01

Efficacy and safety of l-arginine aspartate 8 g combined with 200 mg of adenosine monophosphate (AA) with placebo (PL) alone for intermittent treatment of mild-to-moderate erectile dysfunction (ED) were compared. The study design was a double-blind, PL-controlled, two-way crossover randomized clinical trial with 26 patients. Efficacy was assessed by International Index of Erectile Function (IIEF) and two additional validated questionnaires [the Erection Hardness Score (EHS) and the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS). During each crossover period, separated by a 2-week wash-out period, drugs were administered orally, 1-2 h before sexual intercourse. Primary endpoint was a change in the IIEF. Secondary endpoints were patient and investigator assessments of treatment success. Investigators' and patients' assessment of efficacy was significantly improved by the combination vs. PL (p = 0.01 and p = 0.04 respectively]. EHS and EDITS questionnaires were both improved by the combination (p = 0.015 and p = 0.017 respectively). There was no significant difference in terms of tolerance between AA and PL or severe adverse events. ED patients demonstrated significant improvements in all IIEF domains with the exception of the Sexual Desire and Orgasmic Domains when treated with AA compared with PL. This pilot phase II study showed that the on-demand oral administration at a high dosage of l-arginine aspartate-adenosine monophosphate combination may be effective in patients with mild-to-moderate ED, is very well tolerated and could be tested as a safe first-line therapy in a larger size phase III study. © 2012 American Society of Andrology and European Academy of Andrology.

Mud-bath therapy and oral glucosamine sulfate in patients with knee osteoarthritis: a randomized, controlled, crossover study.

PubMed

Peluso, Rosario; Caso, Francesco; Costa, Luisa; Sorbo, Dario; Carraturo, Nello; Di Minno, Matteo Nicola Dario; Carraturo, Federica; Oriente, Alfonso; Balestrieri, Umberto; Minicucci, Annamaria; Del Puente, Antonio; Scarpa, Raffaele

2016-01-01

To evaluate the efficacy and safety of combined treatment of mud-bath therapy and glucosamine crystalline sulfate (GlcN-S) in patients with knee osteoarthritis (OA). This study was a randomised, controlled, crossover investigation. Patients were randomly assigned (1:1) by the investigators to two groups, named group 1 and 2. Group 1 included twenty-three patients receiving oral GlcN-S treatment from the beginning of the study (T0) to the end of the 3rd month of treatment (T3) and a combined treatment of both mud-bath therapy and GlcN-S from T3 to the end of the study at six months (T6). Group 2 included twenty-two patients receiving a combined treatment of both mud-bath therapy and GlcN-S from T0 to T3 and that discontinued mud-bath therapy, receiving GlcN-S treatment alone, from T3 to T6. Primary endpoints of the study consisted of evaluating OA severity and activity at baseline and at follow-up visits. All 45 patients, eligible for the study, completed the period of the crossover. In group 1, no significant difference was shown in the comparison from T0 to T3, while from T3 to T6 most variables were significantly improved. In group 2, instead, the comparison between T0 and T3 showed a significant difference in different parameters. When comparing T3 and T6, despite an improvement of all the variables, no significant difference was shown. The association of GlcN-S and mud-bath therapy has a positive and safe role in improving pain, function and quality of life in knee OA patients.

Pomegranate juice, but not an extract, confers a lower glycemic response on a high-glycemic index food: randomized, crossover, controlled trials in healthy subjects.

PubMed

Kerimi, Asimina; Nyambe-Silavwe, Hilda; Gauer, Julia S; Tomás-Barberán, Francisco A; Williamson, Gary

2017-12-01

Background: Low-glycemic index diets have demonstrated health benefits associated with a reduced risk of developing type 2 diabetes. Objectives: We tested whether pomegranate polyphenols could lower the glycemic response of a high-glycemic index food when consumed together and the mechanism by which this might occur. Design: We compared the acute effect of a pomegranate juice and a polyphenol-rich extract from pomegranate (supplement) on the bread-derived postprandial blood glucose concentration in 2 randomized, crossover, controlled studies (double-blinded for the supplements), each on 16 healthy volunteers. An additional randomized, crossover, controlled study on 16 volunteers consuming constituent fruit acids in a pH-balanced solution (same pH as pomegranate) and bread was conducted to determine any contributions to postprandial responses caused by acidic beverages. Results: As primary outcome, the incremental area under the curve for bread-derived blood glucose (-33.1% ± 18.1%, P = 0.000005) and peak blood glucose (25.4% ± 19.3%, P = 0.0004) were attenuated by pomegranate juice, compared with a control solution containing the equivalent amount of sugars. In contrast, the pomegranate supplement, or a solution containing the malic and citric acid components of the juice, was ineffective. The pomegranate polyphenol punicalagin was a very effective inhibitor of human α-amylase in vitro, comparable to the drug acarbose. Neither the pomegranate extract nor the individual component polyphenols inhibited 14 C-D-glucose transport across differentiated Caco-2/TC7 cell monolayers, but they inhibited uptake of 14 C-glucose into Xenopus oocytes expressing the human glucose transporter type 2. Further, some of the predicted pomegranate gut microbiota metabolites modulated 14 C-D-glucose and 14 C-deoxy-D-glucose uptake into hepatic HepG2 cells. Conclusions: These data indicate that pomegranate polyphenols, when present in a beverage but not in a supplement, can reduce the postprandial glycemic response of bread, whereas microbial metabolites from pomegranate polyphenols exhibit the potential to further modulate sugar metabolism much later in the postprandial period. This trial was registered at clinicaltrials.gov as NCT02486978, NCT02624609, and NCT03242876. © 2017 American Society for Nutrition.

Crossover between the Gaussian orthogonal ensemble, the Gaussian unitary ensemble, and Poissonian statistics.

PubMed

Schweiner, Frank; Laturner, Jeanine; Main, Jörg; Wunner, Günter

2017-11-01

Until now only for specific crossovers between Poissonian statistics (P), the statistics of a Gaussian orthogonal ensemble (GOE), or the statistics of a Gaussian unitary ensemble (GUE) have analytical formulas for the level spacing distribution function been derived within random matrix theory. We investigate arbitrary crossovers in the triangle between all three statistics. To this aim we propose an according formula for the level spacing distribution function depending on two parameters. Comparing the behavior of our formula for the special cases of P→GUE, P→GOE, and GOE→GUE with the results from random matrix theory, we prove that these crossovers are described reasonably. Recent investigations by F. Schweiner et al. [Phys. Rev. E 95, 062205 (2017)2470-004510.1103/PhysRevE.95.062205] have shown that the Hamiltonian of magnetoexcitons in cubic semiconductors can exhibit all three statistics in dependence on the system parameters. Evaluating the numerical results for magnetoexcitons in dependence on the excitation energy and on a parameter connected with the cubic valence band structure and comparing the results with the formula proposed allows us to distinguish between regular and chaotic behavior as well as between existent or broken antiunitary symmetries. Increasing one of the two parameters, transitions between different crossovers, e.g., from the P→GOE to the P→GUE crossover, are observed and discussed.

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

ERIC Educational Resources Information Center

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

2014-01-01

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

Sensory Adapted Dental Environments to Enhance Oral Care for Children with Autism Spectrum Disorders: A Randomized Controlled Pilot Study

ERIC Educational Resources Information Center

Cermak, Sharon A.; Stein Duker, Leah I.; Williams, Marian E.; Dawson, Michael E.; Lane, Christianne J.; Polido, José C.

2015-01-01

This pilot and feasibility study examined the impact of a sensory adapted dental environment (SADE) to reduce distress, sensory discomfort, and perception of pain during oral prophylaxis for children with autism spectrum disorder (ASD). Participants were 44 children ages 6-12 (n = 22 typical, n = 22 ASD). In an experimental crossover design, each…

In Vitro and in vivo antioxidant and anti-inflammatory capacities of an antioxidant-rich fruit and berry juice blend. Results of a pilot and randomized, double-blinded, placebo-controlled, crossover study

USDA-ARS?s Scientific Manuscript database

This study investigated the in vitro and in vivo antioxidant and anti-inflammatory properties of a juice blend (JB), MonaVie Active, containing a mixture of fruits and berries with known antioxidant activity, including acai, a palm fruit, as the predominant ingredient. The phytochemical antioxidants...

Phenol-enriched olive oils improve HDL antioxidant content in hypercholesterolemic subjects. A randomized, double-blind, cross-over, controlled trial.

PubMed

Farràs, Marta; Fernández-Castillejo, Sara; Rubió, Laura; Arranz, Sara; Catalán, Úrsula; Subirana, Isaac; Romero, Mari-Paz; Castañer, Olga; Pedret, Anna; Blanchart, Gemma; Muñoz-Aguayo, Daniel; Schröder, Helmut; Covas, Maria-Isabel; de la Torre, Rafael; Motilva, Maria-José; Solà, Rosa; Fitó, Montserrat

2018-01-01

At present, high-density lipoprotein (HDL) function is thought to be more relevant than HDL cholesterol quantity. Consumption of olive oil phenolic compounds (PCs) has beneficial effects on HDL-related markers. Enriched food with complementary antioxidants could be a suitable option to obtain additional protective effects. Our aim was to ascertain whether virgin olive oils (VOOs) enriched with (a) their own PC (FVOO) and (b) their own PC plus complementary ones from thyme (FVOOT) could improve HDL status and function. Thirty-three hypercholesterolemic individuals ingested (25 ml/day, 3 weeks) (a) VOO (80 ppm), (b) FVOO (500 ppm) and (c) FVOOT (500 ppm) in a randomized, double-blind, controlled, crossover trial. A rise in HDL antioxidant compounds was observed after both functional olive oil interventions. Nevertheless, α-tocopherol, the main HDL antioxidant, was only augmented after FVOOT versus its baseline. In conclusion, long-term consumption of phenol-enriched olive oils induced a better HDL antioxidant content, the complementary phenol-enriched olive oil being the one which increased the main HDL antioxidant, α-tocopherol. Complementary phenol-enriched olive oil could be a useful dietary tool for improving HDL richness in antioxidants. Copyright © 2017. Published by Elsevier Inc.

A Randomized Crossover Trial on Acute Stress-Related Physiological Responses to Mountain Hiking

PubMed Central

Grafetstätter, Carina; Hartl, Arnulf; Kopp, Martin

2017-01-01

Green exercise, defined as physical activity in natural environments, might have positive effects on stress-related physiological measures. Little is known about the acute effects of green exercise bouts lasting longer than 60 min. Therefore, the aim of the present study was to analyze the acute effects of a three-hour green exercise intervention (mountain hiking) on stress-related physiological responses. Using a randomized crossover design, 42 healthy participants were exposed to three different conditions in a field-based experiment: outdoor mountain hiking, indoor treadmill walking, and sedentary control condition (three hours each). At baseline and at follow-up (five minutes after the condition), stress-related physiological responses (salivary cortisol, blood pressure, and heart rate variability) were measured. Salivary cortisol decreased in all conditions, but showed a larger decrease after both mountain hiking and treadmill walking compared to the sedentary control situation (partial η2 = 0.10). No differences were found between mountain hiking and treadmill walking in salivary cortisol. In heart rate variability and blood pressure, changes from baseline to follow-up did not significantly differ between the three conditions. The results indicate that three hours of hiking indoors or outdoors elicits positive effects on salivary cortisol concentration. Environmental effects seem to play a minor role in salivary cortisol, blood pressure, and heart rate variability. PMID:28800067

Effect of Persian Medicine Remedy on Chemotherapy Induced Nausea and Vomiting in Breast Cancer: A Double Blind, Randomized, Crossover Clinical Trial

PubMed Central

Nazari, Mohammad; Taghizadeh, Ali; Bazzaz, Mojtaba Mousavi; Rakhshandeh, Hassan; Shokri, Sadegh

2017-01-01

Background Chemotherapy induced nausea and vomiting (CINV) is a side effect, and has negative effect on quality of life and continuation of chemotherapy. Despite new regimen and drugs, the problems still remain and standard guidelines, effective treatment and supportive care for refractory CINV are still not yet established. Persian medicine, the old Iranian medical school, offer Persumac (prepared from Rhus Coriaria and Bunium Persicum Boiss). Objective The specific objectives were to assess the effect of Persumac on the number and severity of nausea and vomiting in refractory CINV in acute and delayed phase. Methods This randomized, double blind, crossover clinical trial study was carried out on 93 patients with breast cancer and refractory CINV, who received outpatient high emetogenic chemotherapy in Imam Reza hospital, Mashhad, Iran from October 2015 to May 2016. The study has three stages: in stage I patients received a questionaire and completed it after chemotherapy. In stage II they were randomly divided into intervention group with Persumac and control group with placebo (lactose were used). In stage III, wash out and crossover was conducted. Both groups in all stages received standard antiemetic therapy for CINV. The following were set as the inclusion criteria of the study: female, Age ≥18 years, clinical diagnosis of breast cancer, history of refractory CINV, normal blood tests and at least three courses of chemotherapy remaining. Exclusion criteria of this study were: Total or upper abdominal radiation therapy along with chemotherapy, drugs/therapy for nausea and vomiting not prescribed in this study, hypersensitivity to Sumac or Bunium Persicum, use of sumac and Bunium Persicum in seven days prior to the intervention, clinical diagnosis of digestion disorders, non-chemotherapy induced nausea and vomiting, milk allergy, loss of two consecutive or three intermittent doses of Persumac or placebo. Outcomes were gathered by Persian questionnaire. Number and severity of nausea and vomiting was measured with a self-reporting tool; visual analog scale. Results Demographic data and other characters in both groups have no significant diffrence. Eighty of 93 eligible patients in stage I completed the study and in stage II, eleven declined participation for stage III (crossover). P value of carry over, period and treatment effects demonstrated that they had not affected the results before and after crossover. The mean severity of nausea in acute phase was in stage I: 4.83 ± 1.40, stage II: 4.54 ± 2.0 and stage III: 4.15 ± 0.92 in sequence AB (first Persumac and then placebo in crossover), and in sequence BA (first placebo and then Persumac in crossover) was respectively 4.83 ± 1.40, 4.54 ± 2.0, 4.15 ± 0.92 with p value of carry over effect: 0.03 and period effect: 0.22. Except for severity of nausea in acute phase, the mean number and severity of nausea and vomiting scores significantly decreased in acute and delayed phase of CINV. Conclusion Persumac may control the refractory CINV. The implicable and clinical importance of this research is that another option exists for refractory CINV. Higher doses, different cancers, patients with more various features, and more complete methodology and tools can provide appropriate designs for new research on this topic. Trial registration This trial was registered at the Clinical Trials.gov ID: NCT02787707. Funding This study is part of a Ph.D. thesis and under grant; No: 930735 of Research Chancellery of MUMS. PMID:28243404

Efficacy and safety of creatine supplementation in juvenile dermatomyositis: A randomized, double-blind, placebo-controlled crossover trial.

PubMed

Solis, Marina Yazigi; Hayashi, Ana Paula; Artioli, Guilherme Giannini; Roschel, Hamilton; Sapienza, Marcelo Tatit; Otaduy, Maria Concepción; De Sã Pinto, Ana Lucia; Silva, Clovis Artur; Sallum, Adriana Maluf Elias; Pereira, Rosa Maria R; Gualano, Bruno

2016-01-01

It has been suggested that creatine supplementation is safe and effective for treating idiopathic inflammatory myopathies, but no pediatric study has been conducted to date. The objective of this study was to examine the efficacy and safety of creatine supplementation in juvenile dermatomyositis (JDM) patients. In this study, JDM patients received placebo or creatine supplementation (0.1 g/kg/day) in a randomized, crossover, double-blind design. Subjects were assessed at baseline and after 12 weeks. The primary outcome was muscle function. Secondary outcomes included body composition, aerobic conditioning, health-related quality of life, and muscle phosphocreatine (PCr) content. Safety was assessed by laboratory parameters and kidney function measurements. Creatine supplementation did not affect muscle function, intramuscular PCr content, or any other secondary outcome. Kidney function was not affected, and no side effects were reported. Twelve weeks of creatine supplementation in JDM patients were well-tolerated and free of adverse effects, but treatment did not affect muscle function, intramuscular PCr, or any other parameter. © 2015 Wiley Periodicals, Inc.

The effect of oxytocin nasal spray on social interaction deficits observed in young children with autism: a randomized clinical crossover trial.

PubMed

Yatawara, C J; Einfeld, S L; Hickie, I B; Davenport, T A; Guastella, A J

2016-09-01

Interventions for autism are limited. The synthetic hormone oxytocin may provide a potential treatment to improve core social and behavioral difficulties in autism, but its efficacy has yet to be evaluated in young children who potentially may benefit to a greater extent. We investigated the efficacy, tolerability and safety of oxytocin treatment in young children with autism using a double-blind, randomized, placebo-controlled, crossover, clinical trial. Thirty-one children with autism received 12 International Units (IU) of oxytocin and placebo nasal spray morning and night (24 IU per day) for 5 weeks, with a 4-week washout period between each treatment. Compared with placebo, oxytocin led to significant improvements on the primary outcome of caregiver-rated social responsiveness. Overall, nasal spray was well tolerated, and the most common reported adverse events were thirst, urination and constipation. This study is the first clinical trial to support the potential of oxytocin as an early intervention for young children with autism to help improve social interaction deficits.

The effect of oxytocin nasal spray on social interaction deficits observed in young children with autism: a randomized clinical crossover trial

PubMed Central

Yatawara, C J; Einfeld, S L; Hickie, I B; Davenport, T A; Guastella, A J

2016-01-01

Interventions for autism are limited. The synthetic hormone oxytocin may provide a potential treatment to improve core social and behavioral difficulties in autism, but its efficacy has yet to be evaluated in young children who potentially may benefit to a greater extent. We investigated the efficacy, tolerability and safety of oxytocin treatment in young children with autism using a double-blind, randomized, placebo-controlled, crossover, clinical trial. Thirty-one children with autism received 12 International Units (IU) of oxytocin and placebo nasal spray morning and night (24 IU per day) for 5 weeks, with a 4-week washout period between each treatment. Compared with placebo, oxytocin led to significant improvements on the primary outcome of caregiver-rated social responsiveness. Overall, nasal spray was well tolerated, and the most common reported adverse events were thirst, urination and constipation. This study is the first clinical trial to support the potential of oxytocin as an early intervention for young children with autism to help improve social interaction deficits. PMID:26503762

Bupivacaine 0.5 % versus articaine 4 % for the removal of lower third molars. A crossover randomized controlled trial

PubMed Central

Sancho-Puchades, Manuel; Vílchez-Pérez, Miguel A.; Paredes-García, Jordi; Berini-Aytés, Leonardo; Gay-Escoda, Cosme

2012-01-01

Objective: To compare the anesthetic action of 0.5% bupivacaine in relation to 4% articaine, both with 1:200,000 epinephrine, in the surgical removal of lower third molars. As a secondary objective hemodynamic changes using both anesthetics were analyzed. Study Design: Triple-blind crossover randomized clinical trial. Eighteen patients underwent bilateral removal of impacted lower third molars using 0.5% bupivacaine or 4% articaine in two different appointments. Preoperative, intraoperative and postoperative variables were recorded. Differences were assessed with McNemar tests and repeated measures ANOVA tests. Results: Both solutions exhibited similar latency times and intraoperative efficacy. Statistical significant lower pain levels were observed with bupivacaine between the fifth (p=0.011) and the ninth (p=0.007) postoperative hours. Bupivacaine provided significantly longer lasting soft tissue anesthesia (p<0.05). Systolic blood pressure and heart rate values were significantly higher with articaine. Conclusions: Bupivacaine could be a valid alternative to articaine especially due to its early postoperative pain prevention ability. Key words:Bupivacaine, articaine, third molar, anesthesia, postoperative pain. PMID:22143739

Randomized prospective crossover study of biphasic intermittent positive airway pressure ventilation (BIPAP) versus pressure support ventilation (PSV) in surgical intensive care patients.

PubMed

Elrazek, E Abd

2004-10-01

The aim of this prospective, randomized and crossover study was to assess the role of a relatively new mode of mechanical ventilation, biphasic intermittent positive airway pressure (BIPAP) in comparison to another well established one, pressure-support ventilation (PSV) in surgical intensive care patients. 24 generally stable patients, breathing on their own after short-term (< 24 hours) postoperative controlled mechanical ventilation (CMV) were randomized to start on either PSV or BIPAP, and indirect calorimetry measurements were performed after 1 hour adaptation period at two time intervals; immediately after the investigated ventilatory mode was started and 1 hour later. Statistics included a two-tailed paired t-test to compare the two sets of different data, p < 0.5 was considered significant. Oxygen consumption (VO2), energy expenditure (EE), Carbon dioxide production (VCO2), and respiratory quotient (RQ) did not differ significantly between the two groups. There were also no significant differences regarding respiratory rate (RR), minute volume (MV) and arterial blood gas analysis (ABGs). Both modes of ventilation were well tolerated by all patients. PSV and BIPAP can be used for weaning patients comfortably in surgical intensive care after short-term postoperative ventilation. BIPAP may have the credit of being smoother than PSV where no patient effort is required.

Efficacy of the Ubiquitous Spaced Retrieval-based Memory Advancement and Rehabilitation Training (USMART) program among patients with mild cognitive impairment: a randomized controlled crossover trial.

PubMed

Han, Ji Won; Son, Kyung Lak; Byun, Hye Jin; Ko, Ji Won; Kim, Kayoung; Hong, Jong Woo; Kim, Tae Hyun; Kim, Ki Woong

2017-06-06

Spaced retrieval training (SRT) is a nonpharmacological intervention for mild cognitive impairment (MCI) and dementia that trains the learning and retention of target information by recalling it over increasingly long intervals. We recently developed the Ubiquitous Spaced Retrieval-based Memory Advancement and Rehabilitation Training (USMART) program as a convenient, self-administered tablet-based SRT program. We also demonstrated the utility of USMART for improving memory in individuals with MCI through an open-label uncontrolled trial. This study had an open-label, single-blind, randomized, controlled, two-period crossover design. Fifty patients with MCI were randomized into USMART-usual care and usual care-USMART treatment sequences. USMART was completed or usual care was provided biweekly over a 4-week treatment period with a 2-week washout period between treatment periods. Primary outcome measures included the Word List Memory Test, Word List Recall Test (WLRT), and Word List Recognition Test. Outcomes were measured at baseline, week 5, and week 11 by raters who were blinded to intervention type. An intention-to-treat analysis and linear mixed modeling were used. Of 50 randomized participants, 41 completed the study (18% dropout rate). The USMART group had larger improvements in WLRT score (effect size = 0.49, p = 0.031) than the usual care group. There were no significant differences in other primary or secondary measures between the USMART and usual care groups. Moreover, no USMART-related adverse events were reported. The 4-week USMART modestly improved information retrieval in older people with MCI, and was well accepted with minimal technical support. ClinicalTrials.gov NCT01688128 . Registered 12 September 2012.

Single-case experimental design yielded an effect estimate corresponding to a randomized controlled trial.

PubMed

Shadish, William R; Rindskopf, David M; Boyajian, Jonathan G

2016-08-01

We reanalyzed data from a previous randomized crossover design that administered high or low doses of intravenous immunoglobulin (IgG) to 12 patients with hypogammaglobulinaemia over 12 time points, with crossover after time 6. The objective was to see if results corresponded when analyzed as a set of single-case experimental designs vs. as a usual randomized controlled trial (RCT). Two blinded statisticians independently analyzed results. One analyzed the RCT comparing mean outcomes of group A (high dose IgG) to group B (low dose IgG) at the usual trial end point (time 6 in this case). The other analyzed all 12 time points for the group B patients as six single-case experimental designs analyzed together in a Bayesian nonlinear framework. In the randomized trial, group A [M = 794.93; standard deviation (SD) = 90.48] had significantly higher serum IgG levels at time six than group B (M = 283.89; SD = 71.10) (t = 10.88; df = 10; P < 0.001), yielding a mean difference of MD = 511.05 [standard error (SE) = 46.98]. For the single-case experimental designs, the effect from an intrinsically nonlinear regression was also significant and comparable in size with overlapping confidence intervals: MD = 495.00, SE = 54.41, and t = 495.00/54.41 = 9.10. Subsequent exploratory analyses indicated that how trend was modeled made a difference to these conclusions. The results of single-case experimental designs accurately approximated results from an RCT, although more work is needed to understand the conditions under which this holds. Copyright © 2016 Elsevier Inc. All rights reserved.

Cap Assisted Upper Endoscopy for Examination of the Major Duodenal Papilla: A Randomized, Blinded, Controlled Crossover Study (CAPPA Study).

PubMed

Abdelhafez, Mohamed; Phillip, Veit; Hapfelmeier, Alexander; Elnegouly, Mayada; Poszler, Alexander; Strobel, Kilian; Born, Peter; Dollhopf, Markus; Kassem, Abdel Meguid; Calavrezos, Lenika; Klare, Peter; Schlag, Christoph; Bajbouj, Monther; Schmid, Roland M; von Delius, Stefan

2017-05-01

Examination of major duodenal papilla (MDP) by standard forward-viewing esophagogastroduodenoscopy (S-EGD) is limited. Cap assisted esophagogastroduodenoscopy (CA-EGD) utilizes a cap fitted to the tip of the endoscope that can depress the mucosal folds and thus might improve visualization of MDP. The aim of this study was to compare CA-EGD to S-EGD for complete examination of the MDP. Prospective, randomized, blinded, controlled crossover study. Subjects scheduled for elective EGD were randomized to undergo S-EGD (group A) or CA-EGD (group B) before undergoing a second examination by the alternate method. Images of the MDP were evaluated by three blinded multicenter-experts. Our primary outcome measure was complete examination of the papilla. Secondary outcome measures were duration and overall diagnostic yield. A total of 101 patients were randomized and completed the study. Complete examination of MDP was achieved in 98 patients using CA-EGD compared to 24 patients using S-EGD (97 vs. 24%, P<0.001). Median duration from intubation of the esophagus until localization of the MDP was shorter with CA-EGD (46. vs. 96 s., P<0.001). In group A, 11 extra lesions and 12 additional incidental findings were detected by secondary CA-EGD, whereas neither were detected by secondary S-EGD in group B (22 vs. 0% and 24 vs. 0%, P<0.001 and P<0.001). CA-EGD enabled complete examination of MDP in almost all cases compared to a low success rate of S-EGD. CA-EGD detected a significant amount of lesions and incidental findings when added to S-EGD. CA-EGD is a safe and effective method for examination of MDP.

Turo (qi dance) Program for Parkinson's Disease Patients: Randomized, Assessor Blind, Waiting-List Control, Partial Crossover Study.

PubMed

Lee, Hwa-Jin; Kim, Song-Yi; Chae, Younbyoung; Kim, Mi-Young; Yin, Changshik; Jung, Woo-Sang; Cho, Ki-Ho; Kim, Seung-Nam; Park, Hi-Joon; Lee, Hyejung

2018-03-01

Qigong, Tai-chi and dancing have all been proven effective for Parkinson's disease (PD); however, no study has yet assessed the efficacy of Turo, a hybrid qigong dancing program developed to relieve symptoms in PD patients. To determine whether Turo may provide benefit in addressing the symptoms of PD patients. Randomized, assessor blind, waiting-list control, partial crossover study. Kyung Hee University Korean Medicine Hospital, Seoul, Republic of Korea. A total of 32 PD patients (mean age 65.7 ± 6.8). Participants were assigned to the Turo group or the waiting-list control group. The Turo group participated in an 8-week Turo training program (60-minute sessions twice a week). The waiting-list control group received no additional treatment during the same period; then underwent the same 8-week Turo training. The primary outcome was a score on the Unified Parkinson's Disease Rating Scale (UPDRS), and the secondary outcomes included the perceived health status assessed using the Parkinson's disease Quality of Life questionnaire (PDQL), balance function as assessed by the Berg Balance Scale (BBS) and the results of the Beck Depression Inventory (BDI). The Turo group showed statistically significant improvements in the UPDRS (P < 0.01) and PDQL (P < 0.05) as compared to the control group. The changes in BBS scores displayed a tendency toward improvement, but was not statistically significant (P = 0.051). These findings suggest that Turo PD training might improve the symptoms of PD patients. Copyright © 2018. Published by Elsevier Inc.

Random-effects linear modeling and sample size tables for two special crossover designs of average bioequivalence studies: the four-period, two-sequence, two-formulation and six-period, three-sequence, three-formulation designs.

PubMed

Diaz, Francisco J; Berg, Michel J; Krebill, Ron; Welty, Timothy; Gidal, Barry E; Alloway, Rita; Privitera, Michael

2013-12-01

Due to concern and debate in the epilepsy medical community and to the current interest of the US Food and Drug Administration (FDA) in revising approaches to the approval of generic drugs, the FDA is currently supporting ongoing bioequivalence studies of antiepileptic drugs, the EQUIGEN studies. During the design of these crossover studies, the researchers could not find commercial or non-commercial statistical software that quickly allowed computation of sample sizes for their designs, particularly software implementing the FDA requirement of using random-effects linear models for the analyses of bioequivalence studies. This article presents tables for sample-size evaluations of average bioequivalence studies based on the two crossover designs used in the EQUIGEN studies: the four-period, two-sequence, two-formulation design, and the six-period, three-sequence, three-formulation design. Sample-size computations assume that random-effects linear models are used in bioequivalence analyses with crossover designs. Random-effects linear models have been traditionally viewed by many pharmacologists and clinical researchers as just mathematical devices to analyze repeated-measures data. In contrast, a modern view of these models attributes an important mathematical role in theoretical formulations in personalized medicine to them, because these models not only have parameters that represent average patients, but also have parameters that represent individual patients. Moreover, the notation and language of random-effects linear models have evolved over the years. Thus, another goal of this article is to provide a presentation of the statistical modeling of data from bioequivalence studies that highlights the modern view of these models, with special emphasis on power analyses and sample-size computations.

The kinetochore prevents centromere-proximal crossover recombination during meiosis

PubMed Central

Vincenten, Nadine; Kuhl, Lisa-Marie; Lam, Isabel; Oke, Ashwini; Kerr, Alastair RW; Hochwagen, Andreas; Fung, Jennifer; Keeney, Scott; Vader, Gerben; Marston, Adèle L

2015-01-01

During meiosis, crossover recombination is essential to link homologous chromosomes and drive faithful chromosome segregation. Crossover recombination is non-random across the genome, and centromere-proximal crossovers are associated with an increased risk of aneuploidy, including Trisomy 21 in humans. Here, we identify the conserved Ctf19/CCAN kinetochore sub-complex as a major factor that minimizes potentially deleterious centromere-proximal crossovers in budding yeast. We uncover multi-layered suppression of pericentromeric recombination by the Ctf19 complex, operating across distinct chromosomal distances. The Ctf19 complex prevents meiotic DNA break formation, the initiating event of recombination, proximal to the centromere. The Ctf19 complex independently drives the enrichment of cohesin throughout the broader pericentromere to suppress crossovers, but not DNA breaks. This non-canonical role of the kinetochore in defining a chromosome domain that is refractory to crossovers adds a new layer of functionality by which the kinetochore prevents the incidence of chromosome segregation errors that generate aneuploid gametes. DOI: http://dx.doi.org/10.7554/eLife.10850.001 PMID:26653857

Energy expenditure in people with transtibial amputation walking with crossover and energy storing prosthetic feet: A randomized within-subject study.

PubMed

McDonald, Cody L; Kramer, Patricia A; Morgan, Sara J; Halsne, Elizabeth G; Cheever, Sarah M; Hafner, Brian J

2018-05-01

Energy storing feet are unable to reduce the energy required for normal locomotion among people with transtibial amputation. Crossover feet, which incorporate aspects of energy storing and running specific feet, are designed to maximize energy return while providing stability for everyday activities. Do crossover prosthetic feet reduce the energy expenditure of walking across a range of speeds, when compared with energy storing feet among people with transtibial amputation due to non-dysvascular causes? A randomized within-subject study was conducted with a volunteer sample of twenty-seven adults with unilateral transtibial amputation due to non-dysvascular causes. Participants were fit with two prostheses. One had an energy storing foot (Össur Variflex) and the other a crossover foot (Össur Cheetah Xplore). Other components, including sockets, suspension, and interface were standardized. Energy expenditure was measured with a portable respirometer (Cosmed K4b2) while participants walked on a treadmill at self-selected slow, comfortable, and fast speeds with each prosthesis. Gross oxygen consumption rates (VO 2  ml/min) were compared between foot conditions. Energy storing feet were used as the baseline condition because they are used by most people with a lower limb prosthesis. Analyses were performed to identify people who may benefit from transition to crossover feet. On average, participants had lower oxygen consumption in the crossover foot condition compared to the energy storing foot condition at each self-selected walking speed, but this difference was not statistically significant. Participants with farther six-minute walk test distances, higher daily step counts, and higher Medicare Functional Classification Levels at baseline were more likely to use less energy in the crossover foot. Crossover feet may be most beneficial for people with higher activity levels and physical fitness. Further research is needed to examine the effect of crossover feet on energy expenditure during high-level activities. Copyright © 2018 Elsevier B.V. All rights reserved.

Low-dose naltrexone for the treatment of fibromyalgia: findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels.

PubMed

Younger, Jarred; Noor, Noorulain; McCue, Rebecca; Mackey, Sean

2013-02-01

To determine whether low dosages (4.5 mg/day) of naltrexone reduce fibromyalgia severity as compared with the nonspecific effects of placebo. In this replication and extension study of a previous clinical trial, we tested the impact of low-dose naltrexone on daily self-reported pain. Secondary outcomes included general satisfaction with life, positive mood, sleep quality, and fatigue. Thirty-one women with fibromyalgia participated in the randomized, double-blind, placebo-controlled, counterbalanced, crossover study. During the active drug phase, participants received 4.5 mg of oral naltrexone daily. An intensive longitudinal design was used to measure daily levels of pain. When contrasting the condition end points, we observed a significantly greater reduction of baseline pain in those taking low-dose naltrexone than in those taking placebo (28.8% reduction versus 18.0% reduction; P = 0.016). Low-dose naltrexone was also associated with improved general satisfaction with life (P = 0.045) and with improved mood (P = 0.039), but not improved fatigue or sleep. Thirty-two percent of participants met the criteria for response (defined as a significant reduction in pain plus a significant reduction in either fatigue or sleep problems) during low-dose naltrexone therapy, as contrasted with an 11% response rate during placebo therapy (P = 0.05). Low-dose naltrexone was rated equally tolerable as placebo, and no serious side effects were reported. The preliminary evidence continues to show that low-dose naltrexone has a specific and clinically beneficial impact on fibromyalgia pain. The medication is widely available, inexpensive, safe, and well-tolerated. Parallel-group randomized controlled trials are needed to fully determine the efficacy of the medication. Copyright © 2013 by the American College of Rheumatology.

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

PubMed Central

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

2016-01-01

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

Targeted HIV Screening in Eight Emergency Departments: The DICI-VIH Cluster-Randomized Two-Period Crossover Trial.

PubMed

Leblanc, Judith; Hejblum, Gilles; Costagliola, Dominique; Durand-Zaleski, Isabelle; Lert, France; de Truchis, Pierre; Verbeke, Geert; Rousseau, Alexandra; Piquet, Hélène; Simon, François; Pateron, Dominique; Simon, Tabassome; Crémieux, Anne-Claude

2018-07-01

This study compares the effectiveness and cost-effectiveness of nurse-driven targeted HIV screening alongside physician-directed diagnostic testing (intervention strategy) with diagnostic testing alone (control strategy) in 8 emergency departments. In this cluster-randomized, 2-period, crossover trial, 18- to 64-year-old patients presenting for reasons other than potential exposure to HIV were included. The strategy applied first was randomly assigned. During both periods, diagnostic testing was prescribed by physicians following usual care. During the intervention periods, patients were asked to complete a self-administered questionnaire. According to their answers, the triage nurse suggested performing a rapid test to patients belonging to a high-risk group. The primary outcome was the proportion of new diagnoses among included patients, which further refers to effectiveness. A secondary outcome was the intervention's incremental cost (health care system perspective) per additional diagnosis. During the intervention periods, 74,161 patients were included, 16,468 completed the questionnaire, 4,341 belonged to high-risk groups, and 2,818 were tested by nurses, yielding 13 new diagnoses. Combined with 9 diagnoses confirmed through 97 diagnostic tests, 22 new diagnoses were established. During the control periods, 74,166 patients were included, 92 were tested, and 6 received a new diagnosis. The proportion of new diagnoses among included patients was higher during the intervention than in the control periods (3.0 per 10,000 versus 0.8 per 10,000; difference 2.2 per 10,000, 95% CI 1.3 to 3.6; relative risk 3.7, 95% CI 1.4 to 9.8). The incremental cost was €1,324 per additional new diagnosis. The combined strategy of targeted screening and diagnostic testing was effective. Copyright © 2017 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Randomized, Double-Blind, Placebo- and Active Comparator-Controlled Crossover Study Evaluating the Abuse Potential of the Antiepileptic Drug Lacosamide in Healthy Recreational Drug Users.

PubMed

Schoedel, Kerri A; Andreas, Jens-Otto; Doty, Pamela; Eckhardt, Klaus; Sellers, Edward M

2017-12-01

This phase 1, randomized, double-blind, placebo- and active comparator-controlled crossover study assessed the abuse potential of the antiepileptic drug, lacosamide. After a qualification phase, 38 healthy, recreational central nervous system-depressant users were randomized to treatment sequences comprising single oral therapeutic (200 mg) and supratherapeutic (800 mg) doses of lacosamide, alprazolam (1.5 and 3 mg), and placebo. Subjective effects were assessed for 24 hours following each dose using a range of scales, with a 5- to 9-day washout between treatments. Mean subjective effects for 200 mg lacosamide were statistically similar to placebo and significantly lower than with alprazolam for most end points. Lacosamide 800 mg elicited transient, statistically significant positive effects compared with placebo, but also persistent Bad Drug Effects including statistically greater maximum effect (Emax) scores for Nausea and Dysphoria compared with other treatments (P < 0.0002). Consistent with this, the 800 mg lacosamide dose showed a significantly lower "at this moment" Drug Liking visual analog scale (VAS) Emax compared with 3 mg alprazolam, but was not different from 1.5 mg alprazolam (73.1/100, 85.4/100, and 78.9/100, respectively, where 50 is neutral). Overall Drug Liking VAS and Take Drug Again VAS Emax for 800 mg lacosamide were not significantly different from placebo and were lower than those for both alprazolam doses (P < 0.0001). These results suggest that in recreational central nervous system-depressant users, lacosamide has detectable abuse-related subjective effects, but a relatively low potential for abuse compared with alprazolam. These findings contributed toward placement of lacosamide into Schedule V of the US Controlled Substances Act.

Effects of Silexan on the Serotonin-1A Receptor and Microstructure of the Human Brain: A Randomized, Placebo-Controlled, Double-Blind, Cross-Over Study with Molecular and Structural Neuroimaging

PubMed Central

Baldinger, Pia; Höflich, Anna S.; Mitterhauser, Markus; Hahn, Andreas; Rami-Mark, Christina; Spies, Marie; Wadsak, Wolfgang; Lanzenberger, Rupert

2015-01-01

Background: Recently, Silexan, a patented active substance comprised of an essential oil produced from Lavandula angustifolia flowers, has been authorized in Germany as a medicinal product for the treatment of states of restlessness related to anxious mood. Its efficacy has been shown in several forms of anxiety disorders. Findings from preclinical and clinical studies attribute a major role to the serotonin-1A receptor in the pathogenesis and treatment of anxiety. Methods: To elucidate the effect of Silexan on serotonin-1A receptor binding, 17 healthy men underwent 2 positron emission tomography measurements using the radioligand [carbonyl-11C]WAY-100635 following the daily intake of 160mg Silexan or placebo for a minimum of 8 weeks (randomized, double-blind, cross-over design). Additionally, structural magnetic resonance imaging and voxel-based morphometry analysis was performed to determine potential effects on gray matter microstructure. Results: Serotonin-1A receptor binding potential was shown to be significantly reduced following the intake of Silexan compared with placebo in 2 large clusters encompassing the temporal gyrus, the fusiform gyrus and the hippocampus on one hand as well as the insula and anterior cingulate cortex on the other hand. No effects of Silexan on gray matter volume could be detected in this investigation. Conclusion: This positron emission tomography study proposes an involvement of the serotonin-1A receptor in the anxiolytic effects of Silexan. The study was registered in the International Standard Randomized Controlled Trial Number Register as ISRCTN30885829 (http://www.controlled-trials.com/isrctn/). PMID:25522403

Impact of Virgin Olive Oil and Phenol-Enriched Virgin Olive Oils on the HDL Proteome in Hypercholesterolemic Subjects: A Double Blind, Randomized, Controlled, Cross-Over Clinical Trial (VOHF Study)

PubMed Central

Pedret, Anna; Catalán, Úrsula; Fernández-Castillejo, Sara; Farràs, Marta; Valls, Rosa-M; Rubió, Laura; Canela, Núria; Aragonés, Gerard; Romeu, Marta; Castañer, Olga; de la Torre, Rafael; Covas, Maria-Isabel; Fitó, Montse; Motilva, Maria-José; Solà, Rosa

2015-01-01

The effects of olive oil phenolic compounds (PCs) on HDL proteome, with respect to new aspects of cardioprotective properties, are still unknown. The aim of this study was to assess the impact on the HDL protein cargo of the intake of virgin olive oil (VOO) and two functional VOOs, enriched with their own PCs (FVOO) or complemented with thyme PCs (FVOOT), in hypercholesterolemic subjects. Eligible volunteers were recruited from the IMIM-Hospital del Mar Medical Research Institute (Spain) from April 2012 to September 2012. Thirty-three hypercholesterolemic participants (total cholesterol >200mg/dL; 19 men and 14 women; aged 35 to 80 years) were randomized in the double-blind, controlled, cross-over VOHF clinical trial. The subjects received for 3 weeks 25 mL/day of: VOO, FVOO, or FVOOT. Using a quantitative proteomics approach, 127 HDL-associated proteins were identified. Among these, 15 were commonly differently expressed after the three VOO interventions compared to baseline, with specific changes observed for each intervention. The 15 common proteins were mainly involved in the following pathways: LXR/RXR activation, acute phase response, and atherosclerosis. The three VOOs were well tolerated by all participants. Consumption of VOO, or phenol-enriched VOOs, has an impact on the HDL proteome in a cardioprotective mode by up-regulating proteins related to cholesterol homeostasis, protection against oxidation and blood coagulation while down-regulating proteins implicated in acute-phase response, lipid transport, and immune response. The common observed protein expression modifications after the three VOOs indicate a major matrix effect. Trial Registration International Standard Randomized Controlled Trials ISRCTN77500181. PMID:26061039

Impact of Virgin Olive Oil and Phenol-Enriched Virgin Olive Oils on the HDL Proteome in Hypercholesterolemic Subjects: A Double Blind, Randomized, Controlled, Cross-Over Clinical Trial (VOHF Study).

PubMed

Pedret, Anna; Catalán, Úrsula; Fernández-Castillejo, Sara; Farràs, Marta; Valls, Rosa-M; Rubió, Laura; Canela, Núria; Aragonés, Gerard; Romeu, Marta; Castañer, Olga; de la Torre, Rafael; Covas, Maria-Isabel; Fitó, Montse; Motilva, Maria-José; Solà, Rosa

2015-01-01

The effects of olive oil phenolic compounds (PCs) on HDL proteome, with respect to new aspects of cardioprotective properties, are still unknown. The aim of this study was to assess the impact on the HDL protein cargo of the intake of virgin olive oil (VOO) and two functional VOOs, enriched with their own PCs (FVOO) or complemented with thyme PCs (FVOOT), in hypercholesterolemic subjects. Eligible volunteers were recruited from the IMIM-Hospital del Mar Medical Research Institute (Spain) from April 2012 to September 2012. Thirty-three hypercholesterolemic participants (total cholesterol >200 mg/dL; 19 men and 14 women; aged 35 to 80 years) were randomized in the double-blind, controlled, cross-over VOHF clinical trial. The subjects received for 3 weeks 25 mL/day of: VOO, FVOO, or FVOOT. Using a quantitative proteomics approach, 127 HDL-associated proteins were identified. Among these, 15 were commonly differently expressed after the three VOO interventions compared to baseline, with specific changes observed for each intervention. The 15 common proteins were mainly involved in the following pathways: LXR/RXR activation, acute phase response, and atherosclerosis. The three VOOs were well tolerated by all participants. Consumption of VOO, or phenol-enriched VOOs, has an impact on the HDL proteome in a cardioprotective mode by up-regulating proteins related to cholesterol homeostasis, protection against oxidation and blood coagulation while down-regulating proteins implicated in acute-phase response, lipid transport, and immune response. The common observed protein expression modifications after the three VOOs indicate a major matrix effect. International Standard Randomized Controlled Trials ISRCTN77500181.

Effects of a dynamic core stability program on the biomechanics of cutting maneuvers: A randomized controlled trial.

PubMed

Whyte, E F; Richter, C; O'Connor, S; Moran, K A

2018-02-01

Deficits in trunk control predict ACL injuries which frequently occur during high-risk activities such as cutting. However, no existing trunk control/core stability program has been found to positively affect trunk kinematics during cutting activities. This study investigated the effectiveness of a 6-week dynamic core stability program (DCS) on the biomechanics of anticipated and unanticipated side and crossover cutting maneuvers. Thirty-one male, varsity footballers participated in this randomized controlled trial. Three-dimensional trunk and lower limb biomechanics were captured in a motion analysis laboratory during the weight acceptance phase of anticipated and unanticipated side and crossover cutting maneuvers at baseline and 6-week follow-up. The DCS group performed a DCS program three times weekly for 6 weeks in a university rehabilitation room. Both the DCS and control groups concurrently completed their regular practice and match play. Statistical parametric mapping and repeated measures analysis of variance were used to determine any group (DCS vs control) by time (pre vs post) interactions. The DCS resulted in greater internal hip extensor (P=.017, η 2 =0.079), smaller internal knee valgus (P=.026, η 2 =0.076), and smaller internal knee external rotator moments (P=.041, η 2 =0.066) during anticipated side cutting compared with the control group. It also led to reduced posterior ground reaction forces for all cutting activities (P=.015-.030, η 2 =0.074-0.105). A 6-week DCS program did not affect trunk kinematics, but it did reduce a small number of biomechanical risk factors for ACL injury, predominantly during anticipated side cutting. A DCS program could play a role in multimodal ACL injury prevention programs. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The First National Student Conference: NASA University Research Centers at Minority Institutions

NASA Technical Reports Server (NTRS)

Daso, Endwell O. (Editor); Mebane, Stacie (Editor)

1997-01-01

The conference includes contributions from 13 minority universities with NASA University Research Centers. Topics discussed include: leadership, survival strategies, life support systems, food systems, simulated hypergravity, chromium diffusion doping, radiation effects on dc-dc converters, metal oxide glasses, crystal growth of Bil3, science and communication on wheels, semiconductor thin films, numerical solution of random algebraic equations, fuzzy logic control, spatial resolution of satellite images, programming language development, nitric oxide in the thermosphere and mesosphere, high performance polyimides, crossover control in genetic algorithms, hyperthermal ion scattering, etc.

The effects of the DDS-1 strain of lactobacillus on symptomatic relief for lactose intolerance - a randomized, double-blind, placebo-controlled, crossover clinical trial.

PubMed

Pakdaman, Michael N; Udani, Jay K; Molina, Jhanna Pamela; Shahani, Michael

2016-05-20

Lactose intolerance is a form of lactose maldigestion where individuals experience symptoms such as diarrhea, abdominal cramping, flatulence, vomiting and bowel sounds following lactose consumption. Lactobacillus acidophilus is a species of bacteria known for its sugar fermenting properties. Preclinical studies have found that Lactobacillus acidophilus supplementation may assist in breaking down lactose; however, no human clinical trials exist evaluating its efficacy in alleviating symptoms related to lactose intolerance. The aim of this randomized, double-blind, placebo-controlled, crossover study was to evaluate the effect of a proprietary strain of Lactobacillus acidophilus on relieving discomfort related to lactose intolerance. The study enrolled healthy volunteers between 18 and 75 years of age who complained of lactose intolerance. Screening visits included a lactose challenge visit to confirm eligibility based on a score of 10 or higher on subjective assessment of the following symptoms after lactose challenge: diarrhea, abdominal cramping, vomiting, audible bowel sounds, flatulence, and overall symptoms. Qualified subjects participated in a 2-arm crossover design, with each arm consisting of 4 weeks of intervention of either active or placebo product, with a 2-week washout period during crossover. The study product consisted of the DDS-1 strain of Lactobacillus acidophilus (Nebraska Cultures, Walnut Creek, California). The placebo was formulated from maltodextrin. Study participants were instructed to take the product once daily for 4 weeks. Data collected included subjective symptom scores related to lactose intolerance. Longitudinal comparison between the DDS-1 group and placebo group demonstrated statistically significant reductions in abdominal symptom scores during the 6-h Lactose Challenge at week 4 for diarrhea (p = 0.033), abdominal cramping (p = 0.012), vomiting (p = 0.0002), and overall symptom score (p = 0.037). No adverse events were reported. The present study has found that this unique DDS-1 strain of Lactobacillus acidophilus, manufactured by Nebraska Cultures, is safe to consume and improves abdominal symptom scores compared to placebo with respect to diarrhea, cramping, and vomiting during an acute lactose challenge.

Efficacy of Cognitive-Functional (Cog-Fun) Occupational Therapy Intervention Among Children With ADHD: An RCT.

PubMed

Hahn-Markowitz, Jeri; Berger, Itai; Manor, Iris; Maeir, Adina

2016-09-16

To examine the efficacy of a Cognitive-Functional (Cog-Fun) intervention for children with ADHD. Random allocation of 107 children to study or control groups preceded 10 parent-child weekly Cog-Fun sessions emphasizing executive strategy training in games and daily activities. Controls received treatment after crossover. Study participants were followed up 3 months post-treatment. Outcomes included parent/teacher ratings of executive functions, ADHD symptoms, and parent ratings of quality of life. Eight children withdrew prior to treatment. All children in both groups who began treatment completed it. Mixed effects ANOVA revealed significant Time × Group interaction effects on all parent-reported outcomes. Treatment effects were moderate to large, replicated after crossover in the control group and not moderated by medication. Parent-reported treatment gains in the study group were maintained at follow-up. No significant Time × Group interaction effects were found on teacher outcomes. Cog-Fun occupational therapy (OT) intervention shows positive context-specific effects on parent, but not teacher, ratings. © The Author(s) 2016.

Impact of dry ejaculation caused by highly selective alpha1A-blocker: randomized, double-blind, placebo-controlled crossover pilot study in healthy volunteer men.

PubMed

Shimizu, Fumitaka; Taguri, Masataka; Harada, Yoshiko; Matsuyama, Yutaka; Sase, Kazuhiro; Fujime, Makoto

2010-03-01

Dry ejaculation with loss of seminal emission is reported in patients who have been administered silodosin, an alpha1A-adrenoceptor antagonist. We investigated the impact of dry ejaculation caused by orally administered silodosin on orgasmic function. In a double-blind crossover study, 50 healthy volunteer men were randomly assigned to receive either a single dose of 4-mg silodosin or placebo with 3 days of washout before crossover. Subjects masturbated 4 hours after administering agents. Numerical rating scale (NRS) score from 0 (highest) to 10 (lowest) for subjective quality of orgasm, the subjective number of contractions of the bulbocavernosus/pelvic floor muscles, and the amount of semen were examined. Results. After the administration of silodosin, the NRS score worsened by 1.3 points (P = 0.003), the number of contractions of the bulbocavernosus/pelvic floor muscles decreased by about 1 (P = 0.003), and there was a decrease of 1.8 mL in the amount of semen produced (P < 0.0001). Eleven men overall (22%) on silodosin administration had less than a 50% decrease from baseline in the amount of semen. Silodosin may adversely affect the subjective orgasmic function by causing an abnormal ejaculation with decreased (or no) semen discharge and a decrease in the number of bulbocavernosus/pelvic floor muscle contractions. Semen passing through the urethra and sufficient rhythmic contraction of the muscle of the pelvic floor may contribute to the subjective pleasure of orgasm.

A Randomized Crossover Study of Web-Based Media Literacy to Prevent Smoking

ERIC Educational Resources Information Center

Shensa, Ariel; Phelps-Tschang, Jane; Miller, Elizabeth; Primack, Brian A.

2016-01-01

Feasibly implemented Web-based smoking media literacy (SML) programs have been associated with improving SML skills among adolescents. However, prior evaluations have generally had weak experimental designs. We aimed to examine program efficacy using a more rigorous crossover design. Seventy-two ninth grade students completed a Web-based SML…

Randomized crossover clinical trial of real and sham peripheral prism glasses for hemianopia

PubMed Central

Bowers, Alex R.; Keeney, Karen; Peli, Eli

2013-01-01

Objective To evaluate the efficacy of real relative to sham peripheral prism glasses for patients with complete homonymous hemianopia and without visual neglect. Methods Patients recruited at 13 clinics were allocated by minimization into a double-masked, crossover trial with two groups. One group received real (57Δ) oblique and sham (≤ 5Δ) horizontal prisms; the other received real horizontal and sham oblique, in counterbalanced order. A masked data collector at each clinic administered questionnaires after each 4-week crossover period. Main outcome measure The primary outcome was the overall difference, across the two periods of the crossover, between the proportion of participants who wanted to continue with (said “yes” to) real prisms and the proportion who said yes to sham prisms. The secondary outcome was the difference in perceived mobility improvement between real and sham prisms. Results Of 73 patients randomized, 61 completed the crossover. A significantly higher proportion said yes to real than sham prisms (64% vs. 36%; odds ratio 5.3, 95% CI 1.8 to 21.0). Participants who continued wear after 6 months reported greater improvement in mobility with real than sham prisms at crossover end (p=0.002); participants who discontinued wear reported no difference. Conclusion Real peripheral prism glasses were more helpful for obstacle avoidance when walking than sham glasses, with no differences between the horizontal and oblique designs. Applications to clinical practice Peripheral prism glasses provide a simple and inexpensive mobility rehabilitation intervention for hemianopia. PMID:24201760

Acute effects of pea protein and hull fibre alone and combined on blood glucose, appetite, and food intake in healthy young men--a randomized crossover trial.

PubMed

Mollard, Rebecca C; Luhovyy, Bohdan L; Smith, Christopher; Anderson, G Harvey

2014-12-01

Whether pulse components can be used as value-added ingredients in foods formulated for blood glucose (BG) and food intake (FI) control requires investigation. The objective of this study was to examine of the effects of pea components on FI at an ad libitum meal, as well as appetite and BG responses before and after the meal. In a repeated-measures crossover trial, men (n = 15) randomly consumed (i) pea hull fibre (7 g), (ii) pea protein (10 g), (iii) pea protein (10 g) plus hull fibre (7 g), (iv) yellow peas (406 g), and (v) control. Pea hull fibre and protein were served with tomato sauce and noodles, while yellow peas were served with tomato sauce. Control was noodles and tomato sauce. FI was measured at a pizza meal (135 min). Appetite and BG were measured pre-pizza (0-135 min) and post-pizza (155-215 min). Protein plus fibre and yellow peas led to lower pre-pizza BG area under the curve compared with fibre and control. At 30 min, BG was lower after protein plus fibre and yellow peas compared with fibre and control, whereas at 45 and 75 min, protein plus fibre and yellow peas led to lower BG compared with fibre (p < 0.05). Following the pizza meal (155 min), yellow peas led to lower BG compared with fibre (p < 0.05). No differences were observed in FI or appetite. This trial supports the use of pea components as value-added ingredients in foods designed to improve glycemic control.

The effect of almonds on inflammation and oxidative stress in Chinese patients with type 2 diabetes mellitus: a randomized crossover controlled feeding trial.

PubMed

Liu, Jen-Fang; Liu, Yen-Hua; Chen, Chiao-Ming; Chang, Wen-Hsin; Chen, C-Y Oliver

2013-04-01

Almond consumption is associated with ameliorations in obesity, hyperlipidemia, hypertension, and hyperglycemia. The hypothesis of this 12-week randomized, crossover, controlled feeding trial was that almond consumption would ameliorate inflammation and oxidative stress in Chinese patients with type 2 diabetes mellitus (T2DM) (9 M, 11 F; 58 years; BMI: 26 kg/m²) with mild hyperlipidemia. After a 2-week run-in period, the patients were assigned to either a control NCEP step II diet (control diet) or almond diet for 4 weeks with a 2-week washout period between alternative diets. Almonds approximately at 56 g/day were added to the control diet to replace 20 % of total daily calorie intake. As compared to the control diet, the almond diet decreased IL-6 by a median 10.3 % (95 % confidence intervals 5.2, 12.6 %), CRP by a median 10.3 % (-24.1, 40.5), and TNF-α by a median 15.7 % (-0.3, 29.9). The almond diet also decreased plasma protein carbonyl by a median 28.2 % (4.7, 38.2) as compared to the C diet but did not alter plasma malondialdehyde. The A diet enhanced the resistance of LDL against Cu²⁺-induced oxidation by a median 16.3 % (7.4, 44.3) as compared to the C diet. Serum intercellular adhesion molecule-1 and vascular adhesion molecule-1 were not changed by both diets. Our results suggested that incorporation of almonds into a healthy diet could ameliorate inflammation and oxidative stress in patients with T2DM.

The effect of small solar powered 'Bͻkͻͻ' net fans on mosquito net use: results from a randomized controlled cross-over trial in southern Ghana.

PubMed

Briët, Olivier J T; Yukich, Joshua O; Pfeiffer, Constanze; Miller, William; Jaeger, Mulako S; Khanna, Nitin; Oppong, Samuel; Nardini, Peter; Ahorlu, Collins K; Keating, Joseph

2017-01-03

Long-lasting insecticidal nets (LLINs) are ineffective malaria transmission prevention tools if they are unused. Discomfort due to heat is the most commonly reported reason for not using nets, but this problem is largely unaddressed. With increasing rural electrification and the dropping price of solar power, fans could improve comfort inside nets and be affordable to populations in malaria endemic areas. Here, results are presented from a pilot randomized controlled cross-over study testing the effect of fans on LLIN use. Eighty-three households from two rural communities in Greater Accra, Ghana, randomized into three groups, participated in a 10-month cross-over trial. After a screening survey to identify eligible households, all households received new LLINs. Bͻkͻͻ net fan systems (one fan per member) were given to households in Group 1 and water filters were given to households in Group 2. At mid-point, Group 1 and 2 crossed over interventions. Households in Group 1 and 2 participated in fortnightly surveys on households' practices related to nets, fans and water filters, while households in Group 3 were surveyed only at screening, mid-point and study end. Entomological and weather data were collected throughout the study. Analysis took both 'per protocol' (PP) and 'intention to treat' (ITT) approaches. The mid- and end-point survey data from Group 1 and 2 were analysed using Firth logistic regressions. Fortnightly survey data from all groups were analysed using logistic regressions with random effects. Provision of fans to households appeared to increase net use in this study. Although the increase in net use explained by fans was not significant in the primary analyses (ITT odds ratio 3.24, p > 0.01; PP odds ratio = 1.17, p > 0.01), it was significant in secondary PP analysis (odds ratio = 1.95, p < 0.01). Net use was high at screening and even higher after provision of new LLINs and with follow up. Fan use was 90-100% depending on the fortnightly visit. This pilot study could not provide definitive evidence that fans increase net use. A larger study with additional statistical power is needed to assess this association across communities with diverse environmental and socio-demographic characteristics.

BounceBack capsules for reduction of DOMS after eccentric exercise: a randomized, double-blind, placebo-controlled, crossover pilot study.

PubMed

Udani, Jay K; Singh, Betsy B; Singh, Vijay J; Sandoval, Elizabeth

2009-06-05

Delayed onset muscle soreness (DOMS) is muscle pain and discomfort experienced approximately one to three days after exercise. DOMS is thought to be a result of microscopic muscle fiber tears that occur more commonly after eccentric exercise rather than concentric exercise. This study sought to test the efficacy of a proprietary dietary supplement, BounceBack, to alleviate the severity of DOMS after standardized eccentric exercise. The study was a randomized, double-blind, placebo-controlled, crossover study. Ten healthy community-dwelling untrained subjects, ranging in age from 18-45 years, were enrolled. Mean differences within and between groups were assessed inferentially at each data collection time-point using t-tests for all outcome measures. In this controlled pilot study, intake of BounceBack capsules for 30 days resulted in a significant reduction in standardized measures of pain and tenderness post-eccentric exercise compared to the placebo group. There were trends towards reductions in plasma indicators of inflammation (high sensitivity C-reactive protein) and muscle damage (creatine phosphokinase and myoglobin). BounceBack capsules were able to significantly reduce standardized measures of pain and tenderness at several post-eccentric exercise time points in comparison to placebo. The differences in the serological markers of DOMS, while not statistically significant, appear to support the clinical findings. The product appears to have a good safety profile and further study with a larger sample size is warranted based on the current results.

BounceBack™ capsules for reduction of DOMS after eccentric exercise: a randomized, double-blind, placebo-controlled, crossover pilot study

PubMed Central

Udani, Jay K; Singh, Betsy B; Singh, Vijay J; Sandoval, Elizabeth

2009-01-01

Background Delayed onset muscle soreness (DOMS) is muscle pain and discomfort experienced approximately one to three days after exercise. DOMS is thought to be a result of microscopic muscle fiber tears that occur more commonly after eccentric exercise rather than concentric exercise. This study sought to test the efficacy of a proprietary dietary supplement, BounceBack™, to alleviate the severity of DOMS after standardized eccentric exercise. Methods The study was a randomized, double-blind, placebo-controlled, crossover study. Ten healthy community-dwelling untrained subjects, ranging in age from 18–45 years, were enrolled. Mean differences within and between groups were assessed inferentially at each data collection time-point using t-tests for all outcome measures. Results In this controlled pilot study, intake of BounceBack™ capsules for 30 days resulted in a significant reduction in standardized measures of pain and tenderness post-eccentric exercise compared to the placebo group. There were trends towards reductions in plasma indicators of inflammation (high sensitivity C-reactive protein) and muscle damage (creatine phosphokinase and myoglobin). Conclusion BounceBack™ capsules were able to significantly reduce standardized measures of pain and tenderness at several post-eccentric exercise time points in comparison to placebo. The differences in the serological markers of DOMS, while not statistically significant, appear to support the clinical findings. The product appears to have a good safety profile and further study with a larger sample size is warranted based on the current results. PMID:19500355

Dark chocolate and vascular function in patients with peripheral artery disease: a randomized, controlled cross-over trial.

PubMed

Hammer, Alexandra; Koppensteiner, Renate; Steiner, Sabine; Niessner, Alexander; Goliasch, Georg; Gschwandtner, Michael; Hoke, Matthias

2015-01-01

Flavonoid-rich dark chocolate has positive effects on vascular function in healthy subjects and in patients at risk of atherosclerosis. The impact of dark chocolate on endothelial and microvascular function in patients with symptomatic peripheral artery disease (PAD) has not been investigated so far. In an investigator blinded, randomized, controlled, cross-over trial we assessed the effect of flavonoid-rich dark chocolate and cocoa-free control chocolate on flow-mediated dilatation (FMD) of the brachial artery and on microvascular function (assessed by Laser Doppler fluxmetry) in 21 patients with symptomatic (Fontaine stage II) PAD. Measurements were done in each patient on 2 single days, with an interval of 7 days, at baseline and at 2 hours after ingestion of 50 g dark chocolate or 50 g white chocolate, respectively. FMD remained unchanged after intake of dark chocolate (baseline and 2 hours after ingestion, %: 5.1 [IQR 4.4 to 7.3] and 5.5 [IQR 3.9 to 10.4]; p = 0.57, and after intake of white chocolate (baseline and 2 hours after ingestion, %: 6.4 [IQR 4.5 to 11.4] and 4.4 [IQR 2.6 to 8.7]; p = 0.14. Similarly, microcirculatory parameters were not significantly altered after intake of any chocolate compared with the respective baseline values. In conclusion, a single consumption of 50 g dark chocolate has no effect on endothelial and microvascular function in patients with symptomatic PAD.

Making Friends With Yourself: A Mixed Methods Pilot Study of a Mindful Self-Compassion Program for Adolescents

PubMed Central

Bluth, Karen; Gaylord, Susan A.; Campo, Rebecca A.; Mullarkey, Michael C.; Hobbs, Lorraine

2015-01-01

The aims of this mixed-method pilot study were to determine the feasibility, acceptability, and preliminary psychosocial outcomes of “Making Friends with Yourself: A Mindful Self-Compassion Program for Teens” (MFY), an adaptation of the adult Mindful Self-Compassion program. Thirty-four students age 14–17 enrolled in this waitlist controlled crossover study. Participants were randomized to either the waitlist or intervention group and administered online surveys at baseline, after the first cohort participated in the intervention, and after the waitlist crossovers participated in the intervention. Attendance and retention data were collected to determine feasibility, and audiorecordings of the 6-week class were analyzed to determine acceptability of the program. Findings indicated that MFY is a feasible and acceptable program for adolescents. Compared to the waitlist control, the intervention group had significantly greater self-compassion and life satisfaction and significantly lower depression than the waitlist control, with trends for greater mindfulness, greater social connectedness and lower anxiety. When waitlist crossovers results were combined with that of the first intervention group, findings indicated significantly greater mindfulness and self-compassion, and significantly less anxiety, depression, perceived stress and negative affect post-intervention. Additionally, regression results demonstrated that self-compassion and mindfulness predicted decreases in anxiety, depression, perceived stress, and increases in life satisfaction post-intervention. MFY shows promise as a program to increase psychosocial wellbeing in adolescents through increasing mindfulness and self-compassion. Further testing is needed to substantiate the findings. PMID:27110301

A randomized, double-blind, placebo-controlled, crossover trial evaluating the effect of intranasal insulin on cognition and mood in individuals with treatment-resistant major depressive disorder.

PubMed

Cha, Danielle S; Best, Michael W; Bowie, Christopher R; Gallaugher, Laura Ashley; Woldeyohannes, Hanna O; Soczynska, Joanna K; Lewis, Gary; MacQueen, Glenda; Sahakian, Barbara J; Kennedy, Sidney H; Lui, Jane P; Mansur, Rodrigo B; McIntyre, Roger S

2017-03-01

Cognitive dysfunction in major depressive disorder (MDD) is identified as a primary therapeutic target; no current treatment is approved for the treatment of cognitive dysfunction in MDD. We examined whether intranasal insulin offered a beneficial effect across measures of cognitive function in adults with MDD. Thirty-five adults (18-65 years of age: 47.09±9.89) meeting criteria for a major depressive episode as per the Diagnostic and Statistical Manual (DSM)-IV-Treatment Revised were included in this randomized, double blind, placebo-controlled, crossover design study. Subjects were not stratified based on baseline cognitive deficit. Subjects were randomized to 4 weeks of either intranasal insulin 40 International Units (IU) taken four times a day (i.e., morning, afternoon, evening, and before bed) (QID) (n=19) or placebo (n=16). No between group differences were observed in change from baseline on total Montgomery Åsberg Depression Rating Scale (MADRS) score (25.98±2.81), in either of the Positive or Negative subscales of the Positive and Negative Affect Schedule (PANAS), or on a global index of neurocognition. The possibility of practice and/or carry over effect could not be excluded. Methodological refinement (e.g., stratification of subjects based on baseline cognitive deficit) may have augmented assay sensitivity. Intranasal insulin did not demonstrate statistically significant improvements on overall mood, aspects of emotional processing, neurocognitive function, or self-reported quality of life patient reported outcomes. Copyright © 2016 Elsevier B.V. All rights reserved.

Dose-dependent social-cognitive effects of intranasal oxytocin delivered with novel Breath Powered device in adults with autism spectrum disorder: a randomized placebo-controlled double-blind crossover trial

PubMed Central

Quintana, D S; Westlye, L T; Hope, S; Nærland, T; Elvsåshagen, T; Dørum, E; Rustan, Ø; Valstad, M; Rezvaya, L; Lishaugen, H; Stensønes, E; Yaqub, S; Smerud, K T; Mahmoud, R A; Djupesland, P G; Andreassen, O A

2017-01-01

The neuropeptide oxytocin has shown promise as a treatment for symptoms of autism spectrum disorders (ASD). However, clinical research progress has been hampered by a poor understanding of oxytocin’s dose–response and sub-optimal intranasal delivery methods. We examined two doses of oxytocin delivered using a novel Breath Powered intranasal delivery device designed to improve direct nose-to-brain activity in a double-blind, crossover, randomized, placebo-controlled trial. In a randomized sequence of single-dose sessions, 17 male adults with ASD received 8 international units (IU) oxytocin, 24IU oxytocin or placebo followed by four social-cognitive tasks. We observed an omnibus main effect of treatment on the primary outcome measure of overt emotion salience as measured by emotional ratings of faces (η2=0.18). Compared to placebo, 8IU treatment increased overt emotion salience (P=0.02, d=0.63). There was no statistically significant increase after 24IU treatment (P=0.12, d=0.4). The effects after 8IU oxytocin were observed despite no significant increase in peripheral blood plasma oxytocin concentrations. We found no significant effects for reading the mind in the eyes task performance or secondary outcome social-cognitive tasks (emotional dot probe and face-morphing). To our knowledge, this is the first trial to assess the dose-dependent effects of a single oxytocin administration in autism, with results indicating that a low dose of oxytocin can significantly modulate overt emotion salience despite minimal systemic exposure. PMID:28534875

Effect of knee joint icing on knee extension strength and knee pain early after total knee arthroplasty: a randomized cross-over study.

PubMed

Holm, Bente; Husted, Henrik; Kehlet, Henrik; Bandholm, Thomas

2012-08-01

To investigate the acute effect of knee joint icing on knee extension strength and knee pain in patients shortly after total knee arthroplasty. A prospective, single-blinded, randomized, cross-over study. A fast-track orthopaedic arthroplasty unit at a university hospital. Twenty patients (mean age 66 years; 10 women) scheduled for primary unilateral total knee arthroplasty. The patients were treated on two days (day 7 and day 10) postoperatively. On one day they received 30 minutes of knee icing (active treatment) and on the other day they received 30 minutes of elbow icing (control treatment). The order of treatments was randomized. Maximal knee extension strength (primary outcome), knee pain at rest and knee pain during the maximal knee extensions were measured 2-5 minutes before and 2-5 minutes after both treatments by an assessor blinded for active or control treatment. The change in knee extension strength associated with knee icing was not significantly different from that of elbow icing (knee icing change (mean (1 SD)) -0.01 (0.07) Nm/kg, elbow icing change -0.02 (0.07) Nm/kg, P = 0.493). Likewise, the changes in knee pain at rest (P = 0.475), or knee pain during the knee extension strength measurements (P = 0.422) were not different between treatments. In contrast to observations in experimental knee effusion models and inflamed knee joints, knee joint icing for 30 minutes shortly after total knee arthroplasty had no acute effect on knee extension strength or knee pain.

Dose-dependent social-cognitive effects of intranasal oxytocin delivered with novel Breath Powered device in adults with autism spectrum disorder: a randomized placebo-controlled double-blind crossover trial.

PubMed

Quintana, D S; Westlye, L T; Hope, S; Nærland, T; Elvsåshagen, T; Dørum, E; Rustan, Ø; Valstad, M; Rezvaya, L; Lishaugen, H; Stensønes, E; Yaqub, S; Smerud, K T; Mahmoud, R A; Djupesland, P G; Andreassen, O A

2017-05-23

The neuropeptide oxytocin has shown promise as a treatment for symptoms of autism spectrum disorders (ASD). However, clinical research progress has been hampered by a poor understanding of oxytocin's dose-response and sub-optimal intranasal delivery methods. We examined two doses of oxytocin delivered using a novel Breath Powered intranasal delivery device designed to improve direct nose-to-brain activity in a double-blind, crossover, randomized, placebo-controlled trial. In a randomized sequence of single-dose sessions, 17 male adults with ASD received 8 international units (IU) oxytocin, 24IU oxytocin or placebo followed by four social-cognitive tasks. We observed an omnibus main effect of treatment on the primary outcome measure of overt emotion salience as measured by emotional ratings of faces (η 2 =0.18). Compared to placebo, 8IU treatment increased overt emotion salience (P=0.02, d=0.63). There was no statistically significant increase after 24IU treatment (P=0.12, d=0.4). The effects after 8IU oxytocin were observed despite no significant increase in peripheral blood plasma oxytocin concentrations. We found no significant effects for reading the mind in the eyes task performance or secondary outcome social-cognitive tasks (emotional dot probe and face-morphing). To our knowledge, this is the first trial to assess the dose-dependent effects of a single oxytocin administration in autism, with results indicating that a low dose of oxytocin can significantly modulate overt emotion salience despite minimal systemic exposure.

Modafinil improves real driving performance in patients with hypersomnia: a randomized double-blind placebo-controlled crossover clinical trial.

PubMed

Philip, Pierre; Chaufton, Cyril; Taillard, Jacques; Capelli, Aurore; Coste, Olivier; Léger, Damien; Moore, Nicholas; Sagaspe, Patricia

2014-03-01

Patients with excessive daytime sleepiness (EDS) are at high risk for driving accidents, and physicians are concerned by the effect of alerting drugs on driving skills of sleepy patients. No study has up to now investigated the effect of modafinil (a reference drug to treat EDS in patients with hypersomnia) on on-road driving performance of patients suffering from central hypersomnia. The objective is to evaluate in patients with central hypersomnia the effect of a wake-promoting drug on real driving performance and to assess the relationship between objective sleepiness and driving performance. Randomized, crossover, double-blind placebo-controlled trial conducted among 13 patients with narcolepsy and 14 patients with idiopathic hypersomnia. Patients were randomly assigned to receive modafinil (400 mg) or placebo for 5 days prior to the driving test. Each condition was separated by at least 3 weeks of washout. Mean number of Inappropriate Line Crossings, Standard Deviation of Lateral Position of the vehicle and mean sleep latency in the Maintenance of Wakefulness Test were assessed. Modafinil reduced the mean number of Inappropriate Line Crossings and Standard Deviation of Lateral Position of the vehicle compared to placebo (F(1,25) = 4.88, P < 0.05 and F(1,25) = 3.87, P = 0.06 tendency). Mean sleep latency at the Maintenance of Wakefulness Test significantly correlated with the mean number of Inappropriate Line Crossings (r = -0.41, P < 0.001). Modafinil improves driving performance in patients with narcolepsy and idiopathic hypersomnia. The Maintenance of Wakefulness Test is a suitable clinical tool to assess fitness to drive in this population.

Feasibility and Preliminary Efficacy of the Effects of Flavanoid-Rich Purple Grape Juice on the Vascular Health of Childhood Cancer Survivors: A Randomized, Controlled Crossover Trial

PubMed Central

Blair, Cindy K.; Kelly, Aaron S.; Steinberger, Julia; Eberly, Lynn E.; Napurski, Char; Robien, Kim; Neglia, Joseph P.; Mulrooney, Daniel A.; Ross, Julie A.

2016-01-01

Background Childhood cancer survivors have an increased risk of developing cardiovascular disease following treatment, yet few interventions have been evaluated to reduce this risk. Purple grape juice (pGJ), a rich source of flavonoids with antioxidant properties, has been shown in adults to reduce oxidative stress and improve endothelial function. We examined the effects of supplementing meals with pGJ on microvascular endothelial function and markers of oxidative stress and inflammation in 24 cancer survivors (ages 10–21 years). Procedure In a randomized controlled crossover trial consisting of two, 4 week intervention periods, each preceded by a 4 week washout period, subjects received in random order 6 ounces twice daily of pGJ and clear apple juice (cAJ; similar in calories but lower in flavonoids). Measurements were obtained before and after each supplementation period; change was evaluated using mixed effects ANOVA. Results pGJ did not improve endothelial function, measured using digital reactive hyperemia, compared with cAJ (mean change: pGJ 0.06, cAJ 0.22; difference of mean change [95% CI]: −0.16 [−0.42 – 0.11], P = 0.25). No significant changes in plasma concentrations of oxidized-LDL, myeloperoxidase, or high sensitivity C-reactive protein were observed. Conclusion After 4 weeks of daily consumption of flavonoid-rich pGJ, no measurable change in vascular function was observed in these childhood cancer survivors. Pediatr Blood Cancer 2014;61:2290–2296. PMID:25175762

Reversal of apixaban anticoagulation by four-factor prothrombin complex concentrates in healthy subjects: a randomized three-period crossover study.

PubMed

Song, Y; Wang, Z; Perlstein, I; Wang, J; LaCreta, F; Frost, R J A; Frost, C

2017-11-01

Essentials Prothrombin complex concentrates (PCCs) may reverse the effect of factor Xa (FXa) inhibitors. We conducted an open-label, randomized, placebo-controlled, three-period crossover study in 15 subjects. Both PCCs rapidly reversed apixaban-mediated decreases in mean endogenous thrombin potential. Four-factor PCC administration had no effect on apixaban pharmacokinetics or anti-FXa activity. Background Currently, there is no approved reversal agent for direct activated factor Xa (FXa) inhibitors; however, several agents are under investigation, including prothrombin complex concentrates (PCCs). Objective This open-label, randomized, placebo-controlled, three-period crossover study assessed the effect of two four-factor PCCs on apixaban pharmacodynamics and pharmacokinetics in 15 healthy subjects. Methods Subjects received apixaban 10 mg twice daily for 3 days. On day 4, 3 h after apixaban, subjects received a 30-min infusion of 50 IU kg -1 Cofact, Beriplex P/N (Beriplex), or saline. Change in endogenous thrombin potential (ETP), measured with a thrombin generation assay (TGA), was the primary endpoint. Secondary endpoints included changes in other TGA parameters, prothrombin time (PT), International Normalized Ratio (INR), activated partial thromboplastin time, anti-FXa activity, apixaban pharmacokinetics, and safety. Results Apixaban-related changes in ETP and several other pharmacodynamic measures occurred following apixaban administration. Both PCCs reversed apixaban's effect on ETP; the differences in adjusted mean change from pre-PCC baseline to end of infusion were 425 nm min (95% confidence interval [CI] 219.8-630.7 nm min; P < 0.001) for Cofact, and 91 nm min (95% CI - 31.3 to 212.4 nm min; P > 0.05) for Beriplex. Both PCCs returned ETP to pre-apixaban baseline levels 4 h after PCC infusion, versus 45 h for placebo. For both PCCs, mean ETP peaked 21 h after PCC initiation, and then slowly decreased over the following 48 h. Both PCCs reversed apixaban's effect on TGA peak height, PT, and INR. Apixaban pharmacokinetic and anti-FXa profiles were consistent across treatments. Conclusions Cofact and Beriplex reversed apixaban's steady-state effects on several coagulation assessments. © 2017 International Society on Thrombosis and Haemostasis.

A dose-response evaluation of freeze-dried strawberries independent of fiber content on metabolic indices in abdominally obese individuals with insulin resistance in a randomized, single-blinded, diet-controlled crossover trial.

PubMed

Park, Eunyoung; Edirisinghe, Indika; Wei, Hequn; Vijayakumar, Lakshmi Prabha; Banaszewski, Katarzyna; Cappozzo, Jack C; Burton-Freeman, Britt

2016-05-01

This study evaluated the dose-response relationship of strawberries, an anthocyanin-rich fruit, on postprandial glucose and insulin concentrations in individuals with insulin resistance (IR), including changes in plasma anthocyanins, markers of oxidative stress, and inflammation. In a randomized controlled, four-arm, dose-response, crossover trial, 21 adults with IR consumed a high-carbohydrate, high-fat meal with one of four beverages containing 0 g freeze-dried whole strawberry powder (0g FDS, control), 10, 20, or 40 g FDS, controlled for fiber. Blood was collected at 0 min and at 30 min intervals postmeal until 2 h, then hourly until 6 h. Postmeal insulin concentrations (6 h) were significantly reduced after the 40-g FDS beverage compared to other beverages (p < 0.05). Postmeal 6 h glucose concentrations were not different, although mean insulin:glucose ratio was significantly different among beverages (p < 0.05). Pelargonidin-glucuronide was inversely associated with mean insulin concentrations after the 20 and 40 g FDS (p < 0.05). Oxidized low-density lipoprotein was reduced after 20 g FDS (p < 0.05) and IL-6 was not different among treatments. Strawberry intake reduced the insulin demand to manage postmeal glucose in obese individuals with IR, which was related to plasma anthocyanin/pelargonidin concentrations. The data support a role of strawberries in improving insulin sensitivity in people with IR. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Psychomotor and subjective effects of bilastine, hydroxyzine, and cetirizine, in combination with alcohol: a randomized, double-blind, crossover, and positive-controlled and placebo-controlled Phase I clinical trials.

PubMed

García-Gea, Consuelo; Martínez, Joan; Ballester, Maria Rosa; Gich, Ignasi; Valiente, Román; Antonijoan, Rosa Maria

2014-03-01

The aim of this study was to compare the effects of concomitant administration of alcohol and bilastine versus alcohol alone on the central nervous system. Twenty-four healthy young volunteers of both sexes participated in a randomized, double-blind, double-dummy, crossover, and positive-controlled and placebo-controlled clinical trials. At 1-week intervals, subjects received six different treatments: (i) placebo; (ii) alcohol 0.8 g/kg alone (ALC); (iii) ALC in combination with: bilastine 20 mg (B20 + A); (iv) bilastine 80 mg (B80 + A); (v) cetirizine 10 mg (CET + A); and (vi) hydroxyzine 25 mg (HYD + A). Psychomotor performance tests (fine motor, finger tapping, nystagmus, critical flicker-fusion frequency, temporal estimation, 'd2' cancellation, and simple reaction time) and subjective self-reports (drunkenness, drowsiness, mental slowness, clumsiness, anger, attentiveness, competence, happiness, hostility, interest, and extroversion) were carried out at baseline and multiple points thereafter. All active treatments induced a significant psychomotor impairment. The greatest and most lasting impairment was observed with HYD + A followed by B80 + A and CET + A. In contrast, objective measures showed less impairment with B20 + A and ALC, both with a similar magnitude. Self-reports showed a subjective perception of performance impairment in all active treatments. Concomitant administration of bilastine (at therapeutic dose) and alcohol does not produce greater central nervous system depressant effects than ACL alone. Copyright © 2014 John Wiley & Sons, Ltd.

Next-day residual effects of gabapentin, diphenhydramine, and triazolam on simulated driving performance in healthy volunteers: a phase 3, randomized, double-blind, placebo-controlled, crossover trial.

PubMed

Kay, Gary G; Schwartz, Howard I; Wingertzahn, Mark A; Jayawardena, Shyamalie; Rosenberg, Russell P

2016-05-01

Next-day residual effects of a nighttime dose of gabapentin 250 mg were evaluated on simulated driving performance in healthy participants in a randomized, placebo-controlled, double-blind, multicenter, four-period crossover study that included diphenhydramine citrate 76 mg and triazolam 0.5 mg. At treatment visits, participants (n = 59) were dosed at ~23:30, went to bed immediately, and awakened 6.5 h postdose for evaluation. The primary endpoint was the standard deviation of lateral position for the 100-km driving scenario. Additional measures of driving, sleepiness, and cognition were included. Study sensitivity was established with triazolam, which demonstrated significant next-day impairment on all driving endpoints, relative to placebo (p < 0.001). Gabapentin demonstrated noninferiority to placebo on standard deviation of lateral position and speed deviation but not for lane excursions. Diphenhydramine citrate demonstrated significant impairment relative to gabapentin and placebo on speed deviation (p < 0.05). Other comparisons were either nonsignificant or statistically ineligible per planned, sequential comparisons. Secondary endpoints for sleepiness and cognitive performance were supportive of these conclusions. Together, these data suggest that low-dose gabapentin had no appreciable next-day effects on simulated driving performance or cognitive functioning. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Self-esteem treatment in anxiety: A randomized controlled crossover trial of Eye Movement Desensitization and Reprocessing (EMDR) versus Competitive Memory Training (COMET) in patients with anxiety disorders.

PubMed

Staring, A B P; van den Berg, D P G; Cath, D C; Schoorl, M; Engelhard, I M; Korrelboom, C W

2016-07-01

Little is known about treating low self-esteem in anxiety disorders. This study evaluated two treatments targeting different mechanisms: (1) Eye Movement Desensitization and Reprocessing (EMDR), which aims to desensitize negative memory representations that are proposed to maintain low self-esteem; and (2) Competitive Memory Training (COMET), which aims to activate positive representations for enhancing self-esteem. A Randomized Controlled Trial (RCT) was used with a crossover design. Group 1 received six sessions EMDR first and then six sessions COMET; group 2 vice versa. Assessments were made at baseline (T0), end of first treatment (T1), and end of second treatment (T2). Main outcome was self-esteem. We included 47 patients and performed Linear Mixed Models. COMET showed more improvements in self-esteem than EMDR: effect-sizes 1.25 versus 0.46 post-treatment. Unexpectedly, when EMDR was given first, subsequent effects of COMET were significantly reduced in comparison to COMET as the first intervention. For EMDR, sequence made no difference. Reductions in anxiety and depression were mediated by better self-esteem. COMET was associated with significantly greater improvements in self-esteem than EMDR in patients with anxiety disorders. EMDR treatment reduced the effectiveness of subsequent COMET. Improved self-esteem mediated reductions in anxiety and depression symptoms. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Diuretic Action of Weak and Strong Alcoholic Beverages in Elderly Men: A Randomized Diet-Controlled Crossover Trial.

PubMed

Polhuis, Kristel C M M; Wijnen, Annemarthe H C; Sierksma, Aafje; Calame, Wim; Tieland, Michael

2017-06-28

With ageing, there is a greater risk of dehydration. This study investigated the diuretic effect of alcoholic beverages varying in alcohol concentration in elderly men. Three alcoholic beverages (beer (AB), wine (AW), and spirits (S)) and their non-alcoholic counterparts (non-alcoholic beer (NAB), non-alcoholic wine (NAW), and water (W)) were tested in a diet-controlled randomized crossover trial. For the alcoholic beverages, alcohol intake equaled a moderate amount of 30 g. An equal volume of beverage was given for the non-alcoholic counterpart. After consumption, the urine output was collected every hour for 4 h and the total 24 h urine output was measured. AW and S resulted in a higher cumulative urine output compared to NAW and W during the first 4 h (effect size: 0.25 mL p < 0.003, effect size: 0.18 mL, p < 0.001, respectively), but not after the 24h urine collection ( p > 0.40, p > 0.10). AB and NAB did not differ at any time point (effect size: -0.02 mL p > 0.70). For urine osmolality, and the sodium and potassium concentration, the findings were in line. In conclusion, only moderate amounts of stronger alcoholic beverages, such as wine and spirits, resulted in a short and small diuretic effect in elderly men.

Simvastatin Treatment Does Not Affect Serum Vitamin D Concentrations in Patients with Dyslipidemia: A Randomized Double-blind Placebo-controlled Cross-over Trial.

PubMed

Mazidi, Mohsen; Rokni, Haleh; Sahebkar, Amir Hossein; Mohammadi, Akram; Ghayour-Mobarhan, Majid; Ferns, Gordon A

2016-01-01

Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) are antihyperlipidemic drugs with an established efficacy in stabilizing atherosclerotic plaques and preventing atherogenesis and reducing cardiovascular events. The purpose of this study was to determine the effect of simvastatin on serum Vitamin D status in dyslipidemic patients as Vitamin D status has an impact on monocyte/macrophage function and may also contribute to cardiovascular risk. Selected individuals (n = 102) were treated with simvastatin (40 mg/day), or matching placebo in a randomized, double-blind, placebo-controlled, crossover trial. Each treatment period (with simvastatin or placebo) lasted for 30 days and was separated by a 2-week washout phase. Serum Vitamin D concentration was assessed pre- and post-treatment. Seventy-seven completed the trial, noncompliance with the study protocol and drug intolerance or relocation were the causes for drop-out. No significant carry-over effect was observed for the assessed parameters. There was a reduction in the serum levels of low-density lipoprotein cholesterol (P < 0.001), total cholesterol (P < 0.001), and triglycerides (P < 0.05). Nevertheless, simvastatin therapy did not significantly affect serum level of high-density lipoprotein cholesterol and Vitamin D level (P > 0.05). Short-term treatment with simvastatin (40 mg/day) does not have a significant affect on serum levels of Vitamin D.

Randomized Controlled Trial of Strain-Specific Probiotic Formulation (Renadyl) in Dialysis Patients

PubMed Central

Natarajan, Ranganathan; Mallappallil, Mary C.; Norin, Allen J.; Friedman, Eli A.; Saggi, Subodh J.

2014-01-01

Background. Primary goal of this randomized, double-blind, placebo-controlled crossover study of Renadyl in end-stage renal disease patients was to assess the safety and efficacy of Renadyl measured through improvement in quality of life or reduction in levels of known uremic toxins. Secondary goal was to investigate the effects on several biomarkers of inflammation and oxidative stress. Methods. Two 2-month treatment periods separated by 2-month washout and crossover, with physical examinations, venous blood testing, and quality of life questionnaires completed at each visit. Data were analyzed with SAS V9.2. Results. 22 subjects (79%) completed the study. Observed trends were as follows (none reaching statistical significance): decline in WBC count (−0.51 × 109/L, P = 0.057) and reductions in levels of C-reactive protein (−8.61 mg/L, P = 0.071) and total indoxyl glucuronide (−0.11 mg%, P = 0.058). No statistically significant changes were observed in other uremic toxin levels or measures of QOL. Conclusions. Renadyl appeared to be safe to administer to ESRD patients on hemodialysis. Stability in QOL assessment is an encouraging result for a patient cohort in such advanced stage of kidney disease. Efficacy could not be confirmed definitively, primarily due to small sample size and low statistical power—further studies are warranted. PMID:25147806

A randomized crossover trial to study the effect of personalized, one-to-one interaction using Montessori-based activities on agitation, affect, and engagement in nursing home residents with Dementia.

PubMed

van der Ploeg, Eva S; Eppingstall, Barbara; Camp, Cameron J; Runci, Susannah J; Taffe, John; O'Connor, Daniel W

2013-04-01

Increasingly more attention has been paid to non-pharmacological interventions as treatment of agitated behaviors that accompany dementia. The aim of the current study is to test if personalized one-to-one interaction activities based on Montessori principles will improve agitation, affect, and engagement more than a relevant control condition. We conducted a randomized crossover trial in nine residential facilities in metropolitan Melbourne, Australia (n = 44). Personalized one-to-one activities that were delivered using Montessori principles were compared with a non-personalized activity to control for the non-specific benefits of one-to-one interaction. Participants were observed 30 minutes before, during, and after the sessions. The presence or absence of a selected physically non-aggressive behavior was noted in every minute, together with the predominant type of affect and engagement. Behavior counts fell considerably during both the Montessori and control sessions relative to beforehand. During Montessori activities, the amount of time spend actively engaged was double compared to during the control condition and participants displayed more positive affect and interest as well. Participants with no fluency in English (all from non-English speaking backgrounds) showed a significantly larger reduction in agitation during the Montessori than control sessions. Our results show that even non-personalized social contact can assist in settling agitated residents. Tailoring activities to residents' needs and capabilities elicit more positive interactions and are especially suitable for people who have lost fluency in the language spoken predominantly in their residential facility. Future studies could explore implementation by family members and volunteers to avoid demands on facilities' resources. Australian New Zealand Clinical Trials Registry - ACTRN12609000564257.

Interindividual Responses of Appetite to Acute Exercise: A Replicated Crossover Study.

PubMed

Goltz, Fernanda R; Thackray, Alice E; King, James A; Dorling, James L; Atkinson, Greg; Stensel, David J

2018-04-01

Acute exercise transiently suppresses appetite, which coincides with alterations in appetite-regulatory hormone concentrations. Individual variability in these responses is suspected, but replicated trials are needed to quantify them robustly. We examined the reproducibility of appetite and appetite-regulatory hormone responses to acute exercise and quantified the individual differences in responses. Fifteen healthy, recreationally active men completed two control (60-min resting) and two exercise (60-min fasted treadmill running at 70% peak oxygen uptake) conditions in randomized sequences. Perceived appetite and circulating concentrations of acylated ghrelin and total peptide YY (PYY) were measured immediately before and after the interventions. Interindividual differences were explored by correlating the two sets of response differences between exercise and control conditions. Within-participant covariate-adjusted linear mixed models were used to quantify participant-condition interactions. Compared with control, exercise suppressed mean acylated ghrelin concentrations and appetite perceptions (all ES = 0.62-1.47, P < 0.001) and elevated total PYY concentrations (ES = 1.49, P < 0.001). For all variables, the standard deviation of the change scores was substantially greater in the exercise versus control conditions. Moderate-to-large positive correlations were observed between the two sets of control-adjusted exercise responses for all variables (r = 0.54-0.82, P ≤ 0.036). After adjusting for baseline measurements, participant-condition interactions were present for all variables (P ≤ 0.053). Our replicated crossover study allowed, for the first time, the interaction between participant and acute exercise response in appetite parameters to be quantified. Even after adjustment for individual baseline measurements, participants demonstrated individual differences in perceived appetite and hormone responses to acute exercise bouts beyond any random within-subject variability over time.

Substitution of red meat with legumes in the therapeutic lifestyle change diet based on dietary advice improves cardiometabolic risk factors in overweight type 2 diabetes patients: a cross-over randomized clinical trial.

PubMed

Hosseinpour-Niazi, S; Mirmiran, P; Hedayati, M; Azizi, F

2015-05-01

The objective of this study was to determine the effects of substitution of red meat with legumes in the Therapeutic Lifestyle Change (TLC) diet on cardiometabolic risk factors in type 2 diabetes patients based on dietary education. This study was a randomized, controlled, cross-over trial. Thirty-one participants (24 women and 7 men; age: 58.1 ± 6.0 years) with type 2 diabetes were randomly assigned to consume a control diet (legume-free TLC diet) and legume-based TLC diet for 8 weeks. Legume-based TLC diet was the same as the control diet, but the legume-based TLC group was advised to replace two servings of red meat with legumes, 3 days per week. After the interventional period, a washout period was conducted for 4 weeks. The groups were then advised to follow the alternate treatment for 8 weeks. Cardiometabolic risk factors were measured. Compared with the legume-free TLC diet, the legume-based TLC diet significantly decreased fasting blood glucose (P=0.04), fasting insulin (P=0.04), triglyceride concentrations (P=0.04) and low-density lipoprotein cholesterol (P=0.02). Total cholesterol concentrations decreased after consumption of both TLC diet and legume TLC diet; however, the data did not differ significantly between the two diets. body mass index (BMI), waist circumference, systolic and diastolic blood pressures did not change significantly after consumption of either the legume-free TLC diet or the legume-based TLC diet. Dietary advice given for substitution of red meat with legume intakes within a TLC diet-improved lipid profiles and glycemic control among diabetes patients, which were independent from BMI change. This trial was registered in the Iranian Registry of Clinical Trials (http://www.irct.ir) as IRCT201202251640N7.

Flavanones protect from arterial stiffness in postmenopausal women consuming grapefruit juice for 6 mo: a randomized, controlled, crossover trial.

PubMed

Habauzit, Véronique; Verny, Marie-Anne; Milenkovic, Dragan; Barber-Chamoux, Nicolas; Mazur, Andrzej; Dubray, Claude; Morand, Christine

2015-07-01

The consumption of citrus fruits is associated with health benefits. However, clinical data regarding the effects of grapefruit flavanone consumption on vascular function are lacking. The objective of the present study was to address the role of flavanones in the long-term effects induced by grapefruit juice (GFJ) consumption on vascular function in healthy postmenopausal women. Forty-eight healthy postmenopausal women aged 50-65 y within 3-10 y since menopause, a body mass index (in kg/m(2)) of 19-30, and a waist size >88 cm completed this double-blind, randomized, controlled, crossover trial. These volunteers were randomly assigned to consume 340 mL GFJ/d, providing 210 mg naringenin glycosides, or a matched control drink without flavanones for 6 mo each, with a 2-mo washout between beverages. The primary endpoint was the assessment of endothelial function in the brachial artery by using flow-mediated dilation. Blood pressure, arterial stiffness, and endothelial function in the peripheral arterial bed were also evaluated as indicators of vascular function. These measurements and blood collection for clinical biochemical markers were performed in overnight-fasted subjects before and after the 6-mo treatment periods. The mean ± SD carotid-femoral pulse wave velocity, which reflects central aortic stiffness, was statistically significantly lower after consumption of GFJ (7.36 ± 1.15 m/s) than after consumption of the matched control drink without flavanones (7.70 ± 1.36 m/s), with a P value of 0.019 for the treatment effect. Endothelial function in macro- and microcirculation, blood pressure, anthropometric measures, glucose metabolism, and biomarkers of inflammation and oxidative stress were not affected by the intervention. Regular GFJ consumption by middle-aged, healthy postmenopausal women is beneficial for arterial stiffness. This effect may be related to flavanones present in grapefruit. This trial was registered at clinicaltrials.gov as NCT01272167. © 2015 American Society for Nutrition.

A systematic review identifies shortcomings in the reporting of crossover trials in chronic painful conditions.

PubMed

Straube, Sebastian; Werny, Benedikt; Friede, Tim

2015-12-01

To investigate the reporting of study features of interest in abstracts and full texts of journal publications of crossover trials in chronic painful conditions. Systematic review based on a MEDLINE (PubMed) search (January 1990-August 2014). Ninety-eight publications on crossover studies with 3,513 study participants were eligible for inclusion. Double-blind status and randomized allocation to treatment groups are commonly reported in both abstracts and full texts (90 of 98 publications and 82 of 98 publications, respectively). Adverse events are reported in both abstract and full text in 49 of 98 publications and in the full text only in 44 of 98. A breakdown of results by treatment period is provided only in 23 of 98 publications, and if so, is reported only in the full text, never in the abstract. There is a time trend for the reporting of randomization in abstracts; it is more likely to be reported in recent studies (P = 0.0094). No time trends are detected in the reporting of double-blind status (P = 0.1087) and adverse events (P = 0.6084). The reporting of adverse events in the abstract and the reporting of results specified by crossover period in the full texts of journal publications on crossover pain trials should be improved. Copyright © 2015 Elsevier Inc. All rights reserved.

Spontaneous pushing to prevent postpartum urinary incontinence: a randomized, controlled trial

PubMed Central

Miller, Janis M.; Guo, Ying; Ashton-Miller, James A.; DeLancey, John O. L.; Sampselle, Carolyn M.

2014-01-01

Introduction and hypothesis The risk for urinary incontinence can be 2.6-fold greater in women after pregnancy and childbirth compared with their never-pregnant counterparts, with the incidence increasing with parity. We tested the hypothesis that the incidence of de novo postpartum urinary incontinence in primiparous women is reduced with the use of spontaneous pushing alone or in combination with perineal massage compared with women who experienced traditional directed pushing for second-stage management. Methods This was a prospective clinical trial enrolling and randomizing 249 women into a four-group design: (1) routine care with coached or directed pushing, (2) spontaneous self-directed pushing, (3) prenatal perineal massage initiated in the third trimester, and (4) the combination of spontaneous pushing plus perineal massage. Self-report of incontinence was assessed using analysis of variance (ANOVA) and covariance (ANCOVA) models in 145 remaining women at 12 months postpartum using the Leakage Index, which is sensitive to minor leakage. Results No statistical difference in the incidence of de novo postpartum incontinence was found based on method of pushing (spontaneous/directed) (P value=0.57) or in combination with prenatal perineal massage (P value=0.57). Fidelity to pushing treatment of type was assessed and between-groups crossover detected. Conclusions Spontaneous pushing did not reduce the incidence of postpartum incontinence experienced by women 1 year after their first birth due to high cross-over between randomization groups. PMID:22829349

Spontaneous pushing to prevent postpartum urinary incontinence: a randomized, controlled trial.

PubMed

Low, Lisa Kane; Miller, Janis M; Guo, Ying; Ashton-Miller, James A; DeLancey, John O L; Sampselle, Carolyn M

2013-03-01

The risk for urinary incontinence can be 2.6-fold greater in women after pregnancy and childbirth compared with their never-pregnant counterparts, with the incidence increasing with parity. We tested the hypothesis that the incidence of de novo postpartum urinary incontinence in primiparous women is reduced with the use of spontaneous pushing alone or in combination with perineal massage compared with women who experienced traditional directed pushing for second-stage management. This was a prospective clinical trial enrolling and randomizing 249 women into a four-group design: (1) routine care with coached or directed pushing, (2) spontaneous self-directed pushing, (3) prenatal perineal massage initiated in the third trimester, and (4) the combination of spontaneous pushing plus perineal massage. Self-report of incontinence was assessed using analysis of variance (ANOVA) and covariance (ANCOVA) models in 145 remaining women at 12 months postpartum using the Leakage Index, which is sensitive to minor leakage. No statistical difference in the incidence of de novo postpartum incontinence was found based on method of pushing (spontaneous/directed) (P value = 0.57) or in combination with prenatal perineal massage (P value = 0.57). Fidelity to pushing treatment of type was assessed and between-groups crossover detected. Spontaneous pushing did not reduce the incidence of postpartum incontinence experienced by women 1 year after their first birth due to high cross-over between randomization groups.

Clomiphene citrate before and after withdrawal bleeding for induction of ovulation in women with polycystic ovary syndrome: Randomized cross-over trial.

PubMed

Elbohoty, Ahmed E H; Amer, Mohamed; Abdelmoaz, Mohamed

2016-08-01

To compare the ovarian response to early versus late clomiphene citrate (CC) in women with polycystic ovary syndrome (PCOS). This cross-over randomized controlled clinical trial included 90 infertile amenorrheic women with PCOS. After inducing withdrawal bleeding, patients were randomly divided into two equal groups to receive ovulation induction with CC 100 mg/day for 5 days. Group I started treatment the next day after finishing medroxyprogesterone acetate course for a menstrual cycle, and after a washout period of another menstrual cycle, the treatment was shifted to start on day 2 of withdrawal bleeding. Group II received a reversed protocol: late then early treatment. Women were followed up on transvaginal ultrasonography to monitor follicular growth, endometrial thickness and evidence of ovulation. Human chorionic gonadotropin 10 000 IU was given i.m. to trigger ovulation when at least one mature follicle measured ≥18 mm at day 14. In all cases, early induction protocol resulted in significantly higher proportion of ovulating patients, thicker endometrium and higher number of follicles 14-17 mm in diameter, ≥ 18 mm in diameter and total number of follicles (P < 0.001 for all comparisons). In women with PCOS, early initiation of CC before withdrawal bleeding or during the last days of the luteal phase can achieve a better ovulatory response. © 2016 Japan Society of Obstetrics and Gynecology.

Topical tocopherol for treatment of reticular oral lichen planus: a randomized, double-blind, crossover study.

PubMed

Bacci, C; Vanzo, V; Frigo, A C; Stellini, E; Sbricoli, L; Valente, M

2017-01-01

This randomized, double-blind, placebo-controlled crossover study assessed the efficacy of topical tocopherol acetate compared with placebo in easing oral discomfort in patients with reticular oral lichen planus (ROLP). Thirty-four patients with clinically diagnosed and histologically confirmed ROLP were randomly assigned to two groups, which received first one of two treatments (treatment 1 or 2) for a month, then the other (treatment 2 or 1) for another month, with a two-week washout between them. One treatment contained tocopherol acetate and the other only liquid paraffin. The primary outcome was less discomfort, measured on a visual analog scale (VAS). Secondary outcomes were as follows: length of striae measured and photographed at each follow-up; surface area of lesions; and a modified Thongprasom score. No statistically significant differences emerged between the two treatments (1 vs 2) in terms of VAS scores (P > 0.05; 0.8624) or length of striae (P = 0.0883). Significant differences were seen for surface area of lesions (P < 0.05, P = 0.0045) and modified Thongprasom scores (P = 0.0052). The two treatments differed only in terms of the surface area of the lesions and Thongprasom scores, not in VAS scores for discomfort or the length of patients' striae. Topical tocopherol proved effective in the treatment of ROLP. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Synbiotic Lactobacillus acidophilus NCFM and cellobiose does not affect human gut bacterial diversity but increases abundance of lactobacilli, bifidobacteria and branched-chain fatty acids: a randomized, double-blinded cross-over trial.

PubMed

van Zanten, Gabriella C; Krych, Lukasz; Röytiö, Henna; Forssten, Sofia; Lahtinen, Sampo J; Abu Al-Soud, Waleed; Sørensen, Søren; Svensson, Birte; Jespersen, Lene; Jakobsen, Mogens

2014-10-01

Probiotics, prebiotics, and combinations thereof, that is synbiotics, have been reported to modulate gut microbiota of humans. In this study, effects of a novel synbiotic on the composition and metabolic activity of human gut microbiota were investigated. Healthy volunteers (n = 18) were enrolled in a double-blinded, randomized, and placebo-controlled cross-over study and received synbiotic [Lactobacillus acidophilus NCFM (10(9) CFU) and cellobiose (5 g)] or placebo daily for 3 weeks. Fecal samples were collected and lactobacilli numbers were quantified by qPCR. Furthermore, 454 tag-encoded amplicon pyrosequencing was used to monitor the effect of synbiotic on the composition of the microbiota. The synbiotic increased levels of Lactobacillus spp. and relative abundances of the genera Bifidobacterium, Collinsella, and Eubacterium while the genus Dialister was decreased (P < 0.05). No other effects were found on microbiota composition. Remarkably, however, the synbiotic increased concentrations of branched-chain fatty acids, measured by gas chromatography, while short-chain fatty acids were not affected. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Effects of a 6-month multimodal training intervention on retention of functional fitness in older adults: a randomized-controlled cross-over design.

PubMed

Gudlaugsson, Janus; Gudnason, Vilmundur; Aspelund, Thor; Siggeirsdottir, Kristin; Olafsdottir, Anna S; Jonsson, Palmi V; Arngrimsson, Sigurbjorn A; Harris, Tamara B; Johannsson, Erlingur

2012-09-10

Older adults have the highest rates of disability, functional dependence and use of healthcare resources. Training interventions for older individuals are of special interest where regular physical activity (PA) has many health benefits. The main purpose of this study was to assess the immediate and long-term effects of a 6-month multimodal training intervention (MTI) on functional fitness in old adults. For this study, 117 participants, 71 to 90 years old, were randomized in immediate intervention group and a control group (delayed intervention group). The intervention consisted of daily endurance and twice-a-week strength training. The method was based on a randomized-controlled cross-over design. Short Physical Performance Battery (SPPB), 8 foot up-and-go test, strength performance, six min walking test (6 MW), physical activity, BMI and quality of life were obtained at baseline, after a 6-month intervention- and control phase, again after 6-month crossover- and delayed intervention phase, and after anadditional 6-month follow-up. After 6 months of MTI, the intervention group improved in physical performance compared with the control group via Short Physical Performance Battery (SPPB) score (mean diff = 0.6, 95 % CI: 0.1, 1.0) and 8-foot up-and-go test (mean diff = -1.0 s, 95 % CI: -1.5, -0.6), and in endurance performance via 6-minute walking test (6 MW) (mean diff = 44.2 meters, 95 % CI: 17.1, 71.2). In strength performance via knee extension the intervention group improved while control group declined (mean diff = 55.0 Newton, 95 % CI: 28.4, 81.7), and also in PA (mean diff = 125.9 cpm, 95 % CI: 96.0, 155.8). Long-term effects of MTI on the particpants was assesed by estimating the mean difference in the variables measured between time-point 1 and 4: SPPB (1.1 points, 95 % CI: 0.8, 1.4); 8-foot up-and-go (-0.9 s, 95 % CI: -1.2, -0.6); 6 MW (18.7 m, 95 % CI: 6.5, 31.0); knee extension (4.2 Newton, 95 % CI: -10.0, 18.3); hand grip (6.7 Newton, 95 % CI: -4.4, 17.8); PA (-4.0 cpm, 95 % CI: -33.9, 26.0); BMI (-0.6 kg/m2, 95 % CI: -0.9, -0.3) and Icelandic quality of life (0.3 points, 95 % CI: -0.7, 1.4). Our results suggest that regular MTI can improve and prevent decline in functional fitness in older individuals, influence their lifestyle and positively affect their ability to stay independent, thus reducing the need for institutional care. This study was approved by the National Bioethics Committee in Iceland, VSNb20080300114/03-1.

Control of Meiotic Crossovers: From Double-Strand Break Formation to Designation

PubMed Central

Gray, Stephen

2017-01-01

Meiosis, the mechanism of creating haploid gametes, is a complex cellular process observed across sexually reproducing organisms. Fundamental to meiosis is the process of homologous recombination, whereby DNA double-strand breaks are introduced into the genome and are subsequently repaired to generate either noncrossovers or crossovers. Although homologous recombination is essential for chromosome pairing during prophase I, the resulting crossovers are critical for maintaining homolog interactions and enabling accurate segregation at the first meiotic division. Thus, the placement, timing, and frequency of crossover formation must be exquisitely controlled. In this review, we discuss the proteins involved in crossover formation, the process of their formation and designation, and the rules governing crossovers, all within the context of the important landmarks of prophase I. We draw together crossover designation data across organisms, analyze their evolutionary divergence, and propose a universal model for crossover regulation. PMID:27648641

Cognitive-Functional (Cog-Fun) Dyadic Intervention for Children with ADHD and Their Parents: Impact on Parenting Self-Efficacy.

PubMed

Hahn-Markowitz, Jeri; Berger, Itai; Manor, Iris; Maeir, Adina

2018-03-01

The family context of children with ADHD plays a role in intervention outcomes, especially when parents are involved in treatment. Parental participation in evidence-based treatment for ADHD may play a role in improving their own parenting self-efficacy (PSE) as well as child outcomes. This study examined the impact of Cognitive-Functional (Cog-Fun) intervention in occupational therapy (OT) for school-aged children with ADHD, on PSE. In this randomized controlled trial with crossover design, 107 children were allocated to intervention and waitlist control groups. Intervention participants (n = 50) received Cog-Fun after baseline assessment and waitlist controls (n = 49) received treatment 3 months later. Intervention participants received 3-month follow-up assessment. Treatment included 10 parent-child Cog-Fun weekly sessions. PSE was assessed with the Tool to measure Parenting Self-Efficacy (TOPSE). All children who began treatment completed it. Mixed ANOVA revealed significant Time x Group interaction effects on TOPSE scales of Play and Enjoyment, Control, Self-Acceptance, Knowledge and Learning and Total score, which showed significant improvement with moderate treatment effects for the intervention group. Results were replicated in the control group after crossover. The findings of this study suggest that Cog-Fun OT intervention may be effective for improving aspects of PSE among parents of children with ADHD.

Improving Nurses' Peripheral Intravenous Catheter Insertion Knowledge, Confidence, and Skills Using a Simulation-Based Blended Learning Program: A Randomized Trial.

PubMed

Keleekai, Nowai L; Schuster, Catherine A; Murray, Connie L; King, Mary Anne; Stahl, Brian R; Labrozzi, Laura J; Gallucci, Susan; LeClair, Matthew W; Glover, Kevin R

2016-12-01

Peripheral intravenous catheter (PIVC) insertion is one of the most common invasive procedures performed in a hospital, but most nurses receive little formal training in this area. Blended PIVC insertion training programs that incorporate deliberate simulated practice have the potential to improve clinical practice and patient care. The study was a randomized, wait-list control group with crossover using nurses on three medical/surgical units. Baseline PIVC knowledge, confidence, and skills assessments were completed for both groups. The intervention group then received a 2-hour PIVC online course, followed by an 8-hour live training course using a synergistic mix of three simulation tools. Both groups were then reassessed. After crossover, the wait-list group received the same intervention and both groups were reassessed. At baseline, both groups were similar for knowledge, confidence, and skills. Compared with the wait-list group, the intervention group had significantly higher scores for knowledge, confidence, and skills upon completing the training program. After crossover, the wait-list group had similarly higher scores for knowledge, confidence, and skills than the intervention group. Between the immediate preintervention and postintervention periods, the intervention group improved scores for knowledge by 31%, skills by 24%, and decreased confidence by 0.5%, whereas the wait-list group improved scores for knowledge by 28%, confidence by 16%, and skills by 15%. Results demonstrate significant improvements in nurses' knowledge, confidence, and skills with the use of a simulation-based blended learning program for PIVC insertion. Transferability of these findings from a simulated environment into clinical practice should be further explored.

Study protocol and rationale for a randomized double-blinded crossover trial of phentermine-topiramate ER versus placebo to treat binge eating disorder and bulimia nervosa.

PubMed

Dalai, Shebani Sethi; Adler, Sarah; Najarian, Thomas; Safer, Debra Lynn

2018-01-01

Bulimia nervosa (BN) and binge eating disorder (BED) are associated with severe psychological and medical consequences. Current therapies are limited, leaving up to 50% of patients symptomatic despite treatment, underscoring the need for additional treatment options. Qsymia, an FDA-approved medication for obesity, combines phentermine and topiramate ER. Topiramate has demonstrated efficacy for both BED and BN, but limited tolerability. Phentermine is FDA-approved for weight loss. A rationale for combined phentermine/topiramate for BED and BN is improved tolerability and efficacy. While a prior case series exploring Qsymia for BED showed promise, randomized studies are needed to evaluate Qsymia's safety and efficacy when re-purposed in eating disorders. We present a study protocol for a Phase I/IIa single-center, prospective, double-blinded, randomized, crossover trial examining safety and preliminary efficacy of Qsymia for BED and BN. Adults with BED (n=15) or BN (n=15) are randomized 1:1 to receive 12weeks Qsymia (phentermine/topiramate ER, 3.75mg/23mg-15mg/92mg) or placebo, followed by 2-weeks washout and 12-weeks crossover, where those on Qsymia receive placebo and vice versa. Subsequently participants receive 8weeks follow-up off study medications. The primary outcome is the number of binge days/week measured by EDE. Secondary outcomes include average number of binge episodes, percentage abstinence from binge eating, and changes in weight/vitals, eating psychopathology, and mood. To our knowledge this is the first randomized, double-blind protocol investigating the safety and efficacy of phentermine/topiramate in BED and BN. We highlight the background and rationale for this study, including the advantages of a crossover design. Clinicaltrials.gov identifier NCT02553824 registered on 9/17/2015. https://clinicaltrials.gov/ct2/show/NCT02553824. Copyright © 2017 Elsevier Inc. All rights reserved.

Cue-induced smoking urges deplete cigarette smokers' self-control resources.

PubMed

Hagger, Martin S; Leaver, Eamonn; Esser, Kerstin; Leung, Chung-Ming; Te Pas, Nina; Keatley, David A; Chan, Derwin K-C; Chatzisarantis, Nikos L D

2013-12-01

Exposure to smoking-related cues leads to increased urge to smoke in regular cigarette smokers and resisting these urges requires considerable self-control. Adopting a resource depletion model, two studies tested the hypothesis that resisting smoking urges depletes self-control resources. Adopting a within-participants randomized cross-over design, participants (study 1, N = 19; study 2, N = 32) were exposed to smoking-related (study 1: smoking images; study 2: cigarette cue-exposure task) and neutral (study 1: neutral images; study 2: drinking-straw task) cues with presentation order randomized. After each cue set, participants completed self-control tasks (study 1: handgrip task; study 2: handgrip and Stroop tasks), performance on which constituted dependent measures of self-control. Self-control task performance was significantly impaired when exposed to smoking-related cues compared to neutral cues. No significant presentation-order effects, or interaction effects between stimulus and presentation order, were found. Findings corroborate our hypothesis that resisting smoking urges depletes cigarette smokers' self-control resources and suggests that self-control capacity is governed by a limited resource.

A Randomized, Double-Blind, Placebo-Controlled Crossover Study of the Anti-Inflammatory Compound Anatabine to Treat Pain in GWI Patients

DTIC Science & Technology

2016-10-01

inflammation. Over the last few years we have carried out extensive work on the dietary supplement Anatabine (Rock Creek Pharmaceuticals Inc.), which is a...minor adverse effects reported. Anatabine products are no longer available as dietary supplements as the compound company is pursuing pharmaceutical use...compound, which was available from Rock Creek Pharmaceuticals (RCP) for several years (2010-2014) as a dietary supplement . It is no longer being sold as a

Are glucose levels, glucose variability and autonomic control influenced by inspiratory muscle exercise in patients with type 2 diabetes? Study protocol for a randomized controlled trial.

PubMed

Schein, Aso; Correa, Aps; Casali, Karina Rabello; Schaan, Beatriz D

2016-01-20

Physical exercise reduces glucose levels and glucose variability in patients with type 2 diabetes. Acute inspiratory muscle exercise has been shown to reduce these parameters in a small group of patients with type 2 diabetes, but these results have yet to be confirmed in a well-designed study. The aim of this study is to investigate the effect of acute inspiratory muscle exercise on glucose levels, glucose variability, and cardiovascular autonomic function in patients with type 2 diabetes. This study will use a randomized clinical trial crossover design. A total of 14 subjects will be recruited and randomly allocated to two groups to perform acute inspiratory muscle loading at 2 % of maximal inspiratory pressure (PImax, placebo load) or 60 % of PImax (experimental load). Inspiratory muscle training could be a novel exercise modality to be used to decrease glucose levels and glucose variability. ClinicalTrials.gov NCT02292810 .

Linear combinations come alive in crossover designs.

PubMed

Shuster, Jonathan J

2017-10-30

Before learning anything about statistical inference in beginning service courses in biostatistics, students learn how to calculate the mean and variance of linear combinations of random variables. Practical precalculus examples of the importance of these exercises can be helpful for instructors, the target audience of this paper. We shall present applications to the "1-sample" and "2-sample" methods for randomized short-term 2-treatment crossover studies, where patients experience both treatments in random order with a "washout" between the active treatment periods. First, we show that the 2-sample method is preferred as it eliminates "conditional bias" when sample sizes by order differ and produces a smaller variance. We also demonstrate that it is usually advisable to use the differences in posttests (ignoring baseline and post washout values) rather than the differences between the changes in treatment from the start of the period to the end of the period ("delta of delta"). Although the intent is not to provide a definitive discussion of crossover designs, we provide a section and references to excellent alternative methods, where instructors can provide motivation to students to explore the topic in greater detail in future readings or courses. Copyright © 2017 John Wiley & Sons, Ltd.

Comparison of the inhibitory effects of cilostazol, acetylsalicylic acid and ticlopidine on platelet functions ex vivo. Randomized, double-blind cross-over study.

PubMed

Ikeda, Y; Kikuchi, M; Murakami, H; Satoh, K; Murata, M; Watanabe, K; Ando, Y

1987-05-01

A randomized double-blind cross-over study was conducted to determine the inhibitory effects of acetylsalicylic acid (ASA), ticlopidine (TP) and cilostazol (OPC-13013; in the following briefly called CS), a new antithrombotic agent on platelet functions ex vivo. Nine patients with cerebral thrombosis were enrolled in this study. Patients were given each of the three drugs for one week in a complete cross-over design according to a randomization schedule, followed by a wash-out period with a placebo for one week. It was found that CS and TP significantly inhibited platelet aggregation induced by ADP. Collagen- and arachidonic acid-induced platelet aggregation was all inhibited by CS, TP and ASA. Duncan's multiple range test to compare the anti-platelet effects of the three drugs revealed that: CS greater than ASA and TP greater than ASA in inhibiting ADP-induced platelet aggregation and CS greater than TP and ASA greater than TP in inhibiting arachidonic acid-induced platelet aggregation. These results may suggest that CS is superior to ASA and TP in inhibiting platelet aggregation ex vivo.

Efficacy of topical Rose (Rosa damascena Mill.) oil for migraine headache: A randomized double-blinded placebo-controlled cross-over trial.

PubMed

Niazi, Maria; Hashempur, Mohammad Hashem; Taghizadeh, Mohsen; Heydari, Mojtaba; Shariat, Abdolhamid

2017-10-01

To evaluate the effect of topical formulation of Rosa damascena Mill. (R. damascena) oil on migraine headache, applying syndrome diffrentiation model. Forty patients with migraine headache were randomly assigned to 2 groups of this double-blind, placebo-controlled cross-over trial. The patients were treated for the first 2 consecutive migraine headache attacks by topical R. damascena oil or placebo. Then, after one week of washout period, cross-over was done. Pain intensity of the patients' migraine headache was recorded at the beginnig and ten-sequence time schadule of attacks up to 24h. In addition, photophobia, phonophobia, and nausea and/or vomitting (N/V) of the patients were recorded as secondary outcomes. Finally, gathered data were analysed in a syndrome differentiation manner to assess the effect of R. damascena oil on Hot- and Cold-type migraine headache. Mean pain intensity of the patients' migraine headache in the different time-points after R. damascena oil or placebo use, was not significantly different. Additionally, regarding mean scores of N/V, photophobia, and phonophobia severity of the patients, no significant differences between the two groups were observed. Finally, applying syndrome differentiation model, the mean score of migraine headache pain intensity turned out to be significantly lower in patients with "hot" type migraine syndrome at in 30, 45, 60, 90, and 120min after R. damascena oil application compared to "cold" types (P values: 0.001, 0.001, <0.001, <0.001, and 0.02; respectively). It seems that syndrome differentiation can help in selection of patients who may benefit from the topical R. damascena oil in short-term relief of pain intensity in migraine headache. Further studies of longer follow-up and larger study population, however, are necessitated for more scientifically rigorous judgment on efficacy of R. damascena oil for patients with migraine headache. Copyright © 2017 Elsevier Ltd. All rights reserved.

Efficacy of piracetam in the treatment of tardive dyskinesia in schizophrenic patients: a randomized, double-blind, placebo-controlled crossover study.

PubMed

Libov, Igor; Miodownik, Chanoch; Bersudsky, Yuly; Dwolatzky, Tzvi; Lerner, Vladimir

2007-07-01

Piracetam is a potent antioxidant, a cerebral neuroprotector, a neuronal metabolic enhancer, and a brain integrative agent. More than 20 years ago, an intravenous preparation of piracetam demonstrated an improvement in the symptoms of tardive dyskinesia. The aim of our study was to reexamine the efficacy of piracetam in the treatment of tardive dyskinesia using an oral preparation. The study was conducted at the Be'er Sheva Mental Health Center from May 2003 to December 2004 and involved a 9-week, double-blind, crossover, placebo-controlled trial assessing 40 DSM-IV schizophrenic and schizo-affective patients with DSM-IV-TR tardive dyskinesia. All study subjects received their usual antipsychotic treatment. Initially, subjects were randomly assigned to receive 4 weeks of treatment with either piracetam (4800 mg/day) or placebo. Thereafter, following a washout period of 1 week, they entered the crossover phase of the study for a further 4 weeks. The change in score of the Extrapyramidal Symptom Rating Scale from baseline to the study endpoint was the primary outcome measure. The mean decrease in score from baseline to endpoint in the clinical global impression subscale in patients treated with piracetam was 1.1 points compared to 0.1 points in the placebo group (p = .004). The mean decrease in the tardive parkinsonism subscale was 8.7 points in patients treated with piracetam and 0.6 points in those on placebo (p = .001). The mean decrease in the tardive dyskinesia subscale was 3.0 points in the piracetam group in contrast to deterioration of condition in the placebo group by -0.2 points (p = .003). Piracetam appears to be effective in reducing symptoms of tardive dyskinesia. The specific mechanism by which piracetam may attenuate symptoms of tardive dyskinesia needs to be further evaluated. ClinicalTrials.gov identifier NCT00190008.

Crossover from impurity-controlled to granular superconductivity in (TMTSF) 2ClO4

NASA Astrophysics Data System (ADS)

Yonezawa, Shingo; Marrache-Kikuchi, Claire A.; Bechgaard, Klaus; Jérome, Denis

2018-01-01

Using a proper cooling procedure, a controllable amount of nonmagnetic structural disorder can be introduced at low temperature in (TMTSF) 2ClO4 . Here we performed simultaneous measurements of transport and magnetic properties of (TMTSF) 2ClO4 in its normal and superconducting states, while finely covering three orders of magnitude of the cooling rate around the anion ordering temperature. Our result reveals, with increasing density of disorder, the existence of a crossover between homogeneous defect-controlled d -wave superconductivity and granular superconductivity. At slow cooling rates, with small amount of disorder, the evolution of superconducting properties is well described with the Abrikosov-Gorkov theory, providing further confirmation of non-s -wave pairing in this compound. In contrast, at fast cooling rates, zero resistance and diamagnetic shielding are achieved through a randomly distributed network of superconducting puddles embedded in a normal conducting background and interconnected by proximity effect coupling. The temperature dependence of the ac complex susceptibility reveals features typical for a network of granular superconductors. This makes (TMTSF) 2ClO4 a model system for granular superconductivity where the grain size and their concentration are tunable within the same sample.

Impact of treatment crossovers on clinical outcomes in the rate and rhythm control strategies for atrial fibrillation: Insights from the AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) trial.

PubMed

Maan, Abhishek; Zhang, Zheng; Qin, Ziling; Wang, Yanbing; Dudley, Samuel; Dabhadakar, Kaustubh; Refaat, Marwan; Mansour, Moussa; Ruskin, Jeremy N; Heist, E Kevin

2017-07-01

We investigated the rates and reasons for crossover to alternative treatment strategies and its impact on mortality in patients who were enrolled in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial. Over a mean follow-up period of 3.5 years, 842 patients underwent crossover to the alternative treatment arms in AFFIRM. The rate of crossover from rhythm to rate control (594/2,033, 29.2%) was more frequent than the rate of crossover from rate to rhythm control (248/2,027, 12.2%, P < 0.0001). The leading reasons for crossover from rhythm to rate control were failure to achieve or maintain sinus rhythm (272/594, 45.8%) and intolerable adverse effects (122/594, 20.5%). In comparison, the major reasons for crossover from rate to rhythm control were failure to control atrial fibrillation symptoms (159/248, 64.1%) and intolerable adverse effects (9/248, 3.6%). This difference in crossover pattern was statistically significant (P < 0.0001). There was a significantly decreased risk of all-cause mortality (adjusted HR: 0.61, 95% CI: 0.48-0.78, P < 0.0001) and cardiac mortality (adjusted hazard ratio [HR]: 0.61, 95% confidence interval [CI]: 0.43-0.88, P = 0.008) in the subgroup of patients who crossed over from rhythm to rate control as compared to those who continued in rhythm control. There was a nonsignificant trend toward decreased all-cause (adjusted HR: 0.76, 95% CI: 0.53-1.10, P = 0.14) and cardiac mortality (adjusted HR: 0.70, 95% CI: 0.42-1.18, P = 0.18) in patients who crossed over from rate to rhythm control as compared to those who continued rate control. © 2017 Wiley Periodicals, Inc.

Antibiotic rotation strategies to reduce antimicrobial resistance in Gram-negative bacteria in European intensive care units: study protocol for a cluster-randomized crossover controlled trial.

PubMed

van Duijn, Pleun J; Bonten, Marc J M

2014-07-10

Intensive care units (ICU) are epicenters for the emergence of antibiotic-resistant Gram-negative bacteria (ARGNB) because of high rates of antibiotic usage, rapid patient turnover, immunological susceptibility of acutely ill patients, and frequent contact between healthcare workers and patients, facilitating cross-transmission.Antibiotic stewardship programs are considered important to reduce antibiotic resistance, but the effectiveness of strategies such as, for instance, antibiotic rotation, have not been determined rigorously. Interpretation of available studies on antibiotic rotation is hampered by heterogeneity in implemented strategies and suboptimal study designs. In this cluster-randomized, crossover trial the effects of two antibiotic rotation strategies, antibiotic mixing and cycling, on the prevalence of ARGNB in ICUs are determined. Antibiotic mixing aims to create maximum antibiotic heterogeneity, and cycling aims to create maximum antibiotic homogeneity during consecutive periods. This is an open cluster-randomized crossover study of mixing and cycling of antibiotics in eight ICUs in five European countries. During cycling (9 months) third- or fourth-generation cephalosporins, piperacillin-tazobactam and carbapenems will be rotated during consecutive 6-week periods as the primary empiric treatment in patients suspected of infection caused by Gram-negative bacteria. During mixing (9 months), the same antibiotics will be rotated for each consecutive antibiotic course. Both intervention periods will be preceded by a baseline period of 4 months. ICUs will be randomized to consecutively implement either the mixing and then cycling strategy, or vice versa. The primary outcome is the ICU prevalence of ARGNB, determined through monthly point-prevalence screening of oropharynx and perineum. Secondary outcomes are rates of acquisition of ARGNB, bacteremia and appropriateness of therapy, length of stay in the ICU and ICU mortality. Results will be adjusted for intracluster correlation, and patient- and ICU-level variables of case-mix and infection-prevention measures using advanced regression modeling. This trial will determine the effects of antibiotic mixing and cycling on the unit-wide prevalence of ARGNB in ICUs. ClinicalTrials.gov NCT01293071 December 2010.

A Randomized, Double Crossover Study to Investigate the Influence of Saline Infusion on Sleep Apnea Severity in Men

PubMed Central

Yadollahi, Azadeh; Gabriel, Joseph M.; White, Laura H.; Taranto Montemurro, Luigi; Kasai, Takatoshi; Bradley, T. Douglas

2014-01-01

Study Objectives: Obstructive sleep apnea (OSA) is commoner in patients with fluid-retaining states than in those without fluid retention, in men than in women, and worsens with aging. In men, OSA severity is related to the amount of fluid shifting out of the legs overnight, but a cause-effect relationship is not established. Our objective was to test the hypothesis that mimicking fluid overload during sleep would increase severity of OSA more in older (≥ 40 years) than in younger men (< 40 years). Design: Randomized, single-blind, double crossover study. Setting: Research sleep laboratory. Patients or Participants: Seven older and 10 younger men with non-severe or no sleep apnea, matched for body mass index. Interventions: During the control arm, normal saline was infused to keep the vein open. During intervention, subjects received an intravenous bolus of normal saline (22 mL/kg body weight) after sleep onset while they were wearing compression stockings to prevent fluid accumulation in the legs. Measurements and Results: Compared to younger men, infusion of similar amounts of saline in older men caused a greater increase in neck circumference (P < 0.05) and in the AHI (32.2 ± 22.1 vs. 2.2 ± 7.1, P = 0.002). Conclusions: Older men are more susceptible to the adverse effects of intravenous fluid loading on obstructive sleep apnea severity than younger men. This may be due to age-related differences in the amount of fluid accumulating in the neck or upper airway collapsibility in response to intravenous fluid loading. These possibilities remain to be tested in future studies. Citation: Yadollahi A, Gabriel JM, White LH, Taranto Montemurro L, Kasai T, Bradley TD. A randomized, double crossover study to investigate the influence of saline infusion on sleep apnea severity in men. SLEEP 2014;37(10):1699-1705. PMID:25197812

Impact of palm date consumption on microbiota growth and large intestinal health: a randomised, controlled, cross-over, human intervention study.

PubMed

Eid, Noura; Osmanova, Hristina; Natchez, Cecile; Walton, Gemma; Costabile, Adele; Gibson, Glenn; Rowland, Ian; Spencer, Jeremy P E

2015-10-28

The reported inverse association between the intake of plant-based foods and a reduction in the prevalence of colorectal cancer may be partly mediated by interactions between insoluble fibre and (poly)phenols and the intestinal microbiota. In the present study, we assessed the impact of palm date consumption, rich in both polyphenols and fibre, on the growth of colonic microbiota and markers of colon cancer risk in a randomised, controlled, cross-over human intervention study. A total of twenty-two healthy human volunteers were randomly assigned to either a control group (maltodextrin-dextrose, 37·1 g) or an intervention group (seven dates, approximately 50 g). Each arm was of 21 d duration and was separated by a 14-d washout period in a cross-over manner. Changes in the growth of microbiota were assessed by fluorescence in situ hybridisation analysis, whereas SCFA levels were assessed using HPLC. Further, ammonia concentrations, faecal water genotoxicity and anti-proliferation ability were also assessed using different assays, which included cell work and the Comet assay. Accordingly, dietary intakes, anthropometric measurements and bowel movement assessment were also carried out. Although the consumption of dates did not induce significant changes in the growth of select bacterial groups or SCFA, there were significant increases in bowel movements and stool frequency (P<0·01; n 21) and significant reductions in stool ammonia concentration (P<0·05; n 21) after consumption of dates, relative to baseline. Furthermore, date fruit intake significantly reduced genotoxicity in human faecal water relative to control (P<0·01; n 21). Our data indicate that consumption of date fruit may reduce colon cancer risk without inducing changes in the microbiota.

An efficient early phase 2 procedure to screen medications for efficacy in smoking cessation.

PubMed

Perkins, Kenneth A; Lerman, Caryn

2014-01-01

Initial screening of new medications for potential efficacy (i.e., Food and Drug Administration (FDA) early phase 2), such as in aiding smoking cessation, should be efficient in identifying which drugs do, or do not, warrant more extensive (and expensive) clinical testing. This focused review outlines our research on development, evaluation, and validation of an efficient crossover procedure for sensitivity in detecting medication efficacy for smoking cessation. First-line FDA-approved medications of nicotine patch, varenicline, and bupropion were tested as model drugs, in three separate placebo-controlled studies. We also tested specificity of our procedure in identifying a drug that lacks efficacy, using modafinil. This crossover procedure showed sensitivity (increased days of abstinence) during week-long "practice" quit attempts with each of the active cessation medications (positive controls) versus placebo, but not with modafinil (negative control) versus placebo, as hypothesized. Sensitivity to medication efficacy signal was observed only in smokers high in intrinsic quit motivation (i.e., already preparing to quit soon) and not smokers low in intrinsic quit motivation, even if monetarily reinforced for abstinence (i.e., given extrinsic motivation). A crossover procedure requiring less time and fewer subjects than formal trials may provide an efficient strategy for a go/no-go decision whether to advance to subsequent phase 2 randomized clinical trials with a novel drug. Future research is needed to replicate our results and evaluate this procedure with novel compounds, identify factors that may limit its utility, and evaluate its applicability to testing efficacy of compounds for treating other forms of addiction.

A Randomized, Placebo-Controlled, Crossover Trial of Cannabis Cigarettes in Neuropathic Pain

PubMed Central

Wilsey, Barth; Marcotte, Thomas; Tsodikov, Alexander; Millman, Jeanna; Bentley, Heather; Gouaux, Ben; Fishman, Scott

2016-01-01

The Food and Drug Administration (FDA), Substance Abuse and Mental Health Services Administration (SAMHSA), and the National Institute for Drug Abuse (NIDA) report that no sound scientific studies support the medicinal use of cannabis. Despite this lack of scientific validation, many patients routinely use “medical marijuana,” and in many cases this use is for pain related to nerve injury. We conducted a double-blinded, placebo-controlled, crossover study evaluating the analgesic efficacy of smoking cannabis for neuropathic pain. Thirty-eight patients with central and peripheral neuropathic pain underwent a standardized procedure for smoking either high-dose (7%), low-dose (3.5%), or placebo cannabis. In addition to the primary outcome of pain intensity, secondary outcome measures included evoked pain using heat-pain threshold, sensitivity to light touch, psychoactive side effects, and neuropsychological performance. A mixed linear model demonstrated an analgesic response to smoking cannabis. No effect on evoked pain was seen. Psychoactive effects were minimal and well-tolerated, with some acute cognitive effects, particularly with memory, at higher doses. PMID:18403272

Effect of gum chewing on gastric volume and emptying: a prospective randomized crossover study.

PubMed

Bouvet, L; Loubradou, E; Desgranges, F-P; Chassard, D

2017-11-01

Current fasting guidelines allow oral intake of water up to 2 h before induction of anaesthesia. We assessed whether gum chewing affects gastric emptying of 250 ml water and residual gastric fluid volume measured 2 h after ingestion of water. This prospective randomized observer-blind crossover trial was performed on 20 healthy volunteers who attended two separate study sessions: Control and Chewing gum (chlorophyll flavour, with 2.1 g carbohydrate). Each session started with an ultrasound measurement of the antral area, followed by drinking 250 ml water. Then, volunteers either chewed a sugared gum for 45 min (Chewing gum) or did not (Control). Serial measurements of the antral area were performed during 120 min, and the half-time to gastric emptying (t½), total gastric emptying time, and gastric fluid volume before ingestion of water and 120 min later were calculated. Gastric emptying of water was not different between sessions; the mean (sdsd) t½ was 23 (10) min in the Control session and 21 (7) min in the Chewing gum session (P=0.52). There was no significant difference between sessions in gastric fluid volumes measured before ingestion of water and 120 min later. Chewing gum does not affect gastric emptying of water and does not change gastric fluid volume measured 2 h after ingestion of water. NCT02673307. © The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Short-term effect of strontium- and zinc-containing toothpastes and mouthrinses on volatile sulphur compounds in morning breath: a randomized, double-blind, cross-over clinical study.

PubMed

Soares, Léo G; Jonski, Grazyna; Tinoco, Eduardo M B; Young, Alix

2015-04-01

Zinc (Zn) reduces the formation of volatile sulphur compounds (VSCs) associated with oral malodour. Although strontium (Sr) is included in some products for reducing dental hypersensitivity, it may also have anti-halitosis properties. This randomized, double-blind, cross-over clinical study compared the anti-VSC effect of brushing with commercial toothpastes and rinses containing Zn and Sr. The volunteers (n = 30) either brushed/rinsed with/without tongue brushing using Zn-containing toothpaste/rinse, Sr-containing toothpaste/rinse, or placebo (control). Volatile sulphur compounds [hydrogen sulphide (H2 S) and methyl mercaptan (CH3 SH)] were measured, in morning breath, using gas chromatography. The anti-VSC effects of the test toothpastes and test rinses were significantly better than the anti-VSC effects of the respective controls. Toothbrushing with test toothpastes gave median reductions, compared with the control, of 70% for H2 S and 55-57% for CH3 SH. Rinsing with the Sr- and Zn-containing solutions had the same anti-VSC effect as toothbrushing and tooth- and tongue brushing with the Sr- and Zn-containing toothpastes. Zinc-containing rinse resulted in a significantly higher median salivary level of Zn compared with brushing with Zn-containing toothpaste, although this effect did not correlate with the anti-VSC effect. It can be concluded that the Sr- and Zn-containing toothpastes and the Zn- and Sr-containing rinses, when used in the evening, are equally effective in reducing morning-breath VSCs the following day. © 2015 Eur J Oral Sci.

Hesperidin contributes to the vascular protective effects of orange juice: a randomized crossover study in healthy volunteers.

PubMed

Morand, Christine; Dubray, Claude; Milenkovic, Dragan; Lioger, Delphine; Martin, Jean François; Scalbert, Augustin; Mazur, Andrzej

2011-01-01

Although numerous human studies have shown consistent effects of some polyphenol-rich foods on several intermediate markers for cardiovascular diseases, it is still unknown whether their action could be specifically related to polyphenols. We investigated the effect of orange juice and its major flavonoid, hesperidin, on microvascular reactivity, blood pressure, and cardiovascular risk biomarkers through both postprandial and chronic intervention studies. Twenty-four healthy, overweight men (age 50-65 y) were included in a randomized, controlled, crossover study. Throughout the three 4-wk periods, volunteers daily consumed 500 mL orange juice, 500 mL control drink plus hesperidin (CDH), or 500 mL control drink plus placebo (CDP). All measurements and blood collections were performed in overnight-fasted subjects before and after the 4-wk treatment periods. The postprandial study was conducted at the beginning of each experimental period. Diastolic blood pressure (DBP) was significantly lower after 4 wk consumption of orange juice or CDH than after consumption of CDP (P = 0.02), whereas microvascular endothelium-related reactivity was not significantly affected when measured after an overnight fast. However, both orange juice and CDH ingestion significantly improved postprandial microvascular endothelial reactivity compared with CDP (P < 0.05) when measured at the peak of plasma hesperetin concentration. In healthy, middle-aged, moderately overweight men, orange juice decreases DBP when regularly consumed and postprandially increases endothelium-dependent microvascular reactivity. Our study suggests that hesperidin could be causally linked to the beneficial effect of orange juice. This trial is registered at clinicaltrials.gov as NCT00983086.

Design, Analysis, and Reporting of Crossover Trials for Inclusion in a Meta-Analysis.

PubMed

Li, Tianjing; Yu, Tsung; Hawkins, Barbara S; Dickersin, Kay

2015-01-01

To evaluate the characteristics of the design, analysis, and reporting of crossover trials for inclusion in a meta-analysis of treatment for primary open-angle glaucoma and to provide empirical evidence to inform the development of tools to assess the validity of the results from crossover trials and reporting guidelines. We searched MEDLINE, EMBASE, and Cochrane's CENTRAL register for randomized crossover trials for a systematic review and network meta-analysis we are conducting. Two individuals independently screened the search results for eligibility and abstracted data from each included report. We identified 83 crossover trials eligible for inclusion. Issues affecting the risk of bias in crossover trials, such as carryover, period effects and missing data, were often ignored. Some trials failed to accommodate the within-individual differences in the analysis. For a large proportion of the trials, the authors tabulated the results as if they arose from a parallel design. Precision estimates properly accounting for the paired nature of the design were often unavailable from the study reports; consequently, to include trial findings in a meta-analysis would require further manipulation and assumptions. The high proportion of poorly reported analyses and results has the potential to affect whether crossover data should or can be included in a meta-analysis. There is pressing need for reporting guidelines for crossover trials.

Efficacy of triplet regimen antiemetic therapy for chemotherapy-induced nausea and vomiting (CINV) in bone and soft tissue sarcoma patients receiving highly emetogenic chemotherapy, and an efficacy comparison of single-shot palonosetron and consecutive-day granisetron for CINV in a randomized, single-blinded crossover study

PubMed Central

Kimura, Hiroaki; Yamamoto, Norio; Shirai, Toshiharu; Nishida, Hideji; Hayashi, Katsuhiro; Tanzawa, Yoshikazu; Takeuchi, Akihiko; Igarashi, Kentaro; Inatani, Hiroyuki; Shimozaki, Shingo; Kato, Takashi; Aoki, Yu; Higuchi, Takashi; Tsuchiya, Hiroyuki

2015-01-01

The first aim of this study was to evaluate combination antiemetic therapy consisting of 5-HT3 receptor antagonists, neurokinin-1 receptor antagonists (NK-1RAs), and dexamethasone for multiple high emetogenic risk (HER) anticancer agents in bone and soft tissue sarcoma. The second aim was to compare the effectiveness of single-shot palonosetron and consecutive-day granisetron in a randomized, single-blinded crossover study. A single randomization method was used to assign eligible patients to the palonosetron or granisetron arm. Patients in the palonosetron arm received a palonosetron regimen during the first and third chemotherapy courses and a granisetron regimen during the second and fourth courses. All patients received NK-1RA and dexamethasone. Patients receiving the palonosetron regimen were administered 0.75 mg palonosetron on day 1, and patients receiving the granisetron regimen were administered 3 mg granisetron twice daily on days 1 through 5. All 24 patients in this study received at least 4 chemotherapy courses. A total of 96 courses of antiemetic therapy were evaluated. Overall, the complete response CR rate (no emetic episodes and no rescue medication use) was 34%, while the total control rate (a CR plus no nausea) was 7%. No significant differences were observed between single-shot palonosetron and consecutive-day granisetron. Antiemetic therapy with a 3-drug combination was not sufficient to control chemotherapy-induced nausea and vomiting (CINV) during chemotherapy with multiple HER agents for bone and soft tissue sarcoma. This study also demonstrated that consecutive-day granisetron was not inferior to single-shot palonosetron for treating CINV. PMID:25533447

The effect of music on biochemical markers and self-perceived stress among first-line nurses: a randomized controlled crossover trial.

PubMed

Lai, Hui-Ling; Li, Yin-Ming

2011-11-01

The aim of this study was to examine the effects of music on stress indices and to examine the association between music preference and stress. Although clinical studies have demonstrated the effectiveness of music on stress, study results have been inconsistent. At the time of writing, no known publications had investigated the effects of preferred music on workers in high-stress professions such as nursing. Using a randomized crossover controlled trial, 54 nurses were randomly assigned to a music/chair rest sequence or chair rest/music sequence during the period February to June 2006. Each intervention lasted for 30 minutes. Participants in the music condition listened to self-selected soothing music using headphones for 30 minutes. In the chair rest condition, participants sat quietly for 30 minutes. Serial measurements of participants' heart rate, mean arterial pressure, finger temperature and cortisol levels were taken with a BP monitor and chemillumincent immunoassay every 15 minutes throughout the procedure. Compared with chair rest, participants had a lower perceived stress level, cortisol, heart rate, mean arterial pressure and higher finger temperature while listening to music (P < 0·05). Significant differences were also found between the two conditions in terms of post-test heart rate, cortisol levels, finger temperature and mean arterial pressure (P < 0·05). Music preference scores ranged between 7 and 10, with a mean score of 8·81 (sd = 1·05), and was significantly associated with mean arterial pressure, cortisol levels, self-perceived stress and finger temperature. The findings provided evidence for nurses to use soothing music as a research-based nursing intervention for stress reduction. © 2011 The Authors. Journal of Advanced Nursing © 2011 Blackwell Publishing Ltd.

Baru almond improves lipid profile in mildly hypercholesterolemic subjects: a randomized, controlled, crossover study.

PubMed

Bento, A P N; Cominetti, C; Simões Filho, A; Naves, M M V

2014-12-01

The usual consumption of nuts reduces cardiovascular diseases (CVD) risk by improving serum lipids and oxidation status. Baru almonds (Dipteryxalata Vog.), a native species of Brazilian Savannah, have considerable contents of monounsaturated fatty acids (MUFA), dietary fiber, vitamin E and zinc, which could exert positive effects in serum lipids and markers of oxidation. However, there is no study about the effect of their consumption on human health. Thus, the aim of this study was to evaluate the effect of baru almonds supplementation on lipid profile and oxidation of mildly hypercholesterolemic subjects. A randomized, crossover, placebo controlled study was performed with 20 mildly hypercholesterolemic subjects (total cholesterol (TC) mean ±SEM = 5.8 ± 0.2 mmol/L). The assay had 2 periods of 6 weeks each and a 4-week washout period between the treatments. Subjects were randomly allocated in alternated periods receiving the following treatments per period: supplementation with 20 g/day of baru almonds or placebo (1 corn starch capsule/day). Compared to placebo, supplementation of baru almonds reduced TC (-8.1 ± 2.4%, P = 0.007), low-density lipoprotein cholesterol (LDL-c) (-9.4 ± 2.4%, P = 0.006) and non-high-density lipoprotein cholesterol (non-HDL-c) (-8.1 ± 3.0%, P = 0.013). There were no significant changes on the oxidation biomarkers evaluated. Dietary supplementation of mildly hypercholesterolemic subjects with baru almonds improved serum lipid parameters, so that this food might be included in diets for reducing the CVD risk. Brazilian Registry of Clinical Trials (ReBEC) (website: http://www.ensaiosclinicos.gov.br). Register number: RBR-4zdy9p. Copyright © 2014 Elsevier B.V. All rights reserved.

Olive (Olea europaea L.) leaf polyphenols improve insulin sensitivity in middle-aged overweight men: a randomized, placebo-controlled, crossover trial.

PubMed

de Bock, Martin; Derraik, José G B; Brennan, Christine M; Biggs, Janene B; Morgan, Philip E; Hodgkinson, Steven C; Hofman, Paul L; Cutfield, Wayne S

2013-01-01

Olive plant leaves (Olea europaea L.) have been used for centuries in folk medicine to treat diabetes, but there are very limited data examining the effects of olive polyphenols on glucose homeostasis in humans. To assess the effects of supplementation with olive leaf polyphenols (51.1 mg oleuropein, 9.7 mg hydroxytyrosol per day) on insulin action and cardiovascular risk factors in middle-aged overweight men. Randomized, double-blinded, placebo-controlled, crossover trial in New Zealand. 46 participants (aged 46.4 ± 5.5 years and BMI 28.0 ± 2.0 kg/m(2)) were randomized to receive capsules with olive leaf extract (OLE) or placebo for 12 weeks, crossing over to other treatment after a 6-week washout. Primary outcome was insulin sensitivity (Matsuda method). Secondary outcomes included glucose and insulin profiles, cytokines, lipid profile, body composition, 24-hour ambulatory blood pressure, and carotid intima-media thickness. Treatment evaluations were based on the intention-to-treat principle. All participants took >96% of prescribed capsules. OLE supplementation was associated with a 15% improvement in insulin sensitivity (p = 0.024) compared to placebo. There was also a 28% improvement in pancreatic β-cell responsiveness (p = 0.013). OLE supplementation also led to increased fasting interleukin-6 (p = 0.014), IGFBP-1 (p = 0.024), and IGFBP-2 (p = 0.015) concentrations. There were however, no effects on interleukin-8, TNF-α, ultra-sensitive CRP, lipid profile, ambulatory blood pressure, body composition, carotid intima-media thickness, or liver function. Supplementation with olive leaf polyphenols for 12 weeks significantly improved insulin sensitivity and pancreatic β-cell secretory capacity in overweight middle-aged men at risk of developing the metabolic syndrome.

Efficacy evaluation of a pollen blocker cream against dust-mite allergy: A multicenter, randomized, double-blind, placebo-controlled crossover trial.

PubMed

Li, Yanqing; Cheng, Lei; Chen, Xiaoning; Yang, Beibei; Wang, Dehui

2015-01-01

To further evaluate the efficacy and safety of a pollen blocker cream against dust-mite allergy. A multicenter, randomized, double-blind, placebo-controlled, crossover trial was conducted in a Chinese population. Patients diagnosed with perennial allergic rhinitis, sensitive to dust-mite allergy including Dermatophagoides farinae and Dermatophagoides pteronyssinus were randomly allocated to receive a pollen blocker cream or placebo, which was applied and spread evenly to the lower internal nose region three times daily for a total of 30 days. The primary outcome measurements for efficacy were total nasal symptom score (TNSS) and individual nasal symptom score (iNSS). Adverse events were also monitored. After application of a pollen blocker, the mean TNSS decreased from 23.1 to 13.8, the decrease of the pollen blocker group (9.3) was highly significant compared with the placebo group (5.2; p < 0.001). Similarly, the decreases in iNSSs (rhinorrhea, congestion, sneezing, and itching) between the pollen blocker group and the placebo group were also significant (p < 0.05). In addition, in adults, the pollen blocker led to a remarkably significant decrease in TNSS (9.5) compared with placebo (5.4; p < 0.001); in children, the pollen blocker led to a significant decrease in TNSS (8.6) compared with placebo (4.8; p < 0.05). No statistical difference was found in the incidence of adverse events between the two groups (p > 0.05), and no severe systematic reactions were observed. Pollen Blocker is a safe and effective alternative to the drugs for treatment of AR, especially for Chinese people allergic to dust-mite allergy.

Metabolic and hormonal effects of caffeine: randomized, double-blind, placebo-controlled crossover trial.

PubMed

MacKenzie, Todd; Comi, Richard; Sluss, Patrick; Keisari, Ronit; Manwar, Simone; Kim, Janice; Larson, Robin; Baron, John A

2007-12-01

In short-term studies, caffeine has been shown to increase insulin levels, reduce insulin sensitivity, and increase cortisol levels. However, epidemiological studies have indicated that long-term consumption of beverages containing caffeine such as coffee and green tea is associated with a reduced risk of type 2 diabetes mellitus. There is a paucity of randomized studies addressing the metabolic and hormonal effects of consuming caffeine over periods of more than 1 day. We evaluated the effect of oral intake of 200 mg of caffeine taken twice a day for 7 days on glucose metabolism, as well as on serum cortisol, dehydroepiandrosterone (DHEA), and androstenedione, and on nighttime salivary melatonin. A double-blind, randomized, placebo-controlled crossover study with periods of 7 days and washouts of 5 days comparing caffeine with placebo capsules was conducted. Participants were 16 healthy adults aged 18 to 22 years with a history of caffeine consumption. Blood samples from each subject were assayed for glucose, insulin, serum cortisol, DHEA, and androstenedione on the eighth day of each period after an overnight fast. Nighttime salivary melatonin was also measured. Insulin levels were significantly higher (by 1.80 microU/mL; 95% confidence interval, 0.33-3.28) after caffeine intake than after placebo. The homeostasis model assessment index of insulin sensitivity was reduced by 35% (95% confidence interval, 7%-62%) by caffeine. There were no differences in glucose, DHEA, androstenedione, and melatonin between treatment periods. This study provides evidence that daily caffeine intake reduces insulin sensitivity; the effect persists for at least a week and is evident up to 12 hours after administration.

Does topical amethocaine gel reduce pain from heel prick blood sampling in premature infants? A randomized double-blind cross-over controlled study

PubMed Central

Patel, Amita; Czerniawski, Barbara; Gray, Shari; Lui, Eric

2003-01-01

BACKGROUND: Heel prick blood sampling is the most common painful invasive procedure performed on neonates. Currently, there are no effective ways to provide pain relief from this painful procedure. OBJECTIVE: To assess the efficacy of the topical anesthetic amethocaine 4% gel (Ametop, Smith & Nephew Inc, St Laurent) in reducing the pain of heel prick blood sampling in neonates. METHODS: A randomized, double-blind, placebo controlled, crossover trial was conducted. Neonates between 33 to 37 weeks’ gestational age in their first seven days of life were eligible. Heel prick blood sampling was performed on each participant twice. Each infant was randomly assigned to receive either amethocaine 4% gel or placebo to the heel for the first prick, and then received the alternative agent for the second prick. Prick pain was assessed using both Premature Infant Pain Profile (PIPP) and Neonatal Infant Pain Scale (NIPS). Squeeze pain was assessed by NIPS. RESULTS: Ten babies were recruited. There were no significant differences in the average PIPP and NIPS scores between the treatment and placebo groups for both prick and squeeze pains from heel prick blood sampling. For prick pain, linear-regression showed significant correlation between the PIPP and NIPS scores. No adverse reactions were observed after application of either the active or placebo agents. CONCLUSION: Topical amethocaine 4% gel is not shown to reduce prick and squeeze pains significantly from heel prick blood sampling in neonates between 33 to 37 weeks’ gestational age. Further studies are needed to find ways to provide effective pain relief from this common procedure. PMID:20020001

C2 Nerve Field Stimulation for the Treatment of Fibromyalgia: A Prospective, Double-blind, Randomized, Controlled Cross-over Study.

PubMed

Plazier, Mark; Ost, Jan; Stassijns, Gaëtane; De Ridder, Dirk; Vanneste, Sven

2015-01-01

Fibromyalgia is a condition characterized by widespread chronic pain. Due to the high prevalence and high costs, it has a substantial burden on society. Treatment results are diverse and only help a small subset of patients. C2 nerve field stimulation, aka occipital nerve stimulation, is helpful and a minimally invasive treatment for primary headache syndromes. Small C2 pilot studies seem to be beneficial in fibromyalgia. Forty patients were implanted with a subcutaneous electrode in the C2 dermatoma as part of a prospective, double-blind, randomized, controlled cross-over study followed by an open label follow up period of 6 months. The patients underwent 2 week periods of different doses of stimulation consisting of minimal (.1 mA), subthreshold, and suprathreshold (for paresthesias) in a randomized order. Twenty seven patients received a permanent implant and 25 completed the 6 month open label follow up period. During the 6 week trial phase of the study, patients had an overall decrease of 36% on the fibromyalgia impact questionnaire (FIQ), a decrease of 33% fibromyalgia pain and improvement of 42% on the impact on daily life activities and quality. These results imply an overall improvement in the disease burden, maintained at 6 months follow up, as well as an improvement in life quality of 50%. Seventy six percent of patients were satisfied or very satisfied with their treatment. There seems to be a dose-response curve, with increasing amplitudes leading to better clinical outcomes. Subcutaneous C2 nerve field stimulation seems to offer a safe and effective treatment option for selected medically intractable patients with fibromyalgia. Copyright © 2015 Elsevier Inc. All rights reserved.

Intake and time dependence of blueberry flavonoid-induced improvements in vascular function: a randomized, controlled, double-blind, crossover intervention study with mechanistic insights into biological activity.

PubMed

Rodriguez-Mateos, Ana; Rendeiro, Catarina; Bergillos-Meca, Triana; Tabatabaee, Setareh; George, Trevor W; Heiss, Christian; Spencer, Jeremy Pe

2013-11-01

There are very limited data regarding the effects of blueberry flavonoid intake on vascular function in healthy humans. We investigated the impact of blueberry flavonoid intake on endothelial function in healthy men and assessed potential mechanisms of action by the assessment of circulating metabolites and neutrophil NADPH oxidase activity. Two randomized, controlled, double-blind, crossover human-intervention trials were conducted with 21 healthy men. Initially, the impact of blueberry flavonoid intake on flow-mediated dilation (FMD) and polyphenol absorption and metabolism was assessed at baseline and 1, 2, 4, and 6 h after consumption of blueberry containing 766, 1278, and 1791 mg total blueberry polyphenols or a macronutrient- and micronutrient-matched control drink (0 mg total blueberry polyphenols). Second, an intake-dependence study was conducted (from baseline to 1 h) with 319, 637, 766, 1278, and 1791 mg total blueberry polyphenols and a control. We observed a biphasic time-dependent increase in FMD, with significant increases at 1-2 and 6 h after consumption of blueberry polyphenols. No significant intake-dependence was observed between 766 and 1791 mg. However, at 1 h after consumption, FMD increased dose dependently to ≤766 mg total blueberry polyphenol intake, after which FMD plateaued. Increases in FMD were closely linked to increases in circulating metabolites and by decreases in neutrophil NADPH oxidase activity at 1-2 and 6 h. Blueberry intake acutely improves vascular function in healthy men in a time- and intake-dependent manner. These benefits may be mechanistically linked to the actions of circulating phenolic metabolites on neutrophil NADPH oxidase activity. This trial was registered at clinicaltrials.gov as NCT01292954 and NCT01829542.

Hesperidin displays relevant role in the nutrigenomic effect of orange juice on blood leukocytes in human volunteers: a randomized controlled cross-over study.

PubMed

Milenkovic, Dragan; Deval, Christiane; Dubray, Claude; Mazur, Andrzej; Morand, Christine

2011-01-01

We previously showed, in healthy, middle-aged, moderately overweight men, that orange juice decreases diastolic blood pressure and significantly improves postprandial microvascular endothelial reactivity and that hesperidin could be causally linked to the observed beneficial effect of orange juice. The objective was to determine the effect of chronic consumption of orange juice on the gene expression profile of leukocytes in healthy volunteers and to assess to what extent hesperidin is involved in the effect of orange juice. Volunteers were included in a randomized, controlled, crossover study. Throughout three 4-week periods, volunteers consumed daily: 500 ml orange juice, 500 ml control drink plus hesperidin or 500 ml control drink and placebo. Blood samplings were performed on 10 overnight-fasted subjects after the 4-week treatment period. Global gene expression profiles were determined using human whole genome cDNA microarrays. Both orange juice and hesperidin consumption significantly affected leukocyte gene expression. Orange juice consumption induced changes in expression of, 3,422 genes, while hesperidin intake modulated the expression of 1,819 genes. Between the orange juice and hesperidin consumption groups, 1,582 regulated genes were in common. Many of these genes are implicated in chemotaxis, adhesion, infiltration and lipid transport, which is suggestive of lower recruitment and infiltration of circulating cells to vascular wall and lower lipid accumulation. This study shows that regular consumption of orange juice for 4 weeks alters leukocyte gene expression to an anti-inflammatory and anti-atherogenic profile, and hesperidin displays a relevant role in the genomic effect of this beverage. ClinicalTrials.gov NCT 00983086.

Hesperidin Displays Relevant Role in the Nutrigenomic Effect of Orange Juice on Blood Leukocytes in Human Volunteers: A Randomized Controlled Cross-Over Study

PubMed Central

Milenkovic, Dragan; Deval, Christiane; Dubray, Claude; Mazur, Andrzej; Morand, Christine

2011-01-01

Background We previously showed, in healthy, middle-aged, moderately overweight men, that orange juice decreases diastolic blood pressure and significantly improves postprandial microvascular endothelial reactivity and that hesperidin could be causally linked to the observed beneficial effect of orange juice. The objective was to determine the effect of chronic consumption of orange juice on the gene expression profile of leukocytes in healthy volunteers and to assess to what extent hesperidin is involved in the effect of orange juice. Methodology/Principal Findings Volunteers were included in a randomized, controlled, crossover study. Throughout three 4-week periods, volunteers consumed daily: 500 ml orange juice, 500 ml control drink plus hesperidin or 500 ml control drink and placebo. Blood samplings were performed on 10 overnight-fasted subjects after the 4-week treatment period. Global gene expression profiles were determined using human whole genome cDNA microarrays. Both orange juice and hesperidin consumption significantly affected leukocyte gene expression. Orange juice consumption induced changes in expression of, 3,422 genes, while hesperidin intake modulated the expression of 1,819 genes. Between the orange juice and hesperidin consumption groups, 1,582 regulated genes were in common. Many of these genes are implicated in chemotaxis, adhesion, infiltration and lipid transport, which is suggestive of lower recruitment and infiltration of circulating cells to vascular wall and lower lipid accumulation. Conclusions This study shows that regular consumption of orange juice for 4 weeks alters leukocyte gene expression to an anti-inflammatory and anti-atherogenic profile, and hesperidin displays a relevant role in the genomic effect of this beverage. Trial Registration ClinicalTrials.gov NCT 00983086 PMID:22110589

Exercise frequency and calcium intake predict 4-year bone changes in postmenopausal women.

PubMed

Cussler, Ellen C; Going, Scott B; Houtkooper, Linda B; Stanford, Vanessa A; Blew, Robert M; Flint-Wagner, Hilary G; Metcalfe, Lauve L; Choi, Ji-Eun; Lohman, Timothy G

2005-12-01

The aim of this study was to examine the association of exercise frequency and calcium intake (CI) with change in regional and total bone mineral density (BMD) in a group of postmenopausal women completing 4 years of progressive strength training. One hundred sixty-seven calcium-supplemented (800 mg/day) sedentary women (56.1+/-4.5 years) randomized to a progressive strength training exercise program or to control were followed for 4 years. Fifty-four percent of the women were using hormone therapy (HT) at baseline. At 1 year, controls were permitted to begin the exercise program (crossovers). The final sample included 23 controls, 55 crossovers, and 89 randomized exercisers. Exercisers were instructed to complete two sets of six to eight repetitions of exercises at 70-80% of one repetition maximum, three times weekly. BMD was measured at baseline and thereafter annually using dual-energy X-ray absorptiometry. Four-year percentage exercise frequency (ExFreq) averaged 26.8%+/-20.1% for crossovers (including the first year at 0%), and 50.4%+/-26.7% for exercisers. Four-year total CI averaged 1,635+/-367 mg/day and supplemental calcium intake, 711+/-174 mg/day. In adjusted multiple linear regression models, ExFreq was positively and significantly related to changes in femur trochanter (FT) and neck (FN), lumbar spine (LS), and total body (TB) BMD. Among HT users, FT BMD increased 1.5%, and FN and LS BMD, 1.2% (p<0.01) for each standard deviation (SD) of percentage ExFreq (29.5% or 0.9 days/week). HT non-users gained 1.9% and 2.3% BMD at FT and FN, respectively, (p<0.05) for every SD of CI. The significant, positive, association between BMD change and ExFreq supports the long-term usefulness of strength training exercise for the prevention of osteoporosis in postmenopausal women, especially HT users. The positive relationship of CI to change in BMD among postmenopausal women not using HT has clinical implications in light of recent evidence of an increased health risk associated with HT.

Mosquito larval source management for controlling malaria

PubMed Central

Tusting, Lucy S; Thwing, Julie; Sinclair, David; Fillinger, Ulrike; Gimnig, John; Bonner, Kimberly E; Bottomley, Christian; Lindsay, Steven W

2015-01-01

Background Malaria is an important cause of illness and death in people living in many parts of the world, especially sub-Saharan Africa. Long-lasting insecticide treated bed nets (LLINs) and indoor residual spraying (IRS) reduce malaria transmission by targeting the adult mosquito vector and are key components of malaria control programmes. However, mosquito numbers may also be reduced by larval source management (LSM), which targets mosquito larvae as they mature in aquatic habitats. This is conducted by permanently or temporarily reducing the availability of larval habitats (habitat modification and habitat manipulation), or by adding substances to standing water that either kill or inhibit the development of larvae (larviciding). Objectives To evaluate the effectiveness of mosquito LSM for preventing malaria. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; CABS Abstracts; and LILACS up to 24 October 2012. We handsearched the Tropical Diseases Bulletin from 1900 to 2010, the archives of the World Health Organization (up to 11 February 2011), and the literature database of the Armed Forces Pest Management Board (up to 2 March 2011). We also contacted colleagues in the field for relevant articles. Selection criteria We included cluster randomized controlled trials (cluster-RCTs), controlled before-and-after trials with at least one year of baseline data, and randomized cross-over trials that compared LSM with no LSM for malaria control. We excluded trials that evaluated biological control of anopheline mosquitoes with larvivorous fish. Data collection and analysis At least two authors assessed each trial for eligibility. We extracted data and at least two authors independently determined the risk of bias in the included studies. We resolved all disagreements through discussion with a third author. We analyzed the data using Review Manager 5 software. Main results We included 13 studies; four cluster-RCTs, eight controlled before-and-after trials, and one randomized cross-over trial. The included studies evaluated habitat modification (one study), habitat modification with larviciding (two studies), habitat manipulation (one study), habitat manipulation plus larviciding (two studies), or larviciding alone (seven studies) in a wide variety of habitats and countries. Malaria incidence In two cluster-RCTs undertaken in Sri Lanka, larviciding of abandoned mines, streams, irrigation ditches, and rice paddies reduced malaria incidence by around three-quarters compared to the control (RR 0.26, 95% CI 0.22 to 0.31, 20,124 participants, two trials, moderate quality evidence). In three controlled before-and-after trials in urban and rural India and rural Kenya, results were inconsistent (98,233 participants, three trials, very low quality evidence). In one trial in urban India, the removal of domestic water containers together with weekly larviciding of canals and stagnant pools reduced malaria incidence by three quarters. In one trial in rural India and one trial in rural Kenya, malaria incidence was higher at baseline in intervention areas than in controls. However dam construction in India, and larviciding of streams and swamps in Kenya, reduced malaria incidence to levels similar to the control areas. In one additional randomized cross-over trial in the flood plains of the Gambia River, where larval habitats were extensive and ill-defined, larviciding by ground teams did not result in a statistically significant reduction in malaria incidence (2039 participants, one trial). Parasite prevalence In one cluster-RCT from Sri Lanka, larviciding reduced parasite prevalence by almost 90% (RR 0.11, 95% CI 0.05 to 0.22, 2963 participants, one trial, moderate quality evidence). In five controlled before-and-after trials in Greece, India, the Philippines, and Tanzania, LSM resulted in an average reduction in parasite prevalence of around two-thirds (RR 0.32, 95% CI 0.19 to 0.55, 8041 participants, five trials, moderate quality evidence). The interventions in these five trials included dam construction to reduce larval habitats, flushing of streams, removal of domestic water containers, and larviciding. In the randomized cross-over trial in the flood plains of the Gambia River, larviciding by ground teams did not significantly reduce parasite prevalence (2039 participants, one trial). Authors’ conclusions In Africa and Asia, LSM is another policy option, alongside LLINs and IRS, for reducing malaria morbidity in both urban and rural areas where a sufficient proportion of larval habitats can be targeted. Further research is needed to evaluate whether LSM is appropriate or feasible in parts of rural Africa where larval habitats are more extensive. PMID:23986463

Case-based Learning Outperformed Simulation Exercises in Disaster Preparedness Education Among Nursing Trainees in India: A Randomized Controlled Trial.

PubMed

Aluisio, Adam R; Daniel, Pia; Grock, Andrew; Freedman, Joseph; Singh, Ajai; Papanagnou, Dimitrios; Arquilla, Bonnie

2016-10-01

In resource-constrained environments, appropriately employing triage in disaster situations is crucial. Although both case-based learning (CBL) and simulation exercises (SEs) commonly are utilized in teaching disaster preparedness to adult learners, there is no substantial evidence supporting one as a more efficacious methodology. This randomized controlled trial (RCT) evaluated the effectiveness of CBL versus SEs in addition to standard didactic instruction in knowledge attainment pertaining to disaster triage preparedness. This RCT was performed during a one-day disaster preparedness course in Lucknow, India during October 2014. Following provision of informed consent, nursing trainees were randomized to knowledge assessment after didactic teaching (control group); didactic plus CBL (Intervention Group 1); or didactic plus SE (Intervention Group 2). The educational curriculum used the topical focus of triage processes during disaster situations. Cases for the educational intervention sessions were scripted, identical between modalities, and employed structured debriefing. Trained live actors were used for SEs. After primary assessment, the groups underwent crossover to take part in the alternative educational modality and were re-assessed. Two standardized multiple-choice question batteries, encompassing key core content, were used for assessments. A sample size of 48 participants was calculated to detect a ≥20% change in mean knowledge score (α=0.05; power=80%). Robustness of randomization was evaluated using X 2, anova, and t-tests. Mean knowledge attainment scores were compared using one- and two-sample t-tests for intergroup and intragroup analyses, respectively. Among 60 enrolled participants, 88.3% completed follow-up. No significant differences in participant characteristics existed between randomization arms. Mean baseline knowledge score in the control group was 43.8% (standard deviation=11.0%). Case-based learning training resulted in a significant increase in relative knowledge scores at 20.8% (P=0.003) and 10.3% (P=.033) in intergroup and intragroup analyses, respectively. As compared to control, SEs did not significantly alter knowledge attainment scores with an average score increase of 6.6% (P=.396). In crossover intra-arm analysis, SEs were found to result in a 26.0% decrement in mean assessment score (P < .001). Among nursing trainees assessed in this RCT, the CBL modality was superior to SEs in short-term disaster preparedness educational translation. Simulation exercises resulted in no detectable improvement in knowledge attainment in this population, suggesting that CBL may be utilized preferentially for adult learners in similar disaster training settings. Aluisio AR , Daniel P , Grock A , Freedman J , Singh A , Papanagnou D , Arquilla B . Case-based learning outperformed simulation exercises in disaster preparedness education among nursing trainees in India: a randomized controlled trial. Prehosp Disaster Med. 2016;31(5):516-523.

Behavioral Outcome Effects of Serious Gaming as an Adjunct to Treatment for Children With Attention-Deficit/Hyperactivity Disorder: A Randomized Controlled Trial.

PubMed

Bul, Kim C M; Kato, Pamela M; Van der Oord, Saskia; Danckaerts, Marina; Vreeke, Leonie J; Willems, Annik; van Oers, Helga J J; Van Den Heuvel, Ria; Birnie, Derk; Van Amelsvoort, Thérèse A M J; Franken, Ingmar H A; Maras, Athanasios

2016-02-16

The need for accessible and motivating treatment approaches within mental health has led to the development of an Internet-based serious game intervention (called "Plan-It Commander") as an adjunct to treatment as usual for children with attention-deficit/hyperactivity disorder (ADHD). The aim was to determine the effects of Plan-It Commander on daily life skills of children with ADHD in a multisite randomized controlled crossover open-label trial. Participants (N=170) in this 20-week trial had a diagnosis of ADHD and ranged in age from 8 to 12 years (male: 80.6%, 137/170; female: 19.4%, 33/170). They were randomized to a serious game intervention group (group 1; n=88) or a treatment-as-usual crossover group (group 2; n=82). Participants randomized to group 1 received a serious game intervention in addition to treatment as usual for the first 10 weeks and then received treatment as usual for the next 10 weeks. Participants randomized to group 2 received treatment as usual for the first 10 weeks and crossed over to the serious game intervention in addition to treatment as usual for the subsequent 10 weeks. Primary (parent report) and secondary (parent, teacher, and child self-report) outcome measures were administered at baseline, 10 weeks, and 10-week follow-up. After 10 weeks, participants in group 1 compared to group 2 achieved significantly greater improvements on the primary outcome of time management skills (parent-reported; P=.004) and on secondary outcomes of the social skill of responsibility (parent-reported; P=.04), and working memory (parent-reported; P=.02). Parents and teachers reported that total social skills improved over time within groups, whereas effects on total social skills and teacher-reported planning/organizing skills were nonsignificant between groups. Within group 1, positive effects were maintained or further improved in the last 10 weeks of the study. Participants in group 2, who played the serious game during the second period of the study (weeks 10 to 20), improved on comparable domains of daily life functioning over time. Plan-It Commander offers an effective therapeutic approach as an adjunct intervention to traditional therapeutic ADHD approaches that improve functional outcomes in daily life. International Standard Randomized Controlled Trial Number (ISRCTN): 62056259; http://www.controlled-trials.com/ISRCTN62056259 (Archived by WebCite at http://www.webcitation.org/6eNsiTDJV).

Behavioral Outcome Effects of Serious Gaming as an Adjunct to Treatment for Children With Attention-Deficit/Hyperactivity Disorder: A Randomized Controlled Trial

PubMed Central

2016-01-01

Background The need for accessible and motivating treatment approaches within mental health has led to the development of an Internet-based serious game intervention (called “Plan-It Commander”) as an adjunct to treatment as usual for children with attention-deficit/hyperactivity disorder (ADHD). Objective The aim was to determine the effects of Plan-It Commander on daily life skills of children with ADHD in a multisite randomized controlled crossover open-label trial. Methods Participants (N=170) in this 20-week trial had a diagnosis of ADHD and ranged in age from 8 to 12 years (male: 80.6%, 137/170; female: 19.4%, 33/170). They were randomized to a serious game intervention group (group 1; n=88) or a treatment-as-usual crossover group (group 2; n=82). Participants randomized to group 1 received a serious game intervention in addition to treatment as usual for the first 10 weeks and then received treatment as usual for the next 10 weeks. Participants randomized to group 2 received treatment as usual for the first 10 weeks and crossed over to the serious game intervention in addition to treatment as usual for the subsequent 10 weeks. Primary (parent report) and secondary (parent, teacher, and child self-report) outcome measures were administered at baseline, 10 weeks, and 10-week follow-up. Results After 10 weeks, participants in group 1 compared to group 2 achieved significantly greater improvements on the primary outcome of time management skills (parent-reported; P=.004) and on secondary outcomes of the social skill of responsibility (parent-reported; P=.04), and working memory (parent-reported; P=.02). Parents and teachers reported that total social skills improved over time within groups, whereas effects on total social skills and teacher-reported planning/organizing skills were nonsignificant between groups. Within group 1, positive effects were maintained or further improved in the last 10 weeks of the study. Participants in group 2, who played the serious game during the second period of the study (weeks 10 to 20), improved on comparable domains of daily life functioning over time. Conclusions Plan-It Commander offers an effective therapeutic approach as an adjunct intervention to traditional therapeutic ADHD approaches that improve functional outcomes in daily life. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 62056259; http://www.controlled-trials.com/ISRCTN62056259 (Archived by WebCite at http://www.webcitation.org/6eNsiTDJV). PMID:26883052

Acute dark chocolate and cocoa ingestion and endothelial function: a randomized controlled crossover trial.

PubMed

Faridi, Zubaida; Njike, Valentine Yanchou; Dutta, Suparna; Ali, Ather; Katz, David L

2008-07-01

Studies suggest cardioprotective benefits of dark chocolate containing cocoa. This study examines the acute effects of solid dark chocolate and liquid cocoa intake on endothelial function and blood pressure in overweight adults. Randomized, placebo-controlled, single-blind crossover trial of 45 healthy adults [mean age: 53 y; mean body mass index (in kg/m(2)): 30]. In phase 1, subjects were randomly assigned to consume a solid dark chocolate bar (containing 22 g cocoa powder) or a cocoa-free placebo bar (containing 0 g cocoa powder). In phase 2, subjects were randomly assigned to consume sugar-free cocoa (containing 22 g cocoa powder), sugared cocoa (containing 22 g cocoa powder), or a placebo (containing 0 g cocoa powder). Solid dark chocolate and liquid cocoa ingestion improved endothelial function (measured as flow-mediated dilatation) compared with placebo (dark chocolate: 4.3 +/- 3.4% compared with -1.8 +/- 3.3%; P < 0.001; sugar-free and sugared cocoa: 5.7 +/- 2.6% and 2.0 +/- 1.8% compared with -1.5 +/- 2.8%; P < 0.001). Blood pressure decreased after the ingestion of dark chocolate and sugar-free cocoa compared with placebo (dark chocolate: systolic, -3.2 +/- 5.8 mm Hg compared with 2.7 +/- 6.6 mm Hg; P < 0.001; and diastolic, -1.4 +/- 3.9 mm Hg compared with 2.7 +/- 6.4 mm Hg; P = 0.01; sugar-free cocoa: systolic, -2.1 +/- 7.0 mm Hg compared with 3.2 +/- 5.6 mm Hg; P < 0.001; and diastolic: -1.2 +/- 8.7 mm Hg compared with 2.8 +/- 5.6 mm Hg; P = 0.014). Endothelial function improved significantly more with sugar-free than with regular cocoa (5.7 +/- 2.6% compared with 2.0 +/- 1.8%; P < 0.001). The acute ingestion of both solid dark chocolate and liquid cocoa improved endothelial function and lowered blood pressure in overweight adults. Sugar content may attenuate these effects, and sugar-free preparations may augment them.

MIDAS (Modafinil in Debilitating Fatigue After Stroke): A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Trial.

PubMed

Bivard, Andrew; Lillicrap, Thomas; Krishnamurthy, Venkatesh; Holliday, Elizabeth; Attia, John; Pagram, Heather; Nilsson, Michael; Parsons, Mark; Levi, Christopher R

2017-05-01

This study aimed to assess the efficacy of modafinil, a wakefulness-promoting agent in alleviating post-stroke fatigue ≥3 months after stroke. We hypothesized that 200 mg of modafinil daily for 6 weeks would result in reduced symptoms of fatigue compared with placebo. This single-center phase 2 trial used a randomized, double-blind, placebo-controlled, crossover design. The key inclusion criterion was a multidimensional fatigue inventory score of ≥60. Patients were randomized to either modafinil or placebo for 6 weeks of therapy, then after a 1 week washout period swapped treatment arms for a second 6 weeks of therapy. The primary outcome was the multidimensional fatigue inventory; secondary outcomes included the Montreal cognitive assessment, the Depression, Anxiety, and Stress Scale (DASS), and the Stroke-Specific Quality of Life (SSQoL) scale. The multidimensional fatigue inventory is a self-administered questionnaire with a range of 0 to 100. Treatment efficacy was assessed using linear regression by estimating within-person, baseline-adjusted differences in mean outcomes after therapy. This trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615000350527). A total of 232 stroke survivors were screened and 36 were randomized. Participants receiving modafinil reported a significant decrease in fatigue (multidimensional fatigue inventory, -7.38; 95% CI, -21.76 to -2.99; P <0.001) and improved quality of life (SSQoL, 11.81; 95% CI, 2.31 to 21.31; P =0.0148) compared with placebo. Montreal cognitive assessment and DASS were not significantly improved with modafinil therapy during the study period ( P >0.05). Stroke survivors with nonresolving fatigue reported reduced fatigue and improved quality of life after taking 200 mg daily treatment with modafinil. URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368268. Unique identifier: ACTRN12615000350527. © 2017 The Authors.

High and low negative pressure suction techniques in EUS-guided fine-needle tissue acquisition by using 25-gauge needles: a multicenter, prospective, randomized, controlled trial.

PubMed

Kudo, Taiki; Kawakami, Hiroshi; Hayashi, Tsuyoshi; Yasuda, Ichiro; Mukai, Tsuyoshi; Inoue, Hiroyuki; Katanuma, Akio; Kawakubo, Kazumichi; Ishiwatari, Hirotoshi; Doi, Shinpei; Yamada, Reiko; Maguchi, Hiroyuki; Isayama, Hiroyuki; Mitsuhashi, Tomoko; Sakamoto, Naoya

2014-12-01

EUS-guided FNA (EUS-FNA) has a high diagnostic accuracy for pancreatic diseases. However, although most reports have typically focused on cytology, histological tissue quality has rarely been investigated. The effectiveness of EUS-FNA combined with high negative pressure (HNP) suction was recently indicated for tissue acquisition, but has not thus far been tested in a prospective, randomized clinical trial. To evaluate the adequacy of EUS-FNA with HNP for the histological diagnosis of pancreatic lesions by using 25-gauge needles. Prospective, single-blind, randomized, controlled crossover trial. Seven tertiary referral centers. Patients referred for EUS-FNA of pancreatic solid lesions. From July 2011 to April 2012, 90 patients underwent EUS-FNA of pancreatic solid masses by using normal negative pressure (NNP) and HNP with 2 respective passes. The order of the passes was randomized, and the sample adequacy, quality, and histology were evaluated by a single expert pathologist. EUS-FNA by using NNP and HNP. The adequacy of tissue acquisition and the accuracy of histological diagnoses made by using the EUS-FNA technique with HNP. We found that 72.2% (65/90) and 90% (81/90) of the specimens obtained using NNP and HNP, respectively, were adequate for histological diagnosis (P = .0003, McNemar test). For 73.3% (66/90) and 82.2% (74/90) of the specimens obtained by using NNP and HNP, respectively, an accurate diagnosis was achieved (P = .06, McNemar test). Pancreatitis developed in 1 patient after this procedure, which subsided with conservative therapy. This was a single-blinded, crossover study. Biopsy procedures that combine the EUS-FNA with HNP techniques are superior to EUS-FNA with NNP procedures for tissue acquisition. ( UMIN000005939.). Copyright © 2014 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Effects of a Gentle, Self-Administered Stimulation of Perineal Skin for Nocturia in Elderly Women: A Randomized, Placebo-Controlled, Double-Blind Crossover Trial.

PubMed

Iimura, Kaori; Watanabe, Nobuhiro; Masunaga, Koichi; Miyazaki, Shogo; Hotta, Harumi; Kim, Hunkyung; Hisajima, Tatsuya; Takahashi, Hidenori; Kasuya, Yutaka

2016-01-01

Somatic afferent nerve stimuli are used for treating an overactive bladder (OAB), a major cause of nocturia in the elderly. Clinical evidence for this treatment is insufficient because of the lack of appropriate control stimuli. Recent studies on anesthetized animals show that gentle stimuli applied to perineal skin with a roller could inhibit micturition contractions depending on the roller's surface material. We examined the efficacy of gentle skin stimuli for treating nocturia. The study was a cross-over, placebo-controlled, double-blind randomized clinical study using two rollers with different effects on micturition contractions. Participants were elderly women (79-89 years) with nocturia. Active (soft elastomer roller) or placebo (hard polystyrene roller) stimuli were applied to perineal skin by participants for 1 min at bedtime. A 3-day baseline assessment period was followed by 3-day stimulation and 4-day resting periods, after which the participants were subjected to other stimuli for another 3 days. The primary outcome was change in the frequency of nighttime urination, for which charts were maintained during each 3-day period. Twenty-four participants were randomized, of which 22 completed all study protocols. One participant discontinued treatment because of an adverse event (abdominal discomfort). In participants with OAB (n = 9), change from baseline in the mean frequency of urination per night during the active stimuli period (mean ± standard deviation, -0.74 ± 0.7 times) was significantly greater than that during placebo stimuli periods (-0.15 ± 0.8 times [p < 0.05]). In contrast, this difference was not observed in participants without OAB (n = 13). These results suggest that gentle perineal stimulation with an elastomer roller is effective for treating OAB-associated nocturia in elderly women. Here the limitation was a study period too short to assess changes in the quality of sleep and life. UMIN Clinical Trial Registry (CTR) UMIN000015809.

The Effects of Consumption of Bread Fortified With Soy Bean Flour on Metabolic Profile in Type 2 Diabetic Women: A Cross-over Randomized Controlled Clinical Trial.

PubMed

Moghaddam, Asma Salari; Entezari, Mohammad Hassan; Iraj, Bijan; Askari, Gholam Reza; Maracy, Mohammad Reza

2014-12-01

Diabetes mellitus is one of the most common chronic diseases in the world and has become a major threat for global health. Recent studies reported that the soy has beneficial effects in diabetic mellitus patients. The aim of this study was to assess the effects of soybean flour fortified bread consumption on metabolic profile in type 2 diabetic women. This randomized, cross-over, controlled clinical trial was carried out in 30 type 2 diabetic women. At first, a 2-week run-in period was applied. Then, participants were randomly assigned to either intervention or control groups. Participants in the intervention group were asked to replace 120 g of soybean flour fortified bread with the same amount of their usual bread intake or other cereal products for 6 weeks. After a 4 weeks washout period, participants were crossed over for another 6 weeks. Mean (±standard deviation) age and body mass index of subjects was 45.7 ± 3.8 years and 29.5 ± 3.9 kg/m(2), respectively. The results of our study showed no significant effects of soybean flour fortified bread on metabolic profile. We found a reduction in serum triglycerides (change difference: -3.7, P = 0.82), serum low-density lipoprotein-cholesterol (change difference: -11.2, P = 0.50), insulin (change difference: -3.6, P = 0.7), and homeostatic model assessment of insulin resistance (change differences: -0.57, P = 0.45) after 6 weeks but these changes were not statistically significant. No significant effects of soybean flour fortified bread on serum concentrations of fasting blood sugar, glycated hemoglobin, high-density lipoproteins and total cholesterol levels were found. Six weeks consumption of soybean flour fortified bread among diabetic patients had no significant effects on metabolic profile.

Home Use of Day-and-Night Hybrid Closed-Loop Insulin Delivery in Suboptimally Controlled Adolescents With Type 1 Diabetes: A 3-Week, Free-Living, Randomized Crossover Trial.

PubMed

Tauschmann, Martin; Allen, Janet M; Wilinska, Malgorzata E; Thabit, Hood; Acerini, Carlo L; Dunger, David B; Hovorka, Roman

2016-11-01

This study evaluated the feasibility, safety, and efficacy of day-and-night hybrid closed-loop insulin delivery in adolescents with type 1 diabetes under free-living conditions. In an open-label randomized crossover study, 12 suboptimally controlled adolescents on insulin pump therapy (mean ± SD age 14.6 ± 3.1 years; HbA 1c 69 ± 8 mmol/mol [8.5 ± 0.7%]; duration of diabetes 7.8 ± 3.5 years) underwent two 21-day periods in which hybrid closed-loop insulin delivery was compared with sensor-augmented insulin pump therapy in random order. During the closed-loop intervention, a model predictive algorithm automatically directed insulin delivery between meals and overnight. Participants used a bolus calculator to administer prandial boluses. The proportion of time that sensor glucose was in the target range (3.9-10 mmol/L; primary end point) was increased during the closed-loop intervention compared with sensor-augmented insulin pump therapy by 18.8 ± 9.8 percentage points (mean ± SD; P < 0.001), the mean sensor glucose level was reduced by 1.8 ± 1.3 mmol/L (P = 0.001), and the time spent above target was reduced by 19.3 ± 11.3 percentage points (P < 0.001). The time spent with sensor glucose levels below 3.9 mmol/L was low and comparable between interventions (median difference 0.4 [interquartile range -2.2 to 1.3] percentage points; P = 0.33). Improved glucose control during closed-loop was associated with increased variability of basal insulin delivery (P < 0.001) and an increase in the total daily insulin dose (53.5 [39.5-72.1] vs. 51.5 [37.6-64.3] units/day; P = 0.006). Participants expressed positive attitudes and experience with the closed-loop system. Free-living home use of day-and-night closed-loop in suboptimally controlled adolescents with type 1 diabetes is safe, feasible, and improves glucose control without increasing the risk of hypoglycemia. Larger and longer studies are warranted. © 2016 by the American Diabetes Association.

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

PubMed

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

2015-05-11

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

Bioavailability of epicatechin and effects on nitric oxide metabolites of an apple flavanol-rich extract supplemented beverage compared to a whole apple puree: a randomized, placebo-controlled, crossover trial.

PubMed

Hollands, Wendy J; Hart, David J; Dainty, Jack R; Hasselwander, Oliver; Tiihonen, Kirsti; Wood, Richard; Kroon, Paul A

2013-07-01

Flavanol-rich foods are known to exert beneficial effects on cardiovascular health. The biological effects depend on bioavailability of flavanols which may be influenced by food matrix and dose ingested. We compared the bioavailability and dose-response of epicatechin from whole apple and an epicatechin-rich extract, and the effects on plasma and urinary nitric oxide (NO) metabolites. In a randomized, placebo-controlled, crossover trial, subjects consumed drinks containing 70 and 140 mg epicatechin from an apple extract and an apple puree containing 70 mg epicatechin. Blood and urine samples were collected for 24 h post ingestion. Maximum plasma concentration, AUC(0-24 h) , absorption and urinary excretion were all significantly higher after ingestion of both epicatechin drinks compared with apple puree (p < 0.05). Time to maximum plasma concentration was significantly later for the puree compared with the drinks (p < 0.01). Epicatechin bioavailability was >2-fold higher after ingestion of the 140 mg epicatechin drink compared to the 70 mg epicatechin drink (p < 0.05). Excretion of NO metabolites was higher for all test products compared with placebo, which was significant for the high dose drink (p = 0.016). Oral bioavailability of apple epicatechin increases at higher doses, is reduced by whole apple matrix and has the potential to increase NO bioavailability. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Heart rate variability during acute psychosocial stress: A randomized cross-over trial of verbal and non-verbal laboratory stressors.

PubMed

Brugnera, Agostino; Zarbo, Cristina; Tarvainen, Mika P; Marchettini, Paolo; Adorni, Roberta; Compare, Angelo

2018-05-01

Acute psychosocial stress is typically investigated in laboratory settings using protocols with distinctive characteristics. For example, some tasks involve the action of speaking, which seems to alter Heart Rate Variability (HRV) through acute changes in respiration patterns. However, it is still unknown which task induces the strongest subjective and autonomic stress response. The present cross-over randomized trial sought to investigate the differences in perceived stress and in linear and non-linear analyses of HRV between three different verbal (Speech and Stroop) and non-verbal (Montreal Imaging Stress Task; MIST) stress tasks, in a sample of 60 healthy adults (51.7% females; mean age = 25.6 ± 3.83 years). Analyses were run controlling for respiration rates. Participants reported similar levels of perceived stress across the three tasks. However, MIST induced a stronger cardiovascular response than Speech and Stroop tasks, even after controlling for respiration rates. Finally, women reported higher levels of perceived stress and lower HRV both at rest and in response to acute psychosocial stressors, compared to men. Taken together, our results suggest the presence of gender-related differences during psychophysiological experiments on stress. They also suggest that verbal activity masked the vagal withdrawal through altered respiration patterns imposed by speaking. Therefore, our findings support the use of highly-standardized math task, such as MIST, as a valid and reliable alternative to verbal protocols during laboratory studies on stress. Copyright © 2018 Elsevier B.V. All rights reserved.

Comparing the Effects of Oral Contraceptives Containing Levonorgestrel With Products Containing Antiandrogenic Progestins on Clinical, Hormonal, and Metabolic Parameters and Quality of Life in Women With Polycystic Ovary Syndrome: Crossover Randomized Controlled Trial Protocol

PubMed Central

Amiri, Mina; Nahidi, Fatemeh; Khalili, Davood; Bidhendi-Yarandi, Razieh

2017-01-01

Background Oral contraceptives (OCs) have been used as a first-line option for medical treatment in women with polycystic ovary syndrome (PCOS). Despite theoretical superiority of products containing antiandrogenic progestins compared to OCs containing levonorgestrel (LNG), the clinical advantage of these compounds remains unclear. Objective The aim of this study was to compare the effects of OCs containing LNG with products containing antiandrogenic progestins including cyproterone acetate, drospirenone, and desogestrel on clinical, hormonal, and metabolic parameters and quality of life in women with PCOS. Methods We conducted a 6-arm crossover randomized controlled trial with each arm including OCs containing LNG and one of those 3 OCs containing antiandrogenic progestins. The anthropometric and clinical manifestations and hormonal and biochemical parameters of participants were assessed at 6 time points including baseline, after washout period, and 3 and 6 months after intervention. Results The study is ongoing and follow-up of recruited women will continue until 2018. Conclusions This study will provide scientific evidence on comparability of OCs with the various progesterones that will assist in decision making taking into account cost effectiveness. Trial Registration Iranian Registry of Clinical Trials IRCT201702071281N2; http://www.irct.ir/searchresult.php? keyword=&id=1281&number=2&prt=12869&total=10&m=1 (Archived by WebCite at http://www.webcitation.org/6tSP8FNWo) PMID:28963092

Psyllium supplementation in adolescents improves fat distribution & lipid profile: a randomized, participant-blinded, placebo-controlled, crossover trial.

PubMed

de Bock, Martin; Derraik, José G B; Brennan, Christine M; Biggs, Janene B; Smith, Greg C; Cameron-Smith, David; Wall, Clare R; Cutfield, Wayne S

2012-01-01

We aimed to assess the effects of psyllium supplementation on insulin sensitivity and other parameters of the metabolic syndrome in an at risk adolescent population. This study encompassed a participant-blinded, randomized, placebo-controlled, crossover trial. Subjects were 47 healthy adolescent males aged 15-16 years, recruited from secondary schools in lower socio-economic areas with high rates of obesity. Participants received 6 g/day of psyllium or placebo for 6 weeks, with a two-week washout before crossing over. Fasting lipid profiles, ambulatory blood pressure, auxological data, body composition, activity levels, and three-day food records were collected at baseline and after each 6-week intervention. Insulin sensitivity was measured by the Matsuda method using glucose and insulin values from an oral glucose tolerance test. 45 subjects completed the study, and compliance was very high: 87% of participants took >80% of prescribed capsules. At baseline, 44% of subjects were overweight or obese. 28% had decreased insulin sensitivity, but none had impaired glucose tolerance. Fibre supplementation led to a 4% reduction in android fat to gynoid fat ratio (p = 0.019), as well as a 0.12 mmol/l (6%) reduction in LDL cholesterol (p = 0.042). No associated adverse events were recorded. Dietary supplementation with 6 g/day of psyllium over 6 weeks improves fat distribution and lipid profile (parameters of the metabolic syndrome) in an at risk population of adolescent males. Australian New Zealand Clinical Trials Registry ACTRN12609000888268.

Effect of lavender aromatherapy on menopause hot flushing: A crossover randomized clinical trial.

PubMed

Kazemzadeh, Rafat; Nikjou, Roya; Rostamnegad, Masoumeh; Norouzi, Hosein

2016-09-01

Flushing is generally considered to be the primary symptom of menopause and is typically the most common complaint in menopausal women. Although flushing poses no danger to a woman's health, it decreases the quality of life. Thus, the purpose of this study was to determine the effect of lavender aromatherapy on menopause flushing. This double-blinded crossover clinical trial included 100 menopausal women 45-55 years of age who were referred to various health centers in Ardabil, Iran in 2013-2014. Samples were blocked randomly and divided into two intervention (lavender) and control (diluted milk) groups. Lavender aroma was smelled for 20 minutes twice a day, over a 12-week period. Data were collected using a demographic questionnaire, and flushing numbers were duly recorded. Data analysis was performed by SPSS version 16 (SPSS Inc., Chicago, IL, USA) using the Chi-square and t test. The results of our investigation showed that both groups had no significant difference according to demographic characteristics (p > 0.05). Additionally, the flushing number significantly decreased in the intervention group than in the control group (p < 0.001). This study indicated that the use of lavender aromatherapy reduced menopause flushing. Given the impact of stress on flushing and the undesirable effects of menopause symptoms on the quality of life, it would appear that this simple, noninvasive, safe, and effective method can be used by menopausal women with noticeable benefits. Copyright © 2016. Published by Elsevier Taiwan LLC.

An evaluation of the cognitive and mood effects of an energy shot over a 6h period in volunteers: a randomized, double-blind, placebo controlled, cross-over study.

PubMed

Wesnes, Keith A; Barrett, Marilyn L; Udani, Jay K

2013-08-01

Energy drinks are widely available mostly containing glucose, and several have been demonstrated to improve alertness and cognitive function; these effects generally being identified 30-60min after administration. The present study assessed whether an energy shot without carbohydrates would affect major aspects of cognitive function and also mood in volunteers over a 6h time period. This randomized, double-blind, placebo-controlled,crossover study compared the acute effects of the energy shot with a matching placebo in 94 healthy volunteers. Cognitive function was assessed with a widely used set of automated tests of attention and memory. Mood was assessed with the Bond-Lader, Beck Anxiety Index, Beck Depression Index, Chalder Fatigue Scales (CFS), and the POMS. The volunteers were requested to limit their sleep to between 3 and 6h the night before each testing day. Compared to the placebo, the energy shot significantly improved 6 validated composite cognitive function measures from the CDR System as well as self-rated alertness; the benefits on 4 of the cognitive measures still remaining at 6h. The overall effect sizes of the performance improvements were in the small to medium range and thus notable in this field. In conclusion, an energy shot can significantly improve important aspects of cognitive function for up to 6h compared to placebo in partially sleep-deprived healthy volunteers. Copyright © 2013 Elsevier Ltd. All rights reserved.

Impact of a soy drink on climacteric symptoms: an open-label, crossover, randomized clinical trial

PubMed Central

Tranche, Salvador; Brotons, Carlos; Pascual de la Pisa, Beatriz; Macías, Ramón; Hevia, Eduardo; Marzo-Castillejo, Mercè

2016-01-01

Abstract Objectives: The objective of this study is to evaluate the effects of a soy drink with a high concentration of isoflavones (ViveSoy®) on climacteric symptoms. Methods: An open-label, controlled, crossover clinical trial was conducted in 147 peri- and postmenopausal women. Eligible women were recruited from 13 Spanish health centers and randomly assigned to one of the two sequence groups (control or ViveSoy®, 500 mL per day, 15 g of protein and 50 mg of isoflavones). Each intervention phase lasted for 12 weeks with a 6-week washout period. Changes on the Menopause Rating Scale and quality of life questionnaires, as well as lipid profile, cardiovascular risk and carbohydrate and bone metabolism were assessed. Statistical analysis was performed using a mixed-effects model. Results: A sample of 147 female volunteers was recruited of which 90 were evaluable. In both sequence groups, adherence to the intervention was high. Regular consumption of ViveSoy® reduced climacteric symptoms by 20.4% (p = 0.001) and symptoms in the urogenital domain by 21.3% (p < 0.05). It also improved health-related quality life by 18.1%, as per the MRS questionnaire (p <0.05). Conclusion: Regular consumption of ViveSoy® improves both the somatic and urogenital domain symptoms of menopause, as well as health-related quality of life in peri- and postmenopausal women. PMID:26806546

Antihyperalgesic efficacy of 5% lidocaine medicated plaster in capsaicin and sunburn pain models--two randomized, double-blinded, placebo-controlled crossover trials in healthy volunteers.

PubMed

Gustorff, Burkhard; Hauer, David; Thaler, Johannes; Seis, Astrid; Draxler, Julia

2011-12-01

The aim of this research is to analyze analgesic efficacy of the 5% lidocaine medicated plaster in two randomized, double-blinded, placebo-controlled, crossover studies in 16 healthy volunteers using capsaicin and sunburn pain models. Lidocaine and placebo plasters were simultaneously applied to forearms and thighs at contralateral body sites for three alternating 12-h plaster-on/plaster-off periods. Between the second and third plaster-on period, 4.2-cm circular spots on both pretreated thighs were irradiated with three times the individual minimal erythema dose of UVB light. After the last plaster-on period, 20 μl of 0.1% capsaicin was injected intradermally into both forearms. The study was repeated using a single 12-h plaster application. The area of pinprick hyperalgesia was diminished by 53% (p < 0.003) in the capsaicin model and by 84% (p < 0.0001) in the sunburn model; the intensity of mechanical hyperalgesia to rigid filaments (8 - 512 mN) was reduced in both models. Cold pain perception threshold was reduced (19.7°C ± 8.0 vs 21.8°C ± 6.8 for placebo, p < 0.05, sunburn). Similar effects were observed in the 12-h exposure study. No effect was seen on capsaicin-induced spontaneous pain and flare size, or blood flow in the sunburn area, and heat hyperalgesia in either study. Lidocaine plaster effectively treats mechanical hyperalgesia and cold pain.

A Case Study of Controlling Crossover in a Selection Hyper-heuristic Framework Using the Multidimensional Knapsack Problem.

PubMed

Drake, John H; Özcan, Ender; Burke, Edmund K

2016-01-01

Hyper-heuristics are high-level methodologies for solving complex problems that operate on a search space of heuristics. In a selection hyper-heuristic framework, a heuristic is chosen from an existing set of low-level heuristics and applied to the current solution to produce a new solution at each point in the search. The use of crossover low-level heuristics is possible in an increasing number of general-purpose hyper-heuristic tools such as HyFlex and Hyperion. However, little work has been undertaken to assess how best to utilise it. Since a single-point search hyper-heuristic operates on a single candidate solution, and two candidate solutions are required for crossover, a mechanism is required to control the choice of the other solution. The frameworks we propose maintain a list of potential solutions for use in crossover. We investigate the use of such lists at two conceptual levels. First, crossover is controlled at the hyper-heuristic level where no problem-specific information is required. Second, it is controlled at the problem domain level where problem-specific information is used to produce good-quality solutions to use in crossover. A number of selection hyper-heuristics are compared using these frameworks over three benchmark libraries with varying properties for an NP-hard optimisation problem: the multidimensional 0-1 knapsack problem. It is shown that allowing crossover to be managed at the domain level outperforms managing crossover at the hyper-heuristic level in this problem domain.

Findings From a Prospective Randomized Controlled Trial of an Individualized Music Listening Program for Persons With Dementia.

PubMed

Kwak, Jung; Anderson, Keith; O'Connell Valuch, Katharine

2018-06-01

Music & Memory (M&M) is a passive music intervention that uses personalized music playlists delivered on digital music players. This program has been increasingly adopted in nursing homes across the United States to facilitate communication, engagement, and socialization among persons with dementia (PWDs); however, few studies have evaluated the program's effect on PWDs' outcomes. In the present study, a randomized controlled crossover design was used to examine the impact of the M&M program on 59 PWDs in 10 nursing homes over a 14-week period. Residents' evaluated outcomes included agitation, behavioral symptoms, and use of psychotropic medications. Although trends supported the positive effects of M&M, no statistically significant differences were found in any of the outcomes measured over time. Methodological limitations withstanding, these findings call into question the effectiveness of the M&M program and the ability of facility staff to implement this intervention with fidelity.

How to deal with morning bad breath: A randomized, crossover clinical trial.

PubMed

Oliveira-Neto, Jeronimo M; Sato, Sandra; Pedrazzi, Vinícius

2013-11-01

The absence of a protocol for the treatment of halitosis has led us to compare mouthrinses with mechanical oral hygiene procedures for treating morning breath by employing a hand-held sulfide monitor. To compare the efficacy of five modalities of treatment for controlling morning halitosis in subjects with no dental or periodontal disease. This is a five-period, randomized, crossover clinical trial. Twenty volunteers were randomly assigned to the trial. Testing involved the use of a conventional tongue scraper, a tongue scraper joined to the back of a toothbrush's head, two mouthrinses (0.05% cetylpyridinium chloride and 0.12% chlorhexidine digluconate) and a soft-bristled toothbrush and fluoride toothpaste for practicing oral hygiene. Data analysis was performed using SPSS version 17 for Windows and NCSS 2007 software (P < 0.05). The products and the periods were compared with each other using the Friedman's test. When significant differences (P < 0.05) were determined, the products and periods were compared in pairs by using the Wilcoxon's test and by adjusting the original significance level (0.05) for multiple comparisons by using the Bonferroni's method. The toothbrush's tongue scraper was able to significantly reduce bad breath for up to 2 h. Chlorhexidine reduced bad breath only at the end of the second hour, an effect that lasted for 3 h. Mechanical tongue cleaning was able to immediately reduce bad breath for a short period, whereas chlorhexidine and mechanical oral hygiene reduced bad breath for longer periods, achieving the best results against morning breath.

Ass's milk in children with atopic dermatitis and cow's milk allergy: crossover comparison with goat's milk.

PubMed

Vita, Daniela; Passalacqua, Giovanni; Di Pasquale, Giuseppe; Caminiti, Lucia; Crisafulli, Giuseppe; Rulli, Imma; Pajno, Giovanni B

2007-11-01

Cow milk allergy is a common disease of infancy, often associated with atopic dermatitis (AD). Avoidance of cow milk (CM) implies the use of alternative dietary supports such as mammalian milks. In this study, we assessed the tolerability and clinical effect of ass's milk (AM), when compared with the largely used goat's milk (GM) in a single-blind, controlled, randomized crossover. Twenty-eight children with AD and ascertained allergy to CM were enrolled. The children were randomized to AM or GM for 6 months, then switched to the other milk for further 3 months. The SCORAD index (SI) and a visual analog scale (VAS) were evaluated blindly. After termination of the study, food challenges with GM and AM were performed. An SDS-PAGE analysis of different milks was performed. Two children from the GM group dropped out after randomization and 26 completed the study. Ass milk invariantly led to a significant improvement of SI and VAS of symptoms (p < 0.03 vs. baseline and inter-group), whereas GM had no measurable clinical effect. At the end of the study 23 of 26 children had a positive food challenge with GM and one of 26 with AM. Ass's milk had a protein profile closer to human milk than GM. Ass milk is better tolerated and more effective than GM in reducing symptoms of AD. It may represent a better substitute of CM than the currently used GM.

Flexible chain molecules in the marginal and concentrated regimes: universal static scaling laws and cross-over predictions.

PubMed

Laso, Manuel; Karayiannis, Nikos Ch

2008-05-07

We present predictions for the static scaling exponents and for the cross-over polymer volumetric fractions in the marginal and concentrated solution regimes. Corrections for finite chain length are made. Predictions are based on an analysis of correlated fluctuations in density and chain length, in a semigrand ensemble in which mers and solvent sites exchange identities. Cross-over volumetric fractions are found to be chain length independent to first order, although reciprocal-N corrections are also estimated. Predicted scaling exponents and cross-over regimes are compared with available data from extensive off-lattice Monte Carlo simulations [Karayiannis and Laso, Phys. Rev. Lett. 100, 050602 (2008)] on freely jointed, hard-sphere chains of average lengths from N=12-500 and at packing densities from dilute ones up to the maximally random jammed state.

Acceptability of potential rectal microbicide delivery systems for HIV prevention: a randomized crossover trial.

PubMed

Pines, Heather A; Gorbach, Pamina M; Weiss, Robert E; Hess, Kristen; Murphy, Ryan; Saunders, Terry; Brown, Joelle; Anton, Peter A; Cranston, Ross D

2013-03-01

We assessed the acceptability of three of over-the-counter products representative of potential rectal microbicide (RM) delivery systems. From 2009 to 2010, 117 HIV-uninfected males (79 %) and females (21 %) who engage in receptive anal intercourse participated in a 6-week randomized crossover acceptability trial. Participants received each of three products (enema, lubricant-filled applicator, suppository) every 2 weeks in a randomized sequence. CASI and T-ACASI scales assessed product acceptability via Likert responses. Factor analysis was used to identify underlying factors measured by each scale. Random effects models were fit to examine age and gender effects on product acceptability. Three underlying factors were identified: Satisfaction with Product Use, Sexual Pleasure, and Ease of Product Use. For acceptability, the applicator ranked highest; however, differences between product acceptability scores were greatest among females and younger participants. These findings indicate that RM delivery systems impact their acceptability and should be considered early in RM development to enhance potential use.

Acceptability of Potential Rectal Microbicide Delivery Systems for HIV Prevention: A Randomized Crossover Trial

PubMed Central

Gorbach, Pamina M.; Weiss, Robert E.; Hess, Kristen; Murphy, Ryan; Saunders, Terry; Brown, Joelle; Anton, Peter A.; Cranston, Ross D.

2012-01-01

We assessed the acceptability of three of over-the-counter products representative of potential rectal microbicide (RM) delivery systems. From 2009 to 2010, 117 HIV-uninfected males (79 %) and females (21 %) who engage in receptive anal intercourse participated in a 6-week randomized crossover acceptability trial. Participants received each of three products (enema, lubricant-filled applicator, suppository) every 2 weeks in a randomized sequence. CASI and T-ACASI scales assessed product acceptability via Likert responses. Factor analysis was used to identify underlying factors measured by each scale. Random effects models were fit to examine age and gender effects on product acceptability. Three underlying factors were identified: Satisfaction with Product Use, Sexual Pleasure, and Ease of Product Use. For acceptability, the applicator ranked highest; however, differences between product acceptability scores were greatest among females and younger participants. These findings indicate that RM delivery systems impact their acceptability and should be considered early in RM development to enhance potential use. PMID:23114512

Crossover Control Study of the Effect of Personal Care Products Containing Triclosan on the Microbiome

PubMed Central

Poole, Angela C.; Pischel, Lauren; Ley, Catherine; Suh, Gina; Goodrich, Julia K.; Haggerty, Thomas D.; Ley, Ruth E.

2016-01-01

ABSTRACT Commonly prescribed antibiotics are known to alter human microbiota. We hypothesized that triclosan and triclocarban, components of many household and personal care products (HPCPs), may alter the oral and gut microbiota, with potential consequences for metabolic function and weight. In a double-blind, randomized, crossover study, participants were given triclosan- and triclocarban (TCS)-containing or non-triclosan/triclocarban (nTCS)-containing HPCPs for 4 months and then switched to the other products for an additional 4 months. Blood, stool, gingival plaque, and urine samples and weight data were obtained at baseline and at regular intervals throughout the study period. Blood samples were analyzed for metabolic and endocrine markers and urine samples for triclosan. The microbiome in stool and oral samples was then analyzed. Although there was a significant difference in the amount of triclosan in the urine between the TCS and nTCS phases, no differences were found in microbiome composition, metabolic or endocrine markers, or weight. Though this study was limited by the small sample size and imprecise administration of HPCPs, triclosan at physiologic levels from exposure to HPCPs does not appear to have a significant or important impact on human oral or gut microbiome structure or on a panel of metabolic markers. IMPORTANCE Triclosan and triclocarban are commonly used commercial microbicides found in toothpastes and soaps. It is unknown what effects these chemicals have on the human microbiome or on endocrine function. From this randomized crossover study, it appears that routine personal care use of triclosan and triclocarban neither exerts a major influence on microbial communities in the gut and mouth nor alters markers of endocrine function in humans. PMID:27303746

Does the nature of the definitive impression material influence the outcome of (mandibular) complete dentures?

PubMed

McCord, J Fraser; McNally, Lisa M; Smith, Philip W; Grey, Nicholas J A

2005-09-01

The effects of impression materials on the outcome of complete dentures are poorly understood. This double-blind cross-over randomized controlled trial investigated eleven adult edentulous patients. Each received a maxillary denture and three mandibular dentures (which differed only in the three materials used to record the definitive impressions). The three mandibular dentures were given in a random order. Patients' opinions of each denture were recorded using a Linear Analogue Scale. There was a statistically-significant difference between the outcome of the dentures constructed when zinc-oxide eugenol was used, this material being least favoured (p < 0.001). It would therefore appear that care should be exercised when selecting impression materials when constructing mandibular complete dentures.

Methylphenidate-Related Improvements in Math Performance Cannot Be Explained by Better Cognitive Functioning or Higher Academic Motivation: Evidence From a Randomized Controlled Trial.

PubMed

Kortekaas-Rijlaarsdam, Anne Fleur; Luman, Marjolein; Sonuga-Barke, Edmund; Bet, Pierre; Oosterlaan, Jaap

2017-06-01

This study investigated whether improvements in working memory, reaction time, lapses of attention, interference control, academic motivation, and perceived competence mediated effects of methylphenidate on math performance. Sixty-three children (ADHD diagnosis; methylphenidate treatment; age 8-13; IQ > 70) were randomly allocated to a 7-day methylphenidate or placebo treatment in this double-blind placebo-controlled crossover study and compared with 67 controls. Data were collected at schools and analyzed using mixed-model analysis. Methylphenidate was hypothesized to improve all measures; all measures were evaluated as potential mediators of methylphenidate-related math improvements. Controls mostly outperformed the ADHD group. Methylphenidate did not affect measures of cognitive functioning ( p = .082-.641) or academic motivation ( p = .199-.865). Methylphenidate improved parent ratings of their child's self-perceived competence ( p < .01), which mediated methylphenidate efficacy on math productivity. These results question the necessity of improvements in specific cognitive and motivational deficits associated with ADHD for medication-related academic improvement. They also stimulate further study of perceived competence as a mediator.

Head elevation and lateral head rotation effect on facemask ventilation efficiency: Randomized crossover trials.

PubMed

Matsunami, Sayuri; Komasawa, Nobuyasu; Konishi, Yuki; Minami, Toshiaki

2017-11-01

We performed two prospective randomized crossover trials to evaluate the effect of head elevation or lateral head rotation to facemask ventilation volume. In the first trial, facemask ventilation was performed with a 12-cm high pillow (HP) and 4-cm low pillow (LP) in 20 female patients who were scheduled to undergo general anesthesia. In the second trial, facemask ventilation was performed with and without lateral head rotation in another 20 female patients. Ventilation volume was measured in a pressure-controlled ventilation (PCV) manner at 10, 15, and 20 cmH 2 O inspiratory pressures. In the first trial evaluating head elevation effect, facemask ventilation volume was significantly higher with a HP than with a LP at 15 and 20 cmH 2 O inspiratory pressure (15 cmH 2 O: HP median 540 [ IQR 480-605] mL, LP 460 [400-520] mL, P=0.006, 20 cmH 2 O: HP 705 [650-800] mL, LP 560 [520-677] mL, P<0.001). In the second trial, lateral head rotation did not significantly increase facemask ventilation volume at all inspiratory pressure. Head elevation increased facemask ventilation volume in normal airway patients, while lateral head rotation did not. Copyright © 2017 Elsevier Inc. All rights reserved.

A randomized, placebo-controlled, crossover study of an herbal preparation containing Vernonia cinerea in the treatment of type 2 diabetes.

PubMed

Bin Sayeed, Muhammad Shahdaat; Mostofa, A G M; Ferdous, F M Touhidul Islam; Islam, Md Siddiqul

2013-09-01

A randomized, single-center, double-blind, crossover clinical trial investigated the effects of an herbal preparation containing Vernonia cinerea in patients with type 2 diabetes mellitus. 48 patients with type 2 diabetes mellitus for longer than 6 months were divided into two groups matched for demographic and paraclinical variables. One group received a standard preparation of V. cinerea for 3 months, followed by placebo for another 3 months, and the other group received treatment in the reverse order. All patients received detailed advice on diet, exercise, and lifestyle modification. Glucose level was documented every 2 weeks, and hemoglobin A1c, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, and creatinine levels were determined at recruitment, 3 months, and study completion at 6 months. Glucose, hemoglobin A1c, cholesterol, LDL cholesterol, and triglyceride levels decreased significantly in both groups. No significant differences were seen in aspartate aminotransferase, alanine aminotransferase, or creatinine levels, indicating that use of the herbal preparation had no adverse effect on liver or renal function. Herbal treatment with V. cinerea has a beneficial effect on reducing the glycemic state in patients with type 2 diabetes.

The effects of soy bean flour enriched bread intake on anthropometric indices and blood pressure in type 2 diabetic women: a crossover randomized controlled clinical trial.

PubMed

Salari Moghaddam, Asma; Entezari, Mohammad Hassan; Iraj, Bijan; Askari, Gholamreza; Sharifi Zahabi, Elham; Maracy, Mohammad Reza

2014-01-01

Previous studies showed that soy bean has the potential to improve many aspects of diabetes state and provide metabolic benefits that aid in weight management. We aimed to determine the effects of soy bean flour enriched bread on anthropometric indices and blood pressure among type 2 diabetic patients. This randomized, crossover, clinical trial was performed in 30 type 2 diabetic women. There were two trial periods for 6 weeks and a wash-out period for 4 weeks. In the soy bread diet period, 120 g of soy bean flour enriched bread was consumed each day instead of the same amount of their usual bread or other cereal products. After a 4-week wash-out period, participants were crossed over for another 6 weeks. Mean (±SD) age of study participants was 45.7 ± 3.8 years. The results of our study showed no significant effects of soy bean flour enriched bread on anthropometric indices and blood pressure among diabetic patients. Despite the slight reduction in BMI, waist circumference, and percent of body fat, there were no significant differences in changes of these values between two groups. No significant changes in waist to hip ratio and blood pressure were seen.

The Effects of Soy Bean Flour Enriched Bread Intake on Anthropometric Indices and Blood Pressure in Type 2 Diabetic Women: A Crossover Randomized Controlled Clinical Trial

PubMed Central

Salari Moghaddam, Asma; Entezari, Mohammad Hassan; Iraj, Bijan; Askari, Gholamreza; Sharifi Zahabi, Elham; Maracy, Mohammad Reza

2014-01-01

Previous studies showed that soy bean has the potential to improve many aspects of diabetes state and provide metabolic benefits that aid in weight management. We aimed to determine the effects of soy bean flour enriched bread on anthropometric indices and blood pressure among type 2 diabetic patients. This randomized, crossover, clinical trial was performed in 30 type 2 diabetic women. There were two trial periods for 6 weeks and a wash-out period for 4 weeks. In the soy bread diet period, 120 g of soy bean flour enriched bread was consumed each day instead of the same amount of their usual bread or other cereal products. After a 4-week wash-out period, participants were crossed over for another 6 weeks. Mean (±SD) age of study participants was 45.7 ± 3.8 years. The results of our study showed no significant effects of soy bean flour enriched bread on anthropometric indices and blood pressure among diabetic patients. Despite the slight reduction in BMI, waist circumference, and percent of body fat, there were no significant differences in changes of these values between two groups. No significant changes in waist to hip ratio and blood pressure were seen. PMID:25276127

The acute effect of pleasurable music on craving for alcohol: A pilot crossover study.

PubMed

Mathis, Walter S; Han, Xiaotong

2017-07-01

Chronic administration of drugs of abuse leads to a dopamine deficient state in the mesolimbic system, causing dysphoria in abstinence and contributing to craving and return to use. Recent functional imaging studies have shown that listening to personally pleasing music activates the mesolimbic reward system in a fashion similar to drugs of abuse. It has been proposed that such activation could ameliorate the dysphoria and craving of the hypodopaminergic state. The present study sought to evaluate the efficacy of listening to personally pleasing or moving music on reducing craving in abstinent alcoholics using a single-blind, within-subject randomized block design, with three randomly determined presentations of each condition. Twelve participants with Alcohol Use Disorder on a residential substance rehabilitation unit reported their level of craving with a Visual Analog Scale before and after listening to either the participant-selected song or white noise. Using a mixed model to analyze the crossover design, the music intervention was found to have a statistically significant advantage in craving reduction compared to the noise control. Our results indicate that personally pleasing music might have a role in augmenting substance use disorder treatment via craving reduction. Further study is warranted to elucidate factors which predict the most robust response from this intervention. Copyright © 2017 Elsevier Ltd. All rights reserved.

Alkaline Peroxides Versus Sodium Hypochlorite for Removing Denture Biofilm: a Crossover Randomized Trial.

PubMed

Peracini, Amanda; Regis, Rômulo Rocha; Souza, Raphael Freitas de; Pagnano, Valéria Oliveira; Silva, Cláudia Helena Lovato da; Paranhos, Helena de Freitas Oliveira

2016-01-01

This study evaluated the efficacy of cleanser solutions on denture biofilm removal by a crossover randomized clinical trial. Thirty two edentulous patients were instructed to brush their dentures (specific brush and liquid soap) three times a day (after breakfast, lunch and dinner) and to soak them (≥ 8 h) in: (C) control -water; (AP): alkaline peroxide; or (SH) 0.5% sodium hypochlorite. Each solution was used for 21 days (three cycles of 7 days). At the end of each cycle, the inner surfaces of maxillary dentures were disclosed (1% neutral red) and photographed (HX1 - Sony). Areas (total and stained biofilm) were measured (Image Tool software) and the percentage of biofilm calculated as the ratio between the area of the biofilm multiplied by 100 and total surface area of the internal base of the denture. Data were compared by means of generalized estimating equation (α=5%) and multiple comparisons (Bonferroni; α=1.67%). Immersion in SH reduced biofilm (%) (8.3 ± 13.3B) compared to C (18.2 ± 14.9A) and AP (18.2 ± 16.6A). The 0.5% sodium hypochlorite solution was the most efficacious for biofilm removal. Alkaline peroxides may not lead to further biofilm removal in patients with adequate denture maintenance habits.

Ethical Challenges of Randomized Violence Intervention Trials: Examining the SHARE intervention in Rakai, Uganda

PubMed Central

Wagman, Jennifer A.; Paul, Amy; Namatovu, Fredinah; Ssekubugu, Robert; Nalugoda, Fred

2016-01-01

Objective We identify complexities encountered, including unanticipated crossover between trial arms and inadequate ‘standard of care’ violence services, during a cluster randomized trial (CRT) of a community-level intimate partner violence (IPV) and HIV prevention intervention in Uganda. Methods Concepts in public health ethics - beneficence, social value of research, fairness, standard of care, and researcher responsibilities for post-trial benefits - are used to critically reflect on lessons learned and guide discussion on practical and ethical challenges of violence intervention CRTs. Results Existing ethical guidelines provide incomplete guidance for responding to unexpected crossover in CRTs providing IPV services. We struggled to balance duty of care with upholding trial integrity, and identifying and providing appropriate standard of care. While we ultimately offered short-term IPV services to controls, we faced additional challenges related to sustaining services beyond the ‘short-term’ and post-trial. Conclusion Studies evaluating community-level violence interventions, including those combined with HIV reduction strategies, are limited yet critical for developing evidence-based approaches for effectively preventing IPV. Although CRTs are a promising design, further guidance is needed to implement trials that avoid introducing tensions between validity of findings, researchers’ responsibilities to protect participants, and equitable distribution of CRT benefits. PMID:27453794

Effects of audiovisual distraction in children with special healthcare needs during dental restorations: a randomized crossover clinical trial.

PubMed

Bagattoni, Simone; D'Alessandro, Giovanni; Sadotti, Agnese; Alkhamis, Nadia; Piana, Gabriela

2018-01-01

Audiovisual distraction using video eyeglasses is useful in managing distress and reducing fear and anxiety in healthy children during dental treatments. To evaluate the effect of audiovisual distraction on behavior and self-reported pain of children with special healthcare needs (SHCN) without intellectual disability during dental restorations and its influence on the operator stress and the time of the appointment. This randomized controlled crossover trial comprised 48 children with SHCN requiring at least two dental restorations. One restoration was done wearing the video eyeglasses and one wearing conventional behavior management techniques. Subjective and objective pain was evaluated using the Faces Pain Scale - Revised (FPS-R) and the revised Face, Leg, Activity, Cry, and Consolability scale (r-FLACC). The operator stress using a VAS, the time of the appointment, and the child satisfaction were recorded. The use of video eyeglasses significantly reduced the operator stress. The bivariate analysis showed that the mean FPS-R score and the mean r-FLACC score were significantly lower using the video eyeglasses only during the second clinical session. Audiovisual distraction could be useful in managing distress in SHCN children without intellectual disability but cannot replace the conventional behavior management techniques. © 2017 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Home-based neurologic music therapy for arm hemiparesis following stroke: results from a pilot, feasibility randomized controlled trial.

PubMed

Street, Alexander J; Magee, Wendy L; Bateman, Andrew; Parker, Michael; Odell-Miller, Helen; Fachner, Jorg

2018-01-01

To assess the feasibility of a randomized controlled trial to evaluate music therapy as a home-based intervention for arm hemiparesis in stroke. A pilot feasibility randomized controlled trial, with cross-over design. Randomization by statistician using computer-generated, random numbers concealed in opaque envelopes. Participants' homes across Cambridgeshire, UK. Eleven people with stroke and arm hemiparesis, 3-60 months post stroke, following discharge from community rehabilitation. Each participant engaged in therapeutic instrumental music performance in 12 individual clinical contacts, twice weekly for six weeks. Feasibility was estimated by recruitment from three community stroke teams over a 12-month period, attrition rates, completion of treatment and successful data collection. Structured interviews were conducted pre and post intervention to establish participant tolerance and preference. Action Research Arm Test and Nine-hole Peg Test data were collected at weeks 1, 6, 9, 15 and 18, pre and post intervention by a blinded assessor. A total of 11 of 14 invited participants were recruited (intervention n = 6, waitlist n = 5). In total, 10 completed treatment and data collection. It cannot be concluded whether a larger trial would be feasible due to unavailable data regarding a number of eligible patients screened. Adherence to treatment, retention and interview responses might suggest that the intervention was motivating for participants. ClinicalTrials.gov identifier NCT 02310438.

A randomized, controlled, crossover study in patients with mild and moderate asthma undergoing treatment with traditional Chinese acupuncture

PubMed Central

Pai, Hong Jin; Azevedo, Raymundo Soares; Braga, Alfésio Luís Ferreira; Martins, Lourdes Conceição; Saraiva-Romanholo, Beatriz M; de Arruda Martins, Milton; Lin, Chin An

2015-01-01

OBJECTIVES: This study sought to verify the effects of acupuncture as an adjuvant treatment for the control of asthma. METHODS: This was a randomized, controlled, crossover trial conducted at the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. A total of 74 patients with mild/moderate, persistent asthma were randomized into two therapeutic groups: Group A – 31 patients underwent 10 real weekly acupuncture sessions, followed by a 3-week washout period and 10 sham weekly acupuncture sessions; and Group B - 43 patients underwent 10 sham weekly acupuncture sessions, followed by a 3-week washout period and 10 real weekly acupuncture sessions. Patients used short- and long-acting β-2 agonists and inhaled corticosteroids when necessary. Prior to treatment and after each period of 10 treatment sessions, the patients were evaluated for spirometry, induced sputum cell count, exhaled nitric oxide (NO) and with the Short Form 36 (SF-36) and Questionnaire on Quality of Life-Asthma (QQLA) questionnaires. Daily peak flow and symptom diaries were registered. The level of significance adopted was 5% (α=0.05). RESULTS: In Group B, after real acupuncture, there was a decrease in eosinophils (p=0.035) and neutrophils (p=0.047), an increase in macrophages (p=0.001) and an improvement in peak flow (p=0.01). After sham acupuncture treatment, patients experienced less coughing (p=0.037), wheezing (p=0.013) and dyspnea (p=0.014); similarly, after real acupuncture, patients reported less coughing (p=0.040), wheezing (p=0.012), dyspnea (p<0.001) and nocturnal awakening episodes (p=0.009). In Group A, there was less use of rescue medication (p=0.043). After the sham procedure, patients in Group A experienced less coughing (p=0.007), wheezing (p=0.037), dyspnea (p<0.001) and use of rescue medication (p<0.001) and after real acupuncture, these patients showed improvements in functional capacity (p=0.004), physical aspects (p=0.002), general health status (p<0.001) and vitality (p=0.019). Sham acupuncture also led to significant differences in symptoms, but these were not different from those seen with real acupuncture. Spirometry and exhaled NO levels did not show a difference between sham and real acupuncture treatment. In addition, no significant difference was demonstrated between treatments regarding the quality of life evaluation. CONCLUSION: Real and sham acupuncture have different effects and outcomes on asthma control. The crossover approach was not effective in this study because both interventions led to improvement of asthma symptoms, quality of life and inflammatory cell counts. Thus, sham acupuncture cannot serve as a placebo in trials with acupuncture as the main intervention for asthma. PMID:26598077

Short-term effects of crossover treatment with silodosin and tamsulosin hydrochloride for lower urinary tract symptoms associated with benign prostatic hyperplasia.

PubMed

Miyakita, Hideshi; Yokoyama, Eiji; Onodera, Yasutada; Utsunomiya, Takuji; Tokunaga, Masatoshi; Tojo, Takanori; Fujii, Noriteru; Yanada, Shuichi

2010-10-01

To compare the efficacy and safety of silodosin and tamsulosin in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) by a randomized crossover method. BPH patients with the complaint of LUTS were included in this study, and were randomly divided into two groups: a silodosin-preceding group (4 weeks of twice-daily administration of silodosin at 4 mg, followed by 4 weeks of once-daily administration of tamsulosin at 0.2 mg) or a tamsulosin-preceding group (4 weeks' administration of tamsulosin, followed by 4 weeks' administration of silodosin). No drug withdrawal period was provided when switching the drug. In the first treatment period, both drugs significantly improved the International Prostate Symptom Score total score, but the improvement by silodosin was significantly superior to that by tamsulosin. After crossover treatment, significant improvement was observed only with silodosin treatment. Moreover, intergroup comparison of changes revealed that silodosin showed significant improvement of straining and nocturia with first and crossover treatments, respectively, compared with tamsulosin. Silodosin also significantly improved quality of life (QOL) score in both treatment periods, while tamsulosin significantly improved QOL score only in the first treatment period. The most frequent adverse drug reaction was ejaculatory disorder with silodosin; however, the incidence of dizziness with silodosin was similar to that with tamsulosin. In BPH/LUTS patients, silodosin exhibits excellent efficacy in improving subjective symptoms in both initial and crossover treatment, and it appears to improve the QOL of patients. © 2010 The Japanese Urological Association.

Effects of coarse-graining on the scaling behavior of long-range correlated and anti-correlated signals.

PubMed

Xu, Yinlin; Ma, Qianli D Y; Schmitt, Daniel T; Bernaola-Galván, Pedro; Ivanov, Plamen Ch

2011-11-01

We investigate how various coarse-graining (signal quantization) methods affect the scaling properties of long-range power-law correlated and anti-correlated signals, quantified by the detrended fluctuation analysis. Specifically, for coarse-graining in the magnitude of a signal, we consider (i) the Floor, (ii) the Symmetry and (iii) the Centro-Symmetry coarse-graining methods. We find that for anti-correlated signals coarse-graining in the magnitude leads to a crossover to random behavior at large scales, and that with increasing the width of the coarse-graining partition interval Δ, this crossover moves to intermediate and small scales. In contrast, the scaling of positively correlated signals is less affected by the coarse-graining, with no observable changes when Δ < 1, while for Δ > 1 a crossover appears at small scales and moves to intermediate and large scales with increasing Δ. For very rough coarse-graining (Δ > 3) based on the Floor and Symmetry methods, the position of the crossover stabilizes, in contrast to the Centro-Symmetry method where the crossover continuously moves across scales and leads to a random behavior at all scales; thus indicating a much stronger effect of the Centro-Symmetry compared to the Floor and the Symmetry method. For coarse-graining in time, where data points are averaged in non-overlapping time windows, we find that the scaling for both anti-correlated and positively correlated signals is practically preserved. The results of our simulations are useful for the correct interpretation of the correlation and scaling properties of symbolic sequences.

Effects of coarse-graining on the scaling behavior of long-range correlated and anti-correlated signals

PubMed Central

Xu, Yinlin; Ma, Qianli D.Y.; Schmitt, Daniel T.; Bernaola-Galván, Pedro; Ivanov, Plamen Ch.

2014-01-01

We investigate how various coarse-graining (signal quantization) methods affect the scaling properties of long-range power-law correlated and anti-correlated signals, quantified by the detrended fluctuation analysis. Specifically, for coarse-graining in the magnitude of a signal, we consider (i) the Floor, (ii) the Symmetry and (iii) the Centro-Symmetry coarse-graining methods. We find that for anti-correlated signals coarse-graining in the magnitude leads to a crossover to random behavior at large scales, and that with increasing the width of the coarse-graining partition interval Δ, this crossover moves to intermediate and small scales. In contrast, the scaling of positively correlated signals is less affected by the coarse-graining, with no observable changes when Δ < 1, while for Δ > 1 a crossover appears at small scales and moves to intermediate and large scales with increasing Δ. For very rough coarse-graining (Δ > 3) based on the Floor and Symmetry methods, the position of the crossover stabilizes, in contrast to the Centro-Symmetry method where the crossover continuously moves across scales and leads to a random behavior at all scales; thus indicating a much stronger effect of the Centro-Symmetry compared to the Floor and the Symmetry method. For coarse-graining in time, where data points are averaged in non-overlapping time windows, we find that the scaling for both anti-correlated and positively correlated signals is practically preserved. The results of our simulations are useful for the correct interpretation of the correlation and scaling properties of symbolic sequences. PMID:25392599

A Randomized, Crossover Clinical Trial of Exoskeletal-Assisted Walking to Improve Mobility, Bowel Function, and Cardiometabolic Profiles in Persons with SCI

DTIC Science & Technology

2015-10-01

comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS...participants and at three study sites. It is also designed to determine if the body composition and bowel function benefits that were observed with as few...demonstrated that ten participants were able to use the device to successfully walk for four to six hours per week for three months. It is unknown if a

Very low protein diet reduces indoxyl sulfate levels in chronic kidney disease.

PubMed

Marzocco, Stefania; Dal Piaz, Fabrizio; Di Micco, Lucia; Torraca, Serena; Sirico, Maria Luisa; Tartaglia, Domenico; Autore, Giuseppina; Di Iorio, Biagio

2013-01-01

High levels of indoxyl sulfate (IS) are associated with chronic kidney disease (CKD) progression and increased mortality in CKD patients. The aim of this pilot study was to assess whether a very low protein diet (VLPD; 0.3 g/kg bw/day), with a consequent low phosphorus intake, would reduce IS serum levels compared to a low protein diet (LPD; 0.6 g/kg bw/day) in CKD patients not yet on dialysis. This is a post hoc analysis of a preceding cross-over study aimed to analyze FGF23 during VLPD. Here we performed a prospective randomized controlled crossover study in which 32 patients were randomized to receive either a VLPD (0.3 g/kg bw/day) supplemented with ketoanalogues during the first week and an LPD during the second week (group A, n = 16), or an LPD during the first week and a VLPD during the second week (group B, n = 16 patients). IS serum levels were measured at baseline and at the end of each study period. We compared them to 24 hemodialysis patients (HD) and 14 healthy subjects (control). IS serum concentration was significantly higher in the HD (43.4 ± 12.3 µM) and CKD (11.1 ± 6.6 µM) groups compared to the control group (2.9 ± 1.1 µM; p < 0.001). IS levels also correlated with creatinine values in CKD patients (R(2) = 0.42; p < 0.0001). After only 1 week of a VLPD, even preceded by an LPD, CKD patients showed a significant reduction of IS serum levels (37%). VLPD supplemented with ketoanalogues reduced IS serum levels in CKD patients not yet on dialysis. Copyright © 2013 S. Karger AG, Basel.

Area-specific modulation of neural activation comparing escitalopram and citalopram revealed by pharmaco-fMRI: a randomized cross-over study.

PubMed

Windischberger, Christian; Lanzenberger, Rupert; Holik, Alexander; Spindelegger, Christoph; Stein, Patrycja; Moser, Ulrike; Gerstl, Florian; Fink, Martin; Moser, Ewald; Kasper, Siegfried

2010-01-15

Area-specific and stimulation-dependent changes of human brain activation by selective serotonin reuptake inhibitors (SSRI) are an important issue for improved understanding of treatment mechanisms, given the frequent prescription of these drugs in depression and anxiety disorders. The aim of this neuroimaging study was to investigate differences in BOLD-signal caused by administration of the SSRIs escitalopram and citalopram using pharmacological functional magnetic resonance imaging (pharmaco-fMRI). Eighteen healthy subjects participated in a placebo-controlled, randomized, double-blind study in cross-over repeated measures design. Each volunteer performed facial emotional discrimination and a sensorimotor control paradigm during three scanning sessions. Citalopram (20 mg/d), escitalopram (10 mg/d) and placebo were administered for 10 days each with a drug-free period of at least 21 days. Significant pharmacological effects on BOLD-signal were found in the amygdala, medial frontal gyrus, parahippocampal, fusiform and middle temporal gyri. Post-hoc t-tests revealed decreased BOLD-signal in the right amygdala and left parahippocampal gyrus in both pharmacological conditions, compared to placebo. Escitalopram, compared to citalopram, induced a decrease of BOLD-signal in the medial frontal gyrus and an increase in the right fusiform and left parahippocampal gyri. Drug effects were concentrated in brain regions with dense serotonergic projections. Both escitalopram and citalopram attenuated BOLD-signal in the amygdala and parahippocampal cortex to emotionally significant stimuli compared to control stimuli. We believe that reduced reactivity in the medial frontal gyrus found for escitalopram compared to citalopram administration might explain the response differences between study drugs as demonstrated in previous clinical trials.

A single session of hatha yoga improves stress reactivity and recovery after an acute psychological stress task-A counterbalanced, randomized-crossover trial in healthy individuals.

PubMed

Benvenutti, Mateus J; Alves, Eduardo da Sliva; Michael, Scott; Ding, Ding; Stamatakis, Emmanuel; Edwards, Kate M

2017-12-01

Yoga is promoted as an anti-stress activity, however, little is known about the mechanisms through which it acts. The present study investigated the acute effects of a hatha yoga session, displayed on a video, on the response to and recovery from an acute psychological stressor. Twenty-four healthy young adults took part in a counterbalanced, randomized-crossover trial, with a yoga and a control condition (watching TV). Participants attended the laboratory in the afternoon on two days and each session comprised a baseline, control or yoga task, stress task and recovery. Blood pressure (BP), heart rate (HR) and salivary cortisol responses were measured. State cognitive- and somatic-anxiety along with self-confidence were assessed before and after the stressor. Although no difference in the BP or HR responses to stress were found between conditions, systolic BP (p=0.047) and diastolic BP (p=0.018) recovery from stress were significantly accelerated and salivary cortisol reactivity was significantly lower (p=0.01) in the yoga condition. A yoga session also increased self-confidence (p=0.006) in preparation for the task and after completion. Moreover, self-confidence reported after the stress task was considered debilitative towards performance in the control condition, but remained facilitative in the yoga condition. Our results show that a single video-instructed session of hatha yoga was able to improve stress reactivity and recovery from an acute stress task in healthy individuals. These positive preliminary findings encourage further investigation in at-risk populations in which the magnitude of effects may be greater, and support the use of yoga for stress reactivity and recovery. Copyright © 2017 Elsevier Ltd. All rights reserved.

A fish-based diet intervention improves endothelial function in postmenopausal women with type 2 diabetes mellitus: a randomized crossover trial.

PubMed

Kondo, Keiko; Morino, Katsutaro; Nishio, Yoshihiko; Kondo, Motoyuki; Nakao, Keiko; Nakagawa, Fumiyuki; Ishikado, Atsushi; Sekine, Osamu; Yoshizaki, Takeshi; Kashiwagi, Atsunori; Ugi, Satoshi; Maegawa, Hiroshi

2014-07-01

The beneficial effects of fish and n-3 polyunsaturated fatty acids (PUFAs) consumption on atherosclerosis have been reported in numerous epidemiological studies. However, to the best of our knowledge, the effects of a fish-based diet intervention on endothelial function have not been investigated. Therefore, we studied these effects in postmenopausal women with type 2 diabetes mellitus (T2DM). Twenty-three postmenopausal women with T2DM were assigned to two four-week periods of either a fish-based diet (n-3 PUFAs ≧ 3.0 g/day) or a control diet in a randomized crossover design. Endothelial function was measured with reactive hyperemia using strain-gauge plethysmography and compared with the serum levels of fatty acids and their metabolites. Endothelial function was determined with peak forearm blood flow (Peak), duration of reactive hyperemia (Duration) and flow debt repayment (FDR). A fish-based dietary intervention improved Peak by 63.7%, Duration by 27.9% and FDR by 70.7%, compared to the control diet. Serum n-3 PUFA levels increased after the fish-based diet period and decreased after the control diet, compared with the baseline (1.49 vs. 0.97 vs. 1.19 mmol/l, p < 0.0001). There was no correlation between serum n-3 PUFA levels and endothelial function. An increased ratio of epoxyeicosatrienoic acid/dihydroxyeicosatrienoic acid was observed after a fish-based diet intervention, possibly due to the inhibition of the activity of soluble epoxide hydrolase. A fish-based dietary intervention improves endothelial function in postmenopausal women with T2DM. Dissociation between the serum n-3 PUFA concentration and endothelial function suggests that the other factors may contribute to this phenomenon. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparative effect of a new mouthrinse containing chlorhexidine, triclosan and zinc on volatile sulphur compounds: a randomized, crossover, double-blind study.

PubMed

Mendes, L; Coimbra, J; Pereira, A L; Resende, M; Pinto, M G

2016-08-01

The aims of this study were to compare the volatile sulphur compounds (VSC)-reducing effect of two commercial mouthrinses using a morning bad breath model and to assess the role of mechanical plaque control (MPC) when performed previously to mouthrinse use. Eleven volunteers with good oral health were enrolled in a double-blind, randomized, six-step crossover design study with a 7-day washout period. Two commercial mouthrinses were tested using a saline solution (NaCl 0.9%) as a negative control: one mouthrinse contained 0.05% chlorhexidine, 0.05% cetylpyridinium chloride and 0.14% zinc lactate (CHX-CPC-Zn), while the other contained 0.05% chlorhexidine, 0.15% triclosan and 0.18% zinc pidolate (CHX-triclosan-Zn). A portable sulphide monitor (Halimeter(®) ) was used for VSC quantification. Measurements were made at baseline, and 1, 3 and 5 h after rinsing. Significant differences were detected by analysis of variance. No significant differences between groups were detected at baseline. We were unable to demonstrate a significant influence of mechanical plaque control on the reduction of VSC levels when performed before mouthrinse use (P = 0.631). Both mouthrinses effectively lowered VSC levels in all test intervals (P < 0.05). No statistically significant differences were found between mouthrinses in any of the test intervals (P = 0.629, 0.069 and 0.598 at 1, 3 and 5 h). This study demonstrated that CHX-CPC-Zn and CHX-triclosan-Zn have significant and similar effects in reducing VSC levels, which persist for at least 5 h. Such effects were independent of previous MPC, which failed to improve on the results of mouthrinse use alone. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Comparing the effects of infrastructure on bicycling injury at intersections and non-intersections using a case–crossover design

PubMed Central

Harris, M Anne; Reynolds, Conor C O; Winters, Meghan; Cripton, Peter A; Shen, Hui; Chipman, Mary L; Cusimano, Michael D; Babul, Shelina; Brubacher, Jeffrey R; Friedman, Steven M; Hunte, Garth; Monro, Melody; Vernich, Lee; Teschke, Kay

2013-01-01

Background This study examined the impact of transportation infrastructure at intersection and non-intersection locations on bicycling injury risk. Methods In Vancouver and Toronto, we studied adult cyclists who were injured and treated at a hospital emergency department. A case–crossover design compared the infrastructure of injury and control sites within each injured bicyclist's route. Intersection injury sites (N=210) were compared to randomly selected intersection control sites (N=272). Non-intersection injury sites (N=478) were compared to randomly selected non-intersection control sites (N=801). Results At intersections, the types of routes meeting and the intersection design influenced safety. Intersections of two local streets (no demarcated traffic lanes) had approximately one-fifth the risk (adjusted OR 0.19, 95% CI 0.05 to 0.66) of intersections of two major streets (more than two traffic lanes). Motor vehicle speeds less than 30 km/h also reduced risk (adjusted OR 0.52, 95% CI 0.29 to 0.92). Traffic circles (small roundabouts) on local streets increased the risk of these otherwise safe intersections (adjusted OR 7.98, 95% CI 1.79 to 35.6). At non-intersection locations, very low risks were found for cycle tracks (bike lanes physically separated from motor vehicle traffic; adjusted OR 0.05, 95% CI 0.01 to 0.59) and local streets with diverters that reduce motor vehicle traffic (adjusted OR 0.04, 95% CI 0.003 to 0.60). Downhill grades increased risks at both intersections and non-intersections. Conclusions These results provide guidance for transportation planners and engineers: at local street intersections, traditional stops are safer than traffic circles, and at non-intersections, cycle tracks alongside major streets and traffic diversion from local streets are safer than no bicycle infrastructure. PMID:23411678

Effects of rose hip intake on risk markers of type 2 diabetes and cardiovascular disease: a randomized, double-blind, cross-over investigation in obese persons

PubMed Central

Andersson, U; Berger, K; Högberg, A; Landin-Olsson, M; Holm, C

2012-01-01

BACKGROUND/OBJECTIVES: In studies performed in mice, rose hip powder has been shown to both prevent and reverse high-fat diet-induced obesity and glucose intolerance as well as reduce plasma levels of cholesterol. The aim of this study was to investigate whether daily intake of rose hip powder over 6 weeks exerts beneficial metabolic effects in obese individuals. SUBJECTS/METHODS: A total of 31 obese individuals with normal or impaired glucose tolerance were enrolled in a randomized, double-blind, cross-over study in which metabolic effects of daily intake of a rose hip powder drink over 6 weeks was compared with a control drink. Body weight, glucose tolerance, blood pressure, blood lipids and markers of inflammation were assessed in the subjects. RESULTS: In comparison with the control drink, 6 weeks of daily consumption of the rose hip drink resulted in a significant reduction of systolic blood pressure (−3.4% P=0.021), total plasma cholesterol (−4.9% P=0.0018), low-density lipoprotein (LDL) cholesterol (−6.0% P=0.012) and LDL/HDL ratio (−6.5% P=0.041). The Reynolds risk assessment score for cardiovascular disease was decreased in the rose hip group compared with the control group (−17% P=0.007). Body weight, diastolic blood pressure, glucose tolerance, and plasma levels of high-density lipoprotein (HDL) cholesterol, triglycerides, incretins and markers of inflammation did not differ between the two groups. CONCLUSIONS: Daily consumption of 40 g of rose hip powder for 6 weeks can significantly reduce cardiovascular risk in obese people through lowering of systolic blood pressure and plasma cholesterol levels. PMID:22166897

Spa therapy adjunct to pharmacotherapy is beneficial in rheumatoid arthritis: a crossover randomized controlled trial

NASA Astrophysics Data System (ADS)

Karagülle, Mine; Kardeş, Sinan; Dişçi, Rian; Karagülle, Müfit Zeki

2018-02-01

This study aims to investigate whether 2-week spa therapy, as an adjunct to usual pharmacological therapy, has any beneficial effect in patients with rheumatoid arthritis (RA). In this single-blind crossover study, 50 patients were randomly assigned in a 1:1 manner to receive usual pharmacological therapy plus 2-week spa therapy or usual pharmacological therapy alone (period 1.6 months); after a 9-month washout, patients were crossed over to the opposite assignment (period 2.6 months). Spa therapy program included a daily saline balneotherapy session at 36-37 °C for 20 min except Sundays. The clinical outcomes were evaluated at baseline, after spa therapy (2 weeks) and 3 and 6 months after the spa therapy in both period and were pain (Visual Analogue Scale (VAS)), patient and physician global assessments (VAS), Health Assessment Questionnaire (HAQ), and Disease Activity Score (DAS28). Spa therapy was superior to control therapy in improving all the assessed clinical outcomes at the end of the spa therapy. This superiority persisted significantly in physician global assessment ( p = 0.010) and with a trend in favor of spa group in patient global assessment ( p = 0.058), function ( p = 0.092), and disease activity ( p = 0.098) at 3 months. Statistically significant improvements were found in spa therapy compared to control in disease activity ( p = 0.006) and patient ( p = 0.020) and physician global ( p = 0.011) assessments, and a trend toward improvements in pain ( p = 0.069) and swollen joints ( p = 0.070) at 6 months. A 2-week spa therapy adjunct to usual pharmacological therapy provided beneficial clinical effects compared to usual pharmacological therapy alone, in RA patients treated with traditional disease-modifying antirheumatic drugs. These beneficial effects may last for 6 months.

Curcuma decreases serum hepcidin levels in healthy volunteers: a placebo-controlled, randomized, double-blind, cross-over study.

PubMed

Lainé, Fabrice; Laviolle, Bruno; Bardou-Jacquet, Edouard; Fatih, Nadia; Jezequel, Caroline; Collet, Nicolas; Ropert, Martine; Morcet, Jeff; Hamon, Catherine; Reymann, Jean-Michel; Loréal, Olivier

2017-10-01

Hepcidin, secreted by hepatocytes, controls iron metabolism by limiting iron egress in plasma. Hepcidin is upregulated during inflammation through the activation of the signal transducer and activator of transcription 3 (STAT3) transduction pathway, which decreases iron bioavailability and may explain the anemia of chronic inflammatory disease. In vitro, it has been shown that curcumin can decrease hepcidin synthesis by decreasing STAT3 activity. We conducted a proof-of-concept study to assess the effect of curcuma on hepcidin synthesis in human. This was a placebo-controlled, randomized, double-blind, cross-over, two-period study performed in 18 healthy male volunteers. Subjects received a single oral dose of 6 g curcuma containing 2% of curcumin or placebo. Serum hepcidin and iron parameters were assessed repeatedly until 48 h after dosing. When compared with a placebo curcuma decreased hepcidin levels significantly at 6 h (-19%, P = 0.004), 8 h (-17%, P = 0.009), and 12 h (-17%, P = 0.007) and tended to decrease hepcidin at 24 h (-15%, P = 0.076). Curcuma also significantly increased serum ferritin levels at 6 and 8 h (+7% for both times, P = 0.018, 0.030, respectively) and had no effects on serum iron, transferrin, and transferrin saturation. This pilot study showed that curcuma decreases serum hepcidin levels in human and supports the idea that curcuma could be useful in treating hepcidin overproduction during inflammatory processes. Confirmatory studies in patients with chronic inflammation are now required to determine the optimal dose and therapeutic scheme of curcuma. © 2017 Société Française de Pharmacologie et de Thérapeutique.

Effect of Ginkgo biloba on visual field and contrast sensitivity in Chinese patients with normal tension glaucoma: a randomized, crossover clinical trial.

PubMed

Guo, Xinxing; Kong, Xiangbin; Huang, Rui; Jin, Ling; Ding, Xiaohu; He, Mingguang; Liu, Xing; Patel, Mehul Chimanlal; Congdon, Nathan G

2014-01-07

We evaluated the effect of ginkgo biloba extract on visual field defect and contrast sensitivity in a Chinese cohort with normal tension glaucoma. In this prospective, randomized, placebo-controlled crossover study, patients newly diagnosed with normal tension glaucoma, either in a tertiary glaucoma clinic (n = 5) or in a cohort undergoing routine general physical examinations in a primary care clinic (n = 30), underwent two 4-week phases of treatment, separated by a washout period of 8 weeks. Randomization determined whether ginkgo biloba extract (40 mg, 3 times per day) or placebo (identical-appearing tablets) was received first. Primary outcomes were change in contrast sensitivity and mean deviation on 24-2 SITA standard visual field testing, while secondary outcomes included IOP and self-reported adverse events. A total of 35 patients with mean age 63.7 (6.5) years were randomized to the ginkgo biloba extract-placebo (n = 18) or the placebo-ginkgo biloba extract (n = 17) sequence. A total of 28 patients (80.0%, 14 in each group) who completed testing did not differ at baseline in age, sex, visual field mean deviation, contrast sensitivity, IOP, or blood pressure. Changes in visual field and contrast sensitivity did not differ by treatment received or sequence (P > 0.2 for all). Power to have detected a difference in mean defect as large as previously reported was 80%. In contrast to some previous reports, ginkgo biloba extract treatment had no effect on mean defect or contrast sensitivity in this group of normal tension glaucoma patients. (http://www.chictr.org number, ChiCTR-TRC-08000724).

Treatment of fatigue with methylphenidate, modafinil and amantadine in multiple sclerosis (TRIUMPHANT-MS): Study design for a pragmatic, randomized, double-blind, crossover clinical trial.

PubMed

Nourbakhsh, Bardia; Revirajan, Nisha; Waubant, Emmanuelle

2018-01-01

Fatigue is the most common symptom of multiple sclerosis (MS). Amantadine, modafinil and amphetamine-like stimulants are commonly used in clinical practice for treatment of fatigue; however, the evidence supporting their effectiveness is sparse and conflicting. To describe the design of a trial study funded by Patient-Centered Outcome Research Institute (PCORI) that will compare the efficacy of commonly used fatigue medications in patients with MS. The study is a randomized, placebo-controlled, crossover, four-sequence, four-period, double-blind, multicenter trial of three commonly used medications for the treatment of MS-related fatigue (amantadine, modafinil, methylphenidate) versus placebo in fatigued subjects with MS. Adult patients with MS, with an Expanded Disability Status Scale of <7.0 are eligible to participate. Participants will be randomized to one of four predefined sequences of medication administration. Each sequence comprises four 6-week periods of treatment with one of the 3 study drugs or placebo, and three 2-week washout periods between medication periods. 136 participants will be randomized over two years in two academic centers in the United States starting in the Summer 2017. Complete enrollment is expected by early 2019. The primary outcome of the study is the modified fatigue impact scale (MFIS) score while participants receive the maximally tolerated dose of each study medication (or placebo). Safety and tolerability of the medications and heterogeneity of treatment effect will also be assessed. Results of the proposed study will provide evidence-based and personalized treatment options for patients affected by MS-related fatigue. Clinicaltrials.gov registration number: NCT03185065. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of the 2011 vs 2003 duty hour regulation-compliant models on sleep duration, trainee education, and continuity of patient care among internal medicine house staff: a randomized trial.

PubMed

Desai, Sanjay V; Feldman, Leonard; Brown, Lorrel; Dezube, Rebecca; Yeh, Hsin-Chieh; Punjabi, Naresh; Afshar, Kia; Grunwald, Michael R; Harrington, Colleen; Naik, Rakhi; Cofrancesco, Joseph

2013-04-22

On July 1, 2011, the Accreditation Council for Graduate Medical Education implemented further restrictions of its 2003 regulations on duty hours and supervision. It remains unclear if the 2003 regulations improved trainee well-being or patient safety. To determine the effects of the 2011 Accreditation Council for Graduate Medical Education duty hour regulations compared with the 2003 regulations concerning sleep duration, trainee education, continuity of patient care, and perceived quality of care among internal medicine trainees. Crossover study design in an academic research setting. Medical house staff. General medical teams were randomly assigned using a sealed-envelope draw to an experimental model or a control model. We randomly assigned 4 medical house staff teams (43 interns) using a 3-month crossover design to a 2003-compliant model of every fourth night overnight call (control) with 30-hour duty limits or to one of two 2011-compliant models of every fifth night overnight call (Q5) or a night float schedule (NF), both with 16-hour duty limits. We measured sleep duration using actigraphy and used admission volumes, educational opportunities, the number of handoffs, and satisfaction surveys to assess trainee education, continuity of patient care, and perceived quality of care. RESULTS The study included 560 control, 420 Q5, and 140 NF days that interns worked and 834 hospital admissions. Compared with controls, interns on NF slept longer during the on call period (mean, 5.1 vs 8.3 hours; P = .003), and interns on Q5 slept longer during the postcall period (mean, 7.5 vs 10.2 hours; P = .05). However, both the Q5 and NF models increased handoffs, decreased availability for teaching conferences, and reduced intern presence during daytime work hours. Residents and nurses in both experimental models perceived reduced quality of care, so much so with NF that it was terminated early. Compared with a 2003-compliant model, two 2011 duty hour regulation-compliant models were associated with increased sleep duration during the on-call period and with deteriorations in educational opportunities, continuity of patient care, and perceived quality of care.

DNA methylation epigenetically silences crossover hot spots and controls chromosomal domains of meiotic recombination in Arabidopsis.

PubMed

Yelina, Nataliya E; Lambing, Christophe; Hardcastle, Thomas J; Zhao, Xiaohui; Santos, Bruno; Henderson, Ian R

2015-10-15

During meiosis, homologous chromosomes undergo crossover recombination, which is typically concentrated in narrow hot spots that are controlled by genetic and epigenetic information. Arabidopsis chromosomes are highly DNA methylated in the repetitive centromeres, which are also crossover-suppressed. Here we demonstrate that RNA-directed DNA methylation is sufficient to locally silence Arabidopsis euchromatic crossover hot spots and is associated with increased nucleosome density and H3K9me2. However, loss of CG DNA methylation maintenance in met1 triggers epigenetic crossover remodeling at the chromosome scale, with pericentromeric decreases and euchromatic increases in recombination. We used recombination mutants that alter interfering and noninterfering crossover repair pathways (fancm and zip4) to demonstrate that remodeling primarily involves redistribution of interfering crossovers. Using whole-genome bisulfite sequencing, we show that crossover remodeling is driven by loss of CG methylation within the centromeric regions. Using cytogenetics, we profiled meiotic DNA double-strand break (DSB) foci in met1 and found them unchanged relative to wild type. We propose that met1 chromosome structure is altered, causing centromere-proximal DSBs to be inhibited from maturation into interfering crossovers. These data demonstrate that DNA methylation is sufficient to silence crossover hot spots and plays a key role in establishing domains of meiotic recombination along chromosomes. © 2015 Yelina et al.; Published by Cold Spring Harbor Laboratory Press.

Statistical crossover characterization of the heterotic localized-extended transition.

PubMed

Ugajin, Ryuichi

2003-07-01

We investigated the spectral statistics of a quantum particle in a superlattice consisting of a disordered layer and a clean layer, possibly accompanied by random magnetic fields. Because a disordered layer has localized states and a clean layer has extended states, our quantum system shows a heterotic phase of an Anderson insulator and a normal metal. As the ratio of the volume of these two layers changes, the spectral statistics change from Poissonian to one of the Gaussian ensembles which characterize quantum chaos. A crossover distribution specified by two parameters is introduced to distinguish the transition from an integrable system to a quantum chaotic system during the heterotic phase from an Anderson transition in which the degree of random potentials is homogenous.

Improvement in critical thinking dispositions of undergraduate nursing students through problem-based learning: a crossover-experimental study.

PubMed

Yu, Dehong; Zhang, Yaqing; Xu, Yun; Wu, Juemin; Wang, Caifeng

2013-10-01

Critical thinking (CT) is important to nursing education and practice. Although there is evidence that active learning approaches, such as problem-based learning (PBL), are effective in developing CT dispositions, the findings are inconclusive. This study examines the effect of PBL on the development of CT dispositions in nursing students using a crossover-experimental study in a course offered to nursing students in China. All students were randomly assigned to two parallel groups, with one group receiving PBL and the other receiving lecture-based learning (LBL) as a control. The CT Dispositions Inventory-Chinese Version was administered before and after the semester-long course. Data were collected at three time points. No significant differences between groups were noted in overall and sub-scale scores at baseline; however, pronounced differences in overall posttest scores existed between the PBL and LBL groups. Thus, PBL learning significantly enhanced the CT dispositions of nursing students enrolled in Medical-Surgical Nursing II. Copyright 2013, SLACK Incorporated.

Linkage disequilibrium in HLA cannot be explained by selective recombination.

PubMed

Termijtelen, A; D'Amaro, J; van Rood, J J; Schreuder, G M

1995-11-01

Some combinations of HLA-A, -B and -DR antigens occur more frequently than would be expected from their gene frequencies in the population. This phenomenon, referred to as Linkage Disequilibrium (LD) has been the origin of many speculations. One hypothesis to explain LD is that some haplotypes are protected from recombination. A second hypothesis is that these HLA antigens preferentially recombine after cross-over to create an LD haplotype. We tested these 2 hypotheses: from a pool of over 10,000 families typed in our department, we analyzed 126 families in which HLA-A:B or B:DR recombinant offspring was documented. To overcome a possible bias in our material, we used the non-recombined haplotypes from the same 126 families as a control group. Our results show that the number of cross-overs through LD haplotypes is not significantly lower then would be expected if recombination occurred randomly. Also the number of LD haplotypes created upon recombination was not significantly increased.

Differential-Evolution Control Parameter Optimization for Unmanned Aerial Vehicle Path Planning

PubMed Central

Kok, Kai Yit; Rajendran, Parvathy

2016-01-01

The differential evolution algorithm has been widely applied on unmanned aerial vehicle (UAV) path planning. At present, four random tuning parameters exist for differential evolution algorithm, namely, population size, differential weight, crossover, and generation number. These tuning parameters are required, together with user setting on path and computational cost weightage. However, the optimum settings of these tuning parameters vary according to application. Instead of trial and error, this paper presents an optimization method of differential evolution algorithm for tuning the parameters of UAV path planning. The parameters that this research focuses on are population size, differential weight, crossover, and generation number. The developed algorithm enables the user to simply define the weightage desired between the path and computational cost to converge with the minimum generation required based on user requirement. In conclusion, the proposed optimization of tuning parameters in differential evolution algorithm for UAV path planning expedites and improves the final output path and computational cost. PMID:26943630

Audiovisual distraction for pain relief in paediatric inpatients: A crossover study.

PubMed

Oliveira, N C A C; Santos, J L F; Linhares, M B M

2017-01-01

Pain is a stressful experience that can have a negative impact on child development. The aim of this crossover study was to examine the efficacy of audiovisual distraction for acute pain relief in paediatric inpatients. The sample comprised 40 inpatients (6-11 years) who underwent painful puncture procedures. The participants were randomized into two groups, and all children received the intervention and served as their own controls. Stress and pain-catastrophizing assessments were initially performed using the Child Stress Scale and Pain Catastrophizing Scale for Children, with the aim of controlling these variables. The pain assessment was performed using a Visual Analog Scale and the Faces Pain Scale-Revised after the painful procedures. Group 1 received audiovisual distraction before and during the puncture procedure, which was performed again without intervention on another day. The procedure was reversed in Group 2. Audiovisual distraction used animated short films. A 2 × 2 × 2 analysis of variance for 2 × 2 crossover study was performed, with a 5% level of statistical significance. The two groups had similar baseline measures of stress and pain catastrophizing. A significant difference was found between periods with and without distraction in both groups, in which scores on both pain scales were lower during distraction compared with no intervention. The sequence of exposure to the distraction intervention in both groups and first versus second painful procedure during which the distraction was performed also significantly influenced the efficacy of the distraction intervention. Audiovisual distraction effectively reduced the intensity of pain perception in paediatric inpatients. The crossover study design provides a better understanding of the power effects of distraction for acute pain management. Audiovisual distraction was a powerful and effective non-pharmacological intervention for pain relief in paediatric inpatients. The effects were detected in subsequent acute painful procedures. © 2016 European Pain Federation - EFIC®.

Salivary mutans streptococci and lactobacilli modulations in young children on consumption of probiotic ice-cream containing Bifidobacterium lactis Bb12 and Lactobacillus acidophilus La5.

PubMed

Singh, Richa Polka; Damle, Satyawan Gangaram; Chawla, Amrita

2011-11-01

To compare the levels of mutans streptococci and lactobacilli in saliva of school children, before and after consumption of probiotic and control ice-cream. A double-blind, cross-over, placebo-controlled trial was carried out in forty, 12-14 year-old children, with no clinically detectable caries. The selected children were randomized equally into two groups I and II. Following an initial run-in period of 1 week, children in group I and II were given ice-creams 'A' and 'B', respectively, for 10 days. Being a cross-over study, the ice-creams were interchanged in the two groups after a 2-week wash-out period. Saliva samples at baseline and follow-up were assessed using Dentocult SM and Dentocult LB kits. On statistical evaluation, it was seen that probiotic ice-cream brought about a statistically significant reduction (p-value = 0.003) in salivary mutans streptococci levels with no significant effect on lactobacilli levels. In conclusion, probiotic ice-cream containing Bifidobacterium lactis Bb-12 ATCC27536 and Lactobacillus acidophilus La-5 can reduce the levels of certain caries-associated micro-organisms in saliva.

Effects of Enteric-coated Lactoferrin Tablets Containing Lactobacillus brevis subsp. coagulans on Fecal Properties, Defecation Frequency and Intestinal Microbiota of Japanese Women with a Tendency for Constipation: a Randomized Placebo-controlled Crossover Study

PubMed Central

SUZUKI, Noriyuki; MURAKOSHI, Michiaki; ONO, Tomoji; MORISHITA, Satoru; KOIDE, Misao; BAE, Min Jung; TOTSUKA, Mamoru; SHIMIZU, Makoto; SUGIYAMA, Keikichi; NISHINO, Hoyoku; IIDA, Norio

2013-01-01

The effects of oral administration of enteric-coated tablets containing lactoferrin (LF; 100 mg/tablet) and heat-killed Lactobacillus brevis subsp. coagulans FREM BP-4693 (LB; 6×109 bacteria/tablet) on fecal properties were examined in 32 Japanese women (20–60 years of age) with a tendency for constipation (defecation frequency at equal to or less than 10 times/2 weeks) by a double-blind placebo-controlled crossover design. A significant increase in defecation days per week was obserbed in the subjects who ingested the tablets containing LF and LB compared with the placebo group. The number of bifidobacteria in feces also significantly increased compared with the placebo group. In an in vitro study, LF and tryptic hydrolysate of LF, but not peptic hydrolysate of LF, upregulated the growth of Bifidobacterium longum ATCC15707 when added to the culture. These results demonstrate the capability of the enteric-coated tablets containing LF and LB in improving intestinal function and suggest that they have a growth promoting function for bifidobacteria. PMID:24936358

The sustained effect (12 months) of a single-dose vectored thermal pulsation procedure for meibomian gland dysfunction and evaporative dry eye.

PubMed

Blackie, Caroline A; Coleman, Christy A; Holland, Edward J

2016-01-01

To evaluate the sustained effect (up to 1 year) of a single, 12-minute vectored thermal pulsation (VTP) treatment in improving meibomian gland function and dry eye symptoms in patients with meibomian gland dysfunction and evaporative dry eye. The prospective, multicenter, open-label clinical trial included 200 subjects (400 eyes) who were randomized to a single VTP treatment (treatment group) or twice-daily, 3-month, conventional warm compress and eyelid hygiene therapy (control group). Control group subjects received crossover VTP treatment at 3 months (crossover group). Effectiveness measures of meibomian gland secretion (MGS) and dry eye symptoms were evaluated at baseline and 1, 3, 6, 9, and 12 months. Subjects with inadequate symptom relief could receive additional meibomian gland dysfunction therapy after 3 (treatment group) and 6 months (crossover group). At 3 months, the treatment group had greater mean improvement in MGS (P<0.0001) and dry eye symptoms (P=0.0068), compared to controls. At 12 months, 86% of the treatment group had received only one VTP treatment, and sustained a mean improvement in MGS from 6.4±3.7 (baseline) to 17.3±9.1 (P<0.0001) and dry eye symptoms from 44.1±20.4 to 21.6±21.3 (P<0.0001); 89% of the crossover group had received only one VTP treatment with sustained mean improvement in MGS from 6.3±3.6 to 18.4±11.1 (P<0.0001) and dry eye symptoms from 49.1±21.0 to 24.0±23.2 (P<0.0001). Greater mean improvement in MGS was associated with less severe baseline MGS (P=0.0017) and shorter duration of time between diagnosis and treatment (P=0.0378). A single VTP treatment can deliver a sustained mean improvement in meibomian gland function and mean reduction in dry eye symptoms, over 12 months. A single VTP treatment provides significantly greater mean improvement in meibomian gland function and dry eye symptoms as compared to a conventional, twice-daily, 3-month regimen. Early VTP intervention for meibomian gland dysfunction is associated with improved treatment outcomes.

12-month blood pressure results of catheter-based renal artery denervation for resistant hypertension: the SYMPLICITY HTN-3 trial.

PubMed

Bakris, George L; Townsend, Raymond R; Flack, John M; Brar, Sandeep; Cohen, Sidney A; D'Agostino, Ralph; Kandzari, David E; Katzen, Barry T; Leon, Martin B; Mauri, Laura; Negoita, Manuela; O'Neill, William W; Oparil, Suzanne; Rocha-Singh, Krishna; Bhatt, Deepak L

2015-04-07

Results of the SYMPLICITY HTN-3 (Renal Denervation in Patients With Uncontrolled Hypertension) trial confirmed the safety but not the efficacy of renal denervation for treatment-resistant hypertension at 6 months post procedure. This study sought to analyze the 12-month SYMPLICITY HTN-3 results for the original denervation group, the sham subjects who underwent denervation after the 6-month endpoint (crossover group), and the sham subjects who did not undergo denervation after 6 months (non-crossover group). Eligible subjects were randomized 2:1 to denervation or sham procedure. Subjects were unblinded to their treatment group after the 6-month primary endpoint was ascertained; subjects in the sham group meeting eligibility requirements could undergo denervation. Change in blood pressure (BP) at 12 months post randomization (6 months for crossover subjects) was analyzed. The 12-month follow-up was available for 319 of 361 denervation subjects and 48 of 101 non-crossover subjects; 6-month denervation follow-up was available for 93 of 101 crossover subjects. In denervation subjects, the 12-month office systolic BP (SBP) change was greater than that observed at 6 months (-15.5 ± 24.1 mm Hg vs. -18.9 ± 25.4 mm Hg, respectively; p = 0.025), but the 24-h SBP change was not significantly different at 12 months (p = 0.229). The non-crossover group office SBP decreased by -32.9 ± 28.1 mm Hg at 6 months, but this response regressed to -21.4 ± 19.9 mm Hg (p = 0.01) at 12 months, increasing to 11.5 ± 29.8 mm Hg. These data support no further reduction in office or ambulatory BP after 1-year follow-up. Loss of BP reduction in the non-crossover group may reflect decreased medication adherence or other related factors. (Renal Denervation in Patients With Uncontrolled Hypertension [SYMPLICITY HTN-3]; NCT01418261). Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

The effect of using an audience response system on learning, motivation and information retention in the orthodontic teaching of undergraduate dental students: a cross-over trial.

PubMed

Dhaliwal, Harmeet Kaur; Allen, Mark; Kang, Jing; Bates, Claire; Hodge, Trevor

2015-06-01

New methods of teaching and learning are constantly being sought in the adult learning environment. Audience Response Systems (ARS) have been used in many different learning environments, especially in the field of medical education. The objective of this investigation was to ascertain the effect of ARS use in undergraduate teaching in a UK dental school. A cross-over clustered randomized educational trial. Leeds Dental Institute. Year 4 undergraduate dental students in orthodontics. Students at Leeds Dental Institute were taught two different topics within the curriculum to test the use of ARS in a cross-over trial. A questionnaire was delivered to the test (ARS) and control (non-ARS) groups. The response rate to the questionnaires was 89·5% (test group) and 82·9% (control group). The ARS enabled students to perform better as shown by knowledge retention (P = 0·013). Students found the seminar more interesting (P = 0·013), easier to concentrate (P = 0·025) and easier to participate in (P = 0·020) when ARS was used. When ARS was used, students were more able to answer questions (P<0·0001), were more likely to prepare for the seminar (P<0·0001) and significantly preferred using ARS (P<0·0001). ARS was found to significantly improve student concentration and participation in small group seminar teaching and significantly improved knowledge retention. ARS may be useful in facilitating orthodontic teaching in the future.

Crossover clinical investigation of a whitening chewing gum for inhibiting dental stain formation in conjunction with tooth brushing.

PubMed

Milleman, Jeffery L; Milleman, Kimberly R; Kleber, Carl J; Proskin, Howard M; Dodds, Michael; Kelley, Michael; Ramirez, Lilian

2014-01-01

The purpose of this clinical investigation was to evaluate the effectiveness of a marketed whitening chewing gum compared to a no-gum control in preventing the formation of extrinsic stains on the teeth of stain-forming subjects when chewed over a 12-week period of regular unsupervised use in conjunction with daily tooth brushing. This was a single-center, examiner-blind, randomized, 12-week crossover clinical trial. Stain-forming (after smoking or drinking coffee or tea) adults, starting with a stain-free baseline, either chewed the test gum (Orbit White) unsupervised four times per day, 15 minutes/chew, or used no gum along with daily brushing with a commercially available toothbrush and dentifrice for 12 weeks. At the crossover, all procedures were repeated with subjects assigned the opposite treatment. Extrinsic stain was measured at six and 12 weeks by both the Lobene Stain Index (LSI) and the Modified Lobene Stain Index (MLSI) using separate experienced examiners. After 12 weeks, LSI stain scores showed a significant 25% reduction (p = 0.0008) in new stain formation for subjects using the test chewing gum along with tooth brushing versus tooth brushing alone (no-gum control). The corresponding MLSI stain scores demonstrated a 36% reduction (p < 0.0001) in the formation of extrinsic stain on the teeth. The overall findings of this clinical study demonstrated that regular use of Orbit White chewing gum, soon after smoking or drinking coffee or tea, will supplement daily tooth brushing in preventing unsightly stains from forming on the anterior teeth compared to brushing alone.

Effects of sitagliptin on counter-regulatory and incretin hormones during acute hypoglycaemia in patients with type 1 diabetes: a randomized double-blind placebo-controlled crossover study.

PubMed

Schopman, J E; Hoekstra, J B L; Frier, B M; Ackermans, M T; de Sonnaville, J J J; Stades, A M; Zwertbroek, R; Hartmann, B; Holst, J J; Knop, F K; Holleman, F

2015-06-01

To assess whether the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin affects glucagon and other counter-regulatory hormone responses to hypoglycaemia in patients with type 1 diabetes. We conducted a single-centre, randomized, double-blind, placebo-controlled, three-period crossover study. We studied 16 male patients with type 1 diabetes aged 18-52 years, with a diabetes duration of 5-20 years and intact hypoglycaemia awareness. Participants received sitagliptin (100 mg/day) or placebo for 6 weeks and attended the hospital for three acute hypoglycaemia studies (at baseline, after sitagliptin treatment and after placebo). The primary outcome was differences between the three hypoglycaemia study days with respect to plasma glucagon responses from the initialization phase of the hypoglycaemia intervention to 40 min after onset of the autonomic reaction. Sitagliptin treatment significantly increased active levels of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1. No significant differences were observed for glucagon or adrenergic counter-regulatory responses during the three hypoglycaemia studies. Growth hormone concentration at 40 min after occurrence of autonomic reaction was significantly lower after sitagliptin treatment [median (IQR) 23 (0.2-211.0) mEq/l] compared with placebo [median (IQR) 90 (8.8-180) mEq/l; p = 0.008]. Sitagliptin does not affect glucagon or adrenergic counter-regulatory responses in patients with type 1 diabetes, but attenuates the growth hormone response during late hypoglycaemia. © 2015 John Wiley & Sons Ltd.

Color-coded prefilled medication syringes decrease time to delivery and dosing errors in simulated prehospital pediatric resuscitations: A randomized crossover trial☆, ☆

PubMed Central

Stevens, Allen D.; Hernandez, Caleb; Jones, Seth; Moreira, Maria E.; Blumen, Jason R.; Hopkins, Emily; Sande, Margaret; Bakes, Katherine; Haukoos, Jason S.

2016-01-01

Background Medication dosing errors remain commonplace and may result in potentially life-threatening outcomes, particularly for pediatric patients where dosing often requires weight-based calculations. Novel medication delivery systems that may reduce dosing errors resonate with national healthcare priorities. Our goal was to evaluate novel, prefilled medication syringes labeled with color-coded volumes corresponding to the weight-based dosing of the Broselow Tape, compared to conventional medication administration, in simulated prehospital pediatric resuscitation scenarios. Methods We performed a prospective, block-randomized, cross-over study, where 10 full-time paramedics each managed two simulated pediatric arrests in situ using either prefilled, color-coded-syringes (intervention) or their own medication kits stocked with conventional ampoules (control). Each paramedic was paired with two emergency medical technicians to provide ventilations and compressions as directed. The ambulance patient compartment and the intravenous medication port were video recorded. Data were extracted from video review by blinded, independent reviewers. Results Median time to delivery of all doses for the intervention and control groups was 34 (95% CI: 28–39) seconds and 42 (95% CI: 36–51) seconds, respectively (difference = 9 [95% CI: 4–14] seconds). Using the conventional method, 62 doses were administered with 24 (39%) critical dosing errors; using the prefilled, color-coded syringe method, 59 doses were administered with 0 (0%) critical dosing errors (difference = 39%, 95% CI: 13–61%). Conclusions A novel color-coded, prefilled syringe decreased time to medication administration and significantly reduced critical dosing errors by paramedics during simulated prehospital pediatric resuscitations. PMID:26247145

A double-blind, randomized, placebo/active controlled crossover evaluation of the efficacy and safety of Ritalin ® LA in children with attention-deficit/hyperactivity disorder in a laboratory classroom setting.

PubMed

Schulz, Eberhard; Fleischhaker, Christian; Hennighausen, Klaus; Heiser, Philip; Oehler, Klaus-Uwe; Linder, Martin; Haessler, Frank; Huss, Michael; Warnke, Andreas; Schmidt, Martin; Schulte-Markworth, Michael; Sieder, Christian; Klatt, Jan; Tracik, Ferenc

2010-10-01

The primary objective of this study was to demonstrate efficacy of Ritalin(®) LA 20 mg by showing superiority to placebo and noninferiority to Medikinet(®) Retard in a laboratory classroom setting. Secondary objectives included safety/tolerability and further efficacy parameters. A total of 147 children with attention-deficit/hyperactivity disorder (ADHD) diagnosed by the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS) and aged 6-14 (81% males) and known to be methylphenidate (MPH) responders were enrolled in this multicenter, double-blind, randomized, placebo/active-controlled, three-period (7 days each) crossover study. The Swanson, Kotlin, Agler, M-Flynn, and Pelham (SKAMP) scale was used for efficacy ratings. The mean of SKAMP Combined ratings performed at 10:30 a.m., at 12:00 a.m., and at 1:30 p.m. was defined as the primary parameter. In all, 146 patients completed all treatment periods. Intensity and frequency of adverse events were comparable between the two formulations. Ritalin(®) LA demonstrated superiority compared to placebo (p<0.0001). The observed difference in the SKAMP scores between Ritalin(®) LA and Medikinet(®) Retard between the hours 1.5 until 4.5 did not exceed the noninferiority margin (p=0.0003); therefore, the difference is regarded as not clinically relevant. Similar results were obtained for the secondary efficacy variables. Ritalin(®) LA is an efficacious, well-tolerated treatment option for children aged 6-14 with ADHD.

Evaluation of the effect of topical chamomile (Matricaria chamomilla L.) oleogel as pain relief in migraine without aura: a randomized, double-blind, placebo-controlled, crossover study.

PubMed

Zargaran, Arman; Borhani-Haghighi, Afshin; Salehi-Marzijarani, Mohammad; Faridi, Pouya; Daneshamouz, Saeid; Azadi, Amir; Sadeghpour, Hossein; Sakhteman, Amirhossein; Mohagheghzadeh, Abdolali

2018-05-28

Phytotherapy is a source of finding new remedies for migraine. Traditional chamomile oil (chamomile extraction in sesame oil) is a formulation in Persian medicine (PM) for pain relief in migraine. An oleogel preparation of reformulated traditional chamomile oil was prepared and then standardized based on chamazulene (as a marker in essential oil) and apigenin via gas chromatography (GC) and high-performance liquid chromatography (HPLC) methods, respectively. A crossover double-blind clinical trial was performed with 100 patients. Each patient took two tubes of drug and two tubes of placebo during the study. Visual analog scale (VAS) questionnaires were filled in by the patients and scores were given, ranging from 0 to 10 (based on the severity of pain) during 24 h. Other complications like nausea, vomiting, photophobia, and phonophobia were also monitored. There was 4.48 ± 0.01 μl/ml of chamazulene and 0.233 mg/g of apigenin in the preparation (by correcting the amount with extraction ratio). Thirty-eight patients in the drug-placebo and 34 patients in the placebo-drug groups (a total number of 72 patients as per protocol) completed the process in the randomized controlled trial (RCT). Adapted results from the questionnaires showed that pain, nausea, vomiting, photophobia, and phonophobia significantly (p < 0.001) decreased by using chamomile oleogel on the patients after 30 min. Results supported the efficacy of chamomile oleogel as a pain relief in migraine without aura.

Color-coded prefilled medication syringes decrease time to delivery and dosing errors in simulated prehospital pediatric resuscitations: A randomized crossover trial.

PubMed

Stevens, Allen D; Hernandez, Caleb; Jones, Seth; Moreira, Maria E; Blumen, Jason R; Hopkins, Emily; Sande, Margaret; Bakes, Katherine; Haukoos, Jason S

2015-11-01

Medication dosing errors remain commonplace and may result in potentially life-threatening outcomes, particularly for pediatric patients where dosing often requires weight-based calculations. Novel medication delivery systems that may reduce dosing errors resonate with national healthcare priorities. Our goal was to evaluate novel, prefilled medication syringes labeled with color-coded volumes corresponding to the weight-based dosing of the Broselow Tape, compared to conventional medication administration, in simulated prehospital pediatric resuscitation scenarios. We performed a prospective, block-randomized, cross-over study, where 10 full-time paramedics each managed two simulated pediatric arrests in situ using either prefilled, color-coded syringes (intervention) or their own medication kits stocked with conventional ampoules (control). Each paramedic was paired with two emergency medical technicians to provide ventilations and compressions as directed. The ambulance patient compartment and the intravenous medication port were video recorded. Data were extracted from video review by blinded, independent reviewers. Median time to delivery of all doses for the intervention and control groups was 34 (95% CI: 28-39) seconds and 42 (95% CI: 36-51) seconds, respectively (difference=9 [95% CI: 4-14] seconds). Using the conventional method, 62 doses were administered with 24 (39%) critical dosing errors; using the prefilled, color-coded syringe method, 59 doses were administered with 0 (0%) critical dosing errors (difference=39%, 95% CI: 13-61%). A novel color-coded, prefilled syringe decreased time to medication administration and significantly reduced critical dosing errors by paramedics during simulated prehospital pediatric resuscitations. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Rupatadine does not potentiate the CNS depressant effects of lorazepam: randomized, double-blind, crossover, repeated dose, placebo-controlled study

PubMed Central

García-Gea, Consuelo; Ballester, Maria Rosa; Martínez, Juan; Antonijoan, Rosa Maria; Donado, Esther; Izquierdo, Iñaki; Barbanoj, Manuel-José

2010-01-01

AIM The main objective was to assess whether benzodiazepine intake when rupatadine plasma concentrations were at steady-state would increase the CNS depressant effects. Rupatadine is a new H1-antihistamine which also inhibits platelet activating factor (PAF) release and has been shown to be clinically effective at doses of 10 mg. METHODS Sixteen healthy young volunteers took part in a crossover, randomized, double-blind, placebo controlled trial comprising two experimental periods (repeated administration for 7 days of rupatadine 10 mg or placebo as single oral daily doses, separated by a washout of 14 days). On days 5 and 7, according to a fully balanced design, a single oral dose of lorazepam 2 mg or placebo was added. CNS effects were evaluated on these days by seven objective tests of psychomotor performance and eight subjective visual analogue scales (VAS) at pre-dose and several times after drug intake. Four treatment conditions were evaluated: placebo, rupatadine 10 mg, lorazepam 2 mg and rupatadine 10 mg + lorazepam 2 mg. RESULTS Significant CNS effects, either impairment of psychomotor performance or subjective sedation, were observed when lorazepam was administered, either alone or in combination with steady state concentrations of rupatadine. No significant differences were found between these two conditions. In addition, rupatadine was not different from placebo. All treatments were well tolerated. CONCLUSION Repeated doses of rupatadine (10 mg orally) did not enhance the CNS depressant effects of lorazepam (2 mg orally, single dose) either in objective psychomotor tasks or in subjective evaluations. PMID:20565458

Effect of Extra Virgin Olive Oil on Biomarkers of Inflammation in HIV-Infected Patients: A Randomized, Crossover, Controlled Clinical Trial

PubMed Central

Dokmanović, Sanja Kozić; Kolovrat, Krunoslava; Laškaj, Renata; Jukić, Vedrana; Vrkić, Nada; Begovac, Josip

2015-01-01

Background Premature atherosclerosis in HIV-infected patients is associated with chronic infection by itself and adverse effects of antiretroviral treatment (ART). Extra virgin olive oil (EVOO) has a beneficial effect on the cardiovascular system because of its anti-inflammatory properties. The objective of this study was to determine whether the consumption of EVOO improves inflammation and atherosclerosis biomarkers in HIV-infected patients receiving ART. Material/Methods This randomized, crossover, controlled trial included 39 HIV-positive male participants who consumed 50 mL of EVOO or refined olive oil (ROO) daily. Four participants dropped out of the study. Leukocyte count, erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hsCRP), interleukin-6, fibrinogen, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, malondialdehyde, glutathione-peroxidase, superoxide dismutase, oxidized LDL and von Willebrand factor were determined before the first and after each of the 2 intervention periods. Intervention and washout periods lasted for 20 and 14 days, respectively. Results In participants with >90% compliance (N=30), hsCRP concentrations were lower after EVOO intervention (geometric mean [GM], 1.70 mg/L; 95% confidence interval [CI], 1.15–2.52) compared to ROO administration (GM, 2.92 mg/L; 95% CI, 1.95–4.37) (p=0.035). In participants using lopinavir/ritonavir, ESR and hsCRP concentrations decreased 62% and 151%, respectively, after EVOO administration. In the whole study population (N=35) we found no difference in analyzed biomarkers after EVOO administration. Conclusions Our exploratory study suggests that EVOO consumption could lower hsCRP in patients on ART. PMID:26280823

Timolol LA: a double-masked, active-controlled, randomized, crossover, comfort, ocular safety, and systemic bioavailability study in healthy volunteers.

PubMed

Mundorf, Thomas K; Ogawa, Takahiro; Inui, Noritsugu; Naka, Hiroaki; Novack, Gary D; Crockett, R Stephens

2005-03-01

A new formulation of timolol with sorbic acid, timolol-LA (TLA) (Istaloldagger), has been developed which increases its ocular bioavailability. In the present study, we desired to evaluate the ocular comfort and systemic bioavailability of TLA in healthy volunteers in comparison to standard timolol maleate ophthalmic solution (TIM). This study was a randomized, double-masked, active-controlled, crossover evaluation of 0.5% TLA and 0.5% TIM, bid, in 12 normal healthy volunteers. Visits were at Days 0, 1, 2, 4 and 8 in each period, and there was a minimum 7 day interperiod washout. At all three post-dosing evaluation times (Day 1: Peak, Day 8: Trough, and Day 8: Peak), the 95% confidence interval for the difference between TLA and TIM was not more than 0.37 ng/mL. After administration of TLA, there was a greater incidence of burning/stinging and tearing, but not foreign body sensation, relative to TIM. In general, most symptoms were mild in intensity, and no subject discontinued treatment due to ocular discomfort. Both treatments decreased IOP to a similar level. TLA was relatively comfortable, with a safety profile consistent with further clinical development, and, with bid dosing (exaggerated [2X] that anticipated for clinical use), had a systemic bioavailability similar to that of TIM 0.5%, bid. The incidence of burning and stinging was higher with TLA than with TIM, although reports were mild in severity and did not result in any patient discontin uations. Although the results are of interest, further evaluation in a larger trial may be warranted.

Clinical Trials

MedlinePlus

... pill that has no medicine in it. Most times participants do not know which they are receiving. Other clinical trials involve a crossover design, where participants are randomly assigned to take a ...

Effect of sodium chloride- and sodium bicarbonate-rich mineral water on blood pressure and metabolic parameters in elderly normotensive individuals: a randomized double-blind crossover trial.

PubMed

Schorr, U; Distler, A; Sharma, A M

1996-01-01

To examine the effect of sodium chloride- and sodium bicarbonate-rich mineral water on blood pressure and parameters of glucose and lipid metabolism in elderly normotensive individuals. We examined 21 healthy men and women aged 60-72 years in a randomized, placebo-controlled, double-blind crossover trial. After reducing dietary salt intake to below 100 mmol/day, study participants were randomly assigned to drink 1.5 l daily of a sodium chloride-rich (sodium 84.5 mmol/l, chloride 63.7 mmol/l, bicarbonate 21.9 mmol/l), a sodium bicarbonate-rich (sodium 39.3 mmol/l, chloride 6.5 mmol/l, bicarbonate 48.8 mmol/l) and a low-sodium (placebo: sodium, chloride and bicarbonate < 0.02 mmol/l) mineral water for 4 weeks each in a three-phase crossover order. Each phase was separated by a 2-week washout period in which the study participants remained on a low-salt diet. Compliance was assessed by biweekly urinary electrolyte excretion and five study participants were excluded from analysis for failing to complete the trial or to fulfil the compliance criteria. Mean arterial blood pressure was significantly lower during the periods of consuming low-sodium -7.0 +/- 7.2 mmHg, P < 0.001) or sodium bicarbonate-rich (-5.7 +/- 6.4 mmHg, P < 0.05) water than at baseline. In contrast, blood pressure during the phase of drinking sodium chloride-rich water was identical to that at baseline. Ambulatory 24 h blood pressure, oral glucose tolerance and plasma lipids were not affected by the different regimens. Urinary calcium excretion was significantly reduced by drinking low-sodium or sodium bicarbonate-rich water but was unchanged under the sodium chloride-rich water. Consumption of sodium chloride-rich mineral water can abolish the blood pressure reduction induced by dietary salt restriction in elderly individuals. Sodium bicarbonate-rich mineral water in conjunction with a low-salt diet may have a beneficial effect on calcium homeostasis.

Enriched Air Nitrox Breathing Reduces Venous Gas Bubbles after Simulated SCUBA Diving: A Double-Blind Cross-Over Randomized Trial.

PubMed

Souday, Vincent; Koning, Nick J; Perez, Bruno; Grelon, Fabien; Mercat, Alain; Boer, Christa; Seegers, Valérie; Radermacher, Peter; Asfar, Pierre

2016-01-01

To test the hypothesis whether enriched air nitrox (EAN) breathing during simulated diving reduces decompression stress when compared to compressed air breathing as assessed by intravascular bubble formation after decompression. Human volunteers underwent a first simulated dive breathing compressed air to include subjects prone to post-decompression venous gas bubbling. Twelve subjects prone to bubbling underwent a double-blind, randomized, cross-over trial including one simulated dive breathing compressed air, and one dive breathing EAN (36% O2) in a hyperbaric chamber, with identical diving profiles (28 msw for 55 minutes). Intravascular bubble formation was assessed after decompression using pulmonary artery pulsed Doppler. Twelve subjects showing high bubble production were included for the cross-over trial, and all completed the experimental protocol. In the randomized protocol, EAN significantly reduced the bubble score at all time points (cumulative bubble scores: 1 [0-3.5] vs. 8 [4.5-10]; P < 0.001). Three decompression incidents, all presenting as cutaneous itching, occurred in the air versus zero in the EAN group (P = 0.217). Weak correlations were observed between bubble scores and age or body mass index, respectively. EAN breathing markedly reduces venous gas bubble emboli after decompression in volunteers selected for susceptibility for intravascular bubble formation. When using similar diving profiles and avoiding oxygen toxicity limits, EAN increases safety of diving as compared to compressed air breathing. ISRCTN 31681480.

How to deal with morning bad breath: A randomized, crossover clinical trial

PubMed Central

Oliveira-Neto, Jeronimo M.; Sato, Sandra; Pedrazzi, Vinícius

2013-01-01

Context: The absence of a protocol for the treatment of halitosis has led us to compare mouthrinses with mechanical oral hygiene procedures for treating morning breath by employing a hand-held sulfide monitor. Aims: To compare the efficacy of five modalities of treatment for controlling morning halitosis in subjects with no dental or periodontal disease. Settings and Design: This is a five-period, randomized, crossover clinical trial. Materials and Methods: Twenty volunteers were randomly assigned to the trial. Testing involved the use of a conventional tongue scraper, a tongue scraper joined to the back of a toothbrush's head, two mouthrinses (0.05% cetylpyridinium chloride and 0.12% chlorhexidine digluconate) and a soft-bristled toothbrush and fluoride toothpaste for practicing oral hygiene. Statistical Analysis Used: Data analysis was performed using SPSS version 17 for Windows and NCSS 2007 software (P < 0.05). The products and the periods were compared with each other using the Friedman's test. When significant differences (P < 0.05) were determined, the products and periods were compared in pairs by using the Wilcoxon's test and by adjusting the original significance level (0.05) for multiple comparisons by using the Bonferroni's method. Results: The toothbrush's tongue scraper was able to significantly reduce bad breath for up to 2 h. Chlorhexidine reduced bad breath only at the end of the second hour, an effect that lasted for 3 h. Conclusions: Mechanical tongue cleaning was able to immediately reduce bad breath for a short period, whereas chlorhexidine and mechanical oral hygiene reduced bad breath for longer periods, achieving the best results against morning breath. PMID:24554886

The Sonoma Water Evaluation Trial (SWET): A randomized drinking water intervention trial to reduce gastrointestinal illness in older adults

EPA Science Inventory

Objectives. We estimate the risk of highly credible gastrointestinal illness (HCGI) among adults 55 and older in a community drinking tap water meeting current U.S. standards. Methods. We conducted a randomized, triple-blinded, crossover trial in 714 households (988 indiv...

Hyperbaric Oxygen Therapy Can Diminish Fibromyalgia Syndrome – Prospective Clinical Trial

PubMed Central

Efrati, Shai; Golan, Haim; Bechor, Yair; Faran, Yifat; Daphna-Tekoah, Shir; Sekler, Gal; Fishlev, Gregori; Ablin, Jacob N.; Bergan, Jacob; Volkov, Olga; Friedman, Mony; Ben-Jacob, Eshel; Buskila, Dan

2015-01-01

Background Fibromyalgia Syndrome (FMS) is a persistent and debilitating disorder estimated to impair the quality of life of 2–4% of the population, with 9:1 female-to-male incidence ratio. FMS is an important representative example of central nervous system sensitization and is associated with abnormal brain activity. Key symptoms include chronic widespread pain, allodynia and diffuse tenderness, along with fatigue and sleep disturbance. The syndrome is still elusive and refractory. The goal of this study was to evaluate the effect of hyperbaric oxygen therapy (HBOT) on symptoms and brain activity in FMS. Methods and Findings A prospective, active control, crossover clinical trial. Patients were randomly assigned to treated and crossover groups: The treated group patients were evaluated at baseline and after HBOT. Patients in the crossover-control group were evaluated three times: baseline, after a control period of no treatment, and after HBOT. Evaluations consisted of physical examination, including tender point count and pain threshold, extensive evaluation of quality of life, and single photon emission computed tomography (SPECT) imaging for evaluation of brain activity. The HBOT protocol comprised 40 sessions, 5 days/week, 90 minutes, 100% oxygen at 2ATA. Sixty female patients were included, aged 21–67 years and diagnosed with FMS at least 2 years earlier. HBOT in both groups led to significant amelioration of all FMS symptoms, with significant improvement in life quality. Analysis of SPECT imaging revealed rectification of the abnormal brain activity: decrease of the hyperactivity mainly in the posterior region and elevation of the reduced activity mainly in frontal areas. No improvement in any of the parameters was observed following the control period. Conclusions The study provides evidence that HBOT can improve the symptoms and life quality of FMS patients. Moreover, it shows that HBOT can induce neuroplasticity and significantly rectify abnormal brain activity in pain related areas of FMS patients. Trial Registration ClinicalTrials.gov NCT01827683 PMID:26010952

A pooled analysis of overall survival in COMFORT-I and COMFORT-II, 2 randomized phase III trials of ruxolitinib for the treatment of myelofibrosis.

PubMed

Vannucchi, Alessandro M; Kantarjian, Hagop M; Kiladjian, Jean-Jacques; Gotlib, Jason; Cervantes, Francisco; Mesa, Ruben A; Sarlis, Nicholas J; Peng, Wei; Sandor, Victor; Gopalakrishna, Prashanth; Hmissi, Abdel; Stalbovskaya, Viktoriya; Gupta, Vikas; Harrison, Claire; Verstovsek, Srdan

2015-09-01

Ruxolitinib, a potent Janus kinase 1/2 inhibitor, resulted in rapid and durable improvements in splenomegaly and disease-related symptoms in the 2 phase III COMFORT studies. In addition, ruxolitinib was associated with prolonged survival compared with placebo (COMFORT-I) and best available therapy (COMFORT-II). We present a pooled analysis of overall survival in the COMFORT studies using an intent-to-treat analysis and an analysis correcting for crossover in the control arms. Overall, 301 patients received ruxolitinib (COMFORT-I, n=155; COMFORT-II, n=146) and 227 patients received placebo (n=154) or best available therapy (n=73). After a median three years of follow up, intent-to-treat analysis showed that patients who received ruxolitinib had prolonged survival compared with patients who received placebo or best available therapy [hazard ratio=0.65; 95% confidence interval (95%CI): 0.46-0.90; P=0.01]; the crossover-corrected hazard ratio was 0.29 (95%CI: 0.13-0.63). Both patients with intermediate-2- or high-risk disease showed prolonged survival, and patients with high-risk disease in the ruxolitinib group had survival similar to that of patients with intermediate-2-risk disease in the control group. The Kaplan-Meier estimate of overall survival at week 144 was 78% in the ruxolitinib arm, 61% in the intent-to-treat control arm, and 31% in the crossover-adjusted control arm. While larger spleen size at baseline was prognostic for shortened survival, reductions in spleen size with ruxolitinib treatment correlated with longer survival. These findings are consistent with previous reports and support that ruxolitinib offers a survival benefit for patients with myelofibrosis compared with conventional therapies. (clinicaltrials.gov identifiers: COMFORT-I, NCT00952289; COMFORT-II, NCT00934544). Copyright© Ferrata Storti Foundation.

A six-month crossover chemoprevention clinical trial of tea in smokers and non-smokers: methodological issues in a feasibility study

PubMed Central

2012-01-01

Background Chemoprevention crossover trials of tea can be more efficient than parallel designs but the attrition and compliance rates with such trials are unknown. Methods Attrition (dropouts) and compliance with treatment were assessed in a 25-week randomized, placebo controlled, crossover, feasibility clinical trial of four tea treatments to investigate the effect of tea on oral cancer biomarkers. Each treatment lasted 4 weeks with 2 weeks of washout in between. Participants were 32 smokers and 33 non-smokers without any evidence of premalignant oral lesions. The interventions consisted of packets of green tea, black tea, caffeinated water, or placebo. Participants were assigned to each treatment for four weeks, and were instructed to drink five packets per day while on the treatment. Dropout from the trial and compliance (consumption of ≥ 85% of the prescribed treatment packets) are the main outcome measures reported. Results There was a high rate of dropout (51%) from the study, and the rates were significantly higher among smokers (64%) than non-smokers (36%). Among participants who completed the study the rate of compliance was 72%. The highest rates of dropouts occurred between the first and second treatment visits in both smokers (38% dropout) and non-smokers (18% dropout). Throughout the study smokers were more likely to dropout than non-smokers. Black tea treatment was associated with the highest rates of dropout among smokers (37%), but was associated with the lowest rate of dropout among non-smokers (4%). Conclusions In a study conducted to test the feasibility of a four-treatment crossover tea trial, a high rate of dropout among smokers and non-smokers was observed. Multi-arm crossover tea trials might pose a higher burden on participants and research is needed to improve adherence and treatment compliance in such trials. Trial registration number ISRCTN70410203 PMID:22800470

Home-based neurologic music therapy for arm hemiparesis following stroke: results from a pilot, feasibility randomized controlled trial

PubMed Central

Street, Alexander J; Magee, Wendy L; Bateman, Andrew; Parker, Michael; Odell-Miller, Helen; Fachner, Jorg

2017-01-01

Objective: To assess the feasibility of a randomized controlled trial to evaluate music therapy as a home-based intervention for arm hemiparesis in stroke. Design: A pilot feasibility randomized controlled trial, with cross-over design. Randomization by statistician using computer-generated, random numbers concealed in opaque envelopes. Setting: Participants’ homes across Cambridgeshire, UK. Subjects: Eleven people with stroke and arm hemiparesis, 3–60 months post stroke, following discharge from community rehabilitation. Interventions: Each participant engaged in therapeutic instrumental music performance in 12 individual clinical contacts, twice weekly for six weeks. Main measures: Feasibility was estimated by recruitment from three community stroke teams over a 12-month period, attrition rates, completion of treatment and successful data collection. Structured interviews were conducted pre and post intervention to establish participant tolerance and preference. Action Research Arm Test and Nine-hole Peg Test data were collected at weeks 1, 6, 9, 15 and 18, pre and post intervention by a blinded assessor. Results: A total of 11 of 14 invited participants were recruited (intervention n = 6, waitlist n = 5). In total, 10 completed treatment and data collection. Conclusion: It cannot be concluded whether a larger trial would be feasible due to unavailable data regarding a number of eligible patients screened. Adherence to treatment, retention and interview responses might suggest that the intervention was motivating for participants. Trial registration: ClinicalTrials.gov identifier NCT 02310438. PMID:28643570

Dual Fractal Dimension and Long-Range Correlation of Chinese Stock Prices

NASA Astrophysics Data System (ADS)

Chen, Chaoshi; Wang, Lei

2012-03-01

The recently developed modified inverse random midpoint displacement (mIRMD) and conventional detrended fluctuation analysis (DFA) algorithms are used to analyze the tick-by-tick high-frequency time series of Chinese A-share stock prices and indexes. A dual-fractal structure with a crossover at about 10 min is observed. The majority of the selected time series show visible persistence within this time threshold, but approach a random walk on a longer time scale. The phenomenon is found to be industry-dependent, i.e., the crossover is much more prominent for stocks belonging to cyclical industries than for those belonging to noncyclical (defensive) industries. We have also shown that the sign series show a similar dual-fractal structure, while like generally found, the magnitude series show a much longer time persistence.

Persistent-random-walk approach to anomalous transport of self-propelled particles

NASA Astrophysics Data System (ADS)

Sadjadi, Zeinab; Shaebani, M. Reza; Rieger, Heiko; Santen, Ludger

2015-06-01

The motion of self-propelled particles is modeled as a persistent random walk. An analytical framework is developed that allows the derivation of exact expressions for the time evolution of arbitrary moments of the persistent walk's displacement. It is shown that the interplay of step length and turning angle distributions and self-propulsion produces various signs of anomalous diffusion at short time scales and asymptotically a normal diffusion behavior with a broad range of diffusion coefficients. The crossover from the anomalous short-time behavior to the asymptotic diffusion regime is studied and the parameter dependencies of the crossover time are discussed. Higher moments of the displacement distribution are calculated and analytical expressions for the time evolution of the skewness and the kurtosis of the distribution are presented.

Clinical follow-up after cessation of chronic electrical neuromodulation in patients with severe coronary artery disease: a prospective randomized controlled study on putative involvement of sympathetic activity.

PubMed

Jessurun, G A; DeJongste, M J; Hautvast, R W; Tio, R A; Brouwer, J; van Lelieveld, S; Crijns, H J

1999-10-01

The present study assessed the reoccurrence of myocardial ischemia after withholding electrical neurostimulation. After randomization, in the study or withdrawal group, spinal cord stimulation (SCS) was set active during the first 4 weeks, followed by 4 weeks of withholding stimulation. In the control group, SCS was switched off during 4 weeks before the end of the study. The control group had no crossover period. Measurements were done at baseline, then after 4 and 8 weeks. The first periods at 4 weeks of each sequence of both groups were compared. In addition, a comparison of clinical variables was performed between the study group 4 weeks after withholding stimulation and the control group 4 weeks following randomization. A total number of 24 patients with refractory angina and an implanted spinal cord stimulator were included in the study (n = 12) and control group. Angina pectoris complaints, nitroglycerin intake, ischemia, and heart rate variability using 48-hour ambulatory electrocardiographic monitoring were assessed. In addition, neurohormonal status and symptom-limited aerobic capacity were evaluated. There was no increase of anginal complaints or ischemia after withholding stimulation. Neurohormonal levels and aerobic capacity were not altered. We conclude that there is no adverse clinical rebound phenomenon after withholding neurostimulation in patients with refractory angina pectoris.

The effects of Bifidobacterium animalis ssp. lactis B94 on gastrointestinal wellness in adults with Prader-Willi syndrome: study protocol for a randomized controlled trial.

PubMed

Alyousif, Zainab; Miller, Jennifer L; Sandoval, Mariana Y; MacPherson, Chad W; Nagulesapillai, Varuni; Dahl, Wendy J

2018-04-27

Constipation is a frequent problem in adults with Prader-Willi syndrome. Certain probiotics have been shown to improve transit and gastrointestinal symptoms of adults with functional constipation. The aim of this study is to determine the effect of daily consumption of Bifidobacterium animalis ssp. lactis B94 (B. lactis B94) on stool frequency, stool form, and gastrointestinal symptoms in adults with Prader-Willi syndrome. Adults with Prader-Willi syndrome (18-75 years old, n = 36) will be recruited and enrolled in a 20-week, randomized, double-blind, placebo-controlled, crossover study. Study subjects will be randomized to B. lactis B94 or placebo each for a 4-week period, preceded by a 4-week baseline and followed by 4-week washouts. Subjects will complete daily records of stool frequency and stool form (a proxy of transit time). Dietary intake data also will be collected. Stools, one in each period, will be collected for exploratory microbiota analyses. To our knowledge, this is the first randomized controlled trial evaluating the effectiveness of B. lactis in adults with Prader-Willi syndrome. The results of this study will provide evidence of efficacy for future clinical trials in patient populations with constipation. ClinicalTrials.gov ( NCT03277157 ). Registered on 08 September 2017.

Pyridostigmine bromide versus fludrocortisone in the treatment of orthostatic hypotension in Parkinson's disease - a randomized controlled trial.

PubMed

Schreglmann, S R; Büchele, F; Sommerauer, M; Epprecht, L; Kägi, G; Hägele-Link, S; Götze, O; Zimmerli, L; Waldvogel, D; Baumann, C R

2017-04-01

Evidence for effective treatment options for orthostatic hypotension (OH) in Parkinson's disease (PD) is scarce. Elevation of cholinergic tone with pyridostigmine bromide has been reported as a way to improve blood pressure (bp) regulation in neurogenic hypotension without causing supine hypertension. This was a double-centre, double-blind, randomized, active-control, crossover, phase II non-inferiority trial of pyridostigmine bromide for OH in PD (clinicaltrials.gov NCT01993680). Patients with confirmed OH were randomized to 14 days 3 × 60 mg/day pyridostigmine bromide or 1 × 0.2 mg/day fludrocortisone before crossover. Outcome was measured by peripheral and central bp monitoring during the Schellong manoeuvre and questionnaires. Thirteen participants were enrolled between April 2013 and April 2015 with nine participants completing each trial arm. Repeated measures comparison showed a significant 37% improvement with fludrocortisone for the primary outcome diastolic bp drop on orthostatic challenge (baseline 22.9 ± 13.6 vs. pyridostigmine bromide 22.1 ± 17.0 vs. fludrocortisone 14.0 ± 12.6 mmHg; P = 0.04), whilst pyridostigmine bromide had no effect. Fludrocortisone caused an 11% peripheral systolic supine bp rise (baseline 128.4 ± 12.8 vs. pyridostigmine bromide 130.4 ± 18.3 vs. fludrocortisone 143.2 ± 10.1 mmHg; P = 0.01) but no central mean arterial supine bp rise (baseline 107.2 ± 7.8 vs. pyridostigmine bromide 97.0 ± 12.0 vs. fludrocortisone 107.3 ± 6.3 mmHg; P = 0.047). Subjective OH severity, motor score and quality of life remained unchanged by both study interventions. Pyridostigmine bromide is inferior to fludrocortisone in the treatment of OH in PD. This trial provides first objective evidence of the efficacy of 0.2 mg/day fludrocortisone for OH in PD, causing minor peripheral but no central supine hypertension. In addition to peripheral bp, future trials should include central bp measurements, known to correlate more closely with cardiovascular risk. © 2017 EAN.

A higher-complex carbohydrate diet in gestational diabetes mellitus achieves glucose targets and lowers postprandial lipids: a randomized crossover study.

PubMed

Hernandez, Teri L; Van Pelt, Rachael E; Anderson, Molly A; Daniels, Linda J; West, Nancy A; Donahoo, William T; Friedman, Jacob E; Barbour, Linda A

2014-01-01

The conventional diet approach to gestational diabetes mellitus (GDM) advocates carbohydrate restriction, resulting in higher fat (HF), also a substrate for fetal fat accretion and associated with maternal insulin resistance. Consequently, there is no consensus about the ideal GDM diet. We hypothesized that, compared with a conventional, lower-carbohydrate/HF diet (40% carbohydrate/45% fat/15% protein), consumption of a higher-complex carbohydrate (HCC)/lower-fat (LF) Choosing Healthy Options in Carbohydrate Energy (CHOICE) diet (60/25/15%) would result in 24-h glucose area under the curve (AUC) profiles within therapeutic targets and lower postprandial lipids. Using a randomized, crossover design, we provided 16 GDM women (BMI 34 ± 1 kg/m2) with two 3-day isocaloric diets at 31 ± 0.5 weeks (washout between diets) and performed continuous glucose monitoring. On day 4 of each diet, we determined postprandial (5 h) glucose, insulin, triglycerides (TGs), and free fatty acids (FFAs) following a controlled breakfast meal. There were no between-diet differences for fasting or mean nocturnal glucose, but 24-h AUC was slightly higher (∼6%) on the HCC/LF CHOICE diet (P = 0.02). The continuous glucose monitoring system (CGMS) revealed modestly higher 1- and 2-h postprandial glucose on CHOICE (1 h, 115 ± 2 vs. 107 ± 3 mg/dL, P ≤ 0.01; 2 h, 106 ± 3 vs. 97 ± 3 mg/dL, P = 0.001) but well below current targets. After breakfast, 5-h glucose and insulin AUCs were slightly higher (P < 0.05), TG AUC was no different, but the FFA AUC was significantly lower (∼19%; P ≤ 0.01) on the CHOICE diet. This highly controlled study randomizing isocaloric diets and using a CGMS is the first to show that liberalizing complex carbohydrates and reducing fat still achieved glycemia below current treatment targets and lower postprandial FFAs. This diet strategy may have important implications for preventing macrosomia.

Efficacy of triplet regimen antiemetic therapy for chemotherapy-induced nausea and vomiting (CINV) in bone and soft tissue sarcoma patients receiving highly emetogenic chemotherapy, and an efficacy comparison of single-shot palonosetron and consecutive-day granisetron for CINV in a randomized, single-blinded crossover study.

PubMed

Kimura, Hiroaki; Yamamoto, Norio; Shirai, Toshiharu; Nishida, Hideji; Hayashi, Katsuhiro; Tanzawa, Yoshikazu; Takeuchi, Akihiko; Igarashi, Kentaro; Inatani, Hiroyuki; Shimozaki, Shingo; Kato, Takashi; Aoki, Yu; Higuchi, Takashi; Tsuchiya, Hiroyuki

2015-03-01

The first aim of this study was to evaluate combination antiemetic therapy consisting of 5-HT3 receptor antagonists, neurokinin-1 receptor antagonists (NK-1RAs), and dexamethasone for multiple high emetogenic risk (HER) anticancer agents in bone and soft tissue sarcoma. The second aim was to compare the effectiveness of single-shot palonosetron and consecutive-day granisetron in a randomized, single-blinded crossover study. A single randomization method was used to assign eligible patients to the palonosetron or granisetron arm. Patients in the palonosetron arm received a palonosetron regimen during the first and third chemotherapy courses and a granisetron regimen during the second and fourth courses. All patients received NK-1RA and dexamethasone. Patients receiving the palonosetron regimen were administered 0.75 mg palonosetron on day 1, and patients receiving the granisetron regimen were administered 3 mg granisetron twice daily on days 1 through 5. All 24 patients in this study received at least 4 chemotherapy courses. A total of 96 courses of antiemetic therapy were evaluated. Overall, the complete response CR rate (no emetic episodes and no rescue medication use) was 34%, while the total control rate (a CR plus no nausea) was 7%. No significant differences were observed between single-shot palonosetron and consecutive-day granisetron. Antiemetic therapy with a 3-drug combination was not sufficient to control chemotherapy-induced nausea and vomiting (CINV) during chemotherapy with multiple HER agents for bone and soft tissue sarcoma. This study also demonstrated that consecutive-day granisetron was not inferior to single-shot palonosetron for treating CINV. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Rationale and design of a randomized controlled trial of allogeneic mesenchymal stem cells in patients with nonischemic cardiomyopathy.

PubMed

Greene, Stephen J; Epstein, Stephen E; Kim, Raymond J; Quyyumi, Arshed A; Cole, Robert T; Anderson, Allen S; Wilcox, Jane E; Skopicki, Hal A; Sikora, Sergey; Verkh, Lev; Tankovich, Nikolai I; Gheorghiade, Mihai; Butler, Javed

2017-04-01

This article describes an ongoing study investigating the safety and efficacy of ischemia-tolerant mesenchymal stem cell (MSC) therapy in patients with nonischemic heart failure and dysfunctional viable myocardium without scarring. This study will follow principles of the previously described mechanistic translational-phase concept whereby the effect of the study agent on laboratory and imaging markers of cardiac structure and function will be tested in a small homogenous cohort with the goal to enhance the understanding of the effect of interventions on cardiac remodeling and performance. This single-blind, placebo-controlled, crossover, multicenter, randomized study will assess the safety, tolerability, and preliminary efficacy of a single intravenous (i.v.) dose of allogeneic ischemia-tolerant MSCs in individuals with heart failure of nonischemic cause, ejection fraction 40% or less, and dysfunctional viable myocardium who have been receiving guideline-directed medical therapy. Eligible patients will have no evidence of baseline replacement scarring on delayed-enhancement cardiac magnetic resonance (CMR). Approximately 20 patients will be randomized in a 1 : 1 ratio to receive an i.v. infusion of ischemia-tolerant MSCs or placebo. At 90 days, the two groups will undergo crossover and received the alternative treatment. The primary endpoint is safety, as evaluated through at least 1-year post-MSC infusion. Additional efficacy endpoints will include measures of cardiac structure and function, as evaluated by serial cine-CMR and transthoracic echocardiography at 90 and 180 days post-initial infusion. This pilot study will explore the safety and effects on cardiac structure and function of i.v. injection of ischemia-tolerant MSCs in a small homogenous cohort of nonischemic heart failure patients with reduced ejection fraction and absent replacement scarring on CMR. This study also represents a prospective mechanistic translational-phase study using baseline and serial CMR imaging in heart failure patients and serves as a potential model for design of future heart failure trials (ClinicalTrials.gov identifier: NCT02467387).

Efficacy of a Mandibular Advancement Appliance on Sleep Disordered Breathing in Children: A Study Protocol of a Crossover Randomized Controlled Trial.

PubMed

Idris, Ghassan; Galland, Barbara; Robertson, Christopher J; Farella, Mauro

2016-01-01

Sleep-Disordered Breathing (SDB) varies from habitual snoring to partial or complete obstruction of the upper airway and can be found in up to 10% of children. SDB can significantly affect children's wellbeing, as it can cause growth disorders, educational and behavioral problems, and even life-threatening conditions, such as cardiorespiratory failure. Adenotonsillectomy represents the primary treatment for pediatric SDB where adeno-tonsillar hypertrophy is indicated. For those with craniofacial anomalies, or for whom adenotonsillectomy or other treatment modalities have failed, or surgery is contra-indicated, mandibular advancement splints (MAS) may represent a viable treatment option. Whilst the efficacy of these appliances has been consistently demonstrated in adults, there is little information about their effectiveness in children. To determine the efficacy of mandibular advancement appliances for the management of SDB and related health problems in children. The study will be designed as a single-blind crossover randomized controlled trial with administration of both an "Active MAS" (Twin-block) and a "Sham MAS." Eligible participants will be children aged 8-12 years whose parents report they snore ≥3 nights per week. Sixteen children will enter the full study after confirming other inclusion criteria, particularly Skeletal class I or class II confirmed by lateral cephalometric radiograph. Each child will be randomly assigned to either a treatment sequence starting with the Active or the Sham MAS. Participants will wear the appliances for 3 weeks separated by a 2-week washout period. For each participant, home-based polysomnographic data will be collected four times; once before and once after each treatment period. The Apnea Hypopnea Index (AHI) will represent the main outcome variable. Secondary outcomes will include, snoring frequency, masseter muscle activity, sleep symptoms, quality of life, daytime sleepiness, children behavior, and nocturnal enuresis. In addition, blood samples will be collected to assess growth hormone changes. This study was registered in the Australian New Zealand Clinical Trials Registry (ANZCTR): [ACTRN12614001013651].

Olive (Olea europaea L.) Leaf Polyphenols Improve Insulin Sensitivity in Middle-Aged Overweight Men: A Randomized, Placebo-Controlled, Crossover Trial

PubMed Central

de Bock, Martin; Derraik, José G. B.; Brennan, Christine M.; Biggs, Janene B.; Morgan, Philip E.; Hodgkinson, Steven C.; Hofman, Paul L.; Cutfield, Wayne S.

2013-01-01

Background Olive plant leaves (Olea europaea L.) have been used for centuries in folk medicine to treat diabetes, but there are very limited data examining the effects of olive polyphenols on glucose homeostasis in humans. Objective To assess the effects of supplementation with olive leaf polyphenols (51.1 mg oleuropein, 9.7 mg hydroxytyrosol per day) on insulin action and cardiovascular risk factors in middle-aged overweight men. Design Randomized, double-blinded, placebo-controlled, crossover trial in New Zealand. 46 participants (aged 46.4±5.5 years and BMI 28.0±2.0 kg/m2) were randomized to receive capsules with olive leaf extract (OLE) or placebo for 12 weeks, crossing over to other treatment after a 6-week washout. Primary outcome was insulin sensitivity (Matsuda method). Secondary outcomes included glucose and insulin profiles, cytokines, lipid profile, body composition, 24-hour ambulatory blood pressure, and carotid intima-media thickness. Results Treatment evaluations were based on the intention-to-treat principle. All participants took >96% of prescribed capsules. OLE supplementation was associated with a 15% improvement in insulin sensitivity (p = 0.024) compared to placebo. There was also a 28% improvement in pancreatic β-cell responsiveness (p = 0.013). OLE supplementation also led to increased fasting interleukin-6 (p = 0.014), IGFBP-1 (p = 0.024), and IGFBP-2 (p = 0.015) concentrations. There were however, no effects on interleukin-8, TNF-α, ultra-sensitive CRP, lipid profile, ambulatory blood pressure, body composition, carotid intima-media thickness, or liver function. Conclusions Supplementation with olive leaf polyphenols for 12 weeks significantly improved insulin sensitivity and pancreatic β-cell secretory capacity in overweight middle-aged men at risk of developing the metabolic syndrome. Trial Registration Australian New Zealand Clinical Trials Registry #336317. PMID:23516412

Therapeutic Effects of Standardized Formulation of Stachys lavandulifolia Vahl on Primary Dysmenorrhea: A Randomized, Double-Blind, Crossover, Placebo-Controlled Pilot Study.

PubMed

Monji, Faezeh; Hashemian, Farshad; Salehi Surmaghi, Mohammad-Hossein; Mohammadyari, Fatemeh; Ghiyaei, Saeid; Soltanmohammadi, Alireza

2018-05-09

In Iranian folklore medicine, boiled extract of Stachys lavandulifolia Vahl is reputed to have therapeutic effects in painful disorders. This study evaluated the efficacy of the standardized formulation of S. lavandulifolia Vahl in reducing pain in primary dysmenorrhea, which is known to be a common disorder with significant impact on quality of life. A randomized, double blind, crossover, placebo-controlled pilot study. Bu-Ali Hospital affiliated with Tehran Medical Branch, Islamic Azad University. Twenty-nine patients with primary dysmenorrhea. Patients were enrolled according to medical history and gynecologic sonography. Standardized capsules of S. lavandulifolia were prepared. All the patients were allowed to take mefenamic acid up to 250 mg/q6h if they needed, in the first menstruation cycle to estimate the analgesic consumption at baseline. By the use of an add-on design in the next cycle, they were randomly assigned to receive either herbal or placebo capsules every 4-6 h. Then, they were crossed over to the other group during the course of the trial. At the end of the fourth day of each cycle, the intensity of pain was measured by visual analogue scale and McGill pain questionnaire. Statistical significance was evaluated using repeated-measures one-way analysis of variance. Pain intensity was significantly decreased during consumption of Stachys lavandulifolia capsules in comparison with basic and placebo cycles (p < 0.05). Interestingly, the consumption of mefenamic acid capsules was reduced dramatically in the S. lavandulifolia cycle in comparison with basic and placebo cycles (p < 0.001). It was demonstrated that S. lavandulifolia-prepared formulation can reduce menstrual pain, and can probably be recommended as an add-on therapy or even an alternative remedy to nonsteroidal anti-inflammatory drugs (NSAIDs) with fewer side effects in primary dysmenorrhea.

Ketamine for Social Anxiety Disorder: A Randomized, Placebo-Controlled Crossover Trial.

PubMed

Taylor, Jerome H; Landeros-Weisenberger, Angeli; Coughlin, Catherine; Mulqueen, Jilian; Johnson, Jessica A; Gabriel, Daniel; Reed, Margot O; Jakubovski, Ewgeni; Bloch, Michael H

2018-01-01

Many patients with social anxiety disorder (SAD) experience inadequate symptom relief from available treatments. Ketamine is a potent N-methyl-D-aspartate receptor antagonist with a potentially novel mechanism of action for the treatment of anxiety disorders. Therefore, we conducted a double-blind, randomized, placebo-controlled crossover trial in 18 adults with DSM-5 SAD and compared the effects between intravenous ketamine (0.5 mg/kg over 40 min) and placebo (normal saline) on social phobia symptoms. Ketamine and placebo infusions were administered in a random order with a 28-day washout period between infusions. Ratings of anxiety were assessed 3-h post-infusion and followed for 14 days. We used linear mixed models to assess the impact of ketamine and placebo on anxiety symptoms. Outcomes were blinded ratings on the Liebowitz Social Anxiety Scale (LSAS) and self-reported anxiety on a visual analog scale (VAS-Anxiety). We also used the Wilcoxon signed-rank test to compare the proportion of treatment responders. Based on prior studies, we defined response as a greater than 35% LSAS reduction and 50% VAS-Anxiety reduction. We found ketamine resulted in a significantly greater reduction in anxiety relative to placebo on the LSAS (Time × Treatment: F 9,115 =2.6, p=0.01) but not the VAS-Anxiety (Time × Treatment: F 10,141 =0.4, p=0.95). Participants were significantly more likely to exhibit a treatment response after ketamine infusion relative to placebo in the first 2 weeks following infusion measured on the LSAS (33.33% response ketamine vs 0% response placebo, Wilcoxon signed-rank test z=2.24, p=0.025) and VAS (88.89% response ketamine vs 52.94% response placebo, Wilcoxon signed-rank test z=2.12, p=0.034). In conclusion, this proof-of-concept trial provides initial evidence that ketamine may be effective in reducing anxiety.

Impact of self-assessment questions and learning styles in Web-based learning: a randomized, controlled, crossover trial.

PubMed

Cook, David A; Thompson, Warren G; Thomas, Kris G; Thomas, Matthew R; Pankratz, V Shane

2006-03-01

To determine the effect of self-assessment questions on learners' knowledge and format preference in a Web-based course, and investigate associations between learning styles and outcomes. The authors conducted a randomized, controlled, crossover trial in the continuity clinics of the Mayo-Rochester internal medicine residency program during the 2003-04 academic year. Case-based self-assessment questions were added to Web-based modules covering topics in ambulatory internal medicine. Participants completed two modules with questions and two modules without questions, with sequence randomly assigned. Outcomes included knowledge assessed after each module, format preference, and learning style assessed using the Index of Learning Styles. A total of 121 of 146 residents (83%) consented. Residents had higher test scores when using the question format (mean +/- standard error, 78.9% +/- 1.0) than when using the standard format (76.2% +/- 1.0, p = .006). Residents preferring the question format scored higher (79.7% +/- 1.1) than those preferring standard (69.5% +/- 2.3, p < .001). Learning styles did not affect scores except that visual-verbal "intermediate" learners (80.6% +/- 1.4) and visual learners (77.5% +/- 1.3) did better than verbal learners (70.9% +/- 3.0, p = .003 and p = .033, respectively). Sixty-five of 78 residents (83.3%, 95% CI 73.2-90.8%) preferred the question format. Learning styles were not associated with preference (p > .384). Although the question format took longer than the standard format (60.4 +/- 3.6 versus 44.3 +/- 3.3 minutes, p < .001), 55 of 77 residents (71.4%, 60.0-81.2%) reported that it was more efficient. Instructional methods that actively engage learners improve learning outcomes. These findings hold implications for both Web-based learning and "traditional" educational activities. Future research, in both Web-based learning and other teaching modalities, should focus on further defining the effectiveness of selected instructional methods in specific learning contexts.

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.

Effect of long-term intranasal oxytocin on sexual dysfunction in premenopausal and postmenopausal women: a randomized trial.

PubMed

Muin, Dana A; Wolzt, Michael; Marculescu, Rodrig; Sheikh Rezaei, Safoura; Salama, Mohamed; Fuchs, Carola; Luger, Anton; Bragagna, Elia; Litschauer, Brigitte; Bayerle-Eder, Michaela

2015-09-01

To assess the effect of on-demand intranasal oxytocin administration on female sexual function and activity. Randomized, prospective, double-blind, placebo-controlled, crossover trial with duration of 22 weeks. Academic medical center. Thirty pre-and postmenopausal women with sexual dysfunction. Over 8 weeks, intranasal oxytocin (32 IU) or placebo self-administered by women within 50 minutes before sexual intercourse; after a washout period of 2 weeks, crossover with patients switched to the alternate group for another 8 weeks. Primary outcome parameter: Female Sexual Function Index (FSFI); secondary outcome parameters: Female Sexual Distress Scale (FSDS), Sexual Quality of Life-Female (SQOL-F), Sexual Interest and Desire Inventory-Female (SIDI-F), and Hamilton depression scale (HDS). After oxytocin and placebo, the FSFI score increased by 26% and 31%, SQOL-F score by 144% and 125%, and SIDI-F score by 29% and 23%, respectively (repeated measures analysis of variance between groups). After oxytocin and placebo, the FSDS score decreased by 36% and 45%, respectively (repeated measures analysis of variance between groups). There was no statistically significant treatment, sequence (placebo first/second), or interaction effect. Long-term intranasal oxytocin and placebo administration both improved sexual function and symptoms of depression in women over time with no treatment, sequence (placebo first/second), or interaction effect. NCT02229721. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Fish oil-supplementation increases appetite in healthy adults. A randomized controlled cross-over trial.

PubMed

Damsbo-Svendsen, Signe; Rønsholdt, Mia Dybkjær; Lauritzen, Lotte

2013-07-01

Marine n-3 fatty acids are hypothesized to have beneficial effects on obesity and cancer cachexia possibly via an effect on appetite. The aim of this study was to investigate, if fish oil-supplementation affects appetite in healthy individuals. In a randomized cross-over study, 20 normal-weight subjects (50% females) were given ten 0.5-mL capsules/day of fish oil or soybean oil for 3 weeks separated by 1-week wash-out. In the end of each period, appetite was assessed by 10-cm visual analog scales immediately before and after a standardized breakfast. Results were analyzed in accordance with the paired design considering oil sequence and gender. All subjects completed both periods with a compliance of 96% and oil sequence did not affect the results. There was no difference between the two supplements in any pre-breakfast appetite scores, but the post-prandial sensation of being full was 1.21 cm (0.20; 2.22) lower after the fish oil-period. Furthermore, there was a supplement × gender-interaction on "desire to eat more" due to a score increase of 1.09 cm (0.28; 1.90) in women only. These results suggest that marine n-3 fatty acid may increase appetite. This finding would be potentially beneficial for patients with compromised nutritional status. Copyright © 2013 Elsevier Ltd. All rights reserved.

The effects of alprazolam on tinnitus: a cross-over randomized clinical trial.

PubMed

Jalali, Mir Mohammad; Kousha, Abdorrahim; Naghavi, Sayed Ebrahim; Soleimani, Robabeh; Banan, Rozbeh

2009-11-01

Tinnitus remains a phenomenon with an unknown pathophysiology and for which few therapeutic measures are available. To date there has been insufficient evidence to support the use of alprazolam in the treatment of tinnitus. We sought to evaluate the efficacy of alprazolam for relief of tinnitus. Thirty-six tinnitus sufferers participated in this cross-over, randomized, triple-blind, placebo-controlled trial. Inclusion criteria included patients between ages 21 and 65, with a complaint of non-pulsatile tinnitus of more than 1 year duration. Patients with depressive or anxiety disorders were excluded, as were those using hearing aids. Participants received alprazolam 1.5 mg daily versus placebo in each period. Primary outcome variables included the Tinnitus Handicap Inventory (THI), a Visual Analog Scale (VAS), and tinnitus loudness. Thirty patients completed the study. The average age of patients was 47.58+/-7.65 years. Alprazolam in comparison with placebo did not result in statistically significantly greater relief in THI score and tinnitus loudness. There was a significant improvement in VAS score in the alprazolam group compared with the placebo group (p<0.001). These results suggest that although alprazolam did not improve the THI score or sensation level of loudness significantly, it has a desirable effect on VAS. Further work is needed to determine the beneficial effects of alprazolam in distressed or depressed patients.

Auricular Acupuncture for Exam Anxiety in Medical Students—A Randomized Crossover Investigation

PubMed Central

Klausenitz, Catharina; Hacker, Henriette; Hesse, Thomas; Kohlmann, Thomas; Endlich, Karlhans; Hahnenkamp, Klaus; Usichenko, Taras

2016-01-01

Auricular acupuncture (AA) is effective in the treatment of preoperative anxiety. The aim was to investigate whether AA can reduce exam anxiety as compared to placebo and no intervention. Forty-four medical students were randomized to receive AA, placebo, or no intervention in a crossover manner and subsequently completed three comparable oral anatomy exams with an interval of 1 month between the exams/interventions. AA was applied using indwelling fixed needles bilaterally at points MA-IC1, MA-TF1, MA-SC, MA-AT1 and MA-TG one day prior to each exam. Placebo needles were used as control. Levels of anxiety were measured using a visual analogue scale before and after each intervention as well as before each exam. Additional measures included the State-Trait-Anxiety Inventory, duration of sleep at night, blood pressure, heart rate and the extent of participant blinding. All included participants finished the study. Anxiety levels were reduced after AA and placebo intervention compared to baseline and the no intervention condition (p < 0.003). AA was better at reducing anxiety than placebo in the evening before the exam (p = 0.018). Participants were able to distinguish between AA and placebo intervention. Both AA and placebo interventions reduced exam anxiety in medical students. The superiority of AA over placebo may be due to insufficient blinding of participants. PMID:28033320

Using acupressure and Montessori-based activities to decrease agitation for residents with dementia: a cross-over trial.

PubMed

Lin, Li-Chan; Yang, Man-Hua; Kao, Chieh-Chun; Wu, Shiao-Chi; Tang, Sai-Hung; Lin, Jaung-Geng

2009-06-01

To explore the effectiveness of acupressure and Montessori-based activities in decreasing the agitated behaviors of residents with dementia. A double-blinded, randomized (two treatments and one control; three time periods) cross-over design was used. Six special care units for residents with dementia in long-term care facilities in Taiwan were the sites for the study. One hundred thirty-three institutionalized residents with dementia. Subjects were randomized into three treatment sequences: acupressure-presence-Montessori methods, Montessori methods-acupressure-presence and presence-Montessori methods-acupressure. All treatments were done once a day, 6 days per week, for a 4-week period. The Cohen-Mansfield Agitation Inventory, Ease-of-Care, and the Apparent Affect Rating Scale. After receiving the intervention, the acupressure and Montessori-based-activities groups saw a significant decrease in agitated behaviors, aggressive behaviors, and physically nonaggressive behaviors than the presence group. Additionally, the ease-of-care ratings for the acupressure and Montessori-based-activities groups were significantly better than for the presence group. In terms of apparent affect, positive affect in the Montessori-based-activities group was significantly better than in the presence group. This study confirms that a blending of traditional Chinese medicine and a Western activities program would be useful in elderly care and that in-service training for formal caregivers in the use of these interventions would be beneficial for patients

β-Glucan and dark chocolate: a randomized crossover study on short-term satiety and energy intake.

PubMed

Akyol, Asli; Dasgin, Halil; Ayaz, Aylin; Buyuktuncer, Zehra; Besler, H Tanju

2014-09-23

The aims of this study were to adapt a traditional recipe into a healthier form by adding 3 g of oat β-glucan, substituting milk chocolate to dark chocolate with 70% cocoa, and to examine the effect of these alterations on short-term satiety and energy intake. Study subjects (n = 25) were tested in a randomized, crossover design with four products closely matched for energy content. Four different versions of a traditional recipe including milk chocolate-control (CON), oat β-glucan (B-GLU), dark chocolate (DARK) or oat β-glucan and dark chocolate (B-GLU + DARK) were given to subjects on different test days. After subjects were asked to report visual analog scale (VAS) scores on sensory outcomes and related satiety for four hours ad libitum, lunch was served and energy intake of individuals was measured. VAS scores indicated that none of the test foods exerted an improved effect on satiety feelings. However, energy intake of individuals during ad libitum lunch was significantly lower in dark chocolate groups (CON: 849.46 ± 47.45 kcal versus DARK: 677.69 ± 48.45 kcal and B-GLU + DARK: 691.08 ± 47.45 kcal, p = 0.014). The study demonstrated that substituting dark chocolate for milk chocolate is more effective in inducing satiety during subsequent food intake in healthy subjects.

β-Glucan and Dark Chocolate: A Randomized Crossover Study on Short-Term Satiety and Energy Intake

PubMed Central

Akyol, Asli; Dasgin, Halil; Ayaz, Aylin; Buyuktuncer, Zehra; Besler, H. Tanju

2014-01-01

Aim: The aims of this study were to adapt a traditional recipe into a healthier form by adding 3 g of oat β-glucan, substituting milk chocolate to dark chocolate with 70% cocoa, and to examine the effect of these alterations on short-term satiety and energy intake. Materials and Methods: Study subjects (n = 25) were tested in a randomized, crossover design with four products closely matched for energy content. Four different versions of a traditional recipe including milk chocolate-control (CON), oat β-glucan (B-GLU), dark chocolate (DARK) or oat β-glucan and dark chocolate (B-GLU + DARK) were given to subjects on different test days. After subjects were asked to report visual analog scale (VAS) scores on sensory outcomes and related satiety for four hours ad libitum, lunch was served and energy intake of individuals was measured. Results: VAS scores indicated that none of the test foods exerted an improved effect on satiety feelings. However, energy intake of individuals during ad libitum lunch was significantly lower in dark chocolate groups (CON: 849.46 ± 47.45 kcal versus DARK: 677.69 ± 48.45 kcal and B-GLU + DARK: 691.08 ± 47.45 kcal, p = 0.014). Conclusion: The study demonstrated that substituting dark chocolate for milk chocolate is more effective in inducing satiety during subsequent food intake in healthy subjects. PMID:25251294

Myofascial Induction Effects on Neck-Shoulder Pain in Breast Cancer Survivors: Randomized, Single-Blind, Placebo-Controlled Crossover Design.

PubMed

Castro-Martín, Eduardo; Ortiz-Comino, Lucía; Gallart-Aragón, Tania; Esteban-Moreno, Bernabé; Arroyo-Morales, Manuel; Galiano-Castillo, Noelia

2017-05-01

To (1) investigate the immediate effects of myofascial induction (MI), with placebo electrotherapy as a control, on perceived pain, cervical/shoulder range of motion (ROM), and mood state in breast cancer survivors (BCSs) with shoulder/arm morbidity; and (2) examine the relationships between pain modifications and cervical/shoulder ROM on the side affected by breast cancer. Randomized, single-blind, placebo-controlled crossover study. Physical therapy laboratory. BCSs (N=21) who had a diagnosis of stage I-IIIA breast cancer and had completed adjuvant therapy (except hormonal treatment). During each session, the BCSs received either an MI (fascial unwinding) intervention focused on the upper limb area following the Pilat approach or placebo pulsed shortwave therapy (control group). Each session lasted 30 minutes, and an adequate washout period of 4 weeks between sessions was established. The visual analog scale (VAS) for pain and anxiety, shoulder-cervical goniometry for ROM, the Profile of Mood States for psychological distress, and the Attitudes Towards Massage Scale were used. An analysis of covariance (ANCOVA) revealed significant time × group interactions for VAS affected arm (P=.031) but not for VAS cervical (P=.332), VAS nonaffected arm (P=.698), or VAS anxiety (P=.266). The ANCOVA also revealed significant interactions for affected shoulder flexion (P<.001), abduction (P<.001), external rotation (P=.004), and internal rotation (P=.001). Significant interactions for affected cervical rotation (P=.022) and affected cervical lateral flexion (P=.038) were also found. A significant negative correlation was found between changes in VAS affected arm and shoulder/arm internal rotation ROM (r=-.46; P=.03). A single MI session decreases pain intensity and improves neck-shoulder ROM to a greater degree than placebo electrotherapy for BCSs experiencing pain. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Effects of expiratory ribcage compression before endotracheal suctioning on arterial blood gases in patients receiving mechanical ventilation.

PubMed

Kohan, Mahmoud; Rezaei-Adaryani, Morteza; Najaf-Yarandi, Akram; Hoseini, Fatemeh; Mohammad-Taheri, Nahid

2014-09-01

To investigate the effects of expiratory ribcage compression (ERCC) before endotracheal suctioning on the arterial blood gases (ABG) in patients receiving mechanical ventilation. Endotracheal suctioning is one of the most frequently used methods for airway clearance in patients receiving mechanical ventilation. Chest physiotherapy techniques such as ERCC before endotracheal suctioning can be used as a means to facilitate mobilizing and removing airway secretions and improving alveolar ventilation. A prospective, randomized, controlled cross-over design. A randomized controlled cross-over trial with a convenience sample of 70 mechanically ventilated patients was conducted from 2006 to 2007. The patients received endotracheal suctioning with (experiment-period) or without (control-period) an antecedent 5-min expiratory ribcage. All the patients experienced both periods with at least a 3-h washed-out interval between the two periods. ABG were measured 5 min before and 25 min after endotracheal suctioning. The statistical tests showed that the levels of partial pressure of oxygen (PaO2 )/fraction of inspired oxygen (FiO2 ), partial pressure of carbon dioxide (PaCO2 ) and arterial oxygen saturation (SaO2 ) in the experimental period at 25 min after the intervention were significantly different from the control period. The tests also revealed that the levels of these variables at 25 min after suctioning were also significantly different from baseline values. However, these differences were clinically significant only for PaO2 /FiO2 . By improving the levels of PaO2 /FiO2 , ERCC can reduce the patients' need for oxygen and hence it can at least reduce the side effects of oxygen therapy. Improving PaO2 /FiO2 levels means less need for oxygen therapy. Hence, by applying ERCC we can at least minimize the side effects of oxygen therapy. © 2014 British Association of Critical Care Nurses.

Research: Treatment A randomized crossover study to assess the effect of an oat-rich diet on glycaemic control, plasma lipids and postprandial glycaemia, inflammation and oxidative stress in Type 2 diabetes

PubMed Central

McGeoch, S C; Johnstone, A M; Lobley, G E; Adamson, J; Hickson, K; Holtrop, G; Fyfe, C; Clark, L F; Pearson, D W M; Abraham, P; Megson, I L; MacRury, S M

2013-01-01

Aims In the UK, lifestyle intervention is first-line management in Type 2 diabetes. It is unclear what type of diet is most efficacious for improving glycaemic control. This study investigated the effects of an oat-enriched diet on glycaemic control, postprandial glycaemia, inflammation and oxidative stress compared with standard dietary advice. Methods In a randomized crossover design, 27 volunteers with Type 2 diabetes, managed on diet and lifestyle only, were observed for two consecutive 8-week periods following either the oat-enriched diet or re-enforced standard dietary advice. Volunteers attended at baseline (habitual intake) and 8 and 16 weeks. Measurements included basic clinical measurements and fasted and postprandial (3-h) glucose and insulin in response to a healthy test meal. Markers of inflammation and oxidative stress, including high-sensitivity C-reactive protein, interleukin 6, interleukin 18, tumour necrosis factor-alpha, adiponectin, thiobarbituric acid reactive substances, oxygen radical antioxidant capacity, oxidized LDL and urinary isoprostanes, were also measured at fasting and in the postprandial period. Results There were no diet-related effects on glycaemic control or glycaemic or insulinaemic responses to the test meal. Total cholesterol (5.1 ± 1.0 vs. 4.9 ± 0.8 mmol/l, P = 0.019) concentrations declined following the oat-enriched diet compared with standard dietary advice. There was a postprandial decline in adiponectin concentration (P = 0.009), but no effect of dietary intervention. None of the measures of oxidative stress or inflammation were altered by the oat-enriched diet compared with standard dietary advice. Conclusion The oat-enriched diet had a modest impact on lipid lowering, but did not impact on oxidative stress or inflammation in these volunteers with Type 2 diabetes. PMID:23668675

Results of a Randomized Controlled Multicenter Phase III Trial of Percutaneous Hepatic Perfusion Compared with Best Available Care for Patients with Melanoma Liver Metastases.

PubMed

Hughes, Marybeth S; Zager, Jonathan; Faries, Mark; Alexander, H Richard; Royal, Richard E; Wood, Bradford; Choi, Junsung; McCluskey, Kevin; Whitman, Eric; Agarwala, Sanjiv; Siskin, Gary; Nutting, Charles; Toomey, Mary Ann; Webb, Carole; Beresnev, Tatiana; Pingpank, James F

2016-04-01

There is no consensus for the treatment of melanoma metastatic to the liver. Percutaneous hepatic perfusion with melphalan (PHP-Mel) is a method of delivering regional chemotherapy selectively to the liver. In this study, we report the results of a multicenter, randomized controlled trial comparing PHP-Mel with best alternative care (BAC) for patients with ocular or cutaneous melanoma metastatic to the liver. A total of 93 patients were randomized to PHP-Mel (n = 44) or BAC (n = 49). On the PHP-Mel arm, melphalan was delivered via the hepatic artery, and the hepatic effluent captured and filtered extracorporeally prior to return to the systemic circulation via a venovenous bypass circuit. PHP-Mel was repeatable every 4-8 weeks. The primary endpoint was hepatic progression-free survival (hPFS), and secondary endpoints included overall PFS (oPFS), overall survival (OS), hepatic objective response (hOR), and safety. hPFS was 7.0 months for PHP-Mel and 1.6 months for BAC (p < 0.0001), while oPFS was 5.4 months for PHP-Mel and 1.6 months for BAC (p < 0.0001). Median OS was not significantly different (PHP-Mel 10.6 months vs. BAC 10.0 months), likely due to crossover to PHP-Mel treatment (57.1 %) from the BAC arm, and the hOR was 36.4 % for PHP-Mel and 2.0 % for BAC (p < 0.001). The majority of adverse events were related to bone marrow suppression. Four deaths were attributed to PHP-Mel, three in the primary PHP-Mel group, and one post-crossover to PHP-Mel from BAC. This randomized, phase III study demonstrated the efficacy of the PHP-Mel procedure. hPFS, oPFS, and hOR were significantly improved with PHP-Mel. PHP with melphalan should provide a new treatment option for unresectable metastatic melanoma in the liver.

Randomized Controlled Crossover Trial Comparing the Impact of Sham or Intranasal Tear Neurostimulation on Conjunctival Goblet Cell Degranulation.

PubMed

Gumus, Koray; Schuetzle, Karri L; Pflugfelder, Stephen C

2017-05-01

The aim of the study was to investigate the effects of the Allergan Intranasal Tear Neurostimulator (ITN) on conjunctival goblet cell (GC) degranulation. A randomized, double-masked, placebo-controlled crossover trial. A total of 15 subjects (5 normal and 10 dry eye) were enrolled in a 3-visit study consisting of 1 screening and 2 separate randomized-masked ITN treatments (sham extranasal or intranasal). Tear meniscus height (TMH) was measured by anterior segment optical coherence tomography before and after applications. Impression cytology (IC) was taken from the bulbar conjunctiva of the right eye for periodic acid-Schiff staining and from the left eye for MUC5AC mucin immunostaining at baseline and after each treatment. The ratio of degranulated to nondegranulated GCs was measured as a marker of secretion. In all participants, both inferior bulbar (IB) and temporal bulbar (TB) cytology specimens stained for MUC5AC revealed a significantly higher ratio of degranulated to nondegranulated GCs after the ITN (IB: 2.28 ± 1.27 and TB: 1.81 ± 1.01) compared to baseline (IB: 0.56 ± 0.55, P = .015) (TB: 0.56 ± 0.32, P = .003) and extranasal sham application (IB: 0.37 ± 0.29, P = .001) (TB: 0.39 ± 0.33, P = .001). When the same analysis was repeated in the dry eye or control groups, the ratio was significantly higher after ITN than the baseline ratio and ratio after extranasal application in both groups (P < .05). Moreover, although control subjects had a higher ratio of degranulated to nondegranulated GCs at baseline (0.75 ± 0.52) compared with the dry eye group (0.41 ± 0.27), the ratio became slightly higher in dry eye (2.04 ± 1.12 vs 1.99 ± 1.21 in control) after the ITN application. There was no significant difference between the IB or TB conjunctiva locations in terms of the effectiveness of the ITN application on conjunctival goblet cell secretory response. These preliminary results document that the Allergan ITN can stimulate degranulation of goblet cells in the conjunctiva, which is a promising new approach for the management of dry eye. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Cerebrospinal fluid as a reflector of central cholinergic and amino acid neurotransmitter activity in cerebellar ataxia.

PubMed

Manyam, B V; Giacobini, E; Ferraro, T N; Hare, T A

1990-11-01

Cerebrospinal fluid (CSF) amino acid neurotransmitters, related compounds, and their precursors, choline levels, and acetylcholinesterase activity were measured in the CSF of patients with cerebellar ataxia during a randomized, double-blind, crossover, placebo-controlled clinical trial of physostigmine salicylate. The CSF gamma-aminobutyric acid, methionine, and choline levels, adjusted for age, were significantly lower in patients with cerebellar ataxia compared with controls. Physostigmine selectively reduced the level of CSF isoleucine and elevated the levels of phosphoethanolamine. No change occurred in CSF acetylcholinesterase activity and in the levels of plasma amino compounds in patients with cerebellar ataxia when compared with controls. Median ataxia scores did not statistically differ between placebo and physostigmine nor did functional improvement occur in any of the patients.

Switching to a 10-day Mediterranean-style diet improves mood and cardiovascular function in a controlled crossover study.

PubMed

Lee, Jaime; Pase, Matthew; Pipingas, Andrew; Raubenheimer, Jessica; Thurgood, Madeline; Villalon, Lorena; Macpherson, Helen; Gibbs, Amy; Scholey, Andrew

2015-05-01

Even short-term adherence to a Mediterranean-style diet may benefit aspects of psychological functioning. The aim of the present study was to assess the effects of switching to a 10-d Mediterranean-style diet on mood, cognition, and cardiovascular measures. Using a crossover design, 24 women were randomly assigned to either the diet change (where they switched to a Mediterranean-style diet) or no diet change (normal diet) condition for 10 days before switching to the other condition for the same duration. Mood, cognition, and cardiovascular measures of blood pressure, blood flow velocity, and arterial stiffness were assessed at baseline and at the completion of the two diets (days 11 and 22). Independent of whether the Mediterranean-style diet was undertaken before or after the crossover, it was associated with significantly elevated contentment and alertness, and significantly reduced confusion. Additionally, aspects of cognition, such as memory recall, improved significantly as a result of switching to the Mediterranean-style diet. Regarding cardiovascular measures, there was a significant reduction in augmentation pressure associated with the Mediterranean-style diet intervention, but blood flow velocity through the common carotid artery did not change. This Mediterranean-style diet has the potential to enhance aspects of mood, cognition, and cardiovascular function in a young, healthy adult sample. Copyright © 2015 Elsevier Inc. All rights reserved.

Spinal Muscular Atrophy Biomarker Measurements from Blood Samples in a Clinical Trial of Valproic Acid in Ambulatory Adults

PubMed Central

Renusch, Samantha R.; Harshman, Sean; Pi, Hongyang; Workman, Eileen; Wehr, Allison; Li, Xiaobai; Prior, Thomas W.; Elsheikh, Bakri H.; Swoboda, Kathryn J.; Simard, Louise R.; Kissel, John T.; Battle, Daniel; Parthun, Mark R.; Freitas, Michael A.; Kolb, Stephen J.

2015-01-01

Abstract Background: Clinical trials of therapies for spinal muscular atrophy (SMA) that are designed to increase the expression the SMN protein ideally include careful assessment of relevant SMN biomarkers. Objective: In the SMA VALIANT trial, a recent double-blind placebo-controlled crossover study of valproic acid (VPA) in ambulatory adult subjects with SMA, we investigated relevant pharmacodynamic biomarkers in blood samples from SMA subjects by direct longitudinal measurement of histone acetylation and SMN mRNA and protein levels in the presence and absence of VPA treatment. Methods: Thirty-three subjects were randomized to either VPA or placebo for the first 6 months followed by crossover to the opposite arm for an additional 6 months. Outcome measures were compared between the two treatments (VPA and placebo) using a standard crossover analysis. Results: A significant increase in histone H4 acetylation was observed with VPA treatment (p = 0.005). There was insufficient evidence to suggest a treatment effect with either full length or truncated SMN mRNA transcript levels or SMN protein levels. Conclusions: These measures were consistent with the observed lack of change in the primary clinical outcome measure in the VALIANT trial. These results also highlight the added benefit of molecular and pharmacodynamic biomarker measurements in the interpretation of clinical trial outcomes. PMID:27858735

A randomized placebo-controlled trial of miglustat in cystic fibrosis based on nasal potential difference.

PubMed

Leonard, Anissa; Lebecque, Patrick; Dingemanse, Jasper; Leal, Teresinha

2012-05-01

Preclinical data suggest that miglustat could restore the function of the cystic fibrosis transmembrane conductance regulator gene in cystic fibrosis cells. Single-center, randomized, double-blind, placebo-controlled, crossover Phase II study in 11 patients (mean±SD age, 26.3±7.7 years) homozygous for the F508del mutation received oral miglustat 200 mgt.i.d. or placebo for two 8-day cycles separated by a 14-day washout period. The primary endpoint was the change in total chloride secretion (TCS) assessed by nasal potential difference. No statistically significant changes in TCS, sweat chloride values or FEV(1) were detected. Pharmacokinetic and safety were similar to those observed in patients with other diseases exposed to miglustat. There was no evidence of a treatment effect on any nasal potential difference variable. Further studies with miglustat need to adequately address criteria for assessment of nasal potential difference. Copyright © 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Duloxetine Inhibits Effects of MDMA (“Ecstasy") In Vitro and in Humans in a Randomized Placebo-Controlled Laboratory Study

PubMed Central

Nicola, Valentina G.; Vischer, Nerina; Donzelli, Massimiliano; Krähenbühl, Stephan; Grouzmann, Eric; Huwyler, Jörg; Hoener, Marius C.; Liechti, Matthias E.

2012-01-01

This study assessed the effects of the serotonin (5-HT) and norepinephrine (NE) transporter inhibitor duloxetine on the effects of 3,4–methylenedioxy­methamphetamine (MDMA, ecstasy) in vitro and in 16 healthy subjects. The clinical study used a double-blind, randomized, placebo-controlled, four-session, crossover design. In vitro, duloxetine blocked the release of both 5-HT and NE by MDMA or by its metabolite 3,4-methylenedioxyamphetamine from transmitter-loaded human cells expressing the 5-HT or NE transporter. In humans, duloxetine inhibited the effects of MDMA including elevations in circulating NE, increases in blood pressure and heart rate, and the subjective drug effects. Duloxetine inhibited the pharmacodynamic response to MDMA despite an increase in duloxetine-associated elevations in plasma MDMA levels. The findings confirm the important role of MDMA-induced 5-HT and NE release in the psychotropic effects of MDMA. Duloxetine may be useful in the treatment of psychostimulant dependence. Trial Registration Clinicaltrials.gov NCT00990067 PMID:22574166

The application of Reiki in nurses diagnosed with Burnout Syndrome has beneficial effects on concentration of salivary IgA and blood pressure.

PubMed

Díaz-Rodríguez, Lourdes; Arroyo-Morales, Manuel; Cantarero-Villanueva, Irene; Férnandez-Lao, Carolina; Polley, Marie; Fernández-de-las-Peñas, César

2011-01-01

This study aimed to investigate the immediate effects of the secretory immunoglobulin A (sIgA), α-amylase activity and blood pressure levels after the application of a Reiki session in nurses with Burnout Syndrome. A randomized, double-blind, placebo-controlled, crossover design was conducted to compare the immediate effects of Reiki versus control intervention (Hand-off sham intervention) in nurses with Burnout Syndrome. Sample was composed of eighteen nurses (aged 34-56 years) with burnout syndrome. Participants were randomly assigned to receive either a Reiki treatment or a placebo (sham Reiki) treatment, according to the established order in two different days. The ANOVA showed a significant interaction time x intervention for diastolic blood pressure (F=4.92, P=0.04) and sIgA concentration (F=4.71, P=0.04). A Reiki session can produce an immediate and statistically significant improvement in sIgA concentration and diastolic blood pressure in nurses with Burnout Syndrome.

Effects of a Gentle, Self-Administered Stimulation of Perineal Skin for Nocturia in Elderly Women: A Randomized, Placebo-Controlled, Double-Blind Crossover Trial

PubMed Central

Iimura, Kaori; Watanabe, Nobuhiro; Masunaga, Koichi; Miyazaki, Shogo; Hotta, Harumi; Kim, Hunkyung; Hisajima, Tatsuya; Takahashi, Hidenori; Kasuya, Yutaka

2016-01-01

Background Somatic afferent nerve stimuli are used for treating an overactive bladder (OAB), a major cause of nocturia in the elderly. Clinical evidence for this treatment is insufficient because of the lack of appropriate control stimuli. Recent studies on anesthetized animals show that gentle stimuli applied to perineal skin with a roller could inhibit micturition contractions depending on the roller’s surface material. We examined the efficacy of gentle skin stimuli for treating nocturia. Methods The study was a cross-over, placebo-controlled, double-blind randomized clinical study using two rollers with different effects on micturition contractions. Participants were elderly women (79–89 years) with nocturia. Active (soft elastomer roller) or placebo (hard polystyrene roller) stimuli were applied to perineal skin by participants for 1 min at bedtime. A 3-day baseline assessment period was followed by 3-day stimulation and 4-day resting periods, after which the participants were subjected to other stimuli for another 3 days. The primary outcome was change in the frequency of nighttime urination, for which charts were maintained during each 3-day period. Results Twenty-four participants were randomized, of which 22 completed all study protocols. One participant discontinued treatment because of an adverse event (abdominal discomfort). In participants with OAB (n = 9), change from baseline in the mean frequency of urination per night during the active stimuli period (mean ± standard deviation, −0.74 ± 0.7 times) was significantly greater than that during placebo stimuli periods (−0.15 ± 0.8 times [p < 0.05]). In contrast, this difference was not observed in participants without OAB (n = 13). Conclusions These results suggest that gentle perineal stimulation with an elastomer roller is effective for treating OAB-associated nocturia in elderly women. Here the limitation was a study period too short to assess changes in the quality of sleep and life. Trial Registration UMIN Clinical Trial Registry (CTR) UMIN000015809 PMID:27003163

Low-dose hydrocortisone replacement improves wellbeing and pain tolerance in chronic pain patients with opioid-induced hypocortisolemic responses. A pilot randomized, placebo-controlled trial.

PubMed

Nenke, Marni A; Haylock, Clare L; Rankin, Wayne; Inder, Warrick J; Gagliardi, Lucia; Eldridge, Crystal; Rolan, Paul; Torpy, David J

2015-06-01

Long-term opioid therapy has been associated with low cortisol levels due to central suppression of the hypothalamic-pituitary-adrenal axis. The implications of hypocortisolism on wellbeing have not been established. Our aim was to determine whether intervention with physiologic glucocorticoid replacement therapy improves wellbeing and analgesic responses in patients with chronic non-cancer pain on long-term opioid therapy with mild cortisol deficiency. We performed a pilot randomized, double-blind, placebo-controlled crossover study of oral hydrocortisone replacement therapy in 17 patients recruited from a Pain Clinic at a single tertiary center in Adelaide, Australia. Patients were receiving long-term opioid therapy (≥ 20 mg morphine equivalents per day for ≥ 4 weeks) for chronic non-cancer pain with mild hypocortisolism, as defined by a plasma cortisol response ≤ 350 nmol/L at 60 min following a cold pressor test. The crossover intervention included 28-day treatment with either 10mg/m(2)/day of oral hydrocortisone in three divided doses or placebo. Improvement in wellbeing was assessed using Version 2 of the Short Form-36 (SF-36v2), Brief Pain Inventory-Short Form, and Addison's disease quality of life questionnaires; improvement in analgesic response was assessed using cold pressor threshold and tolerance times. Following treatment with hydrocortisone, the bodily pain (P=0.042) and vitality (P=0.013) subscales of the SF-36v2 were significantly better than scores following treatment with placebo. There was also an improvement in pain interference on general activity (P=0.035), mood (P=0.03) and work (P=0.04) following hydrocortisone compared with placebo. This is the first randomized, double-blind placebo-controlled trial of glucocorticoid replacement in opioid users with chronic non-cancer pain and mild hypocortisolism. Our data suggest that physiologic hydrocortisone replacement produces improvements in vitality and pain experiences in this cohort compared with placebo. Therapeutic Goods Administration Clinical Trials Notification Scheme (Drugs), Trial Number 2012/0476. Copyright © 2015 Elsevier Ltd. All rights reserved.

Randomized sham-controlled, double-blind, multicenter clinical trial on the effect of percutaneous radiofrequency at the ramus communicans for lumbar disc pain.

PubMed

van Tilburg, C W J; Stronks, D L; Groeneweg, J G; Huygen, F J P M

2017-03-01

Investigate the effect of percutaneous radiofrequency compared to a sham procedure, applied to the ramus communicans for treatment of lumbar disc pain. Randomized sham-controlled, double-blind, crossover, multicenter clinical trial. Multidisciplinary pain centres of two general hospitals. Sixty patients aged 18 or more with medical history and physical examination suggestive for lumbar disc pain and a reduction of two or more on a numerical rating scale (0-10) after a diagnostic ramus communicans test block. Treatment group: percutaneous radiofrequency treatment applied to the ramus communicans; sham: same procedure except radiofrequency treatment. pain reduction. Secondary outcome measure: Global Perceived Effect. No statistically significant difference in pain level over time between the groups, as well as in the group was found; however, the factor period yielded a statistically significant result. In the crossover group, 11 out of 16 patients experienced a reduction in NRS of 2 or more at 1 month (no significant deviation from chance). No statistically significant difference in satisfaction over time between the groups was found. The independent factors group and period also showed no statistically significant effects. The same applies to recovery: no statistically significant effects were found. The null hypothesis of no difference in pain reduction and in Global Perceived Effect between the treatment and sham group cannot be rejected. Post hoc analysis revealed that none of the investigated parameters contributed to the prediction of a significant pain reduction. Interrupting signalling through the ramus communicans may interfere with the transition of painful information from the discs to the central nervous system. Methodological differences exist in studies evaluating the efficacy of radiofrequency treatment for lumbar disc pain. A randomized, sham-controlled, double-blind, multicenter clinical trial on the effect of radiofrequency at the ramus communicans for lumbar disc pain was conducted. The null hypothesis of no difference in pain reduction and in Global Perceived Effect between the treatment and sham group cannot be rejected. © 2016 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®.

Heated humidification versus heat and moisture exchangers for ventilated adults and children.

PubMed

Kelly, Margaret; Gillies, Donna; Todd, David A; Lockwood, Catherine

2010-10-01

Humidification by artificial means must be provided when the upper airway is bypassed during mechanical ventilation. Heated humidification (HH) and heat and moisture exchangers (HMEs) are the most commonly used types of artificial humidification in this situation. To determine whether HHs or HMES are more effective in preventing mortality and other complications in people who are mechanically ventilated. We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 4) and MEDLINE, EMBASE and CINAHL (January, 2010) to identify relevant randomized controlled trials. We included randomized controlled trials comparing HMEs to HHs in mechanically ventilated adults and children. We included randomized crossover studies. We assessed the quality of each study and extracted the relevant data. Where appropriate, results from relevant studies were meta-analyzed for individual outcomes. We included 33 trials with 2833 participants; 25 studies were parallel group design (n = 2710) and 8 crossover design (n = 123). Only 3 included studies reported data for infants or children. There was no overall effect on artificial airway occlusion, mortality, pneumonia, or respiratory complications; however, the PaCO(2) and minute ventilation were increased when HMEs were compared to HHs and body temperature was lower. The cost of HMEs was lower in all studies that reported this outcome. There was some evidence that hydrophobic HMEs may reduce the risk of pneumonia and that blockages of artificial airways may be increased with the use of HMEs in certain subgroups of patients. There is little evidence of an overall difference between HMEs and HHs. However, hydrophobic HMEs may reduce the risk of pneumonia and the use of an HMEs may increase artificial airway occlusion in certain subgroups of patients. Therefore, HMEs may not be suitable for patients with limited respiratory reserve or prone to airway blockage. Further research is needed relating to hydrophobic versus hygroscopic HMEs and the use of HMEs in the pediatric and neonatal populations. As the design of HMEs evolves, evaluation of new generation HMEs will also need to be undertaken.

Supervised Home Training of Dialogue Skills in Chronic Aphasia: A Randomized Parallel Group Study

ERIC Educational Resources Information Center

Nobis-Bosch, Ruth; Springer, Luise; Radermacher, Irmgard; Huber, Walter

2011-01-01

Purpose: The aim of this study was to prove the efficacy of supervised self-training for individuals with aphasia. Linguistic and communicative performance in structured dialogues represented the main study parameters. Method: In a cross-over design for randomized matched pairs, 18 individuals with chronic aphasia were examined during 12 weeks of…

The joy of six: how to control your crossovers.

PubMed

Globus, Samuel T; Keeney, Scott

2012-03-30

Meiotic cells tightly regulate the number and distribution of crossovers to promote accurate chromosome segregation. Yokoo and colleagues uncover a metazoan-specific, cyclin-like protein that is crucial for crossover formation. They utilize this protein's unique properties to explore a remarkable example of biological numerology, whereby nearly every meiotic cell in C. elegans makes precisely six crossovers, one for each of its six chromosome pairs. Copyright © 2012 Elsevier Inc. All rights reserved.

Comparison of a robotic-assisted gait training program with a program of functional gait training for children with cerebral palsy: design and methods of a two group randomized controlled cross-over trial.

PubMed

Hilderley, Alicia J; Fehlings, Darcy; Lee, Gloria W; Wright, F Virginia

2016-01-01

Enhancement of functional ambulation is a key goal of rehabilitation for children with cerebral palsy (CP) who experience gross motor impairment. Physiotherapy (PT) approaches often involve overground and treadmill-based gait training to promote motor learning, typically as free walking or with body-weight support. Robotic-assisted gait training (RAGT), using a device such as the Lokomat ® Pro, may permit longer training duration, faster and more variable gait speeds, and support walking pattern guidance more than overground/treadmill training to further capitalize on motor learning principles. Single group pre-/post-test studies have demonstrated an association between RAGT and moderate to large improvements in gross motor skills, gait velocity and endurance. A single published randomized controlled trial (RCT) comparing RAGT to a PT-only intervention showed no difference in gait kinematics. However, gross motor function and walking endurance were not evaluated and conclusions were limited by a large PT group drop-out rate. In this two-group cross-over RCT, children are randomly allocated to the RAGT or PT arm (each with twice weekly sessions for eight weeks), with cross-over to the other intervention arm following a six-week break. Both interventions are grounded in motor learning principles with incorporation of individualized mobility-based goals. Sessions are fully operationalized through manualized, menu-based protocols and post-session documentation to enhance internal and external validity. Assessments occur pre/post each intervention arm (four time points total) by an independent assessor. The co-primary outcomes are gross motor functional ability (Gross Motor Function Measure (GMFM-66) and 6-minute walk test), with secondary outcome measures assessing: (a) individualized goals; (b) gait variables and daily walking amounts; and (c) functional abilities, participation and quality of life. Investigators and statisticians are blinded to study group allocation in the analyses, and assessors are blinded to treatment group. The primary analysis will be the pre- to post-test differences (change scores) of the GMFM-66 and 6MWT between RAGT and PT groups. This study is the first RCT comparing RAGT to an active gait-related PT intervention in paediatric CP that addresses gait-related gross motor, participation and individualized outcomes, and as such, is expected to provide comprehensive information as to the potential role of RAGT in clinical practice. Trial registration ClinicalTrials.gov NCT02196298.

Carnitine for fatigue in multiple sclerosis.

PubMed

Tejani, Aaron M; Wasdell, Michael; Spiwak, Rae; Rowell, Greg; Nathwani, Shabita

2012-05-16

Fatigue is reported to occur in up to 92% of patients with multiple sclerosis (MS) and has been described as the most debilitating of all MS symptoms by 28% to 40% of MS patients. To assess whether carnitine (enteral or intravenous) supplementation can improve the quality of life and reduce the symptoms of fatigue in patients with MS-related fatigue and to identify any adverse effects of carnitine when used for this purpose. A literature search was performed using Cochrane MS Group Trials Register (09 September 2011), Cochrane Central Register of Controlled Trials (CENTRAL) "The Cochrane Library 2011, issue 3", MEDLINE (PubMed) (1966-09 September 2011), EMBASE (1974-09 September 2011), and www.clinicaltrials.gov for ongoing trials retrieval. Reference lists of review articles and primary studies were also screened. A hand search of the abstract book of recent relevant conference symposia was also conducted. Personal contact with MS experts and a manufacturer (Source Naturals, United States) of carnitine formulation was contacted to determine if they knew of other clinical trials. No language restrictions were applied. Full reports of published and unpublished randomized controlled trials and quasi-randomized trials of any carnitine intervention in adults affected by multiple sclerosis with a clinical diagnosis of fatigue associated with multiple sclerosis were included. Data from the eligible trials was extracted and coded using a standardized data extraction form and entered into RevMan 5. Discrepancies were to be resolved by discussion with a third reviewer, however this was not necessary.The quality items to be assessed were method of randomization, allocation concealment, blinding (participants, investigators, outcome assessors and data analysis), intention-to-treat analysis and completeness of follow up. The search identified one ongoing randomized, placebo-controlled, cross-over trial (expected completion 2013) and one completed randomized, active-comparator, cross-over trial. In the completed study, adult patients with relapsing-remitting and secondary progressive MS were exposed to both acetyl L-carnitine 2 grams daily and amantadine 200 mg daily The effects of carnitine on fatigue are unclear. There was no difference between carnitine and amantadine for the number of patients withdrawing from the study due to an adverse event (relative risk ratio 0.20; 95% confidence interval 0.03 to 1.55) and no patients experienced a serious adverse event in either treatment group. Mortality and quality of life were not reported. There is insufficient evidence that carnitine for the treatment of MS-related fatigue offers a therapeutic advantage over placebo or active comparators. Results of the ongoing trial are eagerly anticipated in order to provide clarity.

Circular Data Images for Directional Data

NASA Technical Reports Server (NTRS)

Morpet, William J.

2004-01-01

Directional data includes vectors, points on a unit sphere, axis orientation, angular direction, and circular or periodic data. The theoretical statistics for circular data (random points on a unit circle) or spherical data (random points on a unit sphere) are a recent development. An overview of existing graphical methods for the display of directional data is given. Cross-over occurs when periodic data are measured on a scale for the measurement of linear variables. For example, if angle is represented by a linear color gradient changing uniformly from dark blue at -180 degrees to bright red at +180 degrees, the color image will be discontinuous at +180 degrees and -180 degrees, which are the same location. The resultant color would depend on the direction of approach to the cross-over point. A new graphical method for imaging directional data is described, which affords high resolution without color discontinuity from "cross-over". It is called the circular data image. The circular data image uses a circular color scale in which colors repeat periodically. Some examples of the circular data image include direction of earth winds on a global scale, rocket motor internal flow, earth global magnetic field direction, and rocket motor nozzle vector direction vs. time.

A double blind, placebo controlled, phase II randomised cross-over trial investigating the use of duloxetine for the treatment of chemotherapy-induced peripheral neuropathy.

PubMed

Battaglini, Eva; Park, Susanna B; Barnes, Elizabeth H; Goldstein, David

2018-04-20

Chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of cancer treatment, potentially leading to early cessation of chemotherapy, enduring symptoms and long-lasting disability. Evidence from preclinical and clinical studies suggests that duloxetine, a serotonin-noradrenaline reuptake inhibitor, may be effective in the symptomatic treatment of CIPN. This double blind, placebo controlled, phase II randomised cross-over trial aims to determine whether treatment with duloxetine results in a reduction in chronic neuropathic symptoms experienced as a result of neurotoxic chemotherapy treatment. Participants who have received neurotoxic chemotherapy and experience daily symptoms as a consequence of peripheral neuropathy will be randomly allocated to control or experimental group with a 1:1 allocation, stratified by chemotherapy type. The primary endpoint will be patient-reported CIPN symptoms, as assessed via the FACT/GOG-Ntx. As a secondary objective, the trial will investigate whether duloxetine improves neurophysiological parameters and functional status in patients who have received neurotoxic chemotherapy treatment. This trial will investigate the effectiveness of duloxetine in reducing neuropathic symptoms following chemotherapy treatment, and aims to provide insight into the mechanisms underlying the symptomatic relief that duloxetine may provide. These results will be informative in advancing clinical knowledge regarding the treatment of CIPN. Copyright © 2018 Elsevier Inc. All rights reserved.

Sensory Adapted Dental Environments to Enhance Oral Care for Children with Autism Spectrum Disorders: A Randomized Controlled Pilot Study

PubMed Central

Cermak, Sharon A.; Stein Duker, Leah I.; Williams, Marian E.; Dawson, Michael E.; Lane, Christianne J.; Polido, José C.

2015-01-01

This pilot and feasibility study examined the impact of a sensory adapted dental environment (SADE) to reduce distress, sensory discomfort, and perception of pain during oral prophylaxis for children with autism spectrum disorder (ASD). Participants were 44 children ages 6-12 (n=22 typical, n=22 ASD). In an experimental crossover design, each participant underwent two professional dental cleanings, one in a regular dental environment (RDE) and one in a SADE, administered in a randomized and counterbalanced order three to four months apart. Outcomes included measures of physiological anxiety, behavioral distress, pain intensity, and sensory discomfort. Both groups exhibited decreased physiological anxiety and reported lower pain and sensory discomfort in the SADE condition compared to RDE, indicating a beneficial effect of the SADE. PMID:25931290

Effects of a mixed berry beverage on cognitive functions and cardiometabolic risk markers; A randomized cross-over study in healthy older adults.

PubMed

Nilsson, Anne; Salo, Ilkka; Plaza, Merichel; Björck, Inger

2017-01-01

Berries and associated bioactive compounds, e.g. polyphenols and dietary fibre (DF), may have beneficial implications with respect to the metabolic syndrome, including also cognitive functions. The aim of this study was to evaluate effects on cognitive functions and cardiometabolic risk markers of 5 wk intervention with a mixture of berries, in healthy humans. Forty healthy subjects between 50-70 years old were provided a berry beverage based on a mixture of berries (150g blueberries, 50g blackcurrant, 50g elderberry, 50g lingonberries, 50g strawberry, and 100g tomatoes) or a control beverage, daily during 5 weeks in a randomized crossover design. The control beverage (water based) was matched with respect to monosaccharides, pH, and volume. Cognitive tests included tests of working memory capacity, selective attention, and psychomotor reaction time. Cardiometabolic test variables investigated were blood pressure, fasting blood concentrations of glucose, insulin, blood lipids, inflammatory markers, and markers of oxidative stress. The daily amounts of total polyphenols and DF from the berry beverage were 795 mg and 11g, respectively. There were no polyphenols or DF in the control beverage. The berry intervention reduced total- and LDL cholesterol compared to baseline (both P<0.05), and in comparison to the control beverage (P<0.005 and P<0.01, respectively). The control beverage increased glucose concentrations (P<0.01) and tended to increase insulin concentrations (P = 0.064) from base line, and increased insulin concentrations in comparison to the berry beverage (P<0.05). Subjects performed better in the working memory test after the berry beverage compared to after the control beverage (P<0.05). No significant effects on the other test variables were observed. The improvements in cardiometabolic risk markers and cognitive performance after the berry beverage suggest preventive potential of berries with respect to type 2 diabetes, cardiovascular disease, and associated cognitive decline. Possibly the polyphenols and DF contributed to the beneficial effects. ClinicalTrials.gov: NCT01562392.

Balanced Crystalloids versus Saline in the Intensive Care Unit. The SALT Randomized Trial.

PubMed

Semler, Matthew W; Wanderer, Jonathan P; Ehrenfeld, Jesse M; Stollings, Joanna L; Self, Wesley H; Siew, Edward D; Wang, Li; Byrne, Daniel W; Shaw, Andrew D; Bernard, Gordon R; Rice, Todd W

2017-05-15

Saline is the intravenous fluid most commonly administered to critically ill adults, but it may be associated with acute kidney injury and death. Whether use of balanced crystalloids rather than saline affects patient outcomes remains unknown. To pilot a cluster-randomized, multiple-crossover trial using software tools within the electronic health record to compare saline to balanced crystalloids. This was a cluster-randomized, multiple-crossover trial among 974 adults admitted to a tertiary medical intensive care unit from February 3, 2015 to May 31, 2015. The intravenous crystalloid used in the unit alternated monthly between saline (0.9% sodium chloride) and balanced crystalloids (lactated Ringer's solution or Plasma-Lyte A). Enrollment, fluid delivery, and data collection were performed using software tools within the electronic health record. The primary outcome was the difference between study groups in the proportion of isotonic crystalloid administered that was saline. The secondary outcome was major adverse kidney events within 30 days (MAKE30), a composite of death, dialysis, or persistent renal dysfunction. Patients assigned to saline (n = 454) and balanced crystalloids (n = 520) were similar at baseline and received similar volumes of crystalloid by 30 days (median [interquartile range]: 1,424 ml [500-3,377] vs. 1,617 ml [500-3,628]; P = 0.40). Saline made up a larger proportion of the isotonic crystalloid given in the saline group than in the balanced crystalloid group (91% vs. 21%; P < 0.001). MAKE30 did not differ between groups (24.7% vs. 24.6%; P = 0.98). An electronic health record-embedded, cluster-randomized, multiple-crossover trial comparing saline with balanced crystalloids can produce well-balanced study groups and separation in crystalloid receipt. Clinical trial registered with www.clinicaltrials.gov (NCT 02345486).

Chest Compression With Personal Protective Equipment During Cardiopulmonary Resuscitation: A Randomized Crossover Simulation Study.

PubMed

Chen, Jie; Lu, Kai-Zhi; Yi, Bin; Chen, Yan

2016-04-01

Following a chemical, biological, radiation, and nuclear incident, prompt cardiopulmonary resuscitation (CPR) procedure is essential for patients who suffer cardiac arrest. But CPR when wearing personal protection equipment (PPE) before decontamination becomes a challenge for healthcare workers (HCW). Although previous studies have assessed the impact of PPE on airway management, there is little research available regarding the quality of chest compression (CC) when wearing PPE.A present randomized cross-over simulation study was designed to evaluate the effect of PPE on CC performance using mannequins.The study was set in one university medical center in the China.Forty anesthesia residents participated in this randomized cross-over study.Each participant performed 2 min of CC on a manikin with and without PPE, respectively. Participants were randomized into 2 groups that either performed CC with PPE first, followed by a trial without PPE after a 180-min rest, or vice versa.CPR recording technology was used to objectively quantify the quality of CC. Additionally, participants' physiological parameters and subjective fatigue score values were recorded.With the use of PPE, a significant decrease of the percentage of effective compressions (41.3 ± 17.1% with PPE vs 67.5 ± 15.6% without PPE, P < 0.001) and the percentage of adequate compressions (67.7 ± 18.9% with PPE vs 80.7 ± 15.5% without PPE, P < 0.001) were observed. Furthermore, the increases in heart rate, mean arterial pressure, and subjective fatigue score values were more obvious with the use of PPE (all P < 0.01).We found significant deterioration of CC performance in HCW with the use of a level-C PPE, which may be a disadvantage for enhancing survival of cardiac arrest.

The potential for improvement of outcomes by personalized insulin treatment of type 1 diabetes as assessed by analysis of single-patient data from a randomized controlled cross-over insulin trial.

PubMed

Pedersen-Bjergaard, Ulrik; Kristensen, Peter L; Beck-Nielsen, Henning; Nørgaard, Kirsten; Perrild, Hans; Christiansen, Jens S; Jensen, Tonny; Parving, Hans-Henrik; Thorsteinsson, Birger; Tarnow, Lise

2017-01-01

The evidence for optimal insulin treatment in type 1 diabetes is mainly based on randomised controlled trials applying a parallel-group design. Such trials yield robust general results but crucial individual treatment effects cannot be extracted. We aimed to assess the potential for further improvement of outcomes by personalized insulin therapy by analyzing data from a cross-over trial at individual level. Post hoc analysis of data from a two-year multicentre, prospective, randomised, open, blinded endpoint (PROBE) trial (the HypoAna trial). In a cross-over design 114 patients with type 1 diabetes and recurrent severe hypoglycemia were treated with basal-bolus therapy based on analog (detemir/aspart) or human (NPH/regular) insulin aiming at maintenance of baseline HbA1c levels. For each patient a superior outcome was defined as fewer events of severe hypoglycemia defined by need for third party treatment assistance or a more than 0.4% (4.4mmol/mol) lower HbA1c. Only one quarter had comparable outcome of the two treatments in terms of rate of severe hypoglycemia or HbA1c. Twice as many patients had superior outcome of analog-based as compared to human insulin-based insulin treatment. The rate of severe hypoglycemia with the superior treatment was lower compared to the rates obtained with analog insulin and with human insulin (0.67, 1.09, and 1.57 episode per patient-year, respectively (p<0.0001)). Personalized insulin treatment of type 1 diabetes based on single-patient evidence may improve outcomes significantly compared to a general treatment approach. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A short-term effect of low-dose aspirin on major hemorrhagic risks in primary prevention: a case-crossover design.

PubMed

Wu, I-Chen; Lin, Ming-Yen; Yu, Fang-Jung; Hsieh, Hui-Min; Chiu, Kuei-Fen; Wu, Ming-Tsang

2014-01-01

Very few studies have examined the risk of short-term adverse hemorrhage of low-dose aspirin use in primary prevention. This case-crossover study examined the transient effect of low-dose aspirin use on major hemorrhagic risks. A representative database of 1,000,000 patients randomly sampled from the Taiwan's National Health Insurance Research Database in 2000 was analyzed. The study cohort consisted of a total of 501,946 individuals, aged 30-95 years old, at risk of a major bleeding event in 2000. A case-crossover study was used to retrieve data on 10,905 incident patients with major hemorrhagic complications (3,781 cerebral and 7,124 gastrointestinal) and prescribed low-dose aspirin (≤300 mg/day) from 2000-2008. A 56-day time window (∼2 months) was used as the case period for which the odds ratio (OR) was estimated using the ratio of patients exposed during the 56-day case period only (1-56 days before the index date) compared to its corresponding 56-day control period only (57-112 days before the index date). Four hundred eighty-nine (4.5%) of the 10,905 hemorrhagic patients had used low-dose aspirin during the 56-day case only period; 294 (2.7%) of the same patients had used low-dose aspirin during control only period. Low-dose aspirin use increase the risk of developing a major hemorrhage 1.33-fold (95% CI = 1.13-1.55, P<0.0001). Significance was found prominent in 4,453 non-hypertensive and non-diabetic subjects (Adjusted odds ratio = 1.88, 95% CI = 1.21-2.91). Transient low-dose aspirin use increases risk for major hemorrhagic events in Han Chinese.

Case-crossover design and its implementation in R

PubMed Central

2016-01-01

Case-crossover design is a variation of case-control design that it employs persons’ history periods as controls. Case-crossover design can be viewed as the hybrid of case-control study and crossover design. Characteristic confounding that is constant within one person can be well controlled with this method. The relative risk and odds ratio, as well as their 95% confidence intervals (CIs), can be estimated using Cochran-Mantel-Haenszel method. R codes for the calculation are provided in the main text. Readers may adapt these codes to their own task. Conditional logistic regression model is another way to estimate odds ratio of the exposure. Furthermore, it allows for incorporation of other time-varying covariates that are not constant within subjects. The model fitting per se is not technically difficult because there is well developed statistical package. However, it is challenging to convert original dataset obtained from case report form to that suitable to be passed to clogit() function. R code for this task is provided and explained in the text. PMID:27761445

Individual eigenvalue distributions of crossover chiral random matrices and low-energy constants of SU(2) × U(1) lattice gauge theory

NASA Astrophysics Data System (ADS)

Yamamoto, Takuya; Nishigaki, Shinsuke M.

2018-02-01

We compute individual distributions of low-lying eigenvalues of a chiral random matrix ensemble interpolating symplectic and unitary symmetry classes by the Nyström-type method of evaluating the Fredholm Pfaffian and resolvents of the quaternion kernel. The one-parameter family of these distributions is shown to fit excellently the Dirac spectra of SU(2) lattice gauge theory with a constant U(1) background or dynamically fluctuating U(1) gauge field, which weakly breaks the pseudoreality of the unperturbed SU(2) Dirac operator. The observed linear dependence of the crossover parameter with the strength of the U(1) perturbations leads to precise determination of the pseudo-scalar decay constant, as well as the chiral condensate in the effective chiral Lagrangian of the AI class.

Effect of moderate- versus high-intensity exercise on vascular function, biomarkers and quality of life in heart transplant recipients: A randomized, crossover trial.

PubMed

Dall, Christian H; Gustafsson, Finn; Christensen, Stefan B; Dela, Flemming; Langberg, Henning; Prescott, Eva

2015-08-01

Growing evidence in long-term treatment of heart transplant (HTx) recipients indicates effects of high-intensity interval training (HIIT) on several parameters, including oxygen uptake, vascular function and psychological distress. In this study we compare the effect of HIIT vs continued moderate training (CON) on vascular function, biomarkers and health-related quality of life (HRQoL) in HTx recipients. A randomized, controlled crossover trial of stable HTx recipients >12 months after transplantation was done on patients with 12 weeks of HIIT or 12 weeks of CON, followed by a 5-month washout and crossover. Outcomes included endothelial function, arterial stiffness, biomarkers, HRQoL and markers of anxiety and depression. Sixteen HTx recipients (mean age 52 years, 75% male) completed the study. HIIT increased VO(2peak) more than CON (between-group difference, p < 0.001). The physical component score of the 36-item Short Form (SF-36) was increased significantly in HIIT patients (p = 0.02) and borderline increased in CON patients (p = 0.07), whereas there was no significant effect of exercise on the mental component. Depression score decreased significantly in HIIT patients (p = 0.04) with no change in CON patients (p = 0.75), whereas anxiety score decreased significantly in both HIIT (p < 0.01) and CON (p < 0.05) patients. There were no between-group differences in any of the measures (all p > 0.05). Arterial stiffness and biomarkers were not changed, nor did endothelial function change after HIIT (p = 0.08) or CON (p = 0.68). HIIT and CON are both well tolerated and induce similar improvements in physical components of HRQoL and in markers of anxiety. Effects of either training modality on vascular function and biomarkers could not be confirmed. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

A randomized, placebo-controlled proof-of-concept, crossover trial of phenytoin for hydrocortisone-induced declarative memory changes

PubMed Central

Brown, E. Sherwood; Lu, Hanzhang; Denniston, Daren; Uh, Jinsoo; Thomas, Binu P.; Carmody, Thomas J.; Auchus, Richard J.; Diaz-Arrastia, Ramon; Tamminga, Carol

2013-01-01

Background Corticosteroid excess is associated with declarative memory impairment and hippocampal atrophy. These findings are clinically important because approximately 1% of the population receives prescription corticosteroids at any time, and major depressive disorder is associated with elevated cortisol levels and hippocampal atrophy. In animals, hippocampal changes with corticosteroids are blocked by phenytoin. The objective of the current study was to extend these preclinical findings to humans. We examined whether phenytoin attenuated the effects of hydrocortisone on declarative memory. Functional magnetic resonance imaging (fMRI) assessed task-related hippocampal activation. Methods A randomized, double-blind, placebo-controlled, within-subject crossover study was conducted in 17 healthy adult volunteers. Participants received hydrocortisone (2.5 days), phenytoin (3.5 days), both medications together, or placebo, with 21-day washouts between conditions. Differences between treatments were estimated using a mixed-effects repeated measures analysis. Results Fifteen participants had data from at least two treatment conditions and were used in the analysis. Basal cortisol levels negatively correlated with fMRI BOLD activation in the para-hippocampus with a similar trend observed in the hippocampus. Decrease in declarative memory with hydrocortisone was blocked with concomitant phenytoin administration. Relative to the placebo condition, a significant decrease in hippocampal BOLD activation was observed with hydrocortisone and phenytoin alone, and the two medications in combination. Declarative memory did not show significant correlations with hippocampal activation. Limitations The modest sample size, which limited our statistical power, was a limitation. Conclusions Findings from this pilot study suggest phenytoin attenuated effects of corticosteroids memory in humans, but potentiated the reduction in hippocampal activation. PMID:23453674

Adjunctive treatment with lodenafil carbonate for erectile dysfunction in outpatients with schizophrenia and spectrum: a randomized, double-blind, crossover, placebo-controlled trial.

PubMed

Nunes, Luciana Vargas Alves; Lacaz, Fernando Sargo; Bressan, Rodrigo Affonseca; Nunes, Sandra Odebrecht Vargas Alves; Mari, Jair de Jesus

2013-04-01

INTRODUCTION.: Evidence is accumulating to support the presence of erectile dysfunction in patients with schizophrenia. This dysregulation may be amenable to therapeutic intervention to improve adherence and quality of life of patients who suffer from schizophrenia and schizoaffective disorders. AIM.: We aimed to evaluate the use of adjunctive medication lodenafil for the treatment of erectile dysfunction in outpatients with schizophrenia and spectrum. METHODS.: The design was a randomized, double-blind, crossover, placebo-controlled trial with lodenafil and it was carried at the Schizophrenia Outpatients Program. MAIN OUTCOME MEASURES.: The measures used to assess sexual dysfunction were Arizona Sexual Experiences Scale (ASEX) and International Index of Erectile Function (IIEF). The Positive and Negative Syndrome Scale (PANSS) and the Quality of Life Scale (QLS) were also used. The measures included the levels of prolactin, estradiol, luteinizing hormone, sex hormone-binding globulin, free testosterone, and total testosterone at baseline and end point. Lodenafil and placebo pills were used by the patients for 16 weeks. RESULTS.: Fifty male outpatients fulfilled the criteria and 94% of the participants completed the study. Lodenafil and placebo produced improvement in ASEX, IIEF scale, PANSS, and QLS, and there was no statistical difference between lodenafil and placebo groups in all sexual domains in the results of PANSS and QLS and in the results of hormone levels. CONCLUSION.: These results indicate that both lodenafil and placebo were effective in the treatment of erectile dysfunction for schizophrenia. Placebo effect is very important in patients with schizophrenia and this study showed the importance of discussing sexuality and trying to treat these patients. Further studies designed to test treatments of erectile dysfunction in patients who suffer from schizophrenia are necessary. © 2013 International Society for Sexual Medicine.

Evidence for the Presence of Non-Celiac Gluten Sensitivity in Patients with Functional Gastrointestinal Symptoms: Results from a Multicenter Randomized Double-Blind Placebo-Controlled Gluten Challenge.

PubMed

Elli, Luca; Tomba, Carolina; Branchi, Federica; Roncoroni, Leda; Lombardo, Vincenza; Bardella, Maria Teresa; Ferretti, Francesca; Conte, Dario; Valiante, Flavio; Fini, Lucia; Forti, Edoardo; Cannizzaro, Renato; Maiero, Stefania; Londoni, Claudio; Lauri, Adriano; Fornaciari, Giovanni; Lenoci, Nicoletta; Spagnuolo, Rocco; Basilisco, Guido; Somalvico, Francesco; Borgatta, Bruno; Leandro, Gioacchino; Segato, Sergio; Barisani, Donatella; Morreale, Gaetano; Buscarini, Elisabetta

2016-02-08

Non-celiac gluten sensitivity (NCGS) is characterized by the onset of symptoms after eating gluten-containing food. We aimed to single out NCGS subjects among subjects with functional gastrointestinal symptoms. Patients were enrolled in a multicenter double-blind placebo-controlled trial with crossover. Symptoms and quality of life were evaluated by means of 10-cm VAS and SF36. Iron parameters, transaminases and C reactive protein (CRP) were evaluated. After a three-week-long gluten-free diet (GFD), responsive patients were randomly assigned to gluten intake (5.6 g/day) or placebo for seven days, followed by crossover. The primary endpoint was the worsening of symptoms (VAS increase ≥3 cm) during gluten ingestion compared to placebo. One hundred and forty patients were enrolled and 134 (17 males, mean age 39.1 ± 11.7 years, BMI 22.4 ± 3.8) completed the first period. A total of 101 subjects (10 males, mean age 39.3 ± 11.0 years, BMI 22.3 ± 4.0) reported a symptomatic improvement (VAS score 2.3 ± 1.2 vs. 6.5 ± 2.2 before and after GFD, p = 0.001). 98 patients underwent the gluten challenge and 28 (all females, mean age 38.9 ± 12.7 years, BMI 22.0 ± 2.9) reported a symptomatic relapse and deterioration of quality of life. No parameters were found to be statistically associated with positivity to the challenge. However, 14 patients responded to the placebo ingestion. Taking into account this finding, about 14% of patients responding to gluten withdrawal showed a symptomatic relapse during the gluten challenge. This group is suspected to have NCGS.

Treatment of erectile dysfunction with sildenafil citrate in renal allograft recipients: a randomized, double-blind, placebo-controlled, crossover trial.

PubMed

Sharma, Raj K; Prasad, Narayan; Gupta, Amit; Kapoor, Rakesh

2006-07-01

Erectile dysfunction (ED) is observed frequently in patients with end-stage renal disease, hemodialysis patients, and renal allograft recipients. There are few studies of sildenafil use in renal allograft recipients. The study is designed as a randomized, double-blind, placebo-controlled, crossover trial. Efficacy was assessed by using the self-administered International Index of Erectile Function (IIEF), a 15-question validated measure of ED, and a global efficacy question (Did the treatment improve your erection?). Thirty-two eligible renal transplant recipients were included in this study. After treatment with sildenafil citrate, patients had significantly better scores in 13 of 15 questions, except for questions 11 (desire frequency; P = 0.39) and 12 (desire level; P = 0.61). Treatment efficacy assessed through questions 3 (penetration ability; P < 0.001) and 4 (maintenance frequency; P < 0.001) was significantly better after sildenafil therapy. There were no significant differences between baseline and post-placebo treatment scores, except for question 13 (relationship satisfaction). Patients treated with sildenafil had significantly better scores in 4 domains compared with baseline, but a difference was not observed in the sexual desire domain (P = 0.32). There were no significant differences in scores between placebo and baseline in any domain. On the global efficacy question, 81.3% of patients showed improvement compared with 18.7% with placebo. There were no differences in areas under the curve and maximum cyclosporine concentrations before and after sildenafil therapy. No patient discontinued the drug because of side effects except for 1 patient with visual hallucination. Treatment with sildenafil in renal transplant recipients is a valid option with an effective response.

Pharmacokinetic interaction between domperidone and ketoconazole leads to QT prolongation in healthy volunteers: a randomized, placebo-controlled, double-blind, crossover study

PubMed Central

Boyce, Malcolm J; Baisley, Kathy J; Warrington, Steven J

2012-01-01

AIMS To assess the steady-state pharmacokinetic and QTc effects of domperidone and ketoconazole, given alone and together. METHODS A randomized, placebo-controlled, double-blind, crossover study was carried out. Healthy subjects (14 men, 10 women; age 18–39 years; mean weight 73.5 kg, range 53.8–98.8 kg; 23 Europid, 1 Afro-Caribbean) received orally, for 7 days each, placebo, domperidone 10 mg, four doses daily, at 4 h intervals, ketoconazole 200 mg 12-hourly and domperidone and ketoconazole together. The washout period was 15 days. Pharmacokinetics and serial 12-lead ECGs were assessed on day 7, and serial ECGs on day −1 and at follow-up. Two subjects withdrew before the third treatment period, so data were available for 22–24 subjects. RESULTS Ketoconazole tripled domperidone concentrations at steady-state. Domperidone, ketoconazole and their combination significantly increased QTcF in men. Overall adjusted mean differences from placebo were 4.20 (95% CI 0.77, 7.63), 9.24 (95% CI 5.85, 12.63) and 15.90 (95% CI 12.47, 19.33) ms, respectively. In women, QTcF was not significantly different from placebo on either domperidone or ketoconazole alone, or in combination. However, QTc was positively correlated with plasma drug concentrations, in both men and women. ΔQTcF increased by about 2 ms per 10 ng ml–1 rise in domperidone concentration, and per 1 µg ml–1 rise in ketoconazole concentration. CONCLUSIONS Ketoconazole tripled the plasma concentrations of domperidone. Domperidone and ketoconazole increased QTcF in men, whether given together or separately. The effect of domperidone alone was below the level of clinical importance. The negative result in women is unexplained. PMID:21883386

OROS-methylphenidate efficacy on specific executive functioning deficits in adults with ADHD: a randomized, placebo-controlled cross-over study.

PubMed

Bron, Tannetje I; Bijlenga, Denise; Boonstra, A Marije; Breuk, Minda; Pardoen, Willem F H; Beekman, Aartjan T F; Kooij, J J Sandra

2014-04-01

Attention-deficit/hyperactivity disorder (ADHD) is linked to impaired executive functioning (EF). This is the first study to objectively investigate the effects of a long-acting methylphenidate on neurocognitive test performance of adults with ADHD. Twenty-two adults with ADHD participated in a 6-weeks study examining the effect of osmotic-release oral system methylphenidate (OROS-mph) on continuous performance tests (CPTs; objective measures), and on the self-reported ADHD rating scale (subjective measure) using a randomized, double-blind, placebo-controlled cross-over design. OROS-mph significantly improved reaction time variability (RTV), commission errors (CE) and d-prime (DP) as compared to baseline (Cohen's d>.50), but did not affect hit reaction time (HRT) or omission errors (OE). Compared to placebo, OROS-mph only significantly influenced RTV on one of two CPTs (p<.050). Linear regression analyses showed predictive ability of more beneficial OROS-mph effects in ADHD patients with higher EF severity (RTV: β=.670, t=2.097, p=.042; omission errors (OE): β=-.098, t=-4.759, p<.001), and with more severe ADHD symptoms (RTV: F=6.363, p=.019; HRT: F=3.914, p=.061). Side effects rates were substantially but non-significantly greater for OROS-mph compared to placebo (77% vs. 46%, p=.063). OROS-mph effects indicated RTV as the most sensitive parameter for measuring both neuropsychological and behavioral deficits in adults with ADHD. These findings suggest RTV as an endophenotypic parameter for ADHD symptomatology, and propose CPTs as an objective method for monitoring methylphenidate titration. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Effects of Oral L-Carnitine Administration in Narcolepsy Patients: A Randomized, Double-Blind, Cross-Over and Placebo-Controlled Trial

PubMed Central

Miyagawa, Taku; Kawamura, Hiromi; Obuchi, Mariko; Ikesaki, Asuka; Ozaki, Akiko; Tokunaga, Katsushi; Inoue, Yuichi; Honda, Makoto

2013-01-01

Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness, cataplexy, and rapid eye movement (REM) sleep abnormalities. A genome-wide association study (GWAS) identified a novel narcolepsy-related single nucleotide polymorphism (SNP), which is located adjacent to the carnitine palmitoyltransferase 1B (CPT1B) gene encoding an enzyme involved in β-oxidation of long-chain fatty acids. The mRNA expression levels of CPT1B were associated with this SNP. In addition, we recently reported that acylcarnitine levels were abnormally low in narcolepsy patients. To assess the efficacy of oral l-carnitine for the treatment of narcolepsy, we performed a clinical trial administering l-carnitine (510 mg/day) to patients with the disease. The study design was a randomized, double-blind, cross-over and placebo-controlled trial. Thirty narcolepsy patients were enrolled in our study. Two patients were withdrawn and 28 patients were included in the statistical analysis (15 males and 13 females, all with HLA-DQB1*06:02). l-carnitine treatment significantly improved the total time for dozing off during the daytime, calculated from the sleep logs, compared with that of placebo-treated periods. l-carnitine efficiently increased serum acylcarnitine levels, and reduced serum triglycerides concentration. Differences in the Japanese version of the Epworth Sleepiness Scale (ESS) and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) vitality and mental health subscales did not reach statistical significance between l-carnitine and placebo. This study suggests that oral l-carnitine can be effective in reducing excessive daytime sleepiness in narcolepsy patients. Trial Registration University hospital Medical Information Network (UMIN) UMIN000003760 PMID:23349733

An active video game intervention does not improve physical activity and sedentary time of children at-risk for developmental coordination disorder: a crossover randomized trial.

PubMed

Howie, E K; Campbell, A C; Straker, L M

2016-03-01

Children with developmental coordination disorder (DCD) are highly inactive and sedentary. The purpose of this study was to assess the impact of a home-based active video game intervention on objectively measured physical activity and sedentary behaviour in children at risk for DCD. In a crossover randomized clinical trial, 21 children (mean age 11.0, SD 1.0; n = 11 girls) in Perth, Western Australia participated in two 16-week periods: no active video games (AVGs) control period and AVGs intervention period. Two active input consoles were provided to participants along with a selection of non-violent AVGs for participants to play at home. Participants wore accelerometers at baseline and following each period to determine minutes of sedentary, light, moderate and vigorous times in addition to self-reported types of activities in a diary. Linear mixed models, adjusted for the order of periods, compared physical activity and sedentary time during the last week of each period. There were no significant differences between the intervention and control periods in time spent in sedentary (decrease of -1.0 min/day during the intervention period, 95%CI -12.1, 10.1), light (increase of 2.2 min/day, 95%CI -8.8, 13.2), moderate (decrease of 0.7 min/day, 95%CI -4.6, 3.3) or vigorous (decrease of -0.6 min/day, 95%CI -1.6, 0.4). Among children at risk for DCD, participating in this AVG intervention did not improve objectively measured physical activity and sedentary time. © 2015 John Wiley & Sons Ltd.

EffenDys-Fentanyl Buccal Tablet for the Relief of Episodic Breathlessness in Patients With Advanced Cancer: A Multicenter, Open-Label, Randomized, Morphine-Controlled, Crossover, Phase II Trial.

PubMed

Simon, Steffen T; Kloke, Marianne; Alt-Epping, Bernd; Gärtner, Jan; Hellmich, Martin; Hein, Rebecca; Piel, Maren; Cornely, Oliver A; Nauck, Friedemann; Voltz, Raymond

2016-11-01

Episodic breathlessness is a frequent and burdensome symptom in cancer patients but pharmacological treatment is limited. To determine time to onset, efficacy, feasibility, and safety of transmucosal fentanyl in comparison to immediate-release morphine for the relief of episodic breathlessness. Phase II, investigator-initiated, multicenter, open-label, randomized, morphine-controlled, crossover trial with open-label titration of fentanyl buccal tablet (FBT) in inpatients with incurable cancer. The primary outcome was time to onset of meaningful breathlessness relief. Secondary outcomes were efficacy (breathlessness intensity difference at 10 and 30 minutes; sum of breathlessness intensity difference at 15 and 60 minutes), feasibility, and safety. Study was approved by local ethics committees. Twenty-five of 1341 patients were eligible, 10 patients agreed to participate (four female, mean age 58 ± 11, mean Karnofsky score 67 ± 11). Two patients died before final visits and two patients dropped-out because of disease progression leaving six patients for analysis with 61 episodes of breathlessness. Mean time to onset was for FBT 12.7 ± 10.0 and for immediate-release morphine 23.6 ± 15.1 minutes with a mean difference of -10.9 minutes (95% CI = -24.5 to 2.7, P = 0.094). Efficacy measures were predominately in favor for FBT. Both interventions were safe. Feasibility failed because of too much study demands for a very ill patient group. The description of a faster and greater relief of episodic breathlessness by transmucosal fentanyl versus morphine justifies further evaluation by a full-powered trial. Copyright © 2016. Published by Elsevier Inc.

Evidence for the Presence of Non-Celiac Gluten Sensitivity in Patients with Functional Gastrointestinal Symptoms: Results from a Multicenter Randomized Double-Blind Placebo-Controlled Gluten Challenge

PubMed Central

Elli, Luca; Tomba, Carolina; Branchi, Federica; Roncoroni, Leda; Lombardo, Vincenza; Bardella, Maria Teresa; Ferretti, Francesca; Conte, Dario; Valiante, Flavio; Fini, Lucia; Forti, Edoardo; Cannizzaro, Renato; Maiero, Stefania; Londoni, Claudio; Lauri, Adriano; Fornaciari, Giovanni; Lenoci, Nicoletta; Spagnuolo, Rocco; Basilisco, Guido; Somalvico, Francesco; Borgatta, Bruno; Leandro, Gioacchino; Segato, Sergio; Barisani, Donatella; Morreale, Gaetano; Buscarini, Elisabetta

2016-01-01

Non-celiac gluten sensitivity (NCGS) is characterized by the onset of symptoms after eating gluten-containing food. We aimed to single out NCGS subjects among subjects with functional gastrointestinal symptoms. Patients were enrolled in a multicenter double-blind placebo-controlled trial with crossover. Symptoms and quality of life were evaluated by means of 10-cm VAS and SF36. Iron parameters, transaminases and C reactive protein (CRP) were evaluated. After a three-week-long gluten-free diet (GFD), responsive patients were randomly assigned to gluten intake (5.6 g/day) or placebo for seven days, followed by crossover. The primary endpoint was the worsening of symptoms (VAS increase ≥3 cm) during gluten ingestion compared to placebo. One hundred and forty patients were enrolled and 134 (17 males, mean age 39.1 ± 11.7 years, BMI 22.4 ± 3.8) completed the first period. A total of 101 subjects (10 males, mean age 39.3 ± 11.0 years, BMI 22.3 ± 4.0) reported a symptomatic improvement (VAS score 2.3 ± 1.2 vs. 6.5 ± 2.2 before and after GFD, p = 0.001). 98 patients underwent the gluten challenge and 28 (all females, mean age 38.9 ± 12.7 years, BMI 22.0 ± 2.9) reported a symptomatic relapse and deterioration of quality of life. No parameters were found to be statistically associated with positivity to the challenge. However, 14 patients responded to the placebo ingestion. Taking into account this finding, about 14% of patients responding to gluten withdrawal showed a symptomatic relapse during the gluten challenge. This group is suspected to have NCGS. PMID:26867199

Acute Caffeinated Coffee Consumption Does not Improve Time Trial Performance in an 800-m Run: A Randomized, Double-Blind, Crossover, Placebo-Controlled Study.

PubMed

Marques, Alexandre C; Jesus, Alison A; Giglio, Bruna M; Marini, Ana C; Lobo, Patrícia C B; Mota, João F; Pimentel, Gustavo D

2018-05-23

Studies evaluating caffeinated coffee (CAF) can reveal ergogenic effects; however, studies on the effects of caffeinated coffee on running are scarce and controversial. To investigate the effects of CAF consumption compared to decaffeinated coffee (DEC) consumption on time trial performances in an 800-m run in overnight-fasting runners. A randomly counterbalanced, double-blind, crossover, placebo-controlled study was conducted with 12 healthy adult males with experience in amateur endurance running. Participants conducted two trials on two different occasions, one day with either CAF or DEC, with a one-week washout. After arriving at the data collection site, participants consumed the soluble CAF (5.5 mg/kg of caffeine) or DEC and after 60 min the run was started. Before and after the 800-m race, blood pressure and lactate and glucose concentrations were measured. At the end of the run, the ratings of perceived exertion (RPE) scale was applied. The runners were light consumers of habitual caffeine, with an average ingestion of 91.3 mg (range 6⁻420 mg/day). Time trial performances did not change between trials (DEF: 2.38 + 0.10 vs. CAF: 2.39 + 0.09 min, p = 0.336), nor did the RPE (DEC: 16.5 + 2.68 vs. CAF: 17.0 + 2.66, p = 0.326). No difference between the trials was observed for glucose and lactate concentrations, or for systolic and diastolic blood pressure levels. CAF consumption failed to enhance the time trial performance of an 800-m run in overnight-fasting runners, when compared with DEC ingestion. In addition, no change was found in RPE, blood pressure levels, or blood glucose and lactate concentrations between the two trials.

Combined N-of-1 trials to investigate mexiletine in non-dystrophic myotonia using a Bayesian approach; study rationale and protocol.

PubMed

Stunnenberg, Bas C; Woertman, Willem; Raaphorst, Joost; Statland, Jeffrey M; Griggs, Robert C; Timmermans, Janneke; Saris, Christiaan G; Schouwenberg, Bas J; Groenewoud, Hans M; Stegeman, Dick F; van Engelen, Baziel G M; Drost, Gea; van der Wilt, Gert Jan

2015-03-25

To obtain evidence for the clinical and cost-effectiveness of treatments for patients with rare diseases is a challenge. Non-dystrophic myotonia (NDM) is a group of inherited, rare muscle diseases characterized by muscle stiffness. The reimbursement of mexiletine, the expert opinion drug for NDM, has been discontinued in some countries due to a lack of independent randomized controlled trials (RCTs). It remains unclear however, which concessions can be accepted towards the level 1 evidence needed for coverage decisions, in rare diseases. Considering the large number of rare diseases with a lack of treatment evidence, more experience with innovative trial designs is needed. Both NDM and mexiletine are well suited for an N-of-1 trial design. A Bayesian approach allows for the combination of N-of-1 trials, which enables the assessment of outcomes on the patient and group level simultaneously. We will combine 30 individual, double-blind, randomized, placebo-controlled N-of-1 trials of mexiletine (600 mg daily) vs. placebo in genetically confirmed NDM patients using hierarchical Bayesian modeling. Our results will be compared and combined with the main results of an international cross-over RCT (mexiletine vs. placebo in NDM) published in 2012 that will be used as an informative prior. Similar criteria of eligibility, treatment regimen, end-points and measurement instruments are employed as used in the international cross-over RCT. The treatment of patients with NDM with mexiletine offers a unique opportunity to compare outcomes and efficiency of novel N-of-1 trial-based designs and conventional approaches in producing evidence of clinical and cost-effectiveness of treatments for patients with rare diseases. ClinicalTrials.gov Identifier: NCT02045667.

Impact of different concentrations of an octenidine dihydrochloride mouthwash on salivary bacterial counts: a randomized, placebo-controlled cross-over trial.

PubMed

Lorenz, Katrin; Jockel-Schneider, Yvonne; Petersen, Nicole; Stölzel, Peggy; Petzold, Markus; Vogel, Ulrich; Hoffmann, Thomas; Schlagenhauf, Ulrich; Noack, Barbara

2018-03-02

This bi-centric, placebo-controlled, randomized, evaluator-blinded, incomplete cross-over clinical phase II trial was initialized to identify the most appropriate concentration of octenidine dihydrochloride (OCT) in mouth rinses. Rinses of 0.10, 0.15, and 0.20% OCT were compared to a saline placebo rinse regarding the reduction of salivary bacterial counts (SBCs) in 90 gingivitis patients over 4 days. Changes in plaque (PI) and gingival index (GI), taste perception, and safety issues were evaluated. At baseline, the first OCT (0.10, 0.15, 0.20%) rinse resulted in a decrease of SBC (reduction by 3.63-5.44 log 10 colony forming units [CFU]) compared to placebo (p < 0.001). Differences between OCT concentrations were not verified. After 4 days, the last OCT rinse again resulted in a significant SBC decrease (3.69-4.22 log 10 CFU) compared to placebo (p < 0.001). Overall, SBC reduction between baseline and day 4 was significantly higher in OCT 0.15 and 0.20% groups compared to OCT 0.10% and placebo. Mean GI/PIs were significantly lower in OCT groups than in the placebo group (p < 0.001). Differences in GI/PI between OCT groups were not verified. Adverse effects increased with increasing OCT concentrations. Considering antibacterial efficacy, frequency of adverse events, and user acceptance, 0.10% OCT was identified as the preferred concentration to be used in future clinical trials. Due to its low toxicity and pronounced antibacterial properties, octenidine dihydrochloride (OCT) is a promising candidate for the use in antiseptic mouth rinses. OCT concentrations of 0.10% are recommended for future clinical trials evaluating the plaque-reducing properties of OCT mouth rinses. ( www.clinicaltrials.gov , NCT022138552).

Electrically Assisted Movement Therapy in Chronic Stroke Patients With Severe Upper Limb Paresis: A Pilot, Single-Blind, Randomized Crossover Study.

PubMed

Carda, Stefano; Biasiucci, Andrea; Maesani, Andrea; Ionta, Silvio; Moncharmont, Julien; Clarke, Stephanie; Murray, Micah M; Millán, José Del R

2017-08-01

To evaluate the effects of electrically assisted movement therapy (EAMT) in which patients use functional electrical stimulation, modulated by a custom device controlled through the patient's unaffected hand, to produce or assist task-specific upper limb movements, which enables them to engage in intensive goal-oriented training. Randomized, crossover, assessor-blinded, 5-week trial with follow-up at 18 weeks. Rehabilitation university hospital. Patients with chronic, severe stroke (N=11; mean age, 47.9y) more than 6 months poststroke (mean time since event, 46.3mo). Both EAMT and the control intervention (dose-matched, goal-oriented standard care) consisted of 10 sessions of 90 minutes per day, 5 sessions per week, for 2 weeks. After the first 10 sessions, group allocation was crossed over, and patients received a 1-week therapy break before receiving the new treatment. Fugl-Meyer Motor Assessment for the Upper Extremity, Wolf Motor Function Test, spasticity, and 28-item Motor Activity Log. Forty-four individuals were recruited, of whom 11 were eligible and participated. Five patients received the experimental treatment before standard care, and 6 received standard care before the experimental treatment. EAMT produced higher improvements in the Fugl-Meyer scale than standard care (P<.05). Median improvements were 6.5 Fugl-Meyer points and 1 Fugl-Meyer point after the experimental treatment and standard care, respectively. The improvement was also significant in subjective reports of quality of movement and amount of use of the affected limb during activities of daily living (P<.05). EAMT produces a clinically important impairment reduction in stroke patients with chronic, severe upper limb paresis. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Adjuvant Liraglutide and Insulin Versus Insulin Monotherapy in the Closed-Loop System in Type 1 Diabetes: A Randomized Open-Labeled Crossover Design Trial.

PubMed

Ilkowitz, Jeniece Trast; Katikaneni, Ranjitha; Cantwell, Martin; Ramchandani, Neesha; Heptulla, Rubina A

2016-09-01

The closed-loop (CL) system delivers insulin in a glucose-responsive manner and optimal postprandial glycemic control is difficult to achieve with the algorithm and insulin available. We hypothesized that adjunctive therapy with liraglutide, a once-daily glucagon-like peptide-1 agonist, would be more effective in normalizing postprandial hyperglycemia versus insulin monotherapy in the CL system, in patients with type 1 diabetes. This was a randomized, controlled, open-label, crossover design trial comparing insulin monotherapy versus adjuvant subcutaneous liraglutide 1.2 mg and insulin, using the CL system in 15 patients. Blood glucose (BG), insulin, and glucagon concentrations were analyzed. The liraglutide arm was associated with overall decreased mean BG levels (P = .0002). The average BG levels from 8:00 pm (day 1) to 9:00 pm (day 2) were lower in the liraglutide arm (144.6 ± 36.31 vs 159.7 ± 50.88 mg/dl respectively; P = .0002). Two-hour postbreakfast and lunch BG profiles were better in the liraglutide arm (P < .05) and the insulin and glucagon assay values were lower (P < .0001). Postprandially, the area under the curve (AUC) for 2-hour postbreakfast and lunch BG levels were significant (P = .01, P = .03) and the AUC for glucagon, postbreakfast (P < .0001) and lunch (P < .05), was also significant. The incidence of hypoglycemia did not differ between arms (P = .83, Fisher's exact test). Overall, adjunct liraglutide therapy plus CL was well tolerated even with expected side effects. This is a proof-of-concept study showing liraglutide can be a potential adjunctive therapy in addition to CL with insulin to reduce postprandial hyperglycemia in type 1 diabetes. © 2016 Diabetes Technology Society.

Gastric acid control with esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole: a five-way crossover study.

PubMed

Miner, Philip; Katz, Philip O; Chen, Yusong; Sostek, Mark

2003-12-01

Proton pump inhibitors owe their clinical efficacy to their ability to suppress gastric acid production. The objective of this study was to evaluate and compare intragastric pH following standard doses of esomeprazole, lansoprazole, omeprazole, pantoprazole and rabeprazole. This randomized, open-label, comparative five-way crossover study evaluated the 24-h intragastric pH profile of oral esomeprazole 40 mg, lansoprazole 30 mg, omeprazole 20 mg, pantoprazole 40 mg, and rabeprazole 20 mg once daily in 34 Helicobacter pylori-negative patients aged 18-60 yr with symptoms of gastroesophageal reflux disease. Patients were randomly assigned to one of five treatment sequences and study drug was taken on 5 consecutive mornings 30 minutes prior to a standardized breakfast. A washout period of at least 10 days separated each treatment phase. Thirty-four patients provided evaluable data for all five comparators. The mean number of hours of evaluable pH data was > or =23.75 hours. On day 5, intragastric pH was maintained above 4.0 for a mean of 14.0 h with esomeprazole, 12.1 h with rabeprazole, 11.8 h with omeprazole, 11.5 h with lansoprazole, and 10.1 h with pantoprazole (p < or = 0.001 for differences between esomeprazole and all other comparators). Esomeprazole also provided a significantly higher percentage of patients with an intragastric pH greater than 4.0 for more than 12 h relative to the other proton pump inhibitors (p < 0.05). The frequency of adverse events was similar between treatment groups. Esomeprazole at the standard dose of 40 mg once daily provided more effective control of gastric acid at steady state than standard doses of lansoprazole, omeprazole, pantoprazole, and rabeprazole in patients with symptoms of gastroesophageal reflux disease.

A randomized cross-over controlled study on cognitive rehabilitation of instrumental activities of daily living in Alzheimer disease.

PubMed

Thivierge, Stéphanie; Jean, Léonie; Simard, Martine

2014-11-01

The goal of the study was to investigate the effectiveness of a memory rehabilitation program to re-learn instrumental activities of daily living (IADLs) in patients with Alzheimer disease (AD). This was a 6-month block-randomized cross-over controlled study. All evaluation and training sessions were performed at each patient's home. Twenty participants with mild to moderate AD. The trained IADL was chosen by the patient and his/her caregiver in order to target the patient's needs and interests. Participants were trained twice a week for 4 weeks with the errorless learning (ELL) and spaced retrieval (SR) cognitive techniques. After training, there were several follow-ups over a period of at least 3 months. Performance on the trained IADL was assessed by a Direct Measure of Training (DMT), an observational instrument adapted from a well-validated scale. General cognitive function, everyday memory functioning, quality of life, neuropsychiatric symptoms and ADL/IADL of patients, as well as the caregiver's burden were assessed as secondary outcomes. A statistical significant difference was found between the trained and untrained groups on the DMT immediately following the intervention. Improvements were maintained for a 3-month period. The training did not have effects on any other measures. The present study showed that it is possible for AD patients to relearn significant IADLs with the ELL and SR techniques and to maintain these gains during at least 3 months. The findings of this study emphasize the importance to design robust but individualized intervention tailored on patients' particular needs. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Marked antioxidant effect of orange juice intake and its phytomicronutrients in a preliminary randomized cross-over trial on mild hypercholesterolemic men.

PubMed

Constans, Joël; Bennetau-Pelissero, Catherine; Martin, Jean-François; Rock, Edmond; Mazur, Andrzej; Bedel, Aurélie; Morand, Christine; Bérard, Annie M

2015-12-01

Blond orange juice is the most consumed fruit juice in the world. It is a source of hesperidin, a bioavailable flavonoid reported to exhibit potential vascular protective actions. However, the specific impact on vascular function of Citrus phytomicronutrients, is unknown. For the first time, we investigated the effects of blond orange juice compared with a control beverage mimicking the composition of orange juice (including Vitamin C but no phytomicronutrients), on antioxidant markers, cardiovascular risk factors and endothelial function. Twenty five male volunteers with two cardiovascular risk factors (age over 50 years and LDL-cholesterol between 130 and 190 mg/L) were enrolled in a randomized cross-over study. They received 3 times daily 200 mL of either blond orange juice or control beverage for 4 weeks, spaced by a 5-week wash-out. Endothelial function (flow mediated dilatation and plasma markers), oxidative status, lipid profile and inflammatory markers were assessed. Daily intakes of orange juice significantly led to a marked antioxidant effect which was correlated to hesperetin plasma levels and related with a decrease in reactive oxygen species. A tendency towards reduction of endothelial dysfunction and modest increase in plasma apoA-I concentration were also observed. This allows further experiments demonstrating the specific effect of phytomicronutrients from orange juice. These findings suggest that daily intake of nutritionally relevant dose of blond orange juice may contribute for a significant antioxidant effect through the phytochemicals contained in. Orange juice may be associated to other healthy foods to achieve a significant effect on the vascular function. This study is recorded in ClinicalTrials.com as NCT00539916. Copyright © 2014. Published by Elsevier Ltd.

Influence diagnostics for count data under AB-BA crossover trials.

PubMed

Hao, Chengcheng; von Rosen, Dietrich; von Rosen, Tatjana

2017-12-01

This paper aims to develop diagnostic measures to assess the influence of data perturbations on estimates in AB-BA crossover studies with a Poisson distributed response. Generalised mixed linear models with normally distributed random effects are utilised. We show that in this special case, the model can be decomposed into two independent sub-models which allow to derive closed-form expressions to evaluate the changes in the maximum likelihood estimates under several perturbation schemes. The performance of the new influence measures is illustrated by simulation studies and the analysis of a real dataset.

Parental control, parental warmth, and psychosocial adjustment in a sample of substance-abusing mothers and their school-aged and adolescent children

PubMed Central

Suchman, Nancy E.; Rounsaville, Bruce; DeCoste, Cindy; Luthar, Suniya

2007-01-01

Parenting interventions for substance-abusing adults have been broadly based on two approaches, one emphasizing parental control as a means to managing children’s behavior and the second emphasizing parental warmth and sensitivity as means to fostering children’s psychological development. In this investigation, we examined associations of parental control and parental warmth, respectively, with children’s behavioral and psychological adjustment in a sample of 98 women enrolled in methadone maintenance and their school-aged and adolescent children. Using collateral data collected during the baseline phase of a randomized clinical trial (Luthar, S. S., Suchman, N. E., & Altomare, M. [in press]. Relational Psychotherapy Mothers Group: A randomized clinical trial for substance abusing mothers [in preparation]), we tested predictions that (a) parental control would be more strongly associated with children’s behavioral adjustment and (b) parental warmth would be more strongly associated with children’s psychological adjustment. Both predictions were generally confirmed, although some crossover among parenting and child dimensions was also evident. Results support the theoretical stance that parental limit setting and autonomy support, as well as nurturance and involvement, are important factors, respectively, in children’s behavioral and psychological adjustment. PMID:17175393

No effect of magnesium supplementation on metabolic control and insulin sensitivity in type 2 diabetic patients with normomagnesemia.

PubMed

Navarrete-Cortes, Adrian; Ble-Castillo, Jorge L; Guerrero-Romero, Fernando; Cordova-Uscanga, Ruben; Juárez-Rojop, Isela E; Aguilar-Mariscal, Hidemi; Tovilla-Zarate, Carlos Alfonso; Lopez-Guevara, Maria Del Rocio

2014-01-01

There are limited and conflicting data from clinical trials concerning the beneficial effects of magnesium supplementation on diabetic patients. We investigated the effects of magnesium supplementation on metabolic control and insulin sensitivity in type 2 diabetic patients with normomagnesemia. A total of 98 normomagnesemic subjects with type 2 diabetes were enrolled in a randomized, crossover, double-blind, placebo-controlled trial. Participants were randomly assigned to receive magnesium lactate (360 mg elemental magnesium) or placebo for three months, followed by a three-month washout period. Treatment assignments were then reversed over an additional three months of follow-up. The primary endpoint was a reduction in fasting glucose and HbA1c. A total of 56 subjects completed the follow-up in the magnesium and placebo supplementation groups. Urinary magnesium excretion was increased following magnesium supplementation in the intervention group compared with the placebo group (p = 0.0002). Fasting glucose, HbA1c, insulin and HOMA-IR, as well as lipid profile, did not change significantly during treatment. We concluded that magnesium supplementation does not improve metabolic control or insulin sensitivity in diabetic subjects with normomagnesemia.

Random-walk diffusion and drying of porous materials

NASA Astrophysics Data System (ADS)

Mehrafarin, M.; Faghihi, M.

2001-12-01

Based on random-walk diffusion, a microscopic model for drying is proposed to explain the characteristic features of the drying-rate curve of porous materials. The constant drying-rate period is considered as a normal diffusion process. The transition to the falling-rate regime is attributed to the fractal nature of porous materials which results in crossover to anomalous diffusion.

The effectiveness of topical colloidal silver in recalcitrant chronic rhinosinusitis: a randomized crossover control trial.

PubMed

Scott, John R; Krishnan, Rohin; Rotenberg, Brian W; Sowerby, Leigh J

2017-11-25

Recalcitrant chronic rhinosinusitis without polyposis (CRSsP) is a challenging condition to manage as traditional medical therapies and surgery fail to provide satisfactory clinical improvements. Colloidal silver (CS), a widely used naturopathic agent, has recently shown anti-biofilm properties both in vitro and within a rhinosinusitis animal model. To date, no trials involving humans have been published in world literature. The purpose of this study was to assess the efficacy of CS as a topical nasal spray in patients with refractory CRSsP. A prospective cohort study was conducted using a convenience sample of 20 randomized patients with crossover methodology, comparing nasal sprays with CS versus saline. Patients sprayed twice daily for six weeks with the first intervention and then switched to the second for the next six weeks, with measurements made at baseline and each time point. Primary outcomes were changes in SNOT-22 and Lund-Kennedy (LK) endoscopic scores. All analysis was non-parametric and was conducted using STATA 14. Twenty-two patients were enrolled in the study with 20 completing the entire protocol. Mean 6-week change in SNOT-22 scores were -2.8 and 1.0 for saline and CS, respectively (p = 0.373). Similarly, mean 6-week change in LK scores were -1.4 and -1.1 for saline and CS, respectively (p = 0.794). Significant period effects were observed with the SNOT-22 score between the randomized groups. No participants experienced negative health effects directly attributable to the administration of intranasal CS. Commercially available CS nasal spray did not demonstrate any meaningful subjective or objective improvements in patients with recalcitrant CRSsP. NCT02403479 . Registered on March 1, 2015.

Effects of a new combination of nutraceuticals with Morus alba on lipid profile, insulin sensitivity and endotelial function in dyslipidemic subjects. A cross-over, randomized, double-blind trial.

PubMed

Trimarco, Valentina; Izzo, Raffaele; Stabile, Eugenio; Rozza, Francesco; Santoro, Mario; Manzi, Maria Virginia; Serino, Federica; Schiattarella, Gabriele Giacomo; Esposito, Giovanni; Trimarco, Bruno

2015-06-01

Nutraceuticals (NUT) are forms of compounds with biological activity commonly used to improve health in dosage largely exceeding those obtainable in food. We compared, in a double blind randomized cross-over trial, the effects of two NUT combinations on the control of glico-lipidic metabolism in patients with hypercholesterolemia not on statins. At study start patients were given dietary counseling and received placebo for 2 weeks. After this run-in period, patients were randomized: (1) Combination A [Policosanol, Red yeast rice (Monakolin K 3 mg), Berberine 500 mg, Astaxantine, Folic Acid and Coenzyme Q10] for 4 weeks followed by 4 weeks of Combination B [Red yeast rice (Monakolin K 3.3 mg), Berberine 531.25 mg and leaf extract of Morus alba]; (2) Combination B for 4 weeks followed by 4 weeks of Combination A. Combination B reduced LDL cholesterol below 130 mg/dl in 56.5 % of the patients, and Cambination A only in 21.7 % of them (p ≤ 0.027). Both treatments reduced plasma levels of triglycerides, total and LDL cholesterol and increased HDL cholesterol (all p < 0.03). Total and LDL cholesterol reduction was more pronounced in patients taking Combination B (p < 0.005). Combination B reduced also glycated hemoglobin, fasting glucose and insulin plasma levels as well as HOMA index (p < 0.005). An increased content of Berberin and Monacolin K and the addition of Morus alba extract improves the effect on plasma cholesterol and on glucose metabolism of the NUT Combination. These effects may allow the speculation of a more marked improvement in cardiovascular prognosis.

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

Salvia Miltiorrhiza Root Water-Extract (Danshen) Has No Beneficial Effect on Cardiovascular Risk Factors. A Randomized Double-Blind Cross-Over Trial

PubMed Central

van Poppel, Pleun C. M.; Breedveld, Pauline; Abbink, Evertine J.; Roelofs, Hennie; van Heerde, Waander; Smits, Paul; Lin, Wenzhi; Tan, Aaitje H.; Russel, Frans G.; Donders, Rogier; Tack, Cees J.; Rongen, Gerard A.

2015-01-01

Purpose Danshen is the dried root extract of the plant Salvia Miltiorrhiza and it is used as traditional Chinese medicinal herbal product to prevent and treat atherosclerosis. However, its efficacy has not been thoroughly investigated. This study evaluates the effect of Danshen on hyperlipidemia and hypertension, two well known risk factors for the development of atherosclerosis. Methods This was a randomized, placebo-controlled, double-blind crossover study performed at a tertiary referral center. Participants were recruited by newspaper advertisement and randomized to treatment with Danshen (water-extract of the Salvia Miltiorrhiza root) or placebo for 4 consecutive weeks. There was a wash out period of 4 weeks. Of the 20 analysed participants, 11 received placebo first. Inclusion criteria were: age 40-70 years, hyperlipidemia and hypertension. At the end of each treatment period, plasma lipids were determined (primary outcome), 24 hours ambulant blood pressure measurement (ABPM) was performed, and vasodilator endothelial function was assessed in the forearm. Results LDL cholesterol levels were 3.82±0.14 mmol/l after Danshen and 3.52±0.16 mmol/l after placebo treatment (mean±SE; p<0.05 for treatment effect corrected for baseline). Danshen treatment had no effect on blood pressure (ABPM 138/84 after Danshen and 136/87 after placebo treatment). These results were further substantiated by the observation that Danshen had neither an effect on endothelial function nor on markers of inflammation, oxidative stress, glucose metabolism, hemostasis and blood viscosity. Conclusion Four weeks of treatment with Danshen (water-extract) slightly increased LDL-cholesterol without affecting a wide variety of other risk markers. These observations do not support the use of Danshen to prevent or treat atherosclerosis. Trial Registration ClinicalTrials.gov NCT01563770 PMID:26192328

Effects of Ethnic Attributes on the Quality of Family Planning Services in Lima, Peru: A Randomized Crossover Trial

PubMed Central

Planas, Maria-Elena; García, Patricia J.; Bustelo, Monserrat; Carcamo, Cesar P.; Martinez, Sebastian; Nopo, Hugo; Rodriguez, Julio; Merino, Maria-Fernanda; Morrison, Andrew

2015-01-01

Most studies reporting ethnic disparities in the quality of healthcare come from developed countries and rely on observational methods. We conducted the first experimental study to evaluate whether health providers in Peru provide differential quality of care for family planning services, based on the indigenous or mestizo (mixed ethnoracial ancestry) profile of the patient. In a crossover randomized controlled trial conducted in 2012, a sample of 351 out of the 408 public health establishments in Metropolitan Lima, Peru were randomly assigned to receive unannounced simulated patients enacting indigenous and mestizo profiles (sequence-1) or mestizo and then indigenous profiles (sequence-2), with a five week wash-out period. Both ethnic profiles used the same scripted scenario for seeking contraceptive advice but had distinctive cultural attributes such as clothing, styling of hair, make-up, accessories, posture and patterns of movement and speech. Our primary outcome measure of quality of care is the proportion of technical tasks performed by providers, as established by Peruvian family planning clinical guidelines. Providers and data analysts were kept blinded to the allocation. We found a non-significant mean difference of -0·7% (p = 0·23) between ethnic profiles in the percentage of technical tasks performed by providers. However we report large deficiencies in the compliance with quality standards of care for both profiles. Differential provider behaviour based on the patient's ethnic profiles compared in the study did not contribute to deficiencies in family planning outcomes observed. The study highlights the need to explore other determinants for poor compliance with quality standards, including demand and supply side factors, and calls for interventions to improve the quality of care for family planning services in Metropolitan Lima. PMID:25671664

To Compare PubMed Clinical Queries and UpToDate in Teaching Information Mastery to Clinical Residents: A Crossover Randomized Controlled Trial

PubMed Central

Sayyah Ensan, Ladan; Faghankhani, Masoomeh; Javanbakht, Anna; Ahmadi, Seyed-Foad; Baradaran, Hamid Reza

2011-01-01

Purpose To compare PubMed Clinical Queries and UpToDate regarding the amount and speed of information retrieval and users' satisfaction. Method A cross-over randomized trial was conducted in February 2009 in Tehran University of Medical Sciences that included 44 year-one or two residents who participated in an information mastery workshop. A one-hour lecture on the principles of information mastery was organized followed by self learning slide shows before using each database. Subsequently, participants were randomly assigned to answer 2 clinical scenarios using either UpToDate or PubMed Clinical Queries then crossed to use the other database to answer 2 different clinical scenarios. The proportion of relevantly answered clinical scenarios, time to answer retrieval, and users' satisfaction were measured in each database. Results Based on intention-to-treat analysis, participants retrieved the answer of 67 (76%) questions using UpToDate and 38 (43%) questions using PubMed Clinical Queries (P<0.001). The median time to answer retrieval was 17 min (95% CI: 16 to 18) using UpToDate compared to 29 min (95% CI: 26 to 32) using PubMed Clinical Queries (P<0.001). The satisfaction with the accuracy of retrieved answers, interaction with UpToDate and also overall satisfaction were higher among UpToDate users compared to PubMed Clinical Queries users (P<0.001). Conclusions For first time users, using UpToDate compared to Pubmed Clinical Querries can lead to not only a higher proportion of relevant answer retrieval within a shorter time, but also a higher users' satisfaction. So, addition of tutoring pre-appraised sources such as UpToDate to the information mastery curricula seems to be highly efficient. PMID:21858142

To compare PubMed Clinical Queries and UpToDate in teaching information mastery to clinical residents: a crossover randomized controlled trial.

PubMed

Sayyah Ensan, Ladan; Faghankhani, Masoomeh; Javanbakht, Anna; Ahmadi, Seyed-Foad; Baradaran, Hamid Reza

2011-01-01

To compare PubMed Clinical Queries and UpToDate regarding the amount and speed of information retrieval and users' satisfaction. A cross-over randomized trial was conducted in February 2009 in Tehran University of Medical Sciences that included 44 year-one or two residents who participated in an information mastery workshop. A one-hour lecture on the principles of information mastery was organized followed by self learning slide shows before using each database. Subsequently, participants were randomly assigned to answer 2 clinical scenarios using either UpToDate or PubMed Clinical Queries then crossed to use the other database to answer 2 different clinical scenarios. The proportion of relevantly answered clinical scenarios, time to answer retrieval, and users' satisfaction were measured in each database. Based on intention-to-treat analysis, participants retrieved the answer of 67 (76%) questions using UpToDate and 38 (43%) questions using PubMed Clinical Queries (P<0.001). The median time to answer retrieval was 17 min (95% CI: 16 to 18) using UpToDate compared to 29 min (95% CI: 26 to 32) using PubMed Clinical Queries (P<0.001). The satisfaction with the accuracy of retrieved answers, interaction with UpToDate and also overall satisfaction were higher among UpToDate users compared to PubMed Clinical Queries users (P<0.001). For first time users, using UpToDate compared to Pubmed Clinical Queries can lead to not only a higher proportion of relevant answer retrieval within a shorter time, but also a higher users' satisfaction. So, addition of tutoring pre-appraised sources such as UpToDate to the information mastery curricula seems to be highly efficient.


Intrathecal analgesia by bupivacaine is not enhanced by coadministration of morphine in patients with severe cancer-related pain: a randomized double-blind cross-over study.

PubMed

Reif, Ingalill; Wincent, Anders; Stiller, Carl-Olav

2017-06-01

The objective of this randomized double blind cross-over trial was to determine if patients with severe cancer-related pain and inadequate response to systemic opioids prefer intrathecal (IT) pain relief with a combination of bupivacaine and morphine or bupivacaine only. Adult patients with cancer-related pain (n = 23) scheduled for IT analgesia at the Pain Center at the Karo-linska University Hospital Solna, Stockholm, Sweden, were included. The optimal individual flow rate of IT bupivacaine (2 mg/mL) in addition to bolus doses was titrated and maintained for 4 days. Morphine (1 mg/mL) was added to bupivacaine either on day 2 or 4 according to a randomization protocol. Expression of pain relief preference for morphine instead of control (bupivacaine only) was the primary outcome. Secondary outcomes were difference in pain intensity, pain relief, total use of bupivacaine per 24 hours and number of requested bolus doses. Eight patients dropped out during the 4-day study period for reasons not related to the trial. IT bupivacaine significantly decreased median (interquartile range) pain intensity from 5 (3 - 7) at baseline (before catheter insertion) to 1 (0 - 1) (p = 0.0001; Wilcoxon test). Only 1 patient of 15 with 4-day data expressed any preference for morphine. The addition of IT morphine did not result in any significant change of pain intensity, pain relief score, total use of bupivacaine per 24 hours, or number of requested bolus doses. These results suggest that patients with cancer-related pain treated with high doses of systemic opioids, may start IT treatment with an optimal dose of IT bupivacaine without morphine.
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Acute electromyographic responses of deep thoracic paraspinal muscles to spinal manual therapy interventions. An experimental, randomized cross-over study.

PubMed

Fryer, Gary; Bird, Michael; Robbins, Barry; Johnson, Jane C

2017-07-01

This single group, randomized, cross-over study explored whether manual therapy alters motor tone of deep thoracic back muscles by examining resting electromyographic activity (EMG) after 2 types of manual therapy and a sham control intervention. Twenty-two participants with thoracic spinal pain (15 females, 7 males, mean age 28.1 ± 6.4 years) had dual fine-wire, intramuscular electrodes inserted into deep transversospinalis muscles at a thoracic level where tissues appeared abnormal to palpation (AbP) and at 2 sites above and below normal and non-tender to palpation (NT). A surface electrode was on the contralateral paraspinal mass at the level of AbP. EMG signals were recorded for resting prone, two 3-s free neck extension efforts, two 3-s resisted maximal voluntary isometric contractions (MVIC), and resting prone before the intervention. Randomized spinal manipulation, counterstrain, or sham manipulation was delivered and EMG re-measured. Participants returned 1 and 2 weeks later for the remaining 2 treatments. Reductions in resting EMG followed counterstrain in AbP (median decrease 3.3%, P = 0.01) and NT sites (median decrease 1.0%, P = 0.05) and for the surface electrode site (median decrease 2.0%, P = 0.009). Reduction in EMG following counterstrain during free neck extension was found for the surface electrode site (median decrease 2.7%, P < 0.01). Spinal manipulation produced no change in EMG, whereas counterstrain technique produced small significant reductions in paraspinal muscle activity during prone resting and free neck extension conditions. The clinical relevance of these changes is unclear. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hands-Off Time for Endotracheal Intubation during CPR Is Not Altered by the Use of the C-MAC Video-Laryngoscope Compared to Conventional Direct Laryngoscopy. A Randomized Crossover Manikin Study.

PubMed

Schuerner, Philipp; Grande, Bastian; Piegeler, Tobias; Schlaepfer, Martin; Saager, Leif; Hutcherson, Matthew T; Spahn, Donat R; Ruetzler, Kurt

2016-01-01

Sufficient ventilation and oxygenation through proper airway management is essential in patients undergoing cardio-pulmonary resuscitation (CPR). Although widely discussed, securing the airway using an endotracheal tube is considered the standard of care. Endotracheal intubation may be challenging and causes prolonged interruption of chest compressions. Videolaryngoscopes have been introduced to better visualize the vocal cords and accelerate intubation, which makes endotracheal intubation much safer and may contribute to intubation success. Therefore, we aimed to compare hands-off time and intubation success of direct laryngoscopy with videolaryngoscopy (C-MAC, Karl Storz, Tuttlingen, Germany) in a randomized, cross-over manikin study. Twenty-six anesthesia residents and twelve anesthesia consultants of the University Hospital Zurich were recruited through a voluntary enrolment. All participants performed endotracheal intubation using direct laryngoscopy and C-MAC in a random order during ongoing chest compressions. Participants were strictly advised to stop chest compression only if necessary. The median hands-off time was 1.9 seconds in direct laryngoscopy, compared to 3 seconds in the C-MAC group. In direct laryngoscopy 39 intubation attempts were recorded, resulting in an overall first intubation attempt success rate of 97%, compared to 38 intubation attempts and 100% overall first intubation attempt success rate in the C-MAC group. As a conclusion, the results of our manikin-study demonstrate that video laryngoscopes might not be beneficial compared to conventional, direct laryngoscopy in easily accessible airways under CPR conditions and in experienced hands. The benefits of video laryngoscopes are of course more distinct in overcoming difficult airways, as it converts a potential "blind intubation" into an intubation under visual control.

Effects of ethnic attributes on the quality of family planning services in Lima, Peru: a randomized crossover trial.

PubMed

Planas, Maria-Elena; García, Patricia J; Bustelo, Monserrat; Carcamo, Cesar P; Martinez, Sebastian; Nopo, Hugo; Rodriguez, Julio; Merino, Maria-Fernanda; Morrison, Andrew

2015-01-01

Most studies reporting ethnic disparities in the quality of healthcare come from developed countries and rely on observational methods. We conducted the first experimental study to evaluate whether health providers in Peru provide differential quality of care for family planning services, based on the indigenous or mestizo (mixed ethnoracial ancestry) profile of the patient. In a crossover randomized controlled trial conducted in 2012, a sample of 351 out of the 408 public health establishments in Metropolitan Lima, Peru were randomly assigned to receive unannounced simulated patients enacting indigenous and mestizo profiles (sequence-1) or mestizo and then indigenous profiles (sequence-2), with a five week wash-out period. Both ethnic profiles used the same scripted scenario for seeking contraceptive advice but had distinctive cultural attributes such as clothing, styling of hair, make-up, accessories, posture and patterns of movement and speech. Our primary outcome measure of quality of care is the proportion of technical tasks performed by providers, as established by Peruvian family planning clinical guidelines. Providers and data analysts were kept blinded to the allocation. We found a non-significant mean difference of -0.7% (p = 0.23) between ethnic profiles in the percentage of technical tasks performed by providers. However we report large deficiencies in the compliance with quality standards of care for both profiles. Differential provider behaviour based on the patient's ethnic profiles compared in the study did not contribute to deficiencies in family planning outcomes observed. The study highlights the need to explore other determinants for poor compliance with quality standards, including demand and supply side factors, and calls for interventions to improve the quality of care for family planning services in Metropolitan Lima.

X-Chromosome Control of Genome-Scale Recombination Rates in House Mice.

PubMed

Dumont, Beth L

2017-04-01

Sex differences in recombination are widespread in mammals, but the causes of this pattern are poorly understood. Previously, males from two interfertile subspecies of house mice, Mus musculus musculus and M. m. castaneus , were shown to exhibit a ∼30% difference in their global crossover frequencies. Much of this crossover rate divergence is explained by six autosomal loci and a large-effect locus on the X chromosome. Intriguingly, the allelic effects at this X-linked locus are transgressive, with the allele conferring increased crossover rate being transmitted by the low crossover rate M. m. castaneus parent. Despite the pronounced divergence between males, females from these subspecies exhibit similar crossover rates, raising the question of how recombination is genetically controlled in this sex. Here, I analyze publicly available genotype data from early generations of the Collaborative Cross, an eight-way panel of recombinant inbred strains, to estimate crossover frequencies in female mice with sex-chromosome genotypes of diverse subspecific origins. Consistent with the transgressive influence of the X chromosome in males, I show that females inheriting an M. m. castaneus X possess higher average crossover rates than females lacking the M. m. castaneus X chromosome. The differential inheritance of the X chromosome in males and females provides a simple genetic explanation for sex-limited evolution of this trait. Further, the presence of X-linked and autosomal crossover rate modifiers with antagonistic effects hints at an underlying genetic conflict fueled by selection for distinct crossover rate optima in males and females. Copyright © 2017 by the Genetics Society of America.

Clinical trial of modulatory effects of oxytocin treatment on higher-order social cognition in autism spectrum disorder: a randomized, placebo-controlled, double-blind and crossover trial.

PubMed

Preckel, Katrin; Kanske, Philipp; Singer, Tania; Paulus, Frieder M; Krach, Sören

2016-09-21

Autism spectrum disorders are neurodevelopmental conditions with severe impairments in social communication and interaction. Pioneering research suggests that oxytocin can improve motivation, cognition and attention to social cues in patients with autism spectrum disorder. The aim of this clinical trial is to characterize basic mechanisms of action of acute oxytocin treatment on neural levels and to relate these to changes in different levels of socio-affective and -cognitive functioning. This clinical study is a randomized, double-blind, cross-over, placebo-controlled, multicenter functional magnetic resonance imaging study with two arms. A sample of 102 male autism spectrum disorder patients, diagnosed with Infantile Autistic Disorder (F84.0 according to ICD-10), Asperger Syndrome (F84.5 according to ICD-10), or Atypical Autism (F84.1 according to ICD-10) will be recruited and will receive oxytocin and placebo nasal spray on two different days. Autism spectrum disorder patients will be randomized to determine who receives oxytocin on the first and who on the second visit. Healthy control participants will be recruited and case-control matched to the autism spectrum disorder patients. The primary outcome will be neural network activity, measured with functional magnetic resonance imaging while participants perform socio-affective and -cognitive tasks. Behavioral markers such as theory of mind accuracy ratings and response times will be assessed as secondary outcomes in addition to physiological measures such as skin conductance. Trait measures for alexithymia, interpersonal reactivity, and social anxiety will also be evaluated. Additionally, we will analyze the effect of oxytocin receptor gene variants and how these potentially influence the primary and secondary outcome measures. Functional magnetic resonance imaging assessments will take place at two time points which will be scheduled at least two weeks apart to ensure a sufficient wash-out time after oxytocin treatment. The study has been approved by an ethical review board and the competent authority. Revealing the mechanisms of acute oxytocin administration, especially on the socio-affective and -cognitive domains at hand, will be a further step towards novel therapeutic interventions regarding autism. German Clinical Trial Register DRKS00010053 . The trial was registered on the 8 th of April 2016.

A compartmentalized signaling network mediates crossover control in meiosis

PubMed Central

Zhang, Liangyu; Köhler, Simone; Rillo-Bohn, Regina

2018-01-01

During meiosis, each pair of homologous chromosomes typically undergoes at least one crossover (crossover assurance), but these exchanges are strictly limited in number and widely spaced along chromosomes (crossover interference). The molecular basis for this chromosome-wide regulation remains mysterious. A family of meiotic RING finger proteins has been implicated in crossover regulation across eukaryotes. Caenorhabditis elegans expresses four such proteins, of which one (ZHP-3) is known to be required for crossovers. Here we investigate the functions of ZHP-1, ZHP-2, and ZHP-4. We find that all four ZHP proteins, like their homologs in other species, localize to the synaptonemal complex, an unusual, liquid crystalline compartment that assembles between paired homologs. Together they promote accumulation of pro-crossover factors, including ZHP-3 and ZHP-4, at a single recombination intermediate, thereby patterning exchanges along paired chromosomes. These proteins also act at the top of a hierarchical, symmetry-breaking process that enables crossovers to direct accurate chromosome segregation. PMID:29521627

Acetic acid-guided biopsies in Barrett’s surveillance for neoplasia detection versus non-targeted biopsies (Seattle protocol): A feasibility study for a randomized tandem endoscopy trial. The ABBA study

PubMed Central

Chedgy, Fergus; Fogg, Carole; Kandiah, Kesavan; Barr, Hugh; Higgins, Bernard; McCord, Mimi; Dewey, Ann; De Caestecker, John; Gadeke, Lisa; Stokes, Clive; Poller, David; Longcroft-Wheaton, Gaius; Bhandari, Pradeep

2018-01-01

Background and study aims  Barrett’s esophagus is a potentially pre-cancerous condition, affecting 375,000 people in the UK. Patients receive a 2-yearly endoscopy to detect cancerous changes, as early detection and treatment results in better outcomes. Current treatment requires random mapping biopsies along the length of Barrett’s, in addition to biopsy of visible abnormalities. As only 13 % of pre-cancerous changes appear as visible nodules or abnormalities, areas of dysplasia are often missed. Acetic acid chromoendoscopy (AAC) has been shown to improve detection of pre-cancerous and cancerous tissue in observational studies, but no randomized controlled trials (RCTs) have been performed to date. Patients and methods  A “tandem” endoscopy cross-over design. Participants will be randomized to endoscopy using mapping biopsies or AAC, in which dilute acetic acid is sprayed onto the surface of the esophagus, highlighting tissue through an whitening reaction and enhancing visibility of areas with cellular changes for biopsy. After 4 to 10 weeks, participants will undergo a repeat endoscopy, using the second method. Rates of recruitment and retention will be assessed, in addition to the estimated dysplasia detection rate, effectiveness of the endoscopist training program, and rates of adverse events (AEs). Qualitative interviews will explore participant and endoscopist acceptability of study design and delivery, and the acceptability of switching endoscopic techniques for Barrett's surveillance. Results  Endoscopists’ ability to diagnose dysplasia in Barrett’s esophagus can be improved. AAC may offer a simple, universally applicable, easily-acquired technique to improve detection, affording patients earlier diagnosis and treatment, reducing endoscopy time and pathology costs. The ABBA study will determine whether a crossover “tandem” endoscopy design is feasible and acceptable to patients and clinicians and gather outcome data to power a definitive trial. PMID:29340297

An investigation of the safety and pharmacokinetics of the novel TRPV1 antagonist XEN-D0501 in healthy subjects

PubMed Central

Round, Patrick; Priestley, Anthony; Robinson, Jan

2011-01-01

AIMS XEN-D0501, a novel TRPV1 antagonist, is being developed to treat overactive bladder. This study investigated the safety and pharmacokinetics of repeat-dose XEN-D0501 in healthy subjects. METHODS The study was conducted in two parts. Part 1 was a double-blind, randomized, placebo-controlled, two-way crossover study in three cohorts of 12 young male subjects. Each subject received XEN-D0501 and placebo (in random order) twice daily for 13 days, with a final single dose on day 14. Doses of 1, 2.5 and 5 mg XEN-D0501 were investigated. Part 2 was an open-label, randomized, two-way crossover study in male and female subjects (45 to 65 years). Subjects received single doses of 5 mg XEN-D0501 under fasted and fed conditions in random order. Blood sampling and safety assessments were conducted throughout the study. RESULTS XEN-D0501 was rapidly absorbed (tmax generally 0.5–4 h post dose). XEN-D0501 exposure increased less than proportionally to dose over the range studied and exhibited minimal accumulation with twice daily dosing. Food had no clinically relevant effects on the pharmacokinetics of XEN-D0501. There were no severe or serious adverse events and all doses were well tolerated. A dose-related increase in body temperature was seen with XEN-D0501 which attenuated over time. Differences from placebo in mean maximum core body temperatures were 0.22°C, 0.5°C and 0.74°C following 1 mg, 2.5 mg and 5 mg twice daily XEN-D0501. The observed increase in body temperature was not considered to be of clinical concern. CONCLUSIONS XEN-D0501 appeared safe and well tolerated at doses up to 5 mg twice daily for 14 days in healthy subjects. PMID:21676011

A randomized, double-blind, placebo-controlled, crossover trial of mifepristone in Gulf War veterans with chronic multisymptom illness.

PubMed

Golier, Julia A; Caramanica, Kimberly; Michaelides, Andreas C; Makotkine, Iouri; Schmeidler, James; Harvey, Philip D; Yehuda, Rachel

2016-02-01

No pharmacological treatments have been demonstrated to effectively treat chronic multisymptom illness (CMI) in Gulf War veterans (GWV). This study assessed the effect of the glucocorticoid receptor antagonist mifepristone in GWV with CMI. A randomized, double-blind, cross-over trial of mifepristone, with two six-week treatment phases separated by a one-month washout period, was conducted at a Veterans Affairs (VA) hospital between 2008 and 2011. Participants were randomized to receive either 200mg of mifepristone per day or matched placebo first. The primary clinical outcome measure was change in self-reported physical health. Neurocognitive functioning and self-reported measures of depression, PTSD, and fatigue were secondary outcomes. Sixty-five participants enrolled, of whom 36 were randomized and 32 (mean age, 49.1 (7.2) years) completed the study. Physical and mental health status and neurocognitive functioning were poor at baseline. Mifepristone treatment was not associated with improvement in self-reported physical health (p=0.838) or in other self-reported measures of mental health. Mifepristone treatment was significantly associated with improvements in verbal learning (p=0.008, d=0.508), in the absence of improvement in other cognitive measures (working memory (p=0.914), visual learning (p=0.643) and a global composite measure (p=0.937). Baseline morning cortisol levels and lysozyme IC50-DEX, a measure of peripheral glucocorticoid sensitivity, displayed a significant relationship with endpoint verbal learning scores (p=0.012 and p=0.007, respectively). The magnitude of cortisol change during treatment mediated the improvement in verbal learning. This study was negative for the primary and secondary clinical outcomes. However, the data suggest a moderate dose of mifepristone may have circumscribed cognitive-enhancing effects in CMI. Further study is warranted to determine whether and through which mechanisms mifepristone treatment can yield clinically meaningful improvement in cognitive function in CMI or other neuropsychiatric conditions associated with HPA axis dysregulation. Published by Elsevier Ltd.

The sustained effect (12 months) of a single-dose vectored thermal pulsation procedure for meibomian gland dysfunction and evaporative dry eye

PubMed Central

Blackie, Caroline A; Coleman, Christy A; Holland, Edward J

2016-01-01

Purpose To evaluate the sustained effect (up to 1 year) of a single, 12-minute vectored thermal pulsation (VTP) treatment in improving meibomian gland function and dry eye symptoms in patients with meibomian gland dysfunction and evaporative dry eye. Methods The prospective, multicenter, open-label clinical trial included 200 subjects (400 eyes) who were randomized to a single VTP treatment (treatment group) or twice-daily, 3-month, conventional warm compress and eyelid hygiene therapy (control group). Control group subjects received crossover VTP treatment at 3 months (crossover group). Effectiveness measures of meibomian gland secretion (MGS) and dry eye symptoms were evaluated at baseline and 1, 3, 6, 9, and 12 months. Subjects with inadequate symptom relief could receive additional meibomian gland dysfunction therapy after 3 (treatment group) and 6 months (crossover group). Results At 3 months, the treatment group had greater mean improvement in MGS (P<0.0001) and dry eye symptoms (P=0.0068), compared to controls. At 12 months, 86% of the treatment group had received only one VTP treatment, and sustained a mean improvement in MGS from 6.4±3.7 (baseline) to 17.3±9.1 (P<0.0001) and dry eye symptoms from 44.1±20.4 to 21.6±21.3 (P<0.0001); 89% of the crossover group had received only one VTP treatment with sustained mean improvement in MGS from 6.3±3.6 to 18.4±11.1 (P<0.0001) and dry eye symptoms from 49.1±21.0 to 24.0±23.2 (P<0.0001). Greater mean improvement in MGS was associated with less severe baseline MGS (P=0.0017) and shorter duration of time between diagnosis and treatment (P=0.0378). Conclusion A single VTP treatment can deliver a sustained mean improvement in meibomian gland function and mean reduction in dry eye symptoms, over 12 months. A single VTP treatment provides significantly greater mean improvement in meibomian gland function and dry eye symptoms as compared to a conventional, twice-daily, 3-month regimen. Early VTP intervention for meibomian gland dysfunction is associated with improved treatment outcomes. PMID:27555745

The impact of a multidisciplinary self-care management program on quality of life, self-care, adherence to anti-hypertensive therapy, glycemic control, and renal function in diabetic kidney disease: A Cross-over Study Protocol.

PubMed

Helou, Nancy; Talhouedec, Dominique; Shaha, Maya; Zanchi, Anne

2016-07-19

Diabetic kidney disease, a global health issue, remains associated with high morbidity and mortality. Previous research has shown that multidisciplinary management of chronic disease can improve patient outcomes. The effect of multidisciplinary self-care management on quality of life and renal function of patients with diabetic kidney disease has not yet been well established. The aim of this study is to evaluate the impact of a multidisciplinary self-care management program on quality of life, self-care behavior, adherence to anti-hypertensive treatment, glycemic control, and renal function of adults with diabetic kidney disease. A uniform balanced cross-over design is used, with the objective to recruit 40 adult participants with diabetic kidney disease, from public and private out-patient settings in French speaking Switzerland. Participants are randomized in equal number into four study arms. Each participant receives usual care alternating with the multidisciplinary self- care management program. Each treatment period lasts three months and is repeated twice at different time intervals over 12 months depending on the cross-over arm. The multidisciplinary self-care management program is led by an advanced practice nurse and adds nursing and dietary consultations and follow-ups, to the habitual management provided by the general practitioner, the nephrologist and the diabetologist. Data is collected every three months for 12 months. Quality of life is measured using the Audit of Diabetes-Dependent Quality of Life scale, patient self-care behavior is assessed using the Revised Summary of Diabetes Self-Care Activities, and adherence to anti-hypertensive therapy is evaluated using the Medication Events Monitoring System. Blood glucose control is measured by the glycated hemoglobin levels and renal function by serum creatinine, estimated glomerular filtration rate and urinary albumin/creatinine ratio. Data will be analyzed using STATA version 14. The cross-over design will elucidate the responses of individual participant to each treatment, and will allow us to better evaluate the use of such a design in clinical settings and behavioral studies. This study also explores the impact of a theory-based nursing practice and its implementation into a multidisciplinary context. ClinicalTrials.gov identifier: NCT01967901 , registered on the 18th of October 2013.

A randomized controlled trial oftransfusion-related acute lung injury: is plasma from multiparous blood donors dangerous?

PubMed

Palfi, M; Berg, S; Ernerudh, J; Berlin, G

2001-03-01

Transfusion-related acute lung injury (TRALI) and other posttransfusion reactions may be caused by granulocyte and/or HLA antibodies, which are often present in blood from multiparous donors. The purpose of this study was to compare the effects of plasma from multiparous donors with those of plasma from donors with no history of transfusion or pregnancy (control plasma) in a prospective, randomized, double-blind, crossover study. Intensive care patients, judged to need at least 2 units of plasma, were randomly assigned to receive a unit of control plasma and, 4 hours later, a plasma unit from a multiparous donor (> or = 3 live births) or to receive the plasma units in opposite order. The patients were closely monitored, and body temperature, blood pressure, and heart rate were recorded. Blood samples for analysis of blood gases, TNFalpha, IL-1 receptor antagonist, soluble E selectin, and C3d complement factor were collected at least on four occasions (before and after the transfusion of each unit). Transfusion of plasma from multiparous donors was associated with significantly lower oxygen saturation and higher TNFalpha concentrations than transfusion of control plasma. The mean arterial pressure increased significantly after the transfusion of control plasma, whereas plasma from multiparous donors had no effect on it. Five posttransfusion reactions were observed in 100 patients, in four cases after the transfusion of plasma from multiparous donors. Plasma from multiparous blood donors may impair pulmonary function in intensive care unit patients.

Effect of paricalcitol on renin and albuminuria in non-diabetic stage III-IV chronic kidney disease: a randomized placebo-controlled trial

PubMed Central

2013-01-01

Background Vitamin D receptor activators reduce albuminuria, and may improve survival in chronic kidney disease (CKD). Animal studies suggest that these pleiotropic effects of vitamin D may be mediated by suppression of renin. However, randomized trials in humans have yet to establish this relationship. Methods In a randomized, placebo-controlled, double-blinded crossover study, the effect of oral paricalcitol (2 μg/day) was investigated in 26 patients with non-diabetic, albuminuric stage III-IV CKD. After treatment, plasma concentrations of renin (PRC), angiotensin II (AngII) and aldosterone (Aldo) were measured. GFR was determined by 51Cr-EDTA clearance. Assessment of renal NO dependency was performed by infusion of NG-monomethyl-L-arginine (L-NMMA). Albumin excretion rate (AER) was analyzed in 24-h urine and during 51Cr-EDTA clearance. Results Paricalcitol did not alter plasma levels of renin, AngII, Aldo, or urinary excretion of sodium and potassium. A modest reduction of borderline significance was observed in AER, and paricalcitol abrogated the albuminuric response to L-NMMA. Conclusions In this randomized, placebo-controlled trial paricalcitol only marginally decreased AER and did not alter circulating levels of renin, AngII or Aldo. The abrogation of the rise in albumin excretion by paricalcitol during NOS blockade may indicate that favourable modulation of renal NO dependency could be involved in mediating reno-protection and survival benefits in CKD. Trial registration ClinicalTrials.gov identifier: NCT01136564 PMID:23889806

Efficacy, safety and tolerability of an orally administered cannabis extract in the treatment of spasticity in patients with multiple sclerosis: a randomized, double-blind, placebo-controlled, crossover study.

PubMed

Vaney, C; Heinzel-Gutenbrunner, M; Jobin, P; Tschopp, F; Gattlen, B; Hagen, U; Schnelle, M; Reif, M

2004-08-01

Cannabis may alleviate some symptoms associated with multiple sclerosis (MS). This study investigated the effect of an orally administered standardized Cannabis sativa plant extract in MS patients with poorly controlled spasticity. During their inpatient rehabilitation programme, 57 patients were enrolled in a prospective, randomized, double-blind, placebo-controlled crossover study of cannabis-extract capsules standardized to 2.5 mg tetrahydrocannabinol (THC) and 0.9 mg cannabidiol (CBD) each. Patients in group A started with a drug escalation phase from 15 to maximally 30 mg THC by 5 mg per day if well tolerated, being on active medication for 14 days before starting placebo. Patients in group B started with placebo for seven days, crossed to the active period (14 days) and closed with a three-day placebo period (active drug dose escalation and placebo sham escalation as in group A). Measures used included daily self-report of spasm frequency and symptoms, Ashworth Scale, Rivermead Mobility Index, 10-m timed walk, nine-hole peg test, paced auditory serial addition test (PASAT), and the digit span test. In the 50 patients included into the intention-to-treat analysis set, there were no statistically significant differences associated with active treatment compared to placebo, but trends in favour of active treatment were seen for spasm frequency, mobility and getting to sleep. In the 37 patients (per-protocol set) who received at least 90% of their prescribed dose, improvements in spasm frequency (P = 0.013) and mobility after excluding a patient who fell and stopped walking were seen (P = 0.01). Minor adverse events were slightly more frequent and severe during active treatment, and toxicity symptoms, which were generally mild, were more pronounced in the active phase. A standardized Cannabis sativa plant extract might lower spasm frequency and increase mobility with tolerable side effects in MS patients with persistent spasticity not responding to other drugs.

Randomized controlled trial of transoral incisionless fundoplication vs. proton pump inhibitors for treatment of gastroesophageal reflux disease.

PubMed

Witteman, Bart P L; Conchillo, Jose M; Rinsma, Nicolaas F; Betzel, Bark; Peeters, Andrea; Koek, Ger H; Stassen, Laurents P S; Bouvy, Nicole D

2015-04-01

Transoral incisionless fundoplication (TIF) was developed in an attempt to create a minimally invasive endoscopic procedure that mimics antireflux surgery. The objective of this trial was to evaluate effectiveness of TIF compared with proton pump inhibition in a population consisting of gastroesophageal reflux disease (GERD) patients controlled with proton pump inhibitors (PPIs) who opted for an endoscopic intervention over lifelong drug dependence. Patients with chronic GERD were randomized (2:1) for TIF or continuation of PPI therapy. American Society of Anesthesiologists >2, body mass index >35 kg/m(2), hiatal hernia >2 cm, and esophageal motility disorders were exclusion criteria. Primary outcome measure was GERD-related quality of life. Secondary outcome measures were esophageal acid exposure, number of reflux episodes, PPI usage, appearance of the gastroesophageal valve, and healing of reflux esophagitis. Crossover for the PPI group was allowed after 6 months. A total of 60 patients (TIF n=40, PPI n=20, mean body mass index 26 kg/m(2), 37 male) were included. At 6 months, GERD symptoms were more improved in the TIF group compared with the PPI group (P<0.001), with a similar improvement of distal esophageal acid exposure (P=0.228) compared with baseline. The pH normalization for TIF group and PPI group was 50% and 63%, respectively. All patients allocated for PPI treatment opted for crossover. At 12 months, quality of life remained improved after TIF compared with baseline (P<0.05), but no improvement in esophageal acid exposure compared with baseline was found (P=0.171) and normalization of pH was accomplished in only 29% in conjunction with deteriorated valve appearances at endoscopy and resumption of PPIs in 61%. Although TIF resulted in an improved GERD-related quality of life and produced a short-term improvement of the antireflux barrier in a selected group of GERD patients, no long-term objective reflux control was achieved.

Development of a cross-over randomized trial method to determine the acceptability and safety of novel ready-to-use therapeutic foods.

PubMed

Dibari, Filippo; Bahwere, Paluku; Huerga, Helena; Irena, Abel Hailu; Owino, Victor; Collins, Steve; Seal, Andrew

2013-01-01

To develop a method for determining the acceptability and safety of ready-to-use therapeutic foods (RUTF) before clinical trialing. Acceptability was defined using a combination of three consumption, nine safety, and six preference criteria. These were used to compare a soy/maize/sorghum RUTF (SMS-RUTFh), designed for the rehabilitation of human immunodeficiency virus/tuberculosis (HIV/TB) wasted adults, with a peanut-butter/milk-powder paste (P-RUTF; brand: Plumpy'nut) designed for pediatric treatment. A cross-over, randomized, controlled trial was conducted in Kenya. Ten days of repeated measures of product intake by 41 HIV/TB patients, >18 y old, body mass index (BMI) 18-24 kg · m(-2), 250 g were offered daily under direct observation as a replacement lunch meal. Consumption, comorbidity, and preferences were recorded. The study arms had similar age, sex, marital status, initial BMI, and middle upper-arm circumference. No carryover effect or serious adverse events were found. SMS-RUTFh energy intake was not statistically different from the control, when adjusted for BMI on day 1, and the presence of throat sores. General preference, taste, and sweetness scores were higher for SMS-RUTFh compared to the control (P < 0.05). Most consumption, safety, and preference criteria for SMS-RUTFh were satisfied except for the average number of days of nausea (0.16 versus 0.09 d) and vomiting (0.04 versus 0.02 d), which occurred with a higher frequency (P < 0.05). SMS-RUTFh appears to be acceptable and can be safely clinically trialed, if close monitoring of vomiting and nausea is included. The method reported here is a useful and feasible approach for testing the acceptability of ready-to-use foods in low income countries. Copyright © 2013 Elsevier Inc. All rights reserved.

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

PubMed

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

2016-05-01

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

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.

Laboratory- and community-based health outcomes in people with transtibial amputation using crossover and energy-storing prosthetic feet: A randomized crossover trial

PubMed Central

Morgan, Sara J.; McDonald, Cody L.; Halsne, Elizabeth G.; Cheever, Sarah M.; Salem, Rana; Kramer, Patricia A.

2018-01-01

Contemporary prosthetic feet are generally optimized for either daily or high-level activities. Prosthesis users, therefore, often require multiple prostheses to participate in activities that span a range of mobility. Crossover feet (XF) are designed to increase the range of activities that can be performed with a single prosthesis. However, little evidence exists to guide clinical prescription of XF relative to traditional energy storing feet (ESF). The objective of this study was to assess the effects of XF and ESF on health outcomes in people with transtibial amputation. A randomized crossover study was conducted to assess changes in laboratory-based (endurance, perceived exertion, walking performance) and community-based (step activity and self-reported mobility, fatigue, balance confidence, activity restrictions, and satisfaction) outcomes. Twenty-seven participants were fit with XF and ESF prostheses with standardized sockets, interfaces, and suspensions. Participants were not blinded to the intervention, and wore each prosthesis for one month while their steps were counted with an activity monitor. After each accommodation period, participants returned for data collection. Endurance and perceived exertion were measured with the Six-Minute Walk Test and Borg-CR100, respectively. Walking performance was measured using an electronic walkway. Self-reported mobility, fatigue, balance confidence, activity restrictions, and satisfaction were measured with survey instruments. Participants also reported foot preferences upon conclusion of the study. Differences between feet were assessed with a crossover analysis. While using XF, users experienced improvements in most community-based outcomes, including mobility (p = .001), fatigue (p = .001), balance confidence (p = .005), activity restrictions (p = .002), and functional satisfaction (p < .001). Participants also exhibited longer sound side steps in XF compared to ESF (p < .001). Most participants (89%) reported an overall preference for XF; others (11%) reported no preference. Results indicate that XF may be a promising alternative to ESF for people with transtibial amputation who engage in a range of mobility activities. Trial registration: ClinicalTrials.gov NCT02440711 PMID:29414988

Dietary Effects on Cognition and Pilots' Flight Performance.

PubMed

Lindseth, Glenda N; Lindseth, Paul D; Jensen, Warren C; Petros, Thomas V; Helland, Brian D; Fossum, Debra L

2011-01-01

The purpose of this study was to investigate the effects of diet on cognition and flight performance of 45 pilots. Based on a theory of self-care, this clinical study used a repeated-measure, counterbalanced crossover design. Pilots were randomly rotated through 4-day high-carbohydrate, high-protein, high-fat, and control diets. Cognitive flight performance was evaluated using a GAT-2 full-motion flight simulator. The Sternberg short-term memory test and Vandenberg's mental rotation test were used to validate cognitive flight test results. Pilots consuming a high-protein diet had significantly poorer ( p < .05) overall flight performance scores than pilots consuming high-fat and high-carbohydrate diets.

The effect of fish oil supplements on blood pressure.

PubMed Central

Lofgren, R P; Wilt, T J; Nichol, K L; Crespin, L; Pluhar, R; Eckfeldt, J

1993-01-01

We conducted a double-blind, placebo-controlled crossover study to determine the effects of fish oil supplementation on blood pressure in middle-aged men. Subjects were randomly assigned to consume either 20 g of fish oil or safflower oil for 12 weeks and then consume the other oil for an additional 12 weeks after a 4-week washout period. We found no significant changes from the pretreatment value in systolic or diastolic blood pressure with the use of fish oil supplements. In addition, there were no significant differences in the posttreatment blood pressures comparing the fish and safflower oil phases of the study. PMID:8427339

Randomized Prospective Study of Endoscopic Rubber Band Ligation Compared With Bipolar Coagulation for Chronically Bleeding Internal Hemorrhoids

PubMed Central

Jutabha, Rome; Jensen, Dennis M.; Chavalitdhamrong, Disaya

2013-01-01

OBJECTIVES: Our purpose was to compare the efficacy, complications, success rate, recurrence rate at 1 year, and crossovers of rubber band ligation (RBL) with those of bipolar electrocoagulation (BPEC) treatment for chronically bleeding internal hemorrhoids. METHODS: A total of 45 patients of mean age 51.5 years, who had rectal bleeding from grade II or III hemorrhoids and in whom intensive medical therapy failed, were randomized in a prospective study comparing RBL with BPEC. Treatment failure was predefined as continued bleeding, occurrence of a major complication, or failure to reduce the size of all internal hemorrhoidal segments to grade I in ≤ 3 treatments. Patients were followed up for 1 year. RESULTS: With similar patients, rectal bleeding and other symptoms were controlled with significantly fewer treatments of RBL than of BPEC (2.3±0.2 vs. 3.8±0.4, P < 0.05), and RBL had a significantly higher success rate (92% vs. 62%, P< 0.05). RBL had more cases of severe pain during treatment (8% vs. 0%, P> 0.05), but significantly fewer failures and crossovers (8% vs. 38%). Symptomatic recurrence at 1 year was 10% RBL and 15% BPEC. CONCLUSIONS: For patients with chronically bleeding grade II or III internal hemorrhoids that are unresponsive to medical therapy, safety and complication rates of banding and BPEC were similar. The success rate was significantly higher with RBL than with BPEC. Symptom recurrence rates at 1 year were similar. PMID:19513028

Is the Generally Held View That Intravenous Dihydroergotamine Is Effective in Migraine Based on Wrong "General Consensus" of One Trial? A Critical Review of the Trial and Subsequent Quotations.

PubMed

Bekan, Goran; Tfelt-Hansen, Peer

2016-10-01

The claim that parenteral dihydroergotamine (DHE) is effective in migraine is based on one randomized, placebo-controlled, crossover trial from 1986. The aim of this review was to critically evaluate the original article. It was also found to be of interest to review quotes concerning the results in the more than 100 articles subsequently referring to the article. The correctness of the stated effect of intravenous DHE in the randomized clinical trial (RCT) was first critically evaluated. Then, Google Scholar was searched for references to the article and these references were classified as to whether they judged the reported RCT as positive or negative. The design of the RCT, with a crossover within one migraine attack, only allows evaluation of the results for the first period and the effect of DHE and placebo were quite comparable. About 151 references were found for the article in Google scholar. Among the 95 articles with a judgment on the efficacy of intravenous DHE in the RCT, 90 stated that DHE was effective or likely effective whereas only 5 articles stated that DHE was ineffective. Despite a "negative" RCT, authors of subsequent articles on the efficacy of parenteral DHE overwhelmingly reported this RCT as "positive." This is probably due to the fact that the authors concluded in the abstract that DHE is effective, and to a kind of "wrong general consensus." © 2016 American Headache Society.

Randomized, blinded, placebo- and positive-controlled crossover study to determine the effect of multiple doses of apixaban on the QTc interval.

PubMed

Frost, Charles; Nepal, Sunil; Byon, Wonkyung; Moore, Kenneth; Reeves, Richard A; Boyd, Rebecca; LaCreta, Frank

2015-05-01

Apixaban is an oral, direct factor Xa inhibitor indicated for the prevention and treatment of thromboembolic disease. This randomized, blinded, 4-way crossover study investigated the potential effect of apixaban on the QTc interval. Forty healthy subjects (39 completers) each received 3 days of the following treatments: blinded apixaban 10 mg once daily (QD), 50 mg QD (supratherapeutic), matched apixaban placebo QD, and a single dose of open-label moxifloxacin 400 mg on Day 3, preceded by 2 days of placebo QD. Triplicate electrocardiograms obtained over 24 hours on Days -1 (baseline) and 3 were read by a blinded third party. The mean placebo-adjusted, time-matched, Fridericia-corrected change from baseline QTc (ΔΔQTcF) for apixaban and moxifloxacin was estimated at each time point. The maximum ΔΔQTcF was 1.51 milliseconds (one-sided upper 95% confidence interval [CI] 3.71 milliseconds) after apixaban 50 mg QD, 1.36 milliseconds (one-sided upper 95%CI 3.54 milliseconds) after apixaban 10 mg QD, and 10.21 milliseconds (lower 95%CI 8.07 milliseconds) after moxifloxacin. Concentration-response analysis suggested no evidence of a positive relationship between apixaban concentration and ΔQTcF. Apixaban doses up to 50 mg QD for 3 days were well tolerated and did not prolong the QTc interval in healthy subjects. © 2015, The American College of Clinical Pharmacology.

Effect of Sugar-Free and Regular Toothpaste on Salivary Glucose and pH among Type 2 Diabetes- A Randomized Crossover Trial.

PubMed

Kapadia, Junaid; Dodamani, Arun; Baviskar, Priya; Karibasappa, G N; Pathak, Parag; Bezalwar, Abhishek

2017-07-01

Diabetes is one of the most prevalent diseases of mankind having general as well as oral health manifestations. Also, there is an increase of salivary glucose level in diabetic, inducing saccharolytic bacteria in saliva which can have adverse effects on oral tissue. To assess and compare the effect of sugar-free toothpaste on salivary glucose and pH among Type 2 diabetic and non-diabetic individuals. A randomized controlled-crossover study was carried out on 30 Type 2 diabetic (Group A) and 45 non-diabetic (Group B) subjects. In first half of study, subjects in Group A and Group B were intervened with sugar-free and regular toothpaste respectively. Salivary glucose and pH was assessed before and after brushing at interval of one week for a period of four weeks. In second half, toothpastes were switched over between the groups, after sufficient washout period. Salivary glucose and pH were assessed again in the same manner for both the groups. The data was subjected to paired t-test and unpaired t-test for intragroup and intergroup comparison respectively. Salivary glucose level was significantly reduced and salivary pH was increased significantly (p<0.001) in both groups with sugar free toothpaste when compared to regular toothpaste. Sugar free toothpaste showed beneficial effect on salivary glucose level and salivary pH level on diabetes and non-diabetes population.

Antispasmodic/analgesic associations in primary dysmenorrhea double-blind crossover placebo-controlled clinical trial.

PubMed

de los Santos, A R; Zmijanovich, R; Pérez Macri, S; Martí, M L; Di Girolamo, G

2001-01-01

We studied 125 patients with primary dysmenorrhea in a prospective randomized double-blind crossover study. After an admission pretreatment period without medication, the patients completed three consecutive randomized treatment phases with lysine clonixinate 125 mg plus propinox 10 mg or paracetamol 500 mg plus hyoscine N-butylbromide 10 mg or placebo, according to a fixed-dose schedule of 1 tablet every 6 h, 3 days before onset of menses and for 5 days thereafter. Changes in menstrual pain intensity and duration, amount of bleeding measured according to the number of daily pads used and concomitant symptoms were assessed on the fifth day of each cycle. Every night, the patients recorded the average intensity of menstrual pain during the first 4 days of menstruation in a diary The follow-up visit carried out at day 5 showed significant reduction in pain intensity with both active treatments vs. the other two phases: baseline: 2.72 +/- 0.61; placebo: 1.85 +/- 0.87; lysine clonixinate plus propinox 1.36 +/- 0.81, and paracetamol plus hyosine N-butylbromide: 1.45 +/- 0.87. The patients' diaries showed increasingly lower pain intensities starting from day 1 with the three treatments. Active treatments revealed significantly higher analgesic efficacy from the outset compared with baseline and placebo; however, only the lysine clonixinate plus propinox combination reached a statistically significant difference by days 3 and 4. No changes in duration or intensity of menstrual bleeding or in the incidence of adverse effects were observed during the four study periods.

Intranasal Pharmacokinetics of Morphine ARER, a Novel Abuse-Deterrent Formulation: Results from a Randomized, Double-Blind, Four-Way Crossover Study in Nondependent, Opioid-Experienced Subjects

PubMed Central

Pantaleon, Carmela; Iverson, Matthew; Smith, Michael D.; Kinzler, Eric R.; Aigner, Stefan

2018-01-01

Objective To investigate the pharmacokinetics (PK) of Morphine ARER, an extended-release (ER), abuse-deterrent formulation of morphine sulfate after oral and intranasal administration. Methods This randomized, double-blind, double-dummy, placebo-controlled, four-way crossover study assessed the PK of morphine and its active metabolite, M6G, from crushed intranasal Morphine ARER and intact oral Morphine ARER compared with crushed intranasal ER morphine following administration to nondependent, recreational opioid users. The correlation between morphine PK and the pharmacodynamic parameter of drug liking, a measure of abuse potential, was also evaluated. Results Mean maximum observed plasma concentration (Cmax) for morphine was lower with crushed intranasal Morphine ARER (26.2 ng/mL) and intact oral Morphine ARER (18.6 ng/mL), compared with crushed intranasal ER morphine (49.5 ng/mL). The time to Cmax (Tmax) was the same for intact oral and crushed intranasal Morphine ARER (1.6 hours) and longer for crushed intranasal morphine ER (1.1 hours). Higher mean maximum morphine Cmax, Tmax, and abuse quotient (Cmax/Tmax) were positively correlated with maximum effect for drug liking (R2 ≥ 0.9795). Conclusion These data suggest that Morphine ARER maintains its ER profile despite physical manipulation and intranasal administration, which may be predictive of a lower intranasal abuse potential compared with ER morphine.

A Randomized, Two-Way Crossover Study to Evaluate the Pharmacokinetics of Caffeine Delivered Using Caffeinated Chewing Gum Versus a Marketed Caffeinated Beverage in Healthy Adult Volunteers.

PubMed

Sadek, Paul; Pan, Xiao; Shepherd, Phil; Malandain, Elise; Carney, John; Coleman, Hugh

2017-12-01

Background: This study was conducted to compare the pharmacokinetics of caffeine delivered using caffeinated chewing gum to that delivered using a marketed caffeinated beverage (instant coffee) in 16 healthy adult volunteers. Materials and Methods: This was a controlled open-label, randomized, two-period crossover study. Caffeinated chewing gum and a serving of instant coffee, each containing ∼50 mg caffeine, were administered with blood samples collected before and up to 24 hours after administration starts. Plasma caffeine levels were analyzed using validated liquid chromatography coupled with tandem mass spectrometry methodology. Results: There were no statistical differences between the two caffeine products in t max ( p  = 0.3308) and k a ( p  = 0.3894). Although formulated at ∼50 mg caffeine each, mean dose released from chewing gum was ∼18% less than beverage. Dose-normalized area under the concentration-time curve (AUC) 0-t , AUC 0-∞ , and C max was similar between products. Although the criteria were not set a priori and the study was not powered for concluding bioequivalence, the 90% confidence intervals fell within the bioequivalence limit of 80% to 125%. Conclusions: Existing scientific literature on caffeine, based mostly on data from caffeinated beverages, can be leveraged to support the safety of caffeine delivered by chewing gum and current maximum safe caffeine dose advice should be applicable irrespective of delivery method.

Combined caffeine and bright light reduces dangerous driving in sleep-deprived healthy volunteers: a pilot cross-over randomised controlled trial.

PubMed

Hartley, S L; Barbot, F; Machou, M; Lejaille, M; Moreau, B; Vaugier, I; Lofaso, F; Quera-Salva, M A

2013-06-01

To explore the effects of caffeine and bright light therapy on simulated nighttime driving in sleep-deprived healthy volunteers. Twelve male healthy volunteers aged 20 to 50 years participated in a randomized cross-over study of simulated nighttime driving at a sleep laboratory, followed by recovery sleep with polysomnography at home. The volunteers received variable combinations of caffeine 200mg (C+), caffeine placebo (C-), bright light 10,000 lux (L+), and bright light placebo<50 lux (L-), in four sessions (C+L+, C+L-, C-L+, C-L-), in random order with a wash-out period of 7 days. Treatments were given at 1 a.m. and testing was performed at 1:30 a.m., 3 a.m., 4 a.m., and 6 a.m. Lane drifting was the primary outcome measure. Other measures were reaction times, self-rated fatigue, sleepiness and recovery sleep. Without treatment, lane drifting increased throughout the night, and objective and subjective vigilance declined. Paired comparisons showed that lane drifting was significantly worse at 6 a.m. and at 4 a.m. than at 1:30 a.m. There was a global treatment effect on lane drifting. Lane drifting at 6 a.m. was significantly decreased with C+L+ compared to C-L-. Bright light therapy combined with caffeine administered at 1 a.m. decreased lane drifting by healthy volunteers during simulated nighttime driving. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Effects of Soy Flour Fortified Bread Consumption on Cardiovascular Risk Factors According to APOE Genotypes in Overweight and Obese Adult Women: A Cross-over Randomized Controlled Clinical Trial

PubMed Central

Sharifi-Zahabi, Elham; Maracy, Mohammad R

2015-01-01

Recent studies suggest that inclusion of soy product in the diet may have favorable effects on relief of cardiovascular diseases (CVDs) and risk factors. These effects might be associated with the presence of specific polymorphism in gene. The aim of this study was to examine the effects of consumption of soy flour fortified bread on cardiovascular risk factors in overweight and obese women according to APOE genotype. In a randomized cross-over clinical trial 30 overweight and obese women received a mild weight loss diet and assigned to a regular diet and a soy bread diet, each for 6 weeks and a washout period for 20 days. Subjects in the soy bread diet were asked to replace 120 grams of their daily usual bread intake with equal amount of soy bread. No significant effects of soy bread on serum lipid, systolic blood pressure and anthropometric indices were observed compared to the regular diet (p > 0.05). For diastolic blood pressure (DBP), comparison of mean differences between two groups showed a marginally significant effect of soy bread (p = 0.06). Compared to regular diet, soy bread had a significant effect on DBP in E2 genotype group (ε2/ε2) (p = 0.03). Having ε2 allele may influences responses of CVD risk factor to soy bread consumption. However more nutrigenetic studies are required. PMID:26566517

Effects of 5-aminolevulinic acid supplementation on home-based walking training achievement in middle-aged depressive women: randomized, double-blind, crossover pilot study.

PubMed

Suzuki, Hiroshi; Masuki, Shizue; Morikawa, Akiyo; Ogawa, Yu; Kamijo, Yoshi-Ichiro; Takahashi, Kiwamu; Nakajima, Motowo; Nose, Hiroshi

2018-05-08

Depressive patients often experience difficulty in performing exercise due to physical and psychological barriers. We examined the effects of 5-aminolevulinic acid (ALA) with sodium ferrous citrate (SFC) supplementation during home-based walking training in middle-aged depressive women. Nine outpatients [53 ± 8 (SD) yr] with major depressive disorder participated in the pilot study with randomized, placebo-controlled, double-blind crossover design. They underwent two trials for 7 days, each performing interval walking training (IWT) with ALA + SFC (ALA + SFC) or placebo supplement intake (PLC) intermittently with >a 10-day washout period. For the first 6 days of each trial, exercise intensity for IWT was measured by accelerometry. Before and after each trial, subjects underwent a graded cycling test, and lactate concentration in plasma ([Lac - ] p ), oxygen consumption rate ([Formula: see text]), and carbon dioxide production rate ([Formula: see text]) were measured with depression severity by the Montgomery-Åsberg Depression Rating Scale (MADRS). We found that the increases in [Lac - ] p , [Formula: see text] and [Formula: see text] during the test were attenuated only in ALA + SFC ([before vs. after] × workload; all, P < 0.01), accompanied by increased training days, impulse, and time at fast walking during IWT (all, P < 0.05) with decreased MADRS-score (P = 0.001). Thus, ALA + SFC supplementation increased IWT achievement to improve depressive symptoms in middle-aged women.

The immunologic effects of mesalamine in treated HIV-infected individuals with incomplete CD4+ T cell recovery: a randomized crossover trial.

PubMed

Somsouk, Ma; Dunham, Richard M; Cohen, Michelle; Albright, Rebecca; Abdel-Mohsen, Mohamed; Liegler, Teri; Lifson, Jeffrey; Piatak, Michael; Gorelick, Robert; Huang, Yong; Wu, Yuaner; Hsue, Priscilla Y; Martin, Jeffrey N; Deeks, Steven G; McCune, Joseph M; Hunt, Peter W

2014-01-01

The anti-inflammatory agent, mesalamine (5-aminosalicylic acid) has been shown to decrease mucosal inflammation in ulcerative colitis. The effect of mesalamine in HIV-infected individuals, who exhibit abnormal mucosal immune activation and microbial translocation (MT), has not been established in a placebo-controlled trial. We randomized 33 HIV-infected subjects with CD4 counts <350 cells/mm3 and plasma HIV RNA levels <40 copies/ml on antiretroviral therapy (ART) to add mesalamine vs. placebo to their existing regimen for 12 weeks followed by a 12 week crossover to the other arm. Compared to placebo-treated subjects, mesalamine-treated subjects did not experience any significant change in the percent CD38+HLA-DR+ peripheral blood CD4+ and CD8+ T cells at week 12 (P = 0.38 and P = 0.63, respectively), or in the CD4+ T cell count at week 12 (P = 0.83). The percent CD38+HLA-DR+ CD4+ and CD8+ T cells also did not change significantly in rectal tissue (P = 0.86, P = 0.84, respectively). During the period of mesalamine administration, plasma sCD14, IL-6, D-dimer, and kynurenine to tryptophan ratio were not changed significantly at week 12 and were similarly unchanged at week 24. This study suggests that, at least under the conditions studied, the persistent immune activation associated with HIV infection is not impacted by the anti-inflammatory effects of mesalamine. ClinicalTrials.gov NCT01090102.

The capsaicin analog nonivamide decreases total energy intake from a standardized breakfast and enhances plasma serotonin levels in moderately overweight men after administered in an oral glucose tolerance test: a randomized, crossover trial.

PubMed

Hochkogler, Christina M; Rohm, Barbara; Hojdar, Karin; Pignitter, Marc; Widder, Sabine; Ley, Jakob P; Krammer, Gerhard E; Somoza, Veronika

2014-06-01

Since bolus administration of capsaicin has been shown to reduce appetite and ad libitum energy intake, this study elucidated the satiating effect of the less pungent capsaicin analog, nonivamide, on subjective feelings of hunger, ad libitum food intake, and satiating hormones in moderately overweight male subjects. Following a randomized, crossover design, 24 male subjects (BMI 27.5 ± 1.53 kg/m(2) ) received either 75 g glucose in 300 mL water (control treatment, CT) or the same glucose solution supplemented with 0.15 mg nonivamide (nonivamide treatment, NT). Ratings of hunger were assessed before and 2 h after each intervention by means of visual analog scales. Ad libitum energy and macronutrient intakes from a standardized breakfast 2 h postintervention were calculated. Plasma glucose, insulin, peptide YY (3-36), glucagon-like peptide 1, and serotonin were quantified in blood samples drawn before and 15, 30, 60, 90, and 120 min after each intervention. NT reduced subjective feelings of hunger and ad libitum energy and carbohydrate intakes from a standardized breakfast compared to CT. Plasma analysis revealed higher mean plasma glucagon-like peptide 1 and serotonin concentrations after NT versus CT. Addition of 0.15 mg nonivamide to a glucose solution reduced ad libitum energy intake from a standardized breakfast in moderately overweight men. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Immediate acid-suppressing effects of ranitidine hydrochloride and rabeprazole sodium following initial administration and reintroduction: A randomized, cross-over study using wireless pH monitoring capsules.

PubMed

Ono, Shouko; Kato, Mototsugu; Ono, Yuji; Imai, Aki; Yoshida, Takeshi; Shimizu, Yuichi; Asaka, Masahiro

2009-04-01

Histamine 2 receptor antagonists and proton-pump inhibitors, drugs that are widely used for the treatment of acid-related diseases, have different clinical characteristics. The objective of this study was to compare the acid-suppressing effects of ranitidine hydrochloride and those of rabeprazole sodium at the first administration and re-administration after withdrawal. The study was designed as an open-label, randomized, two-way cross-over trial. Seven Helicobacter pylori-negative healthy volunteers were enrolled in this study. Ranitidine hydrochloride (300 mg/day) or rabeprazole sodium (20 mg/day) was administered from days 1 to 7 and from days 11 to 13. The percentage of time with gastric pH < 4 and the median gastric pH were evaluated for 15 consecutive days by a Bravo capsule fixed to the stomach. On day 1, there was no significant difference between the acid-suppressing effects of the two drugs (ranitidine vs rabeprazole: not significant). Although rabeprazole sodium maintained a potent and stable effect from days 2 to 7 (ranitidine vs rabeprazole: P < 0.05), the effect of ranitidine hydrochloride was attenuated after day 4. In addition, the effect of ranitidine hydrochloride at re-administration was attenuated (days 11, 12, and 13 vs pre-administration: not significant). In view of our observations, we expect symptoms associated with gastric acidity to be more adequately controlled with rabeprazole sodium in the short term when compared to ranitidine hydrochloride.

Placebo-controlled crossover assessment of mecasermin for the treatment of Rett syndrome.

PubMed

O'Leary, Heather M; Kaufmann, Walter E; Barnes, Katherine V; Rakesh, Kshitiz; Kapur, Kush; Tarquinio, Daniel C; Cantwell, Nicole G; Roche, Katherine J; Rose, Suzanne A; Walco, Alexandra C; Bruck, Natalie M; Bazin, Grace A; Holm, Ingrid A; Alexander, Mark E; Swanson, Lindsay C; Baczewski, Lauren M; Mayor Torres, Juan M; Nelson, Charles A; Sahin, Mustafa

2018-03-01

To measure the efficacy of mecasermin (recombinant human insulin-like growth factor 1, rhIGF-1), for treating symptoms of Rett syndrome (RTT) in a pediatric population using a double-blind crossover study design. Thirty girls with classic RTT in postregression stage were randomly assigned to placebo or rhIGF-1 in treatment period 1 and crossed over to the opposite assignment for period 2 (both 20 weeks), separated by a 28-week washout period. The primary endpoints were as follows: Anxiety Depression and Mood Scale (ADAMS) Social Avoidance subscale, Rett Syndrome Behaviour Questionnaire (RSBQ) Fear/Anxiety subscale, Parent Target Symptom Visual Analog Scale (PTSVAS) top three concerns, Clinical Global Impression (CGI), Parent Global Impression (PGI), and the Kerr severity scale. Cardiorespiratory- and electroencephalography (EEG)-based biomarkers were also analyzed. There were no significant differences between randomization groups. The majority of AEs were mild to moderate, although 12 episodes of serious AEs occurred. The Kerr severity scale, ADAMS Depressed Mood subscale, Visual Analog Scale Hyperventilation, and delta average power change scores significantly increased, implying worsening of symptoms. Electroencephalography (EEG) parameters also deteriorated. A secondary analysis of subjects who were not involved in a placebo recall confirmed most of these findings. However, it also revealed improvements on a measure of stereotypic behavior and another of social communication. As in the phase 1 trial, rhIGF-1 was safe; however, the drug did not reveal significant improvement, and some parameters worsened.

Effect of Sugar-Free and Regular Toothpaste on Salivary Glucose and pH among Type 2 Diabetes- A Randomized Crossover Trial

PubMed Central

Dodamani, Arun; Baviskar, Priya; Karibasappa, GN; Pathak, Parag; Bezalwar, Abhishek

2017-01-01

Introduction Diabetes is one of the most prevalent diseases of mankind having general as well as oral health manifestations. Also, there is an increase of salivary glucose level in diabetic, inducing saccharolytic bacteria in saliva which can have adverse effects on oral tissue. Aim To assess and compare the effect of sugar-free toothpaste on salivary glucose and pH among Type 2 diabetic and non-diabetic individuals. Materials and Methods A randomized controlled-crossover study was carried out on 30 Type 2 diabetic (Group A) and 45 non-diabetic (Group B) subjects. In first half of study, subjects in Group A and Group B were intervened with sugar-free and regular toothpaste respectively. Salivary glucose and pH was assessed before and after brushing at interval of one week for a period of four weeks. In second half, toothpastes were switched over between the groups, after sufficient washout period. Salivary glucose and pH were assessed again in the same manner for both the groups. The data was subjected to paired t-test and unpaired t-test for intragroup and intergroup comparison respectively. Results Salivary glucose level was significantly reduced and salivary pH was increased significantly (p<0.001) in both groups with sugar free toothpaste when compared to regular toothpaste. Conclusion Sugar free toothpaste showed beneficial effect on salivary glucose level and salivary pH level on diabetes and non-diabetes population. PMID:28893048

Tolerance of beta blocked hypertensives during orthostatic and altitude stress.

DOT National Transportation Integrated Search

1992-04-01

To evaluate the effects of orthostatic, altitude, and pharmacologic stresses upon civil aviation-specific performance, a double-blind, randomized, crossover trial of atenolol, 100mg, was designed and executed. Hypertensive males are females qualifyin...

Background Material for the Human Studies Review Board's Review of Ezratty 2014

EPA Pesticide Factsheets

Journal article and details of EPA's science and ethics reviews of the study by Ezratty et al. from 2014: Repeated Nitrogen Dioxide Exposures and Eosinophilic Airway Inflammation in Asthmatics: A Randomized Crossover Study.

Peer Assessment Enhances Student Learning: The Results of a Matched Randomized Crossover Experiment in a College Statistics Class.

PubMed

Sun, Dennis L; Harris, Naftali; Walther, Guenther; Baiocchi, Michael

2015-01-01

Feedback has a powerful influence on learning, but it is also expensive to provide. In large classes it may even be impossible for instructors to provide individualized feedback. Peer assessment is one way to provide personalized feedback that scales to large classes. Besides these obvious logistical benefits, it has been conjectured that students also learn from the practice of peer assessment. However, this has never been conclusively demonstrated. Using an online educational platform that we developed, we conducted an in-class matched-set, randomized crossover experiment with high power to detect small effects. We establish that peer assessment causes a small but significant gain in student achievement. Our study also demonstrates the potential of web-based platforms to facilitate the design of high-quality experiments to identify small effects that were previously not detectable.

Breath-stacking and incentive spirometry in Parkinson's disease: Randomized crossover clinical trial.

PubMed

Ribeiro, Rhayssa; Brandão, Daniella; Noronha, Jéssica; Lima, Cibelle; Fregonezi, Guilherme; Resqueti, Vanessa; Dornelas de Andrade, Arméle

2018-05-01

Patients with Parkinson's disease often exhibit respiratory disorders and there are no Respiratory Therapy protocols which are suggested as interventions in Parkinson's patients. The aim of this study is to evaluate the effects of Breathing-Stacking (BS) and incentive spirometer (IS) techniques in volume variations of the chest wall in patients with Parkinson's Disease (PD). 14 patients with mild-moderate PD were included in this randomized cross-over study. Volume variations of the chest wall were assessed before, immediately after, then 15 and 30 min after BS and IS performance by optoelectronic plethysmography. Tidal volume (VT) and minute ventilation (MV) significantly increased after BS and IS techniques (p < 0.05). There was greater involvement of pulmonary and abdominal compartments after IS. The results suggest that these re-expansion techniques can be performed to immediately improve volume. Copyright © 2018 Elsevier B.V. All rights reserved.

Explicit Bias Toward High-Income-Country Research: A Randomized, Blinded, Crossover Experiment Of English Clinicians.

PubMed

Harris, Matthew; Marti, Joachim; Watt, Hillary; Bhatti, Yasser; Macinko, James; Darzi, Ara W

2017-11-01

Unconscious bias may interfere with the interpretation of research from some settings, particularly from lower-income countries. Most studies of this phenomenon have relied on indirect outcomes such as article citation counts and publication rates; few have addressed or proven the effect of unconscious bias in evidence interpretation. In this randomized, blinded crossover experiment in a sample of 347 English clinicians, we demonstrate that changing the source of a research abstract from a low- to a high-income country significantly improves how it is viewed, all else being equal. Using fixed-effects models, we measured differences in ratings for strength of evidence, relevance, and likelihood of referral to a peer. Having a high-income-country source had a significant overall impact on respondents' ratings of relevance and recommendation to a peer. Unconscious bias can have far-reaching implications for the diffusion of knowledge and innovations from low-income countries.

Effects of brain-directed nutrients on cerebral blood flow and neuropsychological testing: a randomized, double-blind, placebo-controlled, crossover trial.

PubMed

Amen, Daniel G; Taylor, Derek V; Ojala, Kristine; Kaur, Jasleen; Willeumier, Kristen

2013-01-01

In a prior open trial of professional football players who displayed the effects of traumatic brain injury, the current reserach team reported significant improvements in clinical symptoms, neuropsychological testing and regional cerebral blood flow (rCBF) following the use of brain-directed nutrients (BDNs) and lifestyle interventions. The current study intended to determine whether supplementation with BDNs improved rCBF and neuropsychological function in healthy individuals. The current study was a randomized, doubleblind, placebo-controlled, crossover trial, which was a more rigorous reseach design than the prior study and did not include lifestyle interventions. Participants underwent evaluation and testing at the Amen Clinics, Inc, a private medical facility in Newport Beach, CA. Thirty healthy adult (15 male and 15 female) participants were recruited from the community though local advertising and met the requirements for eligibility into the study. Twenty-five individuals completed the study, with dropout due to events unrelated to the study itself. The participants were randomly assigned to a treatment order for intervention, either placebo or brain supplements first. The BDNs treatment was comprised of three supplements: fish oil; a high-potency, multiple vitamin/mineral supplement; and a brainenhancement supplement. The placebo treatment was two supplements comprised of rice flour to replace the multiple vitamin/mineral complex and the brain-enhancement supplement and one supplement made of other oils to replace the fish-oil mixture. After 2 mo of this first intervention, a crossover intervention occurred for a final 2 mo, in which participants formerly receiving BDNs received a placebo treatment and participants formerly treated with placebo received the BDNs treatment. Primary outcome measures included (1) an analysis of the changes in rCBF using SPECT and (2) an assessment of the differences in cognitive and emotional function using the MicroCog (cognitive performance), the WebNeuro (emotional state), and three psychological inventories-the Beck Depression Inventory (BDI-II), Brief Symptom Inventory (BSI), and Quality of Life Inventory (QOLI). A region of interest (ROI) analysis for each of the 2-mo phases (baseline, then placebo and treatment according to randomized order) showed significant improvement in rCBF for the BDNs as compared to the placebo (as assigned at the start of the first intervention) in the prefrontal cortex, anterior and posterior cingulate gyrus, hippocampus, and cerebellum. Significant improvements were observed for the BDNs (1) on the MicroCog-reasoning, P=.008; memory, P=.014; information processing accuracy, P=.027; (2) on the WebNeuro-executive function, P=.002, information processing efficiency, P=.015; depressed mood, P=.017, and emotional identification, P=.041; and (3) on the BSI-positive symptom total, P=.024 and reduced hostility, P=.018. For the last, significance occurred upon accounting for the effect of order. This study demonstrates the potential effectiveness of BDNs in enhancing rCBF and neuropsychological function across various cognitive and psychological domains.

A registry-based randomized trial comparing radial and femoral approaches in women undergoing percutaneous coronary intervention: the SAFE-PCI for Women (Study of Access Site for Enhancement of PCI for Women) trial.

PubMed

Rao, Sunil V; Hess, Connie N; Barham, Britt; Aberle, Laura H; Anstrom, Kevin J; Patel, Tejan B; Jorgensen, Jesse P; Mazzaferri, Ernest L; Jolly, Sanjit S; Jacobs, Alice; Newby, L Kristin; Gibson, C Michael; Kong, David F; Mehran, Roxana; Waksman, Ron; Gilchrist, Ian C; McCourt, Brian J; Messenger, John C; Peterson, Eric D; Harrington, Robert A; Krucoff, Mitchell W

2014-08-01

This study sought to determine the effect of radial access on outcomes in women undergoing percutaneous coronary intervention (PCI) using a registry-based randomized trial. Women are at increased risk of bleeding and vascular complications after PCI. The role of radial access in women is unclear. Women undergoing cardiac catheterization or PCI were randomized to radial or femoral arterial access. Data from the CathPCI Registry and trial-specific data were merged into a final study database. The primary efficacy endpoint was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding or vascular complications requiring intervention. The primary feasibility endpoint was access site crossover. The primary analysis cohort was the subgroup undergoing PCI; sensitivity analyses were conducted in the total randomized population. The trial was stopped early for a lower than expected event rate. A total of 1,787 women (691 undergoing PCI) were randomized at 60 sites. There was no significant difference in the primary efficacy endpoint between radial or femoral access among women undergoing PCI (radial 1.2% vs. 2.9% femoral, odds ratio [OR]: 0.39; 95% confidence interval [CI]: 0.12 to 1.27); among women undergoing cardiac catheterization or PCI, radial access significantly reduced bleeding and vascular complications (0.6% vs. 1.7%; OR: 0.32; 95% CI: 0.12 to 0.90). Access site crossover was significantly higher among women assigned to radial access (PCI cohort: 6.1% vs. 1.7%; OR: 3.65; 95% CI: 1.45 to 9.17); total randomized cohort: (6.7% vs. 1.9%; OR: 3.70; 95% CI: 2.14 to 6.40). More women preferred radial access. In this pragmatic trial, which was terminated early, the radial approach did not significantly reduce bleeding or vascular complications in women undergoing PCI. Access site crossover occurred more often in women assigned to radial access. (SAFE-PCI for Women; NCT01406236). Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

High-cocoa polyphenol-rich chocolate improves HDL cholesterol in Type 2 diabetes patients.

PubMed

Mellor, D D; Sathyapalan, T; Kilpatrick, E S; Beckett, S; Atkin, S L

2010-11-01

To examine the effects of chocolate on lipid profiles, weight and glycaemic control in individuals with Type 2 diabetes. Twelve individuals with Type 2 diabetes on stable medication were enrolled in a randomized, placebo-controlled double-blind crossover study. Subjects were randomized to 45 g chocolate with or without a high polyphenol content for 8 weeks and then crossed over after a 4-week washout period. Changes in weight, glycaemic control, lipid profile and high-sensitivity C-reactive protein were measured at the beginning and at the end of each intervention. HDL cholesterol increased significantly with high polyphenol chocolate (1.16 ± 0.08 vs. 1.26 ± 0.08 mmol/l, P = 0.05) with a decrease in the total cholesterol: HDL ratio (4.4 ± 0.4 vs. 4.1 ± 0.4 mmol/l, P = 0.04). No changes were seen with the low polyphenol chocolate in any parameters. Over the course of 16 weeks of daily chocolate consumption neither weight nor glycaemic control altered from baseline. High polyphenol chocolate is effective in improving the atherosclerotic cholesterol profile in patients with diabetes by increasing HDL cholesterol and improving the cholesterol:HDL ratio without affecting weight, inflammatory markers, insulin resistance or glycaemic control.

Recombinant factor VIIa analog in the management of hemophilia with inhibitors: results from a multicenter, randomized, controlled trial of vatreptacog alfa.

PubMed

Lentz, S R; Ehrenforth, S; Karim, F Abdul; Matsushita, T; Weldingh, K N; Windyga, J; Mahlangu, J N

2014-08-01

Vatreptacog alfa, a recombinant factor VIIa (rFVIIa) analog with three amino acid substitutions and 99% identity to native FVIIa, was developed to improve the treatment of hemophilic patients with inhibitors. To confirm the safety and assess the efficacy of vatreptacog alfa in treating bleeding episodes in hemophilic patients with inhibitors. In this international, multicenter, randomized, double-blind, active-controlled, crossover, confirmatory phase III trial (adept(™) 2) in patients with hemophilia A or B and inhibitors, bleeds were randomized 3 : 2 to treatment with vatreptacog alfa (one to three doses at 80 μg kg(-1) ) or rFVIIa (one to three doses at 90 μg kg(-1) ). Treatment failures after three doses of trial product (TP) were managed according to the local standard of care. In the 72 patients enrolled, 567 bleeds were treated with TP. Both vatreptacog alfa and rFVIIa gave 93% effective bleeding control at 12 h. Vatreptacog alfa was superior to rFVIIa in secondary efficacy outcomes, including the number of doses used to treat a bleed and sustained bleeding control 24-48 h after the first dose. Eight patients (11%) developed antibodies against vatreptacog alfa, including four with cross-reactivity against rFVIIa and one with an in vitro neutralizing effect to vatreptacog alfa. This large randomized controlled trial confirmed the well-established efficacy and safety profile of rFVIIa, and showed that vatreptacog alfa had similar or better efficacy than rFVIIa. However, because of the development of anti-drug antibodies, a positive benefit-risk profile is unlikely to be achieved with vatreptacog alfa. © 2014 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

Mechanisms for an effect of acetylcysteine on renal function after exposure to radio-graphic contrast material: study protocol.

PubMed

Sandilands, Euan A; Cameron, Sharon; Paterson, Frances; Donaldson, Sam; Briody, Lesley; Crowe, Jane; Donnelly, Julie; Thompson, Adrian; Johnston, Neil R; Mackenzie, Ivor; Uren, Neal; Goddard, Jane; Webb, David J; Megson, Ian L; Bateman, Nicholas; Eddleston, Michael

2012-02-03

Contrast-induced nephropathy is a common complication of contrast administration in patients with chronic kidney disease and diabetes. Its pathophysiology is not well understood; similarly the role of intravenous or oral acetylcysteine is unclear. Randomized controlled trials to date have been conducted without detailed knowledge of the effect of acetylcysteine on renal function. We are conducting a detailed mechanistic study of acetylcysteine on normal and impaired kidneys, both with and without contrast. This information would guide the choice of dose, route, and appropriate outcome measure for future clinical trials in patients with chronic kidney disease. We designed a 4-part study. We have set up randomised controlled cross-over studies to assess the effect of intravenous (50 mg/kg/hr for 2 hrs before contrast exposure, then 20 mg/kg/hr for 5 hrs) or oral acetylcysteine (1200 mg twice daily for 2 days, starting the day before contrast exposure) on renal function in normal and diseased kidneys, and normal kidneys exposed to contrast. We have also set up a parallel-group randomized controlled trial to assess the effect of intravenous or oral acetylcysteine on patients with chronic kidney disease stage III undergoing elective coronary angiography. The primary outcome is change in renal blood flow; secondary outcomes include change in glomerular filtration rate, tubular function, urinary proteins, and oxidative balance. Contrast-induced nephropathy represents a significant source of hospital morbidity and mortality. Over the last ten years, acetylcysteine has been administered prior to contrast to reduce the risk of contrast-induced nephropathy. Randomized controlled trials, however, have not reliably demonstrated renoprotection; a recent large randomized controlled trial assessing a dose of oral acetylcysteine selected without mechanistic insight did not reduce the incidence of contrast-induced nephropathy. Our study should reveal the mechanism of effect of acetylcysteine on renal function and identify an appropriate route for future dose response studies and in time randomized controlled trials. Clinical Trials.gov: NCT00558142; EudraCT: 2006-003509-18.

Spinal cord stimulation versus repeated lumbosacral spine surgery for chronic pain: a randomized, controlled trial.

PubMed

North, Richard B; Kidd, David H; Farrokhi, Farrokh; Piantadosi, Steven A

2005-01-01

Persistent or recurrent radicular pain after lumbosacral spine surgery is often associated with nerve root compression and is treated by repeated operation or, as a last resort, by spinal cord stimulation (SCS). We conducted a prospective, randomized, controlled trial to test our hypothesis that SCS is more likely than reoperation to result in a successful outcome by standard measures of pain relief and treatment outcome, including subsequent use of health care resources. For an average of 3 years postoperatively, disinterested third-party interviewers followed 50 patients selected for reoperation by standard criteria and randomized to SCS or reoperation. If the results of the randomized treatment were unsatisfactory, patients could cross over to the alternative. Success was based on self-reported pain relief and patient satisfaction. Crossover to the alternative procedure was an outcome measure. Use of analgesics, activities of daily living, and work status were self-reported. Among 45 patients (90%) available for follow-up, SCS was more successful than reoperation (9 of 19 patients versus 3 of 26 patients, P <0.01). Patients initially randomized to SCS were significantly less likely to cross over than were those randomized to reoperation (5 of 24 patients versus 14 of 26 patients, P=0.02). Patients randomized to reoperation required increased opiate analgesics significantly more often than those randomized to SCS (P <0.025). Other measures of activities of daily living and work status did not differ significantly. SCS is more effective than reoperation as a treatment for persistent radicular pain after lumbosacral spine surgery, and in the great majority of patients, it obviates the need for reoperation.

Video-game based therapy performed by children with cerebral palsy: a cross-over randomized controlled trial and a cross-sectional quantitative measure of physical activity.

PubMed

Zoccolillo, L; Morelli, D; Cincotti, F; Muzzioli, L; Gobbetti, T; Paolucci, S; Iosa, M

2015-12-01

Previous studies reported controversial results about the efficacy of video-game based therapy (VGT) in improving neurorehabilitation outcomes in children with cerebral palsy (CP). Primary aim was to investigate the effectiveness of VGT with respect to conventional therapy (CT) in improving upper limb motor outcomes in a group of children with CP. Secondary aim was to quantify if VGT leads children to perform a higher number of movements. A cross-over randomized controlled trial (RCT) for investigating the primary aim and a cross-sectional study for investigating the secondary aim of this study. Outpatients. clinical diagnosis of CP, age between 4 and 14 years, level of GMFC between I and IV. QI<35, severe comorbidities, incapacity to stand even with an external support. Twenty-two children with CP (6.89±1.91-year old) were enrolled in a cross-over RCT with 16 sessions of VGT (using Xbox with Kinect device) and then 16 of CT or vice versa. Upper limb functioning was assessed using the Quality of Upper Extremities Skills Test (QUEST) and hand abilities using Abilhand-kids score. According to the secondary aim of this study a secondary cross-sectional study has been performed. Eight children with CP (6.50±1.60-year old) were enrolled into a trial in which five wireless triaxial accelerometers were positioned on their forearms, legs and trunk for quantifying the physical activity during VGT vs. CT. QUEST scores significantly improved only after VGT (P=0.003), and not after CT (P=0.056). The reverse occurred for Abilhand-kids scores (P=0.165 vs. P=0.013, respectively). Quantity of performed movements was three times higher in VGT than in CT (+198%, P=0.027). VGT resulted effective in improving the motor functions of upper limb extremities in children with CP, conceivably for the increased quantity of limb movements, but failed in improving the manual abilities for performing activities of daily living which benefited more from CT. VGT performed using the X-Box with Kinect device could enhance the number of upper limb movements in children with CP during rehabilitation and in turn improving upper limb motor skills, but CT remained superior for improving performances in manual activities of daily living.

Bayesian analysis of time-series data under case-crossover designs: posterior equivalence and inference.

PubMed

Li, Shi; Mukherjee, Bhramar; Batterman, Stuart; Ghosh, Malay

2013-12-01

Case-crossover designs are widely used to study short-term exposure effects on the risk of acute adverse health events. While the frequentist literature on this topic is vast, there is no Bayesian work in this general area. The contribution of this paper is twofold. First, the paper establishes Bayesian equivalence results that require characterization of the set of priors under which the posterior distributions of the risk ratio parameters based on a case-crossover and time-series analysis are identical. Second, the paper studies inferential issues under case-crossover designs in a Bayesian framework. Traditionally, a conditional logistic regression is used for inference on risk-ratio parameters in case-crossover studies. We consider instead a more general full likelihood-based approach which makes less restrictive assumptions on the risk functions. Formulation of a full likelihood leads to growth in the number of parameters proportional to the sample size. We propose a semi-parametric Bayesian approach using a Dirichlet process prior to handle the random nuisance parameters that appear in a full likelihood formulation. We carry out a simulation study to compare the Bayesian methods based on full and conditional likelihood with the standard frequentist approaches for case-crossover and time-series analysis. The proposed methods are illustrated through the Detroit Asthma Morbidity, Air Quality and Traffic study, which examines the association between acute asthma risk and ambient air pollutant concentrations. © 2013, The International Biometric Society.

The Impact of Virtual Reality Distraction on Pain and Anxiety during Dental Treatment in 4-6 Year-Old Children: a Randomized Controlled Clinical Trial.

PubMed

Asl Aminabadi, Naser; Erfanparast, Leila; Sohrabi, Azin; Ghertasi Oskouei, Sina; Naghili, Armaghan

2012-01-01

Dental practitioners have numerous methods to control anxiety and pain in children, and distracting the child appears to be the most common technique used for behavior management during dental procedures. The aim of the present study was to evaluate the influence of using virtual reality eyeglasses on severity of pain and anxiety during dental procedures in pediatric patients. This study included 120 healthy children aged 4-6 years. Children with no previous anxiety disorder were randomly divided into two groups, each consisting of 60 children. The study consisted of 3 consecutive treatment sessions. During the first visit fluoride therapy was carried out in both groups. In the next sessions, the groups received restorative treatment with and without virtual reality eyeglasses in a randomized single-blind-controlled crossover fashion. Then at the end of each session the subjects' pain severity was assessed using Wong Baker FACES Pain Rating Scale and state anxiety was measured by Faces version of the Modified Child Dental Anxiety Scale [MCDAS (f)]. There was a significant decrease in pain perception (P < 0.001) and state anxiety scores (P < 0.001) with the use of virtual reality eyeglasses during dental treatment. Results of this study showed that virtual reality eyeglasses can successfully decrease pain perception and state anxiety during dental treatment. 201103126036N1.

A randomized, controlled trial of immersive virtual reality analgesia, during physical therapy for pediatric burns.

PubMed

Schmitt, Yuko S; Hoffman, Hunter G; Blough, David K; Patterson, David R; Jensen, Mark P; Soltani, Maryam; Carrougher, Gretchen J; Nakamura, Dana; Sharar, Sam R

2011-02-01

This randomized, controlled, within-subjects (crossover design) study examined the effects of immersive virtual reality as an adjunctive analgesic technique for hospitalized pediatric burn inpatients undergoing painful physical therapy. Fifty-four subjects (6-19 years old) performed range-of-motion exercises under a therapist's direction for 1-5 days. During each session, subjects spent equivalent time in both the virtual reality and the control conditions (treatment order randomized and counterbalanced). Graphic rating scale scores assessing the sensory, affective, and cognitive components of pain were obtained for each treatment condition. Secondary outcomes assessed subjects' perception of the virtual reality experience and maximum range-of-motion. Results showed that on study day one, subjects reported significant decreases (27-44%) in pain ratings during virtual reality. They also reported improved affect ("fun") during virtual reality. The analgesia and affect improvements were maintained with repeated virtual reality use over multiple therapy sessions. Maximum range-of-motion was not different between treatment conditions, but was significantly greater after the second treatment condition (regardless of treatment order). These results suggest that immersive virtual reality is an effective nonpharmacologic, adjunctive pain reduction technique in the pediatric burn population undergoing painful rehabilitation therapy. The magnitude of the analgesic effect is clinically meaningful and is maintained with repeated use. Copyright © 2010 Elsevier Ltd and ISBI. All rights reserved.

A Randomized, Controlled Trial of Immersive Virtual Reality Analgesia during Physical Therapy for Pediatric Burn Injuries

PubMed Central

Schmitt, Yuko S.; Hoffman, Hunter G.; Blough, David K.; Patterson, David R.; Jensen, Mark P.; Soltani, Maryam; Carrougher, Gretchen J.; Nakamura, Dana; Sharar, Sam R.

2010-01-01

This randomized, controlled, within-subjects (crossover design) study examined the effects of immersive virtual reality as an adjunctive analgesic technique for hospitalized pediatric burn inpatients undergoing painful physical therapy. Fifty-four subjects (6–19 years old) performed range-of-motion exercises under a therapist’s direction for one to five days. During each session, subjects spent equivalent time in both the virtual reality and the control conditions (treatment order randomized and counterbalanced). Graphic rating scale scores assessing the sensory, affective, and cognitive components of pain were obtained for each treatment condition. Secondary outcomes assessed subjects’ perception of the virtual reality experience and maximum range-of-motion. Results showed that on study day one, subjects reported significant decreases (27–44%) in pain ratings during virtual reality. They also reported improved affect (“fun”) during virtual reality. The analgesia and affect improvements were maintained with repeated virtual reality use over multiple therapy sessions. Maximum range-of-motion was not different between treatment conditions, but was significantly greater after the second treatment condition (regardless of treatment order). These results suggest that immersive virtual reality is an effective nonpharmacologic, adjunctive pain reduction technique in the pediatric burn population undergoing painful rehabilitation therapy. The magnitude of the analgesic effect is clinically meaningful and is maintained with repeated use. PMID:20692769

An Intervention with Mineral Water Decreases Cardiometabolic Risk Biomarkers. A Crossover, Randomised, Controlled Trial with Two Mineral Waters in Moderately Hypercholesterolaemic Adults.

PubMed

Toxqui, Laura; Vaquero, M Pilar

2016-06-28

Water intake is essential for health maintenance and disease prevention. The effects of an intervention with two mineral waters, sodium-bicarbonated mineral water (BW) or control mineral water low in mineral content (CW), on cardiometabolic risk biomarkers were studied. In a randomised-controlled crossover-trial, sixty-four moderately hypercholesterolaemic adults were randomly assigned to consume 1 L/day of either BW (sodium, 1 g/L; bicarbonate, 2 g/L) or CW with the main meals for eight weeks, separated by an eight-week washout period. Blood lipids, lipid oxidation, glucose, insulin, aldosterone, urine pH, urinary electrolytes, blood pressure, body weight, fluid intake, energy, and nutrients from total diet and beverages were determined. Total cholesterol, LDL cholesterol, and glucose decreased (p < 0.01), oxidised LDL tended to decrease (p = 0.073), and apolipoprotein B increased during the intervention, without water type effect. Energy and carbohydrates from beverages decreased since soft drinks and fruit juice consumptions decreased throughout the trial. BW increased urinary pH (p = 0.006) and reduced calcium/creatinine excretion (p = 0.011). Urinary potassium/creatinine decreased with both waters. Consumption of 1 L/day of mineral water with the main meals reduces cardiometabolic risk biomarkers, likely to be attributed to a replacement of soft drinks by water. In addition, BW does not affect blood pressure and exerts a moderate alkalizing effect in the body.

Psychotherapy Augmentation through Preconscious Priming

PubMed Central

Borgeat, François; O’Connor, Kieron; Amado, Danielle; St-Pierre-Delorme, Marie-Ève

2013-01-01

Objective: To test the hypothesis that repeated preconscious (masked) priming of personalized positive cognitions could augment cognitive change and facilitate achievement of patients’ goals following a therapy. Methods: Twenty social phobic patients (13 women) completed a 36-weeks study beginning by 12 weeks of group behavioral therapy. After the therapy, they received 6 weeks of preconscious priming and 6 weeks of a control procedure in a randomized cross-over design. The Priming condition involved listening twice daily with a passive attitude to a recording of individualized formulations of appropriate cognitions and attitudes masked by music. The Control condition involved listening to an indistinguishable recording where the formulations had been replaced by random numbers. Changes in social cognitions were measured by the Social Interaction Self Statements Test (SISST). Results: Patients improved following therapy. The Priming procedure was associated with increased positive cognitions and decreased negative cognitions on the SISST while the Control procedure was not. The Priming procedure induced more cognitive change when applied immediately after the group therapy. Conclusion: An effect of priming was observed on social phobia related cognitions in the expected direction. This self administered addition to a therapy could be seen as an augmentation strategy. PMID:23508724

Randomized controlled trial of melatonin for children with autistic spectrum disorders and sleep problems.

PubMed

Garstang, J; Wallis, M

2006-09-01

Melatonin is often used for autistic children with sleep disorders, despite a lack of published evidence in this population. A randomized, placebo-controlled double-blind crossover trial of melatonin was undertaken in 11 children with autistic spectrum disorder (ASD). Seven children completed the trial. Sleep latency was 2.6 h [95% confidence intervals (CI) 2.28-2.93] baseline, 1.91 h (95% CI 1.78-2.03) with placebo and 1.06 h (95% CI 0.98-1.13) with melatonin. Wakings per night were 0.35 (95% CI 0.18-0.53) baseline, 0.26 (95% CI 0.20-0.34) with placebo and 0.08 (95% CI 0.04-0.12) with melatonin. Total sleep duration was 8.05 h (95% CI 7.65-8.44) baseline, 8.75 h (95% CI 8.56-8.98) with placebo and 9.84 h (95% CI 9.68-9.99) with melatonin. Although the study was small owing to recruitment difficulties, it still provides evidence of effectiveness of melatonin in children with sleep difficulties and ASD, which we predict a larger study would confirm.

A Single Session of Mirror-based Tactile and Motor Training Improves Tactile Dysfunction in Children with Unilateral Cerebral Palsy: A Replicated Randomized Controlled Case Series.

PubMed

Auld, Megan L; Johnston, Leanne M; Russo, Remo N; Moseley, G Lorimer

2017-10-01

This replicated randomized controlled crossover case series investigated the effect of mirror-based tactile and motor training on tactile registration and perception in children with unilateral cerebral palsy (UCP). Six children with UCP (6-18 years; median 10 years, five male, three-left hemiplegia, four-manual ability classification system (MACS) I, one MACS II and one MACS III) participated. They attended two 90-minute sessions - one of mirror-based training and one of standard practice, bimanual therapy - in alternated order. Tactile registration (Semmes Weinstein Monofilaments) and perception (double simultaneous or single-point localization) were assessed before and after each session. Change was estimated using reliable change index (RCI). Tactile perception improved in four participants (RCI > 1.75), with mirror-based training, but was unchanged with bimanual therapy (RCI < 1.0 for all participants). Neither intervention affected tactile registration. Mirror-based training demonstrates potential to improve tactile perception in children with UCP. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Double-Blind, Placebo-Controlled, Crossover Study of the Efficacy and Safety of Lisdexamfetamine Dimesylate in College Students with ADHD

ERIC Educational Resources Information Center

DuPaul, George J.; Weyandt, Lisa L.; Rossi, Joseph S.; Vilardo, Brigid A.; O'Dell, Sean M.; Carson, Kristen M.; Verdi, Genevieve; Swentosky, Anthony

2012-01-01

Objective: To evaluate stimulant medication on symptoms and functioning for college students with ADHD using double-blind, placebo-controlled, crossover design. Method: Participants included 24 college students with ADHD and 26 college students without psychopathology. Lisdexamfetamine dimesylate (LDX) was examined for ADHD participants over five…

Single and Multiple Ascending-dose Studies of Oral Delafloxacin: Effects of Food, Sex, and Age.

PubMed

Hoover, Randall; Hunt, Thomas; Benedict, Michael; Paulson, Susan K; Lawrence, Laura; Cammarata, Sue; Sun, Eugene

2016-01-01

The objective of this report is describe the results of 2 studies that examined the pharmacokinetic parameters, safety profile, and tolerability of single and multiple ascending doses of oral delafloxacin and the effects of food, sex, and age on oral delafloxacin pharmacokinetic parameters, safety profile, and tolerability. The first study contained 3 parts and used unformulated delafloxacin in a capsule. Part 1 was a randomized, double-blind, placebo-controlled, single (50, 100, 200, 400, 800, 1200, and 1600 mg) ascending-dose study of oral delafloxacin in healthy men. Part 2 was a single-dose crossover study in which 20 men received 250 mg delafloxacin with or without food. Part 2 also included a parallel group, double-blind, placebo-controlled study in 16 women and 16 elderly men and women who were randomized (3:1) to receive 250 mg delafloxacin or placebo. Part 3 was a randomized, double-blind, placebo-controlled, multiple (100, 200, 400, 800, 1200 mg once daily for 5 days) ascending-dose study of oral delafloxacin in healthy men. The second study was a single-dose, randomized, 3-period crossover study in which participants received 900 mg delafloxacin (2 × 450-mg tablets) under fasted conditions, with a high-fat meal, or fasted with a high-fat meal 2 hours after dosing. Serial blood samples were collected, and plasma pharmacokinetic parameters of delafloxacin were determined. Delafloxacin Cmax and AUC0-∞ increased with increasing oral dose over the dose range of 50 to 1600 mg. The increases in delafloxacin AUC0-∞ were dose proportional at doses of ≥200 mg. Steady state was reached by day 3 of dosing with minimal accumulation of delafloxacin. The Cmax of delafloxacin was decreased slightly in the presence of food. No sex difference in delafloxacin pharmacokinetic parameters was observed. In the elderly men and women, mean delafloxacin Cmax and AUC0-∞ were 35% higher than observed for young adults, which could be partially explained by a decrease in the creatinine clearance in the elderly men and women. Delafloxacin was well tolerated at the tested doses, with gastrointestinal adverse effects observed more commonly at doses ≥1200 mg. Delafloxacin exhibits linear pharmacokinetic parameters that reached steady state after 3 days of daily oral dosing with minimal accumulation. Delafloxacin was well tolerated throughout both studies, with gastrointestinal effects observed at the higher doses (≥1200 mg). Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Testing equality and interval estimation in binary responses when high dose cannot be used first under a three-period crossover design.

PubMed

Lui, Kung-Jong; Chang, Kuang-Chao

2015-01-01

When comparing two doses of a new drug with a placebo, we may consider using a crossover design subject to the condition that the high dose cannot be administered before the low dose. Under a random-effects logistic regression model, we focus our attention on dichotomous responses when the high dose cannot be used first under a three-period crossover trial. We derive asymptotic test procedures for testing equality between treatments. We further derive interval estimators to assess the magnitude of the relative treatment effects. We employ Monte Carlo simulation to evaluate the performance of these test procedures and interval estimators in a variety of situations. We use the data taken as a part of trial comparing two different doses of an analgesic with a placebo for the relief of primary dysmenorrhea to illustrate the use of the proposed test procedures and estimators.

An in silico approach helped to identify the best experimental design, population, and outcome for future randomized clinical trials.

PubMed

Bajard, Agathe; Chabaud, Sylvie; Cornu, Catherine; Castellan, Anne-Charlotte; Malik, Salma; Kurbatova, Polina; Volpert, Vitaly; Eymard, Nathalie; Kassai, Behrouz; Nony, Patrice

2016-01-01

The main objective of our work was to compare different randomized clinical trial (RCT) experimental designs in terms of power, accuracy of the estimation of treatment effect, and number of patients receiving active treatment using in silico simulations. A virtual population of patients was simulated and randomized in potential clinical trials. Treatment effect was modeled using a dose-effect relation for quantitative or qualitative outcomes. Different experimental designs were considered, and performances between designs were compared. One thousand clinical trials were simulated for each design based on an example of modeled disease. According to simulation results, the number of patients needed to reach 80% power was 50 for crossover, 60 for parallel or randomized withdrawal, 65 for drop the loser (DL), and 70 for early escape or play the winner (PW). For a given sample size, each design had its own advantage: low duration (parallel, early escape), high statistical power and precision (crossover), and higher number of patients receiving the active treatment (PW and DL). Our approach can help to identify the best experimental design, population, and outcome for future RCTs. This may be particularly useful for drug development in rare diseases, theragnostic approaches, or personalized medicine. Copyright © 2016 Elsevier Inc. All rights reserved.

Upper airway stabilization by osteopathic manipulation of the sphenopalatine ganglion versus sham manipulation in OSAS patients: a proof-of-concept, randomized, crossover, double-blind, controlled study.

PubMed

Jacq, Olivier; Arnulf, Isabelle; Similowski, Thomas; Attali, Valérie

2017-12-20

Osteopathic manipulative treatment (OMT) of the sphenopalatine ganglion (SPG) is used empirically for the treatment of rhinitis and snoring and is thought to increase pharyngeal stability. This trial was designed to study the effects of this treatment on pharyngeal stability evaluated by critical closing pressure in obstructive sleep apnoea syndrome. This single-centre, randomized, crossover, double-blind study compared active manipulation and sham manipulation of the SPG. Randomization was computer-generated. Patients each received one active manipulation and one sham manipulation at an interval of 21 days and were evaluated 30 min and 48 h after each session administered by a qualified osteopath. Neither the patients, nor the investigator performing the evaluations were informed about the order of the two techniques (double-blind). The primary endpoint was the percentage of responding patients presenting increased pharyngeal stability defined by a variation of critical closing pressure (Pcrit) of at least -4 cmH 2 O at 30 min. Secondary endpoints were the variation of Pcrit in absolute values, sleepiness and snoring. Others endpoints were lacrimation (Schirmer's test), induced pain, sensations experienced during OMT. Ten patients were included and nine (57 [50; 58] years, comprising 7 men, with an apnoea-hypopnoea index of 31.0 [25.5; 33.2]/h; (values are median [quartiles])) were analysed. Seven patients were analysed for the primary endpoint and nine patients were analysed for secondary endpoints. Five patients responded after active manipulation versus no patients after sham manipulation (p = 0.0209). Active manipulation induced more intense pain (p = 0.0089), increased lacrimation (ns) and more tactile, nociceptive and gustatory sensations (13 versus 1) compared to sham manipulation. No significant difference was observed for the other endpoints. Osteopathic manipulative treatment of the SPG may improve pharyngeal stability in obstructive sleep apnoea syndrome. This trial validates the feasibility of the randomized, controlled, double-blind methodology for evaluation of this osteopathic treatment. Studies on a larger sample size must specify the efficacy on the apnoea-hypopnoea index. The study was retrospectively registered in the clinicaltrial.gov registry under reference NCT01193738 on 1st September 2010 (first inclusion May 19, 2010).

Language-specific strategy for programming hearing aids - A double-blind randomized controlled crossover study.

PubMed

Matsumoto, Nozomu; Suzuki, Nobuyoshi; Iwasaki, Satoshi; Ishikawa, Kazuha; Tsukiji, Hiroki; Higashino, Yoshie; Tabuki, Tomoko; Nakagawa, Takashi

2018-08-01

Voice-aligned compression (VAC) is a method used in Oticon's hearing aids to provide more comfortable hearing without sacrificing speech discrimination. The complex, non-linear compression curve for the VAC strategy is designed based on the frequency profile of certain spoken Western languages. We hypothesized that hearing aids could be further customized for Japanese-speaking users by modifying the compression curve using the frequency profile of spoken Japanese. A double-blind randomized controlled crossover study was performed to determine whether or not Oticon's modified amplification strategy (VAC-J) provides subjectively preferable hearing aids for Japanese-speaking hearing aid users compared to the same company's original amplification strategy (VAC). The participants were randomized to two groups. The VAC-first group received a pair of hearing aids programmed using the VAC strategy and wore them for three weeks, and then received a pair of hearing aids programmed using VAC-J strategy and wore them for three weeks. The VAC-J-first group underwent the same study, but they received hearing aids in the reverse sequence. A Speech, Spatial and Qualities (SSQ) questionnaire was administered before beginning to use the hearing aids, at the end of using the first pair of hearing aids, and at the end of using the second pair of hearing aids. Twenty-five participants that met the inclusion/exclusion criteria from January 1 to October 31, 2016, were randomized to two groups. Twenty-two participants completed the study. There were no statistically significant differences in the increment of SSQ scores between the participants when using the VAC- or the VAC-J-programmed hearing aids. However, participants preferred the VAC-J strategy to the VAC strategy at the end of the study, and this difference was statistically significant. Japanese-speaking hearing aid users preferred using hearing aids that were fitted with the VAC-J strategy. Our results show that the VAC strategy can be adjusted to the frequency profile of different languages and that participants expressed their subjective preference more clearly than was reflected in the SSQ scores. A similar language-specific strategy may improve user's satisfaction while using hearing devices, and this concept may be extended to implantable hearing devices. R000023191. Copyright © 2017 Elsevier B.V. All rights reserved.

Carnitine for fatigue in multiple sclerosis.

PubMed

Tejani, Aaron M; Wasdell, Michael; Spiwak, Rae; Rowell, Greg; Nathwani, Shabita

2010-02-17

Fatigue is reported to occur in up to 92% of patients with multiple sclerosis (MS) and has been described as the most debilitating of all MS symptoms by 28% to 40% of MS patients. To assess whether carnitine (enteral or intravenous) supplementation can improve the quality of life and reduce the symptoms of fatigue in patients with MS-related fatigue and to identify any adverse effects of carnitine when used for this purpose. A literature search was performed using Cochrane MS Group Trials Register (21 May 2009), Cochrane Central Register of Controlled Trials (CENTRAL) "The Cochrane Library 2009, issue 2, MEDLINE (PubMed) (1966-21 May 2009), EMBASE (1974-21 May 2009). Reference lists of review articles and primary studies were also screened. A hand search of the abstract book of recent relevant conference symposia was also conducted. Personal contact with MS experts and a manufacturer (Source Naturals, United States) of carnitine formulation was contacted to determine if they knew of other clinical trials. No language restrictions were applied. Full reports of published and unpublished randomized controlled trials and quasi-randomized trials of any carnitine intervention in adults with a clinical diagnosis of fatigue associated with multiple sclerosis were included. Data from the eligible trials was extracted and coded using a standardized data extraction form and entered into RevMan 5. Discrepancies were to be resolved by discussion with a third reviewer however this was not necessary. The quality items to be assessed were method of randomization, allocation concealment, blinding (participants, investigators, outcome assessors and data analysis), intention-to-treat analysis and completeness of follow up. The search identified one randomized cross-over trial. In this study patients were exposed to both acetyl L-carnitine (ALCAR(tm)) 2 grams daily and amantadine 200 mg daily in adult patients with relapsing-remitting and secondary progressive MS. The effects of carnitine on fatigue are not clear based on the one included crossover RCT. There was no difference between carnitine and amantadine for the number of patients withdrawing from the study due to an adverse event (relative risk ratio 0.20; 95% confidence interval 0.03 to 1.55. Mortality, serious adverse events, total adverse events, and quality of life were not reported. There is insufficient evidence that carnitine for the treatment of MS-related fatigue offers a therapeutic advantage over placebo or active comparators.

Phenobarbitone versus phenytoin for treatment of neonatal seizures: an open-label randomized controlled trial.

PubMed

Pathak, Garima; Upadhyay, Amit; Pathak, Umesh; Chawla, Deepak; Goel, Sneh P

2013-08-01

To compare the efficacy of phenobarbitone and phenytoin for treatment of neonatal seizures in term and near-term neonates. Open labeled randomized controlled trial. Neonatal intensive care unit of a level II unit from India, from November 2008 to September 2009. All term and late pre-term neonates admitted with clinically apparent seizures and not having any transient metabolic disorders (hypoglycemia or hypocalcemia) were randomly assigned. Phenobarbitone (n=54) or phenytoin (n=55) intravenously 20 mg/kg/dose over 20-30 min. Neonates whose seizures were not controlled by the assigned drug were then crossed over to be treated with other drug in same dose. Clinical control of seizures (seizure free period of 24 hours after giving anticonvulsant). Baseline characteristics including mean birthweight, gestation age and sex were comparable in both groups. Seizures were controlled in 8 of the 55 (14.5%) neonates who received phenytoin, as compared to 39 of 54 (72.2%) neonates who received phenobarbitone (P <0.001). In babies not responding to assigned drugs, after cross-over to the other drug, seizure control was achieved in 44/55 (80%) of the neonates assigned to receive phenytoin first as compared to 49/54 (91%) of those assigned to receive phenobarbitone first (P=0.014). After maximum dose of phenobarbitone seizures were controlled in 49/55(89%) in phenytoin group and 52/54 (96%) in phenobarbitone group (P<0.05). Phenobarbitone is more efficacious than phenytoin in control of clinical seizures in term or near-term neonates, irrespective of etiology. To evaluate serum vascular endothelial growth factor (VEGF) levels in children with acute lymphoblastic leukemia (ALL) during the induction phase of chemotherapy.

Efficacy of a Mandibular Advancement Appliance on Sleep Disordered Breathing in Children: A Study Protocol of a Crossover Randomized Controlled Trial

PubMed Central

Idris, Ghassan; Galland, Barbara; Robertson, Christopher J.; Farella, Mauro

2016-01-01

Background: Sleep-Disordered Breathing (SDB) varies from habitual snoring to partial or complete obstruction of the upper airway and can be found in up to 10% of children. SDB can significantly affect children's wellbeing, as it can cause growth disorders, educational and behavioral problems, and even life-threatening conditions, such as cardiorespiratory failure. Adenotonsillectomy represents the primary treatment for pediatric SDB where adeno-tonsillar hypertrophy is indicated. For those with craniofacial anomalies, or for whom adenotonsillectomy or other treatment modalities have failed, or surgery is contra-indicated, mandibular advancement splints (MAS) may represent a viable treatment option. Whilst the efficacy of these appliances has been consistently demonstrated in adults, there is little information about their effectiveness in children. Aims: To determine the efficacy of mandibular advancement appliances for the management of SDB and related health problems in children. Methods/design: The study will be designed as a single-blind crossover randomized controlled trial with administration of both an “Active MAS” (Twin-block) and a “Sham MAS.” Eligible participants will be children aged 8–12 years whose parents report they snore ≥3 nights per week. Sixteen children will enter the full study after confirming other inclusion criteria, particularly Skeletal class I or class II confirmed by lateral cephalometric radiograph. Each child will be randomly assigned to either a treatment sequence starting with the Active or the Sham MAS. Participants will wear the appliances for 3 weeks separated by a 2-week washout period. For each participant, home-based polysomnographic data will be collected four times; once before and once after each treatment period. The Apnea Hypopnea Index (AHI) will represent the main outcome variable. Secondary outcomes will include, snoring frequency, masseter muscle activity, sleep symptoms, quality of life, daytime sleepiness, children behavior, and nocturnal enuresis. In addition, blood samples will be collected to assess growth hormone changes. Trial registration: This study was registered in the Australian New Zealand Clinical Trials Registry (ANZCTR): [ACTRN12614001013651]. PMID:27594841

Isoflavone supplement composition and equol producer status affect gene expression in adipose tissue: a double-blind, randomized, placebo-controlled crossover trial in postmenopausal women.

PubMed

van der Velpen, Vera; Geelen, Anouk; Hollman, Peter C H; Schouten, Evert G; van 't Veer, Pieter; Afman, Lydia A

2014-11-01

Isoflavone supplements, consumed by women experiencing menopausal symptoms, are suggested to have positive effects on menopause-related adiposity and cardiovascular disease risk profile, but discussions about their safety are still ongoing. The objective was to study the effects of an 8-wk consumption of 2 different isoflavone supplements compared with placebo on whole-genome gene expression in the adipose tissue of postmenopausal women. This double-blind, randomized, placebo-controlled crossover intervention consisted of 2 substudies, one with a low-genistein (LG) supplement (56% daidzein + daidzin, 16% genistein + genistin, and 28% glycitein + glycitin) and the other with a high-genistein (HG) supplement (49% daidzein + daidzin, 41% genistein + genistin, and 10% glycitein + glycitin). Both supplements provided ∼ 100 mg isoflavones/d (aglycone equivalents). After the 8-wk isoflavone and placebo period, whole-genome arrays were performed in subcutaneous adipose tissue of postmenopausal women (n = 26 after LG, n = 31 after HG). Participants were randomized by equol-producing phenotype, and data analysis was performed per substudy for equol producers and nonproducers separately. Gene set enrichment analysis showed downregulation of expression of energy metabolism-related genes after LG supplementation (n = 24) in both equol-producing phenotypes and oppositely regulated expression for equol producers (down) and nonproducers (up) after HG supplementation (n = 31). Expression of inflammation-related genes was upregulated in equol producers but downregulated in nonproducers, independent of supplement type. Only 4.4-7.0% of the genes with significantly changed expression were estrogen responsive. Body weight, adipocyte size, and plasma lipid profile were not affected by isoflavone supplementation. Effects of isoflavones on adipose tissue gene expression were influenced by supplement composition and equol-producing phenotype, whereas estrogen-responsive effects were lacking. LG isoflavone supplementation resulted in a caloric restriction-like gene expression profile for both producer phenotypes and pointed toward a potential beneficial effect, whereas both supplements induced anti-inflammatory gene expression in equol producers. The study was registered at clinicaltrials.gov as NCT01556737. © 2014 American Society for Nutrition.

A randomized, double-blind, placebo-controlled crossover study of the effects of levetiracetam on cognition, mood, and balance in healthy older adults.

PubMed

Schoenberg, Mike R; Rum, Ruba S; Osborn, Katie E; Werz, Mary Ann

2017-09-01

The cognitive and mood effects of levetiracetam (LEV) in older adults are not known. This study compared the cognitive and mood effects of LEV to placebo in healthy older adults. Cognitive, mood, and balance variables were compared between LEV and placebo using a randomized, double-blind, placebo-controlled crossover study with two 5-week treatment periods. Healthy volunteers (n = 20) aged 65-80 (mean age 72.4) received either LEV or placebo in which the LEV target dose was 1,000 mg/day. Volunteers, aged 65-80, were without epilepsy to limit potentially confounding the impact of seizures and/or underlying neuropathology on outcomes. LEV was initiated at 250 mg twice a day for 2 weeks, then increased to 500 mg twice a day for 2 weeks, and then tapered to 250 mg twice a day for 1 week. This was randomized with placebo for the two treatment arms. Measures included standardized neuropsychological, mood, and balance tests yielding 32 variables. Balance was assessed using subjective report (e.g., A-B neurotoxicity scale) and objective data (e.g., Berg Balance Scale). Average LEV serum concentration was 16.9 (standard deviation [SD} 7.7). Repeated-measures analysis of variance (ANOVA) found no differences between LEV and placebo phases for 29 (90.6%) of 32 variables including no change in balance. Performance on LEV was better than placebo on a visual memory (MCG Complex Figure Recall; p = 0.007) and two attention tests (Trail Making Test, Part A, p = 0.009; Stroop Interference, p = 0.004). There was a trend for greater irritability and fatigue (POMS Anger and Fatigue) during the LEV phase (p = 0.029, p = 0.035). Effect-size changes were generally small (Cohen d < 0.5). LEV was well tolerated in this elderly population in terms of cognition, mood, and balance. When anticonvulsant medication is indicated for older adults, LEV has pharmacokinetic advantages, and these data indicate no adverse impact on cognition or balance. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Glycomacropeptide for nutritional management of phenylketonuria: a randomized, controlled, crossover trial12

PubMed Central

Stroup, Bridget M; Clayton, Murray K; Murali, Sangita G; Rice, Gregory M; Rohr, Frances; Levy, Harvey L

2016-01-01

Background: To prevent cognitive impairment, phenylketonuria requires lifelong management of blood phenylalanine (Phe) concentration with a low-Phe diet. The diet restricts intake of Phe from natural proteins in combination with traditional amino acid medical foods (AA-MFs) or glycomacropeptide medical foods (GMP-MFs) that contain primarily intact protein and a small amount of Phe. Objective: We investigated the efficacy and safety of a low-Phe diet combined with GMP-MFs or AA-MFs providing the same quantity of protein equivalents in free-living subjects with phenylketonuria. Design: This 2-stage, randomized crossover trial included 30 early-treated phenylketonuria subjects (aged 15–49 y), 20 with classical and 10 with variant phenylketonuria. Subjects consumed, in random order for 3 wk each, their usual low-Phe diet combined with AA-MFs or GMP-MFs. The treatments were separated by a 3-wk washout with AA-MFs. Fasting plasma amino acid profiles, blood Phe concentrations, food records, and neuropsychological tests were obtained. Results: The frequency of medical food intake was higher with GMP-MFs than with AA-MFs. Subjects rated GMP-MFs as more acceptable than AA-MFs and noted improved gastrointestinal symptoms and less hunger with GMP-MFs. ANCOVA indicated no significant mean ± SE increase in plasma Phe (62 ± 40 μmol/L, P = 0.136), despite a significant increase in Phe intake from GMP-MFs (88 ± 6 mg Phe/d, P = 0.026). AA-MFs decreased plasma Phe (−85 ± 40 μmol/L, P = 0.044) with stable Phe intake. Blood concentrations of Phe across time were not significantly different (AA-MFs = 444 ± 34 μmol/L, GMP-MFs = 497 ± 34 μmol/L), suggesting similar Phe control. Results of the Behavior Rating Inventory of Executive Function were not significantly different. Conclusions: GMP-MFs provide a safe and acceptable option for the nutritional management of phenylketonuria. The greater acceptability and fewer side effects noted with GMP-MFs than with AA-MFs may enhance dietary adherence for individuals with phenylketonuria. This trial was registered at www.clinicaltrials.gov as NCT01428258. PMID:27413125

Glycomacropeptide for nutritional management of phenylketonuria: a randomized, controlled, crossover trial.

PubMed

Ney, Denise M; Stroup, Bridget M; Clayton, Murray K; Murali, Sangita G; Rice, Gregory M; Rohr, Frances; Levy, Harvey L

2016-08-01

To prevent cognitive impairment, phenylketonuria requires lifelong management of blood phenylalanine (Phe) concentration with a low-Phe diet. The diet restricts intake of Phe from natural proteins in combination with traditional amino acid medical foods (AA-MFs) or glycomacropeptide medical foods (GMP-MFs) that contain primarily intact protein and a small amount of Phe. We investigated the efficacy and safety of a low-Phe diet combined with GMP-MFs or AA-MFs providing the same quantity of protein equivalents in free-living subjects with phenylketonuria. This 2-stage, randomized crossover trial included 30 early-treated phenylketonuria subjects (aged 15-49 y), 20 with classical and 10 with variant phenylketonuria. Subjects consumed, in random order for 3 wk each, their usual low-Phe diet combined with AA-MFs or GMP-MFs. The treatments were separated by a 3-wk washout with AA-MFs. Fasting plasma amino acid profiles, blood Phe concentrations, food records, and neuropsychological tests were obtained. The frequency of medical food intake was higher with GMP-MFs than with AA-MFs. Subjects rated GMP-MFs as more acceptable than AA-MFs and noted improved gastrointestinal symptoms and less hunger with GMP-MFs. ANCOVA indicated no significant mean ± SE increase in plasma Phe (62 ± 40 μmol/L, P = 0.136), despite a significant increase in Phe intake from GMP-MFs (88 ± 6 mg Phe/d, P = 0.026). AA-MFs decreased plasma Phe (-85 ± 40 μmol/L, P = 0.044) with stable Phe intake. Blood concentrations of Phe across time were not significantly different (AA-MFs = 444 ± 34 μmol/L, GMP-MFs = 497 ± 34 μmol/L), suggesting similar Phe control. Results of the Behavior Rating Inventory of Executive Function were not significantly different. GMP-MFs provide a safe and acceptable option for the nutritional management of phenylketonuria. The greater acceptability and fewer side effects noted with GMP-MFs than with AA-MFs may enhance dietary adherence for individuals with phenylketonuria. This trial was registered at www.clinicaltrials.gov as NCT01428258. © 2016 American Society for Nutrition.

The role of meal viscosity and oat β-glucan characteristics in human appetite control: a randomized crossover trial.

PubMed

Rebello, Candida J; Chu, Yi-Fang; Johnson, William D; Martin, Corby K; Han, Hongmei; Bordenave, Nicolas; Shi, Yuhui; O'Shea, Marianne; Greenway, Frank L

2014-05-28

Foods that enhance satiety can help consumers to resist environmental cues to eat, and improve the nutritional quality of their diets. Viscosity generated by oat β-glucan, influences gastrointestinal mechanisms that mediate satiety. Differences in the source, processing treatments, and interactions with other constituents in the food matrix affect the amount, solubility, molecular weight, and structure of the β-glucan in products, which in turn influences the viscosity. This study examined the effect of two types of oatmeal and an oat-based ready-to-eat breakfast cereal (RTEC) on appetite, and assessed differences in meal viscosity and β-glucan characteristics among the cereals. Forty-eight individuals were enrolled in a randomized crossover trial. Subjects consumed isocaloric breakfast meals containing instant oatmeal (IO), old-fashioned oatmeal (SO) or RTEC in random order at least a week apart. Each breakfast meal contained 218 kcal (150 kcal cereal, and 68 kcal milk) Visual analogue scales measuring appetite were completed before breakfast, and over four hours, following the meal. Starch digestion kinetics, meal viscosities, and β-glucan characteristics for each meal were determined. Appetite responses were analyzed by area under the curve. Mixed models were used to analyze response changes over time. IO increased fullness (p = 0.04), suppressed desire to eat (p = 0.01) and reduced prospective intake (p < 0.01) more than the RTEC over four hours, and consistently at the 60 minute time-point. SO reduced prospective intake (p = 0.04) more than the RTEC. Hunger scores were not significantly different except that IO reduced hunger more than the RTEC at the 60 minute time-point. IO and SO had higher β-glucan content, molecular weight, gastric viscosity, and larger hydration spheres than the RTEC, and IO had greater viscosity after oral and initial gastric digestion (initial viscosity) than the RTEC. IO and SO improved appetite control over four hours compared to RTEC. Initial viscosity of oatmeal may be especially important for reducing appetite.

Effects of the pure flavonoids epicatechin and quercetin on vascular function and cardiometabolic health: a randomized, double-blind, placebo-controlled, crossover trial.

PubMed

Dower, James I; Geleijnse, Johanna M; Gijsbers, Lieke; Zock, Peter L; Kromhout, Daan; Hollman, Peter C H

2015-05-01

Prospective cohort studies showed inverse associations between the intake of flavonoid-rich foods (cocoa and tea) and cardiovascular disease (CVD). Intervention studies showed protective effects on intermediate markers of CVD. This may be due to the protective effects of the flavonoids epicatechin (in cocoa and tea) and quercetin (in tea). We investigated the effects of supplementation of pure epicatechin and quercetin on vascular function and cardiometabolic health. Thirty-seven apparently healthy men and women aged 40-80 y with a systolic blood pressure (BP) between 125 and 160 mm Hg at screening were enrolled in a randomized, double-blind, placebo-controlled, crossover trial. CVD risk factors were measured before and after 4 wk of daily flavonoid supplementation. Participants received (-)-epicatechin (100 mg/d), quercetin-3-glucoside (160 mg/d), or placebo capsules for 4 wk in random order. The primary outcome was the change in flow-mediated dilation from pre- to postintervention. Secondary outcomes included other markers of CVD risk and vascular function. Epicatechin supplementation did not change flow-mediated dilation significantly (1.1% absolute; 95% CI: -0.1%, 2.3%; P = 0.07). Epicatechin supplementation improved fasting plasma insulin (Δ insulin: -1.46 mU/L; 95% CI: -2.74, -0.18 mU/L; P = 0.03) and insulin resistance (Δ homeostasis model assessment of insulin resistance: -0.38; 95% CI: -0.74, -0.01; P = 0.04) and had no effect on fasting plasma glucose. Epicatechin did not change BP (office BP and 24-h ambulatory BP), arterial stiffness, nitric oxide, endothelin 1, or blood lipid profile. Quercetin-3-glucoside supplementation had no effect on flow-mediated dilation, insulin resistance, or other CVD risk factors. Our results suggest that epicatechin may in part contribute to the cardioprotective effects of cocoa and tea by improving insulin resistance. It is unlikely that quercetin plays an important role in the cardioprotective effects of tea. This study was registered at clinicaltrials.gov as NCT01691404. © 2015 American Society for Nutrition.

Knemometry Assessment of Short-term Growth in Children With Asthma Receiving Fluticasone Furoate for 2 Weeks: A Randomized, Placebo-controlled, Crossover Trial.

PubMed

Wolthers, Ole D; Stone, Sally; Bareille, Philippe; Tomkins, Susan; Khindri, Sanjeev

2017-06-01

A dry powder inhaler formulation of the inhaled corticosteroid fluticasone furoate (FF) is being evaluated for use in children. An important potential risk associated with the use of inhaled corticosteroids in children is growth suppression. Therefore, the aim of this study was to assess the short-term lower leg growth in children with asthma treated for 2 weeks with inhaled FF versus placebo from the ELLIPTA inhaler. Prepubertal children with persistent asthma (n = 60; aged 5 to <12 years) were recruited into a randomized, double-blind, placebo-controlled, 2-way crossover, noninferiority study. The study consisted of four 2-week periods: run-in, 2 treatment periods, 1 washout period, and a 1-week follow-up period. Interventions were FF 50 µg and placebo once daily in the evening. Lower leg length was measured by using knemometry. The randomized ITT population comprised 36 boys and 24 girls with a mean age of 8.7 (standard deviation, 1.5; range, 5-11) years; 58% had a duration of asthma ≥5 years. Fifty-eight subjects completed both treatment periods. The least squares mean growth rate was 0.31 mm/week during treatment with FF and 0.36 mm/week during the placebo period. The difference in adjusted least squares mean growth rates between FF and placebo was -0.052 mm/week with a 95% CI of -0.122 to 0.018. This finding was greater than the prespecified noninferiority margin of -0.20 mm/week. The overall incidence of adverse events was 35% with placebo and 22% with FF. Inhaled FF 50 µg provided once daily for 2 weeks was noninferior to placebo in terms of effects on short-term lower leg growth in children with asthma. To further quantify the risk of growth suppression in children, intermediate-term growth studies should be conducted. Inhaled FF 50 µg was well tolerated in this study population. ClinicalTrials.gov identifier: NCT02502734. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

The role of meal viscosity and oat β-glucan characteristics in human appetite control: a randomized crossover trial

PubMed Central

2014-01-01

Background Foods that enhance satiety can help consumers to resist environmental cues to eat, and improve the nutritional quality of their diets. Viscosity generated by oat β-glucan, influences gastrointestinal mechanisms that mediate satiety. Differences in the source, processing treatments, and interactions with other constituents in the food matrix affect the amount, solubility, molecular weight, and structure of the β-glucan in products, which in turn influences the viscosity. This study examined the effect of two types of oatmeal and an oat-based ready-to-eat breakfast cereal (RTEC) on appetite, and assessed differences in meal viscosity and β-glucan characteristics among the cereals. Methods Forty-eight individuals were enrolled in a randomized crossover trial. Subjects consumed isocaloric breakfast meals containing instant oatmeal (IO), old-fashioned oatmeal (SO) or RTEC in random order at least a week apart. Each breakfast meal contained 218 kcal (150 kcal cereal, and 68 kcal milk) Visual analogue scales measuring appetite were completed before breakfast, and over four hours, following the meal. Starch digestion kinetics, meal viscosities, and β-glucan characteristics for each meal were determined. Appetite responses were analyzed by area under the curve. Mixed models were used to analyze response changes over time. Results IO increased fullness (p = 0.04), suppressed desire to eat (p = 0.01) and reduced prospective intake (p < 0.01) more than the RTEC over four hours, and consistently at the 60 minute time-point. SO reduced prospective intake (p = 0.04) more than the RTEC. Hunger scores were not significantly different except that IO reduced hunger more than the RTEC at the 60 minute time-point. IO and SO had higher β-glucan content, molecular weight, gastric viscosity, and larger hydration spheres than the RTEC, and IO had greater viscosity after oral and initial gastric digestion (initial viscosity) than the RTEC. Conclusion IO and SO improved appetite control over four hours compared to RTEC. Initial viscosity of oatmeal may be especially important for reducing appetite. PMID:24884934

Decomposing Multifractal Crossovers

PubMed Central

Nagy, Zoltan; Mukli, Peter; Herman, Peter; Eke, Andras

2017-01-01

Physiological processes—such as, the brain's resting-state electrical activity or hemodynamic fluctuations—exhibit scale-free temporal structuring. However, impacts common in biological systems such as, noise, multiple signal generators, or filtering by transport function, result in multimodal scaling that cannot be reliably assessed by standard analytical tools that assume unimodal scaling. Here, we present two methods to identify breakpoints or crossovers in multimodal multifractal scaling functions. These methods incorporate the robust iterative fitting approach of the focus-based multifractal formalism (FMF). The first approach (moment-wise scaling range adaptivity) allows for a breakpoint-based adaptive treatment that analyzes segregated scale-invariant ranges. The second method (scaling function decomposition method, SFD) is a crossover-based design aimed at decomposing signal constituents from multimodal scaling functions resulting from signal addition or co-sampling, such as, contamination by uncorrelated fractals. We demonstrated that these methods could handle multimodal, mono- or multifractal, and exact or empirical signals alike. Their precision was numerically characterized on ideal signals, and a robust performance was demonstrated on exemplary empirical signals capturing resting-state brain dynamics by near infrared spectroscopy (NIRS), electroencephalography (EEG), and blood oxygen level-dependent functional magnetic resonance imaging (fMRI-BOLD). The NIRS and fMRI-BOLD low-frequency fluctuations were dominated by a multifractal component over an underlying biologically relevant random noise, thus forming a bimodal signal. The crossover between the EEG signal components was found at the boundary between the δ and θ bands, suggesting an independent generator for the multifractal δ rhythm. The robust implementation of the SFD method should be regarded as essential in the seamless processing of large volumes of bimodal fMRI-BOLD imaging data for the topology of multifractal metrics free of the masking effect of the underlying random noise. PMID:28798694

Randomized Crossover Comparison of the Short-Term Efficacy and Safety of Single Half-Dose Silodosin and Tamsulosin Hydrochoride in Men With Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.

PubMed

Takeshita, Hideki; Moriyama, Shingo; Arai, Yoshiaki; Washino, Satoshi; Saito, Kimitoshi; Chiba, Koji; Horiuchi, Susumu; Noro, Akira

2016-01-01

To compare the efficacy and safety of single half-dose silodosin and single full-dose tamsulosin in Japanese men with lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS/BPH). Japanese men aged ≥50 years with LUTS/BPH and an International Prostate Symptom Score (IPSS) of ≥8 were enrolled in the randomized crossover study and divided into silodosin-preceding (S-T) and tamsulosin-preceding (T-S) groups. The S-T group received 4 mg silodosin once daily for 4 weeks followed by 0.2 mg tamsulosin once daily for 4 weeks. The T-S group received the reverse treatment sequence. A washout period prior to drug crossover was not included. Subjective and objective efficacy parameters including IPSS, quality of life (QOL) index, uroflowmetry, and safety were compared between the two groups. Thirty of 34 men (S-T group n = 16; T-S group n = 14) completed the study. Both drugs significantly improved all IPSS items and QOL index in the first treatment period. Subjective improvement in nocturia by silodosin was observed in both the first and crossover treatment periods. Objective improvement in maximum flow rate by silodosin was only observed in the first treatment period. Adverse events occurred more frequently with silodosin than with tamsulosin; however, none of the adverse events required treatment discontinuation. Ejaculation disorders occurred in three participants (10%) and were associated with silodosin use. Single half-dose silodosin has a similar efficacy to full-dose tamsulosin in Japanese men with LUTS/BPH and thus, may represent an effective, safe, and affordable treatment option. © 2015 Wiley Publishing Asia Pty Ltd.

A Double-Blind Placebo-Controlled Crossover Trial of Intravenous Magnesium Sulfate for Foscarnet-Induced Ionized Hypocalcemia and Hypomagnesemia in Patients with AIDS and Cytomegalovirus Infection

PubMed Central

Huycke, Mark M.; Naguib, M. Tarek; Stroemmel, Mathias M.; Blick, Kenneth; Monti, Katherine; Martin-Munley, Sarah; Kaufman, Chris

2000-01-01

Foscarnet (trisodium phosphonoformate hexahydrate) is an antiviral agent used to treat cytomegalovirus disease in immunocompromised patients. One common side effect is acute ionized hypocalcemia and hypomagnesemia following intravenous administration. Foscarnet-induced ionized hypomagnesemia might contribute to ionized hypocalcemia by impairing excretion of preformed parathyroid hormone (PTH) or by producing target organ resistance. Prevention of ionized hypomagnesemia following foscarnet administration could blunt the development of ionized hypocalcemia. To determine whether intravenous magnesium ameliorates the decline in ionized calcium and/or magnesium following foscarnet infusions, MgSO4 at doses of 1, 2, and 3 g was administered in a double-blind, placebo-controlled, randomized, crossover trial to 12 patients with AIDS and cytomegalovirus disease. Overall, increasing doses of MgSO4 reduced or eliminated foscarnet-induced acute ionized hypomagnesemia. Supplementation, however, had no discernible effect on foscarnet-induced ionized hypocalcemia despite significant increases in serum PTH levels. No dose-related, clinically significant adverse events were found, suggesting that intravenous supplementation with up to 3 g of MgSO4 was safe in this chronically ill population. Since parenteral MgSO4 did not alter foscarnet-induced ionized hypocalcemia or symptoms associated with foscarnet, routine intravenous supplementation for patients with normal serum magnesium levels is not recommended during treatment with foscarnet. PMID:10898688

The Effect of a 12-Week Beta-hydroxy-beta-methylbutyrate (HMB) Supplementation on Highly-Trained Combat Sports Athletes: A Randomised, Double-Blind, Placebo-Controlled Crossover Study

PubMed Central

Jeszka, Jan; Podgórski, Tomasz

2017-01-01

The aim of this study was to verify the effect of beta-hydroxy-beta-methylbutyrate (HMB) supplementation on physical capacity, body composition and the value of biochemical parameters in highly-trained combat sports athletes. Forty-two males highly-trained in combat sports were subjected to 12 weeks of supplementation with HMB and a placebo in a randomized, placebo controlled, double-blind crossover manner. Over the course of the experiment, aerobic and anaerobic capacity was determined, while analyses were conducted on body composition and levels of creatine kinase, lactate dehydrogenase, testosterone, cortisol and lactate. Following HMB supplementation, fat-free mass increased (p = 0.049) with a simultaneous reduction of fat mass (p = 0.016) in comparison to placebo. In turn, after HMB supplementation, the following indicators increased significantly in comparison to the placebo: the time to reach ventilatory threshold (p < 0.0001), threshold load (p = 0.017) and the threshold HR (p < 0.0001), as well as anaerobic peak power (p = 0.005), average power (p = 0.029), maximum speed (p < 0.001) and post-exercise lactate concentrations (p < 0.0001). However, when compared to the placebo, no differences were observed in blood marker levels. The results indicate that supplying HMB promotes advantageous changes in body composition and stimulates an increase in aerobic and anaerobic capacity in combat sports athletes. PMID:28708126

The Effect of a 12-Week Beta-hydroxy-beta-methylbutyrate (HMB) Supplementation on Highly-Trained Combat Sports Athletes: A Randomised, Double-Blind, Placebo-Controlled Crossover Study.

PubMed

Durkalec-Michalski, Krzysztof; Jeszka, Jan; Podgórski, Tomasz

2017-07-14

The aim of this study was to verify the effect of beta-hydroxy-beta-methylbutyrate (HMB) supplementation on physical capacity, body composition and the value of biochemical parameters in highly-trained combat sports athletes. Forty-two males highly-trained in combat sports were subjected to 12 weeks of supplementation with HMB and a placebo in a randomized, placebo controlled, double-blind crossover manner. Over the course of the experiment, aerobic and anaerobic capacity was determined, while analyses were conducted on body composition and levels of creatine kinase, lactate dehydrogenase, testosterone, cortisol and lactate. Following HMB supplementation, fat-free mass increased ( p = 0.049) with a simultaneous reduction of fat mass ( p = 0.016) in comparison to placebo. In turn, after HMB supplementation, the following indicators increased significantly in comparison to the placebo: the time to reach ventilatory threshold ( p < 0.0001), threshold load ( p = 0.017) and the threshold HR ( p < 0.0001), as well as anaerobic peak power ( p = 0.005), average power ( p = 0.029), maximum speed ( p < 0.001) and post-exercise lactate concentrations ( p < 0.0001). However, when compared to the placebo, no differences were observed in blood marker levels. The results indicate that supplying HMB promotes advantageous changes in body composition and stimulates an increase in aerobic and anaerobic capacity in combat sports athletes.

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.

Postprandial serum endotoxin in healthy humans is modulated by dietary fat in a randomized, controlled, cross-over study.

PubMed

Lyte, Joshua M; Gabler, Nicholas K; Hollis, James H

2016-11-05

High-fat diets may contribute to metabolic disease via postprandial changes in serum endotoxin and inflammation. It is unclear how dietary fat composition may alter these parameters. We hypothesized that a meal rich in n-3 (ω3) fatty acids would reduce endotoxemia and associated inflammation but a saturated or n-6 (ω6) fatty acid-rich meal would increase postprandial serum endotoxin concentrations and systemic inflammation in healthy adults. Healthy adults (n = 20; mean age 25 ± 3.2 S.D. years) were enrolled in this single-blind, randomized, cross-over study. Participants were randomized to treatment and reported to the laboratory, after an overnight fast, on four occasions separated by at least one week. Participants were blinded to treatment meal and consumed one of four isoenergetic meals that provided: 1) 20 % fat (control; olive oil) or 35 % fat provided from 2) n-3 (ω3) (DHA = 500 mg; fish oil); 3) n-6 (ω6) (7.4 g; grapeseed oil) or 4) saturated fat (16 g; coconut oil). Baseline and postprandial blood samples were collected. Primary outcome was defined as the effect of treatment meal on postprandial endotoxemia. Serum was analyzed for metabolites, inflammatory markers, and endotoxin. Data from all 20 participants were analyzed using repeated-measures ANCOVA. Participant serum endotoxin concentration was increased during the postprandial period after the consumption of the saturated fat meal but decreased after the n-3 meal (p < 0.05). The n-6 meal did not effect a different outcome in participant postprandial serum endotoxin concentration from that of the control meal (p > 0.05). There was no treatment meal effect on participant postprandial serum biomarkers of inflammation. Postprandial serum triacylglycerols were significantly elevated following the n-6 meal compared to the n-3 meal. Non-esterified fatty acids were significantly increased after consumption of the saturated fat meal compared to other treatment meals. Meal fatty acid composition modulates postprandial serum endotoxin concentration in healthy adults. However, postprandial endotoxin was not associated with systemic inflammation in vivo. This study was retrospectively registered at clinicaltrials.gov as NCT02521779 on July 28, 2015.

The motilin agonist erythromycin increases hunger by modulating homeostatic and hedonic brain circuits in healthy women: a randomized, placebo-controlled study.

PubMed

Zhao, Dongxing; Meyer-Gerspach, Anne Christin; Deloose, Eveline; Iven, Julie; Weltens, Nathalie; Depoortere, Inge; O'daly, Owen; Tack, Jan; Van Oudenhove, Lukas

2018-01-29

The motilin agonist, erythromycin, induces gastric phase III of the migrating motor complex, which in turn generates hunger peaks. To identify the brain mechanisms underlying these orexigenic effects, 14 healthy women participated in a randomized, placebo-controlled crossover study. Functional magnetic resonance brain images were acquired for 50 minutes interprandially. Intravenous infusion of erythromycin (40 mg) or saline started 10 minutes after the start of scanning. Blood samples (for glucose and hormone levels) and hunger ratings were collected at fixed timepoints. Thirteen volunteers completed the study, without any adverse events. Brain regions involved in homeostatic and hedonic control of appetite and food intake responded to erythromycin, including pregenual anterior cingulate cortex, anterior insula cortex, orbitofrontal cortex, amygdala, caudate, pallidum and putamen bilaterally, right accumbens, hypothalamus, and midbrain. Octanoylated ghrelin levels decreased, whereas both glucose and insulin increased after erythromycin. Hunger were higher after erythromycin, and these differences covaried with the brain response in most of the abovementioned regions. The motilin agonist erythromycin increases hunger by modulating neurocircuitry related to homeostatic and hedonic control of appetite and feeding. These results confirm recent behavioural findings identifying motilin as a key orexigenic hormone in humans, and identify the brain mechanisms underlying its effect.

Effect of an essential oil-containing mouth rinse on VSC-producing bacteria on the tongue.

PubMed

Thaweboon, Sroisiri; Thaweboon, Boonyanit

2011-03-01

The objective of the present study was to investigate the inhibitory effect of a commercially available essential oil-containing mouth rinse 12 hours after a single rinse and two weeks of twice daily rinsing, on volatile sulphur compounds (VSC) producing bacteria on the tongue. The study was a randomized, double-blind, controlled crossover design. Thirty-six healthy subjects, aged 20-48 years, volunteered to participate in the study. Subjects were randomly assigned to rinse twice daily with either an essential oil-containing mouth rinse (Cool Mint Listerine Antiseptic) or a negative control rinse. Bacteria samples were taken from the dorsum of the tongue at baseline, after the first rinse and two weeks later. They were plated on OOPS medium to enumerate the VSC-producing bacteria. Intergroup comparisons of log10 transformed colony-forming units of the samples were made using analysis of covariance. Each comparison was performed at a 5% significance level. The mean VSC-producing bacteria in subjects using the essential oil mouth rinse were significantly lower than those using the control rinse twice daily. In healthy subjects, rinsing with an essential oil-containing mouth rinse can have a significant effect on VSC-producing bacteria on the tongue and may be useful for controlling intrinsic oral malodor over prolonged periods.

Electronic bidirectional valve circuit prevents crossover distortion and threshold effect

NASA Technical Reports Server (NTRS)

Kernick, A.

1966-01-01

Four-terminal network forms a bidirectional valve which will switch or alternate an ac signal without crossover distortion or threshold effect. In this network, an isolated control signal is sufficient for circuit turn-on.

Effects of beta-carotene fortified synbiotic food on metabolic control of patients with type 2 diabetes mellitus: A double-blind randomized cross-over controlled clinical trial.

PubMed

Asemi, Zatollah; Alizadeh, Sabihe-Alsadat; Ahmad, Khorshidi; Goli, Mohammad; Esmaillzadeh, Ahmad

2016-08-01

The aim of the present study was to determine the beneficial effects of beta-carotene fortified synbiotic food intake on metabolic status in patients with type 2 diabetes mellitus (T2DM). This randomized double-blinded placebo-controlled crossover clinical trial was conducted among 51 patients with T2DM. Individuals were randomly assigned to take either a beta-carotene fortified synbiotic (n = 51) or control food (n = 51) for 6 weeks. The beta-carotene fortified synbiotic was containing Lactobacillus sporogenes (1 × 10(7) CFU), 0.1 g inulin and 0.05 g beta-carotene. Control food (the same substance without probiotic, inulin and beta-carotene) was packed in identical 9-g packages. Patients were requested to use the beta-carotene fortified synbiotic and control foods three times a day. Beta-carotene fortified synbiotic food consumption resulted in a significant decrease in insulin (-1.00 ± 7.90 vs. +3.68 ± 6.91 μIU/mL, P = 0.002), HOMA-IR (-0.73 ± 3.96 vs. +1.82 ± vbnm4.09, P = 0.002), HOMA-B (-0.52 ± 19.75 vs. +8.71 ± 17.15, P = 0.01), triglycerides (-2.86 ± 49.53 vs. +20.14 ± 50.10 mg/dL, P = 0.02), VLDL-cholesterol levels (-0.57 ± 9.90 vs. +4.03 ± 10.02 mg/dL, P = 0.02) and total-/HDL-cholesterol ratio (-0.01 ± 1.08 vs. +0.64 ± 0.81, P = 0.001) compared to the control food. In addition, beta-carotene fortified synbiotic food consumption led to elevated plasma nitric oxide (NO) (+6.83 ± 16.14 vs. -3.76 ± 16.47 μmol/L, P = 0.001) and glutathione (GSH) (+36.58 ± 296.71 vs. -92.04 ± 243.05 μmol/L, P = 0.01). Beta-carotene fortified synbiotic food intake in patients with T2DM for 6 weeks had favorable effects on insulin, HOMA-IR, HOMA-B, triglycerides, VLDL-cholesterol, total-/HDL-cholesterol ratio, NO and GSH levels. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Fluoride Increase in Saliva and Dental Biofilm due to a Meal Prepared with Fluoridated Water or Salt: A Crossover Clinical Study.

PubMed

Lima, Carolina V; Tenuta, Livia M A; Cury, Jaime A

2018-06-07

Knowledge about fluoride delivery to oral fluids from foods cooked with fluoridated water and salt is scarce, and no study has evaluated fluoride concentrations in saliva or biofilm during meal consumption. In this randomized double-blind crossover study, 12 volunteers ingested meals (rice, beans, meat, and legumes) prepared with nonfluoridated water and salt (control group), fluoridated water (0.70 mg F/L; water group), and fluoridated salt (183.7 mg F/kg; salt group). Whole saliva was collected before meal ingestion, during mastication, and up to 2 h after meal ingestion. Dental biofilm was collected before and immediately after meal ingestion. Fluoride concentrations in saliva and dental biofilm were determined by an ion-specific electrode. The mean (±standard deviation; n = 4) fluoride concentrations in meals prepared for the control, water, and salt groups were 0.039 ± 0.01, 0.43 ± 0.04, and 1.71 ± 0.32 μg F/g, respectively. The three groups had significantly different fluoride concentrations in saliva collected during mastication (p < 0.0001) and after meal ingestion (p < 0.04; salt > water > control). The fluoride concentration in saliva returned to baseline 30 min after meal ingestion in the water group but remained high for up to 2 h in the salt group (p = 0.002). The fluoride concentration in biofilm fluid differed only between the salt and control groups (p = 0.008). The mastication of foods cooked with fluoridated water and salt increases fluoride concentrations in oral fluids and may contribute to the local effect of these community-based fluoride interventions on caries control. © 2018 S. Karger AG, Basel.

The effect of a cinnamon-, chromium- and magnesium-formulated honey on glycaemic control, weight loss and lipid parameters in type 2 diabetes: an open-label cross-over randomised controlled trial.

PubMed

Whitfield, Patricia; Parry-Strong, Amber; Walsh, Emily; Weatherall, Mark; Krebs, Jeremy D

2016-04-01

This randomised controlled trial assessed the acute and long-term effects of daily supplementation of kanuka honey, formulated with cinnamon, chromium and magnesium on glucose metabolism, weight and lipid parameters in individuals with type 2 diabetes. Twelve individuals with type 2 diabetes received 53.5 g of a formulated honey and a control (non-formulated) kanuka honey in a random order for 40 days, using cross-over design. Fasting glucose, insulin, HbA1c, lipids and anthropometric measures were measured at baseline and end of treatment. A meal tolerance test was performed at baseline to assess acute metabolic response. There was no statistically significant difference in acute glucose metabolism between treatment groups, as measured by the Matsuda index and AUC for glucose and insulin. After the 40-day intervention with honey, fasting glucose did not differ significantly between the two treatments (95 % CI -2.6 to 0.07). There was no statistically significant change in HbA1c or fasting insulin. There was a statistically significant reduction in total cholesterol by -0.29 mmol/L (95 % CI -0.57 to -0.23), LDL cholesterol by -0.29 mmol/L (95 % CI -0.57 to -0.23) and weight by -2.2 kg (95 % CI -4.2 to -0.1). There was a trend towards increased HDL and reduced systolic blood pressure in the intervention treatment. The addition of cinnamon, chromium and magnesium supplementation to kanuka honey was not associated with a significant improvement in glucose metabolism or glycaemic control in individuals with type 2 diabetes. Use of the formulated honey was associated with a reduction in weight and improvements in lipid parameters, and should be investigated further.

Modified Veress needle decompression of tension pneumothorax: a randomized crossover animal study.

PubMed

Lubin, Dafney; Tang, Andrew L; Friese, Randall S; Martin, Matthew; Green, D J; Jones, Trevor; Means, Russell R; Ginwalla, Rashna; O'Keeffe, Terence S; Joseph, Bellal A; Wynne, Julie L; Kulvatunyou, Narong; Vercruysse, Gary; Gries, Lynn; Rhee, Peter

2013-12-01

The current prehospital standard of care using a large bore intravenous catheter for tension pneumothorax (tPTX) decompression is associated with a high failure rate. We developed a modified Veress needle (mVN) for this condition. The purpose of this study was to evaluate the effectiveness and safety of the mVN as compared with a 14-gauge needle thoracostomy (NT) in a swine tPTX model. tPTX was created in 16 adult swine via thoracic CO2 insufflation to 15 mm Hg. After tension physiology was achieved, defined as a 50% reduction of cardiac output, the swine were randomized to undergo either mVN or NT decompression. Failure to restore 80% baseline systolic blood pressure within 5 minutes resulted in crossover to the alternate device. The success rate of each device, death, and need for crossover were analyzed using χ. Forty-three tension events were created in 16 swine (24 mVN, 19 NT) at 15 mm Hg of intrathoracic pressure with a mean CO2 volume of 3.8 L. tPTX resulted in a 48% decline of systolic blood pressure from baseline and 73% decline of cardiac output, and 42% had equalization of central venous pressure with pulmonary capillary wedge pressure. All tension events randomized to mVN were successfully rescued within a mean (SD) of 70 (86) seconds. NT resulted in four successful decompressions (21%) within a mean (SD) of 157 (96) seconds. Four swine (21%) died within 5 minutes of NT decompression. The persistent tension events where the swine survived past 5 minutes (11 of 19 NTs) underwent crossover mVN decompression, yielding 100% rescue. Neither the mVN nor the NT was associated with inadvertent injuries to the viscera. Thoracic insufflation produced a reliable and highly reproducible model of tPTX. The mVN is vastly superior to NT for effective and safe tPTX decompression and physiologic recovery. Further research should be invested in the mVN for device refinement and replacement of NT in the field.

Safety of a silicone elastomer vaginal ring as potential microbicide delivery method in African women: A Phase 1 randomized trial.

PubMed

Nel, Annaléne; Martins, Janine; Bekker, Linda-Gail; Ramjee, Gita; Masenga, Gileard; Rees, Helen; van Niekerk, Neliëtte

2018-01-01

Women in sub-Saharan Africa are in urgent need of female-initiated human immunodeficiency virus (HIV) preventative methods. Vaginal rings are one dosage form in development for delivery of HIV microbicides. However, African women have limited experience with vaginal rings. This Phase I, randomized, crossover trial assessed and compared the safety, acceptability and adherence of a silicone elastomer placebo vaginal ring, intended as a microbicide delivery method, inserted for a 12-week period in healthy, HIV-negative, sexually active women in South Africa and Tanzania. 170 women, aged 18 to 35 years were enrolled with 88 women randomized to Group A, using a placebo vaginal ring for 12 weeks followed by a 12-week safety observation period. 82 women were randomized to Group B and observed for safety first, followed by a placebo vaginal ring for 12 weeks. Safety was assessed by clinical laboratory assessments, pelvic/colposcopy examinations and adverse events. Possible carry-over effect was addressed by ensuring no signs or symptoms of genital irritation at crossover. No safety concerns were identified for any safety variables assessed during the trial. No serious adverse events were reported considered related to the placebo vaginal ring. Vaginal candidiasis was the most common adverse event occurring in 11% of participants during each trial period. Vaginal discharge (2%), vaginal odour (2%), and bacterial vaginitis (2%) were assessed as possibly or probably related to the vaginal ring. Thirty-four percent of participants had sexually transmitted infections (STIs) at screening, compared to 12% of participants who tested positive for STIs at crossover and the final trial visit. Three participants (2%) tested HIV positive during the trial. The silicone elastomer vaginal ring had no safety concerns, demonstrating a profile favorable for further development for topical release of antiretroviral-based microbicides.

Safety of a silicone elastomer vaginal ring as potential microbicide delivery method in African women: A Phase 1 randomized trial

PubMed Central

Nel, Annaléne; Bekker, Linda-Gail; Ramjee, Gita; Masenga, Gileard; Rees, Helen; van Niekerk, Neliëtte

2018-01-01

Background Women in sub-Saharan Africa are in urgent need of female-initiated human immunodeficiency virus (HIV) preventative methods. Vaginal rings are one dosage form in development for delivery of HIV microbicides. However, African women have limited experience with vaginal rings. Objectives This Phase I, randomized, crossover trial assessed and compared the safety, acceptability and adherence of a silicone elastomer placebo vaginal ring, intended as a microbicide delivery method, inserted for a 12-week period in healthy, HIV-negative, sexually active women in South Africa and Tanzania. Methods 170 women, aged 18 to 35 years were enrolled with 88 women randomized to Group A, using a placebo vaginal ring for 12 weeks followed by a 12-week safety observation period. 82 women were randomized to Group B and observed for safety first, followed by a placebo vaginal ring for 12 weeks. Safety was assessed by clinical laboratory assessments, pelvic/colposcopy examinations and adverse events. Possible carry-over effect was addressed by ensuring no signs or symptoms of genital irritation at crossover. Results No safety concerns were identified for any safety variables assessed during the trial. No serious adverse events were reported considered related to the placebo vaginal ring. Vaginal candidiasis was the most common adverse event occurring in 11% of participants during each trial period. Vaginal discharge (2%), vaginal odour (2%), and bacterial vaginitis (2%) were assessed as possibly or probably related to the vaginal ring. Thirty-four percent of participants had sexually transmitted infections (STIs) at screening, compared to 12% of participants who tested positive for STIs at crossover and the final trial visit. Three participants (2%) tested HIV positive during the trial. Conclusions The silicone elastomer vaginal ring had no safety concerns, demonstrating a profile favorable for further development for topical release of antiretroviral-based microbicides. PMID:29813074

Clinical and neurobiological effects of aerobic exercise in dental phobia: A randomized controlled trial.

PubMed

Lindenberger, Brigitt L; Plag, Jens; Schumacher, Sarah; Gaudlitz, Katharina; Bischoff, Sophie; Bobbert, Thomas; Dimeo, Fernando; Petzold, Moritz B; Kirschbaum, Clemens; Dudás, Zsuzsa; Ströhle, Andreas

2017-11-01

Physical activity has shown to be effective in anxiety disorders. For specific phobia, no studies are available that systematically examined the effects of an aerobic exercise intervention on phobic fear within a randomized-controlled design. Therefore, we investigated the acute effect of a standardized aerobic training on clinical symptoms of dental phobia as well as on stress-related neurobiological markers. Within a crossover design, 30 patients with dental phobia (mean age: 34.1 years; mean score of the Dental Anxiety Scale: 18.8) underwent two minor dental interventions separated by 7 days. Dental treatment was performed after 30 min of physical activity at either 20% VO 2 max (control) or 70% VO 2 max (intervention), respectively. To control for habituation, patients were randomly assigned to one of the two conditions prior to the first intervention. Moreover, saliva samples were collected at five times in order to determine changes in salivary cortisol (sC) and alpha-amylase (sAA) due to treatment. In comparison to baseline, aerobic exercise within 70% VO 2 max significantly reduced clinical anxiety and sC concentrations before, during, and after the dental treatment. In contrast, the control condition led to decreased sAA levels at different time points of measurement. Habituation occurred at the second study day, independent of the order. Our study provides evidence for an effect of moderate-intense exercise on clinical symptoms and sC in patients with dental phobia. Therefore, acute aerobic exercise might be a simple and low-cost intervention to reduce disorder-specific phobic fear. © 2017 Wiley Periodicals, Inc.

Threshold Levels of Infant and Under-Five Mortality for Crossover between Life Expectancies at Ages Zero, One and Five in India: A Decomposition Analysis.

PubMed

Dubey, Manisha; Ram, Usha; Ram, Faujdar

2015-01-01

Under the prevailing conditions of imbalanced life table and historic gender discrimination in India, our study examines crossover between life expectancies at ages zero, one and five years for India and quantifies the relative share of infant and under-five mortality towards this crossover. We estimate threshold levels of infant and under-five mortality required for crossover using age specific death rates during 1981-2009 for 16 Indian states by sex (comprising of India's 90% population in 2011). Kitagawa decomposition equations were used to analyse relative share of infant and under-five mortality towards crossover. India experienced crossover between life expectancies at ages zero and five in 2004 for menand in 2009 for women; eleven and nine Indian states have experienced this crossover for men and women, respectively. Men usually experienced crossover four years earlier than the women. Improvements in mortality below ages five have mostly contributed towards this crossover. Life expectancy at age one exceeds that at age zero for both men and women in India except for Kerala (the only state to experience this crossover in 2000 for men and 1999 for women). For India, using life expectancy at age zero and under-five mortality rate together may be more meaningful to measure overall health of its people until the crossover. Delayed crossover for women, despite higher life expectancy at birth than for men reiterates that Indian women are still disadvantaged and hence use of life expectancies at ages zero, one and five become important for India. Greater programmatic efforts to control leading causes of death during the first month and 1-59 months in high child mortality areas can help India to attain this crossover early.

An approach to checking case-crossover analyses based on equivalence with time-series methods.

PubMed

Lu, Yun; Symons, James Morel; Geyh, Alison S; Zeger, Scott L

2008-03-01

The case-crossover design has been increasingly applied to epidemiologic investigations of acute adverse health effects associated with ambient air pollution. The correspondence of the design to that of matched case-control studies makes it inferentially appealing for epidemiologic studies. Case-crossover analyses generally use conditional logistic regression modeling. This technique is equivalent to time-series log-linear regression models when there is a common exposure across individuals, as in air pollution studies. Previous methods for obtaining unbiased estimates for case-crossover analyses have assumed that time-varying risk factors are constant within reference windows. In this paper, we rely on the connection between case-crossover and time-series methods to illustrate model-checking procedures from log-linear model diagnostics for time-stratified case-crossover analyses. Additionally, we compare the relative performance of the time-stratified case-crossover approach to time-series methods under 3 simulated scenarios representing different temporal patterns of daily mortality associated with air pollution in Chicago, Illinois, during 1995 and 1996. Whenever a model-be it time-series or case-crossover-fails to account appropriately for fluctuations in time that confound the exposure, the effect estimate will be biased. It is therefore important to perform model-checking in time-stratified case-crossover analyses rather than assume the estimator is unbiased.

Dietary Effects on Cognition and Pilots’ Flight Performance

PubMed Central

Lindseth, Glenda N.; Lindseth, Paul D.; Jensen, Warren C.; Petros, Thomas V.; Helland, Brian D.; Fossum, Debra L.

2017-01-01

The purpose of this study was to investigate the effects of diet on cognition and flight performance of 45 pilots. Based on a theory of self-care, this clinical study used a repeated-measure, counterbalanced crossover design. Pilots were randomly rotated through 4-day high-carbohydrate, high-protein, high-fat, and control diets. Cognitive flight performance was evaluated using a GAT-2 full-motion flight simulator. The Sternberg short-term memory test and Vandenberg’s mental rotation test were used to validate cognitive flight test results. Pilots consuming a high-protein diet had significantly poorer (p < .05) overall flight performance scores than pilots consuming high-fat and high-carbohydrate diets. PMID:29353985

L-theanine and caffeine improve task switching but not intersensory attention or subjective alertness.

PubMed

Einöther, Suzanne J L; Martens, Vanessa E G; Rycroft, Jane A; De Bruin, Eveline A

2010-04-01

Tea ingredients L-theanine and caffeine have repeatedly been shown to deliver unique cognitive benefits when consumed in combination. The current randomized, placebo-controlled, double-blind, cross-over study compared a combination of L-theanine (97 mg) and caffeine (40 mg) to a placebo on two attention tasks and a self-report questionnaire before, and 10 and 60 min after consumption. The combination of L-theanine and caffeine significantly improved attention on a switch task as compared to the placebo, while subjective alertness and intersensory attention were not improved significantly. The results support previous evidence that L-theanine and caffeine in combination can improve attention. Copyright 2010 Elsevier Ltd. All rights reserved.

Treatment Failure With Rhythm and Rate Control Strategies in Patients With Atrial Fibrillation and Congestive Heart Failure: An AF-CHF Substudy.

PubMed

Dyrda, Katia; Roy, Denis; Leduc, Hugues; Talajic, Mario; Stevenson, Lynne Warner; Guerra, Peter G; Andrade, Jason; Dubuc, Marc; Macle, Laurent; Thibault, Bernard; Rivard, Lena; Khairy, Paul

2015-12-01

Rate and rhythm control strategies for atrial fibrillation (AF) are not always effective or well tolerated in patients with congestive heart failure (CHF). We assessed reasons for treatment failure, associated characteristics, and effects on survival. A total of 1,376 patients enrolled in the AF-CHF trial were followed for 37  ±  19 months, 206 (15.0%) of whom failed initial therapy leading to crossover. Rhythm control was abandoned more frequently than rate control (21.0% vs. 9.1%, P < 0.0001). Crossovers from rhythm to rate control were driven by inefficacy, whereas worsening heart failure was the most common reason to crossover from rate to rhythm control. In multivariate analyses, failure of rhythm control was associated with female sex, higher serum creatinine, functional class III or IV symptoms, lack of digoxin, and oral anticoagulation. Factors independently associated with failure of rate control were paroxysmal (vs. persistent) AF, statin therapy, and presence of an implantable cardioverter-defibrillator. Crossovers were not associated with cardiovascular mortality (hazard ratio [HR] 1.11 from rhythm to rate control; 95% confidence interval [95% CI, 0.73-1.73]; P = 0.6069; HR 1.29 from rate to rhythm control; 95% CI, 0.73-2.25; P = 0.3793) or all-cause mortality (HR 1.16 from rhythm to rate control, 95% CI [0.79-1.72], P = 0.4444; HR 1.15 from rate to rhythm control, 95% [0.69, 1.91], P = 0.5873). Rhythm control is abandoned more frequently than rate control in patients with AF and CHF. The most common reasons for treatment failure are inefficacy for rhythm control and worsening heart failure for rate control. Changing strategies does not impact survival. © 2015 Wiley Periodicals, Inc.

A Randomized Crossover Trial Comparing Autotitrating and Continuous Positive Airway Pressure in Subjects With Symptoms of Aerophagia: Effects on Compliance and Subjective Symptoms

PubMed Central

Shirlaw, Teresa; Hanssen, Kevin; Duce, Brett; Hukins, Craig

2017-01-01

Study Objectives: To assess the benefit and tolerance of autotitrating positive airway pressure (APAP) versus continuous positive airway pressure (CPAP) in subjects who experience aerophagia. Methods: This is the report of a prospective, two-week, double-blinded, randomized crossover trial set in an Australian clinical sleep laboratory in a tertiary hospital. Fifty-six subjects who reported symptoms of aerophagia that they attributed to CPAP were recruited. Full face masks were used by 39 of the 56 subjects recruited. Subjects were randomly and blindly allocated to either CPAP at their treatment recommended pressure or APAP 6–20 cm H2O, in random order. Subjects spent two weeks on each therapy mode. Therapy usage hours, 95th centile pressure, maximum pressure, 95th centile leak, and residual apnea-hypopnea index (AHI) were reported at the end of each two-week treatment period. Functional Outcome of Sleepiness Questionnaire, Epworth Sleepiness Scale, and visual analog scale to measure symptoms of aerophagia were also completed at the end of each 2-week treatment arm. Results: The median pressure (P < .001) and 95th centile pressure (P < .001) were reduced with APAP but no differences in compliance (P = .120) and residual AHI were observed. APAP reduced the symptoms of bloating (P = .011), worst episode of bloating (P = .040), flatulence (P = .010), and belching (P = .001) compared to CPAP. There were no differences in Epworth Sleepiness Scale or Functional Outcome of Sleepiness Questionnaire outcomes between CPAP and APAP. Conclusions: APAP therapy reduces the symptoms of aerophagia while not affecting compliance when compared with CPAP therapy. Clinical Trial Registration: Australian and New Zealand Clinical Trials Registry at https://www.anzctr.org.au, trial number ACTRN12611001250921. Commentary: A commentary on this article appears in this issue on page 859. Citation: Shirlaw T, Hanssen K, Duce B, Hukins C. A randomized crossover trial comparing autotitrating and continuous positive airway pressure in subjects with symptoms of aerophagia: effects on compliance and subjective symptoms. J Clin Sleep Med. 2017;13(7):881–888. PMID:28558864

Genetic algorithms applied to the scheduling of the Hubble Space Telescope

NASA Technical Reports Server (NTRS)

Sponsler, Jeffrey L.

1989-01-01

A prototype system employing a genetic algorithm (GA) has been developed to support the scheduling of the Hubble Space Telescope. A non-standard knowledge structure is used and appropriate genetic operators have been created. Several different crossover styles (random point selection, evolving points, and smart point selection) are tested and the best GA is compared with a neural network (NN) based optimizer. The smart crossover operator produces the best results and the GA system is able to evolve complete schedules using it. The GA is not as time-efficient as the NN system and the NN solutions tend to be better.

A randomized, single-blind cross-over design evaluating the effectiveness of an individually defined, targeted physical therapy approach in treatment of children with cerebral palsy.

PubMed

Franki, Inge; Van den Broeck, Christine; De Cat, Josse; Tijhuis, Wieke; Molenaers, Guy; Vanderstraeten, Guy; Desloovere, Kaat

2014-10-01

A pilot study to compare the effectiveness of an individual therapy program with the effects of a general physical therapy program. A randomized, single-blind cross-over design. Ten ambulant children with bilateral spastic cerebral palsy, age four to nine years. Participants were randomly assigned into a ten-week individually defined, targeted or a general program, followed by a cross-over. Evaluation was performed using the Gross Motor Function Measure-88 and three-dimensional gait analysis. General outcome parameters were Gross Motor Function Measure-88 scores, time and distance parameters, gait profile score and movement analysis profiles. Individual goal achievement was evaluated using z-scores for gait parameters and Goal Attainment Scale for gross motor function. No significant changes were observed regarding gross motor function. Only after individualized therapy, step- and stride-length increased significantly (p = 0.022; p = 0.017). Change in step-length was higher after the individualized program (p = 0.045). Within-group effects were found for the pelvis in transversal plane after the individualized program (p = 0.047) and in coronal plane after the general program (p = 0.047). Between-program differences were found for changes in the knee in sagittal plane, in the advantage of the individual program (p = 0.047). A median difference in z-score of 0.279 and 0.419 was measured after the general and individualized program, respectively. Functional goal attainment was higher after the individual therapy program compared with the general program (48 to 43.5). The results indicate slightly favorable effects towards the individualized program. To detect clinically significant changes, future studies require a minimal sample size of 72 to 90 participants. © The Author(s) 2014.

Comparison of the Effects of Intermittent Boluses to Simple Continuous Infusion on Patients' Global Perceived Effect in Intrathecal Therapy for Pain: A Randomized Double-Blind Crossover Study.

PubMed

Eldabe, Sam; Duarte, Rui V; Madzinga, Grace; Batterham, Alan M; Brookes, Morag E; Gulve, Ashish P; Perruchoud, Christophe; Raphael, Jon H; Lorenzana, David; Buchser, Eric

2017-05-01

Intrathecal drug delivery (ITDD) is commonly used for intractable pain management. A paucity of good-quality studies in chronic noncancer patients and concerns over increased dosages have focused interest on different modes of administration. The aim of this international multicenter randomized double-blind crossover trial was to compare the efficacy of the same daily dose of drugs administered by intermittent boluses vs simple continuous infusion. Eligible patients implanted with a programmable ITDD device were randomized to receive two weeks of either intermittent boluses or a simple continuous flow in period 1, followed by a crossover to the alternative mode of administration. The primary outcome measure was the Patients' Global Impression of Change (PGIC) scale. The mean proportion of positive responders (at least "minimally improved") was 38.4% in the continuous condition vs 37.3% in the bolus (difference in proportions = 1.1%, 95% confidence interval [CI] = -21.8-24.0%, P  = 0.93). The mean PGIC in the continuous condition was 3.8 vs 3.9 in the bolus (mean difference = -0.1, -0.6-0.4, P  = 0.72). Exploratory analyses revealed a tendency for the mean proportion of positive responders to be higher at low vs high flow rates for both bolus and continuous administrations. Two patients were withdrawn from the study due to adverse events during the bolus phase, both with symptoms of increased pain, and one patient with additional symptoms of numbness and urinary retention. The mean PGIC and proportion of positive responders was not substantially different after intermittent bolus vs continuous administration. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Impact of Intravenous Lysine Acetylsalicylate Versus Oral Aspirin on Prasugrel-Inhibited Platelets: Results of a Prospective, Randomized, Crossover Study (the ECCLIPSE Trial).

PubMed

Vivas, David; Martín, Agustín; Bernardo, Esther; Ortega-Pozzi, María Aranzazu; Tirado, Gabriela; Fernández, Cristina; Vilacosta, Isidre; Núñez-Gil, Iván; Macaya, Carlos; Fernández-Ortiz, Antonio

2015-05-01

Prasugrel and ticagrelor, new P2Y12-adenosine diphosphate receptor antagonists, are associated with greater pharmacodynamic inhibition and reduction of cardiovascular events compared with clopidogrel in patients with an acute coronary syndrome. However, evidence is lacking about the effects of achieving faster and stronger cyclooxygenase inhibition with intravenous lysine acetylsalicylate (LA) compared with oral aspirin on prasugrel-inhibited platelets. This was a prospective, randomized, single-center, open, 2-period crossover platelet function study conducted in 30 healthy volunteers. Subjects were randomly assigned to receive a loading dose of intravenous LA 450 mg plus oral prasugrel 60 mg or loading dose of aspirin 300 mg plus prasugrel 60 mg orally in a crossover fashion after a 2-week washout period between treatments. Platelet function was evaluated at baseline, 30 minutes, 1 h, 4 h, and 24 h using light transmission aggregometry and vasodilator-stimulated phosphoprotein phosphorylation. The primary end point of the study, inhibition of platelet aggregation after arachidonic acid 1.5 mmol/L at 30 minutes, was significantly higher in subjects treated with LA compared with aspirin: 85.3% versus 44.3%, respectively, P=0.003. This differential effect was observed at 1 hour (P=0.002) and 4 hours (P=0.048), but not at 24 hours. Subjects treated with LA presented less variability and faster and greater inhibition of platelet aggregation with arachidonic acid compared with aspirin. The administration of intravenous LA resulted in a significant reduction of platelet reactivity compared with oral aspirin on prasugrel-inhibited platelets. Loading dose of LA achieves an earlier platelet inhibition and with less variability than aspirin. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02243137. © 2015 American Heart Association, Inc.

Normal and tumoral melanocytes exhibit q-Gaussian random search patterns.

PubMed

da Silva, Priscila C A; Rosembach, Tiago V; Santos, Anésia A; Rocha, Márcio S; Martins, Marcelo L

2014-01-01

In multicellular organisms, cell motility is central in all morphogenetic processes, tissue maintenance, wound healing and immune surveillance. Hence, failures in its regulation potentiates numerous diseases. Here, cell migration assays on plastic 2D surfaces were performed using normal (Melan A) and tumoral (B16F10) murine melanocytes in random motility conditions. The trajectories of the centroids of the cell perimeters were tracked through time-lapse microscopy. The statistics of these trajectories was analyzed by building velocity and turn angle distributions, as well as velocity autocorrelations and the scaling of mean-squared displacements. We find that these cells exhibit a crossover from a normal to a super-diffusive motion without angular persistence at long time scales. Moreover, these melanocytes move with non-Gaussian velocity distributions. This major finding indicates that amongst those animal cells supposedly migrating through Lévy walks, some of them can instead perform q-Gaussian walks. Furthermore, our results reveal that B16F10 cells infected by mycoplasmas exhibit essentially the same diffusivity than their healthy counterparts. Finally, a q-Gaussian random walk model was proposed to account for these melanocytic migratory traits. Simulations based on this model correctly describe the crossover to super-diffusivity in the cell migration tracks.

Gastrointestinal adverse events during methylphenidate treatment of children and adolescents with attention deficit hyperactivity disorder: A systematic review with meta-analysis and Trial Sequential Analysis of randomised clinical trials.

PubMed

Holmskov, Mathilde; Storebø, Ole Jakob; Moreira-Maia, Carlos R; Ramstad, Erica; Magnusson, Frederik Løgstrup; Krogh, Helle B; Groth, Camilla; Gillies, Donna; Zwi, Morris; Skoog, Maria; Gluud, Christian; Simonsen, Erik

2017-01-01

To study in more depth the relationship between type, dose, or duration of methylphenidate offered to children and adolescents with attention deficit hyperactivity disorder and their risks of gastrointestinal adverse events based on our Cochrane systematic review. We use data from our review including 185 randomised clinical trials. Randomised parallel-group trials and cross-over trials reporting gastrointestinal adverse events associated with methylphenidate were included. Data were extracted and quality assessed according to Cochrane guidelines. Data were summarised as risk ratios (RR) with 95% confidence intervals (CI) using the inverse variance method. Bias risks were assessed according to domains. Trial Sequential Analysis (TSA) was used to control random errors. Eighteen parallel group trials and 43 cross-over trials reported gastrointestinal adverse events. All trials were at high risk of bias. In parallel group trials, methylphenidate decreased appetite (RR 3.66, 95% CI 2.56 to 5.23) and weight (RR 3.89, 95% CI 1.43 to 10.59). In cross-over trials, methylphenidate increased abdominal pain (RR 1.61, 95% CI 1.27 to 2.04). We found no significant differences in the risk according to type, dose, or duration of administration. The required information size was achieved in three out of four outcomes. Methylphenidate increases the risks of decreased appetite, weight loss, and abdominal pain in children and adolescents with attention deficit hyperactivity disorder. No differences in the risks of gastrointestinal adverse events according to type, dose, or duration of administration were found.

Blood pressure targets for vasopressor therapy: a systematic review.

PubMed

D'Aragon, Frederick; Belley-Cote, Emilie P; Meade, Maureen O; Lauzier, François; Adhikari, Neill K J; Briel, Matthias; Lalu, Manoj; Kanji, Salmaan; Asfar, Pierre; Turgeon, Alexis F; Fox-Robichaud, Alison; Marshall, John C; Lamontagne, François

2015-06-01

Physicians often prescribe vasopressors to correct pathological vasodilation and improve tissue perfusion in patients with septic shock, but the evidence to inform practice on vasopressor dosing is weak. We undertook a systematic review of clinical studies evaluating different blood pressure targets for the dosing of vasopressors in septic shock. We searched MEDLINE, EMBASE, CENTRAL (to November 2013), reference lists from included articles, and trial registries for randomized controlled trials (RCTs) and observational and crossover intervention studies comparing different blood pressure targets for vasopressor therapy in septic shock. Two reviewers independently selected eligible studies and extracted data on standardized forms. We identified 2 RCTs and 10 crossover trials but no observational studies meeting our criteria. Only one RCT measured clinical outcomes after comparing mean arterial pressure targets of 80 to 85 mmHg versus 65 to 70 mmHg. There was no effect on 28-day mortality, but confidence intervals were wide (hazard ratio, 95% confidence interval [95% CI] 0.84 - 1.38). In contrast, this intervention was associated with a greater risk of atrial fibrillation (relative risk, 2.36; 95% CI, 1.18 - 4.72) and a lower risk of renal replacement therapy in hypertensive patients (relative risk, 0.75; 95% CI, 0.57 - 1.0). Crossover trials suggest that achieving higher blood pressure targets by increasing vasopressor doses increases heart rate and cardiac index with no effect on serum lactate. Our findings underscore the paucity of clinical evidence to guide the administration of vasopressors in critically ill patients with septic shock. Further rigorous research is needed to establish an evidence base for vasopressor administration in this population.