Balanced Trial Research Articles

Effects of vanilla odor on hypoxia-related periodic breathing in premature newborns: A pilot study

BackgroundPeriodic breathing (PB)-related intermittent hypoxia can have long-lasting deleterious consequences in preterm infants. Olfactory stimulation using vanilla odor is beneficial for apnea of prematurity in the first postnatal days/weeks. We aimed to determine for the first time whether vanilla odor can also decrease PB-related intermittent hypoxia. MethodThis pilot study was a balanced crossover clinical trial including 27 premature infants born between 30 and 33+6 weeks of gestation. We performed 12-h recordings on two nights separated by a 24-h period. All infants were randomly exposed to vanilla odor on the first or second study night. The primary outcome was the desaturation index, defined as the number per hour of pulse oximetry (SpO2) values <90 % for at least 5 s, together with a drop of ≥5 % from the preceding value. Univariate mixed linear models were used for the statistical analysis. ResultsOverall, exposure to vanilla odor did not significantly decrease the desaturation index (52 ± 22 events/h [mean ± SD] on the intervention night vs. 57 ± 26, p = 0.2); furthermore, it did not significantly alter any secondary outcome. In a preliminary post hoc subgroup analysis, however, the effect of vanilla odor was statistically significant in infants with a desaturation index of ≥70/h (from 86 ± 12 to 65 ± 23, p = 0.04). ConclusionIn this pilot study, vanilla odor overall did not decrease PB-related intermittent hypoxia in infants born at 30–33+6 weeks of gestation, which is when they are close to term. Preliminary results suggesting a beneficial effect in infants with the highest desaturation index, however, justify further studies in the presence of PB-related intermittent hypoxia as well as in infants born more prematurely.

Exploring the Path of Personal Information Infringement Governance by Web Crawlers

In the era of big data, the explosive growth of data information, network crawler as a new type of data search engine came into being, and gradually become indispensable technology. However, with the continuous penetration of crawler technology, related infringement problems have gradually surfaced. This topic starts from the definition and technical application of network crawlers, further analyzes the specific forms of network crawlers’ personal information infringement, and discusses and summarizes the shortcomings of the legal governance measures involved, and finally draws on the experience of overseas and combines the views of relevant scholars, proposes to improve the relevant legal provisions and clarify the division of responsibility; introduces the rule of balanced trial; establishes the criteria for the reasonable use of data by crawlers; creates a “cyclical protection system”; establishes the “data protection system”; and establishes the “data protection system”. The proposal to establish a cyclical protection system, establish a “data protection officer”, set up an independent regulatory body, form an internal and external linkage mechanism, and then build a scientific governance system for scientific governance.

It’s Time we Get Rid of Jury Trials

This paper shows that the process of jury trails are not needed in a modern society as the trial by a judge is more than enough to meet the tenets of the justice system of a fair, just, balanced, unbiased and impartial trial. We need to totally and completely abolish this giant elephant in the room from medieval ages and make the judicial process more efficient, better and quicker by introducing the trial by single judge as a norm.

Legacy lessons from the COVID-19 era to improve trial participation and retention: Views from trial participants, PPIE contributors and trial staff across the NIHR portfolio.

The Covid-19 pandemic had a profound effect on the delivery of healthcare research. Covid-19 research was prioritised and many non-essential trials were paused. This study explores the engagement experiences of trial participants', PPIE contributors' and trial staff during the Covid-19 pandemic and towards recovery and restoring a diverse and balanced UK clinical trials portfolio. Interviews and focus groups were undertaken with PPIE contributors, trial participants and trial staff members from NIHR research trials across the UK (November 2020-June 2021) across portfolio specialities: Cancer, Oral and Dental Health, Musculoskeletal Disorders, Cardiovascular Disease, Neurological Disorders, Primary Care, and Conditions associated with susceptibility to Covid-19 (Diabetes, Stroke, Respiratory Disorders). Topic guides were developed for each participant group and interviews were conducted over Zoom. The transcripts were analysed using codebook thematic analysis in NVivo (V.12). 106 participants comprising, 45 PPIE contributors, 27 trial participants and 34 trial staff members were recruited. Three themes to engagement with trials during Covid-19 were developed. 1) Ensuring continued contact. Continued and tailored communication, having a trial point of contact and regular updates all enhanced trial engagement and retention. Patients' unfamiliarity with materials being sent electronically reduced engagement and trust. 2) A balanced move to remote consultations. Remote follow-up and monitoring were convenient and allowed for wider recruitment across the UK. Participants were more likely to discuss personal subjects in their own homes. Remote visits lacked a personal touch, some concerns over missed diagnoses or being unable to appreciate the situation, technical abilities or equipment failures were seen as barriers, especially for disadvantaged or older people. 3) The importance of feeling fully informed. Factors that supported attendance were knowledge about trial conduct adherence to Covid-19 regulations, social distancing, clear signage at the site and opportunities to ask questions. Barriers included not knowing what to expect and not feeling safe with rules and regulations. Our findings highlight a number of ways to future proof trial delivery against future pandemics or disruptions such as offering online options to participate in research, ensuring consistent communication between participants and the research team, making sure participants feel fully informed and the continued reassurance of safety in the clinical setting.

Acute Effects of Single Versus Combined Inhaled β2-Agonists Salbutamol and Formoterol on Time Trial Performance, Lung Function, Metabolic and Endocrine Variables

BackgroundHigh prevalence rates of β2-agonist use among athletes in competitive sports makes it tempting to speculate that illegitimate use of β2-agonists boosts performance. However, data regarding the potential performance-enhancing effects of inhaled β2-agonists and its underlying molecular basis are scarce.MethodsIn total, 24 competitive endurance athletes (12f/12m) participated in a clinical double-blinded balanced four-way block cross-over trial to investigate single versus combined effects of β2-agonists salbutamol (SAL) and formoterol (FOR), to evaluate the potential performance enhancement of SAL (1200 µg, Cyclocaps, Pb Pharma GmbH), FOR (36 µg, Sandoz, HEXAL AG) and SAL + FOR (1200 µg + 36 µg) compared to placebo (PLA, Gelatine capsules containing lactose monohydrate, Pharmacy of the University Hospital Ulm). Measurements included skeletal muscle gene and protein expression, endocrine regulation, urinary/serum β2-agonist concentrations, cardiac markers, cardiopulmonary and lung function testing and the 10-min time trial (TT) performance on a bicycle ergometer as outcome variables. Blood and urine samples were collected pre-, post-, 3 h post- and 24 h post-TT.ResultsMean power output during TT was not different between study arms. Treatment effects regarding lung function (p < 0.001), echocardiographic (left ventricular end-systolic volume p = 0.037; endocardial global longitudinal strain p < 0.001) and metabolic variables (e.g. NR4A2 and ATF3 pathway) were observed without any influence on performance. In female athletes, total serum β2-agonist concentrations for SAL and FOR were higher. Microarray muscle gene analysis showed a treatment effect for target genes in energy metabolism with strongest effect by SAL + FOR (NR4A2; p = 0.001). Of endocrine variables, follicle-stimulating hormone (3 h Post–Post-TT), luteinizing hormone (3 h Post–Pre-TT) and insulin (Post–Pre-TT) concentrations showed a treatment effect (all p < 0.05).ConclusionsNo endurance performance-enhancing effect for SAL, FOR or SAL + FOR within the permitted dosages compared to PLA was found despite an acute effect on lung and cardiac function as well as endocrine and metabolic variables in healthy participants. The impact of combined β2-agonists on performance and sex-specific thresholds on the molecular and cardiac level and their potential long-term performance enhancing or health effects have still to be determined.Trial registration: Registered at Eudra CT with the number: 2015-005598-19 (09.12.2015) and DRKS with number DRKS00010574 (16.11.2021, retrospectively registered).

Trusting relationships between patients with non-curative cancer and healthcare professionals create ethical obstacles for informed consent in clinical trials: a grounded theory study

BackgroundClinical trial participation for patients with non-curative cancer is unlikely to present personal clinical benefit, which raises the bar for informed consent. Previous work demonstrates that decisions by patients in this setting are made within a ‘trusting relationship’ with healthcare professionals. The current study aimed to further illuminate the nuances of this relationship from both the patients’ and healthcare professionals’ perspectives.MethodsFace-to-face interviews using a grounded theory approach were conducted at a regional Cancer Centre in the United Kingdom. Interviews were performed with 34 participants (patients with non-curative cancer, number (n) = 16; healthcare professionals involved in the consent process, n = 18). Data analysis was performed after each interview using open, selective, and theoretical coding.ResultsThe ‘Trusting relationship’ with healthcare professionals underpinned patient motivation to participate, with many patients ‘feeling lucky’ and articulating an unrealistic hope that a clinical trial could provide a cure. Patients adopted the attitude of ‘What the doctor thinks is best’ and placed significant trust in healthcare professionals, focusing on mainly positive aspects of the information provided. Healthcare professionals recognised that trial information was not received neutrally by patients, with some expressing concerns that patients would consent to ‘please’ them. This raises the question: Within the trusting relationship between patients and healthcare professionals, ‘Is it possible to provide balanced information?’. The theoretical model identified in this study is central to understanding how the trusting professional-patient relationship influences the decision-making process.ConclusionThe significant trust placed on healthcare professionals by patients presented an obstacle to delivering balanced trial information, with patients sometimes participating to please the ‘experts’. In this high-stakes scenario, it may be pertinent to consider strategies, such as separation of the clinician-researcher roles and enabling patients to articulate their care priorities and preferences within the informed consent process. Further research is needed to expand on these ethical conundrums and ensure patient choice and autonomy in trial participation are prioritised, particularly when the patient’s life is limited.

Could S-1-based non-platinum doublet chemotherapy be a new option as a second-line treatment for advanced non-small cell lung cancer patients? A multicenter retrospective study.

For patients who have contraindications to or have failed checkpoint inhibitors, chemotherapy remains the standard second-line option to treat non-oncogene-addicted advanced non-small cell lung cancer (NSCLC). This study aimed to investigate the efficacy and safety of S-1-based non-platinum combination in advanced NSCLC patients who had failed platinum doublet chemotherapy. During January 2015 and May 2020, advanced NSCLC patients who received S-1 plus docetaxel or gemcitabine after the failure of platinum-based chemotherapy were consecutively retrieved from eight cancer centers. The primary endpoint was progression-free survival (PFS). The secondary endpoint was overall response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. By using the method of matching-adjusted indirect comparison, the individual PFS and OS of included patients were adjusted by weight matching and then compared with those of the docetaxel arm in a balanced trial population (East Asia S-1 Trial in Lung Cancer). A total of 87 patients met the inclusion criteria. The ORR was 22.89% (vs. 10% of historical control, p < 0.001) and the DCR was 80.72%. The median PFS and OS were 5.23 months (95% CI: 3.91-6.55 months) and 14.40 months (95% CI: 13.21-15.59 months), respectively. After matching with a balanced population in the docetaxel arm from the East Asia S-1 Trial in Lung Cancer, the weighted median PFS and OS were 7.90 months (vs. 2.89 months) and 19.37 months (vs. 12.52 months), respectively. Time to start of first subsequent therapy (TSFT) from first-line chemotherapy (TSFT > 9 months vs. TSFT ≤ 9 months) was an independent predictive factor of second-line PFS (8.7 months vs. 5.0 months, HR = 0.461, p = 0.049). The median OS in patients who achieved response was 23.5 months (95% CI: 11.8-31.6 months), which was significantly longer than those with stable disease (14.9 months, 95% CI: 12.9-19.4 months, p < 0.001) or progression (4.9 months, 95% CI: 3.2-9.5 months, p < 0.001). The most common adverse events were anemia (60.92%), nausea (55.17%), and leukocytopenia (33.33%). S-1-based non-platinum combination had promising efficacy and safety in advanced NSCLC patients who had failed platinum doublet chemotherapy, suggesting that it could be a favorable second-line treatment option.

CTIM-33. SEXUAL DIMORPHISM OF HUMAN IMMUNE SYSTEM PREDICTS CLINICAL OUTCOMES IN GLIOBLASTOMA IMMUNOTHERAPY: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract Biological differences based on sex have been documented throughout scientific literature. Glioblastoma, the most common primary malignant brain tumor in adults, has a male sex incidence bias, however, no clinical trial data examining differential effects of treatment between sexes currently exist. We analyzed genomic data, as well as clinical trials, to delineate the effect of sex on the immune system and glioblastoma outcome following immunotherapy. We found that, in general females possess enriched immunological signatures on gene set enrichment analysis, that also stratified patient survival when delineated by sex. Female glioblastoma patients treated with immunotherapy had a statistically significant survival advantage at the 1-year compared to males (RR = 1.15; p = 0.0241). This effect was even more pronounced in vaccine-based immunotherapy, (RR = 1.29; p = 0.0158). Our study shows a meaningful difference in the immunobiology between males and females that also influences overall response to immunotherapy in the setting of glioblastoma. Our study adds to a growing body of literature examining sex differences in male and female immunology. We demonstrate both using large scale omic data sets, as well as clinical trials, that female sexually dimorphic genes are tied to immunological responses, and that females have better outcomes during GBM immunotherapy treatments. This data is critical to better inform treatment practices and further crystalizes the need for balanced trial design and prospective reporting of sex as a variable across all GBM clinical trials.

The effects of cannabidiol and analgesic expectancies on experimental pain reactivity in healthy adults: A balanced placebo design trial.

Despite its frequent use for pain relief, no experimental pain research has tested the analgesic effects of cannabidiol (CBD) in humans. The goal of this study was to experimentally test the effects of CBD and expectancies for receiving CBD on human pain reactivity. Using a crossover, 2 × 2 factorial balanced placebo design, drug administration (given inactive substance or given active CBD) and verbal instruction sets (told inactive substance or told active CBD) were experimentally manipulated. Fifteen healthy adults each completed four separate experimental sessions. Participants were randomly assigned to different counterbalanced manipulation conditions at each session: control (told inactive-given inactive); expectancy (told active CBD-given inactive); drug (told inactive-given active CBD); and expectancy + drug (told active CBD-given active CBD). Primary outcomes were pain threshold, tolerance, intensity, unpleasantness, conditioned pain modulation (CPM), and offset analgesia (OA). There was a significant main effect of instructions on OA, such that the OA response was significantly larger when participants were told that they received CBD, regardless of drug content. Pain unpleasantness was significantly reduced in the drug, expectancy, and expectancy + drug conditions, relative to the control condition. The drug and expectancy conditions separately improved CPM, whereas the expectancy + drug and control conditions produced the lowest CPM change scores. We did not detect significant effects for pain threshold, tolerance, or intensity. Our results indicated that separate pain outcomes can be differentially affected by CBD and/or expectancies for receiving CBD. Future investigations of the psychological and pharmacological mechanisms underlying CBD analgesia are warranted. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Efficacy of nutrition education for the increase of symbiotic intake on nutritional and metabolic status in schizophrenic spectrum disorders: A two-arm protocol.

Background/ObjectivesThe microbiota plays a vital role in the two-way communication between the gastrointestinal tract and numerous neuropsychiatric disorders, such as schizophrenia. Besides, the microbiota modulation through the use of psychobiotics (prebiotics and probiotics with nutraceutical action) is related to the improvement of the physical and psychopathological health. The objective to this study was to test the efficacy of prebiotic/probiotic dietary modulation in patients diagnosed with schizophrenia, attending to the nutritional and cardio-metabolic impact.MethodsTwo-arms, double-blind, randomized in balanced blocks clinical trial of 6 months of intervention, will be developed in a group of 50 individuals. The control group will receive conventional dietary advice individually from specialized mental health nurses. In the intervention group, an individual dietetic-nutritional education program with high prebiotic and probiotic content (dairy and fermented foods, green leafy vegetables, high-fiber fruit, whole grains, etc.) will be developed by these nurses. Data will be collected on the psychopathological state, and blood test (at the beginning, at 3 and 6 months). The estimation of intestinal microbiota and the usual nutritional pattern will also be assessed at the beginning and 6 months, using a stool test. To evaluate the degree of adherence, the intervention group will fill a specific weekly record of the main dishes/food consumed. Anthropometric parameters will also be analyzed monthly.DiscussionThe study is anticipated to establish feasibility an adequate dietary modulation with a high simbiotic content, leads to a significant improvement in the nutritional status and cardio-metabolic. Furthermore, it is presumed to reach a degree of evidence that allows establishing nutritional management as an effective therapeutic intervention in the psychopathological treatment of patients with schizophrenia spectrum disorders.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [NCT04366401].

Two-stage re-estimation adaptive design: a simulation study

&#x0D; &#x0D; &#x0D; Background: adaptive clinical trial design has been proposed as a promising new approach to improve the drug discovery process. Among the many options available, adaptive sample size re-estimation is of great interest mainly because of its ability to avoid a large ‘up-front’ commitment of resources. In this simulation study, we investigate the statistical properties of two-stage sample size re-estimation designs in terms of type I error control, study power and sample size, in comparison with the fixed-sample study.&#x0D; Methods: we simulated a balanced two-arm trial aimed at comparing two means of normally distributed data, using the inverse normal method to combine the results of each stage, and considering scenarios jointly defined by the following factors: the sample size re-estimation method, the information fraction, the type of group sequential boundaries and the use of futility stopping. Calculations were performed using the statistical software SAS™ (version 9.2).&#x0D; Results: under the null hypothesis, any type of adaptive design considered maintained the prefixed type I error rate, but futility stopping was required to avoid the unwanted increase in sample size. When deviating from the null hypothesis, the gain in power usually achieved with the adaptive design and its performance in terms of sample size were influenced by the specific design options considered.&#x0D; Conclusions: we show that adaptive designs incorporating futility stopping, a sufficiently high information fraction (50-70%) and the conditional power method for sample size re-estimation have good statistical properties, which include a gain in power when trial results are less favourable than anticipated. &#x0D; &#x0D;

Matching-adjusted Indirect Comparison of the Efficacy of Loncastuximab Tesirine Versus Treatment in the Chemoimmunotherapy Era for Relapsed/Refractory Diffuse Large B-cell Lymphoma

BackgroundLoncastuximab tesirine (Lonca) and chemoimmunotherapy (CIT) have been assessed in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), but direct evidence from head-to-head randomized clinical trials is not available. Materials and MethodsMatching-adjusted indirect comparison (MAIC) was used to evaluate the efficacy of Lonca versus CIT-era treatment in R/R DLBCL. The analysis used individual patient data from the phase II LOTIS-2 trial of Lonca (NCT03589469) and pooled aggregated data from 2 extension studies of the CORAL trial for CIT. The LOTIS-2 trial included 145 patients who had relapsed or progressed following 2 or more multi-agent systemic treatment regimens; the CORAL extension studies included 203 patients who received 2 prior lines of therapy and 75 patients who relapsed after autologous hematopoietic cell transplantation. MAIC analyses were performed to adjust for cross-trial differences in inclusion/exclusion criteria and the distribution of observed baseline characteristics. Overall response rate (ORR) and overall survival (OS) were compared between the balanced trial populations. ResultsA total of 80 patients in LOTIS-2 were included in the analysis. After matching to the characteristics of 278 patients from the pooled CORAL extension studies, the ORR was significantly higher for Lonca compared with CIT-era treatment (53.4% vs. 40.3%, P < .05). Lonca was also associated with a significantly improved OS compared with CIT-era treatment (median OS 10.8 vs. 6.4 months; adjusted hazard ratio: 0.67 [95% CI: 0.48, 0.92], P < .05). ConclusionThis study indicates that Lonca was associated with significantly improved efficacy compared with CIT-era treatments for R/R DLBCL.

Ursolic acid does not change the cytokine levels following resistance training in healthy men: A pilot balanced, double-blind and placebo-controlled clinical trial.

Ursolic acid (UA) is a natural compound that shows anti-inflammatory actions. However, no human studies have investigated the cytokine profile during the RT and UA consumption. The purpose of this study was to verify if UA is able to potentiate the anti-inflammatory activity after RT, reflecting in the reduction of blood inflammatory markers in healthy men. Twenty-seven participants were allocated to two groups: control (CON) (n=13) and UA (n=14). For 8weeks, each group performed RT and consumed capsules containing a placebo (400mg/day) or UA (400mg/day). Serum cytokine concentrations were evaluated before and after the training period. There was no difference in the serum cytokine concentrations of TNF-α, IL-10 and IL-6 (p>0.05). In conclusion, UA supplementation for 8weeks was not able to change the blood TNF-α, IL-10, and IL-6 concentrations in healthy men undergoing RT. However, further studies are warranted to investigate other inflammatory markers.

The ELSA trial: single versus combinatory effects of non-prohibited beta-2 agonists on skeletal muscle metabolism, cardio-pulmonary function and endurance performance\u2014study protocol for a randomized 4-way balanced cross-over trial

BackgroundAsthma and/or airway hyper-responsiveness (AHR) are common in elite endurance athletes with a high prevalence rate of beta-2 adrenoreceptor (beta-2) agonists use. Nevertheless, there are data on dose-dependent ergogenic effects of beta-2 agonists suggesting increased muscle strength, endurance and neuromuscular performance. Therefore, most beta-2 agonists belong to the World Anti Doping Agency (WADA) list of prohibited substances and it is tempting to speculate that illegitimate use of beta-2 agonists might be a common practice to boost performance in competitive sports. It is currently unknown whether or not inhaled beta-2 agonists enhance performance by stimulatory effects in skeletal and cardiac muscle.MethodsThe ELSA trial is a double-blinded, placebo-controlled, randomized, balanced, four-way cross-over study. Study participants (n=24, 12 ♀, 12 ♂) complete four study arms (i.e. periods with treatment A, placebo; B, salbutamol; C, formoterol; D, formoterol + salbutamol) in random order after an initial preliminary testing session. Participants inhale the study medication 20 min before the 10-min time trial (TT; exercise performance test), where participants cycle 10 min at the highest possible workload. Cardiac output is measured continuously. A skeletal muscle biopsy is collected 3 h after the TT. Study endpoints include measures of skeletal muscle expression of nuclear receptors, hormones and cytokine levels, urinary and plasma concentrations of salbutamol and formoterol, circulating cardiac markers, cardiopulmonary function and exercise performance (average power and peak power during the TT). Blood and urine are collected and respiratory testing is performed 24 h post TT.Summary/conclusionsThis clinical trial evaluates the potential performance-enhancing effects of non-prohibited, not medically indicated inhaled short- and long-acting beta-2 agonists on skeletal muscle gene expression, endocrine regulation, cardiac biomarkers, cardiopulmonary function and acute endurance exercise performance. These data will be used by WADA to adapt the annually published list of prohibited substances (WADA 2021) and will be published in scientific journals.Trial registrationThe trial is registered at the European Clinical Trials Database (Eudra CT) with the number: 2015-005598-19 as well as at the German register for clinical studies (DRKS number 00010574).

Duration of toothbrushing with fixed appliances: a randomized crossover clinical trial.

Fixed orthodontic appliances might result in dental adverse effects, if sufficient oral hygiene is not maintained. Since recommendations on toothbrushing times are lacking scientific justification in orthodontic populations, the aim of the present study was to comparatively quantify the duration of toothbrushing with a manual and a powered toothbrush in two distinct age groups. Two-centre, two-period crossover balanced randomized clinical trial with computer-generated numbers and blinding at the outcome-assessing level. Children and adults with fixed appliances with at least 22 aligned teeth were recruited at a university clinic and private practice in Bavaria, Germany. Plaque was disclosed with staining tablets and participants brushed their teeth with their habitual technique in front of a mirror and without interference until staining was, to their own satisfaction, completely removed. The primary outcome was duration of toothbrushing in seconds. Secondary outcomes were percentage plaque reduction and questionnaire data on dental attitudes and behaviours. Data were analysed with linear mixed models. Twenty-eight participants were randomized to the first and 27 to the second toothbrush sequence. The combined effect of age and toothbrush on the duration of toothbrushing was evident (n = 52, F(1, 50.8) = 5.1, P = 0.028). Children brushed 14.5 seconds less [n = 28, 95% confidence interval (CI) = -31.3 to 2.3, P = 0.090], yet adults 13.3 seconds more (n = 24, 95% CI = -4.6 to 31.3, P = 0.143) with the manual than powered toothbrush. Brushing times ranged from 2 minutes and 45 seconds to 3 minutes and 17 seconds with plaque reduction at 76% and good dental attitudes and behaviours. Both children and adults with fixed appliances might equally reach an effective plaque reduction with either manual or powered toothbrushes and their habitual brushing technique in around three minutes, if plaque is visible. DRKS-German Clinical Trials Register ID: DRKS00012463. Oral-B Procter & Gamble.

One-Week High-Dose β-Alanine Loading Improves World Tour Cyclists' Time-Trial Performance.

Supplementation with β-alanine is becoming a common practice in high-performance athletes. The purpose of the present study was to investigate the effects of a one-week high-dose β-alanine loading phase employing a sustained-release powder on preserving the time-trial performance capacity of world tour cyclists during overreaching training. Per day, 20 g of sustained-release β-alanine was administered during one week (7 days) of intensive team training camp in a randomised balanced placebo-controlled parallel trial design, with six participants in each β-alanine (BA) or placebo (PLA) group. A 10-min time trial (10′ TT) was carried out to analyse performance and biochemical variables. Anthropometry, paresthesia, and adverse event data were also collected. Power-based relative training load was quantified. Compared to placebo, the BA improved mean power (6.21%, 37.23 W; 95% CI: 3.98–70.48 W, p = 0.046), distance travelled (2.16%, p = 0.046) and total work (4.85%, p = 0.046) without differences in cadence (p = 0.506) or RPE. Lactate (p = 0.036) and anion gap (p = 0.047) were also higher in the BA group, without differences in pH or Bicarbonate. High daily and single doses were well tolerated. One-week high-dose β-alanine loading with a sustained-release powder blend can help attenuate 10′ TT performance losses of world tour cyclists due to intensive training.

Comparison of the dento-skeletal effects produced by Leaf expander versus rapid maxillary expander in prepubertal patients: a two-center randomized controlled trial.

This study aimed to compare the skeletal and dentoalveolar effects produced by slow maxillary expansion (SME) with the Leaf expander versus the conventional rapid maxillary expansion (RME) on digital dental casts, lateral and postero-anterior cephalometric radiographs. This is a superiority, two-center, two arms parallel balanced randomization trial. Patients in the mixed dentition were included with a transverse interarch discrepancy of at least 3 mm. An expansion screw using moderate continuous forces (Leaf group) was compared to a conventional RME screw (RME group). The primary response variable was the difference in maxillary intermolar width (U6-U6) measured at baseline (T0) and one-year follow-up (T1) on the digital dental casts. Other dento-skeletal variables were also measured on digital dental casts and cephalograms. Computer-generated block randomization was used with allocation concealed in sequentially numbered opaque sealed envelopes. The examiner was blinded on the type of expander used. Linear models were used for statistical analysis. Twenty-eight patients in the Leaf group and 28 patients in the RME group were randomized and included in the study. There were no dropouts. U6-U6 did not show a statistically significant difference between the two groups (-0.4 mm in favor of the RME group, 95% CI from -1.2 to 0.5, P = 0.365). As for the other secondary variables no statistically significant differences were found between the two groups except maxillary intercanine width (U3-U3, -0.9 mm in favor of the RME group, 95%CI from -1.5 to -0.3, P = 0.005) and maxillary skeletal width (Mx-Mx, -1.4 mm in favor of the RME group, 95%CI from -2.4 to -0.3, P = 0.013). No significant differences between the RME and Leaf groups were detected for any of the analyzed dento-skeletal variables except the T1-T0 differences in U3-U3 and Mx-Mx that were significantly greater in the RME group. The study was registered in the ISRCTN register on 08/11/2016 with the number ISRCTN18263886. No funding or conflict of interest to be declared.

Supplemental Material for The Effects of Cannabidiol and Analgesic Expectancies on Experimental Pain Reactivity in Healthy Adults: A Balanced Placebo Design Trial

Supplemental Material for The Effects of Cannabidiol and Analgesic Expectancies on Experimental Pain Reactivity in Healthy Adults: A Balanced Placebo Design Trial

Farey Trees Explain Sequential Effects in Choice Response Time.

The latencies of successive two-alternative, forced-choice response times display intricately patterned sequential effects, or dependencies. They vary as a function of particular trial-histories, and in terms of the order and identity of previously presented stimuli and registered responses. This article tests a novel hypothesis that sequential effects are governed by dynamic principles, such as those entailed by a discrete sine-circle map adaptation of the Haken Kelso Bunz (HKB) bimanual coordination model. The model explained the sequential effects expressed in two classic sequential dependency data sets. It explained the rise of a repetition advantage, the acceleration of repeated affirmative responses, in tasks with faster paces. Likewise, the model successfully predicted an alternation advantage, the acceleration of interleaved affirmative and negative responses, when a task’s pace slows and becomes more variable. Detailed analyses of five studies established oscillatory influences on sequential effects in the context of balanced and biased trial presentation rates, variable pacing, progressive and differential cognitive loads, and dyadic performance. Overall, the empirical patterns revealed lawful oscillatory constraints governing sequential effects in the time-course and accuracy of performance across a broad continuum of recognition and decision activities.

Comparison between two screws for maxillary expansion: a multicenter randomized controlled trial on patient's reported outcome measures.

The objective of this study was to compare an expansion screw of the maxilla that generates moderate and continuous forces versus a conventional screw for rapid maxillary expansion (RME) on patient-reported outcome measure during the first 12 weeks of treatment. This is a superiority, multicenter, two-arm parallel balanced randomization trial. Patients in the mixed dentition were included with a transverse discrepancy between the two arches of at least 3 mm. An expansion screw using moderate continuous forces (Leaf group, treated with an expansion screw with Ni-Ti springs) was compared to a conventional RME screw that generates intermittent heavy forces (RME group). The primary response variable was the visual analogue scale (VAS) on pain calculated in the first 12 weeks of therapy. The VAS on difficulty on speaking and oral hygiene, patient satisfaction, and complications were also evaluated. A computer-generated block randomization was used with allocation concealed in sequentially numbered opaque-sealed envelopes. Blinding was not applicable. Linear models were used for statistical analysis. Twenty-eight patients in the Leaf group and 28 patients in the RME group were randomized and included in the study. There were no dropouts. The mean of the VAS for pain was 0.3 ± 0.4 in the Leaf group and 0.6 ± 0.5 in the RME group. The difference was -0.3 (95 per cent CI from -0.5 to -0.0; P = 0.017) in favour of the Leaf group. The difference in pain was marked in the first week (Leaf group 2.2 ± 2.3; RME group 3.7 ± 2.6; difference -1.5; 95 per cent CI from -2.7 to -0.3; P = 0.019). Patients in the Leaf group experienced a lower degree of pain, especially during the first week following the application of the expander. For the other variables, no significant differences were reported between the two treatments. The study was registered in the ISRCTN register on 8 November 2016 with the number ISRCTN18263886.