Double-blind Randomized Crossover Trial Research Articles

Mild processing and addition of milk fat globule membrane in infant formula may better mimic intragastric behavior of human milk: A proof of concept trial in healthy males

BackgroundDuring breastfeeding the macronutrient composition of breastmilk changes gradually from relatively low-fat (foremilk) to relatively high-fat (hindmilk), initially exposing the gastrointestinal tract to a relatively low fat concentration. In contrast, infant formulae (IF) are homogenous. Mild processing and addition of milk fat globule membrane (MFGM) may impact gastric emulsion instability, potentially impacting the phased release of nutrients as observed during breastfeeding. ObjectiveTo assess gastric emulsion stability, gastric emptying, and the postprandial plasma metabolome of an experimental minimally processed IF (EF) with an altered fat-globule interface and a control IF (CF). MethodsTwenty healthy males participated in this double-blind randomized crossover trial. Gastric MRI scans and blood samples were obtained before and after consumption of 600 ml CF or EF over a 2-h period. Outcomes included gastric top layer formation, total gastric volume, and blood parameters (free fatty acids (FFA), insulin, glucose, and nuclear magnetic resonance (NMR-)metabolomics). ResultsEF showed an earlier onset (13.4 min, p = 0.017), smaller maximum volume (49.0 ml, p = 0.033), and a shorter time to maximum top layer volume (13.9 min, p = 0.022), but similar AUC (p = 0.915) compared to CF. Total gastric volume did not show a treatment*time effect. Insulin concentrations were lower for EF. FFA and glucose did not differ. EF yielded higher serum concentrations of phospholipid- and cholesterol-related metabolites. ConclusionAn EF displayed faster gastric creaming than a CF, thereby potentially better mimicking the behavior of breastmilk which leads to phased release of nutrients into the intestine. Overall physiological benefits of this difference in gastric behavior remain to be studied further in infants.

Acute effects of a chewable beetroot-based supplement on cognitive performance: a double-blind randomized placebo-controlled crossover clinical trial

BackgroundDietary nitrate (NO3−) has been shown to be useful as an ergogenic aid with potential applications in health and disease (e.g., blood pressure control). However, there is no consensus about the effects of dietary NO3− or beetroot (BR) juice supplementation on cognitive function.ObjectiveThe aim of this study was to evaluate the effects of a single dose of a chewable BR-based supplement on cognitive performance.MethodsA double-blind randomized placebo-controlled two-period crossover clinical trial was carried out based on the extension of the CONSORT guidelines for randomized crossover trials. A total of 44 participants (24 F; 20 M; 32.7 [12.5] years; 66.3 [9.0] kg; 170 [9.2] cm; 22.8 [1.4] kg/m2) were randomly allocated to receive first either four BR-based chewable tablets (BR-CT) containing 3 g of a Beta vulgaris extract (RedNite®) or four tablets of a placebo (maltodextrin). A 4-day washout period was used before crossover. Ninety minutes after ingestion of the treatments, a neuropsychological testing battery was administered in each period. The trial was registered at clinicaltrials.gov NCT05509075.ResultsSignificant improvements with moderate effect size were found on memory consolidation at the short and long term only after BR-CT supplementation via the Rey Auditory Verbal Learning Test immediate (+ 20.69%) and delayed (+ 12.34%) recalls. Likewise, enhancement on both frontal lobe functions (+ 2.57%) and cognitive flexibility (+ 11.16%) were detected after BR-CT. There was no significant change (p < 0.05) on verbal memory of short-term digits, working memory and information processing speed. Mixed results were found on mood and anxiety through the Beck Depression Inventory-II (BDI-II) and the State-Trait Anxiety Inventory (STAI-Y1 and STAI-Y2); however, sequence and period effects were seen on STAI-Y2.ConclusionsThe acute administration of a chewable BR-based supplement improves certain aspects of cognitive function in healthy females and males, particularly memory capacity and frontal skills.

Directional versus ring-mode deep brain stimulation for Parkinson’s disease: protocol of a multi-centre double-blind randomised crossover trial

BackgroundThe effectiveness of Deep Brain Stimulation (DBS) therapy for Parkinson’s disease can be limited by side-effects caused by electrical current spillover into structures adjacent to the target area. The objective of the STEEred versus RING-mode DBS for Parkinson’s disease (STEERING) study is to investigate if directional DBS for Parkinson’s disease results in a better clinical outcome when compared to ring-mode DBS.MethodsThe STEERING study is a prospective multi-centre double-blind randomised crossover trial. Inclusion criteria are Parkinson’s disease, subthalamic nucleus DBS in a ‘classic’ ring-mode setting for a minimum of six months, and optimal ring-mode settings have been established. Participants are categorised into one of two subgroups according to their clinical response to the ring-mode settings as ‘responders’ (i.e., patient with a satisfactory effect of ring-mode DBS) or ‘non-responder’ (i.e., patient with a non-satisfactory effect of ring-mode DBS). A total of 64 responders and 38 non-responders will be included (total 102 patients). After an optimisation period in which an optimal directional setting is found, participants are randomised to first receive ring-mode DBS for 56 days (range 28–66) followed by directional DBS for 56 days (28–66) or vice-versa. The primary outcome is the difference between ring-mode DBS and directional DBS settings on the Movement Disorders Society Unified Parkinson’s Disease Rating Scale – Motor Evaluation (MDS-UPDRS-ME) in the off-medication state. Secondary outcome measures consist of MDS-UPDRS-ME in the on-medication state, MDS-UPDRS Activities of Daily Living, MDS-UPDRS Motor Complications–Dyskinesia, disease related quality of life measured with the Parkinson’s Disease Questionnaire 39, stimulation-induced side-effects, antiparkinsonian medication use, and DBS-parameters. Participants’ therapy preference is measured at the end of the study. Outcomes will be analysed for both responder and non-responder groups, as well as for both groups pooled together.DiscussionThe STEERING trial will provide insights into whether or not directional DBS should be standardly used in all Parkinson’s disease DBS patients or if directional DBS should only be used in a case-based approach.Trial registrationThis trial was registered on the Netherlands Trial Register, as trial NL6508 (NTR6696) on June 23, 2017.

Post-Activation Performance Enhancement (PAPE) After Resisted Sprinting in Recreationally Active Participants: A Double-Blind Randomised Crossover Trial

Sprint performance and therefore sprint training play important roles in a range of sports and numerous methods to enhance sprint performance have been proposed. One such method is resisted sprinting, whereby a predetermined load (% body mass) or a load which elicits a reduction in sprint velocity, is towed over a prescribed distance. Resisted sprint training can be implemented chronically or acutely. The latter is used to elicit a performance enhancement via post-activation potentiation whereby a superior performance may be achieved when the activity is preceded by a specific stimulus, usually as part of the warm up. The purpose of this study was to determine if a post-activation performance enhancement (PAPE) could be achieved following an acute resisted sprint at two different decreases in sprint velocity using novel resisted sprint equipment (Run Rocket). Eleven healthy male, recreationally trained volunteers (age 23.4 ± 1.9 years, height 180.5 ± 3.5 cm, body mass 86.4 ± 14.5 kg) participated in the study. A maximal 15 m baseline body mass only sprint was performed on the initial visit to ascertain 5 and 15 m sprint time. Participants visited a further two times which consisted of a pre-conditioning resisted sprint activity using the Run Rocket at two different resistance settings in a randomised counter-balanced design. A repeated measures analysis of variance (rmANOVA) showed no significant differences in sprint time, velocity or acceleration between the three conditions (p&gt; 0.05). However, when assessing individuals by the smallest worthwhile change, some participants may have decreased their sprint time. Therefore, the use of resisted sprints did not elicit a post-activation performance enhancement in recreationally trained individuals and may not be beneficial for augmenting acute performance in this population. Individual responses to this type of training may vary and should be a consideration for strength coaches.

Fourteen-Days Spirulina Supplementation Increases Hemoglobin, but Does Not Provide Ergogenic Benefit in Recreationally Active Cyclists: A Double-Blinded Randomized Crossover Trial

Spirulina supplementation has been reported to increase hemoglobin concentration as well as a variety of cardiorespiratory and lactate-based performance parameters during maximal and submaximal states of exercise. This study investigates the efficacy of supplementing a 6 g/day dosage of spirulina for 14-days in recreationally active individuals, analyzing cardiorespiratory parameters during maximal and submaximal cycling as well as the potential mechanistic role of hemoglobin augmentation. 17 recreationally active individuals (Male = 14, Female = 3, Age 23 ± 5 years, V̇O2max 43.3 ± 8.6 ml/min·kg) ingested 6 g/day of spirulina or placebo for 14-days in a double-blinded randomized crossover study, with a 14-day washout period between trials. Participants completed a 20-min submaximal cycle at 40% maximal power output (WRmax), followed by a V̇O2max test. Hemoglobin (g/L), WRmax (watts), time to fatigue (seconds), heart rate (bpm), oxygen uptake (ml/min·kg), RER and blood lactate response (mmol/L) were measured and compared between conditions. Cardiorespiratory variables were recorded at 5-min intervals and lactate was measured at 10-min intervals during the submaximal exercise. There was a significant 3.4% increase in hemoglobin concentration after spirulina supplementation in comparison to placebo (150.4 ± 9.5 g/L Vs 145.6 ± 9.4 g/L, p = 0.047). No significant differences existed between either condition in both testing protocols for V̇O2max, WRmax, time to fatigue, heart rate, oxygen uptake, RER and blood lactate response (p > 0.05). 14-days of spirulina supplementation significantly improved hemoglobin concentration but did not lead to any considerable ergogenic improvements during maximal or submaximal exercise at a 6 g/day dosage in recreationally active individuals whilst cycling.

Magnetoencephalographic neurofeedback training decreases β-low-γ phase-amplitude coupling of the motor cortex of healthy adults: a double-blinded randomized crossover feasibility study

Objective. The coupling between the beta (13–30 Hz) phase and low gamma (50–100 Hz) amplitude in the motor cortex is thought to regulate motor performance. Abnormal phase-amplitude coupling (PAC) of beta-low gamma (β-low-γ PAC) is associated with motor symptoms of Parkinson’s disease. However, the causal relationship between β-low-γ PAC and motor performance in healthy subjects is unknown. We hypothesized that healthy subjects could change the strength of the β-low-γ PAC in the resting state by neurofeedback training (NFT) to control the β-low-γ PAC, such that the motor performance changes in accordance with the changes in β-low-γ PAC in the resting state. Approach. We developed an NFT to control the strength of the β-low-γ PAC in the motor cortex, which was evaluated by magnetoencephalography (MEG) using a current source estimation technique. Twenty subjects were enrolled in a double-blind randomized crossover trial to test the feasibility of the MEG NFT. In the NFT for 2 d, the subjects were instructed to reduce the size of a black circle whose radius was proportional (down-training) or inversely proportional (up-training) to the strength of the β-low-γ PAC. The reaction times (RTs) to press a button according to some cues were evaluated before and after training. This study was registered at ClinicalTrials.gov (NCT03837548) and UMIN-CTR (UMIN000032937). Main results. The β-low-γ PAC during the resting state was significantly decreased after down-training, although not significantly after up-training. RTs tended to decrease after both trainings, however the differences were not statistically significant. There was no significant correlation between the changes in β-low-γ PAC during rest and RTs. Significance. The proposed MEG NFT was demonstrated to change the β-low-γ PAC of the motor cortex in healthy subjects. However, a relationship between PAC and RT has not yet been demonstrated.

Consumption of Farmed Fish, Fed with an Olive-Pomace Enriched Diet, and Its Effect on the Inflammatory, Redox, and Platelet-Activating Factor Enzyme Profile of Apparently Healthy Adults: A Double-Blind Randomized Crossover Trial.

A fish-rich diet has a beneficial effect on cardiovascular health. The platelet activating factor (PAF) is involved in the development of atherosclerosis, and in vitro results support the regulating action of bioactive nutrients on PAF metabolism. The purpose of this study is to examine whether the consumption of farmed fish fed with an olive-pomace enriched diet (EF) affects PAF metabolism and the markers of inflammation and oxidative stress compared to the consumption of conventionally fed farmed fish (CF). Thirty apparently healthy adults completed a randomized double-blind crossover trial, during which they consumed both CF and EF twice a week for 8 weeks with a six-week washout period in between. The activities of PAF acetylhydrolase (PAF-AH), lysoPAF acetyltransferase (lysoPAF-AT), DTT-insensitive CDP-choline: 1-alkyl-2-acetyl-sn-glycerol-choline-phosphotransferase (PAF-CPT) in leukocytes, and lipoprotein-associated phospholipase A2 (LpPLA2) in serum were determined. The quantities of interleukin-6 (IL-6), high sensitivity C-reactive protein (hsCRP), oxidized LDL (ox-LDL), thiobarbituric acid-reactive substances (TBARS), and glutathione peroxidase (GPx), as well as the serum oxidation, were also determined. Both types of fish exerted similar effects as there were no statistically significant differences between the two interventions except for an elevated PAF-CPT and reduced arachidonic acid (AA) in the red blood cell (RBC) membrane lipids after the EF intake.

Vascular benefits of vitamin C supplementation against fine particulate air pollution in healthy adults: A double-blind randomised crossover trial

Evidence on the health benefits of vitamin C supplementation in highly polluted areas has not been evaluated. We aimed to evaluate whether dietary vitamin C supplementation can improve vascular health linked to particulate matter (PM) exposure. A randomised double-blind crossover trial involving 58 health young adults was performed in Shijiazhuang, China in 2018. All subjects were randomly assigned to the vitamin C supplementation group (2000 mg/d) or placebo group for a week alternating with a 2 week washout period. Fifteen circulating biomarkers were measured. Linear mixed-effect model was applied to evaluate the effect of vitamin C supplementation on health outcomes. The average concentrations of PM2.5 and PM10 were 164.91 and 327.05 μg/m3, respectively. Vitamin C supplementation was significantly associated with a 19.47% decrease in interleukin-6 (IL-6), 17.30% decrease in tumour necrosis factor-a (TNF-α), 34.01% decrease in C-reactive protein (CRP), 3.37% decrease in systolic blood pressure (SBP) and 6.03% decrease in pulse pressure (PP). Furthermore, glutathione peroxidase (GSH-Px) was significantly increased by 7.15%. Sex-subgroup analysis showed that vitamin C significantly reduced TNF-α by 27.85% in male participants and significantly increased APOB by 6.28% and GSH-Px by 14.47% only in female participants. This study indicated that vitamin C supplementation may protect vascular vessels against PM exposure among healthy young adults in China.

A double-blind randomised crossover trial of low-dose flumazenil for benzodiazepine withdrawal: A proof of concept

IntroductionBenzodiazepines (BZD) are a class of anxiolytics with varying uses, which primarily act on the GABAA receptor resulting in hyperpolarisation. BZDs are often a difficult drug class to cease once neuroadaptation has occurred; recommendations usually involve gradual dose reductions at variable rates. A growing body of evidence has suggested that low-dose flumazenil, a GABAA receptor antagonist, may be a useful agent to allow for rapid detoxification. AimTo collect pilot data on the safety and efficacy of low-dose subcutaneous flumazenil to reduce BZD use, withdrawal symptoms, and craving in participants taking above and below the therapeutic maximum diazepam equivalent of 30 mg to inform on sample size for future trials. MethodIn a randomised double-blinded crossover study design, participants received low-dose flumazenil first (4 mg/24 h for approximately eight days) or placebo first. Groups were divided into those taking < 30 mg diazepam equivalent and ≥ 30 mg diazepam equivalent at baseline. Main outcome measures were percentage reduction in daily diazepam use, withdrawal symptoms, and craving scores from baseline, difference in diazepam use across the placebo first group, and flumazenil related adverse events. ResultsTwenty-eight participants were recruited and randomised to flumazenil first (n = 14) and placebo first (n = 14). In participants taking ≥ 30 mg diazepam equivalent at baseline (n = 15), flumazenil significantly reduced diazepam use by 30.5% (p = 0.024) compared to placebo. ConclusionLow-dose flumazenil may aid in BZD detoxification in participants taking daily diazepam equivalent doses greater than or equal to the therapeutic maximum (≥30 mg) by reducing the need for diazepam.

Plasma Amino Acid Appearance and Status of Appetite Following a Single Meal of Red Meat or a Plant-Based Meat Analog: A Randomized Crossover Clinical Trial

ABSTRACTBackgroundRed meat is a nutrient-dense food and a dietary staple. A new generation of plant-based meat analogs (PBMAs) have been designed to mimic the experience of eating meat, but there is limited evidence about their digestive efficacy and nutritional quality.ObjectivesWe compared the postprandial digestive response of a single meal containing meat commercially raised in New Zealand, including lamb, on-farm pasture-raised beef (Pasture), or grain-finished beef (Grain) with a PBMA (Beyond Burger; Beyond Meat) sold through consumer retail. The primary outcome was the appearance of amino acids in plasma. Secondary outcomes included glucose and insulin, appetite assessment, and anthropometry.MethodsThirty healthy men (20–34 y) participated in a double-blinded randomized crossover trial. Each consumed 1 of the 4 test meals on 4 occasions separated by a washout period of at least 1 wk, following an overnight fast. The meal was a burrito-style wrap containing meat or PBMAs, vegetables, salsa, and seasonings in a flour tortilla. The amount of Pasture, Grain, Lamb, or BB was 220 g raw (∼160 g cooked). Venous blood samples were collected over 4 h. Appetite and hunger status was scored with visual analog scales.ResultsPre-meal amino acid concentrations in plasma did not differ by group (P > 0.9), although several nonessential amino acids differed strongly according to participant BMI. Postprandial amino acids peaked at 2–3 h in all groups. The BB meal produced significantly lower plasma concentrations of total, essential, branched-chain, and non-proteogenic amino acids than the Lamb, Pasture, or Grain meals, based on AUC. There were no significant differences between meal groups in scores for hunger, fullness, or cravings.ConclusionsRed meat meals exhibited greater bioavailability of amino acids compared with the PBMA (BB). Pasture versus Grain origins of the beef had little influence on participants’ responses. This trial was registered at ClinicalTrials.gov as NCT04545398.

The effect of silver fibre gloves on Raynaud's phenomenon in patients with systemic sclerosis: a double-blind randomized crossover trial.

Silver fibre gloves transport heat from the palm to the fingers, possibly reducing the burden of RP in SSc patients. We aim to evaluate the clinical efficiency of this intervention. A multicentre, double-blind, randomized trial was performed, accounting for interindividual differences and external factors using a crossover design. Patients were randomized in two groups: group 1 wore 8% silver fibre gloves in period 1 and normal gloves in period 2 and group 2 vice versa. Each period lasted 6 weeks. The primary outcome was the Raynaud Condition Score (RCS) over time (minimal clinical important difference 1.4), assessed three times per week using an online questionnaire. Secondary outcomes included vascular complications and Scleroderma-Health Assessment Questionnaire (SHAQ). Outcomes were evaluated before unblinding using linear mixed models. A total of 85 SSc patients were included, with 76 completing the study. The mean RCS during 2 weeks before the study (i.e. without gloves) was 6.4 (s.d. 1.6). Both with silver fibre gloves and normal gloves the mean RCS decreased to 3.9 (s.d. 2.3) with a similar course over time. There was no difference in mean RCS over time between the type of gloves [β = 0.067 (95% CI -0.006, 0.19)]. Of secondary outcomes, total SHAQ [β = 0.036 (95% CI 0.026, 0.046)] was slightly higher with silver fibre gloves, which is clinically irrelevant. Three patients developed new digital ulcers with normal gloves vs one patient with silver fibre gloves [odds ratio 3.2 (95% CI 0.32, 31.1)]. Wearing gloves in SSc patients clearly decreases the RP burden. Our results do not support the hypothesis that increased heat transport of 8% silver fibre gloves is associated with less disease burden as measured in this study by the RCS compared with normal gloves. Netherlands Trial register (https://www.trialregister.nl/) NL7904.

Resveratrol treatment does not reduce arterial inflammation in males at risk of type 2 diabetes: a randomized crossover trial.

Resveratrol has shown promising anti-inflammatory effects in in vitro and animal studies. We aimed to investigate this effect on arterial inflammation in vivo. This was an additional analysis of a double-blind randomized crossover trial which included eight male subjects with decreased insulin sensitivity who underwent an 18F-fluoroxyglucose (18F-FDG) PET/CT after 34 days of placebo and resveratrol treatment (150 mg/day). 18F-FDG uptake was analyzed in the carotid arteries and the aorta, adipose tissue regions, spleen, and bone marrow as measures for arterial and systemic inflammation. Maximum target-to-background ratios (TBRmax) were compared between resveratrol and placebo treatment with the non-parametric Wilcoxon signed-rank test. Median values are shown with their interquartile range. Arterial 18F-FDG uptake was non-significantly higher after resveratrol treatment (TBRmax all vessels 1.7 (1.6-1.7)) in comparison to placebo treatment (1.5 (1.4-1.6); p=0.050). Only in visceral adipose tissue, the increase in 18F-FDG uptake after resveratrol reached statistical significance (p=0.024). Furthermore, CRP-levels were not significantly affected by resveratrol treatment (p=0.091). Resveratrol failed to attenuate arterial or systemic inflammation as measured with 18F-FDG PET in subjects at risk of developing type 2 diabetes. However, validation of these findings in larger human studies is needed.

Acute erythropoietin injection increases muscle mitochondrial respiratory capacity in young men: a double-blinded randomized crossover trial.

The aim was to investigate if acute recombinant human erythropoietin (rHuEPO) injection had an effect on mitochondrial function and if exercise would have an additive effect. Furthermore, to investigate if in vitro incubation with rHuEPO had an effect on muscle mitochondrial respiratory capacity. Eight healthy young men were recruited for this double-blinded randomized placebo-controlled crossover study. rHuEPO (400 IU/kg body wt) or saline injection was given intravenously, before an acute bout of exercise. Resting metabolic rate and fat oxidation were measured. Biopsies were obtained at baseline, 120 min after injection, and right after the acute exercise bout. Mitochondrial function (mitochondrial respiration and H2O2 emission) was measured in permeabilized skeletal muscle using high-resolution respirometry and fluorometry. Specific gene expression and enzyme activity were measured. Skeletal muscle mitochondrial respiratory capacity was measured with and without incubation with rHuEPO. Fat oxidation at rest increased after rHuEPO injection, but no difference was found in fat oxidation during exercise. Mitochondrial respiratory capacity was increased after rHuEPO injection when pyruvate was in the assay, which was not the case when saline was injected. No changes were seen in H2O2 emission after rHuEPO injection or acute exercise. Incubation of skeletal muscle fibers in vitro with rHuEPO increased mitochondrial respiratory capacity. Acute rHuEPO injection increased mitochondrial respiratory capacity when pyruvate was used in the assay. No statistical difference was found in H2O2 emission capacity, although a numerical increase was seen after rHuEPO injection. In vitro incubation of the skeletal muscle sample with rHuEPO increases mitochondrial respiratory capacity.NEW & NOTEWORTHY The effect of an acute rHuEPO injection on skeletal muscle mitochondrial function was investigated in young healthy male subjects. rHuEPO has an acute effect on skeletal muscle mitochondrial respiratory capacity in humans, where an increased mitochondrial respiratory capacity was seen. This could be the first step leading to increased mitochondrial biogenesis.

Omega-7 Mixed Fatty Acid Supplementation Fails to Reduce Serum Inflammatory Biomarkers: A Placebo-Controlled, Double-Blind Randomized Crossover Trial

We report the effects of mixed omega-7 fatty acid supplementation on changes in serum hsCRP, TNFα, and IL-6 levels and self-reported outcomes in people with non-specific chronic musculoskeletal discomfort. Design: A double-blind, placebo-controlled, 1:1 randomized single crossover trial composed of 688 mg/day palmiteolate for the verum and an equivalent amount of medium-chain triglycerides for the placebo. Method: Data were analyzed in two independent groups and as a crossover group. Results: From 211 screened participants in 2017–2019, 56 were randomized. Six participants dropped out and fifty completers contributed to the statistical analyses. At baseline, none of the investigated biomarkers were significantly correlated to subjectively assessed musculoskeletal discomfort levels. For the two-group analysis (n = 26 and n = 24), none of the serum biomarkers reached statistical significance; however, a statistically significant placebo effect was found in the subjective outcomes. Conclusion: For the crossover analysis (n = 50), three weeks of supplementation with n7FA containing 688 mg per day of palmiteolate did not reduce serum inflammatory biomarkers nor did it improve subjectively measured quality of life (QoL) compared to placebo. Future studies should explore appropriate biomarkers, sufficient power, length of dosing, inclusion criteria for volunteers with higher BMI, and the verification of cis-palmiteolate versus trans-palmiteolate.

Effect of didecyl dimethyl ammonium chloride-impregnated washcloth wipe whole-body bathing on catheter-related blood stream infections and central venous line-associated infections in adult intensive care units

ObjectiveTo investigate the effect of daily whole-body bathing (WBB) using disposable washcloth wipes/caps impregnated with an antiseptic solution containing the quaternary ammonium base compound didecyl dimethyl ammonium chloride (DDAC). MethodsA prospective double-blind randomized crossover trial was conducted to compare WBB of adult intensive care unit (ICU) patients with washcloth wipes/caps impregnated with either regular cleanser/shampoo or the antiseptic DDAC. The clinical trial was performed in a medical ICU (MICU) and a surgical ICU (SICU). The study period was divided into two 6-month intervals with alternating treatment regimens. ResultsA total of 1540 ICU patients (total length of ICU stay 10 470 days) were included in the trial. Compared to controls, DDAC bathing was found to be associated with reduced incidence rates per 1000 patient days for central-venous-line-associated infections (CLAIs) caused by Gram-positive bacteria (GPB) from 16.39 (95%CI 13.1–20.3) in the control group to 7.28 (95%CI 5.2–9.9) in the intervention group (p 0.01). A stratified analysis by unit showed that the incidence rates of CLAI due to GPB were reduced by the intervention in both the MICU and the SICU from 21.2 (95%CI 15.8–27.7) to 9.3 (95%CI 5.8–14.1) (p < 0.01) and from 12.1 (95%CI 8.3–17.0) to 5.7 (95%CI 3.4–9.1) (p 0.01), respectively. There was a trend towards reduction in catheter-related bloodstream infections (CRBSIs) and bloodstream infections (BSIs); however, this did not reach statistical significance due to carry-over effects and small numbers. ConclusionsGiven the growing need for new concepts to prevent and control healthcare-associated infections, DDAC may be a new and promising agent for WBB of ICU patients.

The health effects of wearing facemasks on cardiopulmonary system of healthy young adults: A double-blinded, randomized crossover trial.

Facemask had increasingly been utilized as a personal protective measure to reduce exposure to ambient particulate matter (PM) during heavily-polluted days and routine life. However, evidence on the potential effects on cardiovascular system by wearing particulate-filtering facemask was limited. We conducted a double-blinded randomized crossover trial (RCT) to evaluate the effects of wearing N95 facemasks on the molecular responses of cardiopulmonary system among 52 healthy college students in Beijing, China. We measured cardiopulmonary health indicators and collected biological samples before and after (up to 5h at multiple time points) a 2-h walk to examine the changes in lung function, biomarkers of respiratory and systemic oxidative stress/inflammation. We applied linear mixed-effect models to evaluate the effect of the facemask-intervention on the health of cardio-pulmonary system. In the trial wearing real facemasks, FEV1 increased by 2.05% (95% CI: 0.27%-3.87%), 2.80% (95% CI: 1.00%-4.63%), and 2.87% (95% CI: 1.07%-4.70%) at V1 (30-min), V2 (3-h), and V3 (5-h) after the 2-h walk outsides, respectively. Compared with participants wearing the sham mask, the percentage change of nitrate in EBC was lower among those wearing the real mask. After the 2-h exposure, urinary MDA levels increased compared to the baseline in both trials. Real trial was lower than sham trial for 6 cytokines (i.e., IL-6, IL-10, IL-13, IL-17A, IFN-γ and TNF-α) in serum at 5-h post-exposure. Wearing facemasks on polluted days produced better improvement, however, on cleaner days, the improvement was weaker. Short-term use of N95 facemasks appeared to effectively reduce the levels of lung function declines, the respiratory oxidative stress, and the systemic inflammation/oxidative stress which may be induced by short-term exposure to PM. Wearing facemasks on polluted days (PM2.5>75μg/m3) presented larger beneficial effects on the cardiopulmonary health than in clean days (PM2.5<75μg/m3).

Dextrose 10% drink is superior to sodium-dextrose drink in increasing blood glucose and sprint speed in soccer players: A double-blinded randomized crossover trial study

This study aimed to examine the effect of dextrose drink (D) on blood glucose, VO 2 max, and sprint speed compared with Sodium-Dextrose drink. Equipment and Methods : We conducted a double-blinded crossover study of 22 young male (19 ± 1.1 years) soccer players, consumed either Dextrose drink or Sodium-Dextrose drink. We compared pre- and post-data of Blood Glucose, VO 2 max, and sprint speed between the dextrose and sodium-dextrose drinks groups. The primary outcome was differences in ΔBlood Glucose between D and Sodium-D group. Secondary outcomes were differences in ΔVO 2 max and Δsprint speed between D and Sodium-D group. The mean BG level was higher in D compared with Sodium-D group [136 ± 22.9 mg/dl vs. 118 ± 21.5 mg/dl] ( P = 0.009). Mean differences of ΔBG of D (mean before and mean after) compared with ΔBG Sodium-D (mean before and mean after) is 16.8 mg/dl ( P = 0.001). The mean of sprint speed is faster in the D group [15.2 ± 1.25 sec vs. 15.9 ± 1.61 sec] ( P = 0.019), but we found no significant differences in VO 2 max between both groups [42.1 ± 3.44 ml/min/kg vs. 42.3 ± 3.98 ml/min/kg] ( P = 0.834). The present study demonstrated that dextrose drink without added sodium has a large influence on increasing blood glucose level and sprint speed. Cette étude visait à examiner l’effet d’une boisson à 10 % de dextrose sur la glycémie, la VO 2 max et la vitesse de sprint par rapport à une boisson Sodium-Dextrose. Équipement et méthodes : Nous avons mené une étude croisée en double insu sur 22 jeunes footballeurs de sexe masculin (19 ± 1,1 ans), consommant une boisson au Dextrose ou une boisson Sodium-Dextrose. Nous avons comparé les données pré- et post- sur la glycémie, la VO 2 max et la vitesse de sprint entre les groupes de boissons Dextrose et Sodium-Dextrose. Le critère de jugement principal était les différences de glycémie Δ entre les groupes Dextrose et Sodium-Dextrose. Les critères de jugement secondaires étaient des différences de vitesse ΔVO 2 max et Δsprint entre les groupes Dextrose et Sodium-Dextrose. Le niveau moyen de glycémie était plus élevé dans D par rapport au groupe Sodium Dextrose [136 ± 22,9 mg/dl vs. 118 ± 21,5 mg/dl] ( p = 0,009). Les différences moyennes de ΔBG de Dextrose 10 % (moyenne avant et moyenne après) par rapport à ΔBG Sodium-D (moyenne avant et moyenne après) sont de 16,8 mg/dl ( p = 0,001). La vitesse moyenne de sprint est plus rapide dans le groupe D [15,2 ± 1,25 s vs. 15,9 ± 1,61 s] ( p = 0,019), mais nous n’avons trouvé aucune différence significative de VO 2 max entre les deux groupes [42,1 ± 3,44 ml/min/43 kg vs. 42,3 ± 3,98 ml/min/kg] ( p = 0,834). La présente étude a démontré que la boisson de dextrose sans sodium ajouté a un effet important sur l’augmentation du taux de glycémie et de la vitesse de sprint.

β-Lactoglobulin Is Insulinotropic Compared with Casein and Whey Protein Ingestion during Catabolic Conditions in Men in a Double-Blinded Randomized Crossover Trial.

Muscle loss during acute infectious disease is mainly triggered by inflammation, immobilization, and malnutrition. The objective was to compare muscle protein kinetics and metabolism following ingestion of the dairy protein supplements β-lactoglobulin (BLG), casein (CAS), and whey (WHE) during controlled catabolic conditions. We used a randomized crossover design (registered at clinicaltrials.gov as NCT03319550) to investigate 9 healthy male participants [age: 20-40 y; BMI (in kg/m2) 20-30] who were randomly assigned servings of BLG, CAS, or WHE (0.6g protein/kg, one-third as bolus and two-thirds as sip every 20min) on 3 separate occasions separated by ∼6-8 wk. The participants received an infusion of lipopolysaccharide (1ng/kg) combined with 36h of fasting and bed rest before each study day, mimicking a clinical catabolic condition. The forearm model and isotopic tracer techniques were used to quantify muscle protein kinetics. Muscle biopsy specimens were obtained and intramyocellular signaling investigated using Western blot. BLG, CAS, and WHE improved the net balance of phenylalanine (NBphe) from baseline with ∼75% (P<0.001) with no difference between interventions (primary outcome, P<0.05). No difference in rates of appearance and disappearance of phenylalanine or in intramyocellular signaling activation was found between interventions (secondary outcomes). The incremental AUC for serum insulin was 62% higher following BLG compared with CAS (P <0.001) and 30% higher compared with WHE (P=0.002), as well as 25% higher in WHE compared with CAS (P=0.006). Following BLG consumption, plasma concentrations of glucose-dependent insulinotropic peptide (GIP) increased 70% compared with CAS (P=0.001) and increased 34% compared with WHE (P=0.06). No significant difference was found between WHE and CAS (P=0.12). BLG, WHE, and CAS have similar effects on muscle in young male participants during catabolic conditions. BLG showed specific, possibly GIP-dependent, insulinotropic properties, which may have future clinical implications.

Acute dose-response effect of coffee-derived chlorogenic acids on the human vasculature in healthy volunteers: a randomized controlled trial

ABSTRACTBackgroundEpidemiological studies have reported lower risk of cardiovascular disease with moderate coffee consumption. In addition, emerging evidence indicates that consumption of coffee beverages enriched in chlorogenic acids (CGAs) may influence blood pressure and endothelial function, suggesting that the beneficial cardiovascular effect of coffee may relate to its CGA content.ObjectivesWe conducted a double-blind randomized crossover trial to test the effect of acute consumption of a decaffeinated green coffee extract (DGCE), rich in CGAs, on endothelial function in healthy subjects.MethodsWe compared 3 different doses of DGCE (302, 604, and 906 mg, respectively) with a placebo. Endothelial function was defined as the percentage change in the internal diameter of the brachial artery in response to flow-mediated dilation (%FMD). In addition, we followed the plasma concentration-time profiles of 25 systemic CGA metabolites over 24 h after DGCE consumption and we explored the relation between systemic concentrations of CGAs and the effect on %FMD.ResultsThe DGCE formulations containing different amounts of CGAs resulted in dose-proportional increases in overall total polyphenol concentrations. The systemic appearance of total CGAs was biphasic, in agreement with previous results suggesting 2 sites of absorption in the gastrointestinal tract. Compared with the placebo group, a significant FMD increase (>1%) was observed 8.5, 10, and 24 h after consumption of 302 mg DGCE (∼156.4 mg CGAs). The differences with placebo observed in the other 2 groups were not statistically significant. Evaluation of the relation between phenolic exposure and %FMD showed a positive tendency toward a larger effect at higher concentrations and different behavior of CGA metabolites depending on the conjugated chemical position.ConclusionsWe demonstrated an acute improvement in %FMD over time after ingestion of a DGCE, explained at least partly by the presence in the blood circulation of CGAs and their metabolites. This trial was registered at clinicaltrials.gov as NCT03520452.

Effect of Differently Fed Farmed Gilthead Sea Bream Consumption on Platelet Aggregation and Circulating Haemostatic Markers among Apparently Healthy Adults: A Double-Blind Randomized Crossover Trial.

Fish consumption beneficially affects coagulation markers. Few dietary intervention studies have investigated differently fed farmed fish against these cardio-metabolic risk factors in humans. This double-blind randomized crossover trial evaluated differently fed farmed gilthead sea bream consumption against platelet aggregation and circulating haemostatic markers among apparently healthy adults. Subjects aged 30–65 years, with a body mass index 24.0–31.0 kg/m2, consuming less than 150 g cooked fish per week, were recruited in Attica, Greece. Participants were randomized (n = 38, 1:1) to one of two sequences; consumption of fish fed with fish oil diet (conventional fish, CF)/fish fed with olive pomace-enriched diet (enriched fish, EF) versus EF/CF. The primary outcomes were ex vivo human platelet aggregation and circulating plasminogen activator inhibitor-1 (PAI-1) and P-selectin (sP-selectin) concentrations. EF consumption had no significant effect on platelet sensitivity or haemostatic markers compared to CF. Platelet sensitivity to platelet-activating factor (PAF) decreased after CF consumption during the second period (p < 0.01). Plasma PAI-1 and sP-selectin concentrations increased after CF consumption during both periods (p < 0.01 for both). Based on current findings, consumption of enriched farmed gilthead sea bream had no greater effect on coagulation markers in adults compared to the conventionally fed fish.