Double-blind Placebo-controlled Crossover Study Research Articles

Effects of phosphodiesterase V inhibition alone and in combination with BNP on cardiovascular and renal response to volume load in human preclinical diastolic dysfunction.

Preclinical diastolic dysfunction (PDD) results in impaired cardiorenal response to volume load (VL) which may contribute to the progression to clinical heart failure with preserved ejection fraction (HFpEF). The objective was to evaluate if phosphodiesterase V inhibition (PDEVI) alone or combination PDEVI plus B‐type natriuretic peptide (BNP) administration will correct the impaired cardiorenal response to VL in PDD. A randomized double‐blinded placebo‐controlled cross‐over study was conducted in 20 subjects with PDD, defined as left ventricular ejection fraction (LVEF) >50% with moderate or severe diastolic dysfunction by Doppler echocardiography and without HF diagnosis or symptoms. Effects of PDEVI with oral tadalafil alone and tadalafil plus subcutaneous (SC) BNP, administered prior to acute volume loading, were assessed. Tadalafil alone did not result in improvement in cardiac response to VL, as measured by LVEF, LV end diastolic volume, left atrial volume (LAV), or right ventricular systolic pressure (RVSP). Tadalafil plus SC BNP resulted in improved cardiac response to VL, with increased LVEF (4.1 vs. 1.8%, p = 0.08) and heart rate (4.3 vs. 1.6 bpm, p = 0.08), and reductions in both LAV (−4.3 ± 10.4 vs. 2.8 ± 6.6 ml, p = 0.03) and RVSP (−4.0 ± 3.0 vs. 2.1 ± 6.0 mmHg, p < 0.01) versus tadalafil alone. Plasma and urinary cyclic guanosine monophosphate (cGMP) excretion levels were higher (11.3 ± 12.3 vs. 1.7 ± 3.8 pmol/ml, 1851.0 ± 1386.4 vs. 173.4 ± 517.9 pmol/min, p < 0.01) with tadalafil plus SC BNP versus tadalafil alone. There was no improvement in renal response as measured by GFR, renal plasma flow, sodium excretion, and urine flow with tadalafil plus SC BNP compared to tadalafil alone. In subjects with PDD, tadalafil alone resulted in no improvement in cardiac adaptation, while tadalafil and SC BNP resulted in enhanced cardiac adaptation to VL.Trial RegistrationClinicalTrials.gov NCT01544998.

D-cycloserine normalizes long-term motor plasticity after transcranial magnetic intermittent theta-burst stimulation in major depressive disorder

ObjectivesMajor Depressive Disorder (MDD) is associated with glutamatergic alterations, including the N-methyl-D-aspartate receptor (NMDA-R). The NMDA-R plays an important role in synaptic plasticity, and individuals with MDD have been shown to have impairments in repetitive Transcranial Magnetic Stimulation (rTMS) motor plasticity. Here, we test whether D-cycloserine, a NMDA-R partial agonist, can rescue TMS motor plasticity in MDD. MethodsWe conducted randomized double-blind placebo-controlled crossover studies in healthy (n = 12) and MDD (n = 12) participants. We stimulated motor cortex using TMS intermittent theta burst stimulation (iTBS) with placebo or D-cycloserine (100 mg). Motor evoked potentials (MEPs) were sampled before and after iTBS. Stimulus response curves (SRC) were characterized at baseline, +90 minutes, and the following day. ResultsAcute iTBS MEP facilitation is reduced in MDD and is not rescued by D-cycloserine. After iTBS, SRCs shift to indicate sustained decrease in excitability in healthy participants, yet increased in excitability in MDD participants. D-cycloserine normalized SRC changes from baseline to the following day in MDD participants. In both healthy and MDD participants, D-cycloserine stabilized changes in SRC. ConclusionMDD is associated with alterations in motor plasticity that are rescued and stabilized by NMDA-R agonism. SignificanceAgonism of NMDA receptors rescues iTBS motor plasticity in MDD.

Effects of 6-(Methylsulfinyl)hexyl Isothiocyanate Ingestion on Muscle Damage after Eccentric Exercise in Healthy Males: A Pilot Placebo-Controlled Double-Blind Crossover Study

An animal study demonstrated that 6-(Methylsulfinyl)hexyl isothiocyanate (6-MSITC), a major bioactive compound in Japanese pungent spice wasabi, has an action of inhibiting the activation of calpain-1 (a protease). Increases in calpain activity can cause continual strength loss after eccentric exercise. It remains to be determined in humans whether 6-MSITC intake would modulate calpain and/or muscle damage responses after eccentric exercise. We performed a randomized, double-blind, crossover design study wherein eight healthy young males were randomly assigned to ingest 9 mg/day of 6-MSITC or placebo from 1 day before exercise to 4 days after exercise (30 maximal isokinetic eccentric contractions of the elbow flexors using an isokinetic dynamometer). Calpain-1 concentration, inflammatory and muscle damage markers (creatine kinase activity, urinary titin concentration, muscle strength, range of motion, muscle soreness and transverse relaxation time) were assessed. Plasma calpain-1 concentration after eccentric exercise was similar between the placebo- and 6-MSITC-treated conditions. All muscle damage and inflammatory markers were not affected by 6-MSITC relative to those in the placebo-treated condition. Our results suggest that 6-MSITC has no effect on plasma calpain-1 concentration and muscle damage and inflammatory markers measured after eccentric exercise.

Role of oxytocin in modulating addictive behaviour

BackgroundThe brain oxytocin system is involved in a wide range of addictive behaviors, inhibiting prime- and cue-induced relapse in preclinical models of substance use disorders. Animal studies linked oxytocin’s effects on drug ingestion to modulation of neurotransmission in the nucleus accumbens (NAc). We set out to investigate whether oxytocin can modulate alcohol cue-induced functional connectivity between the brain reward system and cortical regions.MethodsFifteen male heavy social drinkers were enrolled in a randomized double-blind placebo-controlled cross-over functional magnetic resonance imaging study (fMRI) investigating the effect of 24 IU oxytocin on alcohol cue-modulated functional connectivity.ResultsResults of the functional connectivity analyses show that oxytocin application significantly reduced connectivity between the NAc and cuneus and thalamo-occipital connectivity, while enhancing connectivity between the paracingulate gyrus and precentral gyrus (tow-sided seed-level false discovery rate pFDR &lt; 0.05). These effects were specific to the alcohol presentation and were absent during processing of neutral pictures. In addition, the NAc-cuneus connectivity significantly correlated with subjective alcohol cue-induced craving during the scanning session (r = 0.538, p = 0.024). Conclusion: Results provide initial evidence for condition-specific and significant attenuation of NAc connectivity by oxytocin in a sample of heavy social drinkers that was related to lower subjective alcohol craving during the fMRI task. Oxytocin-induced attenuation of NAc connectivity was specific to processing alcohol stimuli and might reflect an attenuation of alcohol-cue saliency by oxytocin that could lead to a reduction of the sensitivity towards the appetitive aspects of alcohol cues.DisclosureNo significant relationships.

Drug repurposing in autosomal dominant polycystic kidney disease: back to the future with pioglitazone

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cause of end-stage kidney failure. At present, only one drug, tolvaptan, has been approved for use to slow disease progression, but its use is limited by reduced tolerability and idiosyncratic liver toxicity. Thiazolidinediones were first developed as insulin-sensitizers but also regulate gene transcription in multiple tissues, leading to systemic effects on metabolism, inflammation and vascular reactivity. In this issue, Blazer-Yost et al. report the results of a single-centre Phase 1b double-blind placebo-controlled crossover study of the peroxisome proliferator-activated receptor γ (PPAR-γ) agonist pioglitazone in 18 ADPKD patients. Encouragingly, there were no major safety signals, although evidence of efficacy could not be demonstrated due to the small sample size. We review the preclinical evidence for the use of PPAR-γ agonists in ADPKD and speculate on the likely beneficial and adverse clinical effects of this interesting class of compounds in a future trial.

Liraglutide to Improve corONary haemodynamics during Exercise streSS (LIONESS): a double-blind randomised placebo-controlled crossover trial

BackgroundGlucagon-like peptide-1 receptor (GLP-1R) activation may improve myocardial performance in the context of ischaemia, independent of glycaemic control, in individuals with and without type 2 diabetes mellitus.MethodsThe LIONESS trial was a single-centre randomised double-blind placebo-controlled crossover study to determine whether prolonged GLP-1R activation could improve exercise haemodynamics in chronic stable angina patients. Eligibility criteria comprised angiographic evidence of obstructive coronary artery disease (CAD) and an abnormal baseline exercise tolerance test (ETT) demonstrating > 0.1 mV of planar or downsloping ST-segment depression (STD). Those randomised to active agent started with a 1-week run-in phase of 0.6 mg liraglutide daily, an established injectable GLP-1R agonist, followed by 1 week of 1.2 mg liraglutide, after which patients performed a week 2 ETT. Patients then self-administered 1.8 mg liraglutide for a week before completing a week 3 ETT. The placebo arm received visually and temporally matched daily saline injections. Participants then crossed over to a 3-week course of saline injections interspersed with a week 5 ETT and week 6 ETT and vice versa. Co-primary endpoints were rate pressure product (RPP) at 0.1 mV STD and magnitude of STD at peak exercise.ResultsTwenty-two patients (21 without diabetes) were randomised. There was no significant difference between saline versus liraglutide in the co-primary endpoints of RPP achieved at 0.1 mV STD (saline vs. liraglutide 1.2 mg p = 0.097; saline vs. liraglutide 1.8 mg p = 0.48) or the degree of STD at peak exercise (saline vs. liraglutide 1.2 mg p = 0.68; saline vs. liraglutide 1.8 mg p = 0.57). Liraglutide did not cause symptomatic hypoglycaemia, renal dysfunction, acute pancreatitis or provoke early withdrawal from the trial. Liraglutide significantly reduced weight (baseline 88.75 ± 16.5 kg vs. after liraglutide 87.78 ± 16.9 kg; p = 0.0008) and improved the lipid profile (mean total cholesterol: at baseline 3.97 ± 0.88 vs. after liraglutide 3.56 ± 0.71 mmol/L; p < 0.0001).ConclusionLiraglutide did not enhance exercise tolerance or haemodynamics compared with saline placebo during serial treadmill testing in patients with established obstructive CAD. It did, however, significantly reduce weight and improve the lipid profile.Trial Registration ClinicalTrials.gov Identifier NCT02315001. Retrospectively registered on 11th December 2014.

Hydrogen Rich Water Consumption Positively Affects Muscle Performance, Lactate Response, and Alleviates Delayed Onset of Muscle Soreness After Resistance Training.

Botek, M, Krejčí, J, McKune, A, Valenta, M, and Sládečková, B. Hydrogen rich water consumption positively affects muscle performance, lactate response, and alleviates delayed onset of muscle soreness after resistance training. J Strength Cond Res 36(10): 2792-2799, 2022-Positive outcomes of hydrogen rich water (HRW) supplementation on endurance performance have been shown, but the effects of HRW in resistance training are unclear. The aim of this study was to assess the effects of 1,260 ml of HRW intake on physiological, perceptual, and performance responses to a resistance training and after 24 hours of recovery. This randomized, double-blinded placebo-controlled cross-over study included 12 men aged 23.8 ± 1.9 years. Subjects performed a half squat, knee flexion, and extension exercises with the load set at 70% of 1 repetition maximum for 3 sets (10 reps/set). Lunges were performed with a load of 30% of body mass for 3 sets (20 reps/set). Time of each set, lactate, and ratings of perceived exertion were assessed mid-way through exercise and immediately after the exercise. Creatine kinase, muscle soreness visual analog scale ratings, countermovement jump, and heart rate variability were evaluated before the training and at 30 minutes, 6, and 24 hours of recovery. Lunges were performed faster with HRW compared with placebo ( p < 0.001). Hydrogen rich water reduced lactate at mid-way and immediately after the exercise (HRW: 5.3 ± 2.1 and 5.1 ± 2.2, placebo: 6.5 ± 1.8 and 6.3 ± 2.2 mmol·L -1 , p ≤ 0.008). Visual analog scale ratings were significantly lower with HRW (26 ± 11 vs. 41 ± 20 mm, p = 0.002) after 24 hours of recovery. In conclusion, an acute intermittent HRW hydration improved muscle function, reduced the lactate response, and alleviated delayed onset of muscle soreness.

Efficacy of levetiracetam on upper limb movement in multiple sclerosis patients with cerebellar signs: a multicenter double-blind, placebo-controlled, crossover study.

The literature provides contrasting results on the efficacy of levetiracetam (LEV) in multiple sclerosis (MS) patients with cerebellar signs. It was sought to evaluate the efficacy of LEV on upper limb movement in MS patients. In this multicenter double-blind placebo-controlled crossover study, MS patients with prevalently cerebellar signs were randomly allocated into two groups: LEV followed by placebo (group 1) or placebo followed by LEV (group 2). Clinical assessments were performed by a blinded physician at T0 (day 1), T1 (day 22), T2 (2-week wash-out period, day 35) and T3 (day 56). The primary outcome was dexterity in the arm with greater deficit, assessed by the nine-hole peg test (9HPT). Secondary clinical outcomes included responders on the 9HPT (∆9HPT >20%), tremor activity of the daily living questionnaire and self-defined upper limb impairment, through a numeric rating scale. Kinematic evaluation was performed using a digitizing tablet, providing data on normalized jerk, aiming error and centripetal acceleration. Forty-eight subjects (45.2±10.4years) were randomly allocated into two groups (n=24 each). 9HPT significantly improved in the LEV phase in both groups (P<0.001). The LEV treatment phase led to a significant improvement (P<0.01) of all clinical outcomes in group 1 and in dexterity in group 2. No significant changes were reported during both placebo phases in the two groups. Considering the kinematic analysis, only normalized jerk significantly improved after treatment with LEV (T0-T1) in group 1. Levetiracetam treatment seems to be effective in improving upper limb dexterity in MS patients with cerebellar signs.

Effect of the proton-pumpInhibitor pantoprazole on MycoPhenolic ACid exposure in kidney and liver transplant recipienTs (IMPACT study): a randomized trial.

Mycophenolic acid (MPA) is widely utilized as an immunosuppressant in kidney and liver transplantation, with reports suggesting an independent relationship between MPA concentrations and adverse allograft outcome. Proton-pump inhibitors (PPIs) may have variable effects on the absorption of different MPA formulations leading to differences in MPA exposure. A multicentre, randomized, prospective, double-blind placebo-controlled cross-over study was conducted to determine the effect of the PPI pantoprazole on the MPA and its metabolite MPA-glucuronide (MPA-G) area under the curve (AUC) >12 h (MPA-AUC12 h) in recipients maintained on mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS). We planned a priori to examine separately recipients maintained on MMF and EC-MPS for each pharmacokinetic parameter. The trial (and protocol) was registered with the Australian New Zealand Clinical Trials Registry on 24 March 2011, with the registration number of ACTRN12611000316909 ('IMPACT' study). Of the 45 recipients screened, 40 (19 MMF and 21 EC-MPS) were randomized. The mean (standard deviation) recipient age was 58 (11) years with a median (interquartile range) time post-transplant of 43 (20-132) months. For recipients on MMF, there was a significant reduction in the MPA-AUC12 h [geometric mean (95% confidence interval) placebo: 53.9 (44.0-65.9) mg*h/L versus pantoprazole: 43.8 (35.6-53.4) mg*h/L; P = 0.004] when pantoprazole was co-administered compared with placebo. In contrast, co-administration with pantoprazole significantly increased MPA-AUC12 h [placebo: 36.1 (26.5-49.2)mg*h/L versus pantoprazole: 45.9 (35.5-59.3)mg*h/L; P = 0.023] in those receiving EC-MPS. Pantoprazole had no effect on the pharmacokinetic profiles of MPA-G for either group. The co-administration of pantoprazole substantially reduced the bioavailability of MPA in patients maintained on MMF and had the opposite effect in patients maintained on EC-MPS, and therefore, clinicians should be cognizant of this drug interaction when prescribing the different MPA formulations.

Caffeine as a Tool to Explore Active Cognitive Processing Stages in Two-Choice Tasks.

Background: We used caffeine as a tool to explore the active cognitive-processing stages in a simple Go/NoGo task, in terms of the event-related potential (ERP) components elicited by the Go and NoGo stimuli.Methods: Two hundred and fifty milligrams of caffeine was administered to adult participants (N = 24) in a randomized double-blind placebo-controlled repeated-measures crossover study. Two blocks of an equiprobable auditory Go/NoGo task were completed, each with a random mix of 75 tones at 1000 Hz and 75 at 1500 Hz, all 60 dB sound pressure level (SPL).Results: Major ERP effects of caffeine were apparent in enhancements of the Go N1-1, P3b, and Slow Wave (SW), and the NoGo Processing Negativity, SW, and NoGo Late Positivity.Conclusions: Novel differential findings indicate the potential of our caffeine as a tool approach to elucidate the functional nature of ERP markers of active cognitive processing in a range of developmental and clinical populations.

Glutamatergic and GABAergic reactivity and cognition in 22q11.2 deletion syndrome and healthy volunteers: A randomized double-blind 7-Tesla pharmacological MRS study.

Aims:22q11.2 deletion syndrome (22q11.2DS) is associated with impaired cognitive functioning. Glutamatergic pathways have been linked with cognition and are hypothesized to be disrupted in 22q11.2DS patients, possibly ‘shifting’ the excitatory (glutamate)/inhibitory (GABA) balance. Hence, the glutamate/GABA balance may constitute a target for pharmacological treatment. We aimed to examine alterations of glutamate/GABA metabolites in 22q11.2DS in vivo using riluzole, a compound with glutamate/GABA-modulating action, as pharmacological challenge.Methods:Seventeen 22q11.2DS patients and 20 matched healthy controls were enrolled in this randomized double-blind placebo-controlled crossover study. Glutamate and glutamine concentrations in the anterior cingulate cortex (ACC) and striatum, as well as ACC GABA concentrations were obtained after placebo and after a single dose of 50 mg riluzole using 7-Tesla magnetic resonance spectroscopy (MRS). Within the 22q11.2DS group, the relationship between metabolite concentrations and cognition was examined.Results:No group differences were found in ACC and striatal metabolite concentrations following placebo. Riluzole numerically decreased ACC (η2 = 0.094) but not striatal glutamate concentrations as well as ACC GABA concentrations (η2 = 0.176) in all subjects. In both regions, riluzole did not alter glutamine concentration. No interaction effects were found. Although not significant after Bonferroni correction, ACC glutamate concentrations were inversely correlated with cognitive functions in 22q11.2DS patients.Discussion:We did not demonstrate altered ACC and striatal metabolite concentrations in 22q11.2DS. Nevertheless, these results suggest that glutamate and GABA can be modulated with a single dose of riluzole. Possibly, riluzole may have memory-enhancing effects in 22q11.2DS. Future studies should examine the long-term effects of riluzole on cognition.

The interactive effects of test-retest and methylphenidate administration on cognitive performance in youth with ADHD: A double-blind placebo-controlled crossover study

Studies have shown that Methylphenidate (MPH) affects cognitive performance on the neuropsychological tests and clinical symptoms of individuals diagnosed with attention deficit/hyperactivity disorder (ADHD). This study investigated the acute effects of MPH on neuropsychological tests to explore the interaction between MPH and test-retest effects. Twenty youths with ADHD were tested before and after MPH intake in a double-blind placebo-controlled crossover design and compared to twenty matched controls. Participants were tested on a range of standardized tasks including sustained attention to response, N-Back, and Word/Color Stroop. Identical tasks were administered twice each testing day, before and 1 hour after MPH/Placebo administration. Healthy controls were tested similarly with no intervention. Decreases in response time (RT) variability across tasks and in commission errors were found in ADHD after MPH. Conversely, a significant increase in RT variability and increase in omission errors were observed after the placebo. In the control group, RT variability and omission errors increased whereas commission errors decreased, suggesting fatigue and practice effects, respectively. Test-retest reliability was higher in controls than ADHD. It is suggested that cognitive tests are sensitive objective measures for the assessment of responses to MPH in ADHD but are also affected by repetition and fatigue.

Efficacy and safety of 5-Hydroxytryptophan on levodopa-induced motor complications in Parkinson's disease: A preliminary finding

Background and purposeSeveral studies have indicated that altered serotonergic neurotransmission may contribute to the motor features commonly associated with Parkinson's disease (PD) drug treatment such as levodopa-induced dyskinesias (LIDs). 5-Hydroxytryptophan (5-HTP) is the immediate precursor of serotonin. We have recently demonstrated that 5-HTP produces significant antidyskinetic effects in a rat model of PD. To date, there has been inconsistent research on the use of 5-HTP in PD. The purpose of this study was to compare the effects of 5-HTP versus placebo on levodopa-induced motor complications in PD patients. Material and methodsA single-center, randomized, double-blind placebo-controlled cross-over study was performed. A total of 12 PD patients were diagnosed with LIDs and motor fluctuactions and subsequently were randomized to intervention; 11 subjects completed the entire 16-week protocol. Patients received placebo or 50 mg of 5-HTP daily in a cross-over design over a period of 4 weeks. For the assessment of efficacy on the motor functions and motor complications, the UPDRS (parts III and IV), Unified Dyskinesia Rating Scale (UDysRS), Wearing-Off Questionnaire (WOQ-19) and the self-reported 24-h home dyskinesia diaries were obtained at baseline and weeks 4, 8, 12 and 16 (T-end). ResultsRepeated measures analysis revealed a significant improvement of LIDs during the 50 mg 5-HTP treatment as assessed by the UDysRS and UPDRS-IV scores. ConclusionsThis study provides preliminary evidence of clinical benefit of 5-HTP against LIDs in PD. Larger studies with a longer treatment duration and a wider range of doses are warranted to corroborate these findings.

Dopamine and Risky Decision-Making in Gambling Disorder.

Gambling disorder is a behavioral addiction associated with impairments in value-based decision-making and cognitive control. These functions are thought to be regulated by dopamine within fronto-striatal circuits, but the role of altered dopamine neurotransmission in the etiology of gambling disorder remains controversial. Preliminary evidence suggests that increasing frontal dopamine tone might improve cognitive functioning in gambling disorder. We therefore examined whether increasing frontal dopamine tone via a single dose of the catechol-O-methyltransferase (COMT) inhibitor tolcapone would reduce risky choice in human gamblers (n = 14) in a randomized double-blind placebo-controlled crossover study. Data were analyzed using hierarchical Bayesian parameter estimation and a combined risky choice drift diffusion model (DDM). Model comparison revealed a nonlinear mapping from value differences to trial-wise drift rates, confirming recent findings. An increase in risk-taking under tolcapone versus placebo was about five times more likely, given the data, than a decrease [Bayes factor (BF) = 0.2]. Examination of drug effects on diffusion model parameters revealed that an increase in the value dependency of the drift rate under tolcapone was about thirteen times more likely than a decrease (BF = 0.073). In contrast, a reduction in the maximum drift rate under tolcapone was about seven times more likely than an increase (BF = 7.51). Results add to previous work on COMT inhibitors in behavioral addictions and to mounting evidence for the applicability of diffusion models in value-based decision-making. Future work should focus on individual genetic, clinical and cognitive factors that might account for heterogeneity in the effects of COMT inhibition.

Influence of energy drinks on acute hemodynamic parameters in young healthy adults: a randomized double-blind placebo-controlled crossover pilot study

Influence of energy drinks on acute hemodynamic parameters in young healthy adults: a randomized double-blind placebo-controlled crossover pilot study

Phase II double-blind randomised controlled trial of exogenous administration of melatonin in chronic pain (DREAM—CP): a study protocol

IntroductionChronic pain is prevalent, and approximately half of patients with chronic pain experience sleep disturbance. Exogenous melatonin is licensed to treat primary insomnia and there is some evidence for analgesic...

The Hemodynamic Effects of CGRP After Glibenclamide Administration in a Randomized Double-blind Cross-over Placebo-controlled Study With Healthy Volunteers

The Hemodynamic Effects of CGRP After Glibenclamide Administration in a Randomized Double-blind Cross-over Placebo-controlled Study With Healthy Volunteers

Effects of corn syrup solids containing maltobionic acid (maltobionic acid calcium salt) on bone resorption in healthy Japanese adult women: A randomized double-blind placebo-controlled crossover study.

Maltobionic acid is known to have an inhibitory effect on the differentiation of osteoclasts, and it has also been reported in an intervention trial that ingestion of corn syrup solids containing maltobionic acid maintained and increased the bone density of postmenopausal women. However, there is no information on whether maltobionic acid improves bone metabolism in humans. Therefore, we evaluated the influence of corn syrup solids containing maltobionic acid (maltobionic acid calcium salt) on bone resorption markers in healthy Japanese women. Forty‐one individuals were selected from 68 participants and assigned to two groups: 21 individuals in the test food antecedent group and 20 individuals in the placebo food antecedent group; individuals in the first group ingested 4 g of corn syrup solids containing maltobionic acid, and subjects in the second group ingested 4 g of placebo (hydrous crystalline maltose and calcium carbonate) for 4 weeks. Bone resorption marker levels (DPD and u‐NTx) were evaluated by urinalysis. Forty subjects completed the study, and no adverse events related to the test food were observed. Fourteen subjects were excluded prior to the efficacy analysis because of conflict with the control criteria; the remaining 33 subjects were analyzed. Consumption of corn syrup solids containing maltobionic acid was maintained; DPD and u‐NTx values were improved (p < .05). These results indicate that corn syrup solids containing maltobionic acid might contribute to suppress bone resorption and improve bone metabolism in postmenstrual women. (UMIN‐CTR ID: UMIN000034257; Foundation: San‐ei Sucrochemical Co., Ltd.).

Role of Potassium-Sparing Diuretics in the Management of Hypokalemia in Peritoneal Dialysis.

Patients with kidney disease are at a higher risk of experiencing potassium imbalance. The kidney plays an important role in maintaining potassium homeostasis. A common dyskalemia that peritoneal dialysis (PD) patients experience is hypokalemia. Potassium-sparing diuretics such as spironolactone causes increased amounts of sodium and water to be excreted, while potassium is retained. Owing to its potassium-sparing effects, it may correct hypokalemia that PD patients experience. The proper usage of potassium-sparing diuretics in PD patients and data on the efficacy and safety are being explored. Four relevant trials were identified. One randomized double-blind placebo-controlled cross-over study (n = 20), one interventional study without the control group (n = 20), one retrospective single-center chart review (n = 53), and one cross-sectional review (n = 75) trial. The randomized controlled trial did not note a statistically significant change in K levels (P > 0.05); the other 3 trials observed an increase in potassium levels in the potassium-sparing diuretics groups, but trials contained small participants and inadequate statistic rigor. The role of potassium-sparing diuretics use for hypokalemia management in PD patients remains unclear.

Accurate Detection of Dobutamine-induced Haemodynamic Changes by Kino-Cardiography: A Randomised Double-Blind Placebo-Controlled Validation Study

Non-invasive remote detection of cardiac and blood displacements is an important topic in cardiac telemedicine. Here we propose kino-cardiography (KCG), a non-invasive technique based on measurement of body vibrations produced by myocardial contraction and blood flow through the cardiac chambers and major vessels. KCG is based on ballistocardiography and measures 12 degrees-of-freedom (DOF) of body motion. We tested the hypothesis that KCG reliably assesses dobutamine-induced haemodynamic changes in healthy subjects. Using a randomized double-blinded placebo-controlled crossover study design, dobutamine and placebo were infused to 34 volunteers (25 ± 2 years, BMI 22 ± 2 kg/m², 18 females). Baseline recordings were followed by 3 sessions of increasing doses of dobutamine (5, 10, 20 μg/kg.min) or saline solution. During each session, stroke volume (SV) and cardiac output (CO) were determined by echocardiography and followed by a 90 s KCG recording. Measured linear accelerations and angular velocities were used to compute total Kinetic energy (iK) and power (Pmax). KCG sorted dobutamine infusion vs. placebo with 96.9% accuracy. Increases in SV and CO were correlated to iK (r = +0.71 and r = +0.8, respectively, p < 0.0001). Kino-cardiography, with 12-DOF, allows detecting dobutamine-induced haemodynamic changes with a high accuracy and present a major improvement over single axis ballistocardiography or seismocardiography.