Swallowability of Minitablets among Children Aged 6–23 Months: An Exploratory, Randomized Crossover Study

Minitablets have garnered interest as a new paediatric formulation that is easier to swallow than liquid formulations. In Japan, besides the latter, fine granules are frequently used for children. We examined the swallowability of multiple drug-free minitablets and compared it with that of fine granules and liquid formulations in 40 children of two age groups (n = 20 each, aged 6–11 and 12–23 months). We compared the percentage of children who could swallow minitablets without chewing with that of children who could swallow fine granules or liquid formulations without leftover. The children who visited the paediatric department of Showa University Hospital were enrolled. Their caregivers were allowed to choose the administration method. In total, 37 out of 40 caregivers dispersed the fine granules in water. Significantly more children (80%, 95% CI: 56–94%) aged 6–11 months could swallow the minitablets than those who could swallow all the dispersed fine granules and liquid formulations (22%, 95% CI: 6–47% and 35%, 95% CI: 15–59%, respectively). No significant differences were observed in children aged 12–23 months. Hence, minitablets may be easier to swallow than dispersed fine granules and liquid formulations in children aged 6–11 months.

Comparison between 20 and 30 meters in walkway length affecting the 6-minute walk test in patients with chronic obstructive pulmonary disease: A randomized crossover study

Background A 30-m walkway length for the 6-minute walk test (6MWT) is the standard recommendation established by the American Thoracic Society to assess patients with chronic obstructive pulmonary disease (COPD). This study aimed to compare between the distances of 20 and 30 m long corridor affecting 6MWT in COPD patients. Methods A randomized crossover study was conducted with patients. COPD patients were randomized 1:1 to either a 20-m or a 30-m walkway in the first test, then switched to the other in the second test. Physiologic parameters and 6-minute walking distance (6MWD) were recorded. Results Fifty subjects (92% men) were included: age 69.1±7.4 years, body mass index 22.9±5.5 kg/m2, FEV1 63.0±21.3%, and 50% having cardiovascular disease. The 6MWD in a 20-m and a 30-m walkway were 337.82±71.80 m and 359.85±77.25 m, respectively (P<0.001). Mean distance difference was 22.03 m (95% CI -28.29 to -15.76, P<0.001). Patients with a 20-m walkway had more turns than those with a 30-m walkway (mean difference of 4.88 turns, 95% CI 4.48 to 5.28, P<0.001). Also, higher systolic blood pressure was found in patients with a 20-m walkway after 6MWT (4.62 mmHg, P = 0.019). Other parameters and Borg dyspnea scale did not differ. Conclusions The walkway length had significant effect on walking distance in COPD patients. A 30-m walkway length should still be recommended in 6MWT for COPD assessment. Clinical trial registration Clinicaltrials.in.th number: TCTR20200206003.

Orange Juice Attenuates Circulating miR-150-5p, miR-25-3p, and miR-451a in Healthy Smokers: A Randomized Crossover Study

Introduction: Tobacco smoke is associated with oxidative and inflammatory pathways, increasing the risk of chronic-degenerative diseases. Our goal was to evaluate the effects of acute “Pera” and “Moro” orange juice consumption on inflammatory processes and oxidative stress in microRNA (miRNA) expression in plasma from healthy smokers.Methods: This was a randomized crossover study that included healthy smokers over 18 years old. Blood samples were collected before and 11 h after beverage ingestion. Participants were instructed to drink 400 mL of Pera orange juice (Citrus sinensis), Moro orange juice (Citrus sinensis L. Osbeck), or water. Each subject drank the beverages in a 3-way crossover study design. Inflammatory and oxidative stress biomarkers and circulating miRNA expression profiles were determined. The subjects maintained their usual tobacco exposure during the experiment.Results: We included 18 individuals (12 men and 6 women), with 37.0 ± 12.0 years old. All subjects received the 3 interventions. Increased expression of circulating miRNAs (miR-150-5p, miR-25-3p, and miR-451a) was verified after cigarette smoking, which were attenuated after intake of both types of orange juice. There was no difference regarding serum levels of TNF-α, IL-6, MMP-9, and C-reactive protein. Despite the increased activity of serum superoxide dismutase and glutathione peroxidase after “Pera” or “Moro” orange juice intake, respectively, no changes in lipid hydroperoxide levels were detected.Conclusion: Tobaccos smokers showed increased expression of miR-150-5p, miR-25-3p, and miR-451a was noted, and attenuated by orange juice intake. miRNAs were predicted to regulate 244 target genes with roles in oxidative stress, PI3K-Akt, and MAPK signaling, which are pathways frequently involved in smoking-related cardiovascular diseases and cancer.

The Effect of Rice vs. Wheat Ingestion on Postprandial Gastroesophageal Reflux (GER) Symptoms in Patients with Overlapping GERD-Irritable Bowel Syndrome (IBS)

A randomized crossover study in twenty-one patients (18F, age 50 ± 13 years) with overlapping GERD-IBS was conducted to evaluate the effects of rice noodles (low FODMAPs) vs. wheat noodles (high FODMAPs) on typical GER symptoms, and the correlation between GERD symptoms and intestinal gas production. Results: Heartburn and regurgitation scores were highest in most patients (19/21) during the first 15 min after meals. At 15 min after lunch, wheat was significantly associated with more regurgitation and heartburn than rice. Also, at 15 min after breakfast, wheat aggravated more regurgitation than rice. Wheat ingestion was significantly associated with higher H2 and CH4 levels after lunch compared to rice, whereas gas levels before lunch were similar (p > 0.05). The area under the curve of H2 and CH4 concentration 15 min after a lunch of wheat moderately correlated with the regurgitation severity at 15-min (r = 0.56, p < 0.05). Conclusion: Wheat induced more GERD symptoms than rice in patients with overlapping GERD-IBS. This effect, immediately developed after lunch, was associated with more intestinal gas production. Thus, a low FODMAPs diet may relieve postprandial GERD symptoms in GERD patients with overlapping IBS. Wheat inducing more regurgitation than rice after breakfast suggests other mechanism(s) besides gut fermentation.

Atogepant and sumatriptan: no clinically relevant drug–drug interactions in a randomized, open-label, crossover trial

Aim: To evaluate pharmacokinetic interactions of atogepant with sumatriptan, an open-label, randomized, crossover study was conducted. Patients & methods: Thirty healthy adults received atogepant 60 mg, sumatriptan 100 mg, or coadministered drugs. Primary end point was geometric mean ratios (GMRs) and 90% CIs of interventions for area under the plasma concentration–time curve from time 0 to t (AUC0-t) or infinity (AUC0-∞) and peak plasma concentration (Cmax). Results: Atogepant GMRs for AUC0-t and AUC0-∞ versus with sumatriptan were within 90% CI 0.80–1.25, indicating no interaction; atogepant Cmax was reduced by 22% (GMR: 0.78; 90% CI: 0.69–0.89) with sumatriptan. Sumatriptan GMRs for AUC0-t, AUC0-∞ and Cmax versus with atogepant were within 90% CI 0.80–1.25. Conclusion: Atogepant with sumatriptan had no clinically relevant pharmacokinetic interactions.

Preliminary Evidence That Lectins in Infant Soy Formula Apparently Bind Bovine Milk Exosomes and Prevent Their Absorption in Healthy Adults

Background: Milk exosomes and their microRNA (miR) cargos are bioavailable. The content of exosomes and miRs is negligible in infant formulas compared to human milk, and dietary depletion of exosomes led to changes in bacterial communities and impaired gut health in juvenile mice. Adverse effects of formula feeding may be compounded by using soy formulas due to exosome binding by abundant lectins in that matrix. The purpose of this study was to assess the bioavailability of milk exosomes and their miR cargos added to soy formula in adults, as well as the potential role of soy lectins in exosome bioavailability.Methods: Eleven healthy adults (6 men, 5 women) enrolled in this randomized crossover study. Participants consumed 1.0 liter of soy formula without (SF) or with (SFE) bovine milk exosomes added. Concentration-time curves of six plasma miRs were analyzed using reverse transcription quantitative PCR. Lectin affinity chromatography was used to assess the binding of exosomes by soy lectins. Data were analyzed by using paired t test. P < 0.05 was considered statistically significant.Results: Consumption of SF and SFE did not elicit postprandial increases in plasma miRs. Approximately 39% of bovine milk exosome particles were retained by lectin columns.Conclusions: We conclude that fortification of soy formulas with milk exosomes, in the absence of removing lectins, is not a viable strategy for delivering bioavailable exosomes and their miR cargos. Lectins in soy formulas bind glycoprotein on the surfaces of milk exosomes, thereby preventing exosome absorption.Trial RegistrationISRCTN registry ID: 16329971. Retrospectively registered on February 7th, 2019.

Chewing increases postprandial diet-induced thermogenesis

Slow eating, which involves chewing food slowly and thoroughly, is an effective strategy for controlling appetite in order to avoid being overweight or obese. Slow eating also has the effect of increasing postprandial energy expenditure (diet-induced thermogenesis). It is still unclear whether this is due to oral stimuli; that is, the duration of tasting food in the mouth and the duration of chewing. To investigate the effects of oral stimuli on diet-induced thermogenesis in 11 healthy normal weight males, we conducted a randomized crossover study comprising three trials: (1) drinking liquid food normally, (2) drinking liquid food after tasting, and (3) adding chewing while tasting. Oral stimuli (i.e., the duration of tasting liquid food in the mouth and the duration of chewing) significantly increased diet-induced thermogenesis after drinking liquid food. This result demonstrates that the increase in diet-induced thermogenesis is due to oral stimuli rather than the influence of the food bolus. Increased diet-induced thermogenesis induced by chewing and taste stimuli may help to prevent overweight and obesity.