Randomized Crossover Trial Research Articles

Personalized positive end-expiratory pressure in spontaneously breathing patients with acute respiratory distress syndrome by simultaneous electrical impedance tomography and transpulmonary pressure monitoring: a randomized crossover trial.

Personalized positive end-expiratory pressure (PEEP) might foster lung and diaphragm protection in patients with acute respiratory distress syndrome (ARDS) who are undergoing pressure support ventilation (PSV). We aimed to compare the physiologic effects of personalized PEEP set according to synchronized electrical impedance tomography (EIT) and driving transpulmonary pressure (∆PL) monitoring against a classical lower PEEP/FiO2 table in intubated ARDS patients undergoing PSV. A cross-over randomized multicenter study was conducted in 30 ARDS patients with simultaneous recording of the airway, esophageal and transpulmonary pressure, together with EIT during PSV. Following a decremental PEEP trial (18 cmH2O to 4 cmH2O), PEEPEIT-∆PL was identified as the level with the smallest difference between lung overdistension and collapse. A low PEEP/FiO2 table was used to select PEEPTABLE. Each PEEP strategy was applied for 20min, and physiologic data were collected at the end of each step. The PEEP trial was well tolerated. Median PEEPEIT-∆PL was higher than PEEPTABLE (10 [8-12] vs. 8 [5-10] cmH2O; P = 0.021) and, at the individual patient level, PEEPEIT-∆PL level differed from PEEPTABLE in all patients. Overall, PEEPEIT-∆PL was associated with lower dynamic ∆PL (P < 0.001) and pressure-time product (P < 0.001), but there was variability among patients. PEEPEIT-∆PL also decreased respiratory drive and effort (P < 0.001), improved regional lung mechanics (P < 0.05) and reversed lung collapse (P = 0.007) without increasing overdistension (P = 0.695). Personalized PEEP selected using synchronized EIT and transpulmonary pressure monitoring could be associated with reduced dynamic lung stress and metabolic work of breathing in ARDS patients undergoing PSV.

Light Walking Patterns and Postprandial Cardiometabolic Responses in Young Obese Adults: A Randomized Crossover Study.

Recent studies suggest that light-intensity physical activity may enhance cardiometabolic health and reduce mortality risk in adults. However, more information is required to understand the patterns of light-intensity physical activity and postprandial cardiometabolic health. This study examined the effects of different light-intensity walking patterns on postprandial cardiometabolic responses in young obese adults. A randomized crossover trial was conducted. The study was conducted in the laboratory. The study analyzed baseline (fasting) and 6-hour postprandial concentrations of glucose, insulin, triglycerides, and blood pressure (BP) in 16 young obese adults. Participants underwent four 7-hour experimental conditions with a 7-20-day washout period: uninterrupted sitting (SIT), 30-minute light-intensity walking (EX+SIT), 3-minute light-intensity walking every 30 minutes (BR), and 30-minute light-intensity walking with 3-minute light-intensity walking every 30 minutes (EX+BR). Incremental areas under the curve (iAUC) for each outcome and average BP were compared between SIT and walking conditions. Compared with SIT, all walking conditions reduced iAUCs for glucose and average diastolic BP (all p<0.05). Only EX+SIT and EX+BR reduced iAUCs for insulin (p<0.05). No significant differences were found for triglycerides iAUC and systolic BP between the four conditions (all p>0.05). All patterns of light-intensity walking reduced postprandial glucose concentrations and diastolic BP in young obese adults, suggesting benefits for glycemic control. Continuous 30-minute light-intensity walking alone, or combined with brief 3-min bouts also attenuated postprandial insulin concentrations, highlighting light-intensity walking as a promising strategy for improving cardiometabolic health in young obese adults.

Impact of limb occlusion pressure assessment position on performance, cardiovascular, and perceptual responses in blood flow restricted low-load resistance exercise: A randomized crossover trial

ABSTRACT This study investigated the effect of limb occlusion pressure (LOP) position on exercise performance, cardiovascular responses, and perceptual experiences during seated bilateral leg extensions with and without blood flow restriction (BFR). Thirty resistance-trained males (age: 22 ± 2 years; weight: 74.4 ± 13.6 kg; height: 177.4 ± 6.4 cm; BMI: 23.5 ± 3.3 kg/m2) participated. Each performed exercise to failure (4 sets, 30% 1RM, 1 min rest) in three conditions: Supine LOP-BFR, Seated LOP-BFR, and no-BFR. BFR was applied at 60% LOP. Significant interaction effects were found for RPE (p = 0.021, d = 0.76), RPD (p < 0.01, d = 1.72), and DOMS (p < 0.01, d = 2.28). Statistically significant fewer repetitions were completed in Supine LOP-BFR vs. no-BFR (p < 0.01, d = 0.5), Seated LOP-BFR vs. no-BFR (p < 0.01, d = 1.0), and Seated LOP-BFR vs. Supine LOP-BFR (p < 0.01, d = 0.6). RPE was higher in Seated LOP-BFR vs. no-BFR (p < 0.01, d = 0.52). RPD was higher in Supine LOP-BFR vs. no-BFR (p < 0.01, d = 0.62) and Seated LOP-BFR vs. no-BFR (p < 0.01, d = 1.25). DOMS was higher in Supine LOP-BFR vs. no-BFR (p < 0.01, d = 0.77) and Seated LOP-BFR vs. no-BFR (p < 0.01, d = 3.52). Seated LOP-BFR increased perceptual demands and reduced repetitions compared to Supine LOP-BFR. Both LOP-BFR conditions reduced repetitions compared to no-BFR without affecting cardiovascular measures.

The impact of prolonged walking on fasting plasma glucose in type 2 diabetes: A randomised controlled crossover study.

In many low-income countries, fasting glucose is the primary measure for monitoring glycaemic control. Many patients in these countries walk long distances to the clinic, but the impact of walking on fasting glucose in type 2 diabetes is unknown. We aimed to determine the impact of walking on fasting glucose in people with type 2 diabetes. In a randomised crossover trial, the change in glucose from baseline in the fasting state was compared between walking on a treadmill at a predetermined speed of 4.5 km/h for 1 h and not walking (resting) in people with type 2 diabetes. In all, 45 participants were enrolled and all completed both visits; 21/45 (46.7%) were women, and the median age was 51. Glucose during and after walking was similar to glucose while at rest; the glucose difference (walking minus rest) was -0.15 (95% CI: -0.55, 0.26) and -0.10 (95% CI: -0.50, 0.31) mmol/L at 1 and 2 h, respectively, p > 0.4 for both. Fasting plasma glucose is not meaningfully affected by prolonged walking in participants with type 2 diabetes; therefore, the reliability of fasting glucose for monitoring glycaemic burden is unlikely to be altered in patients who walk to the clinic.

Effect of Interrupting Prolonged Sitting with Frequent Activity Breaks on Postprandial Glycemia and Insulin Sensitivity in Adults with Type 1 Diabetes on Continuous Subcutaneous Insulin Infusion Therapy: A Randomized Crossover Pilot Trial.

Objective: This study examined acute effects of interrupting prolonged sitting with short activity breaks on postprandial glucose/insulin responses and estimations of insulin sensitivity in adults with type 1 diabetes (T1D). Method: In a randomized crossover trial, eight adults (age = 46 ± 14 years [mean ± SD], body mass index [BMI] = 27.2 ± 3.8 kg/m2) receiving continuous subcutaneous insulin infusion (CSII) therapy completed two 6-h conditions as follows: uninterrupted sitting (SIT) and sitting interrupted with 3-min bouts of simple resistance activities (SRAs) every 30 min. Basal and bolus insulin were standardized across conditions except in cases of hypoglycemia. Postprandial responses were assessed using incremental area-under-the-curve (iAUC) and total AUC (tAUC) from half-hourly venous sampling. Meal-based insulin sensitivity determined from glucose sensor and insulin pump (SiSP) was assessed from flash continuous glucose monitor and insulin pump data. Outcomes were analyzed using mixed models adjusted for sex, BMI, treatment order, and preprandial values. Results: Glucose iAUC did not differ by condition (SIT: 19.8 ± 3.0 [estimated marginal means ± standard error] vs. SRA: 14.4 ± 3.0 mmol.6 h.L-1; P = 0.086). Despite CSII being standardized between conditions, insulin iAUC was higher in SRA compared to SIT (137.1 ± 22.7 vs. 170.9 ± 22.7 mU.6 h.L-1; P < 0.001). This resulted in a lower glucose response relative to the change in plasma insulin in SRA (tAUCglu/tAUCins: 0.32 ± 0.02 vs. 0.40 ± 0.02 mmol.mU-1; P = 0.03). SiSP was also higher at dinner following the SRA condition, with no between-condition differences at breakfast or lunch. Conclusion: Regularly interrupting prolonged sitting in T1D may increase plasma insulin and improve insulin sensitivity when meals and CSII are standardized. Future studies should explore underlying mechanistic determinants and the applicability of findings to those on multiple daily injections. Trial Registration: Australian and New Zealand Clinical Trial Registry Identifier-ACTRN12618000126213 (www.anzctr.org.au).

Acute exercise boosts NAD+ metabolism of human peripheral blood mononuclear cells

Nicotinamide adenine dinucleotide (NAD+) coenzymes are the central electron carriers in biological energy metabolism. Low NAD+ levels are proposed as a hallmark of ageing and several diseases, which has given rise to therapeutic strategies that aim to tackle these conditions by boosting NAD+ levels. As a lifestyle factor with preventive and therapeutic effects, exercise increases NAD+ levels across various tissues, but so far human trials are mostly focused on skeletal muscle. Given that immune cells are mobilized and redistributed in response to acute exercise, we conducted two complementary trials to test the hypothesis that a single exercise session alters NAD+ metabolism of peripheral blood mononuclear cells (PBMCs). In a randomized crossover trial (DRKS00017686) with 24 young adults (12 female) we show that acute exercise increases gene expression and protein abundance of several key NAD+ metabolism enzymes with high conformity between high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT). In a longitudinal exercise trial (DRKS00029105) with 12 young adults (6 female) we confirm these results and reveal that – similar to skeletal muscle – NAD+ salvage is pivotal for PBMCs in response to exercise. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of NAD+ salvage pathway, displayed a pronounced increase in gene expression during exercise, which was accompanied by elevated intracellular NAD+ levels and reduced serum levels of the NAD+ precursor nicotinamide. These results demonstrate that acute exercise triggers NAD+ biosynthesis of human PBMCs with potential implications for immunometabolism, immune effector function, and immunological exercise adaptions.

Basal insulin analogues in type 1 diabetes – does one size fit all? Lessons from the HypoDeg trial based on single-patient outcomes

AimsIn the HypoDeg trial, a randomised crossover trial in people with type 1 diabetes prone to nocturnal severe hypoglycaemia, treatment with insulin degludec (IDeg) resulted in significantly reduced rates of nocturnal symptomatic hypoglycaemia and all-day severe hypoglycaemia compared to insulin glargine U100 (IGlar). We analysed HypoDeg data at a single-patient level to assess the proportion of participants to whom the overall result applied. MethodsPost hoc analysis using single-patient data (n=133) on nocturnal symptomatic hypoglycaemia, all-day severe hypoglycaemia and HbA1c. The outcome was classified as superior with IDeg, superior with IGlar, or similar between treatments for the three outcomes. We also assessed a composite endpoint based on these outcomes to evaluate the overall superior treatment for each participant. ResultsA higher percentage (38%) had IDeg as superior treatment compared to IGlar (15%) for nocturnal symptomatic hypoglycaemia (p < 0.001). There was no difference between the treatments for all-day severe hypoglycaemia or HbA1c. A higher percentage (44%) had a composite endpoint favouring IDeg compared to IGlar (16%) (p < 0.001). ConclusionsThe superiority of IDeg was confirmed in many of the participants. However, a minority had IGlar as superior treatment, underscoring the need for individualised basal insulin therapy in clinical practice.

The effects of casein glycomacropeptide on general health status in children with PKU: A randomized crossover trial

In PKU, it is suggested that casein glycomacropeptide based protein substitute (GMP) may have physiological advantage when satiety, oxidative stress, renal function and inflammation are considered. Its prebiotic properties may also help gastrointestinal (GI) tolerance.In children with PKU, a randomized/crossover trial comparing phenylalanine-free amino acids (AA) vs GMP as the single source of protein substitute for 12-weeks in each arm was conducted. There was a 4-week wash out period with AA in-between. At baseline and end of each intervention, blood and fecal samples were taken to monitor gut health, oxidative stress, renal function, inflammatory markers and plasma amino acids. Satiety and Pediatric Quality of Life (PedsQL) GI symptoms questionnaires were completed. Usual weekly blood spots for phenylalanine and tyrosine were done.Twelve patients (8 males; aged 4-9y) with PKU participated. GMP improved the following GI symptoms: stomach pain (p = 0.003), heartburn and reflux (p = 0.041) and wind/ bloating (p = 0.018). With GMP, there was also a trend for less constipation (p = 0.068), discomfort with eating (p = 0.065) and nausea and vomiting (p = 0.087). There was no changes on stool gut health markers (IgA, short chain fatty acids and fecal calprotectin). There were no statistically significant differences for renal, oxidative stress, inflammatory and gut health markers or measures of satiety except for adiponectin (p = 0.028) and total antioxidant capacity (p = 0.049), although the latter was possibly without clinical significance. Mean dried blood spot Phe was 114 μmol/L higher with GMP vs AA (p < 0.001). There was no difference in tyrosine levels. In conclusion, GI symptoms significantly improved with GMP versus AA. The phenylalanine content of GMP may present challenges when it is used as the only protein substitute in children with classical PKU with low Phe tolerance.

Comparison of a customized glycemic pellets challenge with the oral sugar test to measure glycemic and insulinemic responses in horses.

Testing for insulin dysregulation (ID) in horses is commonly performed to guide management and therapeutic strategies. To evaluate a newly developed glycemic pellets challenge (GPC) and compare results to those obtained using the low-dose oral sugar test (OST). Twenty-four adult horses with unknown insulin status. A randomized crossover trial was performed. Horses underwent GPC (0.5 g glycemic carbohydrates/kg body weight) and OST (0.15 mL corn syrup/kg body weight) 7 days apart. Feed was withheld before testing and blood samples were collected at T0, T60, T120, and T180 minutes for GPC and at T0, T60, and T90 minutes for OST. Blood glucose concentration was measured using a point-of-care glucometer and insulin by radioimmunoassay. Comparisons were made using nonparametric tests, linear regression, and Bland-Altman agreement analysis. Eighteen horses consumed >85% of the GPC pellets within 10 minutes and had acceptable OST results. Maximum glucose (P = .02) and insulin (P = .007) concentrations were significantly higher for GPC compared with OST. Time to maximum insulin concentration (Tmax[ins]) varied within and between tests and neither Tmax[ins] (P = .28) nor maximum insulin concentration (P = .46) was correlated with the time horses took to consume pellets. The GPC is well tolerated and may offer another diagnostic testing modality for ID. Blood glucose and insulin concentrations increase during GPC and reach higher concentrations than observed with low-dose OST. The Tmax[ins] varied for GPC and OST, emphasizing the importance of identifying the optimal time range for the collection of samples to capture diagnostically relevant changes in insulin concentration.

A novel method in myocardial injury risk stratification using intravenous fat emulsion as sole rapid preparation for unfasted patients to suppress myocardial 18F-fluorodeoxyglucose uptake for optimal cardiac PET imaging: a proof-of-concept randomized-crossover trial.

Optimal imaging of ischemic or inflammed myocardium via 18F-FDG PET imaging requires suppression of background carbohydrate metabolism in normal myocardium. Sole administration of intravenous lipid emulsion has not previously been used to rapidly prepare unfasted patients, such as in emergent clinical situations. In this proof-of-concept pilot, we posited that intravenous fat emulsion suppresses physiological metabolic uptake of in non-ischemic, non-inflammatory myocardium in unprepared and unfasted setting for enhanced cardiac positron emission tomography (PET) imaging. We conducted an ethics-approved, single-blind, prospective randomized crossover trial of 10 healthy volunteers from January 2020 to June 2021. Participants were unfasted and rendered hyperglycemic before being administered either high dose intravenous lipid emulsion-1.5 ml kg of 20% lipid emulsion, followed by 15 ml/kg/hr for 30mins-or saline prior to 18F-FDG injection and subsequent cardiac PET imaging. Assessors undertook image analysis for maximum standard uptake value (SUVmax), minimum standard uptake value (SUVmin) and qualitative assessment, and groups were compared using univariate analysis. The study population age was 44.5 years [IQR 32.5-56.5], with 50% male and a median BMI of 22.75 [IQR 25.0-28.5] kg/m2. The study was feasible and there were no adverse side effects from the interventions. In these participants with normal myocardium, 18F-FDG uptake was reduced by intravenous lipid emulsion as assessed by SUVmax and qualitative assessment (p = 0.042, r = 0.454 and p = 0.009, r = -0.581, respectively). Intravenous lipid emulsion suppresses background metabolic uptake of 18F-FDG even in unprepared and unfasted patients. Our findings prove and expand the possible applications for cardiac 18F-FDG PET in various settings, including in emergent settings as a means of rapid preparation in place of current more time-consuming standard protocols, allowing time-critical management to be effected.

Pregabalin for Neuropathic Pain and Itch in Recessive Dystrophic Epidermolysis Bullosa

Patients with recessive dystrophic epidermolysis bullosa (RDEB) experience neuropathic pain and itch. There is a lack of evidence on any treatment for these symptoms in patients with RDEB. To test the efficacy of pregabalin in the treatment of neuropathic pain and itch in patients with RDEB. A randomized, double-blinded, crossover trial of oral pregabalin (50-300 mg/d) vs placebo was conducted at 2 sites, Toronto (Canada) and Santiago (Chile) from January 1, 2019, to December 31, 2020. Patients eligible to participate were diagnosed with RDEB, aged 8 to 40 years, not pregnant or lactating (if female), and had evidence of probable neuropathic pain and itching defined as distal thermal sensory loss (confirmed by thermal roller), score of 4 or greater on the Douleur Neuropathique 4 questionnaire (DN4), and score greater than 4 on the 10-point visual analog scale [VAS]). Patients with a clinically important or poorly controlled medical or psychiatric condition or pregabalin intolerance or allergy were excluded. Of 41 patients screened, 3 were not eligible and 28 declined enrollment. Data analyses were performed in 2021 through 2023. Participants received both pregabalin and matched placebo (titrated to a maximum-tolerated dose of 300 mg/day) in a randomized sequence so that comparisons could be made within participants and between groups. Difference in the mean pain and itch scores between pregabalin and placebo treatment (measured using VAS) before and after intervention. In all, 10 participants were randomized to 2 groups, 6 patients (mean [SD] age, 26.7 [8.1] years; 3 females [50%]) in group 1, and 4 patients (mean [SD] age, 26.5 [7.8] years, 2 females [50%]) in group 2. Group 1 received a sequence of pregabalin-placebo while group 2 received placebo-pregabalin. Pregabalin significantly reduced mean (SD) pain scores by 1.9 (1.5) points when controlling for sequence and treatment period vs baseline, while placebo had 0.1 (2.0) points of reduction. The effect of pregabalin was a mild but significant reduction in itch compared to baseline (mean [SD] points, 0.9 [2.2]), whereas the placebo produced no reduction (0.1 [2.5]). The mean pregabalin dose was generally well tolerated. The results of this randomized crossover trial indicate that pregabalin significantly reduced pain and itch scores from baseline compared to placebo in patients with RDEB. This feasibility study provided preliminary data on the efficacy of pregabalin in managing pain and itch in RDEB and gathered essential data to inform the design of a larger cohort trial. ClinicalTrials.gov Identifier: NCT03928093.

Clinical trial comparing the use of Orcellex® Brush versus Cervex-Brush® on vaginal vault smear cytology adequacy rate in patients treated with radiotherapy for cervical cancer.

This study aims to evaluate and compare the Cervex-Brush® and Orcellex® Brush as sampling devices for vaginal vault smear cytology in cervical cancer patients treated primarily with radiotherapy. A randomized crossover trial was conducted at a gynecological oncology center in Hong Kong to compare the Cervex-Brush® and Orcellex® Brush in terms of their vault smear adequacy rate in cervical cancer patients who underwent radiotherapy. One hundred sixty cervical cancer patients treated with primary radiotherapy and undergoing follow-up surveillance by vaginal vault cytology were recruited. The smear adequacy rate was 90.6% for Cervex-Brush® and 91.9% for Orcellex® Brush. The rates of low cellularity for both brushes were similar (76.8% for Cervex-Brush® vs. 76.1% for Orcellex® Brush). The detection rates of abnormal smears were also not significantly different (2.8% for Cervex-Brush® vs. 4.2% for Orcellex® Brush). The 2 brushes were also not significantly different in terms of pain score and degree of bleeding. It was further observed that the second smear collection was more painful and patients who were on hormonal replacement therapy demonstrated less bleeding. There was no difference between the Orcellex® brush and the Cervex-Brush® in terms of smear adequacy rate, rate of high cellularity and the detection of abnormal smears. There was also no significant difference between the 2 brushes in terms of pain and the degree of bleeding. Therefore, the Orcellex® Brush can be considered a suitable alternative sampling device for vault smear collection in patients who have undergone radiotherapy for cervical cancer. ClinicalTrials.gov Identifier: NCT04461574.

Suppression of the postprandial hyperglycemia in patients with type 2 diabetes by a raw medicinal herb powder is weakened when consumed in ordinary hard gelatin capsules: A randomized crossover clinical trial.

Contradictory claims about the efficacy of several medicinal plants to promote glycemic control in patients with type 2 diabetes mellitus (T2DM) have been explained by divergences in the administration form and by extrapolation of data obtained from healthy individuals. It is not known whether the antidiabetic effects of traditional herbal medicines are influenced by gelatin capsules. This randomized crossover trial aimed to evaluate the acute effect of a single dose of raw cinnamon consumed orally either dissolved in water as a beverage or as ordinary hard gelatin capsules on postprandial hyperglycemia (>140 mg/dL; >7.8 mmol/L) in T2DM patients elicited by a nutritionally-balanced meal providing 50 g of complex carbohydrates. Fasting T2DM patients (n = 19) randomly ingested a standardized meal in five experimental sessions, one alone (Control) and the other after prior intake of 3 or 6 g of crude cinnamon in the form of hard gelatin capsules or powder dissolved in water. Blood glucose was measured at fasting and at 0.25, 0.5, 0.75, 1, 1.5 and 2 hours postprandially. After each breakfast, its palatability scores for visual appeal, smell and pleasantness of taste were assessed, as well as the taste intensity sweetness, saltiness, bitterness, sourness and creaminess. The intake of raw cinnamon dissolved in water, independently of the dose, decreased the meal-induced large glucose spike (peak-rise of +87 mg/dL and Δ1-hour glycemia of +79 mg/dL) and the hyperglycemic blood glucose peak. When cinnamon was taken as capsules, these anti-hyperglycemic effects were lost or significantly diminished. Raw cinnamon intake did not change time-to-peak or the 2-h post-meal glycaemia, but flattened the glycemic curve (lower iAUC) without changing the shape that is typical of T2DM patients. This cinnamon's antihyperglycemic action confirms its acarbose-like property to inhibit the activities of the carbohydrate-digesting enzymes α-amylases/α-glucosidases, which is in accordance with its exceptionally high content of raw insoluble fiber. The efficacy of using raw cinnamon as a diabetes treatment strategy seems to require its intake at a specific time before/concomitantly the main hyperglycemic daily meals. Trial registration: Registro Brasileiro de Ensaios Clínicos (ReBEC), number RBR-98tx28b.

The Effect of Attention Focus Instructions on Strength and Balance in Subjects With Generalized Joint Hypermobility

ABSTRACT This study aims to examine the effects of different attention focuses on muscle strength and balance performance in individuals with Generalized Joint Hypermobility (GJH). This randomized crossover trial included 32 individuals with GJH whose Beighton score was greater than 5. Subjects performed each task under external attentional focus, internal attentional focus, and neutral attentional focus condition. Knee extensor muscle strength was measured using the Isokinetic Dynamometer. Postural stability was evaluated using the Biodex Balance System, while dynamic balance was assessed using the Y Balance Test. The main effects of attentional focus on the outcomes were analyzed using repeated measures ANOVA and post-hoc corrections with a 95% confidence interval. Subjects produced significantly higher quadriceps peak torque during external focus instruction and internal focus instruction compared to neutral condition (p = .006). Postural stability performance were found to be better during external attention focus compared to the internal focus of attention and the neutral group (p = .008). In addition, an increase in Y balance composite score was observed during external condition compared to internal condition and neutral condition (p < .001). Whether internal or external, the use of attentional focus may be beneficial for optimal force production during training in individuals with GJH. External attention focus enabled better postural stability and dynamic balance performances.

Comparative Effectiveness of Ascorbic Acid vs. Calcium Ascorbate Ingestion on Pharmacokinetic Profiles and Immune Biomarkers in Healthy Adults: A Preliminary Study.

Previous trials have displayed augmented intracellular vitamin C concentrations in the leukocytes at 24 h after acute supplementation with 1000 mg calcium ascorbate (CA), compared to ascorbic acid (AA). The primary objective was to evaluate comparative leukocyte vitamin C accumulation kinetics over 32 h following acute 250 mg or 500 mg doses from the two sources. Secondary objectives were to evaluate neutrophil phagocytic function and lymphocyte differentiation between the two sources of vitamin C. Ninety-three healthy females (250 mg, n = 27; 500 mg, n = 24) and males (250 mg, n = 19; 500 mg, n = 23) were assigned to ingest a single dose of CA or AA providing 250 mg or 500 mg of vitamin C in two separate double-blind, randomized crossover trials. There were no significant differences in the primary or secondary outcomes between the two treatments in the 250 mg low-dose study. Conversely, there was evidence that ingestion of 500 mg of CA increased DHA in plasma, increased neutrophil functionality during the first 8 h of the PK study, promoted increased natural killer cells, and altered weight-adjusted PK profiles, suggesting greater volume distribution and clearance from the blood. These findings indicate that 500 mg of CA may promote some immune benefits compared to 500 mg of AA ingestion.

Mevalonate in blood and muscle: Response to atorvastatin treatment and the relationship to statin intolerance in patients with coronary heart disease.

Statin-associated muscle symptoms are frequently reported and often lead to discontinuation of statin therapy with an increased risk of cardiovascular events. Invitro studies suggest that statin-mediated inhibition of the mevalonate pathway leads to muscle cell toxicity. We aimed to determine the relationship between mevalonate, LDL-cholesterol, and atorvastatin metabolites in patients with coronary heart disease and self-perceived muscle side effects. Furthermore, we assessed the correlation between mevalonate in blood and muscle and the relationship to statin intolerance due to muscle symptoms. We used blood plasma from a randomized crossover trial (n = 70) and muscle biopsies and plasma from a subgroup in a subsequent open intervention study (n = 26). Both studies tested atorvastatin 40 mg/day. Seven patients did not tolerate ≥3 statins throughout the follow-up and were classified as statin-intolerant. Mevalonate in blood plasma decreased during atorvastatin treatment (median difference -38%, range -77% to 43%, p < 0.001), whereas mevalonate in muscle tissue was not lowered (0.05%, range -47% to 145%). Mevalonate correlated poorly with LDL-cholesterol and atorvastatin metabolites (Spearman's rho -0.28 to 0.10). The statin-intolerant patients had a smaller reduction in circulating mevalonate compared with the tolerant patients; median difference -8.1 (-22 to 3.5) nmol/L versus -25 (-93 to 12) nmol/L, p = 0.028. A similar observation was made for LDL-cholesterol. Cutoffs based on these biomarkers classified >50% correctly as tolerant. Inhibition of the mevalonate pathway does not appear to be the mechanism underlying statin intolerance in the present study. Further studies of mevalonate as a biomarker for statin tolerance are needed to clarify the potential.

A Randomized Crossover Trial of Acceptability of Quadruple-Fortified Salt in Women and their Households in Southern India

BackgroundDouble-fortified salt (DFS; iron, iodine) improved iron status in randomized trials and was incorporated into India’s social safety net programs, suggesting opportunities to address other micronutrient deficiencies. ObjectivesTo evaluate acceptability of quadruple-fortified salt (QFS; iron, iodine, folic acid, vitamin B12) in women and their households, using a randomized crossover trial design and triangle tests. MethodsWomen 18-49y (n=77) and their households were randomized to receive QFS or DFS in a randomized crossover design over a 3-week period (week 1: QFS/DFS, 2: iodized salt, 3: DFS/QFS). Each week, participants completed a 9-point hedonic questionnaire (1=dislike extremely to 9=like extremely) to evaluate five sensory domains (color, odor, taste, texture, overall acceptability) of the intervention, and remaining salt was weighed using a digital scale. Triangle tests were conducted among women to evaluate sensory discrimination of salt consumed in rice dishes prepared using standardized recipes. Mixed models were used to examine hedonic ratings and salt use; salt type, sequence, and period were included as fixed effects, and household was included as a random effect. Binomial tests were used to evaluate sensory discrimination of salt type in triangle tests. ResultsMean hedonic ratings for most of the five sensory domains were ≥7 (like moderately) and did not differ by salt type (overall acceptability mean [SD]: QFS: 7.8 [0.7] vs. DFS: 7.7 [1.2]; p=0.68). Household salt use (weighed) did not differ by salt type. During the 3-week intervention period, weighed salt use and hedonic ratings significantly increased, indicating a period effect independent of salt type or sequence. In triangle tests, rice samples prepared with QFS, DFS, or iodized salt were not distinguishable. ConclusionAcceptability of QFS was high, based on individual hedonic ratings and weighed household salt use. Rice dishes prepared with DFS, QFS, and iodized salt were not distinguishable. Findings informed the design of a randomized trial of QFS in this population. Registration numbersNCT03853304 and REF/2019/03/024479.

Mechanisms Underlying Acute Cognitive Impairment following Carbon Dioxide Inhalation in a Randomized Crossover Trial.

Mechanisms Underlying Acute Cognitive Impairment following Carbon Dioxide Inhalation in a Randomized Crossover Trial.

Efficacy and Safety of Pilocarpine Eye Drops Combinations for Treating Presbyopia in a Thai Population: A Randomized Crossover Trial

Objective: This study aimed to assess and compare the effectiveness and side effects of various concentrations of pilocarpine eye drops (1.5%, 1.25%, and 1%), with and without 0.1% brimonidine, in treating presbyopia, specifically in a Thai population. Materials and Methods: A prospective, randomized, double-blinded, and crossover trial was conducted at Siriraj Hospital from August 2022 to April 2023. The study included emmetropic individuals aged 40 to 60 with presbyopia (near visual acuity not exceeding J1+) and refractive errors within +/- 0.5D. The ten subjects were assigned randomly to 6 groups for the different concentrations and type of eyedrops using a computer-generated systematic randomization to receive 1.5%, 1.25%, and 1% pilocarpine with and without 0.1% brimonidine. And visual outcomes including visual acuity at distance and near were measured at 2, 4, and 6 hours post-application, with adverse effects monitored. Primary outcome was visual acuity at near after applied topical eye drops. Results: Among the 10 participants (30% male, median age 46.5 years old), 1.25% pilocarpine and combined 1.25% pilocarpine + 0.1% brimonidine significantly improved near visual acuity at all time points (statistically significant with Bonferroni correction). Adverse effects, such as dry eye and irritation, were more common with 1.5% pilocarpine + 0.1% brimonidine. Conclusion: In this preliminary study, 1.25% pilocarpine and 1.25% pilocarpine + 0.1% brimonidine showed promise in effectively treating presbyopia in the Thai study population, with acceptable side effect rates. Further research with larger sample sizes is needed to confirm these findings and provide more robust insights into presbyopia management in the Asian demographic.

Influence of kilohertz frequency, burst duty cycle and burst duration on evoked torque, discomfort and muscle efficiency: A randomized crossover trial.

This study aimed to investigate the effects of different KFACs on evoked torque, current efficiency, and perceived discomfort. KFACs with frequencies of 1 kHz (Aussie current) and 2.5 kHz (Russian current), along with two duty cycles (10% and 20%), were randomly applied to the triceps surae muscle of healthy participants using a crossover design. The NMES intensity, NMES-evoked torque, NMES efficiency, and NMES discomfort were measured in maximal and submaximal conditions. Statistical analyses were conducted using a two-way mixed-model ANOVA with repeated measures. Forty-four participants were included. Aussie currents produced higher evoked torque and efficiency in maximal and submaximal efforts, with higher perceived discomfort in maximal effort. Although the Australian current may cause greater discomfort at maximal efforts, it matches the Russian current in perceived discomfort at submaximal levels. The 20% duty cycle produced the highest efficiency in submaximal efforts. In both maximal and submaximal efforts, the Aussie current demonstrated superior NMES efficiency, yielding higher torque with lower amplitude than the Russian current. Clinicians should take these findings into consideration when prescribing KFACs to optimize clinical outcomes.