Crossover Design Research Articles

Air Purifiers and Acute Respiratory Infections in Residential Aged Care

ImportanceThe effectiveness of in-room air purification for the reduction of acute respiratory infections (ARIs) in residential aged-care facilities (RACFs) is unknown.ObjectiveTo investigate the effectiveness of in-room air purifiers with high-efficiency particulate air (HEPA)–14 filters in reducing the incidence of ARIs among residents of RACFs.Design, Setting, and ParticipantsThis randomized clinical trial used a multicenter, double-blind, 2-period, 2-treatment crossover design for 6 months from April 7 to October 26, 2023, in 3 RACFs with a bed capacity of 50 to 100 in New South Wales, Australia. The purposive sampling approach included permanent residents in private rooms in the enrolled RACFs. Data collection was performed every 2 weeks and required no additional follow-up beyond the final data collection on October 31, 2023.InterventionAn air purifier containing a HEPA-14 filter was placed in rooms of participants in the intervention group, and an air purifier without a HEPA-14 filter was placed in rooms of the control participants. The groups crossed over after 3 months.Main Outcomes and MeasuresThe primary outcome was the incidence of ARIs, assessed with logistic mixed-model regression.ResultsAmong 135 participants randomized (70 to the intervention-first group and 65 to the control-first group), 78 (57.8%) were female; mean (SD) age was 85.2 (8.6) years. In the intention-to-treat analysis, the use of air purifiers with HEPA-14 filters did not reduce ARIs compared with the control (OR, 0.57; 95% CI, 0.32-1.04; P = .07). Among the 104 participants who completed the entire study, the intervention reduced ARI incidence from 35.6% (37 participants) in the control group to 24.0% (25 participants) in the intervention group (OR, 0.53; 95% CI, 0.28-1.00; P = .048).Conclusions and RelevanceIn this clinical trial investigating use of air purifiers with HEPA-14 filters for reducing ARIs, no significant between-group difference was found in the intention-to-treat analysis. However, a significant reduction in ARIs was identified among participants who completed the entire study. These findings may help inform future large-scale studies of respiratory infectious diseases.Trial RegistrationANZCTR identification: ACTRN12623000347662

Effects of the Dietary Fat Concentration and Fatty Acid Pattern on the Urine Composition, Apparent Nutrient Digestibility, and Selected Blood Values of Healthy Adult Cats

Background/Objectives: The dietary fat concentration and fatty acid profile can influence various aspects of the feline organism. This study examined their effects on the urine composition, apparent nutrient digestibility, and selected blood variables. Methods: Ten healthy adult cats (46.6 ± 14.1 months old, initial body weight 4.99 ± 0.91 kg) received a low-fat basic diet with or without the addition of sunflower oil, fish oil, or lard in a randomized crossover design. The oil and lard were added to the daily amount of food at 0.5 or 1 g/kg body weight of the cats. At the end of each 3-week feeding period, urine, feces, and fasting blood samples were collected. Results: The results demonstrated only small effects of the dietary fat concentration and source on the urine composition of the cats. In addition, the apparent nutrient digestibility was unaffected by the dietary treatments. The supplementation with fish oil, but not sunflower oil or lard, lowered the triglycerides and increased the total and low-density lipoprotein cholesterol concentrations in the plasma of the cats (p < 0.05). However, these blood values were within the physiological reference ranges among all groups. Conclusions: It can be concluded that the dietary fat content and fatty acid profile did not adversely affect the urine composition or nutrient digestibility in healthy adult cats. The lipid metabolism of the animals was modulated by the supplementation with fish oil, a relevant source of n-3 fatty acids. The observed triglyceride-lowering effect should be further investigated in clinical studies.

Influence of Distraction Factors on Performance in Laparoscopic Surgery in Immersive Virtual Reality: Study Protocol of a Cross-Over Trial in Medical Students and Residents-DisLapVR.

Working in an operating room (OR) is physically and mentally challenging: the operation itself demands the surgeon's full attention, while time and cost efficiency constraints, daily planning, and emergency care interfere with the procedure. Thus, multitasking becomes an integral surgical competence. This study aims to examine the effect of disruptions during surgery in a highly immersive virtual reality (IVR) operation environment combined with a virtual reality (VR) laparoscopy simulator. This study aims to identify distractions in the OR and their importance in the clinical setting. An IVR environment was created using a high-resolution, stereoscopic 360° video of the OR. Different distractions were identified, classified as auditory, visual, or audio-visual, and recorded accordingly. The surrounding was combined with a VR laparoscopic simulator. Participants-medical students and surgical residents-received proficiency-based training in basic laparoscopic skills and were blinded to the aim of the experiment. Following a cross-over design, each participant received a unique order of virtual distraction factors while performing tasks on the laparoscopic simulator. During the experiment, subjective passing of time, stress, heart rate, and visually induced motion sickness are recorded. After the experiment, validated questionnaires for usability, immersion, and stress were completed, as well as subjective evaluation of the distractions. The questionnaires used included the system usability scale, Self-Assessment Manikin score, National Aeronautics and Space Administration Task Load Index, and the immersion rating scale as described by Nichols. Performance in the laparoscopic tasks in relation to distractions will be evaluated by the Wilcoxon test and ANOVA for continuous variables. Subgroup analyses in regard to age, gender, and expertise (medical students vs surgical residents) are planned. The described trial started in August 2022 and is ongoing. By July 2024, a total of 30 medical students and 9 surgeons have completed the study. We present a study protocol aiming to identify the impact of different disruptions in OR during laparoscopic training in IVR. Hence, it may lead to an improved awareness of distractions and facilitate accommodations toward an improved work environment. Prior research leads to the hypothesis that the performance of a more experienced surgeon is less impacted by distractions than the performance of inexperienced surgeons and medical students. Furthermore, we investigate which type of distraction has the largest impact on performance. With this knowledge, specific multitasking training can be devised, which may be particularly useful in medical education, for which VR might play a leading role. Additionally, workplace surroundings in the OR can be optimized with this knowledge. German Registry for Clinical Trials DRKS00030033; https://drks.de/search/en/trial/DRKS00030033. DERR1-10.2196/59014.

Enhancing perceptual, attentional, and working memory demands through variable practice schedules: insights from high-density EEG multi-scale analyses.

Contextual interference (CI) enhances learning by practicing motor tasks in a random order rather than a blocked order. One hypothesis suggests that the benefits arise from enhanced early perceptual/attentional processes, while another posits that better learning is due to highly activated mnemonic processes. We used high-density electroencephalography in a multi-scale analysis approach, including topographic analyses, source estimations, and functional connectivity, to examine the intertwined dynamics of attentional and mnemonic processes within short time windows. We recorded scalp activity from 35 participants as they performed an aiming task at three different distances, under both random and blocked conditions using a crossover design. Our results showed that topographies associated with processes related to perception/attention (N1, P3a) and working memory (P3b) were more pronounced in the random condition. Source estimation analyses supported these findings, revealing greater involvement of the perceptual ventral pathway, anterior cingulate and parietal cortices, along with increased functional connectivity in ventral alpha and frontoparietal theta band networks during random practice. Our results suggest that CI is driven, in the random compared to the blocked condition, by enhanced specific processes such as perceptual, attentional, and working memory processes, as well as large-scale functional networks sustaining more general attentional and executive processes.

A controlled trial comparing the impact of guided forest bathing or a mindful urban walk on heart rate, blood pressure, and mood in young Thai adults

Abstract In Thailand, cardiovascular disease and mental health cause a large health and economic burden, with 10% of Thai adults and 32% of adolescents reporting depression. Forest bathing (FB) (mindful nature walking) is growing in popularity globally as a preventative health intervention. Most FB research compares FB with a non‐active control of unguided urban walking, finding improved health and well‐being in FB but not the urban condition. This controlled trial offers a unique and robust comparison of guided FB with an active control of guided mindful urban walking. This is also the first study testing the acceptability and effectiveness of guided FB in Thailand. In a crossover design, heart rate, heart rate variability, blood pressure, and mood in 30 participants were compared before and after 1 h of guided FB and a guided mindful urban walk. MANOVA and t‐test analyses revealed that heart rate and blood pressure reduced in both conditions, but more in the mindful urban condition. Whilst negative mood was reduced in the FB condition but increased in the mindful urban condition. The study offers evidence for the promising health and well‐being benefits of both guided FB and mindful urban walking. Poor mental health and health inequalities are of increasing global concern, hence further research into the effectiveness of alleviating these difficulties through inexpensive interventions such as guided FB and mindful walking are encouraged. The study also offers the first data indicating that FB was acceptable and effective in a Thai population. Read the free Plain Language Summary for this article on the Journal blog.

Effect of Lingual Nerve Block and Localised Somatosensory Abnormalities in Patients With Burning Mouth Syndrome-A Randomised Crossover Double-Blind Trial.

To investigate the effect of a lingual nerve block on spontaneous pain in patients with burning mouth syndrome (BMS) and to estimate associated somatosensory abnormalities by quantitative sensory testing (QST). A standardised QST battery including cold detection threshold (CDT), warmth detection threshold (WDT), thermal sensory limen (TSL), paradoxical heat sensation (PHS), cold pain threshold (CPT), heat pain threshold (HPT), mechanical pain threshold (MPT), wind-up ratio (WUR) and pressure pain threshold (PPT) was performed at the oral mucosa of the most painful site and intraoral control site in 20 BMS patients, and at the tongue and cheek mucosa in 22 age- and gender-matched healthy controls. The effect of a lingual nerve block on spontaneous burning pain reported by the BMS patients on a 0-10 cm visual analogue scale (VAS) was investigated in a randomised double-blind crossover design using (1 mL) lidocaine (lido) or saline (sal) with an interval of 1 week. The BMS patients were grouped into 'central' and 'peripheral' mechanisms based on the effect of the lingual nerve injections. For each BMS patient, Z-scores and Loss/Gain scores were computed. Differences among groups and sites were analysed using a two-way ANOVA. Differences within group were assessed by paired t-test. The 20 BMS patients were characterised on the basis of VAS changes (ΔLido-ΔSal) as a peripheral BMS subgroup (n = 9) with pain relief more than 1 cm on the VAS and a central BMS subgroup (n = 11) with pain relief less than 1 cm. BMS patients (n = 20) had lower sensitivity to thermal stimuli (i.e., CDT, WDT, TSL, CPT, HPT and PPT) and higher sensitivity to mechanical stimuli (i.e., PPT) compared with controls (p ≤ 0.007). Based on Loss/Gain coding, L1G0 (loss of thermal somatosensory function with no somatosensory gain, 55.0%) was the most frequent coding in the BMS group, which was higher than 11.4% in the control group (p < 0.001). Surprisingly, there was no significant difference between the peripheral and central BMS subgroups with regard to the Z-scores of any of the nine QST parameters (p > 0.097). The results of the lingual nerve blocks demonstrated two distinct phenotypes with either peripheral or central mechanisms but no direct impact on somatosensory function. Overall, somatosensory function in BMS patients seems abnormal in the painful areas compared to matched controls with a conspicuous loss of thermosensory function.

Oral but Not Topical Sodium Bicarbonate Improves Repeated Sprint Performance During Simulated Soccer Match Play Exercise in Collegiate Athletes.

This study investigated the effect of oral and topical sodium bicarbonate (SB) on soccer-specific performance during simulated soccer exercise. In a block randomized, double-blind, crossover design, 10 collegiate male soccer players (stature: 181.7 ± 3.2cm, body mass: 81.7 ± 10.5kg) performed soccer-specific performance tests (countermovement jumps, Illinois agility, 8 × 25m repeated sprints) throughout a 90-min soccer-specific aerobic field test (SAFT90) following 0.3g/kg body mass SB in capsules (SB-ORAL), 0.9036g/kg body mass PR Lotion (SB-LOTION), or placebo capsules and lotion (PLA). Soccer-specific performance tests were conducted pre-SAFT90, during half-time and post-SAFT90. Blood samples were analyzed for acid-base balance (pH; bicarbonate, HCO3-) and strong ions (sodium, Na+; potassium, K+). Average sprint times were quicker for SB-ORAL than PLA during half-time (3.7%; p = .049; g = .57) and post-SAFT90 (4.9%; p = .041; g = .66). SB-ORAL increased pH and HCO3- prewarm-up and during half-time (p < .05), and lowered K+ during half-time (p = .035) compared with PLA. SB-LOTION increased pH (p = .019) and lowered K+ (p = .012) during half-time compared with PLA. SB-LOTION increased Na+ postexercise compared with PLA (p = .008). Repeated sprint times during simulated soccer exercise improved for SB-ORAL, which might have been mechanistically underpinned by elevated blood buffering capacity and greater regulation of strong ion concentration. Consuming SB in capsules is a more effective strategy than topical SB application for improving blood buffering capacity and repeated sprint performance throughout competitive soccer matches.

Elevated Plasma IL-6 Coincides with Activation of STAT3 in PBMC After Acute Resistance Exercise.

Changes in plasma concentrations of anti-inflammatory cytokines, such as interleukin-6 (IL-6) and IL-10, after acute resistance exercise (RE) have been widely explored. Whether observed changes in plasma cytokine concentration correspond to the activation of anti-inflammatory signaling pathways in immune cells after acute RE is unknown. This study aimed to determine if changes in plasma cytokines after acute RE resulted in the activation of anti-inflammatory signaling pathways in peripheral blood mononuclear cells (PBMC). Healthy young males (N = 16; age = 23.5 ± 2.7 yr; BMI = 22.4 ± 1.7 kg·m-2) participated in a single session of whole-body RE (4 sets of 4 different exercises at 70% 1-repetition maximum with the last set to failure) and a sedentary control (CON) condition in a randomized crossover design. Blood samples were collected at several time points before and after the exercise bout. Higher plasma IL-6, IL-10, and IL-1 RA concentrations were observed after RE compared with CON. Phosphorylation of STAT3 and protein expression of SOCS3 in PBMC were increased in RE compared with CON. The elevation of plasma IL-6, but not IL-10, coincided with the activation of STAT3 signaling in PBMC. These results highlight a potential mechanism by which RE may exert anti-inflammatory actions in circulating immune cells.

The Effect of a Synthetic-Grass Sport Surface on Physiology and Perception During Intermittent Exercise in Hot Conditions.

The current study aimed to determine the effect of a synthetic-grass sport surface on core body temperature, skin temperature, heart rate, thermal sensation, thermal comfort, and rating of perceived exertion (RPE)during intermittent exercise in hot conditions. Using a randomized crossover design, 13 trained/developmental team-sport athletes completed two 50-minute standardized intermittent running protocols on a synthetic and anatural-grass surface, on separate days (control-condition air temperature 32.6 °C [1.3 °C], relative humidity 43.2% [5.3%]). Final skin temperature was significantly higher on synthetic compared with natural grass at the calf (40.1 °C [2.5 °C] vs 33.4 °C [0.6 °C]; P < .001), shoulder (36.6 °C [1.7 °C] vs 33.7 °C [0.7 °C]; P < .001), and chest (33.2 °C [1.1 °C] vs 31.8 °C [1.2 °C]; P = .02). Thermal sensation (median: 2.3; interquartile range [0.5] vs 2.2 [0.5], P = .03) and sweat rate (1.5 [0.4]L·h-1 vs 1.2 [0.3]L·h-1; P = .02) were also significantly higher on synthetic grass. While final core body temperature was significantly higher on the natural than synthetic grass (38.4 °C [0.3 °C] vs 38.2 °C [0.4 °C]),there were no significant differences in delta core temperature, as well as heart rate, thermal comfort, or RPE. Higher skin temperatures, thermal sensation, and sweat rates suggest that exercising on synthetic grass in hot conditions may increase some markers of heat strain during exercise. However, delta core body temperature, heart rate, thermal comfort, and RPE remained unaffected.

The impact of protocol designs for using massage guns on lower body flexibility: A randomised cross-over design study

The impact of protocol designs for using massage guns on lower body flexibility: A randomised cross-over design study

Effects of active breaks on educational achievement in children with and without ADHD: study protocol and rationale of the Break4Brain project

The Break4Brain project aims to elucidate the effects of both acute and chronic physical activity (PA) on educational achievement in children with and without Attention Deficit Hyperactivity Disorder (ADHD). This study will be conducted in two phases: a cross-over design followed by a hybrid type 1 implementation-effectiveness trial, which includes both a cluster randomized controlled trial (RCT) and a qualitative study. In phase I, 60 children aged 10–12, with 30 each from ADHD and non-ADHD groups, will participate in a laboratory-based study over 4 days within 1 month. They will participate in three counterbalanced experimental conditions: (i) PA with cognitive engagement, (ii) PA without cognitive engagement, and (iii) a cognitively engaging control. This phase will assess acute changes in brain function, academic performance, working memory, inhibitory control, and sustained attention. Phase II will involve 600 children aged 10–12, randomly assigned to either a video-based PA program or a control group (300 children per group) in an 8-week cluster RCT. This phase will also incorporate a qualitative approach to explore the implementation context through pre- and post-intervention semi-structured interviews with teachers and school staff, and questionnaires for students. The outcomes of interest in this phase will include working memory, cognitive flexibility, selective attention, and academic performance. For the cross-over study, we hypothesize that PA conditions will enhance the studied outcomes compared to the control condition. In the RCT, we anticipate that the 8-week active breaks program will result in significant improvements in the selected outcomes compared to the control group. This study is expected to make pioneering contributions by including novel variables and focusing on the ADHD population. Furthermore, if the cluster RCT proves effective, it could offer a practical and cost-effective resource for integrating active breaks into daily school routines.

The Intra-Meatal Application of Tadalafil Cream Versus Oral Administration Efficacy and Safety: Results from a Randomized, Two-Administration Route, Cross-Over Clinical Trial

Background: Tadalafil cream, a topically administered phosphodiesterase-5 inhibitor (PDE5), presents a potential alternative to oral PDE5 inhibitors like tadalafil for the treatment of erectile dysfunction (ED). This study evaluates the non-inferiority and potential superiority of tadalafil cream compared to oral tadalafil. Methods: This randomized controlled trial employed a cross-over design with two treatment periods of two weeks each, separated by a one-week washout phase. Thirty-five male participants aged 18–75 with diagnosed ED (International Index of Erectile Function–Erectile function: IIEF-EF score &lt; 26) were randomized to receive either tadalafil cream or oral tadalafil. Tadalafil cream was applied topically, while tadalafil was taken orally. The primary endpoint was IIEF-EF, and secondary endpoints were measured using the International Index of Erectile Function (IIEF) domain scores. Adverse events and treatment preferences were also assessed. Results: Tadalafil cream showed a higher increase in sexual function across all IIEF domains compared to oral tadalafil. The lower bounds of the confidence interval [improvement: final−baseline scores between tadalafil cream and oral tadalafil 0.72 (95% CI −2.72–4.15)] were above the non-inferiority margin of −3.22, confirming tadalafil cream’s non-inferiority in the erectile function domain. In the intercourse satisfaction domain, tadalafil cream was superior to oral tadalafil. At the end of the trial, 88.57% of participants preferred tadalafil cream (95% CI 73.26%–96.79%), a result significantly above the non-inferiority margin that indicated superiority (p &lt; 0.001). No systemic adverse events were reported for tadalafil cream, and significant differences in dizziness, headache, nasal congestion, and erythema were observed between the two treatments. Conclusions: Tadalafil cream is a safe and effective treatment for erectile dysfunction, demonstrating non-inferiority and potential superiority over oral tadalafil, with a high patient preference. Its topical administration offers a promising alternative for patients, particularly those with cardiovascular diseases where oral PDE5 inhibitors are contraindicated or less well tolerated.

Effects of a feed supplement, containing undenatured type II collagen (UC II®) and Boswellia Serrata, in the management of mild/moderate mobility disorders in dogs: A randomized, double-blind, placebo controlled, cross-over study.

This study was designed as a randomized, placebo-controlled, double-blinded, cross-over trial performed to investigate the effects of a dietary supplement containing undenatured type II collagen (UCII®) and Boswellia Serrata on mobility, pain and joint metabolism in mild moderate osteoarthritis (OA) in dogs. A total of 60 dogs with mobility problems were evaluated and enrolled in the study. Seventeen of these dogs with mild/moderate OA were randomized to receive the product A (UCII® + Boswellia Serrata supplement-UCII®-BW) or product B (Placebo -PL), 1 chew per day for 8 weeks by oral route, and repeated in a crossover design after 4 weeks of washout period. All the subjects had veterinary evaluations during the trial and owners were requested to fill out a questionnaire on mobility impairment using the Liverpool Osteoarthritis in dogs scale (L.O.A.D.) at each time of the study. Objective tools were used to assess mobility, activity, and pain. Metabolomic analysis was performed on synovial fluid of most affected joint at the beginning and the end of the study. The results proved that UCII®+Boswellia serrata supplemented group over a period of eight weeks results in an improvement of mobility impairment, already at 4 weeks of administration, according to the owner´s evaluation. In contrast, its absence increased the risk of OA crisis and decreased the pain threshold on the most affected joint. Furthermore, the synovial fluid metabolic profile showed moderate differences between the beginning and the end of the supplementation period, with a particular influence associated to the time of UCII®-BW administration.

Acute effects of bolus water intake on post-exercise orthostatic hypotension and cardiovascular hemodynamics.

Water intake is known to be effective in preventing orthostatic hypotension (OH). However, it is unknown whether water intake would be effective in acutely preventing exercise-induced OH. Fourteen adults (men/women: 7/7, age: 20 ± 8years) were recruited. Each subject underwent two protocols with and without 500ml water intake using a randomized crossover design (Water vs. Control). Participants underwent 30min of cycle ergometry at the 60-70% predicted VO2 max. OH and hemodynamics were assessed before and after exercise, and immediately (Water 1) and 20min (Water 2) after the water intake. OH was evaluated with a 1-min standing test as the criteria for systolic blood pressure (SBP) < 90mmHg. A cross-spectral analysis for RR and SBP variability was used to evaluate the cardiac autonomic activity and baroreflex sensitivity. In both protocols, the incidence of OH increased after the exercise. The incidence of OH was lower in Water than in Control at Water 1 (OR: 0.093, 95% CI: 0.015-0.591). Heart rate was lower and SBP was higher in Water than in Control at Water 1 and 2 (P < 0.05). High-frequency power of RR variability and transfer function gains in Water were normalized and higher than in Control at Water 1 and 2 (P < 0.05). The ratio of low- to high-frequency power of RR variability in Water was normalized and lower in Water than in Control at Water 1 (P < 0.05). Our findings indicate that water intake may prevent acute exercise-induced OH, accompanied by normalized cardiac autonomic activity and baroreflex sensitivity.

Short-term high-fat and high-carb diet effects on glucose metabolism and hedonic regulation in young healthy men

BackgroundDaily dietary intake of macronutrients and energy is closely associated with long-term metabolic health outcomes, but whether 24-h nutritional intervention under isocaloric conditions leads to changes in metabolism remains unclear. Moreover, the short-term effect of diets with different macronutrient composition on hedonic appetite regulation is less clear.MethodsThis study examined the impact of an acute high-fat (F+) and high-carbohydrate (C+) diet on glucose metabolism and hedonic regulation of food intake in young healthy men under controlled conditions. Using a cross-over design, 19 male participants received a one-day isocaloric diet with different macronutrient composition (F+ = 11% carbohydrates, 74% fat; C+ = 79% carbohydrates, 6% fat) compared to a control diet (CON = 55% carbohydrates, 30% fat). Protein content was set at 15% of energy in all diets. The feeling of hunger, as well as “liking” and “wanting” for foods, was assessed through visual analog scales, and blood samples for glucose, insulin, and cortisol levels were assessed repeatedly during the experimental day. An intravenous glucose tolerance test was conducted the next morning.ResultsPostprandial glucose and insulin levels were lowest in F+ over the 24 h. Except for dinner, the CON diet showed the highest mean values in glucose. F+ diet improved insulin resistance, lowering Homeostatis Model Assessment Insulin Resistance (HOMA-IR) values. Changes in hedonic regulation of food intake were not observed during the intervention between the diets, except for higher feelings of satiety under the CON diet.ConclusionAn acute, isocaloric, high-fat diet improved insulin resistance even in healthy individuals but did not affect hedonic food intake regulation. Macronutrient composition modulate glucose metabolism even under short-term (24-h) and isocaloric diets, which should be considered for personalized preventive dietary treatments.

Syncing the brain’s networks: dynamic functional connectivity shifts from temporal interference

BackgroundTemporal interference (TI) stimulation, an innovative non-invasive brain stimulation approach, has the potential to activate neurons in deep brain regions. However, the dynamic mechanisms underlying its neuromodulatory effects are not fully understood. This study aims to investigate the effects of TI stimulation on dynamic functional connectivity (dFC) in the motor cortex.Methods40 healthy adults underwent both TI and tDCS in a double-blind, randomized crossover design, with sessions separated by at least 48 h. The total stimulation intensity of TI is 4 mA, with each channel’s intensity set at 2 mA and a 20 Hz frequency difference (2 kHz and 2.02 kHz). The tDCS stimulation intensity is 2 mA. Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected before, during, and after stimulation. dFC was calculated using the left primary motor cortex (M1) as the region of interest (ROI) and analyzed using a sliding time-window method. A two-way repeated measures ANOVA (group × time) was conducted to evaluate the effects of TI and tDCS on changes in dFC.ResultsFor CV of dFC, significant main effects of stimulation type (P = 0.004) and time (P &amp;lt; 0.001) were observed. TI showed lower CV of dFC than tDCS in the left postcentral gyrus (P &amp;lt; 0.001). TI-T2 displayed lower CV of dFC than TI-T1 in the left precentral gyrus (P &amp;lt; 0.001). For mean dFC, a significant main effect of time was found (P &amp;lt; 0.001). TI–T2 showed higher mean dFC than tDCS-T2 in the left postcentral gyrus (P = 0.018). Within-group comparisons revealed significant differences between time points in both TI and tDCS groups, primarily in the left precentral and postcentral gyri (all P &amp;lt; 0.001). Results were consistent across different window sizes.Conclusion20 Hz TI stimulation altered dFC in the primary motor cortex, leading to a significant decreasing variability and increasing mean connectivity strength in dFC. This outcome indicates that the 20 Hz TI frequency interacted with the motor cortex’s natural resonance.

Is biomechanical loading reduced in individuals with unilateral transtibial amputation during fast-paced walking when using different ankle/foot prostheses? A pragmatic randomized controlled trial.

Sound side loading is a risk factor for osteoarthritis development, which has been noted to reduce when using advanced prostheses during normal-paced walking in individuals with unilateral transtibial amputation (UTTA). However, descriptions of loading during fast-paced walking remain relatively unreported. Therefore, the aim of this study was to describe the biomechanical loading of individuals with UTTA while using different ankle/foot prostheses during fast-paced walking. A blinded, randomized control trial was conducted in a group of K3-K4 ambulators, who used 3 different prosthetic feet (1. a solid ankle cushioned heel foot prosthesis [SACH], 2. a standard energy storage and return foot prosthesis [ESAR], and 3. a novel ESAR foot prosthesis [N-ESAR]) in a 2-week randomized crossover design. The spatiotemporal and kinetic data of the participants' fast walking pace were collected. Data were analyzed using a mixed model and one-way analysis of variances (p < 0.05) and Cohen d. Twenty individuals with UTTA (age: 40 ± 16 years; height: 1.76 ± 0.09 m; and BMI: 24.72 ± 3.63 kg/m2) participated in this study. There were minimal changes in the spatiotemporal data between the different prosthetic feet. When the participants used the N-ESAR feet, they had a lower peak vertical ground reaction force (p = 0.02) and external knee adduction moment (p = 0.02) on the sound side, as well as a higher distal shank power on the prosthetic side (p < 0.01). Overall fast-paced walking resulted in higher sound side loading forces compared with normal-paced walking. However, use of the N-ESAR prosthesis reduced the biomechanical loading on the sound side in individuals with UTTA while walking at a fast pace compared with the ESAR and SACH prostheses. The percentage change in the biomechanical loading from normal- to fast-paced walking of the N-ESAR foot was also larger compared with the other prostheses, perhaps because of the individuals' ability to achieve a faster walking pace when using the N-ESAR prosthesis. Longitudinal intervention studies should be performed to further investigate the possible benefits of using advanced prostheses.

Calcium propionate is an alkalizing agent in exercising Standardbreds

The objective of this study was to determine if calcium propionate is an alkalizing agent in exercising Standardbreds and if it alters plasma glucose and serum insulin concentrations. This study used a randomized crossover design to test the hypotheses that calcium propionate alters total CO2 (tCO2), Ca++, pH, strong ion difference (SID), glucose, and insulin in Standardbreds completing a simulated race test (SRT) on a high-speed equine treadmill. Blood was collected from eight horses (mean age ± SD = 16 ± 2.7 years; range = 13 - 21 years) at 10 and 5 min prior to treatment or control administration, just prior to the subsequent SRT, directly after the SRT, and at 60- and 90-min post SRT. Plasma pH and plasma concentrations of tCO2, glucose, Ca++, and Na+, K+, Cl-, Lac- (for SID calculation) were measured in duplicate by blood gas analyzer and serum insulin by radioimmunoassay. Data were analyzed by two-way repeated-measures ANOVA. For plasma pH, Na+, K+, Cl-, Lac-, SID, insulin and glucose, no effects of treatment or treatment by sampling-timepoint interaction were found (p>0.05). Plasma tCO2, Ca++, pH, Na+, SID, and glucose concentrations were significantly lower, and Lac- was significantly higher, directly after the SRT compared to all other timepoints (p<0.05). Plasma tCO2, HCO3- and Ca++ were significantly higher in treated than in control horses at multiple sampling timepoints after treatment/control administration (p<0.05). Serum insulin concentration, measured only pre and 30 min post treatment/control administration, was unaffected by treatment. Calcium propionate is an alkalizing agent in horses.

Comparative discontinuation and non-bleeding side effects of Clopidogrel, Prasugrel and Ticagrelor in patients with acute coronary syndromes; a Network Meta-analysis of Randomized Controlled Trials

Abstract Background P2Y12 receptor inhibitors are highly effective treatment options following ACS. However, premature discontinuation compromises their effectiveness. Although extensive literature exists, the clinical assessment of their adherence remains controversial, requiring definitive investigation. Purpose To evaluate treatment discontinuation and non-bleeding adverse effects associatedwith platelet P2Y12 receptor inhibitors in individuals post-ACS through network meta-analysis. Methods Data Sources: MEDLINE, Embase, Cochrane, and clinicaltrials.gov to May 2021 and later updated to October 2022. Study Selection and Outcomes: Reviewers identified RCTs that enrolled patients post-ACS taking Clopidogrel, Ticagrelor, and Prasugrel. Exclusions included non-ACS indications, anticoagulation therapy, observational studies, and crossover designs. The primary outcomesincludedoverall treatment discontinuation, treatment discontinuation attributed to side effects, and dyspnea. Secondary outcomes included bradycardia and atrial fibrillation. Data Extraction and Synthesis:This network meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, employing frequentist random-effects models. The GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework was utilized to assess the certainty of evidence. Results With 139,343 participants in 32 RCTs, the overall treatment discontinuation rate across all studies was 16.57% out of a total of 137,897 participants. Ticagrelor was associated with increased risk for overall treatment discontinuation compared to Clopidogrel (RR, 1.34; 95% CI, 1.19 to 1.49; P&amp;lt;0.0001), Prasugrel (RR, 1.23; 95% CI, 1.07 to 1.41; P=0.0031) and placebo (RR, 1,40; 95% CI, 1.19 to 1.65; P&amp;lt;0.0001). In compatibility to overall treatment discontinuation, Ticagrelor was associated with increased risk for treatment discontinuation due to side effects compared to Clopidogrel (RR, 1.80; 95% CI, 1.36 to 2.38; P&amp;lt;0.0001), Prasugrel (RR, 1.49; 95% CI, 1.06 to 2.10; P=0.0216) and placebo (RR, 1.85; 95% CI, 1.21 to 2.83; P=0.0044). Ticagrelor, Prasugrel and Clopidogrel were associated with an increased risk for dyspnea in comparison to placebo (RR, 2.86; 95% CI, 2.57 to 3.17; P&amp;lt;0.0001; RR, 1.61; 95% CI, 1.35 to 1.91; P&amp;lt;0.0001; RR, 1.60; 95% CI, 1.41 to 1.82; P&amp;lt;0.0001) respectively. Ticagrelor was associated with increased risk for dyspnea compared to Clopidogrel (RR, 1.78; 95% CI, 1.65 to 1.92; P&amp;lt;0.0001) and prasugrel (RR, 1.78; 95% CI, 1.55 to 2.05; P&amp;lt;0.0001). Conclusions The findings of this study suggest that Ticagrelor presents the highest risk for premature discontinuation compared to Clopidogrel and Prasugrel. Additionally, P2Y12 receptor inhibitors, in general, are notably associated with dyspnea, with Ticagrelor showing the highest risk. These results provide health professionals with valuable information for making treatment decisions in patients post-ACS.NMA netgraphsNMA of Overall treatment discontinuation

Atrial fibrillation-related complications following short-term use of antibiotics in patients receiving NOAC or warfarin

Abstract Introduction To study the association of antibiotics with ischaemic stroke/systemic embolism (IS/SE) in patients with atrial fibrillation (AF) receiving anticoagulants. Methods This retrospective population-based cohort study applied electronic health data from a territory-wide medical database. Data were collected for patients with AF who were prescribed non-vitamin K antagonist oral anticoagulants (NOAC) or warfarin between Jan 1, 2010 and Dec 31, 2018. We further identify the patients with and without use antibiotics (any classification of antibiotics with prescription period within 7 days) during the NOAC/warfarin treatment period. The primary outcome is IS/SE and the secondary outcomes including hemorrhagic stroke (HS) and all-cause mortality. Patients were followed up for a median of 3.7 years. A self-control case crossover design was adopted to compare the short-term association between use of antibiotics and outcomes of interest among NOAC and warfarin group. Results This study included 40221 patients, consisted of 30617 NOAC users and 9826 warfarin users, while 9604 patients in NOAC group and 3325 patients in warfarin group had concurrent antibiotics use. At baseline, 46.1% of patients in NOAC group were male and the mean (SD) age was 77.4 (9.8) years, and 56.2% of patients in warfarin group were male and the mean (SD) age was 73.8 (11.3) years. Short-term use of antibiotics is associated with increased risk of IS/SE, HS and all-cause mortality in both NOAC and warfarin groups (NOAC vs. warfarin group: IS/SE: hazard ratio [HR]:3.41 [95%CI, 2.78-4.18]; HR: 2.51 [95%CI, 2.00-3.14]; HS: HR: 2.22 [95%CI, 1.78-2.78]; HR: 2.53 [95%CI, 1.86-3.43]; mortality: HR: 1.96 [95%CI, 1.85-2.08]; HR: 1.87 [95%CI, 1.73-2.02]; all P &amp;lt; 0.001). Conclusion The findings of the present study suggest that the short-term antibiotics use was associated with an increased risk of IS/SE, HS and all-cause mortality among patients in both NOAC and warfarin group. These findings further suggest that use of antibiotics may indicate a higher risk of IS/SE, HS and death for patients with AF, even when receiving NOAC/warfarin and that further investigation is warranted.The study design.The odds ratios of different outcomes.