Double-blind Crossover Clinical Trial Research Articles

Safety and efficacy of a probiotic cocktail containing P. acidilactici and L. plantarum for gastrointestinal discomfort in endurance runners: randomized double-blinded crossover clinical trial.

Probiotics are increasingly used to treat conditions associated with gastrointestinal injury and permeability, including exercise-induced gastrointestinal discomfort. This study assessed safety and efficacy of a probiotic in altering the intestinal milieu and mitigating gastrointestinal symptoms (GIS) in endurance runners. In a double blind, crossover study, 16 runners were randomized to 4 weeks of daily supplementation with a probiotic cocktail containing Pediococcus acidilactici bacteria and Lactobacillus plantarum or placebo. Fasting blood and stool samples were collected for measurement of gut permeability markers, immune parameters, and microbiome analyses. Treadmill run tests were performed before and after treatment; participants ran at 65%-70% of VO2max at 27°C for a maximum of 90 min or until fatigue/GIS developed. A blood sample was collected after the treadmill run test. In healthy individuals, 4 weeks of probiotic supplementation did not alter health parameters, although a marginal reduction in aspartate aminotransferase levels was observed with probiotic treatment only (p=0.05). GIS, gut permeability-associated parameters (intestinal fatty acid binding protein, lipopolysaccharide binding protein, zonulin, and cytokines), and intestinal microbial content were not altered by the probiotic supplementation. Post-run measurements of GIS and gut-associated parameters did not differ between groups; however, the observed lack of differences is confounded by an absence of measurable functional outcome as GIS was not sufficiently induced during the run. Under the current study conditions, the probiotic was safe to use, and did not affect gut- or immune-associated parameters, or intestinal symptoms in a healthy population. The probiotic might reduce tissue damage, but more studies are warranted.

Initial treatment with a single capsule containing half-dose quadruple therapy versus standard-dose dual therapy in hypertensive patients (QUADUAL): statistical analysis plan for a randomized, blinded, crossover trial

BackgroundCombined antihypertensive therapy has obvious advantages over single drug therapy. Hypertension guidelines fully affirm the efficacy of dual combination in initial antihypertensive therapy. Recent studies have also pointed out that the quadruple combination of very low-dose antihypertensive drugs is superior to single drugs. However, whether low-dose quadruple therapy is better than dual combination is unknown.Methods/designA randomized double-blind crossover clinical trial will be conducted to compare the efficacy and safety of low-dose quadruple antihypertensives (irbesartan 75 mg + metoprolol 23.75 mg + amlodipine 2.5 mg + indapamide 1.25 mg) with standard-dose dual antihypertensives (irbesartan 150 mg + amlodipine 5 mg) in the initial treatment of patients with mild to moderate hypertension (140–179/90–109 mmHg). Ninety patients are required and will be recruited and randomly assigned in a 1:1 ratio to two crossover groups. Two groups will receive a different combination therapy for 4 weeks, then switch to the other combination therapy for 4 weeks, with a 2-week wash-out. Antihypertensive effects and related adverse effects of the two antihypertensive combination treatments will be compared. The primary outcome, i.e., mean 24-h systolic blood pressure in ambulatory blood pressure monitoring, will be assessed via linear mixed-effects model.DiscussionThis statistical analysis plan will be confirmed prior to blind review and data lock before un-blinding and is sought to increase the validity of the QUADUAL trial.Trial registrationClinicalTrials.gov, NCT05377203. Registered May 11, 2022, https://clinicaltrials.gov/study/NCT05377203.

Effects of dietary nitrate and vitamin C co-ingestion on blood pressure and hand-grip strength in young adults.

Background: Co-administration of vitamin C and inorganic nitrate ([Formula: see text]) may reduce oxidative stress, boost the conversion of nitrite ([Formula: see text]) into NO and elicit positive vascular effects. Aims: We aimed to test the effects of oral inorganic [Formula: see text] and vitamin C co-supplementation on vascular function, muscular strength, and on concentrations of urinary [Formula: see text], vitamin C, 8-isoprostanes and salivary [Formula: see text] in healthy young adults. Methods: Ten young healthy participants were enrolled in a randomised, double-blind (only for the [Formula: see text] intervention) crossover clinical trial. Participants consumed in random order: 1) nitrate-rich beetroot juice and vitamin C (N+VC), 2) nitrate-rich beetroot juice alone (N) or 3) nitrate-depleted beetroot juice alone (ND). Resting blood pressure (BP) was measured at the research centre and at home. Non-invasive, continuous measurements of BP and cardiac function parameters were performed using a Finometer device. Free-living physical activity and hand-grip strength were assessed. Salivary [Formula: see text] and [Formula: see text] and urinary [Formula: see text], 8-isoprostanes and vitamin C concentrations were measured. Results: There were no significant differences for any of the vascular outcomes between the three interventions groups. However, analyses of within-intervention changes showed a significant lower daily systolic BP in the [Formula: see text]+vitamin C (N+VC) group only (P=0.04). Urinary [Formula: see text] (P=0.002) and salivary [Formula: see text] (P=0.001) were significantly higher in the N+VC group compared to the N and ND groups. Conclusion: These preliminary findings suggest that combining dietary [Formula: see text] with vitamin C could have protective effects on vascular function in young adults and could represent an effective strategy for the maintenance of healthy cardiovascular trajectories.

Emerging strategies for treating autoimmune disorders in patients with type 1 diabetes and multiple sclerosis

In the world as a whole and in Ukraine in partmicular, the incidence of autoimmune pathologies continues to grow steadily. There is an increase in the number of type 1 diabetes mellitus (T1DM) and multiple sclerosis (MS) cases in the population. Both diseases have an autoimmune nature and several common features in terms of onset, diagnosis, lack of effective treatment and deve­lopment of complications that are potentially life-threatening. In addition, both diseases have genetic risk factors associated with human leukocyte antigen. There are also other genetic risk factors, such as T-cell alleles of interleukin-2 and protein tyrosine phosphatase, non-receptor type 22 in MS and T1DM, respectively. The environment also plays a significant role in the development of both diseases, with smoking and exposure to viruses increasing the risk of MS and T1DM. To date, the proposed methods of therapy for both diseases are not completely effective, and some of them even have serious side effects. The authors consider the possibility of using clemastine fumarate as a histamine H1 antagonist in the management of T1DM and MS. This histamine H1 antagonist penetrates the blood-brain barrier more easily and thus leads to a sedative effect. The efficacy of clemastine fumarate to enhance remyelination in MS was recently demonstrated in a double-blind crossover clinical trial. In addition, this compound was effective in the treatment of T1DM and its complications in a number of experimental studies. The currently available data allow us to recommend clemastine fumarate as the drug of choice in the comprehensive management of patients with MS. Attention is focused on the need for clinical studies to prove the effectiveness of clemastine fumarate in the treatment of patients with T1DM.

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

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

Quantitation of Formoterol, Salbutamol, and Salbutamol-4′-O-Sulfate in Human Urine and Serum via UHPLC-MS/MS

The adrenergic beta-2 agonists formoterol and salbutamol are used for the treatment of asthma and COPD but are also misused in sports competitions. Therefore, they are included in WADA regulations. Both drugs are mainly excreted in urine after administration via inhalation. A four-armed, double-blind cross-over clinical trial was conducted involving endurance-trained participants (12 females and 12 males). Inhalation dosages of 36 μg formoterol, 1200 μg salbutamol, a combination of both, or a placebo were administered before exercise. Serum and urine were collected after exercise and 3 and 24 h after administration. Here, we show the successful quantitation of formoterol, salbutamol, and its phase II metabolite salbutamol-4′-O-sulfate in all urine and serum samples using ultra-high performance liquid chromatography–tandem mass spectrometry. In the serum analysis, results of up to 14.2 pg/mL formoterol, 10.0 ng/mL salbutamol, and 21.4 ng/mL salbutamol-4′-O-sulfate (calculated as salbutamol equivalent) were found. In urine, maximum concentrations (after deglucuronidation) were 17.2 ng/mL formoterol, 948.5 ng/mL salbutamol, and 2738.5 ng/mL salbutamol-4′-O-sulfate. Sex-specific differences in serum concentrations as well as in urinary excretion were observed. The results pronounce the importance of the implementation and elucidation of phase II metabolites to quantitation methods in antidoping.

Initial treatment with a single capsule containing half-dose quadruple therapy vs standard-dose dual therapy in hypertensive patients (QUADUAL): Study protocol for a randomized, blinded, crossover trial

Combined antihypertensive therapy has obvious advantages over single drug therapy. Hypertension guidelines fully affirm the efficacy of dual combination in initial antihypertensive therapy. Recent studies have also pointed out that the quadruple combination of very low-dose antihypertensive drugs is superior to single drugs. However, whether low-dose quadruple therapy is better than dual combination is unknown. To evaluate and compare the efficacy and safety of half-dose quadruple therapy vs standard-dose dual therapy in the initial treatment of hypertensive patients with systolic/diastolic blood pressure 140-179/90-109 mm Hg. A randomized double-blind crossover clinical trial will be conducted to compare the efficacy and safety of low-dose quadruple antihypertensives (irbesartan 75 mg+metoprolol 23.75 mg+amlodipine 2.5 mg+indapamide 1.25 mg) with standard-dose dual antihypertensives (irbesartan 150 mg+amlodipine 5 mg) in the initial treatment of patients with mild to moderate hypertension (140-179/90-109 mm Hg). Ninety patients are required and will be recruited and randomly assigned in a 1:1 ratio to 2 crossover groups. Two groups will receive a different combination therapy for 4 weeks, then switch to the other combination therapy for 4 weeks, with a 2-week wash-out. The patients will be followed up for 4 weeks to compare the antihypertensive effects and related adverse effects of the 2 antihypertensive combination treatments. We present the rationale for the design of the QUADUAL trial. The trial started in July 2022 and is expected to be completed by August 2023. The study aims to evaluate if an initial treatment regimen of quadruple combination of half-dose blood pressure medications will result in greater reduction in blood pressure and fewer side effects compared to standard dose dual therapy. www. gov (NCT05377203).

Effectiveness of Bromelain in the control of postoperative pain after periodontal surgery: A crossover randomized clinical trial.

This study aimed to compare the analgesic effects of Ibuprofen and bromelain after periodontal surgery. A double-blinded crossover clinical trial was conducted on 22 patients needing two crown lengthening surgeries without bone surgery or with limited bone surgery on two quadrants of the maxilla, with control and test sides. Each quadrant was randomly assigned to bromelain (500 GUD) or ibuprofen (400 mg). Immediately after the surgery and 6 hours after it, the first dose of the drugs was packaged in the same capsules in A and B. Postoperative pain was evaluated during the first 8 hours and on the following day using a visual analog scale (VAS). Using the VAS, the Ibuprofen group showed significantly lower mean pain scores than the bromelain group at 4 hours (P=0.047). In contrast, there were no significant differences between the two groups at 2, 6, 8, 10, 12, 24, and 48 hours (P>0.05). The effectiveness of bromelain for pain control following periodontal surgery was comparable to that of Ibuprofen. Therefore, bromelain can be an efficient replacement for ibuprofen in managing pain after periodontal surgery, especially in patients with gastric ulceration and increased bleeding tendency.

SATELLITE IMAGE-DERIVED NEIGHBORHOOD CHARACTERICS EXPLAIN REGIONAL VARIATION IN CARDIOMETABOLIC DISEASE

We are aware of no study indicating the effects of synbiotic food consumption on metabolic profiles, inflammation and oxidative stress among diabetic patients. The aim of the current study was to investigate the effects of synbiotic food consumption on metabolic profiles, hs-CRP and biomarkers of oxidative stress in diabetic patients.This randomized double-blinded cross-over controlled clinical trial was performed among 62 diabetic patients aged 35–70 y. After a 2-wk run-in period, subjects were randomly assigned to consume either a synbiotic (n = 62) or control food (n = 62) for 6 weeks. A 3-week washout period was applied following which subjects were crossed over to the alternate treatment arm for an additional 6 weeks. The synbiotic food consisted of a probiotic viable and heat-resistant Lactobacillus sporogenes (1 × 107 CFU), 0.04 g inulin (HPX) as prebiotic with 0.38 g isomalt, 0.36 g sorbitol and 0.05 g stevia as sweetener per 1 g. Control food (the same substance without probiotic bacteria and prebiotic inulin) was packed in identical 9-gram packages. Patients were asked to consume the synbiotic and control foods three times a day. Fasting blood samples were taken at baseline and after a 6-wk intervention to measure metabolic profiles, hs-CRP and biomarkers of oxidative stress.Consumption of a synbiotic food, compared to the control, resulted in a significant decrease in serum insulin levels (changes from baseline: −1.75 ± 0.60 vs. +0.95 ± 1.09 μIU/mL, P = 0.03). Although we failed to find a significant effect of synbiotic food consumption on total- and LDL-cholesterol levels and HOMA-IR, the effects on FPG (22.3 vs. 4.2 mg/dL, P = 0.09), serum triglycerides (45.9 vs. 20.6 mg/dL, P = 0.08) and HDL-cholesterol levels (3.1 vs. −2 mg/dL, P = 0.06) tended to be significant. A significant reduction in serum hs-CRP levels (−1057.86 ± 283.74 vs. 95.40 ± 385.38 ng/mL, P = 0.01) was found following the consumption of synbiotic food compared with the control group. Supplementation with the synbiotic food led to a significant increase in plasma total GSH (319.98 vs. 19.73 μmol/L, P < 0.001) and serum uric acid levels (+0.7 vs. −0.1 mg/dL, P = 0.04) compared to the control food. No significant effect of the synbiotic food was observed on plasma TAC levels.In conclusion, consumption of a synbiotic food for 6 weeks among diabetic patients had significant effects on serum insulin, hs-CRP, uric acid and plasma total GSH levels.Clinical trial registration number: www.irct.ir: IRCT201201195623N1.

Comparison of prilocaine/lidocaine cream with piroxicam gel for reducing pain during cannulation of arteriovenous fistula for adults undergoing haemodialysis: A randomized crossover clinical trial.

Pain is a traumatic experience for most patients on hemodialysis. In this trial, we compared prilocaine/lidocaine cream with piroxicam gel for pain reduction during arteriovenous fistula needling. This randomized double-blind crossover clinical trial was done at dialysis unit of a tertiary care hospital from June to August 2022. Adult patients, aged 18-75 years, on maintenance hemodialysis through an arteriovenous fistula were selected randomly. Pain severity during needling of fistula was assessed during initial two hemodialysis sessions without application of any drug. Patients were then randomized into two groups receiving 5% prilocaine/lidocaine cream or 0.5% piroxicam gel 1 h before the next two hemodialysis sessions. After a 7-day washout period, patients crossed over to other groups for another two hemodialysis sessions. Pain was assessed on all these occasions. Primary outcome was reduction in pain with each intervention. There were 32 patients aged 46.44 ± 11.58 years. Pain intensity was 6.69 ± 0.58, 3.13 ± 1.28, and 4.55 ± 1.95 without any medication, prilocaine/lidocaine cream and piroxicam gel respectively. There was greater pain reduction with prilocaine/lidocaine cream than piroxicam gel (3.56 ± 1.35 vs 2.14 ± 1.78; p = 0.001). Local redness with prilocaine/lidocaine cream was reported by one (3.13%) patient, whereas no side effects were seen with piroxicam gel (p = 1.000). Prilocaine/lidocaine cream provides better pain relief than piroxicam gel during arteriovenous fistula needling.

Efficacy of a new sonic powered toothbrush versus a manual toothbrush in a young population. A randomized cross-over clinical trial.

To compare the effectiveness of dental plaque removal between a new sonic toothbrush and a manual toothbrush. In total, 75 healthy dental students participated in this randomized double-blind crossover clinical trial. Subjects were randomly assigned to one of the two groups (manual or sonic toothbrush) and underwent a single toothbrushing exercise. Seven days after, patients were asked to repeat the same procedure with the other toothbrush. Plaque scores were recorded before and after brushing. A significant mean reduction in the full-mouth plaque index was observed after the use of both type of brushes: 46.2% ± 0.28% (p=0.000) and 50.5% ± 0.24% (p=0.000) for the manual and sonic toothbrush, respectively. However, there were no statistically significant differences between the two types of brushes (p=0.277). Regarding plaque reduction on the distinct tooth surfaces, differences between the groups reached statistical significance in favour of the sonic toothbrush only on the buccal sites (p=0.003). Both devices lead to similar plaque score reduction after a single tooth brushing.

Effects of Descurainia sophia on Oxidative Stress Markers and Thirst Alleviation in Hemodialysis Patients: A Randomized Double-Blinded Placebo-Controlled Cross-Over Clinical Trial.

Patients undergoing hemodialysis (HD) are regularly exposed to oxidative stress and inflammation and may suffer from thirst distress with no definitive treatment to address these complications. Descurainia sophia (DS) has been used to alleviate thirst in traditional Persian medicine. This study aimed to assess the effectiveness of DS on oxidation factors and thirst score in HD patients. This study was conducted on fifty-three HD patients referred to Tehran Shahid Modarres hospital. The patients were randomly divided into two groups: Group 1 received DS for six weeks, then underwent four weeks of washout period followed by six weeks of placebo treatment, while group 2 received placebo initially followed by treatment with DS. Biochemistry, malondialdehyde (MDA), and total antioxidant capacity (TAC) were measured in four phases: at the beginning, before washout, after washout, and at the end of the study. The patient's body weight was recorded at the start of each session to assess interdialytic weight gain. Thirst scores also were measured using a visual analog scale. A total of 53 patients, including 23 (43.4%) male and 30 (56.6%) female subjects, were included in the study. The results showed a reduction in thirst score (p=0.001), cholesterol levels (p=0.046), triglycerides (0.003), and MDA (p < 0.001) following the four-week administration of DS treatment in HD patients. The mean levels of TAC were increased (p < 0.001), and calcium, as well as Na+, remained unchanged (p > 0.05). Also, a significant decrease in the patient's weight was observed (p value <0.001). This effect persisted after shifting to a placebo. However, the two groups had no significant difference (p value = 0.539). DS powder-mixed syrup may benefit HD patients by facilitating free radical scavenging and alleviating thirst distress with minimal adverse effects. The seeds could therefore be utilized as a complementary therapy for hemodialysis patients.

Water-Soluble Tomato Concentrate, a Potential Antioxidant Supplement, Can Attenuate Platelet Apoptosis and Oxidative Stress in Healthy Middle-Aged and Elderly Adults: A Randomized, Double-Blinded, Crossover Clinical Trial.

Increased oxidative stress and platelet apoptotic in middle-aged and elderly adults are important risk factors for atherosclerotic cardiovascular disease (ASCVD). Therefore, it is of great significance to control the oxidative stress and platelet apoptosis in middle-aged and elderly adults. Previous acute clinical trials have shown that water-soluble tomato concentrate (WSTC) from fresh tomatoes could exert antiplatelet benefits after 3 h or 7 h, but its effects on platelet apoptosis and oxidative stress are still unknown, especially in healthy middle-aged and elderly adults. This current study aimed to examine the efficacies of WSTC on platelet apoptosis and oxidative stress in healthy middle-aged and elderly adults via a randomized double-blinded placebo-controlled crossover clinical trial (10 weeks in total). A total of 52 healthy middle-aged and elderly adults completed this trial. The results showed that WSTC could increase the serum total antioxidant capacity levels (p < 0.05) and decrease the serum malondialdehyde levels (p < 0.05) after a 4-week WSTC supplementation in healthy middle-aged and elderly adults. Platelet endogenous reactive oxygen species generation (p < 0.05), mitochondrial membrane potential dissipation (p < 0.05) and phosphatidylserine exposure (p < 0.05) were attenuated. In addition, our present study also found that WSTC could inhibit platelet aggregation and activation induced by collagen or ADP after intervention (p < 0.05), while having no effects on adverse events (p > 0.05). The results suggest that WSTC can inhibit oxidative stress and its related platelet apoptosis, which may provide a basis for the primary prevention of WSTC in ASCVD.

Levetiracetam in Alzheimer's Disease: Do Epileptologists Already Have the Cure?

Effect of Levetiracetam on Cognition in Patients With Alzheimer Disease With and Without Epileptiform Activity: A Randomized Clinical Trial Vossel K, Ranasinghe KG, Beagle AJ, et al. JAMA Neurol. 2021;78(11):1345-1354. doi:10.1001/jamaneurol.2021.3310.Importance:Network hyperexcitability may contribute to cognitive dysfunction in patients with Alzheimer disease (AD).Objective:To determine the ability of the antiseizure drug levetiracetam to improve cognition in persons with AD.Design, setting, and participants:The Levetiracetam for Alzheimer’s Disease–Associated Network Hyperexcitability (LEV-AD) study was a phase 2a randomized double-blinded placebo-controlled crossover clinical trial of 34 adults with AD that was conducted at the University of California, San Francisco, and the University of Minnesota, Twin Cities, between October 16, 2014, and July 21, 2020. Participants were adults 80 years and younger who had a Mini Mental State Examination score of 18 points or higher and/or a Clinical Dementia Rating score of less than 2 points. Screening included overnight video electroencephalography and a 1-hour resting magnetoencephalography examination.Interventions:Group A received placebo twice daily for 4 weeks followed by a 4-week washout period, then oral levetiracetam, 125 mg, twice daily for 4 weeks. Group B received treatment using the reverse sequence.Main outcomes and measures:The primary outcome was the ability of levetiracetam treatment to improve executive function (measured by the National Institutes of Health Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research [NIH-EXAMINER] composite score). Secondary outcomes were cognition (measured by the Stroop Color and Word Test [Stroop] interference naming subscale and the Alzheimer’s Disease Assessment Scale—Cognitive Subscale) and disability. Exploratory outcomes included performance on a virtual route learning test and scores on cognitive and functional tests among participants with epileptiform activity.Results:Of 54 adults assessed for eligibility, 11 did not meet study criteria, and 9 declined to participate. A total of 34 adults (21 women [61.8%]; mean [SD] age, 62.3 [7.7] years) with AD were enrolled and randomized (17 participants to group A and 17 participants to group B). Thirteen participants (38.2%) were categorized as having epileptiform activity. In total, 28 participants (82.4%) completed the study, 10 of whom (35.7%) had epileptiform activity. Overall, treatment with levetiracetam did not change NIH-EXAMINER composite scores (mean difference vs placebo, .07 points; 95% CI, −.18 to .32 points; P = .55) or secondary measures. However, among participants with epileptiform activity, levetiracetam treatment improved performance on the Stroop interference naming subscale (net improvement vs placebo, 7.4 points; 95% CI, .2–14.7 points; P = .046) and the virtual route learning test (t = 2.36; Cohen f2 = .11; P = .02). There were no treatment discontinuations because of adverse events.Conclusions and relevance:In this randomized clinical trial, levetiracetam was well tolerated and, although it did not improve the primary outcome, in prespecified analysis, levetiracetam improved performance on spatial memory and executive function tasks in patients with AD and epileptiform activity. These exploratory findings warrant further assessment of antiseizure approaches in AD.

Effects of trazodone on behavioral and physiological signs of stress in dogs during veterinary visits: a randomized double-blind placebo-controlled crossover clinical trial.

To determine whether a single dose of trazodone administered to dogs before a veterinary visit reduced their behavioral and physiologic signs of stress and owners' stress during veterinary visits. 20 dogs and their owners. In this randomized double-blinded placebo-controlled crossover clinical trial, dogs with a history of anxiety during veterinary visits were scheduled for 2 veterinary visits 1 week apart and randomly assigned to receive a single oral dose of either trazodone (9 to 12 mg/kg) or a placebo 90 minutes before transport to the veterinary clinic for alternate visits between September 21 and November 3, 2019. For each visit, we collected and assessed owner-completed surveys of dog stress score (DSS) and owner stress score; various investigator-reported scores, including from video-recorded behavior analyses; and patient-related physiologic data. Dogs treated with trazodone versus placebo had lower mean DSSs, assessed by owners for physical examination and assessed by video analysis for time spent in the examination room; lower mean SD of normal-to-normal intervals, root mean square of successive heartbeat interval difference, and respiratory rate; and higher mean heart rate. No meaningful differences were observed in other behavioral or physiologic outcomes, including serum cortisol concentrations. A single dose of trazodone before transport reduced signs of stress during veterinary visits for dogs in the present study and may be useful as an anti-anxiety medication for similarly affected dogs, potentially resulting in higher-quality clinical examinations and improved patient welfare.

Short-Term Ingestion of Medium-Chain Triglycerides Could Enhance Postprandial Consumption of Ingested Fat in Individuals with a Body Mass Index from 25 to Less than 30: A Randomized, Placebo-Controlled, Double-Blind Crossover Study.

The elimination of obesity is essential to maintaining good health. Medium-chain triglycerides (MCTs) inhibit fat accumulation. However, studies examining energy expenditure and fat oxidation with continuous ingestion of MCTs show little association with the elimination of obesity. In this study, we conducted a randomized, double-blind crossover clinical trial to investigate the effects of continuous ingestion of MCTs on postprandial energy expenditure and ingested long-chain triglycerides (LCTs) oxidation. A daily 2 g of MCTs were ingested for two weeks by sedentary participants with a body mass index (BMI) from 25 (kg/m2) to less than 30. Ingestion of a meal containing MCTs and isotopic carbon-13-labeled (13C) LCTs increased energy expenditure and consumption of diet-derived LCTs, as determined by postprandial 13C carbon dioxide excretion, compared to canola oil as the placebo control. These results indicate that continuous ingestion of MCTs could enhance postprandial degradation of diet-derived fat and energy expenditure in sedentary, overweight individuals.

Effect of low dose nebulized morphine on respiratory function improvement in mustard gas-exposed patients: A double-blind crossover clinical trial study.

Background:Mustard is one of the most destructive chemical gases used in chemical warfare. Several studies showed effectiveness of inhaled morphine as a secondary treatment for the improvement of dyspnea. Therefore, this study aimed at determining the efficacy of low dose inhaled morphine for respiratory function improvement in patients who were exposed to the mustard gas.Methods:This study was designed as a cross-over double-blinded clinical trial. Patients exposed to mustard gas were randomly assigned into two groups: 1) received 0.4 mg of morphine by inhalation and 2) received 5 ml of normal saline serum as a placebo in the same manner. After a washout period of one week, the first group received the placebo and the second group received morphine for 5 days. Spirometric indices, expiratory flow peak, exercise test, severity of dyspnea, and quality of life were evaluated as respiratory function parameters. Data analysis was done using SPSS software Version 16.Results:The mean maximum expiratory flow was significantly higher among cases who used morphine in comparison with the placebo group (p<0.05). Moreover, the severity of dyspnea, quality of life, and the frequency of coughing during the day were significantly improved among the recipients of morphine (p<0.05) while the spirometric indices and exercise tolerance tests were similar between the two groups (p>0.05), but the mean peak expiratory flow (PEFR) was significantly higher among the patients receiving morphine than the placebo patients (p<0.001).Conclusion:The use of inhaled morphine had a significant positive effect on the respiratory system of people exposed to mustard gas. We can use low doses of inhaled morphine to improve the respiratory function of these patients as a secondary therapy.

Melissa Officinalis and Essential Hypertension

For long plants and herbs have been used to treat cardiovascular diseases and Melissa officinalis (M. officinalis) Is one of those plants. However, there is no conclusive evidence for the effects of the plant on both systolic and diastolic blood pressures in hypertensive patients. Shekarriz and colleagues performed a double-blind cross-over clinical trial with 49 hypertensive patients given either placebo or capsules of the plant (400mg/d) thrice a day for a week. The blood pressure was measured at baseline once and then biweekly for 2.5 months. Their findings revealed that both systolic and diastolic blood pressures were reduced in patients given M. officinalis compared to the placebo. Moreover, no drastic adverse effects were observed. Hence, they conclude that in patients with primary hypertension, both systolic and diastolic blood pressures can be significantly decreased by M. officinalis. Phytother Res. 2021 Dec;35(12):6883-6892.

Effect of Levetiracetam on Cognition in Patients With Alzheimer Disease With and Without Epileptiform Activity

Network hyperexcitability may contribute to cognitive dysfunction in patients with Alzheimer disease (AD). To determine the ability of the antiseizure drug levetiracetam to improve cognition in persons with AD. The Levetiracetam for Alzheimer's Disease-Associated Network Hyperexcitability (LEV-AD) study was a phase 2a randomized double-blinded placebo-controlled crossover clinical trial of 34 adults with AD that was conducted at the University of California, San Francisco, and the University of Minnesota, Twin Cities, between October 16, 2014, and July 21, 2020. Participants were adults 80 years and younger who had a Mini-Mental State Examination score of 18 points or higher and/or a Clinical Dementia Rating score of less than 2 points. Screening included overnight video electroencephalography and a 1-hour resting magnetoencephalography examination. Group A received placebo twice daily for 4 weeks followed by a 4-week washout period, then oral levetiracetam, 125 mg, twice daily for 4 weeks. Group B received treatment using the reverse sequence. The primary outcome was the ability of levetiracetam treatment to improve executive function (measured by the National Institutes of Health Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research [NIH-EXAMINER] composite score). Secondary outcomes were cognition (measured by the Stroop Color and Word Test [Stroop] interference naming subscale and the Alzheimer's Disease Assessment Scale-Cognitive Subscale) and disability. Exploratory outcomes included performance on a virtual route learning test and scores on cognitive and functional tests among participants with epileptiform activity. Of 54 adults assessed for eligibility, 11 did not meet study criteria, and 9 declined to participate. A total of 34 adults (21 women [61.8%]; mean [SD] age, 62.3 [7.7] years) with AD were enrolled and randomized (17 participants to group A and 17 participants to group B). Thirteen participants (38.2%) were categorized as having epileptiform activity. In total, 28 participants (82.4%) completed the study, 10 of whom (35.7%) had epileptiform activity. Overall, treatment with levetiracetam did not change NIH-EXAMINER composite scores (mean difference vs placebo, 0.07 points; 95% CI, -0.18 to 0.32 points; P = .55) or secondary measures. However, among participants with epileptiform activity, levetiracetam treatment improved performance on the Stroop interference naming subscale (net improvement vs placebo, 7.4 points; 95% CI, 0.2-14.7 points; P = .046) and the virtual route learning test (t = 2.36; Cohen f2 = 0.11; P = .02). There were no treatment discontinuations because of adverse events. In this randomized clinical trial, levetiracetam was well tolerated and, although it did not improve the primary outcome, in prespecified analysis, levetiracetam improved performance on spatial memory and executive function tasks in patients with AD and epileptiform activity. These exploratory findings warrant further assessment of antiseizure approaches in AD. ClinicalTrials.gov Identifier: NCT02002819.

Suplementação aguda de arginina não influencia na hipotensão pós-exercício aeróbico

This study evaluated the effects of acute arginine supplementation (ARG) on post-exercise hypotension (HPE). For this, 12 physically active young men participated in this randomized, double-blind crossover clinical trial. All were submitted to two experimental conditions (ARG or placebo – PLA). 45 minutes after supplementation, all participants performed 30 minutes of moderate-intensity aerobic exercise (70-75% of reserve heart rate). Heart rate and systolic and diastolic blood pressures were measured before, 30 and 60 minutes after exercise. In comparison with pre-exercise means, there was a lower systolic blood pressure until to 60 min post-exercise (117.3±6.5 vs. 109.6±7.2 mmHg, p=0.001), lower mean arterial blood pressure (89.1±7.0 vs. 83.8±8.2 mmHg, p=0.024), increased heart rate (67.1±11.9 vs. 84.8±6.8 bpm, p=0.001) and the double product (7988±1372 vs. 9734±990 mmHg.bpm, p=0.006) until 30 min post-exercise. However, there was no significant difference between experimental conditions. Using the methods applied, our results demonstrated no effect of acute ARG supplementation on aerobic HPE in physically active young men.