Placebo-controlled Research Articles

Evaluating efficacy and safety of Saffron add-on treatment in improvement of motor and depressive symptoms of patients with Parkinson’s disease: a randomized, double-blind, placebo-controlled clinical trial

AimEvidence has highlighted neuroprotective effects of saffron in animal models of Parkinson’s disease (PD). The present study investigated the efficacy and safety of add-on saffron on motor and depressive symptoms of patients with PD. MethodsThis study was an 8-week, randomized, double-blind, and parallel-group clinical trial. Known cases of PD with depression were randomized to receive either a routine treatment (levodopa or levodopa-equivalent dose of a dopamine agonist) plus saffron capsule (15 mg bid) or routine treatment plus placebo. All participants were assessed using the Hamilton Depression Rating Scale (HAMD), Geriatric Depression Scale-30 (GDS-30), item 3 of Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part 1, MDS-UPDRS part 3, and H and Y scale at baseline and at week 8. ResultsA total of 52 patients (25 in saffron and 27 in placebo groups) were included. Our results demonstrated that saffron could not improve motor symptoms of PD patients (F=0.53, df=1, p=0.424). However, repeated-measures analysis showed a significant effect of time × treatment (F=8.24, df=1, p=0.006) on HAMD scores, indicating a greater improvement of depressive symptoms in saffron compared to placebo groups. Our study showed nonsignificant findings regarding the secondary outcome measures (GDS-30, item 3 of MDS-UPDRS part 1, and H and Y scale). We showed that treatment with saffron is safe in PD. ConclusionWe substantiated that add-on treatment with saffron significantly improved depression, but not motor symptoms, in PD. Further trials with larger sample sizes and longer follow-ups are needed to confirm our findings.

Zinc supplementation to improve prognosis in patients with compensated advanced chronic liver disease: a multicenter, randomized, double-blind, placebo-controlled clinical trial.

Zinc homeostasis could play a role in compensated advanced chronic liver disease, and its supplementation has been linked to improvement in liver function, a decrease of hepatic complications, and reduction in HCC incidence. Compensated advanced chronic liver disease encompasses a heterogeneous group of patients with variable risks of clinically significant portal hypertension and clinical events. The ANTICIPATE model is a validated model for stratifying these risks. Our aim is to demonstrate that zinc administration can reduce the rate and risk of presenting clinical events (first decompensation, HCC, death, and liver transplantation). This study protocol describes an ongoing phase III, national, multicenter, randomized, double-blind clinical trial that will enroll 300 patients to receive either the trial treatment (zinc acexamate) or placebo. An inclusion period of 42 months is planned, with a minimum follow-up of 2 years. Our principal hypothesis is that zinc could modify the natural history of patients with compensated advanced chronic liver disease, with an overall improvement in prognosis.

Comparing Urtica dioica to Placebo on Vaginal Cytology and pH in Postmenopausal Women: A Randomized, Controlled Trial

IntroductionDecreased estrogen in the period of menopause causes thinning of the vaginal lining, a rise in vaginal acidity, and a drop in vaginal maturation levels. Menopausal women are seeking treatment for bothersome vaginal symptoms, opting for herbal treatments instead of hormone therapy due to their side effects or contraindications. MethodsIn 2021-2022, a triple-blind randomized placebo-controlled clinical trial was carried out on 84 postmenopausal women aged 45-60 from Golestan who had the eligibility criteria and sought services from comprehensive health centers. The qualified females were given 5% vaginal cream containing Urtica dioica extract and a placebo for a duration of 8 weeks. Analysis of data was performed with SPSS. Vaginal PH and maturation value were measured before, as well as four and eight weeks following the intervention. ResultsBefore the intervention, there was no significant difference in the mean (SD) scores of the vaginal pH and VMV between the two groups. During the fourth and eighth weeks post-intervention in the Urtica dioica group, the mean (SD) vaginal pH scores were 4.8 ± 0.7 and 4.3 ± 1.0, while the mean (SD) VMV scores were 50.8 ± 8.8 and 51.3 ± 8.9, respectively. There was a significant difference between the intervention group and the placebo group (P<0.001). ConclusionsAfter using Urtica dioica vaginal cream for eight weeks, postmenopausal women displayed higher vaginal maturation value and lower vaginal pH.

As-Needed Pilocarpine for Radiation-Induced Xerostomia in Head and Neck Cancers.

This study aimed to evaluate the efficacy of as-needed pilocarpine for the management of radiation-induced xerostomia. Additionally, the study sought to assess the side effects associated with an as-needed regimen. A randomized, double-blinded, placebo-controlled crossover study was conducted on patients who had undergone radiation therapy for head and neck cancers and developed xerostomia. Participants took pilocarpine or placebo as needed for symptom relief at 2 weeks per treatment, which included a one-week washout period. The primary outcome measure was the severity of dry mouth symptoms, quantified using the Xerostomia Inventory (XI). The primary outcome was the change in the XI score. Among the 20 participants who completed the crossover study, there was a significant reduction in XI scores during the treatment phase with pilocarpine compared to the scores during the placebo phase. The mean difference in XI scores was -18.05 (95% CI: -17.17, -6.13, p < 0.001), with a-49.77 ± 3.22% change (p < 0.001). Only one participant withdrew due to pilocarpine side effects. As-needed pilocarpine administration is effective in relieving symptoms of radiation-induced xerostomia, with fewer side effects and reduced treatment costs compared to fixed-dose regimens. This study guides the potential shift toward flexible dosing strategies in clinical practice, promoting enhanced patient-centered, tailored care and adherence. According to the Oxford Center for Evidence-Based Medicine 2011 level of evidence guidelines Laryngoscope, 134:4542-4548, 2024.

A parallel-group randomized controlled trial of blue light versus red light for improving sleep, fatigue, and cognition following stroke: Pilot results and recommendations for further study

BackgroundDisordered sleep and fatigue are common in the acute phase of stroke and can impede recovery. ObjectiveA randomized parallel group placebo-controlled pilot study compared daily morning exposure to blue light or red light (placebo) for improving daytime sleepiness, fatigue, nocturnal sleep, and cognition in patients receiving inpatient rehabilitation for acute stroke. Methods43 patients with disordered sleep secondary to first episode stroke (n = 34 ischemic, n = 9 hemorrhagic; aged 66.2 ± 14.1 years) were randomized to receive 25 min of blue or red light for 5 or more days depending on inpatient rehabilitation length of stay (blue-light n = 21, red-light n = 22). At baseline and study discharge, daytime sleepiness was measured with the Karolinska Sleepiness Scale and Wits Pictorial Sleepiness Scale, fatigue with a visual analogue scale, and cognitive function with the Rey Auditory Verbal Learning Test and Trail Making Test (TMT). Wrist actigraphs measured nocturnal sleep parameters. Effect sizes were used to estimate sample sizes for larger studies. ResultsBlue light exposure led to significant improvements in daytime sleepiness, fatigue, auditory verbal learning, and time to sleep onset (all p < .05) relative to red light exposure (effect size range 0.75 to 1.83). Change in TMT, minutes of nocturnal sleep, and number of awakenings after sleep onset were not statistically significant (effect sizes range 0.38 to 0.57). ConclusionMorning blue light exposure for 5 or more days after acute stroke led to greater improvements than red light exposure. Effect sizes suggest a larger study is warranted to confirm generalizability of pilot findings.Trial Registration:ClinicalTrials.govNCT03125967 (Registered 01/01/2017).

Positive Outcomes of Supplementation with Lecithin-Based Delivery Formulation of Curcuma longa and Boswellia serrata in IBS Subjects with Small Bowel Dysbiosis

Background: Small bowel dysbiosis (SBD) is a frequent finding in subjects with irritable bowel syndrome (IBS). The sunflower lecithin (phytosome) formulation of Curcuma longa and Boswellia serrata demonstrated beneficial effects on intestinal microbiota. This study aimed to evaluate the impact of a lecithin-based delivery formulation of Curcuma longa and Boswellia serrata extracts (CUBO) on SBD in IBS subjects. Subjects: Forty-nine adult subjects with IBS and SBD were randomly supplemented for 30 days with CUBO and a low-FODMAP diet (LFD) (intervention) or with LFD and placebo (control group). Results: The intervention group showed a significant reduction in urinary indican (p &lt; 0.001), which was the marker of SBD, and of abdominal bloating (p &lt; 0.001) and abdominal pain (p &lt; 0.001). The pre–post control group analysis did not evidence significant differences. The comparison between the two groups (net effect in intervention minus control subjects) showed that the changes differ significantly for urinary indican p &lt; 0.001 (−42.88; 95% CI: −62.04 to −23.72), abdominal bloating p &lt; 0.001 (−1.50; 95% CI: −1.93 to −1.07), and abdominal pain p &lt; 0.001 (−2.37; 95% CI: −3.61 to −1.13) and for the global assessment of efficacy (p &lt; 0.001). The efficacy was 20% greater in males than in females. Conclusions: In IBS subjects, the intervention with CUBO and LFD shows a significantly higher reduction in SBD, abdominal pain, and bloating compared to LFD and placebo. Additional research is needed to confirm these data.

The effect of intermittent preventive treatment for malaria with dihydroartemisinin–piperaquine on vaccine-specific responses among schoolchildren in rural Uganda (POPVAC B): a double-blind, randomised controlled trial

Several important vaccines differ in immunogenicity and efficacy between populations. We hypothesised that malaria suppresses responses to unrelated vaccines and that this effect can be reversed-at least partially-by monthly malaria intermittent preventive treatment (IPT) in high-transmission settings. We conducted an individually randomised, double-blind, placebo-controlled trial of the effect of malaria IPT with dihydroartemisinin-piperaquine on vaccine responses among schoolchildren aged 9-17 years in Jinja district, Uganda. Participants were recruited from two schools and did not have exposure to vaccines of interest after the age of 5 years, with the exception of human papillomavirus (HPV). Computer-generated 1:1 randomisation was implemented in REDCap. 3-day courses of dihydroartemisinin-piperaquine (dosage by weight) or placebo were administered monthly, including twice before the first vaccination. Trial participants were vaccinated with the live parenteral BCG vaccine (Serum Institute of India, Pune, India) at week 0; yellow fever vaccine (YF-17D; Sanofi Pasteur, Lyon, France); live oral typhoid vaccine (Ty21a; PaxVax, London, UK), and quadrivalent virus-like particle HPV vaccine (Merck, Rahway, NJ, USA) at week 4; and toxoid vaccines (tetanus-diphtheria; Serum Institute of India) and an HPV booster at week 28. An additional HPV vaccination at week 8 was provided to female participants older than 14 years who had not previously been vaccinated, and a tetanus-diphtheria booster was given after completion of the trial at week 52. Primary outcomes were vaccine responses at week 8 and, for tetanus-diphtheria, at week 52, and analysis was done in the intention-to-treat population. Malaria parasite prevalence at enrolment and during follow-up was determined retrospectively by PCR. The safety population comprised all randomly allocated participants. The trial was registered at the ISRCTN Registry (ISRCTN62041885) and is complete. Between May 25 and July 14, 2021, we assessed 388 potential participants for eligibility. We enrolled and randomly allocated 341 participants to the two groups (170 [50%] to dihydroartemisinin-piperaquine and 171 [50%] to placebo); 192 (56%) were female and 149 (44%) participants were male. 145 (85%) participants in the dihydroartemisinin-piperaquine group and 140 participants (82%) in the placebo group were followed up until the week 52 endpoint. At enrolment, 109 (64%) of all participants in the dihydroartemisinin-piperaquine group and 99 (58%) of 170 participants in the placebo group had malaria; this reduced to 6% or lower at all follow-up visits in the dihydroartemisinin-piperaquine group. There was no effect of dihydroartemisinin-piperaquine versus placebo on primary outcomes: BCG-specific IFNγ ELISpot response had a geometric mean ratio (GMR) of 1·09 (95% CI 0·93-1·29), p=0·28; yellow fever neutralising antibody was 1·19 (0·91-1·54), p=0·20 for plaque reduction neutralising reference tests (PRNT50) titres (the reciprocal of the last plasma dilution that reduced by 50%) and 1·24 (0·97-1·58), p=0·09 for PRNT90 titres (reciprocal of the last plasma dilution that reduced by 90%); and IgG to Salmonella enterica serovar Typhi O-lipopolysaccharide was 1·09 (0·81-1·46), p=0·58, HPV-16 was 0·72 (0·44-1·77), p=0·19, HPV-18 was 0·71 (0·47-1·09), p=0·11; tetanus toxoid was 1·22 (0·91-1·62), p=0·18, and diphtheria toxoid was 0·97 (0·83-1·13), p=0·72. There was some evidence that dihydroartemisinin-piperaquine reduced waning of the yellow fever response. IPT for malaria with dihydroartemisinin-piperaquine did not improve peak vaccine responses, despite reducing malaria prevalence. Possible longer-term effects on response waning should be further explored. UK Medical Research Council. For the Luganda translation of the abstract see Supplementary Materials section.

Acute acetaminophen ingestion improves the recovery of neuromuscular fatigue following simulated soccer match-play

ObjectiveThis study aimed to investigate the impact of acute acetaminophen (ACT) ingestion on the responses of neuromuscular function, biomarkers of muscle damage, and physical performance during the 72-h recovery period following simulated soccer match-play. DesignThe study followed a crossover randomized, double-blind, placebo-controlled trial design. MethodsDuring the two experimental sessions, thirteen semi-professional male soccer players completed a 90-min simulated soccer match, 60 min after oral ingestion of 1 g ACT or placebo (PL). Maximal voluntary contraction (MVC) and twitch responses of the knee extensors muscles, elicited through electrical femoral nerve stimulation, were utilized to evaluate both peripheral fatigue (potentiated twitch force, Qtw,pot) and central fatigue (voluntary activation, VA). Performance was assessed through countermovement jump (CMJ) and 20 m sprint tests. Creatine kinase (CK) and lactate dehydrogenase (LDH) were also measured. ResultsSmaller reductions were observed in MVC (−13.3 ± 7.5 % vs. -24.7 ± 11.1 %) and VA (−3.8 ± 4.4 % vs. -12.9 ± 5.4 %) in the ACT compared to the PL condition immediately after simulated soccer match-play (p < 0.05). Afterwards, these parameters were recovered 24 h earlier in the ACT session compared to the PL session. Furthermore, the 20 m sprint performance was significantly better throughout the recovery period in the ACT session compared to the PL session. ConclusionThe findings of this study showed that acute ingestion of 1 g of ACT (1 h before exercise) attenuated the decrease in MVC and VA levels after exercise, as well as improved 20 m sprint performance.

Effect of Beta-Alanine Supplementation on Maximal Intensity Exercise in Trained Young Male Individuals: A Systematic Review and Meta-Analysis.

Beta-alanine is a nonessential amino acid that is commonly used to improve exercise performance. It could influence the buffering of hydrogen ions produced during intense exercise and delay fatigue, providing a substrate for increased synthesis of intramuscular carnosine. This systematic review evaluates the effects of beta-alanine supplementation on maximal intensity exercise in trained, young, male individuals. Six databases were searched on August 10, 2023, to identify randomized, double-blinded, placebo-controlled trials investigating the effect of chronic beta-alanine supplementation in trained male individuals with an age range of 18-40years. Studies evaluating exercise performance through maximal or supramaximal intensity efforts falling within the 0.5-10min duration were included. A total of 18 individual studies were analyzed, employing 18 exercise test protocols and 15 outcome measures in 331 participants. A significant (p = .01) result was observed with an overall effect size of 0.39 (95% confidence interval [CI] [0.09, 0.69]), in favor of beta-alanine supplementation versus placebo. Results indicate significant effects at 4weeks of supplementation, effect size 0.34 (95% CI [0.02, 0.67], p = .04); 4-10min of maximal effort, effect size 0.55 (95% CI [0.07, 1.04], p = .03); and a high beta-alanine dosage of 5.6-6.4g per day, effect size 0.35 (95% CI [0.09, 0.62], p = .009). The results provide insights into which exercise modality will benefit the most, and which dosage protocols and durations stand to provide the greatest ergogenic effects. This may be used to inform further research, and professional or recreational training design, and optimization of supplementation strategies.

Phase 2b randomized clinical trial of amlitelimab, an anti-OX40 ligand antibody, in patients with moderate-to-severe atopic dermatitis

Amlitelimab, a fully human nondepleting monoclonal antibody targeting OX40 ligand on antigen-presenting cells, could prevent T-cell-driven inflammation seen in atopic dermatitis (AD). This trial evaluated the efficacy and safety of amlitelimab in adults with AD. In this 2-part, phase 2b, randomized, double-blinded placebo-controlled trial (NCT05131477), patients received subcutaneous amlitelimab every 4 weeks at doses of 250 mg with 500-mg loading dose, 250 mg, 125 mg, or 62.5 mg, or placebo for 24 weeks in Part 1 (1:1:1:1:1 randomization). In Part 2, clinical responders were reallocated 3:1 to withdraw amlitelimab or continue the previous dose regimen for 28 weeks. The primary end point was percent change in Eczema Area and Severity Index (EASI) from baseline to Week 16. 390 and 190 patients enrolled in Part 1 and Part 2, respectively. Significant percent change decreases in EASI were observed with amlitelimab vs. placebo (P<.001). Clinical responses at Week 24 (Investigator Global Assessment 0/1 and/or EASI-75) were maintained at Week 52 in patients continuing or withdrawn from amlitelimab. In patients maintaining clinical response at Week 52 while off-treatment, >80% had serum amlitelimab concentrations below a 4-μg/mL threshold for several weeks prior to Week 52. Reductions in AD-related biomarkers during Part 1 were maintained through Part 2. Amlitelimab was well tolerated over 52 weeks. Amlitelimab treatment significantly reduced clinical and biomarker responses, and was well tolerated in adults with AD through Week 52. Sustained responses were observed in the majority of patients after amlitelimab withdrawal for 28 weeks.

A double-blind, randomized, placebo-controlled trial of individualized homeopathic medicinal products in the treatment of nocturnal enuresis in children

A double-blind, randomized, placebo-controlled trial of individualized homeopathic medicinal products in the treatment of nocturnal enuresis in children

No benefit from the addition of low-dose ketamine infusion to standard evidence-based care of patients with multiple rib fractures.

Multiple rib fractures from blunt thoracic trauma cause significant morbidity. Optimal current management includes multimodal analgesia, pulmonary hygiene, and early mobilization. Low-dose ketamine infusion (LDKI) has been proposed as an adjunctive analgesic in this setting. A prior study reported decreased pain scores with LDKI in patients with multiple rib fractures. We hypothesized that LDKI would decrease morphine milligram equivalents (MMEs) in patients with multiple rib fractures. A prospective randomized placebo-controlled trial was performed in adult (18 years or older) patients with three or more rib fractures. A prestudy power analysis calculated an 80% chance of identifying a 15% decrease in MMEs with 50 subjects. The study was approved by the institutional review board and informed consent obtained in all subjects. Demographic (age, sex) and injury specific information (Injury Severity Score, number of rib fractures) were obtained. Subjects were randomized 1:1 to receive continuous LDKI (0.1 mg/kg/h) or placebo infusion (0.9% NaCl) for ≤48 hours. All patients received a standard evidence-based multidisciplinary protocol for rib fractures management. Primary outcome measure was MME use or pulmonary complications. Statistical comparison of LDKI versus placebo was performed using the Mann-Whitney U test. All 50 enrolled subjects (placebo, 25; LDKI, 25) received study drug infusion. The two groups were well matched for age, Injury Severity Score, and number of rib fractures. We observed no differences in the Day 1 (p = 0.961), Day 2 (p = 0.373), or total MMEs (p = 0.946) between groups. Similar total MME use was observed when subjects who received ≥40 hours of study drug and were compared (p = 0.924). Use of LDKI did not alter subsequent need for opiate analgesics postinfusion, hospital length of stay, pulmonary complications, or need for readmission. The addition of LDKI to an established multimodal, evidence-based protocol for management of multiple rib fractures did not decrease opiate usage or impact pulmonary complications. Therapeutic/Care Managaement; Level I.

Long-Term Impact of Lumacaftor/Ivacaftor Treatment on Cystic Fibrosis Disease Progression in Children 2-5 Years of Age Homozygous for F508del-CFTR: A Phase 2, Open-Label Clinical Trial.

Rationale: Clinical trials show that lumacaftor/ivacaftor (LUM/IVA) treatment has the potential to modify early cystic fibrosis (CF) disease progression in children as young as 2 years of age. Objectives: To assess the long-term impact of LUM/IVA treatment on CF disease progression in children aged 2-5 years. Methods: This phase 2 trial had two parts: part 1, a 48-week, randomized, double-blind, placebo-controlled study of LUM/IVA in children aged 2-5 years (previously reported) was followed by a 48-week open-label treatment period in which all children received LUM/IVA (part 2; reported here). Endpoints assessed in part 2 included absolute changes from baseline in chest magnetic resonance imaging (MRI) global score at Week 96; weight-for-age, stature-for-age, and body mass index (BMI)-for-age z-scores at Week 96; lung clearance index based on lung volume turnover required to reach 2.5% of starting N2 concentration (LCI2.5) through Week 96; chest MRI morphological score, chest MRI perfusion score, weight, stature, BMI, and microbiology cultures (oropharyngeal swabs) at Week 96; sweat chloride, amount of immunoreactive trypsinogen, fecal elastase-1 concentration, and fecal calprotectin through Week 96; and number of pulmonary exacerbations, time to first pulmonary exacerbation, and number of CF-related hospitalizations. Results: Forty-nine children received one or more doses of LUM/IVA in the open-label period (33 in the LUM/IVA to LUM/IVA group and 16 in the placebo to LUM/IVA group), with a mean exposure of 47.1 (standard deviation [SD], 5.2) weeks. The mean absolute change in MRI global score (negative value indicates improvement) from baseline at Week 96 was -2.7 (SD, 7.0; 95% confidence interval [CI], -5.2 to -0.1) in the LUM/IVA to LUM/IVA group and -5.6 (SD, 6.9; 95% CI, -9.2 to -1.9) in the placebo to LUM/IVA group. Improvements in LCI2.5, sweat chloride concentration, and markers of pancreatic function and intestinal inflammation were also observed in both groups. Growth parameters remained stable in both groups. The majority of children had adverse events considered mild (38.8%) or moderate (40.8%). Two (4.1%) children discontinued LUM/IVA treatment because of adverse events (distal intestinal obstruction syndrome [n = 1] and alanine aminotransferase increase [n = 1]). Conclusions: These findings confirm the potential for early LUM/IVA treatment to alter the trajectory of CF disease progression, including CF lung disease, in children as young as 2 years of age. Clinical trial registered with ClinicalTrials.gov (NCT03625466).

CVN424, a GPR6 inverse agonist, for Parkinson's disease and motor fluctuations: a double-blind, randomized, phase 2 trial

CVN424 is a GPR6 inverse agonist that provides selective pharmacological control of the indirect striatopallidal pathway. We assessed the safety and efficacy of CVN424 as an adjunctive treatment to levodopa for reducing OFF-time in individuals with Parkinson's disease (PD) experiencing motor-fluctuations. This was a randomised, double-blind, placebo-controlled study conducted at 21 sites across the United States to evaluate two doses of CVN424 (NCT04191577). Patients with PD (Hoehn and Yahr stages 2-4) who were on a stable dose of levodopa and experiencing ≥2h of daily OFF-time were randomised (1:1:1) to receive either once-daily CVN424 (50mg or 150mg) or placebo for a 28-day treatment period. The primary endpoints were safety and tolerability. The key secondary endpoint was the change from baseline to Day 27 in OFF-time. The study was conducted from December 23, 2019, to October 14, 2021. Out of 198 participants screened, 141 eligible participants were randomised to one of the three treatment groups (n=47 per group), and 127 participants completed the 28-day treatment period. The most common treatment emergent adverse events (TEAEs) were headache (2% with CVN424 50mg, 9% with CVN424 150mg, and 2% with placebo) and nausea (4% with CVN424 50mg, 6% with CVN424 150mg and 2% with placebo). No serious treatment-related adverse events were reported. On Day 27, the mean±standard deviation (SD) change from baseline in daily OFF-time was-1.3±3.0h in the CVN424 50mg group,-1.6±2.5h in the CVN424 150mg group, and-0.5±2.9h in the placebo group. The placebo-adjusted LS mean±standard error (SE) treatment difference was significant for the CVN424 150mg dose (1.3±0.56h, [95 CI%-2.41 to-0.19], nominal p=0.02). Treatment with CVN424 was safe and well-tolerated. Despite the short study duration and small sample size, the 150mg CVN424 dose provided a clinically meaningful reduction in daily OFF-time. This study supports the development of CVN424 for the treatment of PD. Cerevance.

Impact of D-allulose consumption on Enteric pathogens in human gut Microbiota: A randomized controlled trial study

D-allulose, a rare sugar recognized as Generally Recognized as Safe, has emerged as a potential alternative to sucrose. Despite its growing popularity, research on its effects on the human gut microbiota, including pathogens, remains scarce. To address these concerns, we conducted a 12-week randomized, double-blind, parallel, placebo-controlled study assessing D-allulose’s safety on gut microbiota in humans. Participants consumed 15 g/day of D-allulose or sucralose (placebo) for 12 weeks. Gut microbiota analysis in stool samples, performed through shotgun metagenomics sequencing before and after the intervention, evaluated microbial diversity, taxonomy of prevalent species, changes in pathogenic bacteria (Clostridium difficile, Helicobacter hepaticus, Klebsiella pneumoniae, Bacteroides fragilis, Staphylococcus aureus, and Salmonella enterica), and short-chain fatty acid production. Our findings revealed no significant differences in microbial diversity, pathogenic bacteria levels, or short-chain fatty acid production, suggesting that D-allulose consumption is safe and does not adversely affect the gut microbiome or pathogen presence.

The effect of spironolactone in reducing the risk of postoperative atrial fibrillation in patients undergoing coronary artery bypass graft surgery: randomized single-blind placebo-controlled study.

Postoperative atrial fibrillation (POAF), one of the most common cardiac arrhythmias following coronary artery bypass graft (CABG) surgery is associated with unfavorable outcomes. This study investigated the effect of spironolactone administered two weeks before surgery on the incidence of POAF in patients undergoing CABG. This randomized single-blind placebo-controlled study was conducted on 130 CABG patients. All patients were randomly divided into intervention and control groups including 65 cases for each group. In the intervention group, patients received 50 mg of spironolactone orally daily for 2 weeks before surgery, and in the control group patients received placebo daily from 2 weeks before surgery. All patients were continuously monitored for the occurrence of POAF for two weeks postoperatively. The mean age of the patients in the intervention and control groups was 61.7 ± 5.4 and 60 ± 6.7 years, respectively. The incidence of POAF in the intervention and control groups was 7.7% and 20%, respectively (Odds Ratio = 0.33, P = 0.042). All demographic and clinical variables were similar in patients with and without POAF (all P > 0.05). Our findings revealed that in comparison to placebo, the use of spironolactone is associated with reduced incidence of POAF in CABG candidates.

Influence of the Olfatín Project on the reduction of pain related to intranasal influenza vaccination, as part of a school influenza vaccination program

PurposeTo evaluate the influence of viewing the Olfatín Project video on the assessment of school LAIV-associated pain in three and four-year-old children through the Wong Baker Faces® pain classification scale. Design and methodsA three-arm randomized multicenter clinical trial with a placebo control group was carried out. The main variable measured was pain, assessed through the score on the Wong Baker Faces® Pain Rating Scale. There were a total population of 4591 children three and four-year-olds (born in 2019 and 2020) and who attended the 1st and 2nd year of early childhood education. Before the school vaccination, researchers randomly assigned participant schools corresponding to each of the basic health areas to each of the three study groups: Olfatín's video viewing, a control video viewing not related to influenza and no video viewing. ResultsNo significant differences according to sex, age or the minor's grade according to the assigned intervention were detected. 72.3% of those vaccinated assigned a 0 from the Wong Baker Faces® scale: 75.4% of those who watched Olfatín's video, 68.3% for those in Drilo's group and 72.8% for those who didn't watch any video, but without significant differences (p = 0.08). There were no significant differences either stratifying by sex. ConclusionLAIV is a painless vaccine for children, which has to be taken into account by the health authorities when planning the pediatric influenza vaccination campaign. Practice implicationsOlfatín's cartoon video can be used by professionals to create a greater experience for children and therefore a better acceptance.

No Effects of Omega-3 Supplementation on Kynurenine Pathway, Inflammation, Depressive Symptoms, and Stress Response in Males: A Placebo-Controlled Trial.

Background: Increased inflammation and heightened physiological stress reactivity have been associated with pathophysiology of depressive symptoms. The underlying biological mechanisms by which inflammation and stress may influence neurogenesis are changes in the kynurenine (KYN) pathway, which is activated under stress. Supplementation with n-3 polyunsaturated fatty acids (n-3 PUFAs) has anti-inflammatory properties and can increase stress resilience. Whether n-3 PUFAs alter KYN stress response is unknown. Objectives: This placebo-controlled study investigated the effect of n-3 PUFAs on KYN metabolism, inflammation, depressive symptoms, and mood. Moreover, stress-induced changes following a laboratory stressor have been assessed. Methods: In this placebo-controlled study, 47 healthy male adults received either 4 g n-3 PUFAs per day (Omega-3 group) or a placebo (Placebo group) for 12 weeks. Results: A significant group-by-time interaction was found for the inflammatory markers gp130 (F = 7.07, p = 0.011), IL-6R alpha (F = 10.33, p = 0.003), and TNF_RI (F= 10.92, p = 0.002). No significant group-by-time interactions were found for KYN metabolites, depressive symptoms, and mood (except for Hedonic tone (F = 6.50, p = 0.014)), nor for stress-induced changes in KYN metabolites and mood following a laboratory stressor. Conclusions: Overall, increased n-3 PUFA levels in healthy men ameliorate inflammatory markers but do not ameliorate KYN metabolism, depressive symptoms, mood, or KYN metabolism and mood following a stress induction. This study was registered at ClinicalTrials.gov with the identifier NCT05520437 (30/08/2022 first trial registration).

Astaxanthin improves assisted reproductive technology outcomes in poor ovarian responders through alleviating oxidative stress, inflammation, and apoptosis: a randomized clinical trial

BackgroundPoor ovarian response (POR) to controlled ovarian stimulation (COS) remains challenging, especially in advanced-age women with diminished ovarian reserve, resulting in low live birth rates. Many patients prefer to conceive with their eggs, underscoring the need for improved treatments. This study explores astaxanthin potential as a COS adjuvant to improve ovarian response and assisted reproductive technology (ART) outcomes, considering its impact on oxidative stress (OS), inflammation, and apoptosis, which are key factors in POR.MethodsIn this randomized, triple-blind, placebo-controlled trial, 60 infertile POR patients from POSEIDON Group 4 (the poorest prognosis category, age > 35 and poor ovarian reserve (anti-müllerian hormone < 1.2 ng/ml or antral follicle count < 5) undergoing intracytoplasmic sperm injection were enrolled. Patients were assigned to receive either 12 mg/day AST or placebo for eight weeks. All patients underwent a gonadotropin-releasing hormone antagonist regimen for COS. ART outcomes were compared between groups. Blood serum and follicular fluid (FF) were analyzed for OS markers (superoxide dismutase [SOD], total antioxidant capacity [TAC], and malondialdehyde [MDA]), and pro-inflammatory cytokines (interleukin-6 [IL-6], interleukin-8 [IL-8], and vascular endothelial growth factor [VEGF]) via enzyme-linked immunosorbent assay kits, and cell-free DNA [cfDNA] (apoptotic marker) via ALU quantitative polymerase chain reaction.ResultsAfter the intervention, the AST group exhibited a significant elevation in serum (P = 0.013) and TAC (P = 0.030), accompanied by a significant reduction in serum MDA (P = 0.005). No significant differences between AST and placebo groups were observed in OS markers in FF. AST group showed significant reductions in the serum IL-6 (P < 0.001), IL-8 (P = 0.001), and VEGF (P = 0.002) levels following AST therapy. In the AST group, FF levels of IL-6 (P = 0 < 001), IL-8 (P = 0.036), VEGF (P = 0.006), and cfDNA (P < 0.001) were significantly lower than in the placebo group. Between-group comparisons showed significant differences in the alterations of serum SOD (P = 0.027), IL-6 (P < 0.001), and IL-8 (P = 0.035) levels between AST and placebo groups. The AST group showed significant increases in the number of retrieved oocytes (P = 0.003), MII oocytes (P = 0.004), frozen embryos (P = 0.037), and high-quality embryos (P = 0.014) compared to the placebo group.ConclusionAST shows promise as a COS adjuvant therapy, potentially enhancing some ART outcomes in POR through alleviating OS, inflammation, and apoptosis.Trial registrationClinical trial registration number: IRCT20230223057510N1, URL: https://irct.behdasht.gov.ir/trial/68870, registration date: 2023 March 16.Graphical

Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis

BackgroundWeight reduction has been shown to alleviate symptoms of osteoarthritis of the knee, including pain. The effect of glucagon-like peptide-1 receptor agonists on outcomes in knee osteoarthritis among persons with obesity has not been well studied.MethodsWe conducted a 68-week, double-blind, randomized, placebo-controlled trial at 61 sites in 11 countries. Participants with obesity (a body-mass index [BMI; the weight in kilograms divided by the square of the height in meters] of ≥30) and a clinical and radiologic diagnosis of moderate knee osteoarthritis with at least moderate pain were randomly assigned, in a 2:1 ratio, to receive once-weekly subcutaneous semaglutide (2.4 mg) or placebo, in addition to counseling on physical activity and a reduced-calorie diet. The primary end points were the percentage change in body weight and the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score (on a scale of 0 to 100, with higher scores reflecting worse outcomes) from baseline to week 68. A key confirmatory secondary end point was the physical-function score on the 36-Item Short Form Health Survey (SF-36), version 2 (on a scale of 0 to 100, with higher scores indicating greater well-being).ResultsA total of 407 participants were enrolled. The mean age was 56 years, the mean BMI 40.3, and the mean WOMAC pain score 70.9. A total of 81.6% of the participants were women. The mean change in body weight from baseline to week 68 was −13.7% with semaglutide and −3.2% with placebo (P<0.001). The mean change in the WOMAC pain score at week 68 was −41.7 points with semaglutide and −27.5 points with placebo (P<0.001). Participants in the semaglutide group had a greater improvement in SF-36 physical-function score than those in the placebo group (mean change, 12.0 points vs. 6.5 points; P<0.001). The incidence of serious adverse events was similar in the two groups. Adverse events that led to permanent discontinuation of the trial regimen occurred in 6.7% of the participants in the semaglutide group and in 3.0% in the placebo group, with gastrointestinal disorders being the most common reason for discontinuation.ConclusionsAmong participants with obesity and knee osteoarthritis with moderate-to-severe pain, treatment with once-weekly injectable semaglutide resulted in significantly greater reductions in body weight and pain related to knee osteoarthritis than placebo. (Funded by Novo Nordisk; STEP 9 ClinicalTrials.gov number, NCT05064735.)