Placebo Group Research Articles

Investigating the Additive Effects of Loxacon® Food Supplement Capsules in Patients with Knee Osteoarthritis. A Multicenter, Randomized, Double-Blind, Controlled, Crossover, Follow-Up, Three-Arm Study.

Osteoarthritis is one of the most common locomotor diseases, with a steadily increasing prevalence and incidence. Loxacon® is a food supplement capsule containing vitamins, minerals, and herbal extracts with Boswellia serrata extract and Harpagophytum procumbens extract as its two main active components. The study involved 88 patients at 4 sites. The 88 patients were divided into 3 groups. The first group received physical therapy and Loxacon® capsules for 5 weeks, while the second group (30 patients) received physical therapy only for 5 weeks, and the third group (30 patients) received physical therapy and placebo capsules for 5 weeks. After 5 weeks, physical therapy was discontinued in all three groups and all groups continued Loxacon® capsules exclusively for an additional 60 days. Physical therapy had been carried out by a standard protocol over 5 weeks. Investigated parameters included Western Ontario and McMaster Universities Arthritis Index (WOMAC) testing, European Quality of Life (EQ-5D-5L) quality of life test and the Range of Motion (ROM). Among the 4 visual analogue scale (VAS) values investigated from WOMAC, significant change was seen for functionality in all three groups; however, the extent of change was twice as large in the physical therapy + Loxacon® group at Visit 2 in comparison with the other two groups. In the physical therapy + placebo group, improvement was seen only at the 3rd visit when they were also receiving Loxacon® capsules. The most pronounced difference was seen in the minimum clinically important difference index, calculated from the quality of life-VAS, where those taking Loxacon® capsules had a chance 3 times as high to obtain clinical improvement versus the other two groups. Our study confirmed that a combination of boswellic acid and harpagosides is beneficial as an additional therapy in knee OA.

The impact of renin-angiotensin-aldosterone system inhibitors on the recurrence of chronic subdural hematoma: a systematic review and meta-analysis.

This meta-analysis seeks to investigate the effects of renin-angiotensin-aldosterone system (RAAS) inhibitors on the recurrence of chronic subdural hematoma (cSDH). Following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, this study conducted a comprehensive online search across various databases, including PubMed, EMBASE, CINAHL, Web of Science, and Cochrane, without time restrictions. Two reviewers independently screened titles, abstracts, and full texts based on predetermined criteria, resolving any discrepancies through discussion or consultation with a third reviewer. The quality and risk of bias of the included studies were assessed using the Methodological Index for Non-Randomized Studies (MINORS) and Cochrane's tool for evaluating risk of bias in randomized controlled trials. Six studies aligned with the study objectives were included after a systematic search across 6 databases. The RAAS inhibitors group comprised 404 participants, while the control or placebo group included 1828 participants. Analysis for publication bias using the Egger test indicated no bias in the studies (P = 0.151). The odds ratio for cSDH recurrence with RAAS inhibitor use compared to non-use was reported as OR = 1.06; confidence interval 0.6-1.893, p-value = 0.818, showing no significant association between RAAS inhibitor use and cSDH recurrence. The results suggest no significant link between RAAS inhibitor use and cSDH recurrence. However, due to the limited number and design of studies, as well as the lack of clinical trials, further research is needed to determine the effectiveness of this treatment.

Investigating the impact of tocilizumab on serum cytokines concentrations in Japanese FMF patients: a sub-analysis of the NUH01FMF study

Familial Mediterranean Fever (FMF) is the most common hereditary autoinflammatory disease, characterized by recurrent fever, arthritis, rash, and serositis, and is caused by mutations in the MEFV gene coding for the pyrin protein. The primary treatment goal is to prevent acute attacks and minimize subclinical inflammation to avoid secondary amyloidosis with colchicine as the first-line treatment. However, 10-20% of patients are colchicine-resistant or intolerant. While the therapeutic potential of IL-6 inhibitors such as tocilizumab (TCZ) has been suggested, the detailed serum cytokine profiles after TCZ treatment in patients with FMF remain largely unexplored. This study focused on a sub-analysis of a clinical trial evaluating TCZ in patients with colchicine-resistant FMF (crFMF). We analyzed the serum cytokine profiles at 0, 2, 4, 8, 12, 16, 20, and 24 weeks in the TCZ and placebo groups. Our findings revealed a decrease in serum C-X-C motif chemokine ligand 1 and vascular endothelial growth factor levels in the TCZ group at week 4 compared to baseline, which persisted until week 24, indicating the potential of TCZ to manage crFMF by modulating specific inflammatory cytokines. Further research is required to confirm these findings and optimize the treatment strategies for FMF.

Efficacy of Epidural Steroid in Controlling Pain After Unilateral Biportal Endoscopic Discectomy for Single-Level Lumbar Disc Herniation: A Randomized, Double-Blind, Placebo-Controlled Trial.

The effects of epidural steroid (ES) administration following open or minimally invasive surgery lumbar discectomy have been extensively studied. However, no research has investigated the impact of steroids following the unilateral biportal technique endoscopic lumbar discectomy (UBE-D) for lumbar disc herniation. This study aims to evaluate the efficacy of ES administration in controlling postoperative pain and disability scores following UBE-D for single-level lumbar disc herniation. This double-blind, randomized, placebo-controlled trial was conducted between June 2021 and June 2023. Eighty-two patients were assessed, and 60 were eligible and randomized to receive either ES (n = 30) or saline (placebo; n = 30) after UBE-D. The Outcome measures included visual analog scale scores for pain, Oswestry Disability Index scores, morphine consumption over 24 hours, serum C-reactive protein levels, and the occurrence of complications over a 6-month follow-up period. The baseline characteristics were comparable between the 2 groups, with no significant differences observed. Analysis of visual analog scale scores for back and leg pain, as well as Oswestry Disability Index scores, at various postoperative time points (6 hours, 12 hours, 24 hours, 2 weeks, 6 weeks, 3 months, and 6 months), showed no statistically significant differences between the ES and placebo groups (P values ranged from 0.47-0.94). Additionally, no significant differences were found in morphine consumption within the first 24 hours postoperatively (P = 0.85), length of hospital stay (P = 0.36), or C-reactive protein levels at 24 hours and 3 weeks postoperatively (P values ranged from 0.54-0.79) between the 2 groups. Importantly, no postoperative or steroid-related complications were reported in either group within the 6-month follow-up period. ES administration after UBE-D did not significantly reduce postoperative pain, disability scores, or morphine consumption compared with placebo. The findings suggest that routine use of ESs in this context may not provide additional benefits. Clinicians should reconsider the use of epidural steroids as part of standard postoperative management after UBE-D, as the lack of significant improvement in patient outcomes indicates that alternative pain management strategies may be more effective.

The Impact of Fermented Milk Products Containing Bifidobacterium longum BB536 on the Gut Environment: A Randomized Double-Blind Placebo-Controlled Trial.

Probiotics, particularly those native to the gut microbiota, have a profound influence on the gut environment. In this study, we conducted a randomized placebo-controlled, double-blind, parallel-group comparison trial to investigate the effects of Bifidobacterium longum BB536 (B. longum BB536) on the fecal microbiota and metabolite compositions in healthy individuals. We compared the effects of fermented milk produced solely with Streptococcus thermophiles and Lactobacillus bulgaricus (placebo group) and fermented milk supplemented with B. longum BB536 (BY group). Our findings revealed a significantly greater relative abundance of Faecalibacterium in the BY group than in the placebo group by the 3rd day, a trend that persisted until the end of the trial on the 17th day. Additionally, the BY group presented significantly increased concentrations of tryptophan (Trp), Indole-3-lactic acid, and Indole-3-aldehyde on the 17th day. A significant positive correlation was observed between the relative abundance of Faecalibacterium and the number of viable B. longum BB536 bacteria in the feces. The concentrations of Trp and Indole-3-acetic acid were also significantly correlated with the number of viable B. longum BB536 bacteria in the feces. Our results suggest that B. longum BB536 intake can modulate the gut microbiota and metabolite profiles, which are general indicators for monitoring the gut environment, potentially conferring health benefits to the host.

Impact of synbiotics on disease activity in systemic lupus erythematosus: Results from a randomized clinical trial.

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects various organs in the body. In SLE, inflammatory cytokines play a crucial role in initiating and sustaining the inflammatory process. Synbiotics may help modulate these inflammatory cytokines. This randomized, double-blind, placebo-controlled clinical trial aimed to assess the impact of synbiotics intervention on interleukin-17A (IL-17A) levels, disease activity, and inflammatory factors in patients with SLE. Fifty SLE patients were randomly assigned to receive either standard therapy plus synbiotics (consisting of Streptococcus thermophilus, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus rhamnosus, Lactobacillus salivarius, Lactobacillus reuteri, Bifidobacterium lactis, Bifidobacterium longum, Bifidobacterium bifidum, and the prebiotic fructooligosaccharides) or standard therapy alone for 2 months. The results demonstrated a significant reduction in both protein and mRNA levels of IL-17A, as well as in the Systemic Lupus Erythematosus Disease Activity Index 2000 score, within the synbiotics group after the intervention compared to baseline. In contrast, the placebo group did not experience significant changes in IL-17A levels or disease activity. Synbiotic supplementation shows potential as an adjunctive therapeutic approach for SLE management; however, further research is needed to elucidate its underlying mechanisms. PRACTICAL APPLICATION: This study explores the use of synbiotics as a supplementary treatment for systemic lupus erythematosus, which is typically managed with immunosuppressive therapies.

Effect of ertugliflozin on left ventricular function in type 2 diabetes and pre-heart failure: the Ertu-GLS randomized clinical trial

BackgroundThe therapeutic effects of ertugliflozin, a sodium-glucose cotransporter 2 inhibitor, on cardiovascular outcome are not fully understood. This study aimed to evaluate the efficacy and safety of ertugliflozin on cardiac function in people with type 2 diabetes and pre-heart failure.MethodsWe conducted a 24-week randomized, double-blind, placebo-controlled trial involving individuals with type 2 diabetes inadequately controlled with antidiabetic medications. Participants with left ventricular hypertrophy, E/e’ >15, or impaired left ventricular global longitudinal strain (LVGLS) were randomized 1:1 to receive either ertugliflozin (5 mg once daily) or a placebo. The primary outcome was the change in LVGLS. Secondary outcomes included changes in left ventricular mass index (LVMI) and left ventricular ejection fraction (LVEF). Prespecified exploratory outcomes, including angiotensin-converting enzyme 2 (ACE2) and angiotensin (1–7) levels, were also assessed.ResultsA total of 102 individuals (mean age, 63.9 ± 9.2 years; 38% women) were included. The ertugliflozin group showed a significant improvement in LVGLS (− 15.5 ± 3.1% to − 16.6 ± 2.8%, P = 0.004) compared to the placebo group (− 16.7 ± 2.7% to − 16.4 ± 2.6%, P = 0.509), with a significant between-group difference (P = 0.013). Improvements in LVMI and LVEF were also observed. Additionally, significant reductions in HbA1c, systolic blood pressure, whole-body and visceral fat, uric acid, proteinuria, N-terminal pro–B-type natriuretic peptide, and lipoprotein(a) were noted. ACE2 and angiotensin (1–7) levels significantly increased in the ertugliflozin group compared to the placebo group and correlated with changes in LVGLS [r = 0.456, P < 0.001 for ACE2; r = 0.541, P < 0.001 for angiotensin (1–7)]. Adverse events were similar between the two groups.ConclusionsThis study demonstrated that ertugliflozin has beneficial effects on left ventricular function in individuals with type 2 diabetes and pre-heart failure, and it provided insights into potential underlying mechanisms.Clinical trial registration ClinicalTrials.gov Identifier: NCT03717194.

The Consumption of Lacticaseibacillus rhamnosus HDB1258 Changes Human Gut Microbiota and Induces Immune Enhancement Through NK Cell Activation.

The gut microbiota can play an important role in enhancing the host's complex immune system. In this regard, many studies indicate that probiotics consumption has a beneficial impact on alterations in the composition of the gut microbiota. Our previous study demonstrated that the oral administration of Lacticaseibacillus rhamnosus HDB1258 (HDB1258) enhances immune cell activity and alters the composition of gut microbiota in C57BL/6 mice, thereby showing its potential as a novel immunostimulatory ingredient. Therefore, this clinical trial assessed the effects of HDB1258 on human natural killer (NK) cell activity and changes in gut microbiota. It also investigated the correlation between gut microbiota and NK cell activity following HDB1258 supplementation. Participants (n = 71) were randomized into placebo and HDB1258 groups, and NK cell activity and gut microbiota were investigated at baseline (week 0) and endline (week 8). The present study showed that HDB1258 significantly increased NK cell activity and resulted in positive regulatory effects on the gut microbial balance in subjects compared to the placebo group. HDB1258 affected the gut microbial balance by inducing the growth of beneficial bacteria such as Lactococcus and Sutterella. Especially, the changes in Escherichia-Shigella composition were negatively correlated with the changes in NK cell activity after HDB1258 consumption. There was also a positive correlation between the NK cell activity in the HDB1258 group and the composition of Prevotella 9 and Adlercreutzia. These findings suggest that HDB1258 may improve the host's intestinal environment by regulating gut bacteria related to immune response and promote NK cell activation. This study was registered at clinical research information service (CRIS: KCT0008204).

Allogenic bone marrow–derived mesenchymal stromal cell–based therapy for patients with chronic low back pain: a prospective, multicentre, randomised placebo controlled trial (RESPINE study)

ObjectivesTo assess the efficacy of a single intradiscal injection of allogeneic bone marrow mesenchymal stromal cells (BM-MSCs) versus a sham placebo in patients with chronic low back pain (LBP).MethodsParticipants were...

The effect of prebiotic supplementation on serum levels of tryptophan and kynurenine in obese women with major depressive disorder: a double-blinded placebo-controlled randomized clinical trial

ObjectiveThe objective of the present study was to examine the effect of calorie restricted diet (CRD) plus inulin supplementation on serum levels of tryptophan (Trp), kynurenine (Kyn) and Trp/Kyn ratio in obese women with major depressive disorder (MDD).ResultsIn this double-blind placebo-controlled randomized clinical trial, 51 obese women (BMI = 30–40 kg/m2) with mild MDD were assessed for depression level using Hamilton depression rating scale (HDRS). The patients were randomly allocated into either “Prebiotic group” (received 10 g/day inulin) or “Placebo group” (received 10 g/day maltodextrin). All participants also received individualized CRD. Fasting serum levels of Trp, Kyn, and Trp/Kyn ratio were assessed at baseline and after 8 weeks. Results showed slightly greater increases in serum levels of Trp and Trp/Kyn ratio as well as reductions in serum level of Kyn and HDRS score in prebiotic group than placebo group. However, between group differences in these parameters as well as HDRS score were not statistically significant after adjusting for baseline variables at the end of the trial. Results indicates that CRD accompanied by inulin supplementation (10 g/day) did not influence serum levels of Trp, Kyn and Trp/Kyn ratio as well as HDRS score after 8 weeks.Trial registration: The trial was registered in the Iranian registry of clinical trials at 2018-08-02 (https://www.irct.ir/; registration number: IRCT20100209003320N15).

Study Effect of Esomeprazole on the Treatment of Preeclampsia in Pregnant Women: A Double-Blind Clinical Trial Study

Background: Preeclampsia is one of the most serious complications of pregnancy, leading to various maternal and fetal complications. Objectives: This study aimed to determine the effect of oral esomeprazole in the treatment of preeclampsia in pregnant mothers. Methods: In this double-blind clinical trial, we compared oral esomeprazole with a placebo. The study population included 120 pregnant women with preeclampsia (60 in the esomeprazole 40 mg group and 60 in the placebo group) who were referred to Ba'ath Hospital in Sanandaj in 2023. Patient care and follow-up were conducted from the time of diagnosis of preeclampsia and inclusion in the study groups until delivery and the final condition of the baby. The outcomes investigated included prolongation of pregnancy and maternal, fetal, and neonatal outcomes. Results: The average delivery time in the esomeprazole group was 37.3 ± 1.2 weeks, compared to 37.5 ± 1.7 weeks in the placebo group, with no statistically significant difference (P = 0.75). The frequency of maternal outcomes, such as eclampsia, pulmonary edema, hemolysis, placental abruption, renal failure, hepatic hematoma, ascites, thromboembolism, and maternal death, was not statistically different between the esomeprazole and placebo groups, and no severe complications were observed in either group. Similarly, fetal outcomes, including intrauterine growth restriction (IUGR) and changes in fetal heart rate patterns, did not significantly differ between groups, with no instances of fetal or neonatal death observed. Additionally, neonatal outcomes, such as Apgar scores below 7, NICU admissions, mechanical ventilation, and other severe neonatal complications, were not significantly different between the two groups (P &gt; 0.05). Although the esomeprazole group showed a lower frequency of adverse maternal, fetal, and neonatal outcomes compared to the placebo group, these differences were not statistically significant. Conclusions: The frequency of adverse maternal, fetal, and neonatal outcomes was lower in the esomeprazole group than in the placebo group for most variables, but the differences were not statistically significant. Therefore, it cannot be concluded with certainty that esomeprazole is ineffective in preventing or controlling preeclampsia.

Efficacy and safety of levosimendan in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: The LEVOCEST trial.

Primary angioplasty is the standard procedure for patients with ST-segment elevation myocardial infarction (STEMI). However, myocardial reperfusion results in additional cell damage. Levosimendan, due to its pleiotropic effects, may be a therapeutic alternative to prevent this damage. The objective of this study was to evaluate whether this drug can reduce infarct size in patients with STEMI. Patients were randomized to receive a 24-h infusion of either levosimendan (0.1 μg/kg/min) or placebo after the primary angioplasty. The main objective was to assess the size of the infarct by cardiac resonance at 30 days and 6 months after the event. Other variables such as left ventricular ejection fraction (LVEF) and adverse ventricular remodeling (AVR) were assessed by speckle-tracking echocardiography and magnetic resonance. Major adverse cardiovascular events (MACE) were also collected. 157 patients were analysed (levosimendan, n = 79; placebo, n = 78). We found that after 6 months, patients treated with levosimendan had a greater reduction in infarct size (13.19% ± 9.5% vs.11.79% ± 9%, p = 0.001), compared with those in the placebo group (13.35% ± 7.1% vs. 13.43% ± 7.8%, p = 0.38). There were no significant differences in MACE between both groups. Levosimendan is a safe and effective therapeutic option for reducing infarct size in patients with STEMI.

Nonsteroidal anti-inflammatory drug administration to periparturient cows to reduce postpartum pain-related behaviours

Question In periparturient cows does the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) aid in reducing pain-related behaviours after parturition when compared to cows not administered NSAIDs? Clinical bottom line The category of research question was: Treatment. The number and type of study designs that were critically appraised were: Four randomised control trials. Critical appraisal of the selected papers meeting the inclusion criteria collectively provide zero/weak/moderate/strong evidence in terms of their experimental design and implementation: Moderate. The outcomes reported are summarised as follows… The evidence suggests that NSAIDs can reduce some pain-related behaviours and increase resting behaviours in postpartum cows, with the effect being most consistently observed when administered between 6 and 48 hours before calving or within 3 hours after calving. This effect was most consistently observed in individuals that had experienced uncomplicated calving events and primiparous animals. Primiparous animals administered meloxicam prior to natural calving displayed significantly more lying bouts on the day of calving when compared to primiparous control animals and primiparous animals administered meloxicam postpartum. A separate study reported that cows administered ketoprofen spent less time in lateral recumbency than cows in the placebo group, irrespective of whether calving was assisted. Additionally, when treatment cows were in sternal recumbency, they spent more time with their head in a rested position than the placebo group. There was no significant difference in feeding behaviours postpartum between treatment and placebo animals. There were conflicting results between papers assessing activity levels. In view of the strength of evidence and the outcomes from the studies the following conclusion is made… In some cows, in particular cows with an uncomplicated parturition, NSAIDs can reduce some pain-related behaviours and increase some resting behaviours postpartum. The NSAID should be administered between 6 and 48 hours before calving or within 3 hours after calving.

Efficacy of ursodeoxycholic acid for bile reflux after distal gastrectomy in patients with gastric cancer: A secondary analysis of the PEGASUS-D randomized clinical trial.

Few studies have been conducted on the prevention of bile reflux in gastric cancer patients who have undergone gastrectomy. The aim of this study was to evaluate the efficacy and safety of ursodeoxycholic acid (UDCA) in preventing bile reflux after gastrectomy in patients with gastric cancer. This study was a secondary analysis of the PEGASUS-D trial, a randomized, double-blind, placebo-controlled clinical trial. Adults with a diagnosis of gastric cancer who underwent gastrectomy were enrolled. Eligible participants were randomly assigned to receive 300mg of UDCA, 600mg of UDCA, or placebo at a ratio of 1:1:1. UDCA and placebo were administered daily for 52 weeks. The primary outcomes included bile reflux symptoms at each time point, percentage of participants with bile reflux, and the grade of gastritis. Among 521 participants who underwent randomization, 151, 164, and 150 participants were analyzed from the 300 mg UDCA, 600mg UDCA, and placebo groups, respectively. The difference in symptoms between the three groups was not significant. Bile reflux was less evident in the UDCA group than in the placebo group; however, this difference was significant only in the 300-mg group at 12 months post-operation (odds ratio, 0.44; P = 0.0076). A significant reduction in gastritis was also observed in the 300-mg group at 12 months post-operation (odds ratio, 0.50; P = 0.0368) compared to the placebo group. This study showed that UDCA administration significantly reduced bile reflux and gastritis by approximately 50% at the 12 months-postoperative follow-up in patients who underwent gastrectomy for gastric cancer.

The Macular Choroidal Thickness in Danish Children with Myopia After Two-Year Low-Dose Atropine and One-Year Wash-Out: A Placebo-Controlled, Randomized Clinical Trial.

Our aim in this work was to investigate the macular choroidal thickness (ChT) changes in 6-12-year-old Danish children with myopia during 2years of low-dose atropine treatment and 1-year wash-out vs. placebo in an investigator-initiated, placebo-controlled, double-blind randomized clinical trial. Ninety-seven participants wererandomized to either 0.01% for 2years, 0.1% loading dose for 6months followed by 0.01% for 18months, or placebo, then a 1-year wash-out. The primary outcome was ChT in the sub-foveal and inner and outer superior, nasal, inferior, and temporal sectors. The secondary outcome was axial length (AL). Outcomes were measured at baseline and 6, 12, 24, and 36 months. One-way analysis of variance was used to detect baseline ChT differences between AL-stratified groups (< 24mm, 24-25mm, or > 25mm). To determine the longitudinal changes in ChT and its effect on AL, all eyes were included in linear mixed modeling with individual eyes nested in the study ID as a random effect. Longer eyes had significantly thinner ChT in all choroidal sectors (adj-P < 0.01) at baseline. There was no statistically significant change in any ChT sector after 3years in the placebo group. Sub-foveal and nasal ChT in the 0.1% loading dose and 0.01% group were not significantly different from placebo after 2-year treatment. In the placebo group, a 1-mm increase in AL was significantly associated with a 47-µmthinner nasal ChT after 3years (95% confidence interval (CI): -55; -38, adj-P < 0.001). A 10-µmthicker nasal choroid at baseline was associated with 0.13 mm (95% CI: 0.009; 0.017, adj-P < 0.001) less 3-year axial elongation. The ChT in Danish children with myopia remained stable over the 3-year follow-up. A thinner choroid at myopia onset might predispose to increased axial elongation. Treatment with 0.01% atropine did not change the ChT. We speculate that low-dose atropine does not primarily reduce myopia progression via a choroidal mechanism. ClinicalTrials.gov identifier, NCT03911271.

Early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy: a multicentre double-blind pilot randomised controlled trial

ObjectiveTo examine the feasibility of early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy (HIE).DesignDouble-blind pilot randomised controlled trial.SettingEight neonatal units in South Asia.PatientsNeonates (≥36 weeks) with moderate or severe...

Inflammatory Prostatitis Plus IBS-D Subtype and Correlation with Immunomodulating Agent Imbalance in Seminal Plasma: Novel Combined Treatment.

We recently demonstrated the effectiveness of long-term treatment with rifaximin and the probiotic DSF (De Simone formulation) in improving urogenital and gastrointestinal symptoms in patients with both chronic inflammatory prostatitis (IIIa prostatitis) and diarrhea-predominant irritable bowel syndrome (IBS-D), relative to patients with IBS-D alone. Because the low-grade inflammation of the intestine and prostate may be one of the reasons for co-developing both IIIa prostatitis and IBS-D, we designed the present study to once again evaluate the efficacy of combined rifaximin and DSF treatment in patients affected by IIIa prostatitis plus IBS-D, but we also measured seminal plasma pro-inflammatory (IL-6) and anti-inflammatory (IL-10) cytokines before and after treatment. Methods: We consecutively enrolled 124 patients with IIIa prostatitis and IBS-D (diagnosed using the Rome III criteria). Patients were randomized into two groups: group A (n = 64) was treated with rifaximin (seven days per month for three months) followed by DSF, and group B (n = 60) was treated with a placebo. By the end of the intervention, 68.7% and 62.5% of patients from group A reported improved NIH-CPSI (National Institute of Health's Chronic Prostatitis Symptom Index) and IBS-SSS (Irritable Bowel Syndrome Severity Scoring System) scores, respectively, compared to only 3.3% and 5% of the placebo group. Group A patients also had significantly lower mean seminal plasma levels of IL-6 (11.3 vs. 32.4 pg/mL) and significantly higher mean levels of IL-10 (7.9 vs. 4.4 pg/mL) relative to baseline, whereas the levels of IL-6 and IL-10 did not change in the placebo group. Conclusions: The combined treatment with rifaximin and DSF appears to represent the optimal approach for addressing a syndrome such as irritable bowel syndrome (IBS-D plus), which frequently co-occurs with prostatitis (IIIa prostatitis). This approach is particularly beneficial in cases where the symptoms are not always clearly delineated, the etiology is multifactorial, and the diagnosis is multilevel.

Optimization the design of fixed and group sequential three-arm non-inferiority trials with dichotomous endpoints of risk difference and odds ratio

Although the risk difference (RD) is the most common and well explored functional form for testing efficacy with dichotomous endpoint, odds ratio (OR) is also suggested and well applied measure for non-inferiority (NI) trials. Since the construction and interpretation of these function forms are quite different, this study aims to provide detailed discussions and comprehensive comparisons on the design and testing approach for RD and OR scales for the fixed and group sequential three-arm NI trials under various of situations. The sample size determinations and testing approaches for assessing NI of a new treatment in three-arm clinical trials for RD and OR scales were reviewed comprehensively. Simulation studies are conducted for hundreds of scenarios with parameter configurations of the response rates, randomized allocations, NI margins and interim analysis. The operating characteristic (OC) of RD and OR scales based on the MLE and RMLE methods were thoroughly investigated. A trial example was designed and analyzed to demonstrate the methodologies. It is found that sample size determination on OR scale gives smaller sample size and robust procedure compared to RD scale in the majority of situations. When evaluating the behaviors of the attained power, the RMLE methods based on OR scale outperforms the MLE method and tend to have more power to reject the null hypothesis especially under the small sample size situations. Compared to the fixed design, the group sequential design has better OC, which provides a comparable power while needing smaller total average sample sizes for all cases. In addition, we suggest a lower significance level with a higher power for the sample size determination in the superiority test stage in the group sequential design, which can significantly reduce the total sample sizes while the number of subjects in the placebo group does not increase much. It can offer some recommendations for the investigators to choose the optimal endpoints and parameter configurations to design a three-arm NI trial under certain situations.

The effect of ischemic preconditioning on physical fitness and performance: a meta-analysis in healthy adults.

This meta-analysis aims to assess the impact of ischemic preconditioning (IPC) on physical fitness and performance, with a focus on its specific role in aerobic endurance, anaerobic endurance, explosive power and strength. Systematic searches were conducted across multiple databases (CNKI, CBM, Cochrane Library, Web of Science, PubMed, and Embase) up to September 6, 2023. We included studies that employed randomized controlled trial methods and sham ischemic preconditioning as the placebo group, and two reviewers independently screened literature and extracted data, using Review Manager 5.3 for analysis. This meta-analysis comprises 27 articles with 405 individuals, selected according to specified criteria. IPC significantly increased the blood lactate concentration after anaerobic speed endurance exercise (MD = 0.74, P = 0.03), the blood lactate concentration after incremental exercise (MD = 0.49, P = 0.04), the blood lactate concentration after muscular endurance exercise (MD = 0.68, P = 0.02), and the one-repetition maximum (MD = 1.38, P = 0.00001). Furthermore, it also significantly shortened completion time of the exercises primarily powered by glycolysis (MD = - 0.49, P = 0.01) and completion time of the exercises primarily powered by aerobic system (MD = - 7.27, P = 0.05), while marginally prolonging time to exhaustion (MD = 22.68, P = 0.08). However, IPC had no significant effect on maximum oxygen uptake, blood lactate concentration in fixed-load aerobic endurance exercise, peak power, or peak aerobic power, nor on completion time of the exercises primarily powered by phosphagen system. IPC could serve as a method to enhance physical performance, particularly for exercises primarily powered by aerobic system and glycolysis. Future research might explore how various cycles, locations, and widths of IPC affect the physical performance of participants with different activity levels.

Oral Spore-Based Probiotic Supplementation Alters Post-Prandial Expression of mRNA Associated with Gastrointestinal Health.

Background/Objectives: Unregulated post-prandial dietary endotoxemia may accumulate over time and underlie the development of chronic disease (e.g., leaky gut, inflammatory bowel disease, etc.), for which oral probiotic supplementation may be a prophylactic. The purpose of this study was to determine if 45 d of oral spore-based probiotic supplementation altered gastrointestinal-associated mRNA expression following a high-fat meal. Methods: A subset of apparently healthy individuals from a larger study who had dietary endotoxemia at baseline completed 45 d of supplementation with either a placebo (rice flour; n = 10) or spore-based probiotic (Megasporebiotic™; Novonesis, Kongens Lyngby, Denmark; Bacillus indicus (HU36™), Bacillus subtilis (HU58™), Bacillus coagulans (SC208™), and Bacillus licheniformis (SL-307), and Bacillus clausii (SC109™); n = 10). Venous blood was collected in Paxgene RNA tubes prior to (PRE), 3 h, and 5 h after consumption of a high-fat meal (85% of the daily fat RDA and 65% of the daily calorie needs). Total RNA was analyzed for 579 mRNAs of interest (Nanostring nCounter Sprint; Seattle, WA, USA). After normalization to housekeeping controls and calculation of differential expression relative to PRE and controlled for FDR, 15 mRNAs were determined to be significantly changed at either 3 h and/or 5 h post-prandial in the probiotic group but not in the placebo group. Results: Significant mRNA expressions were associated with gastrointestinal tract barrier function (four mRNAs: BATF3, CCR6, CXCR6, and PDCD2), gastrointestinal immunity (four mRNAs: CLEC5A, IL7, CARD9, and FCER1G), or future IBD risk (seven mRNAs: PD-L1, CSF1R, FAS, BID, FADD, GATA3, and KIR3DL). Conclusions: Collectively, the present findings may support the notion that post-prandial immune response to eating is enhanced following 45 d of probiotic supplementation.