Placebo-controlled Randomized Trial Research Articles

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.

Efficacy of Lactococcus lactis strain Plasma on clearance of anal HPV infection in men who have sex with men: A single-center, double-blinded, randomized placebo-controlled trial (CLEAR HPV study)

Background: Anal cancer is a human papillomavirus-related cancer; specifically, it is preceded by high-grade squamous intraepithelial lesions, which are less likely to regress spontaneously than low-grade intraepithelial lesions. Although most human papillomavirus (HPV) infections are thought to clear spontaneously, anal HPV infection persists, especially in people living with HIV. Preliminary results from a recent small randomized placebo-controlled trial of oral bacteriotherapy using a high dose of probiotics demonstrated clearance of anal high-risk HPV (hr-HPV) infection and lower onset of new high-grade squamous intraepithelial lesions among people living with HIV. Lactococcus lactis strain Plasma is a lactic acid bacterium directly activating plasmacytoid dendritic cells and inducing release of type I and III interferons via Toll-like receptor 9 stimulation. Based on these findings, oral bacteriotherapy with LC-plasma may contribute to clearing anal hr-HPV infection and reducing anal precancerous lesions by activating innate and acquired immune responses. This randomized placebo-controlled trial aims to investigate the efficacy and safety of LC-plasma therapy in clearing anal hr-HPV infection and reducing anal precancerous lesions among men who have sex with men with or without HIV infection. Methods: Participants with anal hr-HPV infection will be included and receive test capsules. A total of 150 patients will be included in the intervention group with follow-up, which will consist of HPV genotype test, cytology by anal pap smear, and biopsy with high-resolution anoscopy. The primary endpoint will be the clearance rate of the hr-HPV genotype infection at the anal site at 180 days. The secondary endpoints will be changes in anal epithelial neoplasia detected using high-resolution anoscopy at 180 days; change in abnormal cytology by anal pap smear at 180 days; change in hr-HPV genotype at the anal site at 180 days; change or percentage change in peripheral blood CD4 positive T-lymphocyte numbers in HIV-infected participants at 180 days; changes in quantitative hepatitis B surface antigen levels at 180 days in the HBV-infected participants; and adherence to the study drugs. Conclusion: This randomized controlled study will provide data on the efficacy and safety of LC-plasma as a treatment for anal HPV infection and grade 2 or 3 anal intraepithelial neoplasia.

Probiotic for Pancreatic β-Cell Function in Type2 Diabetes: A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial.

Many clinical studies have proved the effectiveness of probiotics in metabolic disorders associated with insulin resistance. However, the impact of probiotic therapy on pancreatic β-cell function is ambiguous. The influence of probiotic supplementation vs. placebo on β-cell function in people with type2 diabetes (T2D) was assessed in a double-blind, single-center, randomized, placebo-controlled trial (RCT). Sixty-eight patients with T2D were selected for participation in the RCT. Patients were randomly allocated to consumption of live multistrain probiotics or a placebo for 8weeks, administered as a sachet formulation in double-blind treatment. The primary main outcome was the assessment of β-cell function as change in C-peptide and HOMA-β (homeostasis model assessment-estimated β-cell function), which was calculated using the HOMA2 calculator (Diabetes Trials Unit, University of Oxford). Secondary outcomes were the changes in glycemic control-related parameters, anthropomorphic variables, and cytokines levels. Analysis of covariance was used to assess the difference between groups. Supplementation with live multiprobiotic was associated with slight significant improvement of β-cell function (HOMA-β increased from 32.48 ± 13.12 to 45.71 ± 25.18; p = 0.003) and reduction of fasting glucose level (13.03 ± 3.46 vs 10.66 ± 2.63mmol/L and 234.63 ± 62.36 vs 192.07 ± 47.46mg/dL; p < 0.001) and HbA1c (8.86 ± 1.28 vs 8.48 ± 1.22; p = 0.043) as compared to placebo. Probiotic therapy significantly affects chronic systemic inflammation in people with T2D by reducing pro-inflammatory cytokine levels. Probiotic therapies modestly improved β-cell function in patients with T2D. Modulating the gut microbiota represents a new diabetes treatment and should be tested in more extensive studies. NCT05765292.

Recovery of Breakthrough Asthma Attacks Treated With Oral Steroids While on Monoclonal Antibody Therapy: Protocol for a Prospective Observational Study (BOOST).

Asthma attacks are a common and important problem. Someone experiences an asthma attack in the United Kingdom every 10 seconds. Asthma attacks cause coughing, wheezing, breathlessness, and chest tightness and are highly stressful for patients. They result in reduced quality of life, with days lost from work or school. Asthma attacks are treated with oral corticosteroids (OCSs), but these have many short- and long-term side effects. Asthma monoclonal antibodies (mAbs) have revolutionized the treatment of severe asthma by reducing asthma attacks and OCS burden by over 50%, but some people still experience attacks while on mAbs. The MEX study showed that residual asthma attacks are broadly eosinophilic (high fractional exhaled nitric oxide [FeNO]) or noneosinophilic (low FeNO), but it did not measure response to OCS treatment. There is an evidence gap in understanding the clinical and inflammatory responses that occur when using OCSs to treat residual asthma attacks in patients taking asthma mAbs. The primary objective is to compare the clinical recovery between high-FeNO and low-FeNO attacks after acute treatment with oral prednisolone among people established on long-term asthma mAb treatment. The exploratory objective is to compare the inflammatory response to acute treatment with oral prednisolone between high-FeNO and low-FeNO attacks. BOOST (Breakthrough Asthma Attacks Treated With Oral Steroids) is a single-center, prospective observational study of 60 adults established on long-term asthma mAb treatment who receive acute treatment with oral prednisolone (usual care) for an asthma attack. The primary outcome will be the proportion of treatment failure (the need to start oral prednisolone or antibiotics or an unscheduled health care visit for asthma, following an attack) at day 28. The secondary outcomes will be the change in forced expiratory volume in 1 second and the change in visual analogue scale symptom score between the stable state, attack, day 7, and day 28 visits. The exploratory outcomes include the changes in sputum, nasal, and blood inflammometry between the stable state, attack, day 7, and day 28 visits. The last asthma attack visit is anticipated to occur in December 2023. Data analysis and publication will take place in 2024. We will test the hypothesis that there is a difference in the rate of recovery of clinical and inflammatory measures between high-FeNO and low-FeNO asthma attacks that occur in patients on mAb therapy. The study data will help power a future randomized placebo-controlled trial of prednisolone treatment for nonsevere attacks in patients treated with asthma mAbs and will provide important information on whether corticosteroid treatment should be FeNO-directed. DERR1-10.2196/46741.

Efficiency and safety of Vortioxetine in the treatment of depressive disorders in cardiac patients

Importance of the problem. Diseases of the cardiovascular system are in the first place among the causes of death and disability in most industrialized countries, which is undoubtedly an urgent medical and social problem and causes significant economic damage. The prevalence of depressive disorders in modern society, according to WHO estimates, is quite high, and the causes of depressive disorders and methods for their correction in patients with various somatic diseases have been the subject of study by specialists around the world for many decades. The comorbidity of depressive disorders with cardiac pathology is beyond doubt, and the bidirectional relationship of these disorders significantly aggravates the condition of patients, worsens their quality of life and reduces adherence to treatment. The most important conditions for the use of antidepressants in cardiology practice are good tolerability, absence of toxic effect, minimal interaction with other drugs, and relative safety in case of overdose. Vortioxetine, being a modern multimodal antidepressant, demonstrates not only a sufficiently high antidepressant and anti-anxiety activity, but also has a procognitive effect, as well as minimal side effects and undesirable cross-interactions with other drugs, which is confirmed by international randomized placebo-controlled trials. The aim of this work was to evaluate the efficacy and safety of Vortioxetine in the treatment of concomitant depressive disorders in patients with coronary heart disease (CHD), angina pectoris 2-3 functional class (FC) (I 20.8 according to ICD-10), receiving complex therapy for the main (cardiological) diseases at the inpatient and outpatient stages of therapy. Materials and methods. The study included patients with a diagnosis of coronary artery disease, angina pectoris FC 2-3, hypertension 2-3, aged 45 to 66 years (mean age 57.1±1.1 years), receiving complex therapy for the underlying cardiac disease and Vortioxetine at a dose of 10-15 mg/day. within 8 weeks. Anxiety and depressive manifestations were assessed on the HADS scale, the level of cognitive impairment on the PDQ questionnaire, social functioning on the SF-36 questionnaire, the general clinical impression on the CGI-C scale, and the main indicators of the functioning of the cardiovascular system upon admission to the hospital, after 4 weeks of hospitalization. treatment and another 4 weeks after discharge during the period of outpatient observation.The result of the combined therapy of patients with cardiac pathology and concomitant depressive disorder (basic therapy for CVD and Vortioxetine) was not only an improvement in the cardiovascular system (decrease in heart rate, blood pressure, the frequency of anginal pain, an increase in exercise tolerance), but also the relief of depressive manifestations, which contributed to an increase in the adherence of cardiological patients to the implementation of medical recommendations, and, in turn, led to a decrease in the level of end points—mortality, hospitalization rates, progression of chronic heart failure and disability. Conclusions. Appointment of Vortioxetine to cardiac patients with concomitant depressive disorder of moderate severity is quite effective not only in terms of relief of painful manifestations of the CVS, but also leads to a reduction in anxiety-depressive disorders and an improvement in cognitive and social functioning. The good tolerability of the drug makes it possible to recommend it for the treatment of depressive disorders in cardiological patients in a hospital setting and in outpatient practice.

A commentary on "perioperative versus postoperative calcium and vitamin d supplementation to prevent symptomatic hypocalcemia after total thyroidectomy: a randomized placebo controlled trial".

Department of Gastrointestinal Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang 110032, China Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: Department of Gastrointestinal Surgery, The Fourth Affiliated Hospital, China Medical University, No.4 Chongshan East Road, Shenyang 110032, China. Telephone: +86-189-0091-2404. E-mail address: [email protected] (C-D. Zhang). This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/

P.021 Botulinum toxin type a for Parkinson’s Disease - related painful foot dystonia

Background: Pain is a frequent symptom in Parkinson’s disease (PD), and the therapeutic alternatives are scarce. The goal of this trial was to assess the effects of botulinum toxin type A (BTXA) in the treatment of foot dystonia in PD. Methods: Randomized placebo-controlled trial (RCT) (double-blind parallel-group study) evaluating the safety and efficacy of BTXA for PD-related painful foot dystonia using 100 units of BTXA/placebo, followed by an open-label phase. The primary outcome was a change in pain on the King’s Parkinson’s disease Pain scale and on a visual analogue scale at 6, 12 and 24 weeks. Secondary outcomes included the percentage of responders, clinical global impression, MDS-UPDRS, PDQ-39 scores, and adverse events. Results: 40 subjects were screened and 33 were enrolled. The RCT blind will be opened in March 2023 after the final study visit and data will be available for presentation at the June 2023 conference. The current open-label phase has revealed a preliminary that the toxin is safe and effective in reducing pain in PD-related foot dystonia with 84% of participants noticing a significant benefit. Conclusions: According to our preliminary data, targeted BTXA injections are a safe and effective treatment in patients with foot dystonia and PD.

GS-007 - Faecal microbiota transplant restores gut barrier function and augments ammonia metabolism in patients with advanced cirrhosis: a randomised single-blind placebo-controlled trial

GS-007 - Faecal microbiota transplant restores gut barrier function and augments ammonia metabolism in patients with advanced cirrhosis: a randomised single-blind placebo-controlled trial

Ethical Considerations Surrounding Vaccine Development During A Public Health Crisis

Epidemics and Pandemics have been plaguing mankind since many centuries, and are a cause of major healthcare expense in modern times. The novel coronavirus pandemic of 2019-2020 spread worldwide faster than many previous pandemics, including EBOLA in 2017. Although personal protective equipment, and social distancing slowed the outbreak, a vaccine is needed to ensure global immunization and to stop this deadly outbreak. Developing a vaccine in times of a public health crisis comes with a lot of ethical considerations, including overlooking proper informed consent, the issue of using placebo in control arm of trials, extended timelines of development of vaccines, randomized placebo control trial of secondary vaccine once the first vaccine is approved, and utilizing vulnerable population for trials. These issues are often overlooked due to the urgency of the situation, and the need of developing a cure/vaccine can lead to potential oversight of many regulations. We discuss some of these issues related to vaccine development in a pandemic situation in this commentary paper. We also discuss some of the arguments supporting a secondary vaccine development such as logistical/economic issue, better efficacy, and the conditions of Equipoise.

Evaluating the efficacy of propofol in attenuating the cardiorespiratory response to extubation: single-blinded randomised placebo-controlled trial

Evaluating the efficacy of propofol in attenuating the cardiorespiratory response to extubation: single-blinded randomised placebo-controlled trial

Laughter as medicine: A systematic review and meta-analysis of interventional studies evaluating the impact of spontaneous laughter on cortisol levels.

Laughter as an expression of humor has been recognized as good medicine for centuries. The health benefits of humor-induced well-being remain unclear and thus we conducted a systematic review and meta-analysis of interventional studies to evaluate the impact of spontaneous laughter on stress response as measured by cortisol levels. Systematic review and meta-analysis. MEDLINE/PubMed, EMBASE, PsycINFO, Scopus, and Clinicaltrials.gov. Interventional studies, which could be either randomized placebo-controlled trials (RCTs) or quasi-experimental studies, conducted in adults that compared any spontaneous laughter intervention to a controlled setting and reported changes in cortisol levels were selected. We examined the impact of laughter on percentage change in cortisol levels by calculating pooled estimates of the absolute differences between arithmetic means before and after interventions as compared to control using random-effects model. Eight studies (315 participants; mean age 38.6) met our inclusion criteria; four were RCTs and four were quasi-experiment studies. Five studies evaluated the impact of watching a humor/comedy video, two studies evaluating laughter sessions administered by a trained laughter therapist, and one study evaluating a self-administered laughter program. Pooling these data showed a significant reduction in cortisol levels by 31.9% (95%CI -47.7% to -16.3%) induced by laughter intervention compared to control group with no evidence of publication bias (P = 0.66). Sensitivity analyses demonstrated that even a single laughter session induced a significant reduction of 36.7% in cortisol (95%CI -52.5% to -20.8%). In addition, analyses including the four RCTs reinforced these results by demonstrating a significant reduction in cortisol levels promoted by laughter as compared to the placebo arm [-37.2% (95%CI -56.3% to -18.1%)]. Current evidence demonstrates that spontaneous laughter is associated with greater reduction in cortisol levels as compared with usual activities, suggesting laughter as a potential adjunctive medical therapy to improve well-being. Registration number: CRD42021267972.

The effect of bromelain in periodontal surgery: a double-blind randomized placebo-controlled trial

BackgroundPeriodontitis is a persistent inflammatory condition. Eliminating the infection and reducing its risk factors are the first steps in treating periodontitis. When the anti-infective therapy is complete, there may still be deep periodontal pockets and prolonged inflammation. Surgical pocket reduction or elimination is indicated under these circumstances. We aimed to evaluate the effect of bromelain on bleeding on probing (BOP), gingival index (GI), and plaque index (PI) after pocket elimination surgery.MethodsThis double-blind randomized placebo-controlled trial included 28 candidates for pocket elimination surgery referred to the private office of a periodontist in Bandar Abbas, Iran, from April 18 to August 18, 2021. Patients’ general characteristics, such as age and sex, were recorded. Additionally, periodontal indices including BOP, PI, GI, and pocket probing depth (PPD) were evaluated in all subjects. All patients underwent pocket elimination surgery. Afterwards, they were randomized into two groups. The first group received 500 mg Anaheal (bromelain) capsules twice a day before meal for one week. The second group received placebo, prepared in similar shape and color by the same pharmaceutical company. BOP, PI, GI, and PPD were assessed four weeks after completion of the treatment course (five weeks after surgery).ResultsFour weeks after intervention, BOP was significantly lower with Anaheal compared to placebo (0% vs. 35.7%, P = 0.014). However, there was no significant difference in GI between groups (P = 0.120). Mean PI was lower (17.71 ± 2.12 vs. 18.28 ± 2.49) and mean PPD higher (3.10 ± 0.71 vs. 2.64 ± 0.45) in the Anaheal group, but the differences did not reach statistically significant levels (P = 0.520 and P = 0.051, respectively).ConclusionsOne-week treatment with Anaheal at a dose of 1 g/d after pocket elimination surgery resulted in significantly lower BOP compared to placebo.Trial registrationIranian Registry of Clinical Trials (IRCT), IRCT20201106049289N1. Registered 06/04/2021. Registered prospectively, https://www.irct.ir/trial/52181.

Seizure-free days as a novel outcome in patients with Lennox-Gastaut syndrome: Post hoc analysis of patients receiving cannabidiol in two randomized controlled trials.

In this post hoc analysis, we aimed to assess seizure-free days as a potential new outcome measure to use in randomized placebo-controlled trials (RCTs) of patients with Lennox-Gastaut syndrome (LGS). In two phase 3 RCTs (GWPCARE3, GWPCARE4), eligible patients were randomized to receive plant-derived highly purified cannabidiol (CBD; Epidiolex® in the USA; 100 mg/mL oral solution) at 10 mg/kg/day (CBD10; GWPCARE3 only), at 20 mg/kg/day (CBD20), or matched placebo. The treatment period comprised a 2-week dose titration and a 12-week maintenance period. This post hoc analysis evaluated the least-squares (LS) mean changes from baseline and difference versus placebo in the number of drop or total seizure-free days per 28 days during the treatment period or maintenance period alone. LS mean changes were estimated using an analysis of covariance model, with categorical age and baseline number of drop or total seizure-free days as covariates, and treatment group as a fixed factor. A total of 396 patients were included in this post hoc analysis. During the 14-week treatment period, LS mean changes from baseline in number of drop seizure-free days per 28 days for patients receiving placebo (n = 161), CBD10 (n = 73), and CBD20 (n = 162) were 2.81 (95% confidence interval [CI] = 1.75-3.88), 5.64 (95% CI = 4.08-7.20), and 6.45 (95% CI = 5.39-7.52), respectively. The LS mean differences in number of drop seizure-free days versus placebo were 2.83 (95% CI = .98-4.68) for CBD10 and 3.64 (95% CI = 2.18-5.10) for CBD20. For total seizure-free days, LS mean differences versus placebo were 2.63 (95% CI = .92-4.34) for CBD10 and 3.50 (95% CI = 2.16-4.85) for CBD20. The improvements from baseline in seizure-free days during the maintenance period alone were similar to the entire treatment period. Drop and total seizure-free days represent potential new and clinically meaningful endpoints for future RCTs in patients with LGS.

The Integrated Stress Response Is Modulated by eIF2B Agonist DNL343: Results From Phase 1 Healthy Subject and Phase 1b ALS Patient Studies. (P8-8.010)

The Integrated Stress Response Is Modulated by eIF2B Agonist DNL343: Results From Phase 1 Healthy Subject and Phase 1b ALS Patient Studies. (P8-8.010)

Follow-up Imaging After Thrombolysis: FIAT, A Randomized Trial

Current protocols for treatment of acute ischemic stroke with intravenous thrombolytics, such as alteplase (tPA) and tenecteplase (tNK), recommend the completion of a routine non-contrast head CT at 24 hours post treatment to evaluate for hemorrhage prior to the initiation of antiplatelet therapy for secondary stroke prevention. This guideline was instituted because it had been part of the protocol in the NINDS multicenter randomized placebo-controlled trial that showed the benefit of IV thrombolytics within 3 hours of stroke onset. Recent observational studies indicate that the repeat (stability) head CT rarely alters clinical management, in the absence of neurological worsening or evidence of clinical signs of hemorrhagic conversion, such as seizures, severe headache, or novel acute deficits. A solitary CT carries with it a non-negligible dose of radiation with additive cost to the medical system at large. We aimed to identify, with a randomized, blinded outcome assessment trial, if a routine head CT at 24 hours, in the absence of clinical indication, negatively influences clinical outcomes. We enrolled 58 patients, and evaluated differences between groups with t-tests. We also evaluated differences between outcomes (90 day modified Rankin Scale, mRS and change in National Institutes of Health Stroke Scale, NIHSS) from pretreatment to discharge using multivariable logistic regression, including age, baseline NIHSS, and group as independent variables. We found no added benefit of routine CT on either outcome measure. It is likely safe to forgo follow up imaging after thrombolysis in the absence of clinical decompensation.

The effect of nettle vaginal cream on subjective symptoms of vaginal atrophy in postmenopausal women

Background and objectiveVaginal atrophy is a condition where the vaginal epithelium gets thinner and includes symptoms, such as vaginal dryness, abnormal vaginal discharge, vaginal bleeding, dyspareunia, and sexual problems. Hormone therapy is associated with some problems and some women prefer herbal medicine to reduce vaginal atrophy. Considering the phytoestrogenic compounds present in the nettle, this study aimed to investigate the effect of the nettle vaginal cream on subjective symptoms of vaginal atrophy in postmenopausal women. Materials and methodsThis triple-blind randomized placebo-controlled clinical trial study was conducted on 84 eligible postmenopausal women aged 45–60 years, who referred to comprehensive health service centers in Aliabad Katul in 2021–2022. Women eligible for the study received 5% nettle vaginal cream and placebo for 8 weeks. Subjective symptoms of vaginal atrophy were assessed before, four and eight weeks after the intervention. Data collection tools included a checklist for research unit selection, individual and midwifery characteristics questionnaire, vaginal assessment scale (VAS), vaginal pH, laboratory results of the vaginal maturation value (VMV). Data analysis was performed using SPSS software (version 21) and independent t-test, Mann-Whitney, chi-square, Two-way analysis of variance and analysis of covariance. P value less than 0.05 was considered significant. ResultsSubjective symptoms of vaginal atrophy decreased significantly after the intervention compared to before the intervention in both the nettle and placebo groups (p < 0.001), but in the comparison between groups four weeks and eight weeks after the intervention, the subjective symptoms of vaginal atrophy in nettle group decreased significantly (p < 0.001). In the nettle group, the scores of vaginal burning, vaginal dryness, vaginal itching and dyspareunia significantly improved after the intervention compared to before the intervention (p < 0.001). Also, in the nettle group compared to the placebo group, after the intervention, vaginal burning and vaginal dryness score (p < 0.001) and vaginal itching score (0.004) improved significantly. ConclusionBased on the results of the present study, Nettle vaginal cream reduced subjective symptoms of vaginal atrophy, including vaginal burning, vaginal dryness, vaginal itching, and dyspareunia in postmenopausal women, so it is a cost-effective, available and do not have the side effects product that can be useful for menopausal women.

Abstract 5247: The effect of aspirin on the transcriptional landscape of the colon

Abstract Colorectal cancer (CRC) remains the second leading cause of cancer mortality in the United States. Aspirin is the most promising CRC prevention agent with significant data supporting long-term use with a reduction in the incidence of adenomatous polyps and colorectal cancer. The adoption of aspirin as a preventive agent has been limited by an incomplete understanding of aspirin’s mode of action in humans. To elucidate the mechanism of aspirin prevention, we sought to identify aspirin-associated transcriptional changes within the colon. To accomplish this objective, we performed RNA sequencing of biopsy-derived colonic epithelial cells from participants enrolled (N=180) in our ongoing aspirin randomized placebo-control trial (RCT) program, “ASPirin Intervention for the REDuction of colorectal cancer risk” (ASPIRED). Individuals with a recent resection of an adenoma were eligible. Participants for whom epithelial cells from rectosigmoid mucosal biopsies were successfully obtained at both pre- and post-treatment timepoints (n=130) were included in this analysis. Participants were randomized to once-daily placebo (n=45), low-dose aspirin (81 mg) (n=46), or standard-dose aspirin (325 mg) (n=39) for 8-12 weeks. For each timepoint, we performed Illumina RNA 100-bp paired-end sequencing of 4,000 fluorescence-activated cell-sorted (FACS) colonic epithelial cells (CD45-; EpCAM+). Transcriptomic read alignment and read counts per gene were obtained using STAR and Salmon. Quality control measures removed 52 participants (20 placebo, 18 low-dose aspirin, and 14 standard-dose aspirin) from the analysis. No significant differences in age, gender, ethnicity, or BMI were observed between placebo and aspirin-treated participants. We then identified genes whose expression is modulated by aspirin exposure (low and standard dose aspirin) while controlling for baseline gene expression differences between placebo and aspirin-exposed patients and for intra-sample gene expression variability using Dream. We found 57 genes were significantly differentially expressed in aspirin-treated participants at an FDR &amp;lt; 0.10. AGR2, which is a CRC oncogene that is upregulated by prostaglandin E2 (PGE2), was significantly downregulated by aspirin treatment suggesting aspirin modules the expression of PGE2 responsive genes in the colonic epithelium. Gene enrichment analysis found aspirin significantly downregulated scaffold proteins (e.g. KRT8, KRT18, and ACTB) and structural ribosomal RNA binding proteins. These pathways are critical processes in epithelial cell differentiation. This finding supports previous in vitro evidence that aspirin results in cell composition changes within the colonic epithelium favoring stem-like cell states, which may underlie its preventive effect. Citation Format: Jonathan M. Downie, Connor M. Geraghty, Thaddeus S. Stappenbeck, Ömer H. Yilmaz, David A. Drew, Andrew T. Chan. The effect of aspirin on the transcriptional landscape of the colon. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5247.

Prevention of Dry Socket with Ozone Oil-Based Gel after Inferior Third Molar Extraction: A Double-Blind Split-Mouth Randomized Placebo-Controlled Clinical Trial

Tooth extraction is followed by a sequence of elaborate local changes affecting hard and soft tissues. Dry socket (DS) can occur as intense pain around and in the extraction site, with an incidence from 1-4% after generic tooth extraction to 45% for mandibular third molars. Ozone therapy has gained attention in the medical field because of its success in the treatment of various diseases, its biocompatible properties and its fewer side effects or discomfort than drugs. To investigate the preventive effect of the sunflower oil-based ozone gel Ozosan® (Sanipan srl, Clivio (VA), Italy) on DS, a double-blind split-mouth randomized placebo-controlled clinical trial was conducted according to the CONSORT guidelines. Ozosan® or the placebo gel were put in the socket, and the gels were washed off 2 min later. In total, 200 patients were included in our study. The patient population comprised 87 Caucasian males and 113 Caucasian females. The mean age of the included patients was 33.1 ± 12.4 years. Ozosan reduced the incidence of DS after inferior third molar extraction from 21.5% of the control to 2% (p < 0.001). Concerning the dry socket epidemiology, the incidence was not significantly correlated with gender, smoking or mesioangular, vertical or distoangular Winter's classification. Post hoc power calculation showed a power of 99.8% for this data, with alpha = 0.001.

(162) A Multicenter Randomized Placebo-Controlled Trial of Intravenous Thyroxine for Heart-Eligible Brain-Dead Organ Donors

(162) A Multicenter Randomized Placebo-Controlled Trial of Intravenous Thyroxine for Heart-Eligible Brain-Dead Organ Donors

Systematic review and meta-analysis of randomized control trials addressing efficacy and safety of desmopressin for females with nocturia

Aim:To conduct a systematic review and meta-analysis of all randomized placebo-controlled trials (RCTs) that evaluated the efficacy and safety of desmopressin versus placebo among females with nocturia. Methods:PubMed, Scopus, Web of Science, CENTRAL, and Google Scholar databases were searched from inception until 15-November-2022. The included studies were evaluated for risk of bias (Cochrane Tool). The endpoints were summarized as mean difference (MD) or risk ratio (RR) with 95% confidence interval (CI). Subgroup analysis based on the dose of desmopressin ( ≤50μg and >50μg) was conducted. In addition, meta-regression was performed to examine the impact of age and body mass index (BMI) on the endpoints. Results:Nine RCTs with 2852 patients (desmopressin=1110, placebo=1742) were analyzed. The overall risk of bias was low. Compared with placebo, desmopressin significantly reduced the mean number of nocturnal voids (MD=-0.51, 95% CI [-0.70, -0.31], p<0.001), prolonged the duration of the first sleep period (MD=69.06 min, 95% CI [46.54, 91.59], p<0.001), and increased the 33% responder rate (RR=1.30, 95% CI [1.13, 1.50], p<0.001). Subgroup analyses according to desmopressin dose ( ≤50μg and >50μg) showed similar significant differences compared with placebo. Meta-regression showed less improvement in the number of nocturnal voids with the increased age and BMI. There was no significant difference between both groups regarding the rate of overall adverse events (RR=1.11, 95% [0.94, 1.32], p=0.22). Conclusion:Desmopressin was safe and effective in improving nocturia among females. Higher dose of desmopressin (>50μg) correlated with better efficacy. Age and BMI impacted the mean number of nocturnal voids.