Participants In Placebo Group Research Articles

A Meta-Analysis of Levofloxacin for Contacts of Multidrug-Resistant Tuberculosis.

Data from randomized trials evaluating the effectiveness of tuberculosis (TB) preventive treatment for contacts of multidrug-resistant (MDR)-TB are lacking. Two recently published randomized trials that did not achieve statistical significance provide the opportunity for a meta-analysis. We conducted combined analyses of two phase 3 trials of levofloxacin MDR-TB preventive treatment - Levofloxacin for the Prevention of Multidrug-Resistant Tuberculosis (VQUIN) trial and the Levofloxacin preventive treatment in children exposed to MDR-TB (TB-CHAMP) trial. Following MDR-TB household exposure, VQUIN enrolled mainly adults in Vietnam; TB-CHAMP enrolled mainly young children in South Africa. Random assignment in both trials was 1:1 at the household level to daily levofloxacin or placebo for 6 months. The primary outcome was incident TB by 54 weeks. We estimated the treatment effect overall using individual participant data meta-analysis. The VQUIN trial (n=2041) randomly assigned 1023 participants to levofloxacin and 1018 participants to placebo; TB-CHAMP (n=922) assigned 453 participants to levofloxacin and 469 participants to placebo. Median age was 40 years (interquartile range 28 to 52 years) in VQUIN and 2.8 years (interquartile range 1.3 to 4.2 years) in TB-CHAMP. Overall, 8 levofloxacin-group participants developed TB by 54 weeks versus 21 placebo-group participants; the relative difference in cumulative incidence was 0.41 (95% confidence interval [CI] 0.18 to 0.92; P=0.03). No association was observed between levofloxacin and grade 3 or above adverse events (risk ratio 1.07, 95% CI 0.70 to 1.65). Musculoskeletal events of any grade occurred more frequently in the levofloxacin group (risk ratio 6.36, 95% CI 4.30 to 9.42), but not among children under 10 years of age. Overall, four levofloxacin-group participants and three placebo-group participants had grade 3 events. In this meta-analysis of two randomized trials, levofloxacin was associated with a 60% relative reduction in TB incidence among adult and child household MDR-TB contacts, but with an increased risk of musculoskeletal adverse events. (Funded by the Australian National Health and Medical Research Council, UNITAID, and others.).

Xylitol for the prevention of acute otitis media episodes in children aged 1–5 years: a randomised controlled trial

ObjectiveTo investigate the regular use of xylitol, compared with sorbitol, to prevent acute otitis media (AOM), upper respiratory tract infections (URTIs) and dental caries.DesignBlinded randomised controlled trial with a 6-month...

Icosapent ethyl therapy for very high triglyceride levels: a 12-week, multi-center, placebo-controlled, randomized, double-blinded, phase III clinical trial in China

ObjectivesEicosapentaenoic acid in its ethyl ester form is the single active component of icosapent ethyl (IPE). This study was a phase III, multi-center trial assessing the safety and efficiency of IPE for treating very high triglyceride (TG) in a Chinese cohort.MethodsPatients having TG levels (5.6–22.6 mmol/L) were enrolled and randomly assigned to receive a treatment of oral intake of 4 g or 2 g/day of IPE, or placebo. Before and after 12 weeks of treatment, TG levels were assessed and the median was calculated to determine the change between the baseline and week 12. In addition to examining TG levels, the impact of such treatments on other lipid changes was also investigated. The official Drug Clinical Trial Information Management Platform has registered this study (CTR20170362).ResultsRandom assignments were performed on 373 patients (mean age 48.9 years; 75.1% male). IPE (4 g/day) lowered TG levels by an average of 28.4% from baseline and by an average of 19.9% after correction for placebo (95% CI: 29.8%-10.0%, P < 0.001). In addition, plasma concentration of non-high-density lipoprotein cholesterol (non-HDL-C), very low-density lipoprotein (VLDL) cholesterol, and VLDL-TG remarkedly reduced after IPE (4 g/day) treatment by a median of 14.6%, 27.9%, and 25.2%, respectively compared with participants in placebo group. Compared to the placebo, neither 4 nor 2 g of IPE daily elevated LDL-C levels with statistical significance. IPE was well tolerated by all the treatment groups.ConclusionsIPE at 4 g/day dramatically lowered other atherogenic lipids without a noticeable increase in LDL-C, thereby decreasing TG levels in an exceptionally high-TG Chinese population.

Novel Method for Management of Bothersome Bleeding Associated With Etonogestrel Drug Implant [ID: 1380127

INTRODUCTION: Nexplanon (etonogestrel drug implant [EDI]) is an effective, implantable subdermal contraceptive that releases progestin over 3 years for suppression of ovulation and thickening of cervical mucus. A significant portion of EDI patients will remove their device prematurely because of bothersome episodes of frequent/prolonged bleeding. In patients with abnormal uterine bleeding, induction of a withdrawal bleed, with the goal of reducing excessive bleeding, is a common approach. There is no standard approach to treating prolonged and/or excessive bleeding with EDI in place. METHODS: This is a randomized double-blinded placebo-controlled trial of 51 patients desiring EDI for contraception. Patients received norethindrone (NTA) 5 mg or placebo daily for 1 week every 4 weeks for a total of 6 months. RESULTS: No patients in the treatment arm requested removal because of bothersome bleeding as defined by International Federation of Gynecology and Obstetrics/World Health Organization criteria. In contrast, 24% of the placebo group participants requested removal of the device at or before 6 months from placement for a variety of reasons including bothersome bleeding. 9% from the treatment group requested early removal; however, none for bothersome bleeding. 80% of the treatment group participants had a satisfactory bleeding pattern. One participant in the treatment arm complained of unsatisfactory amenorrhea. CONCLUSION: We propose a novel method to manage bothersome bleeding associated with EDI. Our data suggest that cyclic NTA is an effective method to treat bothersome bleeding in patients using etonogestrel implants for contraception and warrants further study.

Beyond migraine headache day reduction: Clinically meaningful improvement in disability (MIDAS score) in the absence of greater than 50% reductions in monthly migraine days with galcanezumab (P10-12.008)

Beyond migraine headache day reduction: Clinically meaningful improvement in disability (MIDAS score) in the absence of greater than 50% reductions in monthly migraine days with galcanezumab (P10-12.008)

Abstract WP153: Tirofiban Increase Symptomatic Intracranial Hemorrhage After Endovascular Therapy In Cardio-embolized Stroke Patients: Insight From Rescue Bt Trial

Introduction: Efficacy and safety of tirofiban in endovascular therapy among cardio-embolized ischemic stroke patients remains controversial. We aimed to assess effects of tirofiban before endovascular therapy in cardio-embolized stroke patients. Methods: This is a post hoc analysis of Endovascular Treatment With vs Without Tirofiban for Patients with Large Vessel Occlusion Stroke (RESCUE BT) trial. Before endovascular therapy, participants were randomized to tirofiban or placebo group in ratio of 1:1. Tirofiban was administrated as a bolus dose of 10 ug/kg, followed by continuous infusion of 0.15 ug/kg /min for up to 24-hour. We collected cardio-embolized stroke patients according to Trial of Org 10172 in Acute Stroke Treatment classification. The efficacy outcome was global disability at 90-day assed by modified Rankin Scale (mRS). The primary safety outcome was symptomatic intracranial hemorrhage (sICH) assessed by Heidelberg bleeding classification within 48-hour. Secondary safety outcome was any radiologic intracranial hemorrhage and death at 90-day. Results: 406 cardio-embolized stroke patients were collected. Tirofiban did not correlated to favorable shift to lower 90-day mRS (adjusted odds ratio [aOR], 0.91; 95% CI, 0.64-1.3; P = 0.617). However, tirofiban subgroup had a significantly higher risk of sICH within 48-hour (aOR, 3.26; 95% CI, 1.4-7.57; P = 0.006) compared with placebo group. The aOR was 1.44 (95% CI, 0.94-2.19; P = 0.094) for any intracranial hemorrhage and 1.48 (95% CI, 0.88-2.52; P = 0.143) for death at 90-day. Conclusions: Tirofiban increased symptomatic intracranial hemorrhage after endovascular therapy in cardio-embolized stroke patients. Figure 1 . Outcomes of endovascular therapy in cardio-embolic stroke participants in tirofiban vs placebo group.

Sensory stimulation improves daily functions in Alzheimer’s disease

AbstractBackgroundAbnormal neuronal function in Alzheimer’s disease (AD) is characterized by unbalanced neuronal excitatory‐inhibitory tone, distorted neuronal synchrony, and network oscillations, presumably contributing to the pathogenesis of the disease and accelerating disease progression. The probability that abnormal neuronal activity directly contributes to the pathogenesis of the disease has been recently proposed. It has been demonstrated that induction of synchronized gamma oscillation of neuronal networks by sensory stimulation reverses AD‐related pathological markers in transgenic mice carrying AD‐related human pathological genes. The current study evaluated whether non‐invasive sensory stimulation inducing cortical 40 Hz gamma oscillation is clinically beneficial for patients in AD spectrum.MethodThe data studied here is from Overture clinical trial (NCT03556280). The study included a treatment group, where participants received daily, 1‐hour, 40Hz gamma visual and auditory stimulation for 6‐months at home, and a placebo group. To assess the treatment efficacy on daily functional abilities, the Alzheimer’s Disease Cooperative Study ‐ Activities of Daily Living (ADCS‐ADL) scale was used. Assessments were made at baseline and every four weeks throughout the study. ADCS‐ADL consists of 23‐items where each item aims to assess different functional abilities. The change in ADCS‐ADL as well as change in each individual item’s score between the treatment group (n = 33) and the placebo group (n‐ = 19) were compared using a mixed model for repeated measures (MMRM).ResultWe observed that treatment group participants were able to maintain their functional abilities while placebo group participants showed a decline as assessed by ADCS‐ADL, p&lt;0.001. Within the instrumental ADCS‐ADL individual items, the most significant differences between the two groups, all favoring treatment group, were observed in: (1) Attentive participation in conversations, p&lt;0.001, and (2) Finding personal belongings, p&lt;0.043.ConclusionOur results suggest that daily, 1‐hour 40Hz gamma sensory stimulation may help prevent functional decline in patients with AD spectrum disorder. Preventing functional loss would help both patients and caregivers. Furthermore, it may reduce the need for institutionalization and reduce healthcare costs. Larger studies are planned to confirm these initial findings on the benefits of gamma sensory stimulation on function.

Science, Medicine, and the Anesthesiologist

Science, Medicine, and the Anesthesiologist

34420 Perspective of patients with erythropoietic protoporphyria treated with dersimelagon, a selective melanocortin-1 receptor agonist: Results of the ENDEAVOR study exit questionnaire

Background: Erythropoietic protoporphyria (EPP) imposes a significant burden on the quality of life (QoL) of patients. Dersimelagon, a novel synthetic, orally administered, selective melanocortin-1 receptor agonist, has demonstrated statistically and clinically significant improvement from baseline in average daily time to first prodromal symptoms in a phase 2 clinical trial. Methods: ENDEAVOR was a multicenter, phase 2, randomized double-blind, placebo-controlled study with a 16-week treatment and 6-week follow-up period. Here we report the results of a post hoc analysis assessing the clinical benefit of dersimelagon treatment and patient perspective of QoL using an online exit questionnaire composed of 28 close-ended questions completed after week 22 visit or post study completion. Participants rated their perceived change since the start of the study. Results: Of 102 participants, 75 (placebo, n = 24; dersimelagon, 100 mg, n = 28, 300 mg n = 23) completed the questionnaire. More recipients of dersimelagon (100 mg, 57.6%; 300 mg 31.4%) rated their EPP as “very much better” than placebo group participants (5.9%). They were also “much more often” (100 mg, 69.7%; 300 mg 48.6%) able to be outside at the end of the study than patients in the placebo group (8.8%). More participants who received dersimelagon (100 mg, 72.7%; 300 mg 62.9%) reported being “very satisfied” with the study drug vs placebo recipients (14.7%). Conclusions: A greater proportion of patients who received dersimelagon reported improvements in their EPP and associated disease impacts than placebo group participants. The findings from the exit questionnaire support the results from the primary analysis and the potential use of dersimelagon for treatment of patients with EPP.

Tixagevimab–cilgavimab for treatment of patients hospitalised with COVID-19: a randomised, double-blind, phase 3 trial

BackgroundTixagevimab–cilgavimab is a neutralising monoclonal antibody combination hypothesised to improve outcomes for patients hospitalised with COVID-19. We aimed to compare tixagevimab–cilgavimab versus placebo, in patients receiving remdesivir and other standard care.MethodsIn a randomised, double-blind, phase 3, placebo-controlled trial, adults with symptoms for up to 12 days and hospitalised for COVID-19 at 81 sites in the USA, Europe, Uganda, and Singapore were randomly assigned in a 1:1 ratio to receive intravenous tixagevimab 300 mg–cilgavimab 300 mg or placebo, in addition to remdesivir and other standard care. Patients were excluded if they had acute organ failure including receipt of invasive mechanical ventilation, extracorporeal membrane oxygenation, vasopressor therapy, mechanical circulatory support, or new renal replacement therapy. The study drug was prepared by an unmasked pharmacist; study participants, site study staff, investigators, and clinical providers were masked to study assignment. The primary outcome was time to sustained recovery up to day 90, defined as 14 consecutive days at home after hospital discharge, with co-primary analyses for the full cohort and for participants who were neutralising antibody-negative at baseline. Efficacy and safety analyses were done in the modified intention-to-treat population, defined as participants who received a complete or partial infusion of tixagevimab–cilgavimab or placebo. This study is registered with ClinicalTrials.gov, NCT04501978 and the participant follow-up is ongoing.FindingsFrom Feb 10 to Sept 30, 2021, 1455 patients were randomly assigned and 1417 in the primary modified intention-to-treat population were infused with tixagevimab–cilgavimab (n=710) or placebo (n=707). The estimated cumulative incidence of sustained recovery was 89% for tixagevimab–cilgavimab and 86% for placebo group participants at day 90 in the full cohort (recovery rate ratio [RRR] 1·08 [95% CI 0·97–1·20]; p=0·21). Results were similar in the seronegative subgroup (RRR 1·14 [0·97–1·34]; p=0·13). Mortality was lower in the tixagevimab–cilgavimab group (61 [9%]) versus placebo group (86 [12%]; hazard ratio [HR] 0·70 [95% CI 0·50–0·97]; p=0·032). The composite safety outcome occurred in 178 (25%) tixagevimab–cilgavimab and 212 (30%) placebo group participants (HR 0·83 [0·68–1·01]; p=0·059). Serious adverse events occurred in 34 (5%) participants in the tixagevimab–cilgavimab group and 38 (5%) in the placebo group.InterpretationAmong patients hospitalised with COVID-19 receiving remdesivir and other standard care, tixagevimab–cilgavimab did not improve the primary outcome of time to sustained recovery but was safe and mortality was lower.FundingUS National Institutes of Health (NIH) and Operation Warp Speed.

Topical lidocaine anesthesia for nasopharyngeal sampling – a double-blind randomized placebo-controlled trial

Introduction and aim. The aim of this study is to evaluate the effects of topical lidocaine application for nasopharyngeal sampling, on pain perception, the comfort of the patients, and the application difficulty for healthcare staff. Material and methods. This study conducted with 100 healthy volunteers (50 participants in Lidocaine group and 50 participants in Placebo group). Two ml of a solution containing 10 mg/ml of lidocaine was applied to each nostril of the participants in the Lidocaine group, and the same dose of 0.9% NaCl to the Placebo group. We compared the changes in pain intensity and discomfort intensity using two numerical rating scales, the frequency of undesirable reactions, and the judgment of the practitioner staff. Results. There were statistically significant decreases in pain and discomfort scores in the Lidocaine group. Similarly, there were statistically significant decreases in the frequency of all undesirable reactions except “grimace”, in the second sampling in the Lidocaine group, however, there was a statistically significant decrease only in “holding staff’s hand” in second sampling in the Placebo group. Conclusion. Intranasal lidocaine application reduces the pain that occurs during nasopharyngeal sampling and makes the procedure easier for the patient and the healthcare worker.

Effect of Memantine on Prolonging Safe Driving in Early AD: a Pilot Study.

BackgroundTo determine the feasibility of conducting an RCT on the potential effectiveness of memantine hydrochloride in prolonging safe driving in mild AD.MethodsA placebo-controlled, double blind randomized trial was conducted. Forty-three individuals ≥60 with mild AD met screening criteria and were randomized. Driving ability was measured by a standardized on-road driving test. Outcomes were driving capacity at 6 and 12 months and completion of the 12-month intervention.ResultsOf 43 participants randomized, 59% of the memantine group and 52% of the placebo group completed the on-road test at 12 months (p = .66). All 13 memantine group participants maintained their driving status at 12 months, whereas only 8 of the 11 placebo group participants did (p = .040, OR = 4.45).ConclusionsResults provide the framework for designing a rigorous multisite clinical trial of memantine effect on maintaining driving capacity in mild AD.

Safety and efficacy of a three-dose regimen of Plasmodium falciparum sporozoite vaccine in adults during an intense malaria transmission season in Mali: a randomised, controlled phase 1 trial

WHO recently approved a partially effective vaccine that reduces clinical malaria in children, but increased vaccine activity is required to pursue malaria elimination. A phase 1 clinical trial was done in Mali, west Africa, to assess the safety, immunogenicity, and protective efficacy of a three-dose regimen of Plasmodium falciparum sporozoite (PfSPZ) Vaccine (a metabolically active, non-replicating, whole malaria sporozoite vaccine) against homologous controlled human malaria infection (CHMI) and natural P falciparum infection. We recruited healthy non-pregnant adults aged 18-50 years in Donéguébougou, Mali, and surrounding villages (Banambani, Toubana, Torodo, Sirababougou, Zorokoro) for an open-label, dose-escalation pilot study and, thereafter, a randomised, double-blind, placebo-controlled main trial. Pilot study participants were enrolled on an as-available basis to one group of CHMI infectivity controls and three staggered vaccine groups receiving: one dose of 4·5 × 105, one dose of 9 × 105, or three doses of 1·8 × 106 PfSPZ via direct venous inoculation at approximately 8 week intervals, followed by homologous CHMI 5 weeks later with infectious PfSPZ by direct venous inoculation (PfSPZ Challenge). Main cohort participants were stratified by village and randomly assigned (1:1) to receive three doses of 1·8 × 106 PfSPZ or normal saline at 1, 13, and 19 week intervals using permuted block design by the study statistician. The primary outcome was safety and tolerability of at least one vaccine dose; the secondary outcome was vaccine efficacy against homologous PfSPZ CHMI (pilot study) or against naturally transmitted P falciparum infection (main study) measured by thick blood smear. Combined artesunate and amodiaquine was administered to eliminate pre-existing parasitaemia. Outcomes were analysed by modified intention to treat (mITT; including all participants who received at least one dose of investigational product; safety and vaccine efficacy) and per protocol (vaccine efficacy). This trial is registered with ClinicalTrials.gov, number NCT02627456. Between Dec 20, 2015, and April 30, 2016, we enrolled 56 participants into the pilot study (five received the 4·5 × 105 dose, five received 9 × 105, 30 received 1·8 × 106, 15 were CHMI controls, and one withdrew before vaccination) and 120 participants into the main study cohort with 60 participants assigned PfSPZ Vaccine and 60 placebo in the main study. Adverse events and laboratory abnormalities post-vaccination in all dosing groups were few, mainly mild, and did not differ significantly between vaccine groups (all p>0·05). Unexpected severe transaminitis occured in four participants: one participant in pilot phase that received 1·8 × 106 PfSPZ Vaccine, one participant in main phase that received 1·8 × 106 PfSPZ Vaccine, and two participants in the main phase placebo group. During PfSPZ CHMI, approximately 5 weeks after the third dose of 1·8 × 106 PfSPZ, none of 29 vaccinees and one of 15 controls became positive on thick blood smear; subsequent post-hoc PCR analysis for submicroscopic blood stage infections detected P falciparum parasites in none of the 29 vaccine recipients and eight of 15 controls during CHMI. In the main trial, 32 (58%) of 55 vaccine recipients and 42 (78%) of 54 controls became positive on thick blood smear during 24-week surveillance after vaccination. Vaccine efficacy (1-hazard ratio) was 0·51 per protocol (95% CI 0·20-0·70; log-rank p=0·0042) and 0·39 by mITT (0·04-0·62; p=0·033); vaccine efficacy (1-risk ratio) was 0·24 per-protocol (0·02-0·41; p=0·031) and 0·22 mITT (0·01-0·39; p=0·041). A three-dose regimen of PfSPZ Vaccine was safe, well tolerated, and conferred 51% vaccine efficacy against intense natural P falciparum transmission, similar to 52% vaccine efficacy reported for a five-dose regimen in a previous trial. US National Institute of Allergy and Infectious Diseases, National Institutes of Health, Sanaria. For the French translation of the abstract see Supplementary Materials section.

Anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.

Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung disease caused by aspergillus-induced hypersensitivity with a prevalence of 2% to 15% in people with cystic fibrosis. The mainstay of treatment includes corticosteroids and itraconazole. The treatment with corticosteroids for prolonged periods of time, or repeatedly for exacerbations of allergic bronchopulmonary aspergillosis, may lead to many adverse effects. The monoclonal anti-IgE antibody, omalizumab, has improved asthma control in severely allergic asthmatics. The drug is given as a subcutaneous injection every two to four weeks. Since allergic bronchopulmonary aspergillosis is also a condition resulting from hypersensitivity to specific allergens, as in asthma, it may be a candidate for therapy using anti-IgE antibodies. Therefore, anti-IgE therapy, using agents like omalizumab, may be a potential therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. This is an updated version of the review. To evaluate the efficacy and adverse effects of anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Last search: 09 September 2021. We searched two ongoing trial registries (Clinicaltrials.gov and the WHO trials platform). Date of latest search: 16 August 2021. Randomized and quasi-randomized controlled trials comparing anti-IgE therapy to placebo or other therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. Two review authors independently extracted data and assessed the risk of bias in the included study. They planned to perform data analysis using Review Manager. Only one study enrolling 14 participants was eligible for inclusion in the review. The double-blind study compared a daily dose of 600 mg omalizumab or placebo along with twice daily itraconazole and oral corticosteroids, with a maximum daily dose of 400 mg. Treatment lasted six months but the study was terminated prematurely and complete data were not available. We contacted the study investigator and were told that the study was terminated due to the inability to recruit participants into the study despite all reasonable attempts. One or more serious side effects were encountered in six out of nine(66.67%) and one out of five(20%) participants in omalizumab group and placebo group respectively. There is lack of evidence for the efficacy and safety of anti-IgE (omalizumab) therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis. There is a need for large prospective randomized controlled studies of anti-IgE therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis with both clinical and laboratory outcome measures such as steroid requirement, allergic bronchopulmonary aspergillosis exacerbations and lung function.

Efficacy and Safety of Aronia, Red Ginseng, Shiitake Mushroom, and Nattokinase Mixture on Insulin Resistance in Prediabetic Adults: A Randomized, Double-Blinded, Placebo-Controlled Trial.

We determined whether oral consumption of Aronia, red ginseng, shiitake mushroom, and nattokinase mixture (3.4: 4.1: 2.4: 0.1 w/w; AGM) improved glucose metabolism and insulin resistance in prediabetic adults in a 12-week randomized, double-blinded clinical trial. Participants with fasting serum glucose concentrations of 100–140 mg/dL were recruited and randomly assigned to an AGM or placebo group. Participants of the AGM group (n = 40) were given an AGM granule containing 4 g of freeze-dried Aronia, red ginseng, shiitake mushroom, and nattokinase (3.4: 4.1: 2.4: 0.1 w/w) twice daily for 12 weeks, and the placebo group participants (n = 40) were provided with corn starch granules identical in appearance, weight, and flavor for 12 weeks. Serum glucose and insulin concentrations were measured during oral-glucose tolerance tests (OGTT) after administering 75 g of glucose in a fasted state. HOMA-IR, liver damage, and inflammation indices were determined, and safety parameters and adverse reactions were assessed. As determined by OGTT, serum glucose concentrations were not significantly different between the AGM and placebo groups after the intervention. However, changes in serum insulin concentrations in the fasted state and Homeostatic model assessment-insulin resistance (HOMA-IR) index after the intervention were significantly lower in the AGM group than in the placebo group (−3.07 ± 7.06 vs. 0.05 ± 6.12, p = 0.043 for serum insulin; −0.85 ± 2.14 vs. 0.07 ± 1.92, p = 0.049 for HOMA-IR). Serum adiponectin concentrations were reduced by intervention in the placebo group but not in the AGM group. Changes in liver damage indexes, including serum activities of the γ-glutamyl transferase, alanine aminotransferase, and aspartate aminotransferase, were lower in the AGM group and significantly reduced in the AGM group more than in the placebo group (p < 0.05). Changes in serum high sensitive-C-reactive protein concentrations in AGM and placebo groups were significantly different (−0.12 ± 0.81 vs. 0.51 ± 1.95, p = 0.06). In conclusion, AGM possibly improves insulin sensitivity and β-cell function and reduces liver damage and inflammation in prediabetic adults.

Ethical Considerations for Unblinding and Vaccinating COVID-19 Vaccine Trial Placebo Group Participants.

The Pfizer-BioNTech, Moderna, and Johnson & Johnson COVID-19 vaccinations have been approved under “Emergency Use Authorization” by the United States Food and Drug Administration (FDA). Other vaccines, such as the Sputnik V and AstraZeneca vaccines, have begun to be distributed in other nations around the world after the publication of promising efficacy results. Multiple more vaccine candidates are likely to follow, which will still require safety and efficacy testing. As vaccines have been distributed in a tiered fashion to the public, there has been discussion and disagreement regarding the matter of vaccination of placebo groups from the past or upcoming trials (1). It has been argued that only trial participants (placebo group) who would be otherwise offered the vaccine outside of the trial [i.e., high risk participants or healthcare workers (HCWs)] should be unblinded and given the vaccine, while all other participants should remain blinded (2, 3). We argue that, once proven efficacious, vaccine makers and researchers have an ethical obligation to unblind the placebo groups of COVID-19 vaccine trials and offer them vaccine, based on the four principles of medical ethics.

The Effects of Vitamin E on Non-proliferative Diabetic Retinopathy in Type 2 Diabetes Mellitus

Vitamin E, which exhibits anti-oxidant, anti-inflammatory, and anti-thrombogenesis properties, has been shown to improve retinal blood flow in diabetic retinopathy. This study aim to investigate the effects of Vitamin E (Tocovid) on retinal microhaemorrhages and diabetic macular edema (DME) in diabetic retinopathy. A total of 30 participants were randomly allocated to the treatment group or placebo group. The participants in the treatment group (n = 19) received 200 mg Tocovid twice daily while participants in placebo group (n = 21) received placebo twice daily for 12 weeks.

Lavender essential oil on postmenopausal women with insomnia: Double-blind randomized trial

BackgroundTo evaluate the effect of Lavandula angustifolia essential oil inhalation on sleep and menopausal symptoms in postmenopausal women with insomnia. Participants35 postmenopausal women with a clinical diagnosis of insomnia were included, 17 in Aroma Group (AG) and 18 in Placebo Group (PG). MethodsIn this double-blind, randomized controlled trial, PG participants inhaled sunflower oil and AG participants inhaledLavandula angustifolia essential oil, for 29 days. Both groups received sleep hygiene guidelines before the intervention and weekly follow-up during it. Evaluations were performed before and after intervention. All statistical analyses and intention-to-treat test were performed in SPSS 22. Sleep quality (Primary outcome) was measured by Pittsburgh Sleep Quality Index. Secondary outcomes were polysomnography data, severity of insomnia, anxiety and depression symptoms, and postmenopausal symptoms. ResultsThere were no significant differences between groups after intervention in the primary outcome (P = 0.22; effect size=0.69); however, a tendency of improvement in wake after sleep onset (WASO) was observed (P = 0.07; effect size=0.81; B = 42.2). Both groups presented better sleep quality over time (AG P < 0.001; PG P = 0.011). AG participants showed a significant decrease in sleep onset latency (P = 0.001), depression levels (P = 0.025), hot flashes (P < 0.001), postmenopausal symptoms (P < 0.001) and, in polysomnography data, increased sleep efficiency (P = 0.002) compared to baseline. ConclusionAlthough no significant differences were observed between groups, our data presented a tendency of improvement in WASO. Moreover, AG participants had enhanced overall sleep pattern, quality and sleep efficiency. Weekly follow-up and sleep hygiene instructions were essential for both groups to show improvement in almost all outcomes. Clinical trial registrationBrazilian Registry of Clinical Trials, www.ensaiosclinicos.gov.br, RBR-5q5t5z.

Early and sustained Lactobacillus plantarum probiotic therapy in critical illness: the randomised, placebo-controlled, restoration of gut microflora in critical illness trial (ROCIT).

PurposeIn adults requiring treatment in an intensive care unit, probiotic therapy using Lactobacillus plantarum 299v may reduce nosocomial infection. The aim of this study was to determine whether early and sustained L. plantarum 299v therapy administered to adult ICU patients increased days alive and at home.MethodsA multicentre, parallel group, placebo-controlled, randomised clinical trial was conducted. Adult patients within 48 h of intensive care admission and expected to require intensive care beyond the day after recruitment were eligible to participate. L plantarum 299v or placebo were administered immediately after enrolment and continued for 60 days. The primary outcome was days alive and out of hospital to Day 60 (DAOH60). Secondary outcomes included nosocomial infections.ResultsThe median [interquartile range (IQR)] number of DAOH60 in the probiotic (n = 110) and placebo group (n = 108) was 49.5 (IQR 37.0–53.0) and 49.0 (IQR 43.8–53.0) respectively, between-group difference of 0.0 [95% confidence interval (CI) − 6.10 to 7.1, P = 0.55]. Nosocomial infection occurred in 8 (7.3%) and 5 (4.6%) of the probiotic and placebo group participants, respectively, odds ratio 1.62 (95% CI 0.51–5.10), P = 0.57. There were no serious, or probiotic-associated adverse events.ConclusionEarly and sustained untargeted administration of probiotic therapy with Lactobacillus plantarum 299v to adult patients admitted to the ICU is safe, but not associated with improved patient outcomes.Electronic supplementary materialThe online version of this article (10.1007/s00134-020-06322-w) contains supplementary material, which is available to authorized users.

Clinical efficacy of fecal microbiota transplantation for patients with small intestinal bacterial overgrowth: a randomized, placebo-controlled clinic study

BackgroundSmall intestinal bacterial overgrowth (SIBO) is characterized by the condition that bacteria overgrowth in the small intestine. Fecal microbiota transplantation (FMT) has been applied as an effective tool for reestablishing the structure of gut microbiota. However, whether FMT could be applied as a routine SIBO treatment has not been investigated.MethodsIn this trial, 55 SIBO patients were enrolled. All participants were randomized in two groups, and were given FMT capsule or placebo capsules once a week for 4 consecutive weeks. Measurements including the lactulose hydrogen breath test gastrointestinal symptoms, as well as fecal microbiota diversity were assessed before and after FMT therapy.ResultsGastrointestinal symptoms significantly improved in SIBO patients after treatment with FMT compared to participants in placebo group. The gut microbiota diversity of FMT group had a significant increase, while placebo group showed none.ConclusionsThis study suggests that applying FMT for patients with SIBO can alleviate gastrointestinal symptoms, indicating that FMT may be a promising and novel therapeutic regimen for SIBO.Trial registryThis study was retrospectively registered with the Chinese Clinical Trial registry on 2019.7.10 (ID: ChiCTR1900024409, http://www.chictr.org.cn).