Placebo-controlled Parallel Study Research Articles

Actazin® green kiwifruit powder consumption at 600 mg per day for 28 days improves stool form and relieves occasional constipation in healthy individuals: A randomized controlled trial

Constipation is a global issue which impacts quality of life. Kiwifruit promote laxation without the urgency induced by therapeutic laxatives. Actazin® is a skinless, seedless, cold-processed green kiwifruit powder previously shown to improve laxation at 2400 mg daily dosages. Here we investigated the laxation support provided by a 600 mg daily dosage of Actazin.A randomized, double-blinded, placebo-controlled parallel study for 28 days across four North American sites (NCT03462199) enrolled 85 participants with non-pathological constipation who had ≤3 complete spontaneous bowel movements (CSBM) per week. Participants consuming Actazin reported improved Bristol stool form scores (BSFS) over placebo (p < 0.05), improving the normality of stool form. Both Actazin and placebo showed improvements of >1 CSBM per week over baseline (p < 0.05). Actazin was safe and well tolerated by participants and resulted in changes (p < 0.05) in the relative abundance of fecal bacterial taxa consistent with consumption of kiwifruit cell wall components.This study demonstrated that once daily supplementation of 600 mg Actazin green kiwifruit powder resulted in clinically significant improvements in stool form and improved participant bowel habits in healthy individuals with occasional constipation. To the best of our knowledge this is the first recorded observation of this BSFS improvement over placebo by a kiwifruit product.

The mechanism of Sangdantongluo granule in treating post-stroke spasticity based on multimodal fMRI combined with TMS: Study protocol

IntroductionPost-stroke spasticity (PSS) is among the prevalent complications of stroke, greatly affecting motor function recovery and reducing patients' quality of life without timely treatment. Sangdantongluo granule, a modern traditional Chinese patent medicine, has significant clinical efficacy in treating PSS. However, the mechanism of Sangdantongluo granule in treating PSS is still unknown. We designed this study to explore the mechanism of Sangdantongluo granule in treating PSS through multimodal functional magnetic resonance imaging (fMRI) combined with transcranial magnetic stimulation (TMS). Methods and analysisIn a single-center, randomized, double-blind, parallel placebo-controlled study, 60 PSS patients will be recruited in China and randomly assigned to either the experimental or control groups at a ratio of 1:1. For eight weeks, Sangdantongluo granule or placebo will be utilized for intervention. The main outcome is the Modified Ashworth Scale (MAS), the secondary outcome includes the Fugl-Meyer Assessment Scale-upper Extremity (FMA-UE), National Institute of Health Stroke Scale (NIHSS), and Modified Rankin Scale (mRS), the mechanism measure is the changes in cortical excitability and multimodal fMRI at baseline and after eight weeks. Ethics and disseminationThis study was approved by the Ethics Committee of the Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine (approval number: [202364]). Clinical trial registrationChinese Clinical Trial Registry, identifier: ChiCTR2300074793. Registered on 16 August 2023.

Docosahexaenoic Acid Supplementation for Neonatal Hyperbilirubinemia: A Double-Blind, Randomized Clinical Trial.

Docosahexaenoic acid (DHA) is an essential component for brain development during fetal and early postnatal life. Hyperbilirubinemia is characterized by abnormally high levels of bilirubin in the bloodstream, frequently leading to jaundice in newborns. In severe instances, this condition can progress to neurological damage or kernicterus, a form of brain damage. Initial cell-based experiments conducted by our research team revealed that DHA significantly enhances the survival rate of nerve cells treated with bilirubin and diminishes the oxidative stress indicated by reduced peroxide activity caused by unconjugated bilirubin (UCB). Further investigations through animal studies demonstrated that DHA effectively mitigates bilirubin-induced brain injury in neonatal rats. However, the potential of DHA to decrease the incidence of bilirubin-induced brain damage in clinical settings has not been previously explored or reported. Infants with neonatal hyperbilirubinemia (n = 30 per group) participated in a double-blind, randomized, placebo-controlled parallel study. They received either 100 mg/d DHA or placebo syrup immediately when they were diagnosed. The study found that the bilirubin level at 48 hours of treatment, serum neuron-specific enolase (NSE) levels, mean phototherapy duration, and abnormal rate of cranial magnetic resonance imaging (MRI) were lower in the DHA group than those in the control group (P < .05). These results suggested that DHA is effective as an adjuvant treatment for hyperbilirubinemia in children. It can reduce the incidence of neonatal hyperbilirubinemia brain injury and plays a certain protective role. Clinical study on protective effect of DHA on neonatal bilirubin injury is registered at Chinese Clinical Trial Registry as ChiCTR2300070250.

Interindividual differences in aronia juice tolerability linked to gut microbiome and metabolome changes—secondary analysis of a randomized placebo-controlled parallel intervention trial

BackgroundAronia melanocarpa is a berry rich in polyphenols known for health benefits. However, the bioavailability of polyphenols has been questioned, and the individual taste acceptance of the fruit with its specific flavor varies. We recently observed substantial differences in the tolerability of aronia juice among healthy females, with half of the individuals tolerating aronia juice without complaints. Given the importance of the gut microbiome in food digestion, we investigated in this secondary analysis of the randomized placebo-controlled parallel intervention study (ClinicalTrials.gov registration: NCT05432362) if aronia juice tolerability was associated with changes in intestinal microbiota and bacterial metabolites, seeking for potential mechanistic insights into the impact on aronia polyphenol tolerance and metabolic outcomes.ResultsForty females were enrolled for this 6-week trial, receiving either 100 ml natural aronia juice (verum, V) twice daily or a polyphenol-free placebo (P) with a similar nutritional profile, followed by a 6-week washout. Within V, individuals were categorized into those who tolerated the juice well (Vt) or reported complaints (Vc). The gut microbiome diversity, as analyzed by 16S rRNA gene-based next-generation sequencing, remained unaltered in Vc but changed significantly in Vt. A MICOM-based flux balance analysis revealed pronounced differences in the 40 most predictive metabolites post-intervention. In Vc carbon-dioxide, ammonium and nine O-glycans were predicted due to a shift in microbial composition, while in Vt six bile acids were the most likely microbiota-derived metabolites. NMR metabolomics of plasma confirmed increased lipoprotein subclasses (LDL, VLDL) post-intervention, reverting after wash out. Stool samples maintained a stable metabolic profile.ConclusionIn linking aronia polyphenol tolerance to gut microbiota-derived metabolites, our study explores adaptive processes affecting lipoprotein profiles during high polyphenol ingestion in Vt and examines effects on mucosal gut health in response to intolerance to high polyphenol intake in Vc. Our results underpin the importance of individualized hormetic dosing for beneficial polyphenol effects, demonstrate dynamic gut microbiome responses to aronia juice, and emphasize personalized responses in polyphenol interventions.Graphical DsmAL-oYwbuhyB_vVwEdDjVideo

A double-blind, randomised, placebo-controlled parallel study to investigate the effect of sex and dietary nitrate on COVID-19 vaccine-induced vascular dysfunction in healthy men and women: protocol of the DiNOVasc-COVID-19 study

BackgroundCardiovascular events, driven by endothelial dysfunction, are a recognised complication of COVID-19. SARS-CoV-2 infections remain a persistent concern globally, and an understanding of the mechanisms causing endothelial dysfunction, particularly the role of inflammation, nitric oxide, and whether sex differences exist in this response, is lacking. We have previously demonstrated important sex differences in the inflammatory response and its impact on endothelial function and separately that the ingestion of inorganic nitrate can protect the endothelium against this dysfunction. In this study, we will investigate whether sex or a dietary inorganic nitrate intervention modulates endothelial function and inflammatory responses after the COVID-19 vaccine.MethodsDiNOVasc-COVID-19 is a double-blind, randomised, single-centre, placebo-controlled clinical trial. A total of 98 healthy volunteers (49 males and 49 females) will be recruited. Participants will be randomised into 1 of 2 sub-studies: part A or part B. Part A will investigate the effects of sex on vascular and inflammatory responses to the COVID-19 vaccine. Part B will investigate the effects of sex and dietary inorganic nitrate on vascular and inflammatory responses to the COVID-19 vaccine. In part B, participants will be randomised to receive 3 days of either nitrate-containing beetroot juice (intervention) or nitrate-deplete beetroot juice (placebo). The primary outcome for both sub-studies is a comparison of the change in flow-mediated dilatation (FMD) from baseline after COVID-19 vaccination. The study has a power of > 80% to assess the primary endpoint. Secondary endpoints include change from baseline in inflammatory and leukocyte counts and in pulse wave analysis (PWA) and pulse wave velocity (PWV) following the COVID-19 vaccination.DiscussionThis study aims to evaluate whether sex or dietary influences endothelial function and inflammatory responses in healthy volunteers after receiving the COVID-19 vaccine.Trial registrationClinicalTrials.gov NCT04889274. Registered on 5 May 2023. The study was approved by the South Central – Oxford C Research Ethics Committee (21/SC/0154).

Evaluation of efficacy and safety of Bacillus coagulans SNZ 1969 supplementation for irritable bowel syndrome: a randomized, double-blind, placebo-controlled study

Background: Probiotic potential (efficacy and safety) of Bacillus coagulans SNZ 1969 has been studied in patients with constipation-predominant irritable bowel syndrome (IBS-C) and-diarrhea predominant IBS (IBS-D).Methods: This randomized, double-blind, two-arm, placebo-controlled parallel study randomized 92 patients (1:1) to receive either 500 million CFU of Bacillus coagulans SNZ 1969 (treatment group) or placebo (placebo group) twice daily for 60 days under two subtypes of IBS, IBS-D (n=46) and IBS-C (n=46). Primary outcomes were changes in IBS symptom severity noted using the gastrointestinal symptom rating scale-IBS version (GSRS-IBS) on days 30, 60, and 75, and the number of treatment responders defined by subject’s global assessment (SGA) of relief ≤3 and ≤2 at days 30 and 60, respectively. We also assessed patient’s quality of life.Results: The GSRS-IBS scores reduced from day 30 through 75 in both IBS groups treated with Bacillus coagulans SNZ1969 compared to placebo (p&lt;0.05). Higher GSRS-IBS score was noted in patients with IBS-C in the treatment group (22.45±2.7) than the placebo group (3.55±3.02; p&lt;0.0001), and this trend was similar in IBS-D patients (p&lt;0.0001). Most patients (90%) with IBS-C and all with IBS-D responded to Bacillus coagulans SNZ 1969 compared to no responders with placebo (p&lt;0.0001). The SF-8 scores significantly reduced in patients receiving Bacillus coagulans SNZ 1969 than placebo for both IBS subtypes. One adverse event unrelated to the study treatments was reported in IBS-D group.Conclusions: Bacillus coagulans SNZ 1969 is safe, effective in alleviating IBS-associated clinical symptoms, and improves quality of life.

Effect of Repetitive Transcranial Magnetic Stimulation on Serum Levels of Steroid Adrenal Hormones in Parkinson's Disease: Sex Differences.

In a parallel placebo-controlled study, we examined the effect of repetitive transcranial magnetic stimulation (rTMS) on serum concentrations of cortisol and dehydroepiandrosteron sulfate (DHEAS), and their relationships with clinical symptoms in men and women with Parkinson's disease. A 20-day course of real rTMS reduced the UPDRS and UPDRS III scores in patients with Parkinson's disease in comparison with the basal parameters (before rTMS), regardless of their sex. The level of cortisol did not change in men and women; at the same time, the content of DHEAS in men increased and before rTMS negatively correlated with the UPDRS scores. Sham rTMS had no effects on clinical parameters or hormonal levels. Possible mechanisms of sex-dependent differences in the effect of rTMS on the level of the neurosteroid hormone DHEAS are discussed.

The effect of a probiotic on gastrointestinal symptoms due to menstruation in healthy adult women on oral contraceptives: randomized, double-blind, placebo-controlled trial protocol

IntroductionFor many women, uncomfortable and stressful symptoms accompany the menstrual cycle each month, sometimes in a debilitating manner. Previous studies have reported that gastrointestinal symptoms in healthy women significantly differ by the day of the menstrual cycle, but few studies have assessed interventions intended to minimize these symptoms. Probiotics supplements have been shown to attenuate gastrointestinal symptom severity as well as self-reported feelings of stress in various populations. This study evaluates the effect of a probiotic on abdominal pain and gastrointestinal symptoms in healthy women who take an oral contraceptive, have regular menses, and typically experience these symptoms during menstruation with the primary aim being change in abdominal pain intensity related to the menstrual cycle with probiotic versus placebo supplementation.Methods and analysisIn this randomized, double-blind, placebo-controlled parallel study, participants will receive either a probiotic or placebo supplement. Participants will begin answering questionnaires approximately 7 days before the start of menstruation (i.e., active bleeding), and 3 days later, they will begin consuming the study supplement for 8 weeks. The questionnaires administered will collect data about abdominal pain severity (primary outcome) and duration related to the menstrual cycle, digestive health, dietary intake, stress, and digestion-associated quality-of-life. A subgroup of women will provide weekly vaginal swabs and stool samples to examine the effect of the probiotic supplement on microbiota composition and diversity for exploratory purposes. Two-sided tests using a linear model and a type I error rate of α = 0.05 will be employed to test all hypotheses. Continuous variables will be presented as means with standard errors and categorical variables, as counts or proportions.Ethics and disseminationThis study was reviewed and approved by the University of Florida Institutional Review Board 01. Written informed consent will be obtained from all participants prior to any study activities. Study findings will be disseminated at scientific conferences and publication in the trial registry or in a peer-reviewed journal. Any protocol amendments will be reported in the final manuscript of this study.Trial registrationClinicalTrials.gov NCT04457401. Registered prospectively on 07 July 2020. The trial was completed in December of 2021.Protocol versionV4.0 (11-04-2020)Trial statusCurrently recruiting. Recruitment began in November 2020 and extend until December 2021.

A multicenter, double-blind, placebo-controlled parallel study to evaluate the role of Yinhua Miyanling tablets in the prevention of bacterial biofilm formation on ureteral stents: a randomised trial.

Yinhua Miyanling tablet (YMT) not only has the functions of clearing away heat and toxin, dredging drenching and diuresis, but also has antibacterial activity. The formation of bacterial biofilm in ureteral stent and its related infection have plagued the clinic. Antibacterial traditional Chinese medicine is a potential method. This multicenter, randomized, double-blind, placebo-controlled study was designed to enroll patients who underwent ureteroscopic lithotripsy associated with indwelling ureteral stents at six centers between March 2019 and June 2020. The eligible patients were randomly assigned to the experimental group to take YMT 2 g qid orally or the control group to take dummy YMT 2 g qid orally from the first day after the operation according to a random number table. The unused drugs were recalled 14±3 days after the operation and record the body temperature. Relevant laboratory tests (urinalysis and urine culture) were performed before extubation. The ureteral stent was removed. The specimen was collected for scanning electron microscopy (SEM). Biofilm formation, USSQ scores, postoperative infectious complications, stone formation, and adverse drug reactions were compared between the two groups. Of the 211 patients enrolled, 165 were included in the per-protocol set (PPS), including 86 in the control group and 79 in the experimental group. No significant difference was found between the two groups in baseline parameters (P>0.05). The prevalence of biofilm formation in the control group (47%) was significantly higher than that in the experimental group (22.7%, P=0.001). There was no significant difference in total USSQ score and domain score between the two groups (all P>0.05). There were more patients with symptomatic urinary tract infection (UTI) in the control group (12.9%) than in the experimental group (2.6%, P=0.017). The incidence of other complications did not show a significant difference between the two groups (all P>0.05). The incidence of stone formation on the ureteral stent surface and adverse drug reactions did not show a significant difference between the two groups (all P>0.05). YMT is helpful to reduce the formation of bacterial biofilms on ureteral stents and the incidence of symptomatic UTIs related to ureteral stenting after surgery for ureteral calculi. Chinese Clinical Trial Registry ChiCTR2000041399.

Polyphenol-rich tart cherries (Prunus Cerasus, cv Montmorency) improve sustained attention, feelings of alertness and mental fatigue and influence the plasma metabolome in middle-aged adults: a randomised, placebo-controlled trial.

Tart Montmorency cherries (MC) are a particularly rich source of anthocyanins and other polyphenols that have been shown to elicit antioxidant, anti-inflammatory and vasomodulatory actions. The current study aimed to determine the influence of chronic MC supplementation on cognitive function and mood. In a 3-month double-blinded, placebo-controlled parallel study, middle-aged adults (mean ± sd: 48 ± 6 years) were randomly assigned to either 30 ml twice daily of MC (n 25) or the same amount of an isoenergetic placebo (n 25). Cognitive function and mood were assessed before and after supplementation using a computerised cognitive task battery and visual analogue scales. Cerebral blood flow was also monitored by near-infrared spectroscopy during the task battery, and questionnaires were administered to determine subjective sleep and health status and plasma metabolomics were analysed before and after supplementation. After 3 months, the MC resulted in higher accuracy in digit vigilance (mean difference: 3·3, 95 % CI: 0·2, 6·4 %) with lower number of false alarms (mean difference: -1·2, 95 % CI: -2·0, -0·4) compared with the placebo. There was also a treatment effect for higher alertness (mean difference: 5·9, 95 % CI: 1·3, 10·5 %) and lower mental fatigue ratings (mean difference -9·5, 95 % CI: -16·5, -2·5 %) with MC. Plasma metabolomics revealed an increase in a number of amino acids in response to MC intake, but not placebo. These data suggest an anti-fatiguing effect of MC supplementation as well as the ability to improve sustained attention during times of high cognitive demand, this could be related to changes in amino acid metabolism.

Efficacy of Melaleuca alternifolia and chlorhexidine mouth rinses in reducing oral malodor and Solobacterium moorei levels. A 1 week, randomized, double-blind, parallel study.

OBJECTIVES:The objective is to evaluate the association of Solobacterium moorei (S. moorei) to halitosis and to also check for the effects of two different mouth rinses on levels of S. moorei in saliva and tongue coating and its impact on oral halitosis.MATERIALS AND METHODS:This was a placebo-controlled parallel study of 160 individuals who were randomized and the study was performed using double-blinded protocol. Enrolled individuals filled a structured questionnaire regarding demographic data, oral hygiene habits, and dietary habits. Full mouth organoleptic odor scores (OLR), volatile sulfur compounds levels, Miyazaki's tongue coating index, and Plaque scores were recorded before intervention (baseline) and after 1-week post treatment. Microbiological samples obtained from the tongue and saliva was investigated for S. moorei levels using real time polymerase chain reaction. Participants were randomly assigned for two test mouth rinses (Melaleuca alternifolia and Chlorhexidine) and placebo groups.RESULTS:All salivary and tongue coating samples were tested positive for S. moorei in the halitosis group. One week post-treatment S. moorei counts in saliva and tongue coating samples of test group showed a significant reduction at P < 0.001. Paired t-test results showed that Melaleuca alternifolia was comparable with chlorhexidine in reduction of OLR, and VSC scores (P < 0.001). Salivary levels of S. moorei in Melaleuca alternifolia group showed a higher reduction (5.67 log10 copies/mL) than chlorhexidine group (5.1log10 copies/mL).CONCLUSION:S. moorei showed a positive correlation with oral halitosis scores. Both Melaleuca alternifolia and chlorhexidine were equally effective in reducing S. moorei levels and halitosis score.

A Randomized, Double-Blind, Placebo-Controlled Parallel Study on the Efficacy and Safety of Centella asiatica L. Extract for Reducing Alanine Transaminase (ALT) Level in Subjects with Elevated ALT

The liver is an important organ that detoxifies various metabolites, synthesizes proteins, and produces biochemicals necessary for life. There are many medications on the market to treat liver diseases, but these can be a strain on the liver due to the need for a detoxification process in the organ. Herbal medicines are replacing synthetic drugs. In the present study, we aimed to evaluate the efficacy and safety of Centella aisatica L. extract for reducing alanine transaminase (ALT) levels using a randomized, double-blind, placebo-controlled parallel study. Investigators performed a clinical trial in which an herbal treatment was administered every morning for 12 weeks to 80 patients in two groups. The study protocol number was SYN/RM/CA-008. The results demonstrated improved ALT levels with a positive change in the investigational product (IP) group (−19.9) compared to the placebo group (1.8) (p &lt; 0.0001). In addition, IP treatment was safe and non-toxic. The current data indicate that CA-HE50 exhibits clinically significant changes for all hepatoprotective efficacy parameters, suggesting potential for development and applicability as a hepatoprotective substance.

An Evaluation of the Effects of a Non-caffeinated Energy Dietary Supplement on Cognitive and Physical Performance: A Randomized Double-Blind Placebo-Controlled Study.

A large and growing body of research shows that non-caffeinated plant-based nutritional supplements can increase cognitive and physical performance. This study aimed to build on this work by investigating the possibility that a specific botanical blend (consisting of Bacopa monnieri bacosides, Kaempferia parviflora methoxy flavones, pomegranate peel polyphenols, and Moringa oleifera leaf saponins) could improve cognitive and physical performance. To this end, we carried out a randomized, double-blind, placebo-controlled 21-day parallel study on 36 healthy adults. We compared the effects of the botanical blend at baseline to a caffeine and a placebo condition on 1) self-reported alertness, anxiety, and headaches; 2) multiple measures of attention and cognition; 3) physical performance; and 4) stress biomarkers. We found that relative to baseline and compared to the Caffeine and Placebo groups, the botanical blend increased alertness and improved cognitive performance. The cognitive effects were most robust for attention measures. The botanical blend did not improve physical performance on a time to exhaustion (TTE) test. Of note, there was not the expected increase in catecholamine response after the TTE on Day 21, suggesting that long-term botanical blend use decreases the catecholamine stress response of a physical endurance task. In conclusion, we show that, within the confines of this study, a combination of the botanical blend could serve as a safe and effective nutritional supplement to improve cognitive performance.

The Influence of Tart Cherry (Prunus cerasus, cv Montmorency) Concentrate Supplementation for 3 Months on Cardiometabolic Risk Factors in Middle-Aged Adults: A Randomised, Placebo-Controlled Trial.

Background: Tart Montmorency cherries (MC) have been shown to be rich in anthocyanins and other phytochemicals known to have anti-inflammatory properties and influence pathways that might improve cardiometabolic health. However, there is limited evidence for the longer-term use of tart cherries on these indices. The aim of the current study was to investigate the influence of MC concentrate on cardiometabolic health indices following a 3-month supplementation period. Methods: Fifty middle-aged adults (34 males and 16 females; mean ± SD age: 48 ± 6 years and BMI: 27.6 ± 3.7 kg/m2) completed a randomised, placebo-controlled parallel study in which they either received MC or an isocaloric placebo. Participants drank 30 mL of their allocated treatment twice per day for 3 months. Vascular function (blood pressure [BP], heart rate [HR], pulse wave velocity and analysis [PWV/A], and flow mediated dilation [FMD]) as well as indices of metabolic health (insulin, glucose, lipid profiles, and high sensitivity C reactive protein) were measured following an overnight fast before and after the 3 months. Results: No effect of the intervention between the groups was observed for vascular function or metabolic health variables following the intervention (p > 0.05). However, MC concentrate was shown to be safe and well-tolerated and, importantly, did not have any deleterious effects on these outcomes. In conclusion, MC has no influence on cardiometabolic indices in middle-aged adults.

The effect of consuming an anthocyanin-containing supplement derived from Bilberry (Vaccinium myrtillus) on eye function: A Randomized, Double-Blind, Placebo-Controlled Parallel Study

Objective: The purpose of this study was to determine the effects of 6-week consumption of anthocyanin-containing supplement on eye function.Methods: This was a randomized, placebo-controlled, double-blind, parallel-group comparison study involving 32 healthy Japanese adults with eye fatigue after using visual display terminals (VDTs). Subjects were randomly allocated into either the active group (bilberry-derived anthocyanin 43.2 mg per capsule) or placebo group using a random number generator. Subjects consumed either one active or placebo capsule once a day for 6 weeks. The primary outcome measured was the change in percentage of pupillary response pre- and post-VDT use, whereas the secondary outcomes were tear film break-up time, Schirmer's value, muscle hardness, and subjective symptoms. Experimental data was analyzed using Student's t-test, the two-way analysis of covariance, or Mann–Whitney U-test.Results: Each group included 15 subjects in the efficacy analysis. The active group showed a significant improvement in the logarithmic conversion values of the percentage of pupillary response (active group: 0.2 ± 0.4, placebo group: 0.0 ± 0.3; P = 0.043) and pupillary response/near point (active group: 0.1 ± 0.4, placebo group: −0.1 ± 0.3; P = 0.049) pre- and post-VDT use at 6 weeks compared with the placebo group in a subgroup analysis per eye. No adverse events were reported.Conclusions: The consumption of the supplement containing anthocyanins extracted from bilberry for 6 weeks inhibited the decrease in the accommodative function caused by oxidative stress due to VDT use.Trial registration: UMIN-CTR: UMIN000037039.Foundation: BGG Japan Co., Ltd. and Arysta Health and Nutrition Sciences Corp.

Effectiveness of Pre-operative Rectal Misoprostol in Reducing Blood Loss during Cesarean Section for Placenta Previa and Manual Removal of Retained Placenta: A Parallel Placebo-Controlled Study

BACKGROUND: Primary postpartum hemorrhage (PPH) contributes significantly to the high maternal mortality ratio, especially in the low resource nations. Placenta previa and retained placenta are major causes of postpartum hemorrhage. Uterotonics like misoprostol are medication used to improve uterine contractility with the purpose of reducing uterine bleeding after delivery of baby. Most studies on misoprostol for the prevention of obstetric hemorrhage have been focusing on its postpartum use.&#x0D; AIM: The aim of this study was to assess the effectiveness of pre-operative misoprostol in reducing blood loss during cesarean section for placental previa and manual removal of retained placenta.&#x0D; METHODS: This was a placebo-controlled study involving 154 women who were randomly assigned to the treatment and control groups. The study group received 400 ug of misoprostol rectally just before the commencement of the procedure. Estimation of blood loss was done in a standardized way. Data were analyzed using SPSS version 23. The level of significance was set at p &lt; 0.05.&#x0D; RESULTS: The average age of the participants was 31.64 years. The overall incidence of PPH was comparable in both groups (0.070), however, misoprostol group experienced lower incidence of severe PPH compared to the placebo (p = 0.013). Other maternal and perinatal outcomes were comparable.&#x0D; CONCLUSION: Excessive intraoperative and immediate post-operative bleeding can be prevented with pre-operative misoprostol. It should be made available for high-risk obstetrics procedures.

Is sulthiame effective and tolerated as add-on therapy for infants with epilepsy? A Cochrane Review summary with commentary.

Is sulthiame effective and tolerated as add-on therapy for infants with epilepsy? A Cochrane Review summary with commentary.

Efficacy of melatonin for sleep disturbance in middle-aged primary insomnia: a double-blind, randomised clinical trial

BackgroundThe aim of this study was to determine the efficacy of exogenous melatonin supplementation for sleep disturbances in patients with middle-aged primary insomnia. MethodsThis is a randomized double-blind, placebo-controlled parallel study. Participants were recruited from Tianlin community, Xuhui district, Shanghai. Ninety-seven consecutive middle-aged patients with primary insomnia were randomized to receive 3 mg fast-release melatonin (n = 51) or placebo (n = 46) for four-weeks. Objective sleep parameters tested by overnight polysomnography, subjective sleep performance and daytime somnolence obtained from the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI) and Epworth Sleepiness Scale (ESS) were obtained at baseline and after treatment. Treatment was taken daily 1 h before bedtime. Serious adverse events and side-effects were monitored. ResultsMelatonin supplementation significantly decreased early wake time [−30.63min (95% CI, −53.92 to −7.34); P = 0.001] and percentage of N2 sleep [−7.07% (95% CI, −13.47% to −0.68%); P = 0.031]. However, melatonin had no significant effect on other objective sleep parameters including sleep latency, sleep efficiency, wake during the sleep and percent of N1, N3 and REM sleep. Melatonin had no effect on insomnia symptoms and severity on the PSQI [1.53(95% CI, −0.55 to 3.61); p = 0.504]; ISI [0.81 (95% CI, −2.27 to 3.88); p = 0.165] and ESS [−0.83 (95% CI, −3.53 to 1.88); p = 0.147]. No serious adverse events were reported. ConclusionsMelatonin supplementation over a four-week period is effective and safe in improving some aspects of objective sleep quality such as total sleep time, percentage of rapid eye movement and early morning wake time in middle-aged patients with insomnia. Trial registrationIdentifier: ChiCTR-TRC-13003997; Prospectively registered on 2 December 2013.

The Effect of Long-Term Aronia melanocarpa Extract Supplementation on Cognitive Performance, Mood, and Vascular Function: A Randomized Controlled Trial in Healthy, Middle-Aged Individuals.

Cognitive decline is associated with lifestyle-related factors such as overweight, blood pressure, and dietary composition. Studies have reported beneficial effects of dietary anthocyanins on cognition in older adults and children. However, the effect of anthocyanin-rich Aronia melanocarpa extract (AME) on cognition is unknown. Therefore, this study aimed to determine the effect of long-term supplementation with AME on cognitive performance, mood, and vascular function in healthy, middle-aged, overweight adults. In a randomized double-blind placebo-controlled parallel study, 101 participants either consumed 90 mg AME, 150 mg AME, or placebo for 24 weeks. The grooved pegboard test, number cross-out test, and Stroop test were performed as measures for psychomotor speed, attention, and cognitive flexibility. Mood was evaluated with a visual analogue scale, serum brain-derived neurotrophic factor (BDNF) was determined, and vascular function was assessed by carotid ultrasounds and blood pressure measurements. AME improved psychomotor speed compared to placebo (90 mg AME: change = −3.37; p = 0.009). Furthermore, 150 mg AME decreased brachial diastolic blood pressure compared to 90 mg AME (change = 2.44; p = 0.011), but not compared to placebo. Attention, cognitive flexibility, BDNF, and other vascular parameters were not affected. In conclusion, AME supplementation showed an indication of beneficial effects on cognitive performance and blood pressure in individuals at risk of cognitive decline.

LDL-cholesterol lowering effect of hydroxytyrosol (HTEssenceandreg;): A randomized double-blind, placebo-controlled parallel study

Background: Nutraceuticals containing hydroxytyrosol have been shown to exert a wide range of beneficial effects on the cardiovascular system like lipid modification and cholesterol reduction. The aim of this randomized doubleblind, placebo-controlled parallel study was to investigate the effects of a pure, synthetic form of hydroxytyrosol (HTEssence®) on the lipid profile in subjects with elevated LDL-cholesterol level. Methods: 92 subjects underwent a 12-week intervention with hydroxytyrosol or placebo. At baseline, after 6 and 12 weeks of intervention the lipid profile of the subjects was assessed.The study was conducted in accordance with the guidelines for Good Clinical Practice (GCP) andwas registered in the German Clinical Trials Register (DRKS00015251). Results: A significant delta change of LDL-cholesterol levels was observed in the hydroxytyrosol group after 12 weeks of intervention comparedto the placebo group (p=0.0454). The absolute difference between placebo and hydroxytyrosol accounted for 8.46mg/dL.With regard to the changes within the intervention groups after 12 weeks, a slight decrease of LDL-cholesterol could be observed in the hydroxytyrosol group (-2.70 mg/dL, 95% CI: -8.15- 2.75) and, in contrast, an increase of this parameter in the placebo group (5.76 mg/dL, 95% CI: 0.23– 11.28). Regarding the other parameters of lipid status including total cholesterol, HDL-cholesterol, LDL/HDL-ratio and triglycerides, no lipid modifying effects were observed. Conclusion: Data of the current clinical study support the evidence for hydroxytyrosol being a nutraceutical with anti-atherogenic effects.