Placebo-controlled Pilot Study Research Articles

EEG changes as an indication of central nervous system involvement following cyclopentolate 1% eye drops; a randomized placebo-controlled pilot study in a pediatric population

ABSTRACT To compare EEG-patterns after instillation of cyclopentolate versus placebo eye drops. Prospective, randomized, placebo-controlled, and observational pilot study is presented. Ophthalmology outpatient clinic Dutch metropolitan hospital. Healthy 6- to 15-year-old volunteers with normal or low BMI requiring a cycloplegic refraction/retinoscopy. Randomized; 1 visit 2 drops cyclopentolate-1% and 1 visit 2 drops placebo (saline-0.9%). Single-blind: conducting researcher. Double blind: subjects, parents, clinical-neurophysiology staff, neurologist, and statistician. A 10-min baseline EEG-recording, drop-application, and follow-up to at least 45 min. Primary outcome: Detection of CNS changes, i.e. EEG-pattern changes, following two drops of cyclopentolate-1%. Secondary outcome: Determination of the extent of these pattern changes. Thirty-six cyclopentolate-1% saline-0.9% EEG registrations were made in 33 subjects; 18 males and 15 females. Three subjects were tested twice (interval 7 months). Nine out of fourteen (64%) of the 11- to 15-year-old children reported impaired memory, attention, alertness, as well as mind wandering following cyclopentolate. Drowsiness and sleep were seen in EEG-recordings of 11 subjects (33%) following cyclopentolate. We observed no drowsiness nor sleep during placebo recordings. The mean time to drowsiness was 23 min. Nine subjects arrived in stage-3 sleep but none arrived in REM-sleep. In subjects without sleep (N=24), significant changes compared to placebo-EEG were present for many leads and parameters. The main findings during awake eye-open recording were as follows: 1) a significant increase of temporal Beta-1,2 and 3-power, and 2) a significant decrease in: a) the parietal and occipital Alpha-2-power, b) the frontal Delta-1-power, c) the frontal total power, and d) the occipital and parietal activation synchrony index. The former finding reflects cyclopentolate uptake in the CNS, and the latter findings provide evidence for CNS suppression. Cyclopentolate-1% eye drops can affect the CNS and may cause altered consciousness, drowsiness, and sleep with concomitant EEG results in both young children and children in puberty. There is evidence that cyclopentolate has the potency to act as a short acting CNS depressant. Nevertheless, however, cyclopentolate-1% can safely be used in children and young adolescents.

Study design and methods for the pilot study of muscadine grape extract supplement to improve fatigue among older adult cancer survivors (FOCUS) trial

IntroductionFatigue is a prevalent symptom among both cancer survivors and older adults. Negative consequences of fatigue include increased sedentary behavior, decreased physical activity and function, and lower quality of life. Few pharmacologic interventions improve fatigue. Our preclinical and clinical data show promising effects of a muscadine grape extract supplement (MGES) on oxidative stress, mitochondrial bioenergetics, the microbiome, and the symptom of fatigue. This pilot study seeks to translate these observations to cancer survivorship by testing the preliminary effect of MGE supplementation on older adult cancer survivors with self-reported fatigue. Materials and MethodsWe designed a double-blinded placebo-controlled pilot study to evaluate preliminary efficacy of MGE supplementation versus placebo on fatigue among older adult cancer survivors (aged ≥65 years) who report baseline fatigue. Sixty-four participants will be enrolled and randomized 1:1 to twice daily MGES (four tablets twice daily) versus placebo for 12 weeks. The primary outcome is change in Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue score from baseline to 12 weeks. Secondary outcomes are change in self-reported physical function, physical fitness (6-min walk test), self-reported physical activity, global quality of life (QOL), and the Fried frailty index. Correlative biomarker assays will assess changes in 8-hydroxy-2 deoxyguanosine, peripheral blood mitochondrial function, inflammatory markers, and the gut microbiome. DiscussionThis pilot study builds on preclinical and clinical observations to estimate effects of MGE supplementation on fatigue, physical function, QOL, and biologic correlates in older adult cancer survivors.Trial registration #: CT.govNCT04495751; IND 152908.

Arketamine as adjunctive therapy for treatment-resistant depression: A placebo-controlled pilot study

BackgroundRacemic ketamine is a mixture of (R)-ketamine (arketamine) and (S)-ketamine (esketamine), with the latter regarded as the main isomer for antidepressant effects. However, preclinical data and one open-label human trial suggest arketamine might exert a more potent and longer-lasting antidepressant effect with fewer side effects. We aimed to explore the feasibility of a randomized controlled trial of arketamine for treatment-resistant depression (TRD) and to assess its efficacy and safety compared to placebo. MethodsThis is a, randomized, double-blind, crossover, pilot trial (n = 10). All participants received saline and arketamine (0.5 mg/kg) with a one-week interval. Treatment effects were analyzed with a linear mixed effects (LME) model. ResultsOur analysis suggested the presence of a carryover effect, so the main efficacy analysis was limited to the first week, which demonstrated a main effect of time (p = 0.038) but not for treatment (p = 0.40) or their interaction (p = 0.95). This indicates that depression improved over time, but without significant difference between arketamine and placebo. Analyzing the two weeks together, findings were the same. Dissociation and other adverse events were minimal. LimitationsThis was a pilot study with a small sample and underpowered. ConclusionsArketamine was not superior to placebo for TRD but demonstrated to be extremely safe. Our findings reinforce the importance of continuing studies with this drug, with better powered clinical trials, perhaps considering a parallel design with higher or flexible doses and repeated administrations.

Fecal microbiota transplantation in Parkinson's disease-A randomized repeat-dose, placebo-controlled clinical pilot study.

The intestinal microbiome plays a primary role in the pathogenesis of neurodegenerative disorders and may provide an opportunity for disease modification. We performed a pilot clinical study looking at the safety of fecal microbiota transplantation (FMT), its effect on the microbiome, and improvement of symptoms in Parkinson's disease. This was a randomized, double-blind placebo-controlled pilot study, wherein orally administered lyophilized FMT product or matching placebo was given to 12 subjects with mild to moderate Parkinson's disease with constipation twice weekly for 12 weeks. Subjects were followed for safety and clinical improvement for 9 additional months (total study duration 12 months). Fecal microbiota transplantation caused non-severe transient upper gastrointestinal symptoms. One subject receiving FMT was diagnosed with unrelated metastatic cancer and was removed from the trial. Beta diversity (taxa) of the microbiome, was similar comparing placebo and FMT groups at baseline, however, for subjects randomized to FMT, it increased significantly at 6 weeks (p = 0.008) and 13 weeks (p = 0.0008). After treatment with FMT, proportions of selective families within the phylum Firmicutes increased significantly, while proportion of microbiota belonging to Proteobacteria were significantly reduced. Objective motor findings showed only temporary improvement while subjective symptom improvements were reported compared to baseline in the group receiving FMT. Constipation, gut transient times (NS), and gut motility index (p = 0.0374) were improved in the FMT group. Subjects with Parkinson's disease tolerated multi-dose-FMT, and experienced increased diversity of the intestinal microbiome that was associated with reduction in constipation and improved gut transit and intestinal motility. Fecal microbiota transplantation administration improved subjective motor and non-motor symptoms. ClinicalTrial.gov, identifier: NCT03671785.

Effects of Testosterone+Finasteride on Bone After Spinal Cord Injury: A Randomized, Double-Blind, Placebo-Controlled Pilot Study

Effects of Testosterone+Finasteride on Bone After Spinal Cord Injury: A Randomized, Double-Blind, Placebo-Controlled Pilot Study

The Beneficial Effects of a Multispecies Probiotic Supplement on Glycaemic Control and Metabolic Profile in Adults with Type 1 Diabetes: A Randomised, Double-Blinded, Placebo-Controlled Pilot-Study.

In this pilot-study, the effects of a multispecies probiotic supplement on glycaemic control and metabolic parameters in adults with type 1 diabetes (T1DM) were explored. A total of 50 T1DM patients were enrolled and randomly placed into a group receiving capsules containing multi-probiotic strains (Bifidobacterium longum, Lactobacterium bulagricumi, Streptococcus thermophilus) and insulin (probiotics group, n =27) or a group receiving a placebo and insulin (placebo group, n = 23). All patients underwent continuous glucose monitoring at baseline and 12 weeks after intervention. The primary outcomes were determined by comparing factors such as changes in fasting blood glucose (FBG) and haemoglobin A1c (HbA1c) between the groups. Probiotic supplementation significantly reduced FBG (-1.0±4.7 vs 1.8±4.7mmol/L, p = 0.048), 30 min postprandial glucose (-0.5 ± 4.6 vs 1.9 ± 3.3 mmol/L, p = 0.0495), and low-density lipoprotein cholesterol (-0.07 ± 0.45 vs 0.32±0.78mmol/L, p =0.0413), compared with the placebo. Althoughnotstatisticallysignificant, probiotic supplementation also lowered HbA1c levels by 0.49% (-5.33 mmol/mol, p = 0.310). Besides, no significant difference was observed in the continuous glucose monitoring (CGM) parameters between the two groups. Further subgroup analysis revealed a significant reduction in mean sensor glucose (MSG; -0.75 (-2.11, 0.48) mmol/L vs 1.51 (-0.37, 2.74)mmol/L, p = 0.010) and time above range (TAR; -5.47 (-20.1, 3.04)% vs 18.9 (-1.11, 35.6)%, p =0.006), as well as an greater improvement in the time in range (TIR; 9.32 (-4.84, 16.6)% vs -19.9 (-31.4, 0.69)%, p =0.005) in male patients than female patients in the probiotics group. Multispecies probiotics exerted beneficial effects on fasting and postprandial glucose and lipid profiles in adult T1DM patients, especially for male patients and those with higher baseline FBG levels.

The Effects of β-myrcene on Simulated Driving and Divided Attention: A Double-Blind, Placebo-Controlled, Crossover Pilot Study.

β-myrcene, one of the most common terpenes found in cannabis, has been associated with sedation. We propose that β-myrcene contributes to driving impairment even in the absence of cannabinoids. To conduct a double-blind, placebo-controlled crossover pilot study of the effect of β- myrcene on performance on a driving simulator. A small sample (n=10) of participants attended two experimental sessions, one in which they were randomized to receive 15 mg of pure β-myrcene in a capsule versus a canola oil control. Each session, participants completed a baseline block and three follow-up blocks on a STISIM driving simulator. β-myrcene was associated with statistically significant reductions in speed control and increased errors on a divided attention task. Other measures did not approach statistical significance but fit the pattern of results consistent with the hypothesis that β-myrcene impairs simulated driving. This pilot study produced proof-of-principle evidence that the terpene β-myrcene, an agent commonly found in cannabis, can contributes to impairment of driving-related skills. Understanding how compounds other than THC affect driving risk will strengthen the field's understanding of drugged driving.

Does Inspiratory Muscle Training Affect Static Balance in Soccer Players? A Pilot Randomized Controlled Clinical Trial.

Inspiratory muscle training (IMT) is effective in improving postural stability and balance in different clinical populations. However, there is no evidence of these effects in soccer players. A single-blind, two-arm (1:1), randomized, placebo-controlled pilot study on 14 soccer players was performed with the main aim of assessing the effect of IMT on static balance, and secondarily, of examining changes in the respiratory muscle function. The experimental group (EG) received an IMT program with progressive intensity, from 20% to 80%, of the maximal inspiratory pressure (MIP). The sham group (SG) performed the same program with a fixed load of 20% of the MIP. Static balance and respiratory muscle function variables were assessed. A two-factor analysis of variance for repeated measures was used to assess differences after training. Statistical significance was set at p < 0.05. Significant increases were observed in the EG on length of sway under eyes open (from 2904.8 ± 640.0 to 3522.4 ± 509.0 mm, p = 0.012) and eyes closed (from 3166.2 ± 641.3 to 4173.3 ± 390.8 mm, p = 0.004). A significant increase in the maximal voluntary ventilation was observed for both groups (EG p = 0.005; SG p = 0.000). No significant differences existed between the groups. IMT did not improve the static balance in a sample of soccer players. Conducting a high-scale study is feasible and could refine the results and conclusions stemming from the current pilot study.

Could melatonin prevent Vancomycin-induced nephrotoxicity in critically ill patients? A randomized, double-blinded controlled trial.

Previous research showed some clinical benefits regarding the nephroprotective effect of melatonin. So, this study aimed to evaluate the beneficial effect of oral melatonin on preventing acute kidney injury (AKI) in patients who received vancomycin therapy in the intensive care unit (ICU). We performed a randomized, double-blinded, placebo-controlled pilot study in an academic hospital. Adult patients admitted to the ICU who received vancomycin with normal gastrointestinal and kidney function were randomized into treatment or placebo groups. After that, enrolled patients received a tablet of melatonin (3 mg) or placebo twice daily for seven consecutive days. The occurrence of AKI was assessed by RIFLE criteria (by measurement of serum creatinine (SCr)) and plasma neutrophil gelatinase-associated lipocalin (NGAL) concentration. Moreover, other data related to renal functions and SOFA were also compared between groups. A total of 90 patients were included in the study, while 21patients in the placebo group and 20 in the intervention group completed the study. There were no significant differences between groups regarding baseline SCr, BUN, urine output, NGAL, SOFA, and glomerular filtration rate (GFR). Our results showed that these differences remained insignificant after a 7-day follow-up between groups. However, the incidence of AKI was significantly lower in the melatonin group based on the NGAL cutoff (> 150 ng/mL). We detected a significant decrease in vancomycin-induced nephrotoxicity incidence in patients receiving melatonin compared to placebo. However, more clinical trials in a larger population were required to confirm this result.

A randomized, placebo-controlled pilot study of upamostat, a host-directed serine protease inhibitor, for outpatient treatment of COVID-19

ObjectivesWe performed a pilot study of upamostat, a serine protease inhibitor, in outpatients with symptomatic COVID-19 before a pivotal trial. MethodsSARS-CoV-2 patients with ≥2 moderate-severe symptoms onset within 5 days were randomized to oral upamostat 200 or 400 mg or placebo daily for 14 days. Patients completed COVID-19 symptom questionnaires daily for 28 days, then thrice weekly for 4 weeks, and underwent physical and laboratory examinations periodically. ResultsA total of 61 patients enrolled of which 20 received a placebo or upamostat 200 mg daily; 21 received upamostat 400 mg daily. Treatment was well tolerated; only one patient (upamostat 400) reported a drug-related adverse event, mild skin rash; no patient discontinued owing to a drug-related adverse event. The median time to a sustained recovery from severe symptoms was 8, 4, and 3 days for the three treatment groups, respectively. New severe symptoms developed in 20% of the placebo group vs 2.4% in the combined upamostat groups, (P = 0.036). Three placebo patients (15%) versus no upamostat patients were hospitalized for worsening COVID (P= 0.03). The mean d-dimer level remained constant in placebo patients but decreased by 38% and 48% in upamostat 200 and 400 patients, respectively. ConclusionUpamostat was well tolerated, shortened recovery time, and decreased new severe symptoms and hospitalization.

Anti-IL-17A blockade did not significantly reduce inflammatory lesions in a placebo-controlled pilot study in adult patients with moderate to severe acne

BackgroundCJM112 is a potent anti-IL-17A monoclonal antibody, whose clinical efficacy in psoriasis was recently documented. This study aimed to assess the effect of IL-17A blockade, using CJM112, in patients with moderate to severe acne.MethodsA randomized, placebo-controlled, double-blind, parallel-group, proof-of-concept study was conducted on patients with moderate to severe acne. Patients received CJM112 300 mg, 75 mg, or placebo subcutaneously during Treatment Period 1 (0–12 weeks). Patients receiving placebo were re-randomized to receive CJM112 300 mg or 75 mg during Treatment Period 2 (12–24 weeks). The primary endpoint was the number of inflammatory facial lesions at Week 12.ResultsAs the futility criterion was met during the interim analysis, only 52/75 (69.3%) patients were recruited. In total, 48/52 (92.3%) and 26/41 (63.4%) completed Treatment Periods 1 and 2, respectively. All groups exhibited a reduction in facial inflammatory lesions, with no difference observed between CJM112 and placebo (CJM112 300 mg 27.6 ± 20.7; CJM112 75 mg 30.4 ± 34.8; placebo 23.6 ± 13.6; primary endpoint). Additionally, no differences were observed between groups in other secondary and exploratory endpoints at Week 12.ConclusionsAnti-IL-17A therapy was not significantly different compared to the placebo in reducing inflammatory lesions in patients with moderate to severe acne.

The Influence of a Single Instrument-Assisted Manual Therapy (IAMT) for the Lower Back on the Structural and Functional Properties of the Dorsal Myofascial Chain in Female Soccer Players: A Randomised, Placebo-Controlled Trial.

Background: Instrument-assisted manual therapy (IAMT) is indicated to improve flexibility, reduce pain, and induce hyperaemia locally and along myofascial chains. The underlying effects are largely unclear. This randomised, placebo-controlled pilot study aimed to gain first insights into these effects, primarily on the structural level, through ultrasonography. Methods: 67 healthy female soccer players aged 20.9 (±3.9) years were examined after right lumbar intervention (IAMT: intervention group (IG), heat application: comparison group (CG), pressure-less placebo: placebo group (PG)). Ultrasonography (absolute movement and shear motion), flexibility tests (passive straight leg raise test (PSLR), lumbar and thoracic double inclinometry), and superficial skin temperature were recorded before (t0), immediately (t1) and 45 min after the intervention (t2). Results: IAMT decreased the absolute mobility of the superficial lamina and its shear motion to the superficial fascia compared with the PG (t1; p < 0.05). PSLR improved in the IG compared with the CG (t2) and PG (t1, t2; p < 0.05). The temperature increased in the IG and CG compared with the PG (t1, t2) and in the CG compared with the IG (t1; p < 0.05). Conclusion: IAMT of the lumbar back briefly reduces absolute mobility of the superficial lamina and its shear motion to the superficial fascia, improves flexibility, and increases the temperature.

The Impact of Lactobacillus Plantarum PCS26 Supplementation on the Treatment and Recurrence of Urinary Tract Infections in Children-A Pilot Study.

Urinary tract infections (UTI) are frequent bacterial infections in childhood. Considering the known beneficial effects of probiotics in the gastrointestinal field, they could also help to alleviate UTIs. In our clinical pilot study, we sought to verify the positive effects of the specific probiotic strain on the course and prevention of UTI in children. Thirty children with UTIs were enrolled and sequentially sampled into two groups (placebo/control and probiotic/test) in a double-blind, randomized, placebo-controlled clinical pilot study. We chose Lactobacillus plantarum PCS 26 (Lp26) derived from local Slovenian cheese in Pathogen Combat Project, which showed a good in vitro antimicrobial effect on Escherichia coli (E. coli). Several parameters were followed to look for differences between both groups in the acute phase of the UTI and after 6 months of taking probiotic or placebo supplementation. Our results showed no statistically significant differences between both groups; however, two children in the placebo group suffered a recurrence of febrile UTI within 6 months of the follow-up period, while there were no recurrences of UTI in the probiotic group. In the test group, the number of febrile days after the initiation of antibiotics with probiotics was shorter, although not reaching statistical significance (p = 0.084). According to our results, probiotics might be helpful in alleviating UTI symptoms and in UTI prevention. Further research with a larger sample size is warranted. Additionally, basic scientific studies for the selection of proper immunobiotic strains of probiotics should be performed.

Pilot Study of Vocacapsaicin for Treatment of Pain After Open Laparotomy

Introduction: Postoperative mobilization requires effective management of pain with movement. Vocacapsaicin (formerly CA-008) is a water-soluble prodrug of capsaicin, a well-characterized TRPV1 receptor agonist. Intraoperative injection of vocacapsaicin reduced pain and opioid consumption for 2 weeks after total knee arthroplasty and bunionectomy. This randomized, double-blind, placebo-controlled pilot study evaluated safety and efficacy of vocacapsaicin after open laparotomy for ventral hernia repair (VHR). Methods: After internal review board approval and written informed consent, patients underwent elective, open VHR with mesh (Rives-Stoppa) under general anesthesia with standard-of-care perioperative analgesia including bilateral bupivacaine rectus blocks and peri-incisional bupivacaine infiltration. (ClinicalTrials.gov:NCT04774328). Before closing, placebo or vocacapsaicin 24 mg in 80 mL saline was infiltrated into the surgical site. Endpoints included serial numerical rating scales (NRS) for pain with activity (coughing, ambulation) and opioid consumption over 96 hours. Multiple local and systemic safety endpoints, including wound healing, were measured repeatedly through postoperative day 28. Results: Twenty-four patients were enrolled. Through the first 96 hours, vocacapsaicin reduced pain on coughing 46% (p = 0.02, ANOVA), pain on ambulation 35% (p = 0.08), pain at rest 21% (p = nonsignificant [NS]) and cumulative opioid consumption 26% (p = NS). A trend towards improved analgesia persisted through 8 days. There was no difference between vocacapsaicin and placebo in the safety analysis through day 28. Conclusion: This pilot study suggests that a single intraoperative dose of vocacapsaicin provides clinically meaningful pain reduction for 96 hours after open laparotomy when added to a standard-of-care analgesic regimen. There were no safety concerns. The results are consistent with previous results in orthopaedic surgery.

Activation of mitochondrial telomerase reverses relative lymphopenia post myocardial infarction: results from the randomised, double-blinded TACTIC phase IIa pilot trial

Abstract Background Immune ageing is a phenomenon which includes lymphopenia, expansion of pro-inflammatory T-lymphocyte subsets and telomere shortening. While lymphopenia predicts mortality after myocardial infarction (MI), MI itself leads to both an increase in terminally differentiated memory CD8+ T-lymphocytes (CD8+ TEMRAs) and a decrease in telomere length. Activation of telomerase has been shown to ameliorate lymphopenia, and improve heart function after MI in mouse models. TA-65 is an oral telomerase activator, which may ameliorate immune ageing and improve outcome after MI. Methods This double-blinded, randomized placebo-controlled pilot study evaluated the use of TA-65 in 90 MI patients over 65 years, the average onset age for immune ageing. Patients were randomised to either TA-65 (16 mg daily, n=45) or placebo (n=45) for 12 months. The majority of patients underwent percutaneous coronary intervention (87%) or coronary artery bypass surgery (2%) as treatment for their index MI. The pre-defined primary endpoint was the proportion of CD8+ TEMRA T-lymphocytes at 12 months, a marker of immune ageing. A linear mixed effects model was used for the analysis. Results The proportion of CD8+ TEMRAs after 12 months did not differ between the 2 treatment groups, although only increased significantly in the placebo group (+2.2%, 95% CI: 0.14–4.24). TA-65 was well tolerated, with total adverse events lower in the treatment group (TA-65 vs. placebo group: n=130 vs. n=185). We observed at 12 months a 62% reduction in mean high-sensitivity CRP (hsCRP: TA-65 vs. placebo group: 1.1±0.9 vs. 2.9±6.4 mg/L) and a 15%-increase in mean peripheral blood lymphocytes in TA-65 after 12 months. In the whole sample, among those who were treated with TA-65 compared to Placebo, after 12 months peripheral blood lymphocytes increased (+285 cells /μl, 95% CI: 117–452). The latter was due to significant increases in the TA-65 group from baseline to 12 months across all major lymphocyte populations: CD3+ (+15%), CD4+ (+14%),CD8+ T-lymphocytes (+19%), B-lymphocytes (+17%) and natural killer cells (+12%), while no changes occurred in major lymphocyte populations in the placebo group over the course of the study. Conclusion In this randomised clinical trial, we found that while CD8+ TEMRAs were not significantly altered after 12 months, the telomerase activator TA-65 significantly increased all major lymphocyte subsets and substantially reduced hsCRP at 12 months in patients with MI. These findings suggest TA-65 holds great promise in potentially reducing inflammation while improving an age-related decline in major lymphocyte populations, thereby enhancing immunity. A larger, multicentre, powered phase IIb efficacy trial to examine the potential effect of TA-65 in prognosis and heart function after MI is therefore warranted. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): TA-Science, New York, USA

Effects of a Novel Amino Acid Formula on Nutritional and Metabolic Status, Anemia and Myocardial Function in Thrice-Weekly Hemodialysis Patients: Results of a Six-Month Randomized Double-Blind Placebo-Controlled Pilot Study.

(1) Background: Chronic Kidney Disease (CKD) induces metabolic derangement of amino acid (AA) kinetics, eliciting severe damage to the protein anabolism. This damage is further intensified by a significant loss of AAs through hemodialysis (HD), affecting all tissues with a high metabolic turnover, such as the myocardium and body muscle mass. (2) Aim: to illustrate the effects of a novel AA mixture in boosting mitochondrial energy production. (3) Methods: A strict selection of 164 dialysis patients was carried out, allowing us to finally identify 22 compliant patients who had not used any form of supplements over the previous year. The study design envisaged a 6-month randomized, double-blind trial for the comparison of two groups of hemodialysis patients: eleven patients (67.2 ± 9.5 years) received the novel AA mix (TRG), whilst the other eleven (68.2 10.5 years) were given a placebo mix that was indistinguishable from the treatment mix (PLG). (4) Results: Despite the 6-month observation period, the following were observed: maintenance of target hemoglobin values with a reduced need for erythropoiesis-stimulating agents in TRG > 36% compared to PLG (p < 0.02), improved phase angle (PhA) accompanied by an increase in muscle mass solely in the TRG group (p < 0.05), improved Left Ventricular Ejection Fraction (LVEF > 67%) in the TRG versus PLG group (p < 0.05) with early but marked signs of improved diastolic function. Increased sensitivity to insulin with greater control of glycemic levels in TRG versus PLG (p = 0.016). (5) Conclusions: the new AA mix seemed to be effective, showing a positive result on nutritional metabolism and cardiac performance, stable hemoglobin levels with the need for lower doses of erythropoietin (EPO), insulin increased cell sensitivity, better muscle metabolism with less loss of mass.

Efficacy of antiseptic mouthrinses against SARS-CoV-2: A prospective randomized placebo-controlled pilot study

ObjectivesCoronavirus-disease-19 (COVID-19) continues to affect millions of individuals worldwide. Antiviral activity of mouthrinses remains an important research area as the oral cavity is a site of SARS-CoV-2 initial replication. The aim of this study was to assess the effectiveness of three different mouthrinses in reducing the oral/oropharyngeal SARS-CoV-2 viral load. MethodsAdult patients, hospitalized with confirmed COVID-19 were recruited for the study. Oral/oropharyngeal baseline SARS-CoV-2 samples were collected and analyzed by Real-Time-PCR. Subsequently, patients were instructed to rinse with 1 % hydrogen peroxide (H2O2), 0.12 % chlorhexidine (CHX), 1 % povidone‑iodine (PVP-I) or Sodium Chloride 0.9 % (placebo). Viral loads were measured right after (T1), and at 45 min (T2) from the rinse. ResultsIn the PVP-I 1 % group, 5/8 (62.5 %) patients at T1, and 3/8 (37.5 %) patients at T2, SARS-CoV-2 was not detectable in the swab specimens. In the H2O2 1 % group, 2/11 (18.2 %) patients at T1, and 2/11 (18.2 %) other patients at T2 showed no SARS-CoV-2 loads. One (12.5 %) patient in the CHX 0.12 % group showed SARS-CoV-2 negativity at T2. One (9.1 %) patient at T1, and another (9.1 %) patient at T2 showed no SARS-CoV-2 loads in the placebo group. ConclusionsOral SARS-CoV-2 loads were reduced at T1 in the PVP-I 1 % and H2O2 1 % groups. Clinical relevancePVP-I 1 % was the most effective rinse especially in patients with low viral copy numbers at baseline.

Using the posterior TAP block for postoperative analgesia for major liver surgery in pediatrics

Anesthesiological provision of pediatric liver surgery is associated with problems related to perioperative analgesia. Standard methods of anesthesia can have contraindications and complications.The objective: To evaluate the safety and efficacy of the posterior TAP block for postoperative analgesia in pediatric liver surgery.Subjects and Methods. A prospective, single, blind, placebo-controlled pilot study was conducted. The participants were children aged 2 to 7 who underwent liver resection. The patients were divided into groups. In Control Group, combined anesthesia was performed. In Study Group, it was combined with a bilateral posterior TAP block. Pain in the postoperative period was assessed by the FLACC scale.Results. The intensity of pain in the postoperative period was higher in Control Group. More patients required tramadol administration in Control Group. There was no difference in the occurrence of the PONV syndrome. No complications associated with the block were noted.Conclusion. The posterior TAP block has a clinically significant analgesic effect and can be used for perioperative pain relief during pediatric liver surgery. This method is relatively safe. Impaired hemostasis system is not an absolute contraindication to a TAP block.

Mango (Mangifera indica L.) Polyphenols Enhanced by Supplemental Probiotics Improve Biomarkers for Inflammation and Cognitive Function in Lean and Obese Individuals

ObjectivesThis study was designed to investigate the effects of daily mango supplementation with probiotics for 8 weeks on inflammation and cognitive function in lean and obese individuals. It was hypothesized that mango supplementation with probiotic consumption has a synergistic benefit by enhancing the bioavailability of their metabolites and their beneficial activities. MethodsThis double-blind, randomized, placebo-controlled pilot study was conducted in 50 healthy lean (BMI 18–23 kg/m2) and 44 obese (BMI 27–35 kg/m2) participants aged 18–55. Participants consumed 400 g of mango pulp with one placebo/probiotics capsule over 8 weeks. On days 1 and 54, participants underwent cognitive function tests and blood-collections. In addition, participants took 10 sessions of visual cognitive function testing on days 43–54.< ResultsMango intake with probiotics for 8 weeks reduced plasma levels of TNF-a and IL-10 (p = 0.037 and 0.049, respectively) compared to mango placebo group in obese participants but had no significant effect in lean participants. Visual cognitive performance was greater in lean participants (p = 0.050) but training responses were similar to obese. Probiotic resulted in lower visual cognitive performance (p = 0.018) but similar training responses as compared to placebo. In the trail making test (Attention) and digit span test (Memory), mango intake significantly improved overall cognitive performance in the lean participants, but only on the digit span backward test in obese participants. Simultaneous intake of mango and probiotics was not significantly different compared to mango with placebo in the trail making test but showed a synergistic effect in the digit span test. The amount of plasma metabolites was directly correlated with BMI (p = 0.0176, r = –0.1753, Spearman correlation) and IFN-g (p = 0.0336, r = 0.1572, Spearman correlation). ConclusionsMango consumption improved cognitive performance in lean individuals, whereas simultaneous intake of mango and probiotics had a synergistic effect in attenuating inflammation and improving cognitive functioning in obese individuals, at least in part due to increased bioavailability of mango polyphenols. Funding SourcesUSDA-AMS-National Mango Board.

A pilot study of combined oral minocycline and narrowband UVB phototherapy in vitiligo: A randomized, double-blind, placebo-controlled trial.

Narrowband ultraviolet B (NBUVB) phototherapy is an effective therapeutic option for generalized vitiligo. Previous reports showed the potential benefit of minocycline to stop disease progression in vitiligo. Meanwhile, minocycline has antioxidative, anti-inflammatory, and immunomodulating properties. There is no clinical study combining oral minocycline and NBUVB for treating generalized vitiligo. This study aims to compare the efficacy and safety of the combination treatment of NBUVB plus oral minocycline with NBUVB alone in generalized vitiligo. A randomized, double-blinded, placebo-controlled pilot study was conducted. Patients were randomly treated with either combined oral minocycline 100 mg per day plus NBUVB phototherapy or placebo plus NBUVB. All patients recieved NBUVB two times per week, for 12 weeks. The outcomes were assessed using Vitiligo Area Scoring Index score (VASI) percent change, quartile grading scale (QGS) of repigmentation, and Vitiligo Disease Activity Index (VIDA) score. Fourteen generalized vitiligo patients were included, and seven cases were assigned in each group. At week 12, the mean VASI score was decreased by 28.87% (24.15) in the minocycline group compared to 27.26% (7.98) in placebo group (p= 0.886). No significant difference was observed between both treatment modalities in QGS of repigmentation and mean VIDA score change. Two of the seven patients (29%) receiving minocycline developed hyperpigmentation, dark-brown and muddy brown discoloration, which was only confined to some vitiliginous patches. In conclusion, combination therapy with oral minocycline does not enhance the efficacy of NBUVB in generalized vitiligo. Due to the high incidence of drug-induced skin hyperpigmentation, minocycline plus NBUVB should be avoided.