Double-blind Study Research Articles

Low-Dose Oral Ginger Improves Daily Symptom Scores in Asthma

Background/Objective: A significant number of individuals with asthma have poorly controlled daily symptoms and utilize dietary supplements such as ginger in a quest for improved symptom control; however, its effectiveness at improving the control of symptoms is unproven. We questioned whether low-dose oral ginger would improve subjective and objective measurements of asthma control in mild-to-moderate asthmatics. Methods: We performed a randomized, placebo-controlled, double-blinded study of a low dose (1 g twice daily) of a dietary supplement of ginger in 32 mild-to-moderate uncontrolled asthmatics over a 2-month trial period while maintaining daily conventional asthma therapies. The planned primary outcomes included an increased tolerance to inhaled methacholine and decreased concentrations of fractional excretion of exhaled nitric oxide (FeNO). Secondary planned outcomes included measurements of asthma control by the Asthma Control Test (ACT), a 2-week symptom recall test, and the Juniper mini Asthma Quality of Life Questionnaire (AQLQ), and blood eosinophils and asthma-associated cytokines. Results: Exhaled nitric oxide or blood eosinophils were not changed by oral ginger. However, three different measures of asthma symptom control were improved by the 28-day time point of oral ginger. Asthma-associated serum cytokines (IL-13 and IL-17A) were modulated by oral ginger. Conclusions: This is the first demonstration that a small daily dose of a dietary supplement of ginger may improve asthma symptoms and reduce inflammation in human asthmatics. These findings support the need for additional studies using larger doses of ginger in specific endotypes of asthmatics that may identify a novel therapeutic for asthma.

A Clinical Study to evaluate the therapeutic effect of Akulyaabdadi Kashaya in Madhumeha (Type-II Diabetes Mellitus)

Introduction: In 2024 approximately 540 million adults (20-70 years) are living with diabetes as per data of IDF (international diabetes Federation). WHO states that diabetes will be 7th leading cause of death by 2030. Ayurveda says Madhumeha is a variety of Vataja Parmeha where the patient passes the urine with sweetness and astringency. The main symptoms involved are Prabhoota Mootrata (excessive urination) and Avila-Mootrata (non-transparency of urine). The major cause of disease is sedentary lifestyle and indulgence in Kapha-Medakar Aahara along with Divaswapana (day sleeping), avoidance of any form of exercise, hence indicating Santarpanjanya origin of disease. Methods: Akulyaabdadi Kashaya, the first Kashaya mentioned in Pramehahara Kashayas if Sahasrayoga is taken for single blind clinical study on 30 patients and the efficacy is established post 30-days of treatment. Results: During the study, it was found that signs and symptoms like polyuria, turbidity in urine, polyphagia, excessive thirst, burning sensation and numbness in feet, weakness, excessive sweating and lassitude were significantly reduced and Akulyaabdadi Kashaya, the trial drug was found highly significant at 0.1% level with p- value <0.001 to improve the FBS, PPBS, urine glucose (FUS & PPUS) and establishes it as a good treatment of Diabetes as a long term drug.

Efficacy and safety of lemborexant in subjects with insomnia disorder receiving medications for depression or anxiety symptoms.

Individuals with insomnia frequently have comorbid depression or anxiety. This study sought to provide a preliminary indication of the effects of lemborexant (LEM) in subjects treated for mild depression/anxiety symptoms. E2006-G000-303 (NCT02952820; EudraCT 2015-001463-39; SUNRISE-2) was a 12-month, phase 3, randomized, placebo-controlled, double-blind study where subjects with insomnia disorder were randomized (1:1:1) to placebo, LEM 5 mg (LEM5), or LEM 10 mg (LEM10) for 6 months. During the second 6 months (not reported), placebo-treated subjects were re-randomized to LEM5 or LEM10. In this post hoc analysis, changes from baseline (CFB) in subject-reported (subjective) sleep onset latency (sSOL), sleep efficiency (sSE), wake after sleep onset (sWASO), total sleep time (sTST), Fatigue Severity Scale, and Insomnia Severity Index were evaluated in subjects treated with medications for symptoms of depression/anxiety (subpopulation). Of 949 randomized subjects, 61 treated with medications for symptoms of depression/anxiety were included. In the subpopulation, CFB comparing LEM with placebo were generally smaller than the overall population due to a larger placebo response in the subpopulation. However, the magnitudes of CFB within the active treatment groups for sSOL, sWASO, sTST, and sSE were similar between the subpopulation and the overall population. No new safety signals were observed in the subpopulation. LEM treatment benefited subjects with insomnia treated with medications for depression/anxiety symptoms, with no new safety signals. A greater placebo response in the subpopulation than in the overall population decreased the drug versus placebo effect size for LEM, as has been reported for other insomnia medications.

Double-blinded, randomized tolerance study of a biologically enhanced Nanogel with endothelin-1 and bradykinin receptor antagonist peptides via intra-articular injection for osteoarthritis treatment in horses

BackgroundOsteoarthritis is a leading cause of pain and retirement in athletic horses. Hydro-expansive functionalized nanogels, acting as Drug Delivery Systems, constitute one of the current therapeutic prospects. These nanogels have the potential to combine mechanical benefits through polymers with the biological effect of prolonged release of bioactive molecules. The purpose of this double-blinded randomized tolerance study versus negative control was to evaluate the response of healthy joints to a single injection of the expected efficient dose (further referred to as the trial dose) and overdose of nanogels composed of chitosan and hyaluronic acid and featuring a type A endothelin receptor antagonist and a type B1 bradykinin receptor antagonist. The metacarpophalangeal joints of 8 healthy horses were randomly injected with 2.4 mL of functionalized nanogels and 2.4 mL of saline as control on the contralateral limb. Injections were repeated twice at one-week intervals, followed by injection of a triple dose of nanogel on week four. Clinical, ultrasonographic and synovial fluid cellular and biochemical follow-ups were performed up to three months following the first injection.ResultsNo change in general clinical parameters, lameness or sensitivity to passive flexion of the fetlocks was noted. Mild to moderate synovitis was noted on the day following injection in the treated group, with a significant difference (p < 0.05) compared to the control group. It spontaneously resolved on day 3 following the injections and did not increase with repeated injections. Similar effects were noted after injection of the triple dose but lasted for a week. Synovial fluid markers of inflammation also showed a transient significant increase in the treated group one week after each injection, but no differences were detected at the end of the study.ConclusionsInjections of the expected therapeutic dose of functionalized nanogel in healthy joints induced a mild transient inflammatory response in the joint. Three injections of the trial dose at one-week intervals and injection of thrice the trial dose induce a mildly greater inflammation without harmful effects on joints. Functionalized nanogels are well tolerated prospects for the treatment of osteoarthritis in horses. Their beneficial effects on arthritic joints have yet to be evaluated to determine their therapeutic potential.

Diet and Immune Effects Trial (DIET)- a randomized, double-blinded dietary intervention study in patients with melanoma receiving immunotherapy

BackgroundGut microbiome modulation is a promising strategy for enhancing the response to immune checkpoint blockade (ICB). Fecal microbiota transplant studies have shown positive signals of improved outcomes in both ICB-naïve and refractory melanoma patients; however, this strategy is challenging to scale. Diet is a key determinant of the gut microbiota, and we have previously shown that (a) habitual high dietary fiber intake is associated with an improved response to ICB and (b) fiber manipulation in mice impacts antitumor immunity. We recently demonstrated the feasibility of a controlled high-fiber dietary intervention (HFDI) conducted in melanoma survivors with excellent compliance and tolerance. Building on this, we are now conducting a phase II randomized trial of HFDI versus a healthy control diet in melanoma patients receiving ICB.MethodsThis is a randomized, double-blind, fully controlled feeding study that will enroll 45 melanoma patients starting standard-of-care (SOC) ICB in three settings: adjuvant, neoadjuvant, and unresectable. Patients are randomized 2:1 to the HFDI (target fiber 50 g/day from whole foods) or healthy control diet (target fiber 20 g/day) stratified by BMI and cohort. All meals are prepared by the MD Anderson Bionutrition Core and are isocaloric and macronutrient-controlled. The intervention includes a 1-week equilibration period and then up to 11 weeks of diet intervention. Longitudinal blood, stool and tumor tissue (if available) are collected throughout the trial and at 12 weeks post intervention.DiscussionThis DIET study is the first fully controlled feeding study among cancer patients who are actively receiving immunotherapy. The goal of the current study is to establish the effects of dietary intervention on the structure and function of the gut microbiome in patients with melanoma treated with SOC immunotherapies. The secondary endpoints include changes in systemic and tumor immunity, changes in the metabolic profile, quality of life, symptoms, disease response and immunotherapy toxicity.Trial registrationThis protocol is registered with the U.S. National Institutes of Health trial registry, ClinicalTrials.gov, under the identifier NCT04645680. First posted 2020-11-27; last verified 2024-06.

Ivermectin 1% Combined With Intense Pulsed Light Treatment for Dry Eye Disease Secondary to Demodex Blepharitis.

To examine the safety and efficacy of combined treatment with topical ivermectin 1% and intense pulsed light (IPL) for dry eye disease (DED) secondary to demodex blepharitis. A retrospective review of medical files of patients treated at a private clinic specializing in DED between November 2022 and February 2024 was performed. Sixty-one patients aged 18 years or older with DED because of demodex blepharitis, who received the IPL and ivermectin 1% combination therapy, were included. IPL was applied to the periocular area 4 times at 2- to 3-week intervals, and ivermectin 1% once daily for 1 to 2 months. Both eyes (n = 122) of each patient were evaluated before and immediately after treatment cessation. Blepharitis, meibomian gland secretion, corneal staining, patient satisfaction, and overall clinical improvement were recorded. Mean age was 59.6 ± 17.6 years and 50.8% (n = 31) were males. Meibomian gland secretion grading improved significantly after treatment from 2.74 ± 0.63 to 1.63 ± 0.63 (P < 0.001). Blepharitis was eliminated after treatment in 77.0% of patients (23.0% after treatment vs. 100.0% before, P < 0.001). The patient satisfaction rate was moderate to high (range 0-2, mean 1.54 ± 0.60). Clinical improvement rate was moderate to high as well (range 0-2, mean 1.52 ± 0.50). No significant side effects were observed. The combined application of topical ivermectin and IPL to the facial area induced significant improvement of demodex blepharitis and meibomian gland secretion grading along with a high rate of patient satisfaction. Further randomized controlled double-blinded studies are needed.

Safety and therapeutic potential of allogeneic adipose-derived stem cell spray transplantation in ischemic cardiomyopathy: a phase I clinical trial

BackgroundIschemic cardiomyopathy, characterized by coronary artery atherosclerosis, impairs the myocardial tissue. Coronary artery bypass grafting (CABG) is commonly used to revascularize affected areas and improve patient survival rates; however, it can fail to enhance cardiac function. Impaired capillary blood flow may obstruct functional recovery, prompting interest in treatments, such as angiogenic factor administration. Adipose-derived stem cells (ADSCs), which are known for immune evasion, have shown the potential to construct capillary networks and improve myocardial function. This clinical trial aimed to evaluate the safety and efficacy of ADSC spray therapy combined with CABG.MethodsThis single-center, randomized, double-blind study involved patients with ischemic cardiomyopathy who were scheduled for CABG and who had a left ventricular ejection fraction ≤ 40%. The participants were randomized to receive CABG as well as ADSC spray therapy or placebo. The primary endpoints were safety, changes in late gadolinium-enhanced (LGE) magnetic resonance imaging (MRI) volumes, and feasibility. The secondary endpoints included left ventricular function, exercise tolerance, and heart failure symptoms.ResultsSeven patients were enrolled; of them, six were randomized to receive ADSC therapy (n = 3) or placebo (n = 3). The procedure was successfully completed with minimal adverse events. One patient in the ADSC group developed pleural effusion that was resolved with drainage. The LGE-MRI volumes decreased in the ADSC group but remained unchanged in the placebo group. Improvements in left ventricular function and exercise tolerance were noted in the ADSC group, with heart failure symptoms improving to New York Heart Association class I. In contrast, the placebo group showed no significant changes, with one patient experiencing worsening symptoms.ConclusionsADSC spray therapy combined with CABG demonstrated safety and efficacy at enhancing cardiac function. ADSC likely contributes to capillary network reconstruction, thereby augmenting the benefits of CABG. Future phase II and III trials are warranted to confirm its therapeutic efficacy and long-term outcomes. This novel approach represents a significant advancement in the treatment of ischemic cardiomyopathy and offers a viable strategy for improving myocardial function and patient prognosis.Trial registration This study was registered with the Japan Registry of Clinical Trials (jRCT2053190103) and ClinicalTrials.gov (NCT04695522)Graphical

Comparative Study Between Intravenous Dexmedetomidine And Fentanyl For Attenuation Of Haemodynamic Response To Laryngoscopy And Endotracheal Intubation: A Randomized Control Trial

Background: The degree of haemodynamic changes that are observed may vary depending on a number of factors, including the level of anaesthesia, the kind of anaesthetic drug used, whether any safety measures are followed prior to airway manipulation, the duration of the laryngoscopy or intubation, and others The main mechanism generating hypertension and tachycardia, the sympathetic response, may be heightened by catecholamine activity. Pressor response has been linked to intraoperative myocardial infarction, abrupt left ventricular failure, dysrhythmias, or intracranial haemorrhage in patients with end organ decompensation. Dexmedetomidine is a highly selective and specific α-2 adrenoceptor agonist with an α2:α1 binding selectivity ratio of 20:1, whereas clonidine has a ratio of 220:1. Clonidine and dexmedetomidine bind to and activate α-1 and α-2 receptors, respectively.Additionally, a plethora of studies has shown that dexmedetomidine reduces the haemodynamic response to laryngoscopy and intubation. One of the most powerful analgesics is fentanyl, a synthetic opioid that, when given before induction, lowers the haemodynamic response to intubation. A comparative study between dexmedtomidine and fentanyl is necessary to determine whether medicine is more beneficial, as both medications have the ability to decrease the sympathetic response to endotracheal intubation and laryngoscopy. Materials and Methods: A prospective randomized, and double-blind study was conducted in 60 ASA Grade I and II patients of either gender, aged between 18 and 65 years, undergoing various surgical procedure under spinal-anesthesia and developing shivering. The patients were randomized into two groups of n = 30 each to receive either dexmedetomidine - 0.6 µg/kg (Group D) Fenatnyl- 2 µg/kg (Group F) as an intravenous just before intubation. Blood pressures (systolic, diastolic and mean) recordings. Apart from general physical and systemic examination, routine investigations, blood urea, serum creatinine, serum electrolytes, ECG and X- Ray chest was performed in all patients SPSS-20 was used for statistical analysis, unpaired t-test for numerical data and chisquare test for categorical data. Results: The mean age was between 39 to 40 years and mean BMI was around 26. Similarly, the mean duration of surgery was 70 minutes for both the groups. Total males in study were 29 and females were 31. There was statistically significant difference in Mean arterial blood pressure (MAP) in both study groups after intubation and at 1 minute. The mean MAP in F group was more than D group at all the time intervals. The mean heart rate was statistically higher in F group as compared to D group at all time after intubation. The frequency of bradycardia was nil in F group as compared to 20% in D group. Frequency of hypotension was13% in D group and nausea or vomiting was 20% in F group. Conclusion: Our research shows that a single intravenous dose of Fentanyl (2µg/kg body weight) given over 2 minutes prior to induction and Dexmedetomedine 0.6µg/kg body weight infused over 10 minutes are both effective at obstructing the hemodynamic stress response to laryngoscopic endotracheal intubation without causing any appreciable side effects. On the other hand, when it comes to reducing the hemodynamic stress response following laryngoscopic endotracheal intubation, IV Dexmedetomidine works better and more efficiently than Fentanyl

Novel Lipid Formulation Increases Absorption of Oral Cannabidiol (CBD)

Background: Cannabidiol (CBD) is an approved treatment for childhood epilepsies and a candidate treatment for several other CNS disorders. However, it has poor oral bioavailability. We investigated the effect of a novel lipid formulation on its absorption in humans and on its tissue distribution in mice. Methods: In a double-blind crossover study in fasting healthy volunteers, we compared the pharmacokinetics of a single dose of 1000 mg of CBD in the lipid formulation and in a powder formulation (ClinicalTrials.gov: NCT05032807). In a second study, male CD1 mice were administered CBD in either the lipid formulation or dissolved in water, via oral gavage (n = 1 per timepoint). The tissue distribution of CBD was assessed using matrix-assisted laser desorption/ionization mass spectrometric imaging. Results: Plasma exposure (AUC0–48) of CBD was nine times greater for the lipid formulation than the powder formulation (611.1 ng·h/mL [coefficient of variation {CV%}: 104.6] and 66.8 ng·h/mL [CV%: 50.7], respectively). With the powder formulation, the AUC0–48 was related to the concentration of specific gastrointestinal bacteria and bile acids. These associations were attenuated with the lipid formulation. In the animal study, after treatment with the lipid formulation, measurable concentrations of CBD were identified in all organs. For the aqueous formulation, tissue concentrations of CBD were below the limit of quantification. Conclusions: Administering oral CBD in a lipid formulation was associated with an increase in its gastrointestinal absorption, as well as an attenuation of the relationship between its absorption and features of the gut microbiome.

Comparing the efficacy of intra-articular injection of Platelet Rich Plasma (PRP) with corticosteroids (CS) in patients with chronic zygapophyseal joint low back pain confirmed by double intra-articular diagnostic blocks: A triple-blinded randomized multicentric controlled trial with a 6-month follow-up

ObjectiveTo compare the safety and effectiveness in improving function and reducing pain of autologous PRP to corticosteroid (CS) zygapophyseal (Z-joint) intra-articular (IA) injections at six months for patients with chronic osteoarthritis Z-joint mediated low back pain (LBP). DesignProspective triple-blinded multicentric randomized controlled trial. MethodsFifty participants with radiological signs of Z-joint OA and chronic Z-joint mediated LBP confirmed by a ≥80 % pain improvement after two IA local anesthetic injections were randomized into PRP and CS groups, using a 1:1 ratio. Participants completed questionnaires at baseline, and at 1-, 3- and 6-month post-treatment, with adverse effect data collected at 1 month. Function (Oswestry disability index (ODI)), pain (Numeric Rating Scale (NRS)), treatment satisfaction (modified MacNab criteria), and quality of life (Short Form survey 36 (SF-36)) were assessed at each follow-up. The primary outcome was the percentage of participants improving their function (ODI score) above the minimal clinically important difference (MCID) of 17 points. The secondary outcomes were the percentage of participants with a >50 % NRS improvement, satisfaction to treatment and mean score improvement. Proportions were compared between groups using a chi-square test. Mean scores were compared using a two-way ANOVA or the nonparametric Brunner & Langer test. ResultsBoth groups were similar at baseline, no major adverse effects occurred, and no participants were lost at follow-up. The proportion of participants improving their ODI scores above the MCID, the proportion of participants with a >50 % NRS improvement, and mean ODI scores were significantly different between groups in favor of PRP at 6 months. Modified MacNab satisfaction scale, NRS and SF36 mean scores were not statistically different between groups, but all followed the same pattern: the CS groups had a greater improvement a one month, both groups were equivalent at three months and the PRP group had a greater improvement at six months. ConclusionThis first triple-blinded multicentric RCT demonstrates the safety of PRP IA Z-joint injections and its superiority in improving pain and function at six months post-treatment compared to CS for patients with chronic OA Z-joint mediated LBP. To perform a blinded control study, two intra-articular treatments were compared. However, knowing that radiofrequency neurotomy (RFN) of the medial branch diagnosed by branch blocks has been standard of care for pain originating from Z-joints, further studies comparing PRP to RFN are still needed. Clinicaltrials gov registry numberNCT05188820.

MELATONIN ON SLEEP IN PARKINSON’S DISEASE: A RANDOMIZED DOUBLE BLIND PLACEBO CONTROLLED TRIAL

BackgroundSleep disturbances are one of the most common non-motor symptoms in Idiopathic Parkinson’s Disease (IPD) patients. However, the effect of melatonin on sleep problems in Parkinson's disease patients is unclear. Aims and objectivesTo study the effect of melatonin on sleep in IPD patients through subjective and objective assessment. MethodsBetween August 2023 to February 2024, we conducted a randomized, double-blind, placebo-controlled trial on IPD patients. We randomized eligible subjects to melatonin (3mg) (n=43) or placebo (n=43) for 8 weeks. The primary endpoint was sleep quality assessed through the Pittsburgh sleep quality index and daytime sleepiness using Epworth sleepiness scale. Secondary endpoints were polysomnographic sleep parameters, quality of life, motor and non-motor symptoms. Assessments were done at baseline and at the end of 8 weeks. ResultsWe screened 107 IPD patients and 86 patients were included in the study. Seventy three patients (melatonin, 35 and placebo, 38) completed the study. The mean change in Pittsburgh Sleep Quality Index (PSQI) score between the two groups was 1.87 (95% CI: 1.5–2.1; p = 0.001) and Epworth Sleepiness Scale (ESS) score was 1.25 (95% CI: 0.80-1.71; p = 0.001) favoring melatonin. The mean difference between the two groups for Non-Motor Symptoms Scale (NMSS) was 6.11 (95% CI 5.27-6.92; p = 0.001), Parkinson's Disease Questionnaire (PDQ 39) 8.12 (95% CI 6.97-9.50; p = 0.001) & Polysomnography (PSG) parameters [sleep latency 8.36 (95% CI 4.38-12.34; p = 0.001) and total sleep time 14.51 (95% CI 5.00-24.41; p = 0.005)] favoring melatonin. Side effects attributable to melatonin were minimal. ConclusionMelatonin is an effective and safe treatment option for sleep problems in PD patients, and beneficial effects on sleep quality are associated with improved non-motor symptoms and quality of life. We need to emphasize the fact that though we had statistically significant changes in our outcomes, it is not clear whether such changes would have real-life impact (meaningfulness) that would be relevant to licensing authorities or management as patients in our study are young, have short disease duration, have high use of anticholinergics and on modest levodopa equivalent dose. So, we are doubtful if this could be generalized to the typical PD population who are older, have longer disease duration and are on potentially sedating medications or not.

Effect of preoperative clove oil gargle on postoperative sore throat in adults after surgery: A randomized placebo-controlled blinded study

Effect of preoperative clove oil gargle on postoperative sore throat in adults after surgery: A randomized placebo-controlled blinded study

A three-arm clinical study to compare pharmacokinetic and pharmacodynamic similarity of the denosumab biosimilar LY06006 with reference denosumab in healthy male subjects

ABSTRACT Background This study aimed to evaluate the pharmacokinetic (PK), pharmacodynamic (PD) similarity, comparable safety, and immunogenicity between LY06006, European Union-sourced denosumab (EU-DEN), and United States-sourced denosumab (US-DEN). Research design and methods In this double-blind, parallel-group, and single-dose study, 300 healthy male subjects were randomized 1:1:1 to receive a 60 mg dose of either LY06006, EU-DEN, or US-DEN subcutaneously. This study lasted for 253 days. Primary PK endpoints included maximum serum concentration (Cmax), area under the concentration-time curve (AUC) from time zero to last quantifiable concentration (AUC0-t), and AUC from time zero to infinity (AUC0-inf). Pharmacokinetic equivalence was concluded if the two-sided 90% confidence interval (CI) for the geometric least squares mean ratio (GLSMR) of primary endpoints were within 80%-125%. Other PK parameters, PD parameters, safety, and immunogenicity assessments were also conducted during the study. Results The 90% CIs for ratios of GLSMR were within the predefined equivalence margin for AUC0-inf (89.0%–111.1%), AUC0-t (89.7%–111.3%), and Cmax (92.3%–106.7%). The PD parameters, safety, and immunogenicity of LY06006 were also comparable to US-DEN and EU-DEN. Conclusion LY06006 was highly similar to US-DEN and EU-DEN in terms of PK, PD, safety and immunogenicity in healthy male subjects. Clinical trial registration www.clinicaltrials.gov identifier is NCT06095427

Effectiveness of Virtual Reality Glasses on Surgical Fear and Anxiety in Patients Before Open-heart Surgery: A Double-blind Randomized Controlled Trial

PurposeFear and anxiety in open-heart surgery patients can adversely affect their physiological well-being and recovery. Although virtual reality glasses (VR-G) have been advanced for preoperative anxiety management, their effectiveness specifically for open-heart surgery patients remains under-researched. This study aims to evaluate the efficacy of watching a video through VR-G on surgical fear and anxiety levels of patients undergoing open-heart surgery. DesignA randomized controlled and double-blind study. MethodsIn total, 90 patients were randomly assigned to the VR-G intervention group or control group. On the surgery morning, intervention group patients watched a 360-degree video with nature sounds through VR-G before being transferred to the operating theater. The surgical fear and anxiety levels of the patients were evaluated at three stages using the Surgical Fear Questionnaire and Visual Analog Scale-Anxiety: initial evaluation in the morning, second evaluation before being transferred, and third evaluation in the waiting room of the operating theater. FindingsThe surgical fear level of the intervention group at the third evaluation was significantly lower than the control group (P < .000). There was no significant difference between the anxiety levels of the study groups (P > .05). ConclusionsWatching a 360-degree video with nature sounds through VR-G is an effective intervention in reducing surgical fear levels of patients before undergoing open-heart surgery. Use of VR-G interventions may be a practical and fast-resulting nursing strategy to manage patients’ surgical fear in the preoperative period. RegistrationNCT06165861

Effect of a constant rate infusion of ketamine on left ventricular systolic and diastolic function in dogs anesthetized with propofol

ObjectiveTo evaluate the effect of a constant rate infusion of ketamine on left ventricular systolic and diastolic function in dogs anesthetized with propofol. Study designProspective randomized, blinded clinical study. AnimalsSixteen healthy dogs. MethodsDogs were randomized into two groups, the propofol-ketamine group (GPK) and propofol group (GP), with eight animals each. Anesthesia was induced with propofol and maintained with a constant rate infusion (CRI) of propofol at a rate of 0.8 mg/kg/min. All dogs were mechanically ventilated throughout the study. Thirty-five minutes after anesthesia started, the GPK received a bolus of ketamine (0.5 mg/kg IV, over 2 minutes) followed by the CRI of ketamine at 30 μg/kg/min, while the GP received the same volume of 0.9% NaCl over 2 minutes followed by the CRI of 0.9% NaCl at the same rate. Hemodynamic and echocardiographic variables were recorded 15 min after initiating CRI of propofol (M0), immediately after each treatment bolus (M1), and 20 (M2) and 40 min (M3) after initiating CRI of ketamine or 0.9% NaCl solution in both groups. ResultsCardiac index, stroke index, and peripheral vascular resistance index were not significantly different between treatments. No significant differences in left ventricular systolic and diastolic functions derived from echocardiographic variables were observed between groups. Conclusions and clinical relevanceDuring treatment with CRI of ketamine at the proposed rate, hemodynamic parameters and echocardiographic variables, used to measure left ventricular systolic and diastolic function, were maintained stable in healthy dogs anesthetized with propofol.

Ketamine for treatment-resistant obsessive-compulsive disorder: Double-blind active-controlled crossover study.

Obsessive-Compulsive Disorder (OCD) may respond to ketamine treatment. To examine the responsiveness and tolerability of treatment-refractory OCD to intramuscular (IM) ketamine compared to IM fentanyl. This was a randomised double-blind psychoactive-controlled study with single doses of racemic ketamine 0.5 mg/kg, 1.0 mg/kg or fentanyl 50 µg (psychoactive control). Pre-dosing with 4 mg oral ondansetron provided nausea prophylaxis. Eligible participants were aged between 18 and 50 years with severe treatment-resistant OCD. The primary efficacy measure was the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Tolerability was measured with the Clinician-Administered Dissociative States Scale (CADSS). Repeated measures analysis of variance with orthogonal polynomial trends was used to assess the effect of drug treatment on Y-BOCS and CADSS scores. Twelve participants were randomised and 10 completed the study (7 females, 3 males, mean age 33 years). Two participants dropped out due to not tolerating dissociative effects associated with the study medication. The reductions in Y-BOCS scores were greater and statistically dose-related for both ketamine doses than fentanyl (dose [linear], F(1, 9) = 6.5, p = 0.031). Score changes for all treatments were maximal at 1-2 h with a steady separation of scores out to 168 h. Ketamine was associated with short-term dissociative and cardiovascular effects. We provide further preliminary evidence for the efficacy and tolerability of IM ketamine in an outpatient cohort of OCD. Additional work is required to establish the optimal dosing regimen and longer-term role of ketamine for OCD. These findings are encouraging given the well-known limitations that exist for treatments in this area.

Diagnosis of early-stage bladder cancer via unprocessed urine samples at the point of care.

Diagnostic kits for the optical detection of bladder cancer in urine can facilitate effective screening and surveillance. However, the heterogeneity of urine samples, owing to patients with bladder cancer often presenting with haematuria, interfere with the transduction of the optical signal. Here we describe the development and point-of-care performance of a device for the detection of bladder cancer that obviates the need for sample processing. The device leverages the enzymatic release of organogel particles carrying solvatochromic fluorophores in the presence of urinary hyaluronidases-a bladder cancer biomarker. Owing to buoyancy, the particles transfer from the urine sample into the organic phase, where the change in fluorescence can be measured via a smartphone without interference from blood proteins. In a double-blind study with 80 unprocessed urine samples from patients with bladder cancer (including samples with haematuria) or other genitourinary diseases and with 25 samples from healthy participants, our system distinguished the cancerous samples, including those with early-stage bladder cancer, with accuracies of about 90%. Obviating the need for sample pretreatment may facilitate the at-home detection of bladder cancer.

Bihemispheric Transcranial Direct Current Stimulation over Primary Motor Cortex Potentiates Improvement of Neurological but not Upper Limb Motor Functions in Ischemic Stroke Patients Treated with Routine Physical Therapy: A Randomized, Double-Blind, Sham-Controlled Trial.

We investigated the therapeutic effect of transcranial direct current stimulation (tDCS) combined with routine physiotherapy on the neurological and upper limb motor function in ischemic stroke patients with hemiplegia. In a Randomized double-blind controlled trial study, 52 eligible stroke patients were assigned to real tDCS receiving bihemispheric electrical current with 1.5 mA for 30 minutes over the primary motor cortex, and sham tDCS with a current intensity of 0.5 mA for 30 seconds. Both groups received routine physiotherapy, 5 sessions per week for two weeks. The National Institute of Health Stroke Scale (NIHSS) and the Medical Research Council Scale for Muscle Strength were used to assess the neurological and upper limb motor functions, respectively. Both therapeutic approaches begot a significant improvement in upper limb motor function and neurological impairment at the last session of therapy and follow-up study. However, the treatment-induced neurological amelioration at the last session of therapy in real tDCS was significantly more than sham, especially in those identified as female and under 60 years old. A gender and age-specific protocol of real tDCS combined with routine physiotherapy might be beneficial to improve neurological impairment but not upper limb motor dysfunction after stroke.

A Phase 1b/2a Single Ascending Dose Study of a Half-life Extended RSV Neutralizing Antibody, Clesrovimab, in Healthy Preterm and Full-term Infants.

Clesrovimab is an investigational monoclonal antibody with an extended half-life targeting site IV of the respiratory syncytial virus (RSV) fusion protein for the prevention of RSV disease in infants. In this phase 1b/2a, double-blind study,183 healthy preterm and full-term infants 2 weeks to 8 months of age were randomized 4:1 within 5 panels (preterm: 20, 50, 75 or 100-mg, full-term: 100 mg) to receive one dose of clesrovimab or placebo. The objectives were to evaluate safety, pharmacokinetics, serum neutralizing antibodies (SNA), and anti-drug antibodies (ADA). The incidence of RSV-associated endpoints [medically-attended lower respiratory tract infection (MALRI), hospitalization, and acute respiratory infection (ARI)] were also evaluated through 150 days postdose. The most common adverse event (AE) through day 14 was irritability; no treatment-related serious AEs were reported. Clesrovimab serum concentrations displayed a geometric mean apparent half-life of 44.9 days. Of participants receiving clesrovimab, 51 (36.7%) developed ADA with no apparent impact in pharmacokinetics. SNA titers increased in a dose-dependent manner at day 150. The incidences of RSV-associated endpoints were lower in infants treated with clesrovimab compared with placebo. Clesrovimab was generally well tolerated and exhibited an extended half-life compared to typical IgG1 antibodies supporting its ongoing development in late-stage trials. Clinicaltrials.gov, NCT03524118.

A Randomized Double-Blind Placebo-Controlled Study on the Safety and Efficacy of Probiotics for Insulin Resistance and Oxidative Stress Markers in Diabetic Patients With End-Stage Renal Disease on Hemodialysis

A Randomized Double-Blind Placebo-Controlled Study on the Safety and Efficacy of Probiotics for Insulin Resistance and Oxidative Stress Markers in Diabetic Patients With End-Stage Renal Disease on Hemodialysis