Double-blind Study Research Articles

Effect of continuous infusion in alleviating pain during male urethral catheterization

AimsThe aim of this study was to explore whether continuous infusion causing lubrication can effectively alleviate pain during male urethral catheterization.MethodsThis prospective, multicenter, double-blinded study included 190 male patients scheduled for urethral catheterization. Patients were randomly allocated into four groups: Group A: the catheter was lubricated with paraffin; Group B: the catheter was lubricated with compound lidocaine gel; Group C: the pump continuously infusing with sterilized water; Group D: the pump continuously infusing with 2% lidocaine. The primary outcome was the visual analogue scale (VAS) scores. Statistical analysis system (SAS) (version 9.4) was used to perform all the statistical analyses. Significance for all results was set at P < 0.05.ResultsThe VAS of Group D was the lowest (18.90 ± 11.44), followed by the Group C (33.00 ± 11.07), and the VAS of Group A was the highest (53.98 ± 14.76). There were significant differences in VAS in Group D compared to Group A(P < 0.0001), Group B(P < 0.0001) and Group C (P < 0.0001), Group C compared to Group A (P < 0.0001) and Group B(P < 0.0001), Group B compared to Group A (P < 0.0001), indicating that patients treated with lidocaine infusion (Group D) experienced significantly less pain than did those in the other three groups.ConclusionsContinuous infusion with sterilized water during catheterization is an efficient method for lubricating the urethral mucosa; furthermore, infusion with 2% lidocaine provides better analgesia as well as lubrication.Trial registrationThe study protocol was registered in the Chinese Clinical Trial Registry (ChiCTR2300070866) (https://www.chictr.org.cn/showproj.html?proj=194591) on Apr. 25th, 2023.

The potential utility of synovial C-reactive protein, interleukin-6, and presepsin in diagnostics of periprosthetic joint infection

Background. Diagnostics of infectious complications in joint replacement surgery remains a significant challenge, particularly when microbiological analysis of biological material fails to reveal pathogen growth. The aim of the study was to determine threshold values for C-reactive protein, interleukin-6, and presepsin levels, and to assess their diagnostic value in detecting periprosthetic joint infection. Methods. A prospective cohort single-center blinded study was conducted involving cases of revision arthroplasty for periprosthetic joint infection (PJI) and aseptic prosthetic loosening. The study included 66 patients divided into two groups: Group I (n = 17), with confirmed PJI using the 2018 ICM criteria, and Group II (n = 49), with aseptic prosthetic loosening. Synovial fluid samples were subjected to bacteriological and cytological analysis, measuring levels of C-reactive protein (CRP), presepsin, and interleukin-6 (IL-6). ROC analysis, sensitivity, specificity, accuracy, and threshold values were determined for laboratory data. Results. The highest diagnostic accuracy in distinguishing between PJI and aseptic loosening was observed in the leukocyte count in synovial fluid (AUC 0.928; 95% CI: 0.837-0.977, p0.0001). Elevated synovial CRP levels were associated with infection, with an AUC of 0.776 (95% CI: 0.656-0.870, p = 0.0004), and IL-6 had an AUC of 0.712 (95% CI: 0.583-0.820; p = 0.0048). Presepsin levels, however, showed no significant difference between groups (AUC 0.582; 95% CI: 0.453-0.703; p = 0.3344). Threshold values were set at 5.6 mg/l for CRP, 1212.0 pg/ml for presepsin, and 988.5 pg/ml for IL-6. Sensitivity, specificity, and accuracy for PJI diagnosis were determined for CRP at 62.5%, 85.7%, and 80.0%; for IL-6 at 87.5%, 63.0%, and 69.4%; and for presepsin at 43.8%, 79.6%, and 70.8%, respectively. Conclusion. In cases where synovial leukocyte counts are at borderline levels, the additional assessment of synovial fluid cellular composition and simple, cost-effective markers such as synovial CRP and IL-6 may be recommended to confirm PJI.

A novel model of age estimation in mixed dentition population in Western India – A retrospective study

Objectives: Age estimation is an integral part of legal investigations for forensic purposes. When the chronological age of the individual is not documented or he/she is under the conflict of the law, age estimation comes into play. The need for age estimation may arise in various legal incidences involving children, and juveniles, for civil aspects such as adoption, child labor, or other criminal proceedings such as rape, kidnapping, and illegal immigration. An accurate and dependable method, that can estimate age with high probability, can aid in narrowing down the list of possible victims or even play a decisive role in such cases. The reliability of the method and the probability of correct age estimation play a decisive role in the court of law. Bedek et al’s model (2019) was recently developed and tested in Croatian and South Indian populations with satisfactory results. As there is no evidence of study in the Western Indian population, looking into the accessibility of the population group, the present study aims to evaluate the validity and reliability of the Bedek method in the Western Indian population. Materials and Methods: Approval was sought from the Institutional Ethical Committee. Five hundred and twenty-five orthopantomographs (OPG) of patients aged 5–15 were obtained. A double-blinded study was done, where the radiographs were analyzed using ImageJ software, independently by two investigators. The data were tabulated and subjected to statistical analysis for accuracy of age estimation and intra- as well as inter-observer reliability. Results: There was an underestimation by a range of −1.3038 to −0.74536. There was underestimation in all the models of Bedek with P &lt; 0.005, for all the teeth models except, the three- and two-teeth model (P &gt; 0.005). Conclusion: In our study, we found that the accuracy of age estimation increases significantly with the number of teeth used. Seven four-teeth models were the most suitable for age estimation on OPG. All models except the three-teeth model and two-teeth model were found to be more accurate.

Combination of Topical Heparin and Levomenol in the Treatment of Atopic Dermatitis: A SCORing Atopic Dermatitis (SCORAD) Analysis

Background/Objectives: A prior placebo-controlled, double-blind clinical study demonstrated the superiority of a topical combination of heparin and levomenol over the control and single active constituents. The effect on pruritus and the total SCORAD index were used to evaluate efficacy, but not the effect on the individual SCORAD items. This analysis investigates the overall efficacy of the treatment and the relative contributions of heparin and levomenol to symptom relief in atopic dermatitis, including the effects on the affected body area and its implications for sleeplessness. Methods: The ITT group (combination group A: n = 79; levomenol group B: n = 80; heparin group C: n = 78; placebo group D: n = 41) of the previously published study was re-analysed. Results: The combination significantly improved symptoms such as erythema, edema/papulation, excoriations, and skin dryness compared to the control after eight weeks of treatment. No significant differences were observed for oozing/crust and lichenification among the active groups. Levomenol and heparin exhibited significant advantages over the control for erythema and excoriations, while heparin improved edema/papulation significantly. The inflamed body area significantly decreased using the combination or single active constituents, and sleeplessness significantly improved with the combination or with heparin alone compared to the control. Conclusions: These findings highlight the efficacy of the combination and individual active constituents in addressing specific symptoms of atopic dermatitis, providing insights into their therapeutic effects. The combination’s advantage over the control is most evident in improving excoriations, skin dryness, inflamed skin area, and sleeplessness, justifying its documented use as an intervention in the early stages of atopic dermatitis episodes.

Fixed Dose Versus Height and Weight Adjusted Dose of Bupivacaine for Spinal Anesthesia in Elective Caesarean Section

Background: Spinal anesthesia is gaining global popularity. Caesarian section with spinal anesthesia are considered one of the comment applied surgeries. Hypotension is one of most frequent side effect of spinal anesthesia, if uncorrected causes adverse effect on the mother and neonate . The aim of this study is to assess the hemodynamic measures and anesthetic outcome between fixed dose and adjusted for weight and height dose of bupivacaine. Patients and method: A comparative clinical trial double-blinded study was conducted in the operation theatre of the obstetric surgical department, Baghdad Teaching Hospital, Baghdad, Iraq during the period from the 1st of April 2022 to the 1st of July 2023. A total of 100 pregnant women were included in this study who underwent cesarean section under spinal anesthesia and met the inclusion criteria. These women were allocated randomly into two groups: Group A: Fixed dose group: 50 patients received an intrathecal dose of heavy bupivacaine (0.5%) 2.5 ml. Group B: adjusted dose group: 50 patients received intrathecal adjusted dose heavy bupivacaine (0.5% ) according to height and weight of patient from Hartens chart. Results: A higher mean SBP was reported among the adjusted dose group at 15 min., 20 min., 30 min., and 40 min. (P=0.002, 0.002, &lt;0.001, and &lt;0.001 respectively). A higher mean DBP was reported among the adjusted dose group at 10 min., and 20 min. (P=0.037, and 0.005 respectively). A higher mean MBP was reported among the adjusted dose group at 30 min., and 40 min. (P=0.001, and &lt;0.001 respectively). A lower mean HR due to bradycardia among some cases was reported among the fixed-dose group at 10 min., 30 min., and 40 min. (P=0.024, 0.034, and &lt;0.001 respectively) lowest 10 min., 30 min., and 40 min. (P=0.024, 0.034, and &lt;0.001 respectively). There 40.0% (20) patients in the fixed-dose group received an ephedrine dose once and 24.0% (12) patients in the fixed-dose group received an ephedrine dose more than once, and this was significantly higher than the adjusted dose (P=0.027). Conclusion: Adjusting bupivacaine dose in spinal anesthesia for elective cesarean sections provides favorable hemodynamic stability with adequate anesthetic outcome in both groups

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 &lt;0.001 to improve the FBS, PPBS, urine glucose (FUS &amp; 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

Efficacy and Safety of Budesonide Orodispersible Tablets for Eosinophilic Esophagitis up to 3 Years: an Open-Label Extension Study.

Budesonide orodispersible tablets (BOT) have been shown to be safe and effective in phase 3 double-blind trials of induction and 48-week maintenance therapy of eosinophilic esophagitis (EoE). We now analyzed the long-term efficacy and safety of BOT in a 96-week open-label extension (OLE) study. All EoE patients in the 48-week double-blind maintenance study were eligible to receive BOT treatment for up to 96 weeks. Dosage was 0.5 or 1.0 mg BOT, twice daily, at investigator's discretion. Clinical, histologic, endoscopic, quality of life, and safety measures were assessed. A total of 186 patients participated in the OLE up to 96 weeks. At week 96, 81.9% of patients had clinical remission, defined as an EoE Symptom Activity Index (EEsAI) score of ≤ 20, versus 77.7% at OLE baseline. A further 80.1% of patients were in histologic remission, defined as peak eosinophils per high-power field of <5, at week 96 versus 91.8% at OLE baseline. Mean EoE endoscopic reference scores (EREFS) were 1 at all time points measured. Mean EoE Quality of Life (EoE-QoL-A) Scale scores improved from 3.3 at OLE baseline to 3.5 at week 96. No new safety concerns were observed across 96 weeks of treatment. Suspected symptomatic candidiasis occurred at similar rates to prior BOT studies, and was predominantly mild and resolved with treatment. Clinical and histological remission of EoE could be maintained with BOT in a large majority of patients for up to 96 weeks, and for up to 144 weeks in patients with uninterrupted BOT therapy across all trials. No additional safety concerns were identified with long-term BOT treatment. (ClinicalTrials.gov, Number: NCT02493335).

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.

Gadoxetic acid disodium (Gd-EOB-DTPA) contrast-enhanced abbreviated magnetic resonance imaging (MRI) for hepatocellular carcinoma surveillance in at-risk patients: a multi-center study in China.

Given the limited capacity and suboptimal sensitivity of ultrasonography (US), gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) demonstrates good diagnostic performance for hepatocellular carcinoma (HCC). Some researchers have proposed that the abbreviated MRI (AMRI) protocols have potential as a surveillance tool. However, few studies have compared multiple AMRI protocols with complete Gd-EOB-DTPA contrast-enhanced MRI for HCC surveillance. We aimed to explore and compare the diagnostic performance of 3 AMRI protocols as HCC surveillance in high-risk patients. This multi-center, retrospective, blinded reader study conducted in China consecutively enrolled 339 patients with hepatitis and/or cirrhosis who underwent complete Gd-EOB-DTPA contrast-enhanced MRI for HCC surveillance from 2020 to 2023. We extracted 3 additional AMRI protocols: noncontrast-AMRI [NC-AMRI: T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI)]; dynamic-AMRI (Dyn-AMRI: early and late arterial phases, portal venous phase, and DWI); and hepatobiliary phase-AMRI (HBP-AMRI: T2WI, DWI, and HBP). Then, 2 independent radiologists assessed the AMRI and complete Gd-EOB-DTPA contrast-enhanced MRI protocols. Patients were classified as HCC positive/HCC negative based on the reference standard. Agreement was assessed using Kappa statistics. The acquisition time differences of the 4 MRI protocols were analyzed by analysis of variance (ANOVA). Per-lesion HCC diagnostic performances were compared by Cochran's Q test. Receiver operating characteristic (ROC) curves for the 3 AMRI protocols were evaluated, and the area under the ROC curve (AUROC) was calculated and compared by DeLong's test. A total of 353 lesions were detected in the 339 included patients, and 21/339 patients were diagnosed with HCC (prevalence, 6.2%). The inter-observer agreement was good for all 4 MRI protocols (k>0.75). Acquisition times differed significantly (P<0.001), from the shortest to the longest: NC-AMRI (263.44±5.05s) < HBP-AMRI (269.18±4.93 s) < Dyn-AMRI (307.71±4.93 s) < complete Gd-EOB-DTPA contrast-enhanced MRI (582.03±3.59s). The sensitivity (Cochran's Q=14.667, P=0.002) and specificity (Cochran's Q=59.682, P<0.001) of 4 MRI protocols were statistically significant. HBP-AMRI showed the highest sensitivity (84.00%), whereas Dyn-AMRI exhibited the highest specificity (99.39%) among 3 AMRI protocols. The per-lesion positive predictive value (PPV) for the NC-AMRI, Dyn-AMRI, and HBP-AMRI was 41.66%, 88.89%, and 47.72%, the corresponding negative predictive value (NPV) was 96.21%, 97.31%, and 98.70%, and the number needed to diagnose (NND) for the NC-AMRI, Dyn-AMRI, HBP-AMRI, and complete Gd-EOB-DTPA contrast-enhanced MRI was: 1.865, 1.577, 1.234, and 1.569, respectively. DeLong's test showed the AUROC value of either Dyn-AMRI or HBP-AMRI was significantly higher than that of NC-AMRI (Z=2.330, P=0.019; Z=2.680, P=0.007, respectively), but no significant difference between HBP-AMRI and Dyn-AMRI (Z=1.643, P=0.100). AMRI protocols can be implemented in clinical practice as a patient-centered and tailored regimen for HCC surveillance in China. NC-AMRI might become an optional tool due to its minimal scanning time, lower cost, and exemption from contrast agents. Dyn-AMRI, achieving the highest specificity, is a reliable surveillance strategy. HBP-AMRI as a favorable alternative showed a high sensitivity and NPV while maintaining considerable specificity and NND.

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.

Endoscopic sleeve gastroplasty plus lifestyle intervention in patients with MASH: a multicentre, sham-controlled, randomized trial.

Metabolic dysfunction-associated steatohepatitis(MASH) is commonly seen in biopsy proven steatotic liver disease(SLD). Life-style intervention reaching a weight loss higher than 10% promotes MASH resolution, but this goal is only achieved by a small number of patients. Endoscopic sleeve gastroplasty(ESG) has recently emerged as a safe and effective option to promote weight loss in obese population. We report the results of a multicenter, randomized, controlled and double-blind study to evaluate the effectiveness and safety of ESG in MASH patients METHODS: Forty patients were randomized 1:1 to ESG plus lifestyle modification vs. sham endoscopy (SE) plus lifestyle intervention. Inclusion criteria included biopsy proven MASH with NAS≥3 and fibrosis stage F0-F3. Eighteen patients from the ESG group and 19 from the ESI group completed follow-up during 72 weeks. Baseline to end of follow-up changes in body weight, liver tests, liver stiffness(VCTE) and liver histology were recorded RESULTS: Total Body weight loss(TBWL) was 9.47%(±9.38) in ESG group vs 3.91%(±5.43) in ESI group(p<0.05). Liver stiffness decreased 5.63(±7.17) KPa in ESG group vs 0.2(±5.38) KPa in ESI group(p<0.05). Steatosis was significantly reduced in ESG group(-0.94±0.87) vs ESI group(-0.26±0.99)[p= 0.033]. No differences on NAS(-1.89±2.11 vs -1.47±2.01) score neither fibrosis(-0.1±0.91 vs -0.84±1.21) was seen. In patients achieving weight loss>10% we found a significant improvement on NAS score(-4±0.94 vs. -0.81±1.62, p<0.01), but not in fibrosis stage(-0.3±1.06 vs -0.59±1.25). Only 2 patients of ESG group had adverse events that required admission that resolved conservatively in 72 hours CONCLUSION: ESG is an effective and safe method to promote weight reduction associated with significant improvement in patients with MASH and obesity.

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