Parallel-arm Study Research Articles

P2.14B.03 A Phase II Parallel Arm Study of Sacituzumab Govitecan-Hziy in Patients with Advanced Thymoma and Thymic Carcinoma

P2.14B.03 A Phase II Parallel Arm Study of Sacituzumab Govitecan-Hziy in Patients with Advanced Thymoma and Thymic Carcinoma

Safety and efficacy of decoction obtained from Asparagus officinalis and Cucumis melo in the management of nephrolithiasis: single blind, randomized, active controlled parallel arm study

Background: Nephrolithiasis (Hisah-al-kulya) is a common and painful condition where the stone formation is due to crystallization of lithogenic factors in the upper urinary tract. There are a number of medications listed in classical Unani literature that are intended to treat nephrolithiasis. Haliyun (Asparagus officinalis) and Tukhm-e-Kharpaza (Seeds of Cucumis melo) are among those drugs which are said to have lithotriptic properties. To evaluate the safety and therapeutic efficacy of oral administration of decoction of Asparagus officinalis and seeds of Cucumis melo in the management of nephrolithiasis. Methods: In a single blind, active controlled two arm study, 44 patients were randomly allocated in test and control group. To check the efficacy, subjective assessment was done after every two weeks of treatment. Investigations including objective and safety parameters were performed only at 0 day and after completion of the treatment. 20 patients from each group completed the trial and the result data obtained was analyzed using student t-test, Wilcoxon, chi-square and McNemar test. Results: The symptoms like flank pain, dysuria and hematuria were graded using arbitrary grading scales ranging from absent, mild, moderate or severe and the results obtained, using Wilcoxon matched pair test and chi-square test, are significant. The ultra-sonography and X-ray data clearly reveals the improvement by the test drug compared to control drug. Conclusion: The current study has shown that the Unani formulation, decoction of Asparagus officinalis and Cucumis melo seeds, possess lithotriptic activity and is safe and effective in the management of Nephrolithiasis.

Shoden promotes Relief from stress and anxiety: A randomized, double-blind, placebo-controlled study on healthy subjects with high stress levels

BackgroundThis randomized placebo-controlled study examined the effect of ashwagandha root and leaf extract 60 mg (AE60) and 120 mg (AE120) (35 % withanolide glycosides, Shoden) in physically healthy subjects with higher stress and anxiety. It is hypothesized that a low dose extract with higher withanolide glycosides would decrease cortisol and increase testosterone thereby reducing stress and anxiety. MethodsThis parallel arm study recruited 60 subjects with an allocation ratio of 1:1:1 (AE60:AE120: placebo) for 60 days. Subjects who fulfilled the DSM –IV Criteria for generalized anxiety disorder (GAD) with a Hamilton Anxiety Rating Scale, HAMA score >20, and morning serum cortisol >25 mcg/dl were included in the study. The participants did not have depression symptoms and were screened using Montgomery-Asberg Depression Rating Scale. The primary outcome measure was HAMA and the secondary measures were morning serum cortisol, testosterone, perceived stress scale (PSS), clinical global impressions scale (CGI), and patient's global impression of change scale (PGIC). ResultsAfter 60 days, significant differences were observed between the treatment groups and placebo. HAMA scores decreased by 59 % in both AE60 and AE120 groups compared to a negligible increase of 0.83 % in the placebo group (p < 0.0001). Morning serum cortisol levels decreased by 66 % in AE60 and 67 % in AE120, compared to a 2.22 % change in the placebo group (p < 0.0001). Testosterone levels increased by 22 % in AE60 and 33 % in AE120, compared to a 4 % increase in males in the placebo group (p < 0.0001). PSS scores decreased by 53 % in AE60 and 62 % in AE120, CGI-severity scores decreased by 72 % in AE60 and 68 % in AE120, and PGIC scores improved by 60 % in both AE60 and AE120 groups, all showing significant differences compared to the placebo group. ConclusionAshwagandha extract with 35 % withanolide glycosides (Shoden) at 60 mg and 120 mg was significantly effective in reduced morning serum cortisol and increasing total testosterone. Therefore, it can be recommended for reducing high stress and anxiety. Clinical trial registrationThe study was prospectively registered in Clinical Trial Registry, India with registration number CTRI/2022/04/042133 [Registered on: April 25, 2022].

Magnesium-L-threonate improves sleep quality and daytime functioning in adults with self-reported sleep problems: A randomized controlled trial

Objective/BackgroundSleep problems challenge overall wellbeing. Magnesium has been implicated to benefit sleep, although the clinical evidences varied based on the magnesium source used. Magnesium L-threonate (MgT) is a promising intervention due to its brain bioavailability and effects on cognition, memory and mood. We investigated MgT supplementation on sleep quality and daily function. Patients/methodsEighty 35–55-year-olds with self-assessed sleep problems participated in a randomized, double-blind, placebo-controlled, parallel-arm study, taking 1 g/day of MgT or placebo for 21 days. Sleep and daily behaviors were measured subjectively using standardized questionnaires including the Insomnia Severity Index, Leeds Sleep Evaluation Questionnaire, and Restorative Sleep Questionnaire, and objectively using an Oura ring. The Profile of Mood States questionnaire and a daily diary were used to evaluate mood, energy and productivity, and record any safety concerns. ResultsThe MgT group maintained good sleep quality and daytime functioning, while placebo declined. From objective Oura ring measurements, MgT significantly (p < 0.05) improved vs placebo deep sleep score, REM sleep score, light sleep time, and activity and readiness parameters activity score, activity daily movement score, readiness score, readiness activity balance, and readiness sleep balance. From subjective questionnaires, MgT significantly (p < 0.05) improved vs placebo behavior upon awakening, energy and daytime productivity, grouchiness, mood and mental alertness. MgT was safe and well tolerated. ConclusionsThis showed MgT improved sleep quality, especially deep/REM sleep stages, improved mood, energy, alertness, and daily activity and productivity. These are consistent with how MgT works in neuron cells and animal models, suggesting broader positive impacts on overall brain health.

Effects of Far Infrared Radiation and Sitz Bath on Perineal Wound Healing and Pain in Primiparous Women Undergoing an Episiotomy: A Randomized Prospective Parallel Arm Study.

Introduction Episiotomy is a common surgical procedure done during childbirth. The study aims to assess the efficacy of far-infrared (FIR) and sitz bath (SB) effects on pain relief and healing of perineal wounds in primiparous women who had undergone an episiotomy. Materials and methods A randomized prospective parallel arm study was conducted among 208 primigravida women who underwent episiotomy in a tertiary hospital in the southern part of India from December 2020 to March 2022. Participants were randomized into the FIR (n-104) and SB therapy groups (n-104) and their efficacy was assessed for pain relief and healing of perineal wounds using the Visual Analog Scale (VAS), Redness, Oedema, Ecchymosis, and Discharge, the Approximation Scale (REEDA) and the Modified Oxford Scale (MOS). The variables were compared using an independent two-sample t-test and chi-square test (p ≤ 0.05). Results Pain was evaluated using VAS, and by the sixth week postpartum, 90.4% (94) of the FIR group reported mild to no pain compared to 88.5% (92) of the SB group. Wound integrity assessment using the REEDA scale showed better results among the FIR group (94, 90.4%) than the SB group (93, 89.4%) on the second day postpartum. Perineal muscle tone, measured by the MOS, was slightly better in the FIR group (59, 62.8%) than the SB group (55, 59.8%) at the sixth week postpartum, although these differences were not statistically significant. Conclusion FIR therapy reduces postpartum discomfort, promotes wound healing, and improves perineal muscle tone better than SB therapy. FIR also enhanced patient compliance and efficacy.

Lipoprotein(a) and diet: consuming sugar-sweetened beverages lowers lipoprotein(a) levels in obese and overweight adults

Lipoprotein(a) [Lp(a)] contributes to cardiovascular disease risk. A genetically determined size polymorphism in apolipoprotein(a) [apo(a)], determined by the number of Kringle (K) repeats, inversely regulates Lp(a) levels. Nongenetic factors including dietary saturated fat influence Lp(a) levels. However, less is known about the effects of carbohydrates including dietary sugars. In this double-blind, parallel arm study among 32 overweight/obese adults, we investigated the effect of consuming glucose- or fructose-sweetened beverages providing 25% of energy requirements for 10 weeks on Lp(a) level and assessed the role of the apo(a) size polymorphism. The mean (±SD) age of participants was 54 ± 8 years, 50% were women, and 75% were of European descent. Following the 10-week intervention, Lp(a) level was reduced by an average (±SEM) of −13.2% ± 4.3% in all participants (P = 0.005); −15.3% ± 7.8% in the 15 participants who consumed glucose (P = 0.07); and −11.3% ± 4.5% in the 17 participants who consumed fructose (P = 0.02), without any significant difference in the effect between the two sugar groups. Relative changes in Lp(a) levels were similar across subgroups of lower versus higher baseline Lp(a) level or carrier versus noncarrier of an atherogenic small (≤22K) apo(a) size. In contrast, LDL-C increased. In conclusion, in older, overweight/obese adults, consuming sugar-sweetened beverages reduced Lp(a) levels by ∼13% independently of apo(a) size variability and the type of sugar consumed. The Lp(a) response was opposite to that of LDL-C and triglyceride concentrations. These findings suggest that metabolic pathways might impact Lp(a) levels.

Reduced nicotine in cigarettes in a marketplace with alternative nicotine systems: randomized clinical trial

Reducing cigarette addictiveness has the potential to avert millions of yearly tobacco-related deaths worldwide. Substantially reducing nicotine in cigarettes decreases cigarette consumption, but no large clinical trial has determined the effects of reduced-nicotine cigarettes when other nicotine-containing products are available. The aim of this study was to examine the effects of reduced-nicotine cigarettes in the context of the availability of alternative nicotine delivery systems. In a U.S. six-site, open-label, parallel-arm study, smokers were randomized for twelve weeks to an experimental marketplace containing cigarettes with either 0.4mg or 15.8mg nicotine per gram of tobacco; all had access to non-combusted alternative nicotine delivery systems (e.g., e-cigarettes; medicinal nicotine). Group differences in the primary outcomes (cigarettes per day, number of smoke-free days) were examined using linear and negative binomial regression, respectively (Trial Registration: NCT03272685). Among 438 randomized participants (mean [standard deviation (SD), range] age, 44.5 [11.9, 20-73] years, 225 [51.4%] women, 282 [64.4%] White and 339 [77.4%] trial completers), those in the 0.4mg vs. 15.8mg nicotine cigarette condition experienced significantly lower cigarettes per day at the end of intervention (mean [SD], 7.05 [7.88] vs. 12.95 [9.07], adjusted mean difference,-6.21 [95% CI,-7.66 to-4.75], P<0.0001) and greater smoke-free days during intervention (mean [SD], 18.59 [27.97] vs. 5.06 [13.77], adjusted rate ratio, 4.25 [95% CI, 2.58-6.98], P<0.0001). A reduced-nicotine cigarette standard in the context of access to other non-combusted nicotine products has the potential to benefit public health. U.S. NIH/FDA U54DA03165.

Effect of Incorporating 1 Avocado per Day Versus Habitual Diet on Vascular Function in Adults With Abdominal Obesity: An Ancillary Study of HAT, a Randomized Controlled Trial.

Abdominal obesity is associated with endothelial dysfunction and poorer vascular health. Avocado consumption improves postprandial endothelial function; however, the longer-term effects remain unclear. It was hypothesized that the daily addition of 1 avocado to a habitual diet for 6 months would improve flow-mediated dilation (FMD) and carotid-femoral pulse wave velocity in individuals with abdominal obesity (waist circumference ≥35 in for women, ≥40 in for men), compared with a habitual diet low in avocados. HAT (Habitual Diet and Avocado Trial) was a multicenter, randomized, controlled, parallel-arm study that investigated the health effects of adding 1 avocado per day to a habitual diet in individuals with abdominal obesity. At the Pennsylvania State University, University Park study center (n=134; age, 50 ± 13 years; women, 78%; body mass index, 32.6 ± 4.8 kg/m2), markers of vascular function were measured, including endothelial function, assessed via brachial artery flow-mediated dilation, and arterial stiffness, assessed via carotid-femoral pulse wave velocity. Between-group differences in 6-month change in flow-mediated dilation and carotid-femoral pulse wave velocity were assessed using independent t tests. Prespecified subgroup analyses were conducted using linear regression. No significant between-group differences in flow-mediated dilation (mean difference=-0.62% [95% CI, -1.70 to 0.46]) or carotid-femoral pulse wave velocity (0.25 m/s [95% CI, -0.13 to 0.63]) were observed. Results of the subgroup analyses were consistent with the primary analyses. Longer-term consumption of 1 avocado per day as part of a habitual diet did not improve measures of vascular function compared with a habitual diet low in avocados in individuals with abdominal obesity. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03528031.

Effect of glycocalyx-targeted therapy on vascular function in older adults: a randomized controlled trial.

Advancing age increases cardiovascular disease risk, in part, because of impaired glycocalyx thickness and endothelial dysfunction. Glycocalyx-targeted therapies, such as Endocalyx Pro, could improve both glycocalyx thickness and endothelial function in older adults; however, this has yet to be tested. We hypothesized that Endocalyx Pro supplementation would increase glycocalyx thickness and endothelial function in older adults. Twenty-three older adults aged 66 ± 7 yr (52% female) were enrolled in a randomized, double-blind, placebo-controlled, parallel-arms study to investigate the effect of 12-wk Endocalyx Pro supplementation (3,712 mg/day) on glycocalyx thickness and endothelial function. Glycocalyx thickness was assessed using the GlycoCheck, and endothelial function was determined via brachial artery flow-mediated dilation (FMD). Between-group comparisons revealed Endocalyx Pro did not increase glycocalyx thickness in microvessels 4-25 µm (P = 0.33), 4-7 µm (P = 0.07), or 10-25 µm (P = 0.47) in diameter when compared with placebo. In addition, Endocalyx Pro did not significantly improve FMD [mean ratio (95%) confidence interval [CI]) for between-group comparisons, 1.16 (0.77-1.74); P = 0.48]. However, Endocalyx Pro improved FMD normalized to shear rate (SR) area under the curve [mean ratio (95% CI) for between-group comparisons, 2.41 (1.14,4.13); P = 0.001]. Moreover, Endocalyx Pro increased capillary glycocalyx thickness more than placebo in individuals not taking antihypertensive medication [mean difference (95% CI) for between-group comparison, -0.08 (-0.15, -0.01); P = 0.02]. Our pilot study suggests that Endocalyx Pro supplementation is feasible in older adults but has no measurable effect on overall glycocalyx thickness and FMD. However, Endocalyx Pro may have select effects on capillary glycocalyx thickness and FMD normalized to shear rate among older adults, but further investigation is warranted.NEW & NOTEWORTHY Endothelial glycocalyx thickness and vascular endothelial function decline with advancing age. Endocalyx Pro is a glycocalyx-targeted therapy that may improve endothelial glycocalyx thickness and vascular endothelial function in older adults. This study demonstrated that 12-wk Endocalyx Pro supplementation did not improve overall endothelial glycocalyx thickness or flow-mediated dilation in older adults; however, Endocalyx Pro did increase capillary glycocalyx thickness in individuals not taking antihypertensive medication and improve flow-mediated dilation normalized to the shear stimulus.

Silymarin-choline combination versus ursodeoxycholic acid in non-alcoholic fatty liver disease: A randomized double-blind clinical trial

Silymarin-choline combination versus ursodeoxycholic acid in non-alcoholic fatty liver disease: A randomized double-blind clinical trial

Oral isotretinoin with desloratadine compared with oral isotretinoin alone in the treatment of moderate to severe acne: a randomized, assessor-blinded study.

Our aim was to measure the effectiveness of oral isotretinoin with desloratadine compared with oral isotretinoin alone in treating moderate to severe acne at a tertiary care teaching hospital in North India. In this study, 90 patients with moderate to severe acne were enrolled to participate based on their fulfilling the inclusion criteria. A randomized, assessor-blinded, parallel-arm study was conducted. Randomization was done using computer-generated tables to allocate treatments in a 1:1 ratio. A low-dose oral isotretinoin at a dose of 0.3 mg/kg/day with tab desloratadine at 5 mg/day was applied to the study group and compared against the same patients going without the dosage when controls were conducted. Follow-up was at 4, 8, and 12 weeks. The primary outcome was an improved global acne grading system (GAGS) score and decreased acne lesion count. patient satisfaction with treatment. The 90 participants were randomized and 15 participants dropped out of the study, leaving 75 participants for intention to treat analysis (n = 41, n = 30). At week 12, the GAGS score and acne lesion count between the study and control groups were comparable (P > 0.05). Pruritus reported was 9.76% in the study versus 33.33% in the control group (P = 0.018). Also, 53.66% of participants reported "excellent" treatment satisfaction in the study group versus 36.67% in the control group. The addition of desloratadine to an isotretinoin regimen has a role in reducing disease and therapy-related pruritus in acne and leads to improved patient satisfaction.

Abstract P176: Consumption of Sugar-Sweetened Beverages Lowers Lipoprotein(a) Levels in Obese and Overweight Adults: Findings in a Double-Blind Parallel-Arm Study

Elevated levels of lipoprotein(a) [Lp(a)] are a genetically regulated, causal, and prevalent risk factor for atherosclerotic cardiovascular disease. A size polymorphism in the apolipoprotein(a) [apo(a)] gene, determined by the number of Kringle (K) repeats, inversely regulates Lp(a) plasma levels. Despite strong genetic regulation, non-genetic factors such as diet influence Lp(a) levels. However, the relationship between Lp(a) level and sugar consumption remains understudied. In this double-blinded parallel arm study, we investigated the effect of consuming glucose- or fructose-sweetened beverages providing 25% of energy requirements for 10 weeks on plasma Lp(a) levels in 32 overweight/obese adults. Lp(a) levels were measured using an apo(a) size insensitive ELISA and apo(a) isoform sizes were determined by Western blotting. The mean (SD) age of participants was 54 ± 8 years, 50% were women, and 75% were of European descent. The mean body mass index was 29 ± 3 kg/m 2 and 28% of participants had metabolic syndrome. In all participants, baseline median Lp(a) level was 10.3 mg/dL (IQR: 4, 28 mg/dL). At the end of the 10-week intervention, Lp(a) levels were reduced by an average of -4 mg/dL (-13%) in all participants, by -4 mg/dL (-15%) in the glucose group (n=15) and by -5 mg/dL (-11%) in the fructose group (n=17), respectively. The mean percent changes in Lp(a) levels in the low (≤25 mg/dL) (n=23) vs high (&gt;25 mg/dL) (n=9) baseline Lp(a) groups were similar: -14% (-2 mg/dL) vs -11% (-11 mg/dL), respectively. Notably, the carrier status of an atherogenic small (≤22K repeats) apo(a) size did not substantially impact Lp(a) responses as the mean Lp(a) changes were similar in carriers (-15%) (n=8) vs non-carriers (-13%) (n=24). In conclusion, in overweight/obese adults, consuming sugar-sweetened beverages providing 25% of energy requirements for 10 weeks reduced Lp(a) levels by ~13% independent of apo(a) size variability. The findings suggest that pathways involving carbohydrates and fatty acid metabolism might potentially impact Lp(a) levels. The specific mechanisms underlying the effect of sugar-sweetened beverage consumption to reduce circulating Lp(a) levels warrant further investigation.

Effect of Sevoflurane, Isoflurane, and Desflurane on the Random Blood Glucose Levels in Non-diabetic Patients Undergoing General Anesthesia: A Randomized, Single-Blind Study.

Volatile anesthetic agents like sevoflurane, isoflurane, and desflurane are widely used for maintaining general anesthesia (GA). Their effect on the autonomic system is different and can impact the blood sugar homeostasis. This study compares the intraoperative blood glucose levels in non-diabetic patients undergoing non-cardiac surgery under GA with the three volatile agents. A randomized, single-blind, parallel-arm study recruited 105 non-diabetic patients into three groups. GA induction and maintenance were standardized except for the volatile agent. Capillary blood sugar levels were measured at different time points and compared between and within the groups. A p-value of <0.05 was considered significant. Entire participants completed the study, and their baseline characteristics were statistically indifferent. Intraoperative blood glucose rise and variation were the highest in the desflurane group and the lowest in the isoflurane group; the differences were statistically significant at 15, 30, and 45 minutes. The highest blood sugar level was noted at 60 minutes in all groups; after that, the level started falling. However, none of the raises were beyond 140 mg% to categorize them as hyperglycemia. Intraoperative glycemic variation was evident with isoflurane, sevoflurane, and desflurane. The maximum increase from the pre-induction level was noted at 60 minutes. However, none of the readings reached the hyperglycemia level. The rise was significantly higher in desflurane-based anesthesia than in isoflurane. This study was, however, conducted in non-diabetic patients; hence, results might not be extrapolated to diabetic patients.

Changes in biomarkers of exposure and withdrawal symptom among Chinese adult smokers after completely or partially switching from combustible cigarettes to an electronic nicotine delivery system.

This study assessed changes in biomarkers of exposure (BoE) after 5 days of completely or partially switching to an electronic nicotine delivery system (ENDS) use, compared with continued use of combustible cigarettes and smoking abstinence among Chinese adult smokers. A randomized, open-label, parallel-arm study was conducted among Chinese adult smokers who were naive ENDS users. Forty-six subjects were randomized to 4 study groups (n = 11-12 per group): exclusive ENDS use, dual use of ENDS and cigarettes, exclusive cigarettes use, and smoking abstinence. Subjects were confined in clinic for 5 consecutive days and product use was ad libitum. Nicotine and its metabolites (cotinine and 3-hydroxycotinine), and BoEs (AAMA, CEMA, HEMA, HMPMA, 3-HPMA, SPMA, exhaled CO, and exhaled NO) were measured. Withdrawal symptom was measured using MNWS throughout the 5-day period. Six urine BoEs of volatile organic compounds decreased by 55.1-84.1% in the exclusive ENDS use group, which is similar to the smoking abstinence group (67.2-87.4%). The level of decrease was 56.8-70.4% in the dual use group and 10.7-39.0% in the cigarettes group. Urine total nicotine exposure had a non-significant increase in the exclusive ENDS use group, and plasma nicotine and cotinine showed a trend of increasing day by day. After completely or partially switching to ENDS use among Chinese smokers, exposure to selected toxicants were significantly decreased. The results of this study add to the body of evidence that exposure to toxic substance decreased among smokers after complete or partial switch from combustible cigarettes to ENDS use. As part of transition to experienced ENDS use, this study found that smokers of the initial stage who have no prior ENDS experience may increase nicotine intake after switching to ENDS use.

One Avocado per Day as Part of Usual Intake Improves Diet Quality: Exploratory Results from a Randomized Controlled Trial

BackgroundFew clinical trials have evaluated diet quality change as a predictor of intervention effectiveness. ObjectivesThe aim of this study was to examine changes in the Healthy Eating Index (HEI)-2015 after a food-based intervention, and assess the associations between HEI-2015 change and intervention effects on cardiometabolic risk–related outcomes. MethodsThe Habitual Diet and Avocado Trial was a 26-wk, multicenter, randomized, controlled parallel-arm study. Participants were 1008 individuals aged ≥25 y with abdominal obesity (females ≥ 35 inches; males ≥ 40 inches). The avocado-supplemented diet group was provided 1 avocado per day, and the habitual diet group maintained their usual diet. Change in diet quality was assessed using the HEI-2015 from a single 24-h recall conducted at 4 time points. Mixed models were used for analysis. ResultsThe avocado-supplemented diet group had a greater increase in the HEI-2015 (4.74 points; 95% CI: 2.93, 6.55) at 26 wk than the habitual diet group. Compared with the habitual diet group, the avocado-supplemented diet group had greater increases in the following HEI-2015 components from baseline: total vegetables (0.99 points; 95% CI: 0.77, 1.21), fatty acid ratio (2.25 points; 95% CI: 1.74, 2.77), sodium (1.03 points; 95% CI: 0.52, 1.55), refined grains (0.82 points; 95% CI: 0.32, 1.31), and added sugars (0.84 points; 95% CI: 0.49, 1.19). No differences in HEI-2015 improvements were observed by race, ethnicity, study site, body mass index, or age category. In the avocado-supplemented diet compared with the habitual diet group, the HEI-2015 increased in females (6.50 points; 95% CI: 4.39, 8.62) but not in males (0.02 points; 95% CI: −3.44, 3.48). Median HEI-2015 change was not associated with intervention-related changes in cardiometabolic disease risk factors. ConclusionsIntake of 1 avocado per day for 26 wk in adults with abdominal obesity increased adherence to the Dietary Guidelines for Americans. Changes in diet quality did not predict changes in risk factors for cardiometabolic disease.This trial was registered at clinicaltrials.gov as NCT03528031 (https://clinicaltrials.gov/study/NCT03528031).

Bifidobacterium lactis IDCC 4301 (B. lactis Fit™) supplementation effects on body fat, serum triglyceride, and adipokine ratio in obese women: a randomized clinical trial.

Obesity is a common metabolic disease characterized by abnormal fat accumulation. It contributes to health issues, such as type 2 diabetes, cardiovascular disease, and dyslipidemia, necessitating continuous management through diet and physical activity. Probiotics, particularly Bifidobacterium lactis IDCC 4301 (B. lactis Fit™), have shown promise in positively regulating the gut microbiota. Therefore, this study aimed to evaluate the anti-obesity effect of B. lactis IDCC 4301 (B. lactis Fit™) in obese women. A randomized, double-blind, placebo-controlled, parallel-arm study was performed in 99 volunteers with a body mass index (BMI) of 25-30 kg m-2. The participants were randomly assigned to probiotics (n = 49, >5.0 × 109 CFU day-1) or placebo (n = 50) groups. Body fat, lipid profiles, and adipokine levels were assessed at baseline and at 12 weeks. After 12 weeks, changes in total fat (placebo -0.16 ± 0.83 kg; probiotics -0.45 ± 0.83 kg; p = 0.0407), trunk fat (placebo -0.03 ± 0.50 kg; probiotics -0.22 ± 0.51 kg; p = 0.0200), and serum triglyceride concentration (placebo 13 ± 60 mg dL-1; probiotics -15 ± 62 mg dL-1; p = 0.0088) were significantly different between the groups. The difference in total fat mass change between groups among postmenopausal women was greater than that of all women. A significant positive correlation was found between the change in total fat mass and log leptin/adiponectin ratio (R = 0.371, p = 0.0112) in the probiotics group. In addition, BMI (26.6 ± 1.9 kg m-2 to 26.4 ± 2.0 kg m-2, p = 0.0009) and leg fat (42 ± 5% to 41 ± 5%, p = 0.0006) significantly decreased in the probiotics group after 12 weeks, but there was no difference in the placebo group. In conclusion, B. lactis IDCC 4301 (B. lactis Fit™) may be associated with body fat loss through changes in metabolic health parameters, such as serum triglyceride and adipokine levels. The clinical trial registry number is KCT0007425 (https://cris.nih.go.kr).

Results of a randomized, double-blind, placebo-controlled trial of lorcaserin in cocaine use disorder

BackgroundCocaine use disorder (CUD) is a major public health problem for which there is no approved pharmacotherapy. The primary purpose of this study was to evaluate the ability of lorcaserin, a 5-hydroxytryptamine2 C (5-HT2 C) receptor agonist, to facilitate abstinence in individuals seeking treatment for CUD. MethodsThis was a 12-site, randomized, parallel arm study with a 13-week Treatment Phase that included a 1-week, single-blind run-in period when all participants received twice daily 15mg acetazolamide capsules (a medication adherence marker), followed by randomization to either twice daily 10mg lorcaserin or placebo capsules for the remaining 12 weeks. Pre-randomization data were utilized in an enrichment strategy aimed at achieving high levels of medication adherence and low placebo response rates in a subgroup of participants that qualified for the “efficacy population.” For lorcaserin vs. placebo, the primary efficacy endpoint was the proportion of participants in the efficacy population achieving abstinence during the last three weeks of treatment, as evidenced by self-report of no cocaine use, confirmed by urine testing. Results: Within the efficacy population, 1.1% of 91 participants receiving lorcaserin and 4.3% of 92 receiving placebo achieved abstinence during the last 3 weeks of treatment. Among all randomized participants, 2.5% of 118 receiving lorcaserin and 5.6% of 124 receiving placebo achieved similar abstinence. Study participants receiving lorcaserin exhibited significantly greater reductions in body weight and BMI, indicating that medication adherence was sufficient to produce a pharmacological effect. Conclusions: Twice daily 10mg lorcaserin failed to demonstrate efficacy in the treatment of CUD.

Safety and efficacy of paromomycin/miltefosine/liposomal amphotericin B combinations for the treatment of post-kala-azar dermal leishmaniasis in Sudan: A phase II, open label, randomized, parallel arm study.

Treatment for post-kala-azar dermal leishmaniasis (PKDL) in Sudan is currently recommended only for patients with persistent or severe disease, mainly because of the limitations of current therapies, namely toxicity and long hospitalization. We assessed the safety and efficacy of miltefosine combined with paromomycin and liposomal amphotericin B (LAmB) for the treatment of PKDL in Sudan. An open-label, phase II, randomized, parallel-arm, non-comparative trial was conducted in patients with persistent (stable or progressive disease for ≥ 6 months) or grade 3 PKDL, aged 6 to ≤ 60 years in Sudan. The median age was 9.0 years (IQR 7.0-10.0y) and 64% of patients were ≤12 years old. Patients were randomly assigned to either daily intra-muscular paromomycin (20mg/kg, 14 days) plus oral miltefosine (allometric dose, 42 days)-PM/MF-or LAmB (total dose of 20mg/kg, administered in four injections in week one) and oral miltefosine (allometric dose, 28 days)-AmB/MF. The primary endpoint was a definitive cure at 12 months after treatment onset, defined as clinical cure (100% lesion resolution) and no additional PKDL treatment between end of therapy and 12-month follow-up assessment. 104/110 patients completed the trial. Definitive cure at 12 months was achieved in 54/55 (98.2%, 95% CI 90.3-100) and 44/55 (80.0%, 95% CI 70.2-91.9) of patients in the PM/MF and AmB/MF arms, respectively, in the mITT set (all randomized patients receiving at least one dose of treatment; in case of error of treatment allocation, the actual treatment received was used in the analysis). No SAEs or deaths were reported, and most AEs were mild or moderate. At least one adverse drug reaction (ADR) was reported in 13/55 (23.6%) patients in arm 1 and 28/55 (50.9%) in arm 2, the most frequent being miltefosine-related vomiting and nausea, and LAmB-related hypokalaemia; no ocular or auditory ADRs were reported. The PM/MF regimen requires shorter hospitalization than the currently recommended 60-90-day treatment, and is safe and highly efficacious, even for patients with moderate and severe PKDL. It can be administered at primary health care facilities, with LAmB/MF as a good alternative. For future VL elimination, we need new, safe oral therapies for all patients with PKDL. ClinicalTrials.gov NCT03399955, https://clinicaltrials.gov/study/NCT03399955 ClinicalTrials.gov ClinicalTrials.gov.

Comparison of the Efficacy of Opioid-Free Anesthesia With Conventional Opioid-Based Anesthesia for Nasal Surgeries - A Prospective Randomized Parallel Arm Triple-Blinded Study.

Introduction In the setting of nasal surgeries, the use of opioid-free anesthesia involving the use ofdexmedetomidine,and lignocaine is being investigated as a potential alternative to opioids. This combination of drugs provides sympatholysis, pain relief, and sedative properties, thereby aiming at reducing the negative effects commonly associated with opioid usage. The objective of this study is to evaluate and compare the effectiveness of opioid-free anesthesia using dexmedetomidineand lignocaineversus conventional opioid anesthesia with fentanylfor nasal surgeries. The comparison will be based on the primary outcome of postoperative visual analog scale(VAS) scores. Secondary outcomes assessed were the amount of rescue analgesic consumption, intraoperative sevoflurane usage, intraoperative blood loss, hemodynamic stability, postoperative nausea and vomiting (PONV) scores, and postoperative Ramsay Sedation Scores. Methods A triple-blind, prospective, randomized, parallel arm study in which 48 patients planned for elective nasal surgery were allocated randomly to one of two groups. In the study, the population labeled as Group D, comprising 24 participants, received dexmedetomidine at a dosage of 1 mcg.kg-1 via intravenous infusion lasting for a duration of 10 minutes prior to the induction of anesthesia. This was followed by a continuous infusion of 0.6 mcg.kg-1 h-1 throughout the intraoperative period, and intravenous Lignocaine 1.5 mg.kg-1 was administered three minutes prior to induction, subsequently an intraoperative infusion of 1.5 mg.kg-1 h-1. In Group F, consisting of 24 participants,intravenous fentanyl of 2 mcg.kg-1was administered three minutes before the induction. This was subsequently followed by a fentanyl infusion of 0.5 mcg.kg-1h-1in the intraoperative period. Results The study findings indicate that Group D had considerably lower postoperative VAS scores from 30 minutes to two hours compared to Group F (p<0.05). The utilization of sevoflurane during the intraoperative period was comparatively reduced in Group D in order to achieve the desired bispectral index (BIS) range of 40-60 (p<0.01). Mean intraoperative blood loss was also lower in Group D (85 ml) compared to Group F (115 ml )(p<0.01). Additionally, Group D had significantly lower rescue analgesic consumption and lower incidence of PONV up to 60 minutes compared to Group F (P-value <0.01).A statistically significant difference was observed between Group D and Group F in terms of lower mean values of both mean arterial pressure (MAP) and heart rate in Group D(p<0.01). The results indicate that the postoperative sedation scores within the first two hours were significantly greater in Group D compared to Group F(p<0.01). Conclusion The usage of opioid-free anesthesia has been found to be superior to a traditional opioid-based approach in various aspects, including the provision of sufficient pain relief after surgery, maintenance of stable hemodynamics during the operation, and reduction in occurrences of postoperative nausea and vomiting.

Atracurium Versus Cis-Atracurium for Laryngeal Relaxation and Hemodynamic Stability in Pediatric Patients: A Randomized, Double-Blind Study.

Background and aim Equipotent dose of atracurium and cis-atracurium has failed to show clinically equi-effective muscle relaxation actions required for laryngoscopy and endotracheal intubation (LETI) in adults. There needs to be more data on children. We aimed to compare the efficacy of equipotent atracurium and cis-atracurium for producing optimal LETI. We also compared the hemodynamic stability and side effects. Methods With approvals and informed consent, 104 children between three and 12 years were enrolled in the present randomized, double-blind, parallel-arm study. Fifty-two participants were recruited in each group and received either 2ED95 atracurium (0.5mg/kg) or 2ED95 cis-atracurium (0.1mg/kg). Three-point scale, i.e., excellent, good, and poor, were assigned based on jaw relaxation, vocal cords, diaphragmatic movement, coughing, and resistance to the laryngoscope blade. Basic hemodynamics and adverse events like flushing, hemodynamic instability, and airway spasms were noted. The groups were compared using Wilcoxon-Mann-Whitney U or Chi-square tests as applicable; a p-value <0.05 was considered significant. Results Entire enrolled participants completed the study. Excellent LETI conditions were significantly higher in the atracurium than in cis-atracurium (53.8% versus 19.2%, p-value <0.001). In the present study, blunted laryngoscopy-related sympathetic surge containing the increase in hemodynamic parameters within 20% from the baseline was noted in both groups, but the blunting and fall back of hemodynamic towards the baseline was rapid in the atracurium (within 7 minutes of LETI) group than cis-atracurium, i.e., 72 minutes; p-value <0.001. Only one flushing was noted in the atracurium group compared to none in the cis-atracurium. Conclusion 2ED95 dose of cis-atracurium (0.1mg/kg), although have minor advantages of maintaining hemodynamic better, has lower adverse events, it provides significantly lower 'Excellent LETI conditions' when compared to 2ED95 dose of atracurium (0.5mg/kg) in children of age three to 12 years.