Double-blind Randomized Study Research Articles

The comparison of efficacy of Escitalopram and Bupropion in treatment of depression symptoms in patients with heart failure: randomized clinical trial

Objective: This study aims to compare the effects of two medicines, Escitalopram and Bupropion, on HF patients who have depression symptoms. Methods: This double-blind randomized clinical trial study was conducted on HF patients with depression symptoms at the Heart Failure Clinics affiliated with Babol University of Medical Sciences. In this study, 80 participants were examined for depression based on the Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HDRS). They were randomly allocated into 2 groups of 40 participants treated with Bupropion 75 mg and Escitalopram 5 mg. Following the intervention, the individuals were assessed in terms of their depression score at 4, 8, and 12-week intervals. Finally, the data was analyzed using SPSS version 22.0. Results: In the examination of Beck and Hamilton scores in the two research groups during different follow-ups, a significant decrease was found over time (P<0.001 for both medicines). While the effectiveness of the two medicines was the same at different times (P>0.05 in all cases). Comparing the side effects between the two intervention groups, the orgasm disorder (P=0.018) and sexual dysfunction (P<0.001) were reported significantly more in the Escitalopram group than in the Bupropion group. Conclusions: The findings of this study showed that Escitalopram has the same efficacy as Bupropion in the treatment of depression symptoms in HF patients.

A double-blinded randomised control study to compare the effectiveness and safety of intralesional vitamin D3 with intralesional triamcinolone and its correlation with tissue expression of vitamin D receptors in patients with keloid.

Intralesional steroids commonly used for keloid treatment have adverse effects like cutaneous atrophy and telangiectasias. Safer and more effective therapies are needed. Preliminary studies suggest intralesional vitamin D as a potential alternative treatment. The aim of this study was to compare efficacy and safety of intralesional vitamin D with triamcinolone for keloids, and correlate tissue expression of vitamin D receptors (VDRs) with treatment outcomes. Sixty patients were randomly assigned to two groups: Group A (intralesional vitamin D) and Group B (intralesional triamcinolone). Four injections were given at 4-week intervals, with an 8-week follow-up. Biopsies were taken pre- and post-treatment to examine VDR expression levels and treatment response correlation. The primary outcome of interest was the proportion of patients achieving a 50% reduction in Vancouver Scar Scale (VSS). Secondary outcomes included incidence of adverse effects, and changes in VDR expression before and after treatment. Baseline VSS scores were 9.73 ± 1.01 (vitamin D group) and 10.13 ± 1.07 (triamcinolone group). After treatment, mean VSS decreased to 5.17 ± 0.59 (vitamin D group, p < 0.001) and 4.77 ± 0.77 (triamcinolone group, p < 0.001), with significantly better response in latter (p = 0.03). More than 50% reduction in VSS score was higher in the triamcinolone group (76.7% vs. 50%, p = 0.032). No recurrences were noted during the 8-week follow-up. Hypopigmentation (80% vs. 36.7%, p < 0.001) and atrophy (73.3% vs. 40%, p = 0.009) were more common in the triamcinolone group. No significant difference in pre- and post-treatment VDR receptor expression was observed in either group. Both triamcinolone acetonide and vitamin D were effective for keloids. Triamcinolone was more efficacious, whereas vitamin D was safer, suggesting it as a viable alternative for keloid management.

The Safety and Feasibility of Transcranial Direct Current Stimulation Combined with Conservative Treatment for Patients with Cervicogenic Headaches: A double-blinded randomized control study protocol

The Safety and Feasibility of Transcranial Direct Current Stimulation Combined with Conservative Treatment for Patients with Cervicogenic Headaches: A double-blinded randomized control study protocol

Intranasal administration of insulin on the incidence of postoperative delirium in middle-aged patients undergoing elective on-pump cardiac surgery (INIPOD-MOPS): a prospective double-blinded randomized control study protocol

BackgroundDelirium, marked by acute cognitive decline, poses a life-threatening issue among older individuals, especially after cardiac surgery, with prevalence ranging from 15 to 80%. Postoperative delirium is linked to increased morbidity and mortality. Although clinical trials suggest preventability, there is limited research on intranasal insulin (INI) for cardiac surgery-related delirium. INI has shown promise in managing cognitive disorders. It rapidly elevates brain hormone levels, enhancing memory even in non-impaired individuals. While effective in preventing delirium in gastrointestinal surgery, its impact after cardiac surgery remains understudied, especially for middle-aged patients.MethodThis is a prospective randomized, double-blind, single-center controlled trial. A total of 76 eligible participants scheduled for elective on-pump cardiac surgery will be enrolled and randomly assigned in a 1:1 ratio to either receive Intranasally administered insulin (INI) or intranasally administered normal saline. The primary outcome of our study is the incidence of postoperative delirium (POD). Secondary outcomes include duration of ICU, postoperative hospital length of stay, all in-hospital mortality, the change in MMSE scores pre- and post-operation, and incidence of postoperative cognitive dysfunction at 1 month, 3 months, and 6 months after operation. Moreover, we will subjectively and objectively evaluate perioperative sleep quality to investigate the potential impact of nasal insulin on the development of delirium by influencing sleep regulation.DiscussionOur study will aim to assess the impact of intranasal administration of insulin on the incidence of postoperative delirium in middle-aged patients undergoing on-pump elective cardiac surgery. If intranasal insulin proves to be more effective, it may be considered as a viable alternative for preventing postoperative delirium.Trial registrationChiCTR ChiCTR2400081444. Registered on March 1, 2024.

TO ASSESS THE ROLE OF NASAL TAPENTADOL AS PRE-EMPTIVE ANALGESIA, IN BREAST SURGERY PATIENTS

Patients undergoes moderate to severe postoperative pain after surgery, which is troublesome during the postoperative period. Inadequately treated acute post operative pain causes prolonged morbidity to patients. Pre-emptive analgesic minimises the pain in perioperative period by central neuro sensitization. We assessed the role of Nasal Tapentadol in breast surgery patients, as a pre-emptive analgesic, in the reduction of post-operative analgesic requirement. In a double blinded prospective randomized control study, sixty breast surgery patients, received nasal spray of tapentadol (Group A) or saline Spray (Group B), 30 minutes prior to general anaesthesia. Perioperative analgesic requirement, time taken for first analgesic requirement in post operative period, post operative pain and sedation scores, we compared the following parameters in the first 24h during the postoperative period in all patients: Analgesic requirement during perioperative period, time taken for first post operative analgesic dose, pain score and sedation score in postoperative period.Data Of all sixty patients were analysed. Patients in Tapentadol Group A had significantly lower requirement of analgesics and lower Visual analog scale (VAS) than Saline group in the post operative period. However, Ramsay sedation score was more in Tapentadol group, immediately after shifting the patient to the postanaesthetic care unit. Single Pre-emptive nasal spray of tapentadol (45mg) is an effective intervention to, reduce the surgical pain and lesser requirement of analgesics, in post operative period, without added side effects.

Effects of supplementing extracorporeal shockwave therapy (ESWT) to hyaluronic acid (HA) injection among patients with rotator cuff lesions without complete tear: A prospective double-blinded randomized study.

The study investigates the combined efficacy of subacromial hyaluronic acid (HA) injections and extracorporeal shockwave therapy (ESWT) in managing rotator cuff lesions without complete tears. Eligible patients were randomized into three groups: 3 HA injections combined with 2 sham ESWT (HA), 3 HA injections combined with 1 ESWT and 1 sham ESWT (HA + 1 ESWT), or 3 HA injections combined with 2 ESWT (HA + 2 ESWT) with an allocation ratio of 1:1:1. Visual Analogue Scale (VAS), Constant-Murley Score (CMS), range of motion (ROM), and muscle power of shoulder abduction (MP) were assessed pre-intervention and at 1, 3, 6, and 12 months post-initial HA injection. Shoulder magnetic resonance imaging (MRI) was conducted before and twelve months after the intervention. All pertinent parameters showed no significant between-group differences at baseline but demonstrated significant within-group improvement throughout the study. The HA + 1 ESWT group demonstrated superior improvements in MP (P=0.011) and CMS (P=0.018) at 1 month, and in MP (P=0.014) and CMS (P=0.005) at 6 months, compared to the HA group. The HA + 2 ESWT group showed greater improvements in FF (P=0.027), IR (P=0.019), and SROM (P=0.025) at 1 month, and in ABD (P=0.022) at 6 months, compared to the HA group. Notably, the HA + 2 ESWT group exhibited greater improvements in FF (P=0.013), IR (P=0.019), and SROM (P=0.025) at 1 month, and in FF (P=0.007) at 3 months, than the HA + 1 ESWT group. Moreover, no deterioration in tendinopathy grading or tear status occurred in the HA + 1 ESWT group on MRI scans. ESWT provides additional benefits when combined with HA injections for patients with rotator cuff lesions lacking complete tears.

Magnesium sulphate to prevent perioperative atrial fibrillation in cardiac surgery: a randomized clinical trial

BackgroundPostoperative atrial fibrillation (POAF) is a common and potentially serious complication post cardiac surgery. Hypomagnesaemia is common after cardiac surgery and recent evidence indicates that supplementation of magnesium may prevent POAF. We aim to investigate the effectiveness of continuous intravenous magnesium sulphate administration in the perioperative period to prevent POAF as compared to placebo.MethodsThe (POMPAE) trial is a phase 2, single-center, double-blinded randomized superiority clinical study. It aims to assess the impact of perioperative continuous intravenous magnesium administration on the occurrence of cardiac surgery-related POAF. A total of 530 patients will be included. Eligible patients will be randomized in 1:1 ratio to the intervention or placebo group with stratification based on the presence of valvular surgery. The objective of the infusion is to maintain ionized magnesium levels between 1.5 and 2.0 mmol/L.DiscussionThe primary outcome measure is the incidence of de novo POAF within the first 7 days following surgery, with censoring at hospital discharge. This trial may generate crucial evidence for the prevention of POAF and reduce clinical adverse events in patients following cardiac surgery.Trial registrationThe POMPAE trial was registered at ClinicalTrials.gov under the following identifier NTC05669417, https://clinicaltrials.gov/ct2/show/NCT05669417. Registered on December 30, 2022.Protocol versionVersion 3.3, dated 13–01-2023.

Interplay of yoga, physical activity, and probiotics in irritable bowel syndrome management: A double-blind randomized study

ObjectivesThis study aimed to explore the synergistic impact of online yoga, mindfulness practices, and probiotics on irritable bowel syndrome (IBS) by evaluating changes in physical fitness, mental health, and gut microbiota composition. Design, setting and interventionsThe six-week randomized, double-blinded, placebo-controlled trial included 31 IBS patients categorized into three groups: online yoga with probiotics (EP), online yoga with a placebo (EC), and probiotics only (P). Assessments involved physical fitness tests, subjective questionnaires (IBS-QOL, BSRS-5), and gut microbiome analysis. Main outcome measuresParticipants self-collected stool samples and were given a set of questionnaires at baseline and after six weeks of intervention. Their symptoms were measured by changes in the gut microbiota, physical fitness and quality of life, and psychological well-being. ResultsThe EP group demonstrated improved cardiovascular endurance (P < 0.001) and a significant reduction in Klebsiella bacterial strains (P < 0.05). Both the EP and EC groups exhibited significantly decreased IBS-QOL scores (P < 0.001 and P < 0.05, respectively), indicating enhanced quality of life. While BSRS-5 scores decreased in both groups, the reduction was statistically insignificant. ConclusionIntegrating online yoga, mindfulness practices, and probiotics demonstrated comprehensive benefits for IBS patients. This intervention improved physical fitness and mental well-being and positively influenced gut microbiota composition. The study highlights the potential of this multifaceted approach in managing IBS symptoms and enhancing overall health, emphasizing the relevance of the gut-muscle-brain axis in understanding and addressing IBS complexities. Trial registrationTaiwanese Registry of Institutional Review Board IRBHP210009/CH11000259.

P-082 Use of TetraSOD® in male infertility: double-blind randomized placebo-controlled study

Abstract Study question Can the use of TetraSOD® (microalgae with high content of the antioxidant enzyme superoxide dismutase) improve semen quality and reduce oxidative stress in sperm? Summary answer The use of TetraSOD® reduces the oxidative stress of sperm, increasing the total sperm count in oligozoospermia and reducing the double-stranded DNA sperm fragmentation. What is known already Male factor is present in approximately 50% of the infertile couples, a large number of them of unknown or idiopathic origin. It has been demonstrated that semen quality is deteriorating over time, perhaps as a result of exposure to several environmental factors related with lifestyle that could impact both directly and indirectly on the complex process of spermatogenesis. Some of these bad habits of lifestyle increase the levels of oxidative stress in semen, which is associated with lower sperm concentration and motility. In this scenario, the use of antioxidants can be useful to increase sperm quality. Study design, size, duration Double-blind randomized placebo-controlled clinical study to assess the effect of 250 mg of TetraSOD® (microalgae with high content of the primary antioxidant enzyme superoxide dismutase). Eighty patients with idiopathic infertility showing asthenozoospermia, oligozoospermia or oligoasthenozoospermia were recruited and randomized to receive 250 mg of TetraSOD® (TSOD group) or placebo (Placebo group) for 3 months. Participants/materials, setting, methods Men with asthenozoospermia, oligozoospemia or aligoastenozoospermia and idiopatic infertility were recruited after informed consent signature. Patients were randomized into two groups. TetraSOD® group received 250 mg of TetraSOD®during 3 months, and Placebo group received capsules without TetraSOD® during the same period of time. Seminogram, double-strand sperm DNA fragmentation (COMET assay) and sORP (static oxidation- reduction potential) were studied at baseline (V0) and after 3 months (V3). Main results and the role of chance TetraSOD® consumption for three months elicited a statistically significant increase (Wilcoxon matched-pairs signed rank test; p=0.02) in the average number of sperms per ejaculate (from 17.06 x 106 to 41.94 x 106) in participants displaying oligozoospermia (&amp;lt;39 x 106 sperms) at V0. In contrast, the lower variation in the measured values in the Placebo group was not statistically significant. Regarding sORP, a statistically significant decrease (Wilcoxon matched-pairs signed rank test; p=0.0233) was observed in participants who displayed a value at V0 between 1.34-10. After TetraSOD® consumption, the average changed from 2.96 to 1.91 mv/106 sperm/ml from V0 to V3. However, not statistically significant changes were detected in the Placebo group between sORP values at V0 and V3. Moreover, in relation to double-stranded DNA breaks, a statistically significant decrease (Wilcoxon matched-pairs signed rank test; p=0.01) in the average percentages (from 31.81% to 25.93%) was measured after consumption of TetraSOD® at V3 in participants displaying a compromised redox status (sORP&amp;gt;1.34-10) at V0. No significant changes were found in the Placebo group. Limitations, reasons for caution The study was performed only in one ethnic group, so in future studies other ethnicities should be included. Wider implications of the findings TetraSOD® may improve male fertility because increases the number of sperms per ejaculate in oligozoospermia and reduces double-stranded DNA fragmentation in sperm when individuals display an altered redox status in semen. Such results might be related to the indirect antioxidant effect of TetraSOD®, reducing oxidative stress in seminal fluid. Trial registration number Not applicable

A Comparison and Safety Evaluation of Micellar versus Standard Vitamin D3 Oral Supplementation in a Randomized, Double-Blind Human Pilot Study.

The aim of this pilot study was to evaluate and compare bioavailability and safety of two Vitamin D3 formulations (softgels) in healthy adults, at single daily doses of 1000 and 2500 IU, over a 60-day period. A total of 69 participants were initially screened for eligibility in a double-blind randomized study with a four-arm parallel design; 35 participants were randomized to treatment groups: (1) standard Vitamin D3 1000 IU (STD1000), (2) micellar Vitamin D3 1000 IU (LMD1000), (3) standard Vitamin D3 2500 IU (STD2500), and (4) micellar Vitamin D3 2500 IU (LMD2500). Serum Vitamin D concentrations were determined through calcifediol [25(OH)D] at baseline (=before treatment), at day 5, 10, and 15 (=during treatment), at day 30 (=end of treatment), and at day 45 and 60 (=during follow-up/post treatment). Safety markers and minerals were evaluated at baseline and at day 30 and day 60. The pharmacokinetic parameters with respect to iAUC were found to be significantly different between LMD1000 vs. STD1000: iAUC(5-60): 992 ± 260 vs. 177 ± 140 nmol day/L; p < 0.05, suggesting up to 6 times higher Vitamin D3 absorption of LMD when measured incrementally. During follow-up, participants in the LMD1000 treatment group showed approx. 7 times higher Vitamin D3 concentrations than the STD1000 group (iAUC(30-60): 680 ± 190 vs. 104 ± 91 nmol day/L; p < 0.05). However, no significant differences were found between the pharmacokinetics of the higher dosing groups STD2500 and LMD2500. No significant changes in serum 1,25(OH)2D concentrations or other biochemical safety markers were detected at day 60; no excess risks of hypercalcemia (i.e., total serum calcium > 2.63 mmol/L) or other adverse events were identified. LMD, a micellar delivery vehicle for microencapsulating Vitamin D3 (LipoMicel®), proved to be safe and only showed superior bioavailability when compared to standard Vitamin D at the lower dose of 1000 IU. This study has clinical trial registration: NCT05209425.

The effects of grape seed extract supplementation on cardiovascular risk factors, liver enzymes and hepatic steatosis in patients with non-alcoholic fatty liver disease: a randomised, double-blind, placebo-controlled study.

Despite the high antioxidant potential of grape seed extract (GSE), very limited studies have investigated its effect on non-alcoholic fatty liver disease (NAFLD). Therefore, this study was conducted with the aim of investigating the effect of GSE on metabolic factors, blood pressure and steatosis severity in patients with NAFLD. In this double-blind randomized clinical trial study, 50 NAFLD patients were divided into two groups of 25 participants who were treated with 520mg/day of GSE or the placebo group for 2 months. The parameters of glycemic, lipid profile, blood pressure and steatohepatitis were measured before and after the intervention. The GSE group had an average age of 43.52 ± 8.12 years with 15 women and 10 men, while the placebo group had an average age of 44.88 ± 10.14 years with 11 women and 14 men. After 2 months of intervention with GSE, it was observed that insulin, HOMA-IR, TC, TG, LDL-c, ALT, AST, AST/ALT, SBP, DBP and MAP decreased and QUICKi and HDL-c increased significantly (p-value for all < 0.05). Also, before and after adjustment based on baseline, the average changes indicated that the levels of insulin, HOMA-IR, TC, TG, LDL-c, SBP, DBP, MAP in the GSE group decreased more than in the control group (p for all < 0.05). Furthermore, the changes in HDL-c were significantly higher in the GSE group (p < 0.05). The between-groups analysis showed a significant decrease in the HOMA-β and AST before and after adjustment based on baseline levels (p < 0.05). Moreover, the changes in QUICKi after adjustment based on baseline levels were higher in the GSE group than in the control group. Also, between-groups analysis showed that the severity of hepatic steatosis was reduced in the intervention group compared to the placebo group (P = 0.002). It seems that GSE can be considered one of the appropriate strategies for controlling insulin resistance, hyperlipidemia, hypertension and hepatic steatosis in NAFLD patients. The clinical trial was registered in the Iranian Clinical Trial Registration Center (IRCT20190731044392N1). https://irct.behdasht.gov.ir/trial/61413 . (The registration date: 30/03/2022).

In the article “Double blind randomized placebocontrolled study of the efficacy and safety of proroxan in the complex therapy of generalized anxiety disorder”

In the article “Double blind randomized placebocontrolled study of the efficacy and safety of proroxan in the complex therapy of generalized anxiety disorder”

A randomised trial comparing block characteristics of a mixture versus sequential injections of lignocaine and ropivacaine for supraclavicular brachial plexus nerve block in patients undergoing upper limb surgery.

There is no consensus on the appropriate use of mixtures of local anaesthetic drugs in various combinations for nerve blocks. We intended to compare short-acting lignocaine and long-acting ropivacaine as a mixture versus undiluted sequential injections on block characteristics of ultrasound-guided (USG) supraclavicular brachial plexus block for upper limb surgeries. A double-blinded randomised study was conducted on 64 adult patients scheduled for upper limb surgery who received 15 mL each of 2% lignocaine with adrenaline and 0.75% ropivacaine as a 1:1 mixture in the mixed group (Group M) or sequential injections in the sequential group (Group S) by using a USG technique. The primary outcome was the percentage of participants with complete four nerve sensory blocks at 10 minutes post block injection. Secondary outcomes were sensory and motor block characteristics till 30 minutes, total duration of analgesia, sensory and motor block, and complications. Demographic characteristics and time taken for the procedure were similar. The percentage of participants with a complete four-nerve sensory block at 10 minutes was higher in Group S (69%) versus Group M (41%) (P = 0.04). Complete sensory and motor block rates were similar at 30 minutes. The block procedure time, total duration of analgesia, and sensory and motor block were similar in both groups. There were no major complications. Sequential lignocaine-ropivacaine, compared to the mixed injection technique, has a higher initial rate of sensory and motor block onset with a similar total block duration.

The Effect of Oral Gabapentin and Pregabalin as a Prodrug in Pain Control after Orthopedic Surgery on the Upper Limb: A Double-Blind Parallel Randomized Clinical Trial Study.

To compare the effects of oral gabapentin (GBP) and pregabalin (PGB) in pain control after orthopedic surgery on the upper limb. In this double-blind randomized clinical trial study, 80 patients who were the candidates for elective orthopedic surgery on one of the parts of the upper limb were divided into two groups using balance-block randomization. For the first group, a 150 mg capsule of PGB (one hour before the surgery) and for the second group, a 300 mg capsule of GBP (two hours before the surgery) were prescribed. Patients were subjected to standard monitoring at the beginning and during surgery. The pain scores were evaluated at before surgery, in PACU (postanesthesia care unit), and 6 and 12 hours after the surgery by VAS (visual analog scale). In this study, 37 subjects were allocated to each group. The participation rate was 92.5%. The mean with 95% confidence interval (CI) of pain scores over 4 times in the PGB group was 4.03 (3.25-4.79), 3.76 (3.02-4.49), 3.65 (3.06-4.23), and 3.41 (2.88-3.93) and in the GBP group was 4.08 (3.33-4.83), 2.78 (2.11-4.45), 2.3 (2.05-2.54), and 2 (1.51-2.50), respectively. The within-group comparisons showed a significant decrease in the pain score over time (P < 0.001). Also, the between-group comparison showed significant differences between the two groups in terms of pain score (P < 0.001). In the end, results showed that there is a significant interaction between time and intervention for pain score (P=0.042). Although two medicines led to a reduction in the pain score, but the rate reduction in the PGB group was significantly more than that in the GBP group. This trial is registered with IRCT20211013052759N1.

Physiological variables for the objective detection of nerve block failure in dogs

ObjectiveTo identify physiological variables for objectively detecting nociception indicative of intraoperative peripheral nerve block failure. Study designA double-blinded randomized clinical study. AnimalsA sample of 14 male (40.8 ± 12 kg; mean ± standard deviation) and 16 female (34.3 ± 11.4 kg) client-owned dogs. MethodsDogs were randomly assigned to one of three groups for psoas compartment and proximal sciatic nerve blocks (0.2 mL kg–1 per site): guided bupivacaine (GBB), or saline (GSB) block or a blind bupivacaine block (BBB). Guided blocks were performed using an ultrasound-peripheral nerve locator combination. Premedication consisted of medetomidine 0.01 mg kg–1 and morphine 0.3 mg kg–1. General anaesthesia was induced with propofol and maintained with isoflurane in oxygen. Receiver operator characteristic curve analysis was used to compare actual values and change in values of physiological variables between GSB and GBB. The Youden index and associated criterion for each physiological variable were used to determine an objective measure for nociception. Fisher’s exact t test, McNemar’s test and Cohen’s kappa statistical analysis were used to determine association, differences and inter-score reliability between the objective and subjective scoring for BBB. ResultsCardiovascular variables had good discriminating ability to identify a nociceptive response (p < 0.01). The Youden indices for mean (MAP) and diastolic (DAP) arterial pressure were most reliable in detecting nociception. The highest sensitivity was that of ΔMAP (100%) with good agreement between the subjective and objective scores of Δheart rate or systolic arterial pressure (SAP). The use of ΔMAP, ΔSAP, ΔDAP had the best ability in indicating peripheral nerve block failure (p < 0.001). Conclusions and clinical relevanceBlood pressure values can detect a response to surgical stimulus in adequately anaesthetized dogs. The use of ΔMAP, ΔSAP or ΔDAP may be considered as objective measures to detect nerve block failure.

Pain Reduction of Ibuprofen Sodium Dihydrate Alone and in Combination with Acetaminophen in an Untreated Endodontic Pain Model: A Randomized, Double-blind Investigation

IntroductionMost pain studies have been based on a postsurgical, third molar model using ibuprofen (IBU)/acetaminophen (APAP). Studies have found quicker onset of pain relief with a newer formulation of IBU - ibuprofen sodium dihydrate (ISD). The purpose of this study was to compare pain reduction of ISD/APAP to ISD in an acute endodontic pain model of untreated patients experiencing moderate to severe pain with symptomatic apical periodontitis. Methods and MaterialsIn this double-blind randomized study, 64 adult emergency patients in acute moderate to severe pain, a pulpal diagnosis of symptomatic irreversible pulpitis or necrosis, and symptomatic apical periodontitis participated. Each patient randomly received either one dose of 768 mg ISD/1000 mg APAP or one dose of 768 mg ISD. Pain intensity scores were recorded every 15 minutes over 240 minutes using the Heft-Parker VAS along with time to first sign of pain relief, time to meaningful pain relief, and time to 50% pain relief also recorded. The data were analyzed statistically. ResultsBoth ISD and ISD/APAP groups showed a progressive decrease in pain from baseline to 120 minutes after medication administration. Afterward, a relative plateau was seen in the patients’ pain. There was no difference in the VAS scores between the ISD and ISD/APAP at any given time point, time to first sign of pain relief, time to meaningful pain relief, and time to 50% pain relief. ConclusionsThe addition of APAP to ISD for pain control in an untreated endodontic pain model did not differ significantly from ISD alone.

Effectiveness of Combined Treatment of Transcranial Direct Current Stimulation and Treatment as Usual on Depression, Anxiety and Anger in Adolescents with Bipolar Disorder

Objectives: Bipolar disorder (BD) is a prevalent psychological disorder associated with depressive symptoms. Transcranial direct current stimulation (tDCS) is a portable and non-invasive technique for brain stimulation. The present study was conducted to determine the effectiveness of the combined treatment of tDCS and routine medication on the symptoms of depression, anxiety, and anger in BD adolescents. Methods: In this double-blind randomized clinical trial study, forty adolescents with BD referred to the outpatient clinic of child and psychiatry of Golestan Ahvaz Teaching Hospital were included. Eligible patients aged 12 - 18 years were randomly divided into 2 groups receiving routine medications plus active tDCS (intervention group) or routine medications plus sham tDCS (control group). Transcranial direct current stimulation intervention with an intensity of 2 mA was applied to the dorsolateral prefrontal cortex in two sessions for 20 minutes each day, for 5 consecutive days. Data were collected at baseline, one week, and one month after the start of the intervention using the Hamilton Depression Rating Scale (HDRS-21), Hamilton Anxiety Rating Scale (HDRS), and State-Trait Anger Expression Inventory. Results: Based on our findings, age and gender were not considerably different between the two groups (P = 0.592, P = 0.1, respectively). In both groups, scores of depression (control: 12.25 ± 3.97, intervention: 0.75 ± 1.44, mean [SD]), anxiety (13.55 ± 2.58, 25.0 ± 0.55), and anger (52.65 ± 8.27, 47.25 ± 4.86) improved significantly one month after treatment (P &lt; 0.0001). After one month of treatment, the severity of bipolar symptoms in the intervention group (slightly: 10%, moderately: 50%, and markedly: 40%) improved significantly compared to the control group (slightly: 15%, moderately: 10%, and markedly: 0%) (P &lt; 0.0001). The improvement rate of HDRS in the intervention group was 81.29% and 95.24% at one week and one month after treatment, while these values were 8.41% and 23.04% in the control group, respectively (P &lt; 0.0001). All patients tolerated the treatment well without serious side effects. There was no significant difference between the side effects observed in both groups (P = 0.185). Conclusions: The combination of tDCS with routine medications can reduce depressive symptoms and improve bipolar symptoms. Therefore, tDCS add-on could be an effective, safe, and tolerable intervention for bipolar depression.

Investigation of the probiotic supplement's effect on obese adults demonstrated a reduction in fasting insulin levels: a double-blind randomized clinical trial.

Regarding the importance of obesity concerns and trying to help obese individuals, we planned to develop an effective probiotic formula for weight control. So, this double-blind randomized clinical trial study investigated the impact of probiotics supplementation on anthropometric and biochemical parameters in obese adults. In this study, 66 obese patients with BMI in the range of 30-40kg/m2, were enrolled and randomly assigned to either the probiotic or placebo group. They all received advice to maintain a reduction in daily caloric intake and for 3 months received two unlabeled placebo or probiotic (Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus casei and Bifidobacterium langum) capsules per day. For each participant demographic and medical history questionnaire, semi-quantitative food frequency questionnaire (FFQ), and modifiable activity questionnaire (MAQ) were completed at the beginning of the study and anthropometric and biochemical measurements were done before and after intervention. At the end of the trial 25 subjects in the probiotic group and 26 subjects in the placebo group were analyzed. After the intervention, in the probiotic group, the level of fasting insulin was reduced significantly (P < 0.05). Weight, body mass index, waist circumference, and hip circumference decreased within both groups. This reduction amount's mean was higher in the probiotic group. Also, total cholesterol, triglycerides, and LDL levels were decreased, but not statistically significant. This study may suggest the potential of this combined probiotic supplement for treating obesity and related metabolic disorders. However, further researches are warranted for a definitive determination of its properties.

Study of the pharmacokinetics, pharmacodynamics, and safety of the biosimilar pembrolizumab RPH-075 compared to Keytruda® in patients with malignant neoplasms

Introduction: Pembrolizumab is a humanized monoclonal antibody selectively blocking the interaction between the PD-1 receptor and its ligands. The drug RPH-075 is a biosimilar to the original Keytruda®.Objective: To establish the equivalence of pharmacokinetic (PK) properties, as well as pharmacodynamic (PD) parameters, safety, and immunogenicity of the drug RPH-075 compared to Keytruda® in patients with malignant tumors.Materials and Methods: This multicenter double-blind randomized study included 90 patients with melanoma and non-small cell lung cancer who were randomized into two treatment groups (RPH-075 and Keytruda ®) in 1:1 ratio. In both groups, pembrolizumab was administered as monotherapy at a dose of 200 mg intravenously every 3 weeks until progression or intolerable toxicity. The primary aim of the study was to assess PK after the first administration. The primary endpoint for PK assessment was AUC(0–504), and for safety, it was the frequency of adverse events (AE). The decision on PK equivalence was planned to be made if the two-sided 90 % confidence interval (CI) for the geometric mean ratio of AUC(0–504) after a single administration of each drug would be within 80.00–125.00 %. Secondary endpoints included Cmax after the first administration, as well as the other PK, safety, and immunogenicity parameters. This study also assessed PK and PD parameters after multiple administrations, and a pilot efficacy assessment was planned.Results: This article presents the analysis of data from the first stage of the study (after the first drug administration with a 3‑week observation period). The data analysis was blinded, and the treatment groups were coded as A and B. The 90 % CI for the geometric mean ratio of AUC(0–504) after the administration of drug A to AUC(0–504) of drug B was 93.50–121.16 %, and for the ratio of B to A, it was 82.54–106.95 %. The obtained intervals met the specified equivalence limit of 80.00–125.00 %, allowing us to conclude that RPH-075 and original Keytruda® are PK equivalent. Both drugs demonstrated comparably high saturation of PD-1 receptors on CD4+ / CD8+ lymphocytes at the end of the first cycle (day 22). Binding antibodies to pembrolizumab were detected in 2 patients (one in each group) over the analyzed period, indicating comparably low immunogenicity for both drugs. Safety profile analysis during this period revealed 7 AEs in 4 patients in group A and 4 AEs in 3 patients in group B. The frequency of AEs did not significantly differ between the groups.Conclusions: PK, PD, immunogenicity, and safety parameters of the pembrolizumab biosimilar RPH-075 were equivalent to those of the original Keytruda®.

(029) Safety and Efficacy of Botulinum Neurotoxin in the Treatment of Erectile Dysfunction Refractory to Phosphodiesterase Inhibitors: Results of a Randomized Controlled Trial

Abstract Introduction There has been recent interest in the use of botulinum neurotoxin (BoNT) in the field of Andrology, whereby it has been investigated in the treatment of penile retraction and premature ejaculation. Objective To evaluate the safety and efficacy of intracavernosal BoNT-A injection in the treatment of patients with erectile dysfunction (ED) refractory to oral phosphodiesterase inhibitors (PDE5Is). Methods A double-blind randomized placebo-controlled prospective comparative study conducted at one center and involved 70 patients with ED refractory to PDE5Is. At baseline, the following data were collected: erection hardness score (EHS), peak systolic velocity (PSV), end diastolic velocity (EDV), sexual health inventory for men (SHIM), and the sexual encounter profile 2&amp;3 (SEP-2&amp;3) questionnaires. Treatment group (n = 35) received a single ICI of 100 units of BoNT-A in 2 ml of saline and control group (n = 35) received a single ICI of 2 ml of saline. EHS, PSV, and EDV were assessed at 2 weeks post treatment. SHIM, SEP-2, SEP-3, and global assessment questionnaire (GAQ-Q1&amp;Q2) were completed at 2-, 6-, and 12-weeks post treatment. Results Two weeks post treatment, the treatment group showed a statistically significant improvement in the mean EHS, PSV, EDV, and GAQ-Q1 positive responders (p &amp;lt; 0.001) compared to the control group. At 6- and 12-weeks post treatment, the treatment group showed a statistically significant improvement in the SHIM scores, SEP-2, and GAQ-Q1&amp;Q2 positive responders compared to the control group. At 6 weeks, where there was a 5-point improvement in the mean SHIM score of the treatment group (10±5.9 from 5.4±1.7 at baseline) versus no improvement in the placebo group, 18 patients in the treatment group (53%) were able to have an erection hard enough for vaginal penetration versus only one patient in the control group. Conclusions BoNT-A is safe and effective as a potential treatment for ED refractory to PDE5I therapy. Disclosure No.