Double-blind Randomized Study Research Articles

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 (<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>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”

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.

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.

Effect of Silybum Marianum on Reduction of Chemotherapy-Induced Peripheral Neurotoxicity with Cisplatin.

Chemotherapy-induced peripheral neurotoxicity (CIPN) is one of the major complications of chemotherapy regimens commonly used in the treatment of solid and hematologic cancers. Given the high incidence of CIPN in antitumor therapies in patients and limited studies on antioxidants, this study was aimed to investigate the effect of Silybum marianum (SM) on cisplatin-induced peripheral neuropathy. This double-blind randomized clinical trial study was performed on 60 cancer patients treated with cisplatin chemotherapy at Seyyed-o-Shohada Hospital of Isfahan during 2019-2020. The patients were divided into two parallel groups as intervention (treated by SM) and placebo, and DN4 (Douleur neuropathique 4 questions) and CIPNAT (chemotherapy-induced peripheral neuropathy assessment tool) were completed for patients in the before and after intervention groups and compared between the two groups. The mean of DN4 score in the before and after study in the intervention group was in 1.76 ± 1.24 and 2.07 ± 2.03, respectively (P = 0.38), and in the control group was 1.41 ± 1.28 ± 3.11 ± 2.86, respectively (P = 0.012). The mean CIPNAT score in the intervention groups was 5.93 ± 3.65 and 4.20 ± 3.23 (P = 0.01), and in the control group was 4.20 ± 4.22 and 4.16 ± 4.03 (P = 0.39). Based on our data, SM is an effective agent in reducing peripheral neuropathy. The use of SM was associated with decreased scores of peripheral neuropathy and was helpful in patients undergoing chemotherapy with cisplatin.

Effect of corticosteroids on ischemia-reperfusion injury of deep inferior epigastric perforator flap after re-exploration for anastomosis thrombosis: A prospective randomized trial

Patients undergoing breast reconstruction with the deep inferior epigastric perforator (DIEP) flap are at risk of arterial and venous thrombosis, necessitating flap salvage surgery. However, this carries the risk of ischemia-reperfusion injury (IRI) and potential significant partial or complete flap loss. The objective of this study was to evaluate the potential benefit of corticosteroids in reducing IRI related complications in DIEP flaps that are returned to the operation theater for attempted salvage after venous or arterial failure.A double-blinded prospective randomized study was conducted between January 2012 and January 2023 on patients scheduled for secondary unilateral breast reconstruction using the DIEP flap technique. Patients were included if they developed post-operative venous or arterial flap thrombosis and experienced DIEP flap IRI following operative take-back and anastomosis revision. The treatment group (TG) received a 5-day course of corticosteroids, while the control group (CG) did not receive any specific treatment. Forty-six patients were enrolled in the study. In the CG, two cases of total flap loss and eight cases of partial flap necrosis were observed, while the TG had only 1 case of partial flap necrosis (p < 0.05). The complete resolution of clinical signs of IRI occurred within 13 ± 2.1 days for the TG and 21 ± 3.5 days for the CG (p = 0.00001). The TG had a significantly shorter hospital stay (11.13 ± 0.38 days) compared with the CG (15.47 ± 1.27 days; p < 0.0001). Targeted corticosteroid therapy following a salvage procedure for vascular thrombosis in DIEP flaps has shown promise as an effective treatment for subsequent IRI. This approach may be considered as a viable option for managing IRI in free flaps. However, further studies involving a larger number of patients are required to substantiate our hypothesis.

Gastric peroral endoscopic myotomy versus botulinum toxin injection for the treatment of refractory gastroparesis: results of a double-blind randomized controlled study.

Gastric peroral endoscopic myotomy (G-POEM) is a promising technique for treating refractory gastroparesis. We present the first double-blind randomized study comparing the clinical efficacy of G-POEM versus pyloric botulinum toxin injection (BTI). This randomized study, conducted in two expert centers, enrolled patients with refractory gastroparesis, medically managed for >6 months and confirmed by gastric emptying scintigraphy (GES), into two groups, G-POEM versus BTI, with follow-up of 1 year. The primary end point was the 3-month clinical efficacy, defined as a >1-point decrease in the mean Gastroparesis Cardinal Symptom Index (GCSI) score. Secondary end points were: 1-year efficacy, GES evolution, adverse events, and quality of life. 40 patients (22 women; mean age 48.1 [SD 17.4]), with mean symptom duration of 5.8 (SD 5.7) years, were randomized. Etiologies included idiopathic (n=18), diabetes (n=11), postoperative (n=6), and mixed (n=4). G-POEM showed a higher 3-month clinical success than BTI (65% vs. 40%, respectively; P=0.10), along with non-significantly higher 1-year clinical success (60% vs. 40%, respectively) on intention-to-treat analysis. The GCSI decreased in both groups at 3 months and 1 year. Only three minor adverse events occurred in the G-POEM group. The GES improvement rate was 72% in the G-POEM group versus 50% in the BTI group (non-significant). G-POEM seems to have a higher clinically relevant success rate than BTI, but this was not statistically demonstrated. This study confirms the interest in treatments targeting the pylorus, either mechanically or chemically, for managing refractory gastroparesis.

The value of lung ultrasound score in neonatal respiratory distress syndrome: a prospective diagnostic cohort study.

The accurate diagnosis of critically ill patients with respiratory failure can be achieved through lung ultrasound (LUS) score. Considering its characteristics, it is speculated that this technique might also be useful for patients with neonatal respiratory distress syndrome (NRDS). Thus, there is a need for precise imaging tools to monitor such patients. This double-blind randomized cohort study aims to investigate the impact of LUS and related scores on the severity of NRDS patients. This study was conducted as a prospective double-blind randomized study. Bivariate correlation analysis was conducted to investigate the relationship between LUS score and Oxygenation Index (OI), Respiratory Index (RI), and Sequential Organ Failure Assessment (SOFA) score. Spearman's correlation coefficient was used to generate correlation heat maps, elucidating the associations between LUS and respective parameters in different cohorts. Receiver Operating Characteristic (ROC) curves were employed to calculate the predictive values, sensitivity, and specificity of different scores in determining the severity of NRDS. This study ultimately included 134 patients admitted to the intensive care unit (ICU) between December 2020 and June 2022. Among these patients, 72 were included in the NRDS cohort, while 62 were included in the Non-NRDS (N-NRDS) cohort. There were significant differences in the mean LUS scores between NRDS and N-NRDS patients (p < 0.01). The LUS score was significantly negatively correlated with the OI (p < 0.01), while it was significantly positively correlated with the RI and SOFA scores (p < 0.01). The correlation heatmap revealed the highest positive correlation coefficient between LUS and RI (0.82), while the highest negative correlation coefficient was observed between LUS and OI (-0.8). ROC curves for different scores demonstrated that LUS score had the highest area under the curve (0.91, 95% CI: 0.84-0.98) in predicting the severity of patients' conditions. The combination of LUS and other scores can more accurately predict the severity of NRDS patients, with the highest AUC value of 0.93, significantly higher than using a single indicator alone (p < 0.01). Our double-blind randomized cohort study demonstrates that LUS, RI, OI, and SOFA scores can effectively monitor the lung ventilation and function in NRDS. Moreover, these parameters and their combination have significant predictive value in evaluating the severity and prognosis of NRDS patients. Therefore, these results provide crucial insights for future research endeavors.

Phytocannabinoids and gingival inflammation: Preclinical findings and a placebo-controlled double-blind randomized clinical trial with cannabidiol.

The aim of this study was to: (1) evaluate the anti-inflammatory effects of cannabidiol (CBD) on primary cultures of human gingival fibroblasts (HGFs) and (2) to clinically monitor the effect of CBD in subjects with periodontitis. The use of phytocannabinoids is a new approach in the treatment of widely prevalent periodontal disease. Cannabinoid receptors were analyzed by western blot and interleukin production detected using enzyme immunoassay. Activation of the Nrf2 pathway was studied via monitoring the mRNA level of heme oxygenase-1. Antimicrobial effects were determined by standard microdilution and 16S rRNA screening. In the clinical part, a placebo-control double-blind randomized study was conducted (56 days) in three groups (n = 90) using dental gel without CBD (group A) and with 1% (w/w) CBD (group B) and corresponding toothpaste (group A - no CBD, group B - with CBD) for home use to maintain oral health. Group C used dental gel containing 1% chlorhexidine digluconate (active comparator) and toothpaste without CBD. Human gingival fibroblasts were confirmed to express the cannabinoid receptor CB2. Lipopolysaccharide-induced cells exhibited increased production of pro-inflammatory IL-6 and IL-8, with deceasing levels upon exposure to CBD. CBD also exhibited antimicrobial activities against Porphyromonas gingivalis, with an MIC of 1.5 μg/mL. Activation of the Nrf2 pathway was also demonstrated. In the clinical part, statistically significant improvement was found for the gingival, gingival bleeding, and modified gingival indices between placebo group A and CBD group B after 56 days. Cannabidiol reduced inflammation and the growth of selected periodontal pathogenic bacteria. The clinical trial demonstrated a statistically significant improvement after CBD application. No adverse effects of CBD were reported by patients or observed upon clinical examination during the study. The results are a promising basis for a more comprehensive investigation of the application of non-psychotropic cannabinoids in dentistry.

Comparative study between rocuronium and magnesium sulfate as adjuvants to local anesthetics for peribulbar block

Background &amp; Objective: Peribulbar anesthesia is frequently used in cataract surgeries. Compared to retrobulbar anesthesia, this approach is associated with less significant consequences. However, the prolonged onset of orbital akinesia and the frequent need for block replenishment are considered drawbacks. We aimed to investigate the impact of adding rocuronium and magnesium sulfate to a commonly used local anesthetic combination on the onset of corneal anesthesia and the degree of lid and globe akinesia during peribulbar block in ocular surgeries.&#x0D; Patients and Methods: This prospective double-blinded randomized study was conducted in the ophthalmic surgery operating theater, Ain Shams University Hospital from January 2019 to April 2020. We enrolled 75 patients from both sexes, with American Society of Anesthesiology (ASA) physical status I–III, ages 40-80 y, and an axial globe length less than or equal to 26 mm planned for cataract surgery under peribulbar block in the study following institutional ethical board approval and written informed patient consents. Patients were randomly divided into three groups, 25 patients per group, based on the drugs they received: Group O (control group): received local anesthetic + 0.9% normal saline (1 ml). Group M: received local anesthetic + magnesium sulphate 50 mg in normal saline. Group R: received local anesthetic + rocuronium at a dose of 0.06 mg/kg (maximum 5 mg) in normal saline.&#x0D; Results: Our study found statistically significant more rapid onset of action (mean time to start surgery) in rocuronium group (7.00 ± 1.22 min) than control group and magnesium sulfate group (9.00 ± 1.47 and 9.00 ± 1.15 min) respectively, (P &lt; 0.001); Moreover, no significant difference was noted between control group and magnesium sulfate group. In addition, no relevant difference was reported regarding duration of surgery between the groups.&#x0D; Conclusion: During cataract surgery, the addition of rocuronium to the local anesthetic mixture in the peribulbar nerve block has been found to enhance ocular akinesia and corneal anesthesia. Furthermore, the use of rocuronium demonstrated a significantly faster onset and shorter time needed to achieve the appropriate conditions to initiate the surgical procedure compared to the use of magnesium sulfate. Addition of magnesium sulfate showed good results regarding akinesia, corneal anesthesia and need for supplementary injections but it did not significantly fasten the onset of block and hence the time to start surgery.&#x0D; Key words: Cataract; Magnesium Sulfate; Peribulbar Block; Rocuronium&#x0D; Citation: Nagy M, Abo El-Ella S, El-Shafey MA, Helal AM, Zekry MR. Comparative study between rocuronium and magnesium sulfate as adjuvants to local anesthetics for peribulbar block. Anaesth. pain intensive care 2024;28(1):55−61; DOI: 10.35975/apic.v28i1.2157&#x0D; Received: February 18, 2023; Reviewed: July 30, 2023; Accepted: December 23, 2023

Antioxidant treatment for oligoasthenoteratozoospermia and varicocele: a DBPC trial to evaluate the impact of age and body mass index.

Oxidative stress is one of the main mechanisms responsible for male infertility. Various conditions such as varicocele, obesity, advanced age, and lifestyle can lead to an increase in reactive oxygen species, causing an oxidative imbalance in the reproductive environment. Spermatozoa are sensitive to reactive oxygen species and require energy to carry out their main function of fertilizing the egg. Excessive reactive oxygen species can affect sperm metabolism, leading to immobility, impaired acrosome reaction, and cell death, thereby impairing reproductive success. This double-blind randomized study evaluated the effect of supplementation with L-carnitine, acetyl-L-carnitine, vitamins, and other nutrients on semen quality in 104 infertile patients with or without varicocele, while also investigating the impact of factors such as obesity and advanced age on treatment. Sperm concentration significantly increased in the supplemented group compared to the placebo group (P = 0.0186). Total sperm count also significantly increased in the supplemented group (P = 0.0117), as did sperm motility (P = 0.0120). The treatment had a positive effect on patients up to 35 years of age in terms of sperm concentration (P = 0.0352), while a body mass index (BMI) above 25 kg m-2 had a negative effect on sperm concentration (P = 0.0110). Results were not showing a net benefit in stratifying patients in accordance with their BMI since sperm quality increase was not affected by this parameter. In conclusion, antioxidant supplementation may be beneficial for infertile patients and has a more positive effect on younger patients with a normal weight.

Successful treatment of solar lentigines by topical application of stabilized cysteamine: A vehicle-controlled, double-blind randomized study.

Solar lentigines are common hyperpigmented lesions typically appearing after 50 years of age and associated with negative psychological effects in affected individuals. Topical depigmenting products, such as hydroquinone and even the Kligman's formula, are usually ineffective for treating lentigines. Stabilized cysteamine has been recently shown to be as effective as the modified Kligman's formula for treating melasma. In this study, we evaluated the therapeutic effect of a stabilized cysteamine on solar lentigines. A vehicle-controlled, double-blind, and randomized study was performed on 30 patients with solar lentigines. Stabilized cysteamine or vehicle control creams were applied on solar lentigines on the dorsum of the hands daily for 12 weeks. Clinical measurements with colorimetry and visual analog scale were performed at baseline, 4, 8, and 12 weeks. Statistically significant results were obtained in the cysteamine group versus the vehicle control group. Stabilized cysteamine provided a 40% reduction in colorimetric values (p < 0.002) versus a 2% reduction in the vehicle group (p < 0.405). Cysteamine also provided a 40% reduction in VAS (p < 0.001) versus a 2% reduction in the vehicle group (p < 0.245). Significant improvement of solar lentigines was observed after 12 weeks of application of stabilized cysteamine by all evaluation methods. Stabilized cysteamine represents a highly effective topical treatment for solar lentigines and can be considered as one of the first topical therapies effective on this hyperpigmentary disorder.

Comparative evaluation of nebulised dexmedetomidine vs fentanyl for the treatment of post-dural puncture headache (PDPH) in parturients after caesarean section under spinal anaesthesia: A randomised controlled study.

The incidence of post-dural puncture headache (PDPH) following spinal anaesthesia in the obstetric population is around 0.5%-2%. Hydration, bed rest, caffeine, paracetamol, non-steroid anti-inflammatory drugs, epidural blood patches, etc., are the various modalities used for its management. This study aims to compare nebulised dexmedetomidine versus fentanyl for the treatment of PDPH in parturients after caesarean section under spinal anaesthesia. Ninety obstetric patients aged 18-35 years with American Society of Anesthesiologists (ASA) physical status II/III and suffering from PDPH as per the criteria of the International Headache Society after caesarean section under spinal anaesthesia were recruited in this double-blinded randomised study. Patients were randomised to Group D (dexmedetomidine 1 µg/kg nebulisation), Group F (fentanyl 1 µg/kg nebulisation), and Group S (saline nebulisation 4mL). The nebulisation was done 12 hourly for 72 hours. Assessment parameters included pain score and the requirement of additional treatment such as paracetamol, caffeine, and epidural blood patch. Analysis of variance test was used for continuous quantitative variables, and the Kruskal-Wallis test was used for quantitative discrete data. The pain scores at 1, 6, 12, 24, 48, and 72 hours following nebulisation were significantly lower in Group D in comparison to groups F and S (P < 0.001). The number of patients requiring additional analgesic therapy was lower in Group D in comparison to patients in other groups (P < 0.001). Dexmedetomidine nebulisation resulted in effective reduction in PDPH symptoms and pain scores. Nebulisation with fentanyl did not alleviate PDPH symptoms when compared to the control group.

Cognitive-Motor Training Improves Reading-Related Executive Functions: A Randomized Clinical Trial Study in Dyslexia.

Children with developmental dyslexia (DD) often struggle with executive function difficulties which can continue into adulthood if not addressed. This double-blinded randomized clinical trial study evaluated the short-term effects of the Verbal Working Memory-Balance (VWM-B) program on reading-related executive functions, reading skills, and reading comprehension in Persian children with DD. The active control group [12 children with DD with a mean age of 9 years (SD = 0.90)] received training using the single-task VWM program, while the experiment group [15 children with DD with a mean age of 8 years (SD = 0.74)] received training with the dual-task VWM-B program. Both groups received fifteen training sessions, and assessments were conducted before and after the intervention. The groups were homogenized for possible confounders of age, gender, IQ level, and attention level. The study employed separate mixed ANOVA analyses to estimate the impact of training programs on various measured functions. Significant improvements were observed in the outcome measures of backward digit span, text comprehension, verbal fluency, Stroop color-word test and interference, and the reading subtests. Additionally, significant correlations were found between reading skills and backward digit span, text comprehension, verbal fluency, and Stroop variables. In conclusion, the dual-task VWM-B program was found to be more effective than the single-task VWM program in improving selective attention, cognitive inhibition, verbal working memory capacity, information processing speed, naming ability, and lexical access speed. These enhanced executive functions were associated with improved reading skills in children with DD.