Blind Randomized Clinical Trial Research Articles

Ellagic acid effects on disease severity, levels of cytokines and T-bet, RORγt, and GATA3 genes expression in multiple sclerosis patients: a multicentral-triple blind randomized clinical trial.

Multiple sclerosis (MS) is a chronic autoimmune disease. Ellagic acid is a natural polyphenol and affects the fate of neurons through its anti-inflammatory and antioxidant properties. The present study aimed to investigate ellagic acid effects on disease severity, the expression of involved genes in the pathogenesis of MS, and the levels of related cytokines. The present study was a triple-blind clinical trial. Eligible patients were randomly assigned to two groups: Ellagic acid (25 subjects) for 12 weeks, receiving 180 mg of Ellagic acid (Axenic, Australia) and the control group (25 subjects) receiving a placebo, before the main meals. Before and after the study, the data including general information, foods intake, physical activity, anthropometric data, expanded disability status scale (EDSS), general health questionnaire (GHQ) and pain rating index (PRI), fatigue severity scale (FSS) were assessed, as well as serum levels of interferon-gamma (IFNγ), interleukin-17 (IL-17), interleukin-4 (IL-4) and transforming growth factor-beta (TGF-β), nitric-oxide (NO) using enzyme-linked immunoassay (ELISA) method and expression of T-box transcription factor (Tbet), GATA Binding Protein 3 (GATA3), retinoic acid-related orphan receptor-γt (RORγt) and Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) genes were determined using Real-Time Quantitative Reverse Transcription PCR (RT-qPCR) method. Ellagic acid supplementation led to a reduction in IFNγ, IL-17, NO and increased IL-4 in the ellagic acid group, however in the placebo group no such changes were observed (-24.52 ± 3.79 vs. -0.05 ± 0.02, p < 0.01; -5.37 ± 0.92 vs. 2.03 ± 1.03, p < 0.01; -18.03 ± 1.02 vs. -0.06 ± 0.05, p < 0.01, 14.69 ± 0.47 vs. -0.09 ± 0.14, p < 0.01, respectively). Ellagic acid supplementation had no effect on TGF-β in any of the study groups (p > 0.05). Also, the Tbet and RORγt genes expression decreased, and the GATA3 gene expression in the group receiving ellagic acid compared to control group significantly increased (0.52 ± 0.29 vs. 1.51 ± 0.18, p < 0.01, 0.49 ± 0.18 vs. 1.38 ± 0.14, p < 0.01, 1.71 ± 0.39 vs. 0.27 ± 0.10, p < 0.01). Also, ellagic acid supplementation led to significant decrease in EDSS, FSS and GHQ scores (p < 0.05), and no significant changes observed in PRI score (p > 0.05). Ellagic acid supplementation can improve the health status of MS patients by reduction of the inflammatory cytokines and Tbet and RORγt gene expression, and increment of anti-inflammatory cytokines and GATA3 gene expression.Clinical trial registration: (https://en.irct.ir/trial/53020), IRCT20120415009472N22.

The Role of Zinc in Acute Bronchiolitis in children less than 2 years old

Background: Bronchiolitis is an acute respiratory illness which is the leading cause of respiratory distress in infancy and early childhood with its greatest morbidity in infants. Although zinc supplementation is effective in both preventing and treating pneumonia but its role in acute bronchiolitis has rarely been examined.&#x0D; Objective: To assess the effect of zinc sulfate to improve the clinical manifestations of acute bronchiolitis (Severe cases) in children less than 2 years of age.&#x0D; Materials and Methods: This was a double blind randomized clinical trial on 70 patients aged 2 to 23 months admitted in the Pediatric ward of Khwaja Yunus Ali Medical College and Hospital from September 2019 to September 2020 with the diagnosis of acute bronchiolitis. Patients were randomly divided equally into 2 groups: a case group was assigned oral zinc sulfate and the control group received placebo.&#x0D; Results: Mean age of case group was 174.63±98.7 days and control group 176.86±97.43 days ( p=0.924) with male predominance in both groups. Symptoms and signs of acute bronchiolitis (Severe cases) were compared between the 2 groups during admission and then at 24, 48 and 72 hours after initiation of treatment. No statistically significant differences were observed between the 2 groups in improvement of symptoms and signs including fever, fast breathing, chest indrawing and wheezing on 48 and 72 hours after treatment with zinc sulfate ( p&gt;0.05). The duration of hospitalization was 4.2±2.6 days in the case group and 4.4±2.2 days in the control group and this difference was not significant.&#x0D; Conclusion: The present study showed that zinc sulfate has no benefit in improving the clinical manifestations of acute bronchiolitis.&#x0D; Northern International Medical College Journal Vol. 12 No.2 Jan 2021, Page 535-538

Analgesic Sparing Effect of Dexamethasone with Levobupivacaine in Quadratus Lumborum Block in Patients Undergoing Unilateral Inguinal Hernia Repair

Abstract Background The QLB is an effective analgesic technique for various abdominal wall incisinos. The QLB covers T7 to L2 dermatomes. Levobupivacaine is a long-acting LA agent, commonly used for peripheral nerve block due to its better safety profile than that of bupivacaine. Dexamethasone as an adjuvant to LA has been shown to prolong the duration of pain-free period, less requirement for rescue opioids consumption, more patient satisfaction and lesser incidence of nausea and vomiting. Objective To assess the analgesic sparing effect of adding dexamethasone to levobupivacaine in quadratus lumborum block in patients undergoing unilateral inguinal hernia repair under general anesthesia. Patients and Methods After approval of the anesthesiology department and scientific and ethical committees, this prospective double blind randomized clinical trial study was conducted in Ain Shams University Hospitals. Sixty patients scheduled for elective ingunial surgeries under general anesthesia were included in this study. Results Our study did not have any complications associated with the use of dexamethasone with levobupivacaine in QLB. Type 1 QLB failed to provide postoperative analgesia in surgeries involving dissection in the retroperitoneal area as there were high chances of damaging the thoracolumbar fascia. Conclusion The addition of dexamethasone to levobupivacaine in QLB in unilateral inguinal hernia repair surgery provides a prolonged duration of postoperative analgesia, with reduced analgesic requirements, a better quality of analgesia in terms of NRS compared to levobupivacaine alone group.

Cross-Training and Resistance Training in Adults with Type B Acute Lymphoblastic Leukemia during the Induction Phase: A Randomized Blind Pilot Study.

Patients with acute lymphoblastic leukemia (ALL) undergoing induction decrease their physical capacity, lose muscle mass, and decrease their quality of life (QOL). The safety, feasibility, and benefits of exercise during chemotherapy have been proven, but the effects of cross-training activities have yet to be analyzed. To measure the effects of cross-training on body composition, physical performance, and QOL, a blind randomized clinical trial was carried out. A total of 33 patients were included and randomized into a cross-training exercise group (CEG), a resistance exercise group (REG), and a control group (CG). During induction, patients received an exercise routine three to five days a week for 30 to 50 min each. Body composition, QOL, and physical performance were measured at baseline, up to discharge, and at a follow-up of two months. Body composition improved in the REG and CEG. In the CG, muscle mass decreased and fat mass increased (p = 0.020 and 0.020, respectively). The REG and CEG had significant positive improvements in physical performance compared to the CG. QOL showed no differences in any group (p = 0.340). Cross-training and resistance exercise are essential to improve body composition and physical performance during induction. Considering the prognostic value of physical performance, we propose integrated training exercises as adjuvant therapy in adult patients with ALL.

Wireless transcutaneous electric nerve stimulation (TENS) for chemotherapy-induced peripheral neuropathy (CIPN): A proof-of-concept, placebo-controlled, randomized clinical trial (RCT).

e24134 Background: Chronic CIPN affects approximately 30%-60% of people who receive neurotoxic chemotherapy. CIPN is associated with impaired quality of life and function and has few effective treatments. Methods: This 6-site, subject and assessor blinded RCT was designed to assess (1) preliminary efficacy (i.e., alpha pre-specified at 0.2) of a wearable, app-controlled, TENS device for chronic CIPN and (2) feasibility of conducting a confirmatory trial within the NCI Community Oncology Research Program (NCORP) (NCT 04367480). The primary outcome was the EORTC-CIPN20. The main secondary outcomes were hot/burning pain, sharp/shooting pain, tingling, numbness, and cramping (7-day daily diary, 0 – 10 numeric rating scales). The TENS device applies stimulation for 1hr treatment sessions followed by 1 hour rest periods. The placebo TENS device is identical, except it delivers only 2.5 mins of stimulation in the treatment period. Subjects were asked to wear the device for 5 hrs/day (i.e., 3 treatment sessions) for 6 weeks. The primary analysis used an ANCOVA with the 6-week EORTC-CIPN20 score as the dependent variable, arm as fixed effect, and baseline EORTC-CIPN20 and site as covariates. Secondary analyses used similar ANCOVA models (excluding site) for each symptom on subgroups of subjects who reported at least 4 out 10 for that symptom at baseline. Results: 142 eligible subjects were randomized and received a device; 130 (91%) completed the study. Subjects were on average 63 years old, 65% female, and 85% white. The most common chemotherapies were taxanes (37%), platinums (36%), or their combination (15%). 88% of study completers received at least 3 treatment sessions on at least 70% of study days. The median time since chemotherapy was 16 months (IQR: 7, 34). See Table for efficacy results. Conclusions: A RCT of an app-controlled, wireless TENS device for chronic CIPN with excellent adherence and retention rates is feasible in NCORP. Preliminary efficacy evidence suggests that TENS is promising for pain and cramping from CIPN, but less likely to improve numbness and tingling. A confirmatory RCT of TENS for painful CIPN is highly warranted. Clinical trial information: NCT04367480 . [Table: see text]

Outcomes After Endovascular Therapy With Procedural Sedation vs General Anesthesia in Patients With Acute Ischemic Stroke

General anesthesia and procedural sedation are common practice for mechanical thrombectomy in acute ischemic stroke. However, risks and benefits of each strategy are unclear. To determine whether general anesthesia or procedural sedation for anterior circulation large-vessel occlusion acute ischemic stroke thrombectomy are associated with a difference in periprocedural complications and 3-month functional outcome. This open-label, blinded end point randomized clinical trial was conducted between August 2017 and February 2020, with final follow-up in May 2020, at 10 centers in France. Adults with occlusion of the intracranial internal carotid artery and/or the proximal middle cerebral artery treated with thrombectomy were enrolled. Patients were assigned to receive general anesthesia with tracheal intubation (n = 135) or procedural sedation (n = 138). The prespecified primary composite outcome was functional independence (a score of 0 to 2 on the modified Rankin Scale, which ranges from 0 [no neurologic disability] to 6 [death]) at 90 days and absence of major periprocedural complications (procedure-related serious adverse events, pneumonia, myocardial infarction, cardiogenic acute pulmonary edema, or malignant stroke) at 7 days. Among 273 patients evaluable for the primary outcome in the modified intention-to-treat population, 142 (52.0%) were women, and the mean (SD) age was 71.6 (13.8) years. The primary outcome occurred in 38 of 135 patients (28.2%) assigned to general anesthesia and in 50 of 138 patients (36.2%) assigned to procedural sedation (absolute difference, 8.1 percentage points; 95% CI, -2.3 to 19.1; P = .15). At 90 days, the rate of patients achieving functional independence was 33.3% (45 of 135) with general anesthesia and 39.1% (54 of 138) with procedural sedation (relative risk, 1.18; 95% CI, 0.86-1.61; P = .32). The rate of patients without major periprocedural complications at 7 days was 65.9% (89 of 135) with general anesthesia and 67.4% (93 of 138) with procedural sedation (relative risk, 1.02; 95% CI, 0.86-1.21; P = .80). In patients treated with mechanical thrombectomy for anterior circulation acute ischemic stroke, general anesthesia and procedural sedation were associated with similar rates of functional independence and major periprocedural complications. ClinicalTrials.gov Identifier: NCT03229148.

Effects of backward walking exercise using lower body positive pressure treadmill on knee symptoms and physical function in individuals with knee osteoarthritis: a protocol for RCT

ObjectivesThe primary aim is to compare the effects of backward walking exercise to forward walking exercise on knee pain, knee functions, and thigh muscle strength in individuals with mild to moderate knee osteoarthritis using lower body positive pressure, in addition to mobility functions, balance, and self-reported health status.MethodsThe study is a single blind randomized clinical trial with two independent groups. This study will enroll 26 participants with mild to moderate knee osteoarthritis. The participants will be randomized into either experimental group (backward walking exercise) or control group (forward walking exercise). Both groups will use lower body positive pressure treadmill for walking exercise. Both groups will perform regular conventional exercise and worm-up exercise before walking exercise. The treatment will be three times a week for six weeks. Walking session will be up to 30 min each session. Data collection will be collected during pre- and post- intervention including primary outcomes including numeric pain rating scale (NPRS), knee injury and osteoarthritis outcome score (KOOS), and thigh muscle strength test. The secondary outcomes include five times sit to stand test (FTSTS), 3-meter backward walk test (3MBWT), timed up and go test (TUG), four square step test (FSST), functional reach test (FRT), 10-meter walk test (10-MWT), six minute walk test (6MWT), medical outcomes study short form 12 (SF-12), patient health questionnaire -9 (PHQ-9), and rapid assessment of physical activity (RAPA). An independent t-test will be used to evaluate the effect of treatment on the outcome measures.ResultsNot applicable.ConclusionUsing lower body positive pressure may have promising results against knee osteoarthritis. Moreover, walking backward exercise using lower body positive pressure might add more benefits to individuals with knee osteoarthritis and help clinicians in decision making.Trial registration: This study was registered in ClinicalTrails.gov (ID: NCT05585099).

Prevention of relapse in drug sensitive pulmonary tuberculosis patients with and without vitamin D3 supplementation: A double blinded randomized control clinical trial.

The immunomodulatory effects of vitamin D are widely recognized and a few studies have been conducted to determine its utility in the treatment of tuberculosis, with mixed results. This study was conducted to see if vitamin D supplementation in patients with active pulmonary tuberculosis (PTB) in the Indian population contributed to sputum smear and culture conversion as well as the prevention of relapse. This randomized double-blind placebo-controlled trial was conducted in three sites in India. HIV negative participants aged 15-60 years with sputum smear positive PTB were recruited according to the Revised National Tuberculosis Control Program guidelines and were randomly assigned (1:1) to receive standard anti-tubercular treatment (ATT) with either supplemental dose of oral vitamin D3 (60,000 IU/sachet weekly for first two months, fortnightly for next four months followed by monthly for the next 18 months) or placebo with same schedule. The primary outcome was relapse of PTB and secondary outcomes were time to conversion of sputum smear and sputum culture. A total of 846 participants were enrolled between February 1, 2017 to February 27, 2021, and randomly assigned to receive either 60,000 IU vitamin D3 (n = 424) or placebo (n = 422) along with standard ATT. Among the 697 who were cured of PTB, relapse occurred in 14 participants from the vitamin D group and 19 participants from the placebo group (hazard risk ratio 0.68, 95%CI 0.34 to 1.37, log rank p value 0.29). Similarly, no statistically significant difference was seen in time to sputum smear and sputum culture conversion between both groups. Five patients died each in vitamin D and placebo groups, but none of the deaths were attributable to the study intervention. Serum levels of vitamin D were significantly raised in the vitamin D group as compared to the placebo group, with other blood parameters not showing any significant difference between groups. The study reveals that vitamin D supplementation does not seem to have any beneficial effect in the treatment of PTB in terms to the prevention of relapse and time to sputum smear and culture conversion. CTRI/2021/02/030977 (ICMR, Clinical trial registry-India).

Eff ectiveness of Menthol and Chlorhexidine Mouth Rinses on Reduction of Plaque, Gingivitis, and Streptococcus mutans Count in Saliva

Introduction: Menthol is a new product made from mint that is the most eff ective approach to avoid infections. There has been little human research on using menthol as a mouth rinse ingredient, and there is little information on the subject. Aim: This study aimed to know the eff ectiveness of menthol and chlorhexidine mouth rinses in reducing plaque, gingivitis, and Streptococcus mutans in saliva among 21 to 45 years old subjects. Material and method: The study is a placebo-control, parallel-group blind randomized clinical trial consisting of a 2-week period. Forty subjects were selected and randomized into 2 groups consisting of 20 subjects: group A (menthol) and group B (chlorohexidine). The subjects were clinically examined for plaque accumulation using the plaque index (Turesky et al.) and gingival infl ammation using the gingival index (loe and silness). The saliva samples were collected for estimation of S. mutans count on the fi rst day of baseline and after the 14th day using an assigned mouth rinse. Results: Menthol mouth rinse showed lower scores in plaque index, gingival index, and S. mutans count compared to the chlorhexidine mouth rinse which was statistically signifi cant (p = 0.05). Mouth rinse with menthol is better compared to mouth rinse with chlorohexidine. Conclusion: Menthol mouthwash has therapeutic potential and can be prescribed by a dentist as part of routine oral hygiene practice

Comparative study between surgical wound catheter, femoral nerve block, and adductor canal block for postoperative analgesia after knee arthroplasty: A double blind randomized clinical trial.

The present study compared the surgical wound catheter (SWC), femoral nerve block (FNB), and adductor canal block (ACB) for postoperative analgesia after knee arthroplasty. The study included (180) patients scheduled for unilateral total knee replacement and were randomly allocated into three groups. Patients received postoperative analgesia via continuous infusion of ropivacaine 0.2% (10 ml bolus followed by continuous infusion of 5 ml/hour) through the SWC, FNB, or ACB groups. All groups received supplemental analgesia by IV morphine using patient controlled analgesia. Pain scores were assessed at rest and during movements, the worst and least pain scores, and how often were in worst pain during the first 72 hours. The functional activity and patient's satisfaction were also recorded. The study showed significant reductions in pain scores at rest and during movements in all groups compared to the baseline scores. Significant reductions in pain scores were observed in both ACB and FNB groups compared to the SWC group (P < 0.05). The worst pain scores were (6.15 ± 2.9, 5.85 ± 2.7, and 5.025 ± 1.513), least pain scores (2.06 ± 0.72, 1.92 ± 1.34 and 1.89 ± 1.76), percentage of time in worst pain (17.67 ± 9.15, 11.42 ± 7.50, and 9.8.8 ± 8.14) and the total morphine consumption (39.24 ± 6.82, 34.55 ± 7.86, and 26.40 ± 8.47 mg) in the SWC, FNB, and ACB groups, respectively. Functional assessments and patient's satisfaction, at 6 and 24 hours, were significantly better in ACB followed by SWC, and lastly FNB group (P < 0.5). No significant differences in the incidence of side effects (P > 0.05). Local anesthetic leak from the SWC was a continuous concern by the orthopedic surgeons. In terms of efficiency, ACB provided the highest quality of analgesia in terms of pain relief, functional activity, and patient's satisfaction. Both ACB and FNB provided higher quality of analgesia compared to the SWC. While ACB and SWC provided better functional improvements compared to FNB.

Effect of Argatroban Plus Intravenous Alteplase vs Intravenous Alteplase Alone on Neurologic Function in Patients With Acute Ischemic Stroke

Previous studies suggested a benefit of argatroban plus alteplase (recombinant tissue-type plasminogen activator) in patients with acute ischemic stroke (AIS). However, robust evidence in trials with large sample sizes is lacking. To assess the efficacy of argatroban plus alteplase for AIS. This multicenter, open-label, blinded end point randomized clinical trial including 808 patients with AIS was conducted at 50 hospitals in China with enrollment from January 18, 2019, through October 30, 2021, and final follow-up on January 24, 2022. Eligible patients were randomly assigned within 4.5 hours of symptom onset to the argatroban plus alteplase group (n = 402), which received intravenous argatroban (100 μg/kg bolus over 3-5 minutes followed by an infusion of 1.0 μg/kg per minute for 48 hours) within 1 hour after alteplase (0.9 mg/kg; maximum dose, 90 mg; 10% administered as 1-minute bolus, remaining infused over 1 hour), or alteplase alone group (n = 415), which received intravenous alteplase alone. Both groups received guideline-based treatments. The primary end point was excellent functional outcome, defined as a modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]) of 0 to 1 at 90 days. All end points had blinded assessment and were analyzed on a full analysis set. Among 817 eligible patients with AIS who were randomized (median [IQR] age, 65 [57-71] years; 238 [29.1%] women; median [IQR] National Institutes of Health Stroke Scale score, 9 [7-12]), 760 (93.0%) completed the trial. At 90 days, 210 of 329 participants (63.8%) in the argatroban plus alteplase group vs 238 of 367 (64.9%) in the alteplase alone group had an excellent functional outcome (risk difference, -1.0% [95% CI, -8.1% to 6.1%]; risk ratio, 0.98 [95% CI, 0.88-1.10]; P = .78). The percentages of participants with symptomatic intracranial hemorrhage, parenchymal hematoma type 2, and major systemic bleeding were 2.1% (8/383), 2.3% (9/383), and 0.3% (1/383), respectively, in the argatroban plus alteplase group and 1.8% (7/397), 2.5% (10/397), and 0.5% (2/397), respectively, in the alteplase alone group. Among patients with acute ischemic stroke, treatment with argatroban plus intravenous alteplase compared with alteplase alone did not result in a significantly greater likelihood of excellent functional outcome at 90 days. ClinicalTrials.gov Identifier: NCT03740958.

PRIMARY SCLEROSING CHOLANGITIS AND AUTOIMMUNE HEPATITIS: OVERLAPPING CHALLENGES IN DIAGNOSIS AND TREATMENT

Abstract Overlap syndromes (OS) describe the simultaneous presentation of more than one immune-mediated liver disease in a singular patient, and present unique challenges both in diagnosis and treatment. Here we report a case of primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) OS, ultimately treated with Vancomycin. A 30-year-old female with known ulcerative pancolitis (UC) and alcoholic cirrhosis in the setting of AIH presented to the ED with severe abdominal pain, bloody diarrhea, and bilious emesis. Initial labs showed ESR 48 mm/hr, CRP 32.97 mg/L, fecal calprotectin 1131.2 µg/mg, AST 45 IU/L, and total protein 9.1 g/dL. Clostridium Difficile and stool studies were negative. Patient was admitted with concern for acute UC flare. CT scan showed mild worsening of intrahepatic and extrahepatic biliary ductal dilatation suspicious for PSC, and a cirrhotic liver with signs of portal hypertension and splenomegaly (Fig. 1a). Endoscopy revealed multiple non-bleeding duodenal ulcers and grade II esophageal varices. Colonoscopy found moderately active UC Mayo score 2, worsened from prior exam. MRCP was significant for cirrhotic liver morphology with nodular surface contour, and intrahepatic and extrahepatic biliary dilatation with beading and irregularity of the intrahepatic biliary tree and cystic duct, consistent with PSC (Fig. 1b). She was diagnosed with PSC-AIH OS and underwent treatment with Prednisone, Azathioprine, and Ustekinumab with minimal improvement. Only after the addition of Vancomycin was there normalization of biochemical markers and clinical status. Autoimmune liver disease is generally categorized into hepatic (AIH) or cholestatic (PSC and PBC) predominance. PSC is known to be associated with IBD, specifically UC. It is hypothesized that PSC evolves in UC patients due to uptake into the enterohepatic circulation of proinflammatory cells from the colon; these agents typically concentrate in the biliary system where they ultimately cause the biliary ductal damage frequently seen with PSC. By targeting enteric bacteria, Vancomycin decreases the absorption of these inflammatory biliary toxins. For PSC patients with UC and co-occurring AIH, the addition of Vancomycin could significantly reduce mortality and disease burden. Several case reports and one pilot study have investigated Vancomycin’s role in the treatment of PSC. However, it remains a vastly underutilized therapy, and its role specifically in PSC-AIH OS has not been previously reported. There remains an evident need for a large double blind randomized placebo-controlled clinical trial to further support the addition of Vancomycin to the standard treatment regimen for PSC, and to establish clear parameters on effective dosage and length of treatment. In the meantime, clinicians should be aware of the possible use of Vancomycin to treat patients with PSC +/- AIH and IBD. Figure 1a: CT abdomen pelvis with IV contrast highlighting stigmata of cirrhosis with portal hypertension and splenomegaly. Image also shows worsening of intrahepatic and extrahepatic biliary ductal dilatation in the setting of PSC given the patient’s underlying history of ulcerative colitis. Figure 1b: MRCP showing beading and irregularity of the intrahepatic biliary tree and cystic duct, in keeping with known history of primary sclerosing cholangitis. This image also highlights the dilation of the intrahepatic and extrahepatic biliary system.

Probiotics on chronic urticaria: A randomized clinical trial study.

Urticaria is a common itchy skin condition characterized by swelling and erythema. A variety of treatments is available today. The purpose of this study was to evaluate the clinical effects of probiotic use in patients with chronic resistant urticaria. This four-way blind randomized clinical trial was conducted between June 2019 and June 2020. Study population consisted of patients with chronic urticaria who did not respond well to first line treatment with antihistamines. For the intervention group, antihistamine (cetirizine) and probiotics (femilact capsule) and for the control group, antihistamine (cetirizine) and placebo were administered twice a day for 8 weeks. The "Urticarial Activity for 7 Days" (UAS7) questionnaire was used to assess urticaria activity and the Dermatology Life Quality Index (DLQI) questionnaire was used to assess the quality of life of patients. Patients' age range was 7 to 30 years with a mean and standard deviation of 23.6±9.2 years. 31 (81.57%) cases were females and 7 (18.42%) cases were males. Twenty patients were in the intervention group and eighteen patients were in the control group. The mean scores of UAS7 questionnaire were reduced in both groups, but it was more significant in the intervention group (9.6±6.4) compared to the control group (12.7±8.1) at the end of week eight of treatment (P=0.036). Also, there was no significant difference in the quality of life between the two groups after 8 weeks (P=0.805). This study showed that probiotic consumption along with antihistamines significantly improved the activity of urticaria but not the quality of life of patients.

PS-BPC09-2: EFFECTIVENESS OF OROPHARYNGEAL EXERCISES AND PRANAYAMA ON BLOOD PRESSURE, AND QUALITY OF SLEEP AMONG HYPERTENSIVE WITH MODERATE OBSTRUCTIVE SLEEP APNEA.

Introduction and Objectives: Burden of cardiovascular disease around the global is a major health concern and prevalence is high in adults with obstructive sleep apnea (OSA). Lowering blood pressure (BP) can greatly reduce cardiovascular disease risk and lifestyle modification including regular physical activity is routinely prescribed to achieve this goal. The relationship between sleep disordered breathing especially obstructive sleep apnea (OSA) and hypertension has been well investigated in both cross sectional and longitudinal studies. Many people with OSA suffer from severe fatigue and daytime sleepiness with poor exercise intolerance due to poor sleep quality and nocturnal hypoxemia. The objectives of this study was To evaluate the efficacy of a 6 week oropharyngeal exercises and Pranayama training program for reducing blood pressure and improving sleep quality in hypertensive patients with OSA . Design and method: This is a single site double blind randomized clinical trial. Total 40 patients with history of hypertension and moderate sleep apnea were selected that further divided into two groups oropharyngeal exercises and Pranayama group and control group. Patients were evaluated at study entry and at end by evaluating blood pressure pulse rate anthropometric measurements snoring frequency (range 0 to 4) and Pittsburgh sleep quality (0 to 21) questionnaires. After initial evaluation oropharyngeal exercises and Pranayama along with regular brisk walking for 30 to 40 mins 5 days in week is prescribed to experimental group. Pranayama consists of three phases: Puraka (inhalation) kumbhaka (retention) and rechaka (exhalation) that can be either fast or slow. Oropharyngeal exercises refers to 12 exercises of the 20 minutes duration involving tongue (4 exercises) soft palate (2 exercises) jaw (2 exercises) and lateral pharyngeal wall (4 exercises) to be performed twice a day for 6 weeks. The exercises were taught individually and were supplemented with a pamphlet for reinforcement. And only regular brisk walking for 30 to 40 mins 5 days in week is prescribed to control group. Results: Experimental group significantly (p &lt; 0.05) decreased systolic &amp; diastolic blood pressure snoring neck circumference and improved sleep quality. Heart rate changes were insignificant (p = 0.9). Conclusions: Oropharyngeal exercises and Pranayama are effective in reducing blood pressure and snoring in hypertensive patients with moderate OSA. Its also effective in improving in quality of sleep in these patients.

Comparison of the effects of therapeutic exercise with either an educational booklet or vitamin-D3 supplement in the management of chronic low back pain: study protocol for an assessor blinded multicenter randomized clinical trial

Background: It is important to know the best intervention approach to replenish serum vitamin D levels along with therapeutic interventions for chronic low back pain (CLBP) patients. From the researcher’s knowledge, no study compared “vitamin D supplement” or “booklet education on sun exposure, nutrition and lifestyle” with therapeutic exercise for CLBP cases. Researchers hypothesize that multidimensional comprehensive management of therapeutic exercise and an education booklet (TEB) on sun exposure, nutrition, and lifestyle might be superior to therapeutic exercise and oral vitamin D supplement (TED) for CLBP patients with vitamin D deficiency. Methods: We planned for an assessor-blinded two-arm multicenter Randomized Clinical Trial (RCT) protocol to compare the efficacy of TEB compared to TED for CLBP patients with vitamin D deficiency at 2 months and 6 months after baseline recruitment in designated centers in Dhaka city. The primary outcome measures will include pain by Brief Pain Inventory (BPI), and serum vitamin D3 level and secondary outcome measures will include disability by Ronald Morris Disability Questionnaire (RMDQ). Discussion: This study will provide evidence for an appropriate prescription for the management of CLBP patients having vitamin D deficiency. Registration: Clinical Trials Registry India (CTRI/2022/11/047074).

Vitamin D and COVID-19: Narrative Review after 3 Years of Pandemic.

Active vitamin D [1,25(OH)2D3-calcitriol] is a secosteroid hormone whose receptor is expressed on all cells of the immune system. Vitamin D has a global anti-inflammatory effect and its role in the management of a SARS-CoV-2 infection has been investigated since the beginning of the COVID-19 pandemic. In this narrative review, the laboratory and clinical results of a vitamin D supplementation have been collected from both open-label and blinded randomized clinical trials. The results are generally in favor of the utility of maintaining the serum concentrations of calcifediol [25(OH)D3] at around 40 ng/mL and of the absolute usefulness of its supplementation in subjects with deficient serum levels. However, two very recent large-scale studies (one open-label, one placebo-controlled) have called into question the contribution of vitamin D to clinical practice in the era of COVID-19 vaccinations. The precise role of a vitamin D supplementation in the anti-COVID-19 armamentarium requires further investigations in light of the breakthrough which has been achieved with mass vaccinations.

Analgesic and anti-inflammatory effects of diclofenac and ketoprofen patches in two different rat models of acute inflammation

ObjectivesTopical forms of Non-steroidal anti-inflammatory drugs (NSAIDs) used to treat pain, fever and inflammation ensure reduced occurrence of systemic adverse effects that are common with oral application. Compared to the systemic therapy, topical applications of NSAIDs require lower doses to achieve pain relief, and thus pose lower risk of major drug interactions. We aimed to evaluate analgesic and anti-inflammatory effects of diclofenac and ketoprofen patch in the rat model of acute inflammation. MethodsWistar male rats, body weight 220–290 g were randomized into five groups with six rats. Two groups were treated with diclofenac patch at different doses, two with ketoprofen patch at different doses, while a placebo patch was administered to the control group. After patches removal and initial measurements of pain, gait, body temperature, paw temperature, color and paw volume, the models of acute inflammation were applied: yeast-induced hyperalgesia and carrageenan-induced edema. Measurements were repeated one, three and five hours after inflammation induction. ResultsAcute inflammations induced by both used models did not affect the whole-body temperature. However, there were significant (p < 0.05) differences in pain, gait, paw temperature, color and volume between low and high dose diclofenac and ketoprofen groups compared to the control group in different time points, in both models. ConclusionsOur results confirm the analgesic and anti-inflammatory efficacy of diclofenac and ketoprofen patches when used in two well-established rat models of inflammation. These findings suggests that diclofenac patch would be a useful formulation in clinical practice as a novel treatment option. However, new prospective double blind randomized clinical trials are necessary to evaluate analgesic and anti-inflammatory effect of topically applied NSAIDs when used in specific pain and inflammation indications.

A double blind randomized clinical trial of the effectiveness of low frequency rTMS over right DLPFC or OFC for treatment of obsessive-compulsive disorder

We compared the effectiveness of low frequency repetitive transcranial magnetic stimulation over right dorsolateral prefrontal cortex (DLPFC), right orbitofrontal cortex (OFC) and sham for treatment of obsessive-compulsive disorder (OCD) and sought to determine possible predictors of effective treatment. Sixty OCD patients participated and were randomly allocated to one of the 3 treatment groups. Treatment was administered daily for 10 days. Assessments were made at the beginning and end of therapy as well as three months later using the Yale-Brown obsessive compulsive scale (Y-BOCS), Hamilton Anxiety Rating Scale (HAM-A), Beck Depression Inventory (BDI), and Clinical Global Impression – Severity scale (CGI-S). There were no significant demographic or clinical differences between the groups at baseline. One-way repeated measures ANOVA showed that participants in all 3 groups improved their scores on all rating scales following treatment. A two-way repeated measures ANOVA revealed a significant time and group interaction due to the fact that both active treatment groups outperformed the sham group, although there was no significant difference between the two. Percent improvement had significant negative correlations with the following factors: duration of illness, baseline Y-BOCS, HAM-A, and BDI. We conclude that rTMS over either right DLPFC or OFC has a therapeutic effect on OCD symptoms. Patients with lower Y-BOCS and fewer comorbidities responded best to rTMS.

Midodrine in treatment of post coronary revascularization vasoplagia; pilot, open label, assessor blinded randomized clinical trial

Abstract Purpose Post cardiac surgery hypotension and inotrope dependence are among major causes of prolonged intensive care unit (ICU) stay. Besides routine managements, catecholamine inotrope-vasopressors are the traditional treatment. However, there is an increasing interest to catecholamine-sparing agents, such as Midodrine, oral alfa1 agonist, in patients with vasoplegia. Up to now there are no randomized study with midodrine on post cardiac surgery patients. Material and method In this pilot, open label, assessor blind, randomized clinical trial from June 2020 to December 2021, 65 patients with refractory (more than 24 hours inotropes) hypotension after coronary revascularization were included. Patients were randomly assigned to receive Midodrine add-on therapy (10 mg stat and 5 mg po every 12 hours) or placebo add-on routine treatment. The primary outcome was liberation time from IV inotrope-support. Secondary outcomes were ICU admission time and total vasopressor dosage after randomization. Results 32 patients enrolled in Midodrine group, with a mean age of 60.72, and 33 patients received placebo with mean age of 63.27. Median liberation time from inotrope was 27 hours in Midodrine group and 49 hours in placebo group (p=0.022). ICU admission time for Midodrine and placebo groups were 115 and 121 hours, respectively (p=0.990). Total vasopressor dosage after randomization were similar in two studied groups, 4352 μg in Midodrine group and 5637 μg in placebo group (p=0.405). No adverse event was observed in Midodrine group. Conclusion Midodrine add-on inotrope therapy was a safe medication with appropriate compliance in ICU admitted patients after cardiac surgery, which seems to decrease the inotrope dependent time. Funding Acknowledgement Type of funding sources: None.

Minimizing complications following transinguinal preperitoneal modified Kugel mesh herniorrhaphy: a double blind prospective randomized clinical trial

Transinguinal preperitoneal (TIPP) single-layer mesh herniorrhaphy has been proven effective. Mesh manufacturers make either a single-unit, two-layer mesh design or a separate optional onlay with the pre-peritoneal mesh. For peace of mind, most surgeons still incorporate the optional onlay. This study evaluated any counterproductive effects of adding the onlay to single-layer TIPP mesh herniorrhaphy and compared the long-term efficacy. This prospective, single-surgeon, single-center, randomized trial compared two groups of 50 consecutive patients at a 1 to 1 ratio. The control group received a single-layer modified Kugel mesh in the preperitoneal space, while the study group received the optional onlay mesh in the inguinal canal with preperitoneal mesh placement. A single surgeon performed the same operation to place the preperitoneal mesh in both groups, the only difference being the placement of the optional onlay mesh in the study group. A blinded researcher performed post-operative interviews using a series of questions at 1, 3, 6, and 12 months after surgery, and another unblinded researcher organized and performed statistical analysis of the peri-operative and post-operative data. The primary endpoints included foreign body sensation, pain, and any other discomfort in the inguinal region following surgery; and the secondary endpoints included recurrence and any complications related to surgery. The patient demographics were similar between the two groups. The average follow-up period was 29 months. Two patients in the 1-layer group and one patient in the 2-layer group were lost to follow-up. Postoperative pain, numbness and soreness were similar between groups. No patients experienced a foreign body sensation after 3 months in the 1-layer group, while five patients still had a foreign body sensation at 12 months in the 2-layer group. No recurrence was noted in either group during the follow-up period. Adequate dissection of the preperitoneal space is the key to a successful single-layer TIPP herniorrhaphy. With decreased materials in the inguinal canal, single-layer TIPP has a lower rate of long-term postoperative discomfort without increasing the risk of future recurrence.Trial registration: ISRCTN 47111213