Prospective Double-blind Randomized Control Trial Research Articles

Efficacy of Intrawound Vancomycin in Prevention of Periprosthetic Joint Infection After Primary Total Knee Arthroplasty: A Prospective Double-Blinded Randomized Control Trial

BackgroundPeriprosthetic joint infection (PJI) after total knee arthroplasty (TKA) is a devastating complication. Intrawound vancomycin powder has been shown to reduce infection rates in spine surgery, but its role in arthroplasty remains controversial. This prospective randomized control trial aimed to evaluate the efficacy of intrawound vancomycin in preventing PJI after primary TKA. MethodsA total of 1,022 patients were randomized to the study group (n = 507, who received 2 grams intrawound vancomycin powder before arthrotomy closure) or to the control group (n = 515, no local vancomycin) with a minimum follow-up of 12-months. The primary outcome was the incidence of PJI or surgical site infection (SSI). Secondary outcomes included associated minor complications such as stitch abscess, persistent wound drainage, and delayed stitch removal. Other parameters evaluated include reoperation rates and incidences of nephrotoxicity. ResultsThe overall infection rate in 1,022 patients was 0.66%. There was no significant difference in PJI rate in the study group (N = 1; 0.2%) versus the control group (N = 3; 0.58%), P = .264. Reoperation rates in the study group (N = 4; 0.78%) and control (N = 5; 0.97%), and SSI rates in the study (N = 1; 0.2%) and control groups (N = 2; 0.38%) were comparable. The Vancomycin cohort, however, demonstrated a significantly higher number of minor wound complications (n = 67; 13.2%) compared to the control group (n = 39; 7.56%, P < .05). Subgroup analysis showed diabetics in the study group to also have a higher incidence of minor wound complications (24 [14.1%] versus 10 [6.2%]; P < 05]. Multivariate analyses found that vancomycin use (odds ratio = 1.64) and smoking (odds ratio = 1.85) were associated with an increased risk of developing minor wound complications. No cases of nephrotoxicity were reported. ConclusionsIntrawound vancomycin powder does not appear to reduce PJI/SSI rate in primary total knee arthroplasties, including high-risk groups. Although safe from a renal perspective, intrawound vancomycin was associated with an increase in postoperative aseptic wound complications. Intrawound vancomycin may not be effective in reducing the rate of PJI in primary TKA.

The Effect of Intracuff Low Dose Alkalinized Lidocaine With and Without Dexamethasone on Extubation Response: A Prospective, Double-Blind, Randomized Control Trial

Background: Intubation with a cuffed endotracheal tube is the gold standard for securing a definitive airway. Bucking over the tube during extubation can result in a potentially dangerous hemodynamic response. Tracheal tube cuff can be used as a reservoir for drugs to blunt this response. Lidocaine, a local anesthetic can achieve this by anesthetizing the airway. Dexamethasone has been known to potentiate the effect of lidocaine and has an intrinsic anti-inflammatory property. Methods: A prospective double-blind randomized control trial was conducted in a tertiary hospital for patients undergoing elective surgeries under general anesthesia requiring endotracheal intubation. Sixty patients were randomized equally into one of three groups. Cuff was inflated with saline (Group-S), 40 mg alkalinized lidocaine (Group-L), 40 mg alkalinized lidocaine with 8 mg dexamethasone (Group-LD). Heart rate, blood pressure and bucking were recorded during extubation, and post-operative sore throat were assessed. Results: All groups were comparable with regard to demographics, quantity of drug instilled in the cuff, duration of extubation and baseline hemodynamics. Group-L had the lowest incidence of hemodynamic changes during extubation, even lower than Group-LD. (p=0.020). Group-L and Group-LD had a lower incidence of bucking when compared to placebo (p&lt;0.001). Both Group-L and Group-LD revealed a lower grade of sore throat in the early post-operative period. Conclusion: Instilling endotracheal tube cuff with 40 mg alkalinized significantly blunts hemodynamic response and bucking during extubation, and sore throat in the early post-operative period compared to placebo. Addition of 8 mg dexamethasone does not improve hemodynamic extubation response.

P205 Modified pectoral nerve block conducted Intraoperatively by surgeons Is effective for postmastectomy pain control: A prospective double-blinded randomized control trial

P205 Modified pectoral nerve block conducted Intraoperatively by surgeons Is effective for postmastectomy pain control: A prospective double-blinded randomized control trial

Is There any Role for Granulocyte Colony Stimulating Factor in Improvement of Implantation in Intrauterine Insemination? A Prospective Double-Blind Randomized Control Trial.

Granulocyte colony stimulating factor (GCSF) has been introduced as an immunomodulatory agent by increasing implantation rate in vitro fertilization (IVF) patients but it has not been studied in intrauterine insemination (IUI) patients. The aim of this study is to answer the role of GCSF in implantation rate of IUI. In this prospective double-blind randomized control trial, 320 eligible patients were enrolled, who were referred to the referral infertility clinic of Shiraz University of Medical Sciences from February 2018 till the end of 2019. They were divided into two groups randomly. After collecting the demographic data, all patients received clomiphene citrate from the 5th day of the menstruation cycle for 5 days. 50-150 units of recombinant purified follicle-stimulating factor (FSH) were started from the 8th day of the cycle. Follicle monitoring was done by transvaginal sonography till a mature follicle of 18 mm or more was developed. Human chorionic gonadotropin (HCG) injection was done in both groups with intrauterine administration of 300 μg GCSF in the case group and normal saline in the control group simultaneously. After 36 hours, IUI was performed. The clinical pregnancy, miscarriage, and ongoing pregnancy rates of both groups were calculated by SPSS software. The results showed improvement of clinical pregnancy rate [15.38% vs. 13.81% OR=1.17 (0.62-2.21)], miscarriage rate [3.84% vs. 5.26% OR=0.74 (0.25-2.20)] and ongoing pregnancy rate [11.53% vs. 8.55% OR=1.37 (0.65-2.92)] in the GCSF group compared to the control. However, the results revealed no statistically significance (P>0.05). Although it was not statistically significant, 300 μg Intrauterine GCSF administration simultaneously with hCG injection in standard IUI procedure might increase the pregnancy outcomes. Further studies are warranted (registration number: IRCT201212079281N2).

Nebulized Salbutamol with or without Magnesium Sulphate in the Management of Acute Asthma in Children in India: A Randomized Controlled Trial

There is inconclusive evidence on the role of nebulized magnesium sulphate (MgSO4) in the management of acute asthma in paediatric population. Whether the use of nebulized salbutamol with or without MgSO4 in the management of acute asthma results in clinically significant improvement in lung function in Indian children? The primary outcome measure was to assess improvements in peak expiratory flow rate (PEFR), heart rate, respiratory rate and SpO2. This was a single centre; prospective double-blind randomized control trial conducted in paediatric intensive care unit of a tertiary care centre. Ninety children of 6-14 years with acute exacerbations of bronchial asthma were enrolled to receive either inhaled magnesium sulphate (95 mg) with salbutamol (5 mg) or inhaled salbutamol (5 mg) alone. All patients got three nebulizations done during the first hour at 20 min intervals, two nebulizations during the second hour at 30 min intervals, hourly for the next 2 h and then at 24 and 48 h. Eighty-five patients were finally analysed as per protocol analysis. The trial showed that PEFR increased gradually in both groups over the study duration, but it was statistically not significant. Heart rate decreased significantly in both groups over the study duration. Respiratory rate decreased significantly between the groups at 24 and 48 h only. SpO2 improved too in both groups but was not significant statistically. The addition of nebulized MgSO4 to salbutamol does not seem to result in improvement in lung function in the management of acute asthma in Indian children.

Is Olfactory Function Affected by Endoscopic Transsphenoidal Skull Base Surgery?

The endoscopic endonasal transsphenoidal approach is an effective technique commonly utilized for resection of sellar and parasellar lesions, such as pituitary adenomas, Rathke cleft cysts, craniopharyngiomas, and select meningiomas. Resultant skull base defects can be repaired effectively with free grafts and/or vascularized pedicled nasoseptal flaps (NSF) to prevent cerebrospinal fluid leaks, with excellent outcomes overall, or for coverage of critical neurovascular structures. The proximity of the surgical site during the approach (and donor site for the NSF) to olfactory mucosa raises concern for compromise of the olfactory mucosa, which, if not preserved, can drastically affect postoperative quality of life. Thus, consideration should be given to preservation of olfaction whenever possible during these approaches to minimize sinonasal morbidity. Considering the available evidence investigating olfaction after endoscopic pituitary resection, can the transsphenoidal approach be safely performed while preserving olfactory function? A prospective double-blinded randomized control trial was conducted in 2020 by Chou et al. to investigate postoperative olfaction among 31 patients undergoing endoscopic endonasal skull base surgery with or without NSF harvest.1 Half of these patients underwent skull base reconstruction using an NSF; of these, eight were randomized to flap harvest from the dominant olfaction side and the remaining six were randomized to the olfaction nondominant side. The control group patients did not undergo NSF harvest. UPSIT (University of Pennsylvania Smell Identification Test) scores between the control and treatment groups at 6 to 12 months postoperatively revealed no significant differences in olfactory function between the two groups (2.7-point decrease in UPSIT score in control group vs 1.7-point decrease in NSF group, P = .45). Their findings suggest that NSF use in endoscopic endonasal skull base surgery does not pose a significant risk of hyposmia, nor does the side from which the flap is harvested appear to affect olfactory outcomes (2.3-point decrease on dominant side vs 1.2-point decrease on nondominant side, P = .79). Similarly, Chaaban et al. prospectively studied 18 patients undergoing endoscopic transnasal pituitary surgery.2 UPSIT scores preoperatively and 3 to 4 months postoperatively were not statistically significant, including those patients who underwent skull base reconstruction using NSFs. New hyposmia occurred in only 1.5% of all patients who preoperatively reported normal olfactory function. Normosmia was maintained in 95.8% of patients at 3 months and 95.1% of patients at 1 year post-surgery. Preoperative (31.3 ± 0.4) and postoperative (30.5 ± 0.5) UPSIT scores—with patients serving as their own controls—were not significantly different (P = .54). Those who underwent NSF harvest had scores similar to those patients who did not (29.4 ± 1.1 vs 28.6 ± 1.3, P = .87). Work by Harvey et al. demonstrates that there is also evidence suggesting an anatomically oriented basis for preservation of olfaction. Outcomes were measured using the Sino-Nasal Outcome Test (SNOT-22) in 98 patients undergoing surgery with purposeful olfactory preservation by minimizing dissection of the “olfactory strip,” which is located in the posterosuperior septum adjacent to the superior turbinate.3 The patients were grouped into pituitary resection (N = 40) and sinonasal tumor resection (N = 58), of which the latter group did not undergo NSF harvest. Preoperative scores were compared to those at 1 and 6 months after surgery. Their results suggested that SNOT-22 scores were actually improved between baseline and 6-months postoperatively in the pituitary resection group (P = .046), and there was no difference in UPSIT scores between these two time points (P = .68). Olfactory fibers can extend down over the medial surface of the superior turbinate, a structure which must be either resected or otherwise manipulated for full access to the skull base in transsphenoidal surgery. Given concern for surgical compromise of these olfactory fibers when the superior turbinate is partially resected, Li et al. performed a retrospective cohort study to compare olfactory function after either partial resection (PRST) or intentional lateralization of the superior turbinate (ILST) on the right.4 They measured their outcomes using the Sniffin' Sticks threshold test and the Sniffin' Sticks 12-Item Identification Test (SIT-12). At 6 months postoperatively, there was a significantly lower score on the threshold test in the partial resection group compared to the lateralization group (9.0 in PRST vs 10.0 in ILST, P = .036); however, SIT-12 scores at this same time point were not significantly different (9.0 in both groups, P = .325). Postoperative worsening of olfaction as compared to preoperative scores was similar in both groups (21.6% in PRST and 16.2% in ILST, P = .401). They therefore concluded that partial resection of the superior turbinate did not portend an increased risk of olfactory dysfunction. Finally, Pucinelli et al. performed a prospective cohort study to determine olfactory preservation among 22 patients undergoing septal incisions for posterior septectomy and/or NSF harvest during skull base surgery using cold knife (n = 10) or monopolar electrocautery (n = 12).5 This study is based on the hypothesis that cautery may lead to thermal conduction to the surrounding olfactory fibers, which may adversely affect olfactory outcomes. Their comparisons of preoperative, 3- and 12-month postoperative UPSIT (P > .80 at all time points) and SNOT-22 (P > .22 at all time points) scores revealed no significant differences between the two treatment groups. This suggests a similar safety profile for these two techniques for upper septal limb incisions in long-term olfactory preservation. In the case of endoscopic transsphenoidal skull base surgery, routine and purposeful preservation of olfactory function is possible, even with dissection and manipulation of relevant anatomical structures (i.e., superior turbinate and septum) for access, and regardless of use of cold knife or electrocautery for dissection in this area (Table I). The duration of transient olfactory dysfunction is not widely specified but improvement appears to occur reliably by 6 months on average. Furthermore, the use of NSF in reconstruction after skull base surgery has not been shown to increase the risk of postoperative hyposmia or anosmia. There remains a need for future studies focused on olfactory preservation in more extensive skull base approaches for lesions extending beyond the sella and sphenoid sinus, with possible risk of compromising larger portions of olfactory mucosa. Furthermore, maintaining the head in a flexed position and favoring a low approach to the sella are techniques that can be employed to protect the mucosa in wider resections. No significant differences in olfaction scores at 3–4 months postoperatively as compared to preoperative baseline No significant differences in olfaction scores between those with and without NSF harvest Improvement in quality-of-life scores at 6 months between baseline and 6-months postoperatively in patients who underwent pituitary resection group No significant differences in olfaction scores as compared to preoperative baseline Conclusions are based on a randomized control trial1 (level 1 evidence), prospective cohort studies2, 3, 5 (level 2 evidence), and a retrospective cohort study4 (level 3 evidence).

Electrolyzed hydrogen-rich water for oxidative stress suppression and improvement of insulin resistance: a multicenter prospective double-blind randomized control trial.

Electrolyzed hydrogen-rich water (EHW) is known to have suppressive effects on oxidative stress (OS). However, its benefit in type 2 diabetes mellitus (T2DM) remains unclear. This study aimed to investigate the effect of EHW on T2DM. This was a multicenter, prospective, double-blind, randomized controlled trial of 50 patients with T2DM who were assigned to the EHW or filtered water (FW) groups. The primary endpoint was changes in insulin resistance (IR) evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR). OS markers such as urinary 8-hydroxy-2'-deoxyguanosine excretion (8-OHdG), plasma diacron-reactive oxygen metabolites (d-ROM), and plasma biological antioxidant potential (BAP) and other clinical data, including serum lactate concentration (lactate), were evaluated. There were no significant differences in the changes in HOMA-IR between the EHW and FW groups. However, lactate levels decreased significantly in the EHW group, and this decrease was significantly correlated with a reduction in HOMA-IR, fasting plasma glucose, and fasting plasma insulin level. Serum lactate level also significantly correlated to decreased insulin bolus secretion after 90min with glucose loading in the EHW subjects with HOMA-IR > 1.73. No EHW treatment-related adverse effects were observed. There were no significant effect of EHW in the change in HOMA-IR in this study; larger-scale and longer-term study are needed to verify the effects of EHW in T2DM patients. The online version contains supplementary material available at 10.1007/s13340-021-00524-3.

MOSES™ Technology for Holmium Laser Enucleation of the Prostate: A Prospective Double-Blind Randomized Control Trial. Reply.

No AccessJournal of UrologyReply to Letters to the Editor1 Sep 2021MOSES™ Technology for Holmium Laser Enucleation of the Prostate: A Prospective Double-Blind Randomized Control Trial. Reply.is a reply to letterMOSES™ Technology for Holmium Laser Enucleation of the Prostate: A Prospective Double-Blind Randomized Control Trial. Letter. Nicholas Kavoussi, and Nicole Miller Nicholas KavoussiNicholas Kavoussi Department of Urology, Vanderbilt University Medical Center, Nashville, Tennessee More articles by this author , and Nicole MillerNicole Miller Vanderbilt University Medical Center, Nashville, Tennessee More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001882AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "MOSES™ Technology for Holmium Laser Enucleation of the Prostate: A Prospective Double-Blind Randomized Control Trial. Reply.." The Journal of Urology, 206(3), pp. 786–787

Effects of Mefenamic Acid in Pain Control during Loop Electrical Excision Procedure:A Prospective Double-Blind Randomized Control Trial.

Objective: To investigate the effectiveness of pre-procedural oral mefenamic acid compared with placebo in women undergoing Loop Electrosurgical Excision Procedure (LEEP) with intracervical lidocaine injection. Study designs:A prospective double-blinded randomized control trial. Materials, Setting, Methods:Women undergoing LEEP for any indications were asked to participate in the study. The participants were randomly allocated into two groups. In group 1 (oral mefenamic acid), the participants were offered oral mefenamic acid (500 mg) for 30 minutes before procedures. In group 2 (placebo), the patients were given oral placebo (identical tablet) for 30 minutes before operation. All participants received immediate 10 mL of 2% lidocaine with 1:100,000 of epinephrine intracervical injection before undergoing the LEEP. All participants were excised in one piece of LEEP. No top-hat excision in this study. The patients graded their pain on a 10-cm visual analog scale (VAS) at different points during the procedure, including speculum insertion, at starting excision, and 30 minutes post excision. Primary outcomes revealed the difference of VAS during all steps of LEEP by generalized estimating equations procedure. Results:Sixty participants (30 in mefenamic group and 30 in placebo group) participated in this study. The study did not find differences of VAS during all steps of LEEP and analgesic drug requirement at 30 minutes after LEEP procedure. All patients reported no immediate complications and no intervention-related adverse events were observed. Conclusion:Using pre-procedural oral mefenamic acid before LEEP procedure was not associated with pain reduction during all steps of excision.

Efficacy and safety of Chinese herbal medicine versus Lopinavir-Ritonavir in adult patients with coronavirus disease 2019: A non-randomized controlled trial

BackgroundTreatments for coronavirus disease 2019 (COVID-19) are limited by suboptimal efficacy. MethodsFrom January 30, 2020 to March 23, 2020, we conducted a non-randomised controlled trial, in which all adult patients with laboratory-confirmed COVID-19 were assigned to three groups non-randomly and given supportive treatments: Group A, Lopinavir-Ritonavir; Group B, Huashi Baidu Formula (a Chinese medicineformula made by the China Academy of Chinese Medical Sciences to treat COVID-19, which is now in the clinical trial period) and Lopinavir-Ritonavir; and Group C, Huashi Baidu Formula. The use of antibiotics, antiviruses, and corticosteroids was permitted in Group A and B. Traditional Chinese medicine injections were permitted in Group C. The primary outcomes were clinical remission time (interval from admission to the first time the patient tested negatively for novel coronavirus or an obvious improvement was observed from chest CT) and clinical remission rate (number of patients whose clinical time was within 16 days/total number of patients). ResultsA total of 60 adult patients with COVID-19 were enrolled at sites in Wuhan, China, and the sample size of each group was 20. In Groups A, B and C, the clinical remission rates were 95.0%%(19/20), 100.0%%(20/20) and 100.0%%(20/20), respectively. Compared with Groups A and B, the clinical remission time of Group C was significantly shorter (5.9 days vs. 10.8 days, p < 0.05; 5.9 days vs. 9.7 days, p < 0.05). There was no significant difference among Groups A, B, and C in terms of the time taken to be released from quarantine. The clinical biochemical indicators and safety indexes showed no significant differences among the three groups. ConclusionsOur findings suggest that Lopinavir-Ritonavir has some efficacy in the treatment of COVID-19, and the Huashi Baidu Formula might enhance this effect to an extent. In addition, superiority was displayed in the treatment of COVID-19 through a combination of the Huashi Baidu Formula and traditional Chinese medicine injection. In future, well-designed prospective double-blinded randomised control trials are required to confirm our findings.

4553 An investigation into the use of curcumin, a topical herbal agent, for the treatment of cervical intraepithelial neoplasia

OBJECTIVES/GOALS: Cervical cancer is the fourth most common cancer among women worldwide, with approximately 570,000 newly diagnosed cases and 311,000 related deaths among women in 2018.In the United States, approximately 13,000 new cases of cervical cancer are diagnosed annually with approximately 4,000 women dying each year from cervical cancer. Nearly all cervical cancer is caused by oncogenic strains of the human papillomavirus (HPV). Prevention strategies to reduce cervical cancer after HPV exposure entail treatment of cervical dysplasia at the premalignant state, specifically low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL), along with the eventual clearance of HPV.The most common treatment for persistent LSIL or HSIL is the loop electrical excisional procedure (LEEP). This procedure is unfortunately not widely available in resource-limited countries and is associated with potential significant morbidities, including decreased fertility, preterm birth, premature rupture of membranes and cervical incompetence. Despite undergoing standard of care treatment, in certain high-risk populations, specifically HIV-infected women, there is a higher rate of premalignant HPV-related cervical disease persistence, progression and recurrence.There is a paramount need for novel nonsurgical treatments to stabilize or treat precancerous lesions of the cervix and to decrease the persistence of HPV infection. Medical treatment with the natural herb curcumin may allow subjects to receive treatment of cervical lesions without undergoing a surgical procedure.Curcumin is a major active component extracted from turmeric with anti-inflammatory, anti-infectious, and anti-cancer properties.Topical intravaginal curcumin has the promise of delivering this drug directly to the site of disease, ensuring adequate concentrations at the site of disease while avoiding systemic side effects. This proposed study will determine if there are higher rates of HPV clearance after curcumin administration among women with and without HIV who have premalignant HPV-related cervical disease, specifically LSIL or recently treated (with a LEEP) HSIL. METHODS/STUDY POPULATION: We are proposing a prospective double-blind randomized control trial to investigate the utility of topical intra-vaginal curcumin in increasing rates of HPV clearance and mitigating the high rates of disease recurrence in women with and without HIV. A sample of approximately 200 women with and without HIV who have biopsy-proven LSIL or recently treated HSIL will be randomized to one of two arms: 2000 mg of curcumin powder in capsules or placebo inserted intravaginally at bedtime once weekly for 20 weeks (excluding the time of menses). Cervical cytology and HPV testing will be performed at baseline and 6 months post-randomization. If a participant has abnormal cytology or a positive high-risk HPV test 6 months post-randomization, they will be scheduled to undergo a colposcopy with biopsies of all suspicious cervical lesions. If biopsy results are HSIL or greater, subjects will be referred back to routine clinical treatment, which may include a LEEP. Clinicians performing the colposcopies and the study participants will be blinded since the placebo has the same appearance as the curcumin capsules. At the end of the study, study participants will be offered the opportunity to participate in 2-3 hour focus groups to discuss acceptability of the product as a treatment for premalignant HPV-related cervical disease until data saturation is achieved. Power and sample size calculations are based on the primary outcome of interest, which is clearance of HPV at 6 months. Basu et al (2013) documented HPV clearance in as many as 80% of subjects with topical curcumin. To account for an expected lower success rate in HIV-infected women, who will also be included in the study, we intend to power our study to determine a more conservative 20% improvement in clearance rate at 6 months with curcumin treatment, assuming an expected clearance rate of HPV in HIV-infected women of 25%. In order to detect a 20% difference of HPV clearance among those treated with intravaginal curcumin vs. placebo at 6 months, about 80 patients per arm would achieve 80% power at the 5% significance level. To account for up to 20% loss to follow-up or discontinuation, the total sample size in each arm would be 100 subjects with a total of approximately 200 subjects enrolled in both arms. RESULTS/ANTICIPATED RESULTS: We are currently in the process of collecting data for this study. We hypothesize that intravaginal curcumin will have a 20% higher rate of HPV clearance at 6 months as compared to placebo. Primary outcome measures will include clearance of HPV at 6 months in curcumin vs. placebo. Secondary outcomes measures will include recurrence of disease by either cytologic or histologic abnormality requiring further surveillance or treatment at 6 months. We also hypothesize that intravaginal curcumin administered once weekly at bedtime for 20 weeks will be safe, acceptable, and well tolerated. This is based off of previous findings from the Phase 1 trial of intravaginal curcumin that we performed. During this Phase 1 trial, we explored daily intravaginal administration of 2000 mg of curcumin to further understand curcumin’s tolerability. Our focus group participants displayed an overwhelming consensus that daily administration affected quality of life, specifically due to the yellow-colored vaginal discharge from the medication. Study participants expressed that once or twice weekly administration was more tolerable and feasible. Our proposed study would therefore test the tolerability and effects of weekly curcumin administration and its ability to clear HPV infection. The primary outcome measure will be the proportion of study participants who discontinue treatment for any reason (acceptability) and the proportion of study participants who discontinue treatment due to adverse effects (tolerability). DISCUSSION/SIGNIFICANCE OF IMPACT: Non-surgical treatments that decrease the morbidity and risk of progression of premalignant HPV-related cervical disease are greatly needed, especially in low-resource settings and among women experiencing barriers to care and/or at high risk for disease progression. Medical treatment with the natural herb curcumin is an emerging strategy that may allow subjects to receive treatment of cervical lesions without undergoing a surgical procedure.Several preclinical and clinical studies have shown curcumin’s ability to reduce tumors and precancerous lesions in animal and human cancer cells. Curcumin can suppress the activation of transcription factor NF-κB and the expression and activity of VEGF and p16INK4a, biomarkers known to be elevated in premalignant HPV-related cervical disease.Studies have also shown that curcumin alters HPV-associated molecular pathways in cancer cells, suppressing cervical cancer growth by inhibiting the transcription of oncoproteins HPV16 and HPV18 (designated as E6 and E7) and restoring p53 and retinoblastoma function. Our proposed study would therefore test the tolerability and effects of weekly curcumin administration and its ability to clear HPV infection. Our results will generate novel data as to what is an acceptable and well-tolerated dosing regimen of intravaginal curcumin, which would be crucial in designing further curcumin intervention studies. The results of our proposal will explore the effect of intravaginal curcumin as a standalone and adjuvant therapy to a LEEP among women with premalignant HPV-related cervical disease. The potential to not just excise diseased tissue, but to directly augment the clearance of the causative agent HPV, would have profound long-term ramifications in resource-limited settings and among women experiencing barriers to care and/or at high risk for disease progression.

Does the use of monopolar energy as the preferred mode of dissection effectively reduce seroma formation in laparoscopic total extra peritoneal hernioplasty? A prospective double-blinded randomized control trial.

Seroma is a commonly encountered sequela after hernia repair. Tremendous effort has been spent to investigate the effective way to prevent this "complication" including the modification of surgical technique, use of per-peritoneal drainage, etc. There were debates about the use of monopolar diathermy versus blunt dissection in laparoscopic TEP in the prevention of seroma formation. This randomized study aims to compare the effects of using 2 techniques in laparoscopic TEP on pre-peritoneal drain output and seroma formation. From 1.9.2018 to 30.9.2019, all male and female patients presented with the first occurrence, unilateral inguinal hernia anticipated for laparoscopic TEP were enrolled into the study after informed consent. Patients were randomized into "monopolar dissection preferred" (MDP) group and "blunt dissection-preferred" (BDP) group just before commencing of operation after general anesthesia. Surgeons were instructed to use monopolar energy as main dissection method for the whole operation if possible (MDP), whereas blunt dissection is the preferred choice in BDP group, but the use of monopolar energy was allowed if needed. Total energy time was measured by a specially designed homemade device attaching to the monopolar pedals as accurate as to millisecond (ms). Pre-peritoneal drains were inserted for drainage and removed 23h after operation. Drainage output, total operating time, energy time, clinical and ultrasonic seroma sizes at day 1, day 6, 1-month post operations, recurrence are compared between 2 groups. A total of 103 patients where included. There was no significant difference in age, gender, co-morbidities, side of hernia, mean defect size, operating time, fixation adjuncts, or postoperative stay. The drain volume in BDP group is 71.13 ± 31.42mL while it in MDP group is 56.36 ± 21.46mL. The MDP group had significantly fewer drain output at 23h post operation (p = 0.007) and lower seroma incidence on days 6 (p = 0.036). Overall incidence of seroma formation was 12% on postoperative day 1, 11% on postoperative day 7. No statistically differences in postoperative pain score or complications were observed at the first week, 1- and 3-months' post operation. There was no correlation with energy time to the drain output. No recurrence was found in subsequent follow-up. Pre-peritoneal drainage is clinically safe in laparoscopic totally extra-peritoneal hernioplasty and can effectively reduce the size and incidence of seroma. The seroma formation can be further reduced by appropriate use of monopolar energy as preferred dissection approach in lap TEP. Due to limitation in measuring the actual energy time, the result should be further validated by randomized multi-centers trial on its potential benefit in hernia repair by a more accurate measuring device on energy used.

Pain during intravenous Propofol injection and its prevention in the pediatric population. A randomized controlled trial.

Objectives: The aim of our study is to observe the pain difference as experienced by the pediatric patient when administered different preparations of propofol utilizing the verbal rating scale. Study Design: Prospective double-blind randomized control trial. Setting: A large tertiary care hospital in Karachi, Pakistan. Period: 6 months from June 2016 to November 2016. Material &amp; Methods: The final patient population included in the study was n= 180 and were divided into six groups. These patients received general anesthesia and underwent surgery. Patients in Group A received 2ml of normal saline and a mixture of propofol and normal saline after waiting for half a minute. Group B patients received 0.5mg/kg Lidocaine followed by normal saline after waiting for half a minute. Group C received 2ml of normal saline followed by a mixture of propofol and Lidocaine after half a minute. Group D received 0.2mg/kg of Ketamine followed by a mixture of normal saline and propofol. Group E patients received 2ml of normal saline followed by a mixture of propofol and Ketamine half a minute later. And finally, patients belonging to group F received 2ml of normal saline followed by a mixture of propofol M/LCT and normal saline half a minute later respectively. Results: The gender, age, body weight and ASA grade of all the pediatric patients were similar having a P value of &gt;0.05. The incidence rate of propofol injection pain in the groups were found to be Group A= 76.66%, Group B= 66.66%, Group C= 50%, Group D= 60%, Group E= 63.33%, Group F= 60% respectively. The incidence rate for adverse events was significantly lower in all the groups as compared to Group A that is the normal saline and propofol group having a p-value of less than 0.01. And the incidence rate of adverse events was lower in Groups C, D, E, and F were significantly lower than Group B having a p-value of less than 0.05. All the experimental groups had significantly lower scores of the VRS scale as compared to the control group (Group A) and the intergroup differences were found to be statistically significant having a p-value of less than 0.01. Conclusion: In our study, we found that the injection pain of propofol administration in the pediatric population was significantly reduced when using M/LCT pre-injection, 0.5mg/kg lidocaine or 0.2mg/kg of Ketamine. Another good combination is mixing 180mg propofol with 40mg of lidocaine or mixing propofol with 16mg of Ketamine.

Intra-articular steroid for adhesive capsulitis: does hydrodilatation give any additional benefit? A randomized control trial.

To assess the benefit offered by capsular hydrodilatation in addition to intra-articular steroid injections in cases of adhesive capsulitis, assess outcomes in diabetic patients with capsular hydrodilatation as compared to non-diabetics and correlate duration of symptoms with outcome based on the type of intervention given. This prospective double-blinded randomized control trial included patients presenting with clinical features of adhesive capsulitis with no evidence of rotator cuff pathology and randomized them into two groups-intra-articular steroid with hydrodilatation (distension group) and only intra-articular steroid (non-distension group) with intervention being performed as per the group allotted. Primary outcome measure was Shoulder Pain and Disability Index (SPADI) scores which were taken pre-intervention, at 1.5, 3 and 6months post-intervention, which were assessed by generalized linear model statistics and Pearson correlation. Although there was statistically significant drop in SPADI in both groups over time [F(1.9, 137.6) = 112.2; p < 0.001], mean difference in SPADI between the 2 groups was not statistically significant (1.53; CI:-3.7 to 6.8; p = 0.56). There was no significant difference between both groups among diabetics [F(1,38) = 0.04; p = 0.95] and no significant difference between diabetic and non-diabetic patients who received hydrodilatation [F(1.8, 60) = 2.26; p = 0.12]. There was no significant correlation between the reduction in SPADI scores and duration of symptoms in any subset of the study population. Shoulder joint hydrodilatation offered no additional benefit compared to intra-articular steroid injections for shoulder adhesive capsulitis. Outcome for diabetics and non-diabetics were similar and there was no correlation between duration of symptoms and outcome.

A Clinical Study on the Insulin Resistance Improvement Effects of Electrolyzed Hydrogen Rich Water in Type 2 Diabetes Patients: A Multicenter Prospective Double-Blind Randomized Control Trial

Background: Electrolyzed hydrogen rich water (EHW) is known to possess reactive oxygen species suppressive effects. However, its influence on diabetes is still unclear. The aim of this study is to identify the influence of EHW on diabetes.   Methods: In a multicenter, prospective, double-blind, randomized controlled trial, 50 patients with type 2 diabetes were assigned to EHW or filtered water (FW) groups. Changes in insulin resistance evaluated by HOMA-IR were set as the primary endpoint and oxidative stress markers and other clinical data were evaluated.   Findings: The delta change in HOMA-IR was +0.04 (95% CI: -0.48 to 0.59, p = 0.850) in the FW group and -0.27 (95% CI: -0.69 to 0.09, p = 0.105) in the EHW group, and no significant change was observed between two groups (p = 0.282). However, EHW ingestion significantly improved insulin resistance in the subjects who had higher insulin resistance (HOMA-IR > 1.73) at baseline period. Oxidative stress marker was also significantly improved by EHW ingestion only in subjects who had higher value at the baseline period. The suppression of marker for reactive oxygen species correlated strongly with suppression of serum lactate. No adverse effect was observed by EHW treatment.   Interpretation: Drinking EHW improved insulin resistance and redox status only in patients with deteriorated parameters. This effect seemed to be through a reduced gluconeogenesis. Even if normal subjects drink electrolyzed hydrogen water, it did not appear to manifest reactive oxygen species suppressive actions or insulin resistance improvement effects beyond desirable ranges.   Trial Registration Number: This trial was registered with University Hospital Medical Information Network (UMI19032). Funding: Nihon-Trim Co. Ltd.   Declaration of Interest: YO and SK are employees of Nihon Trim Co., Ltd. (Osaka, Japan). Authors declare there is no other conflict of interest. Ethical Approval: This study complied with the Helsinki Declaration and was conducted with the approval of the each Medical Ethics Committee of Tohoku University, Tohoku central hospital and Iwate Prefectural Takata Hospital. All participants provided their full informed consent.

POST OPERATIVE BOWEL MOVEMENT

Objectives: To compare early return of bowel movements in patients withelective stoma closure with or without nasogastric tube. Place and Duration: Single surgicalunit, Civil Hospital, Karachi, from January 2015-August 2016. Methods: This prospective doubleblind randomized control trial of 114 patients for elective stoma (Ileostomy, colostomy) closurein which lottery method was used to divide the patients into control group (with nasogastrictube) and study group (without nasogastric tube). Post operatively total duration from thesurgery till the patient passed first flatus was recorded in hours between the control and studygroups. Result: Comparison between two groups, the passage of first flatus after reversal ofstoma a mean difference of 19.7 was observed in hours between the control and study groups.Conclusion: Prophylactic nasogastric decompression in stoma closure patients can be omittedfrom routine postoperative period without any management problem.

Effect of vitamin D supplementation on insulin kinetics and cardiovascular risk factors in polycystic ovarian syndrome: a pilot study.

To assess the effect of vitamin D supplementation on parameters of insulin sensitivity/resistance (IS/IR) and insulin secretion in subjects with polycystic ovarian syndrome (PCOS). A prospective double-blind randomized control trial was conducted to assess the effect of vitamin D on insulin kinetics in women with PCOS. The trial was conducted in a tertiary care research hospital. A total of 36 subjects with PCOS, aged 18–35 years, were included in this study. Vitamin D3 4000 IU/day versus placebo was given once a month for 6 months and both groups received metformin. IS (by whole-body IS index or Matsuda index), IR (by homeostasis model assessment IR (HOMA-IR)), and insulin secretion (by insulinogenic index; II30) were the main outcome measures. Secondary outcome included blood pressure (BP), lipid profile, disposition index (DI), and vascular stiffness. Out of 36 subjects who consented, 32 completed the study. Subjects were randomized into two groups: group A (n=15; metformin and vitamin D 4000 IU/day) or group B (n=17; metformin and placebo). Oral glucose tolerance tests with 75 g glucose were carried out at baseline and 6 months after supplementation. Hypovitaminosis D was observed in 93.8% of all subjects with mean serum 25 hydroxy vitamin D level of 7.30±4.45 ng/ml. After 6 months of vitamin D supplementation, there was no significant difference in any of the parameters of IS/IR (area under curve (AUC)–glucose, AUC–insulin, insulin:glucose ratio, HOMA-IR, Matsuda index, insulinogenic index, and DI), II30, and cardiovascular risk factors between the two groups. Supplementation of vitamin D, at a dose of 4000 IU/day for 6 months, did not have any significant effect on parameters of IS/IR and insulin secretion in subjects with PCOS.

Role of Intraoperative Ropivacaine in Post‐tonsillectomy Pain Control: Randomized Control Trial Using a Paired Design

Objectives: 1) Evaluate the efficacy of ropivacaine in post-tonsillectomy pain management in adults using a paired design. 2) Evaluate the timing of intraoperative ropivacaine administration in post-tonsillectomy pain control. Methods: A prospective double-blinded randomized control trial with a paired design was performed on 25 consecutive adults undergoing a tonsillectomy. One side was injected with saline and the other side with ropivacaine. Patients were also pre-randomized into those receiving injections immediately before or after the tonsillectomy. Laterality of the injection was alternated and all surgery performed by the senior author. Patient responses were obtained via telephone interview and written questionnaire. Results: 3/25 patients were excluded from the study. 16/22 patients had pain lateralize to one side during recovery. There was no statistically significant difference in pain control between ropivacaine and normal saline. Local anesthetic decreased pain in 7/22 patients while more pain was experienced on the side with local anesthetic in 9/22 patients. 6/22 patients had no difference in pain. The time to equalization of pain based on laterality was 8.8 and 6.8 days, respectively, in the pre- and post-tonsillectomy group. Conclusions: Multiple studies have examined the role of local anesthetic in controlling post-tonsillectomy pain with equivocal results. This is the first study examining the role of local anesthetic in tonsillectomies using a paired design. Administration of ropivacaine does not affect post-tonsillectomy pain. Moreover, timing of injection does not have an effect on postoperative pain. We recommend against the use of intraoperative ropivacaine for pain control in patients undergoing tonsillectomy.

Impact of vitamin D fortified milk supplementation on vitamin D status of healthy school children aged 10–14 years

Vitamin D deficiency is a major public health problem, needing immediate attention. We studied the effect of vitamin D fortification of milk in school children. Our results show that fortification of milk is safe and effective strategy to deal with widespread vitamin D deficiency. Vitamin D deficiency among school children and adolescents is a well-documented major public health problem, needing immediate attention. To assess the effect of vitamin D fortified milk on serum 25 hydroxy vitamin D [S.25(OH)D] levels, we carried out a prospective double-blind randomized control trial in apparently healthy school children, aged 10-14 years. Of 776 subjects recruited out of 796 who consented, 713 (boys-300; girls-413) completed the study. Subjects were randomized into three groups. Group A (n = 237) received 200 ml of unfortified milk per day while group B (n = 243) and group C (n = 233) received 200 ml of milk fortified with 600 IU (15 μg) and 1,000 IU (25 μg) of vitamin D per day for 12 weeks. Serum calcium, phosphate, alkaline phosphatase, S.25(OH)D, and urinary calcium/creatinine ratio were estimated at baseline and after supplementation. Hypovitaminosis D [25(OH)D < 20 ng/ml] was observed in 92.3 % subjects with mean S.25(OH)D level of 11.69 ± 5.36 ng/ml. There was no significant difference in S.25(OH)D levels among the three groups at baseline. The mean percentage change in S.25(OH)D level in groups B (137.97 %) and C (177.29 %.) were significantly greater than group A (-5.25 %). The percentage of subjects having S.25(OH)D levels >20 ng/ml following supplementation were 5.9 % in group A, 69.95 % in group B, and 81.11 % in group C in comparison to 6.32 %, 4.9 % and 12 %, respectively, at baseline. Fortification of milk with vitamin D is an effective and safe strategy in improving S.25(OH)D levels in children aged 10-14 years.

Efficacy of intravenous dexamethasone to reduce incidence of postoperative sore throat: A prospective randomized controlled trial.

Background:Sore throat and hoarseness are common complications of endotracheal intubation. It may be very distressing for the patient and may lead to sleep disturbances and unpleasant memories.Materials and Methods:This prospective double-blinded randomized control trial was aimed to determine the efficacy of prophylactic intravenous dexamethasone to reduce the incidence of postoperative sore throat at 1 hour after tracheal extubation. Ninety six patients of either sex aged between 18 to 60 years scheduled for elective surgeries needing general anesthesia with endotracheal intubation, were randomly allocated into two groups A and B. The patients received either intravenous 0.2 mg/kg dexamethasone (group A, n = 48) or normal saline (group B, n = 47) just before induction. Trachea was intubated with appropriate size disposable endotracheal tubes for securing the airway. Follow up for the incidence of sore throat, cough and hoarseness was done at 1, 6 and 24 hours post-extubation.Results:At 1 hour post-extubation, the incidence of sore throat in the control group was 48.9% compared with 18.8% in the dexamethasone group (P<0.002).Conclusions:Prophylactic intravenous dexamethasone in a dose of 0.2 mg/kg can reduce the incidence of postoperative sore throat at 1 hour post-extubation by around 30%, with the efficacy being around 60%.