Placebo Gel Group Research Articles

In Vitro and In Vivo Evaluation of Metformin Hydrochloride Hydrogels Developed with Experimental Design in the Treatment of Burns.

Burns alter the normal skin barrier and affect various host defense processes that help prevent infections. An ineffective repair process can lead to serious damage, such as the onset of an infection or skin loss, which can then harm the surrounding tissues and ultimately the entire organism. This study aims to prepare in situ gels containing metformin hydrochloride, a compound known for its wound healing properties. To achieve this, in situ gels were prepared using three different gelling agents (Poloxamer 407®, Carbopol 934®, and sodium carboxymethyl cellulose (Na-CMC)) and three different concentrations of metformin hydrochloride (4 mg/g, 6 mg/g, and 8 mg/g), which were optimized through experimental design. Metformin concentration and gelling agent type were independent variables, and the loaded amount and the percentage of metformin released after 150 min were chosen as dependent variables in the optimization process. After determining the optimum values of the dependent variables according to the ANOVA analysis results, in vivo studies were conducted with optimized hydrogel formulations. Two groups, each consisting of seven Wistar rats with a burn model, were treated with metformin-poloxamer 407® gels at doses of 4 mg/g and 8 mg/g for 29 days. The results were then compared to untreated and placebo gel groups. Rats treated with in situ Poloxamer 407® hydrogels containing metformin hydrochloride showed a significant reduction in the size of the burned area after 29 days of treatment. However, for a comprehensive understanding of the wound healing mechanism, further studies such as immuno-histochemical and cell culture studies are needed.

Acceptability of Single-dose Clindamycin Gel for Bacterial Vaginosis: A Randomized Controlled Trial

The goal of this study was to assess the acceptability of a single-dose bioadhesive 2% clindamycin vaginal gel for bacterial vaginosis (BV). This double-blind, placebo-controlled, randomized study compared a new clindamycin gel with placebo gel (2:1 ratio). The primary objective was efficacy; secondary objectives were safety and acceptability. Subjects were evaluated at screening, days 7 to 14 (Day 7-14), and days 21 to 30 (test-of-cure [TOC]). An acceptability questionnaire with 9 questions was administered at the Day 7-14 visit, and a subset of questions (#7-#9) was asked again at the TOC visit. At Visit 1, subjects were provided with a daily electronic diary (e-Diary) to collect information regarding study drug administration, vaginal discharge, odor, itching, and any other treatments used. Study site staff reviewed e-Diaries at the Day 7-14 and TOC visits. A total of 307 women with BV were randomized to treatment (204 to the clindamycin gel group and 103 to the placebo gel group). Most (88.3%) reported at least one previously diagnosed BV episode, and more than one half (55.4%) had experience with other vaginal treatments for BV. At the TOC visit, almost all (91.1%) of the clindamycin gel subjects described their overall experience with the study drug as "satisfied" or "very satisfied," 95.8% indicated that they would be "likely" or "very likely" to use the product again if it became available after the study and they had BV again, and 93.7% would be "likely" or "very likely" to recommend their treatment to a friend who had BV. Almost all (90.2%) clindamycin-treated subjects responded that application was "clean" or "fairly clean," as opposed to "neither clean nor messy," "fairly messy," or "messy." Although 55.4% experienced leakage in the days after application, only 26.9% of those indicated that it was bothersome. Subjects receiving clindamycin gel also reported improvement in both odor and discharge, commencing shortly after dosing and continuing through the assessment period, regardless of whether they met the critical cure criteria. A single dose of a new bioadhesive 2% clindamycin vaginal gel showed rapid resolution of symptoms and was highly acceptable as a treatment for bacterial vaginosis. gov identifier: NCT04370548.

A Placebo-Controlled Trial to Evaluate Two Locally Delivered Antibiotic Gels (Piperacillin Plus Tazobactam vs. Doxycycline) in Stage III-IV Periodontitis Patients.

Background and objectives: this study aims to evaluate the clinical and microbiological effects of a single subgingival administration of a locally delivered antibiotic gel containing piperacillin plus tazobactam and compare it with a slow-release doxycycline (14%) gel and a placebo gel, following subgingival instrumentation (SI) in patients with severe periodontitis. Materials and methods: sixty-four patients diagnosed with stage III-IV periodontitis were enrolled, were randomly assigned into three groups, and were treated additionally with a single subgingival administration of piperacillin plus tazobactam gel (group A); doxycycline gel (group B); and placebo gel (group C). The primary outcome variable was the change in mean probing pocket depth (PPD) 6 months after the intervention. Secondary outcome variables were changes in mean full-mouth bleeding score (FMBS); full-mouth plaque score (FMPS); overall bleeding index (BOP); pocket closure; and clinical attachment level (CAL), along with changes in the numbers of five keystone bacteria: Aggregatibacter actinomycetemcomitans (A.a.), Porphyromonas gingivalis (P.g.), Prevotella intermedia (P.i.), Tannerella forsythia (T.f.), and Treponema denticola (T.d.). Intergroup and intragroup differences were evaluated at 3 and 6 months. Results: at baseline, the three groups were comparable. An improvement in clinical parameters such as PPD, CAL, and BOP between groups was observed at 3 and 6 months, but without statistical significance (p > 0.05). At 6 months, the intragroup analysis showed a significant reduction in clinical parameters. Even though the piperacillin plus tazobactam group showed slightly higher PPD reduction, this was not statistically significant when compared to both control groups. Conclusions: The groups had similar results, and subgingival instrumentation can be executed without adjunctive antimicrobials, reducing the costs for the patient and the working time/load of the professional.

Prophylactic Oral Dextrose Gel and Neurosensory Impairment at 2-Year Follow-up of Participants in the hPOD Randomized Trial

Prophylactic oral dextrose gel reduces neonatal hypoglycemia, but later benefits or harms remain unclear. To assess the effects on later development of prophylactic dextrose gel for infants born at risk of neonatal hypoglycemia. Prospective follow-up of a multicenter randomized clinical trial conducted in 18 Australian and New Zealand hospitals from January 2015 to May 2019. Participants were late preterm or term at-risk infants; those randomized in 9 New Zealand centers (n = 1359) were included and followed up between January 2017 and July 2021. Infants were randomized to prophylactic 40% dextrose (n = 681) or placebo (n = 678) gel, 0.5 mL/kg, massaged into the buccal mucosa 1 hour after birth. The primary outcome of this follow-up study was neurosensory impairment at 2 years' corrected age. There were 44 secondary outcomes, including cognitive, language, and motor composite Bayley-III scores (mean [SD], 100 [15]; higher scores indicate better performance). Of eligible infants, 1197 (91%) were assessed (581 females [49%]). Neurosensory impairment was not significantly different between the dextrose and placebo gel groups (20.8% vs 18.7%; unadjusted risk difference [RD], 2.09% [95% CI, -2.43% to 6.60%]; adjusted risk ratio [aRR], 1.13 [95% CI, 0.90 to 1.41]). The risk of cognitive and language delay was not significantly different between the dextrose and placebo groups (cognitive: 7.6% vs 5.3%; RD, 2.32% [95% CI, -0.46% to 5.11%]; aRR, 1.40 [95% CI, 0.91 to 2.17]; language: 17.0% vs 14.7%; RD, 2.35% [95% CI, -1.80% to 6.50%]; aRR, 1.19 [95% CI, 0.92 to 1.54]). However, the dextrose gel group had a significantly higher risk of motor delay (2.5% vs 0.7%; RD, 1.81% [95% CI, 0.40% to 3.23%]; aRR, 3.79 [95% CI, 1.27 to 11.32]) and significantly lower composite scores for cognitive (adjusted mean difference [aMD], -1.30 [95% CI, -2.55 to -0.05]), language (aMD, -2.16 [95% CI, -3.86 to -0.46]), and motor (aMD, -1.40 [95% CI, -2.60 to -0.20]) performance. There were no significant differences between groups in the other 27 secondary outcomes. Among late preterm and term infants born at risk of neonatal hypoglycemia, prophylactic oral 40% dextrose gel at 1 hour of age, compared with placebo, resulted in no significant difference in the risk of neurosensory impairment at 2 years' corrected age. However, the study may have been underpowered to detect a small but potentially clinically important increase in risk, and further research including longer-term follow-up is required. anzctr.org.au Identifier: ACTRN12614001263684.

Oral dextrose gel for the treatment of hypoglycaemia in newborn infants.

Neonatal hypoglycaemia, a common condition, can be associated with brain injury. It is frequently managed by providing infants with an alternative source of glucose, often given enterally with milk-feeding or intravenously with dextrose solution, which may decrease breastfeeding success. Intravenous dextrose also often requires that mother and baby are cared for in separate environments. Oral dextrose gel is simple and inexpensive, and can be administered directly to the buccal mucosa for rapid correction of hypoglycaemia, in association with continued breastfeeding and maternal care. This is an update of a previous review published in 2016. To assess the effectiveness of oral dextrose gel in correcting hypoglycaemia in newborn infants from birth to discharge home and reducing long-term neurodevelopmental impairment. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase from database inception to October 2021. We also searched international clinical trials networks, the reference lists of included trials, and relevant systematic reviews identified in the search. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing oral dextrose gel versus placebo, no treatment, or other therapies for the treatment of neonatal hypoglycaemia in newborn infants from birth to discharge home. Two review authors independently assessed study quality and extracted data; they did not assess publications for which they were study authors. We contacted investigators to obtain additional information. We used fixed-effect models and the GRADE approach to assess the certainty of evidence. We included two studies conducted in high-income countries, involving 312 late preterm and at-risk term infants and comparing oral dextrose gel (40% concentration) to placebo gel. One study was at low risk of bias, and the other (an abstract) was at unclear to high risk of bias. Oral dextrose gel compared with placebo gel probably increases correction of hypoglycaemic events (rate ratio 1.08, 95% confidence interval (CI) 0.98 to 1.20; rate difference 66 more per 1000, 95% CI 17 fewer to 166 more; 1 study; 237 infants; moderate-certainty evidence), and may result in a slight reduction in the risk of major neurological disability at age two years or older, but the evidence is uncertain (risk ratio (RR) 0.46, 95% CI 0.09 to 2.47; risk difference (RD) 24 fewer per 1000, 95% CI 41 fewer to 66 more; 1 study, 185 children; low-certainty evidence). The evidence is very uncertain about the effect of oral dextrose gel compared with placebo gel or no gel on the need for intravenous treatment for hypoglycaemia (RR 0.78, 95% CI 0.46 to 1.32; RD 37 fewer per 1000, 95% CI 91 fewer to 54 more; 2 studies, 312 infants; very low-certainty evidence). Investigators in one study of 237 infants reported no adverse events (e.g. choking or vomiting at the time of administration) in the oral dextrose gel or placebo gel group (low-certainty evidence). Oral dextrose gel compared with placebo gel probably reduces the incidence of separation from the mother for treatment of hypoglycaemia (RR 0.54, 95% CI 0.31 to 0.93; RD 116 fewer per 1000, 95% CI 174 fewer to 18 fewer; 1 study, 237 infants; moderate-certainty evidence), and increases the likelihood of exclusive breastfeeding after discharge (RR 1.10, 95% CI 1.01 to 1.18; RD 87 more per 1000, 95% CI 9 more to 157 more;1 study, 237 infants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Oral dextrose gel (specifically 40% dextrose concentration) used to treat hypoglycaemia in newborn infants (specifically at-risk late preterm and term infants) probably increases correction of hypoglycaemic events, and may result in a slight reduction in the risk of major neurological disability at age two years or older. Oral dextrose gel treatment probably reduces the incidence of separation from the mother for treatment and increases the likelihood of exclusive breastfeeding after discharge. No adverse events have been reported. Oral dextrose gel is probably an effective and safe first-line treatment for infants with neonatal hypoglycaemia in high-income settings. More evidence is needed about the effects of oral dextrose gel treatment on later neurological disability and the need for other treatments for hypoglycaemia. Future studies should be conducted in low-and middle-income settings, in extremely and moderately preterm infants, and compare oral dextrose gel with other therapies such as intravenous dextrose. There are two ongoing studies that may alter the conclusions of this review when published.

Effects of Pueraria mirifica on vaginal artery vascularization in postmenopausal women with genitourinary syndrome of menopause

ObjectiveTo compare the effects of 6% Pueraria mirifica vaginal gel with those of placebo gel on vaginal blood flow, vaginal maturation index (VMI), vaginal health index (VHI), endometrial thickness and genitourinary symptoms in postmenopausal women. Study designIn a randomized, double-blinded, placebo-controlled study (TCTR20200624007), 72 postmenopausal women were randomized into the P. mirifica or the placebo gel group. Both groups were followed up at week 4 and week 12. Main outcome measureDoppler ultrasonography pulsatility index (PI) and resistance index (RI), VMI, VHI, endometrial thickness and genitourinary symptoms were evaluated at baseline, at week 4 and week 12 of treatment. ResultsSixty-three participants completed the study. After 4 and 12 weeks of treatment, PI and RI had significantly decreased in the P. mirifica group compared with the placebo group. At week 12, PI in the P. mirifica group and in the placebo group were 3.03 + 1.09 and 6.88 + 2.16, respectively (p = 0.002). Similar changes were also demonstrated in the resistance indices. The P. mirifica group demonstrated a markedly higher mean VMI at week 12 compared with the placebo group, 55.19 ± 18.53 and 20.29 ± 28.46 (p = 0.012). In addition, all parameters of VHI based on the vaginal physical findings at week 12 in the P. mirifica group were significantly higher than in the placebo group (p < 0.001). ConclusionIn this study, 6% P. mirifica vaginal gel for 12 weeks in postmenopausal women with GSM appeared to increase vaginal artery circulation and restore atrophic vaginal tissue. Clinical Trial Registration NumberTCTR20200624007.

Comparison of Casein Phosphopeptide with Potassium Nitrate and Sodium Monofluorophosphate Desensitizing Efficacy after In-Office Vital Bleaching—A Randomized Trial

Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), potassium nitrate, and sodium monofluorophosphate are desensitizing agents that help in reducing teeth sensitivity. However, indecisive evidence exists regarding their efficacy. Therefore, this study was conducted to compare the desensitizing efficacy of casein phosphopeptide-amorphous calcium phosphate and potassium nitrate with sodium monofluorophosphate agents after in-office vital bleaching. A randomized controlled trial was conducted on 2011 patients. The patients were randomly and equally divided into the CPP-ACP group (group 1), potassium nitrate with sodium monofluorophosphate group (group 2), and placebo gel (group 3). The upper and lower anterior teeth including the first premolar were isolated with a rubber dam, then the bleaching agents were applied on the labial surface of all the teeth, followed by light activation for 15 min. The procedure was repeated 3 times with an interval of 5 min in-between. After carrying out the bleaching procedure, patients were given a desensitizing gel or placebo gel in unmarked syringes with an instruction to apply it every 12 h for up to 3 days. The intensity of pain was recorded using a discomfort interval scale (DIS). A decrease in pain was observed 24 h after the application of the desensitizing gel in groups 1 and 2. However, in group 3, the pain persisted, with 46 (69.69%) patients having moderate pain and 14 (21.21%) developing severe pain over time. A significant difference in discomfort level with time was noted in group 1 (p = 0.015) and group 2 (p = 0.036). However, no significant difference was found in group 3 (p = 0.085). It was concluded that both desensitizing agents performed exceptionally well in reducing teeth sensitivity.

Effect of Topical Clove (Syzygium aromaticum (L.) Merr. &amp; L.M.Perry) Gel on Premature Ejaculation: A Pilot Randomized Double-Blind Placebo-Controlled Clinical Trial

Premature ejaculation is one of the most common sexual disorders worldwide without a satisfying treatment. In this study, we investigated the efficacy of a topical formulation of clove oil in premature ejaculation patients. Eligible patients were randomly divided into two groups to use either Syzygium aromaticum (SA) 1% gel or placebo gel 10 minutes before the intercourse for a period of 8 weeks. Outcome measurement were Premature Ejaculation Diagnostic Tool (PEDT) and International Index of Erectile Function (IIEF) questionnaires in addition to Intravaginal Ejaculation Latency Time (IELT). A total number of 22 (11 patients in each group) participants completed the study. At the end of the intervention, the IELT scores changed from 29.84 ± 18.59 to 97.09 ± 91.86 and 42.51 ± 13.98 to 52.45 ± 32.7 seconds in SA gel and placebo groups, respectively (p-value = 0.003). Also, the changes of PEDT scores in the SA gel group (from 14 ± 3.55 to 9.2 ± 4.56) comparing to that of placebo gel group (from 14.63 ± 3.61 to 13.5 ± 3.78) was significantly different (p-value =0.001). Moreover, results of IIEF questionnaire revealed significant improvement of “Intercourse Satisfaction” in SA gel group (p-value = 0.016). No adverse event was observed. It seems that SA gel could be beneficial in the treatment of premature ejaculation; however, it should be further evaluated in larger studies.

THE EFFECT OF RAMANIA LEAF (Bouea macrophylla Griff) EXTRACT GEL ON COLLAGEN FIBERS DENSITY IN INCISIONAL WOUND OF MALE WISTAR RATS

ABSTRACTBackground: Ramania leaf (Bouea macrophylla Griff) extract gel has secondary metabolites in the form of flavonoids, steroids, phenols and terpenoids which have a role as antioxidant. They will protect the body from excessive production of reactive oxygen species (ROS) by increasing endogenous antioxidants SOD, CAT and GPX, so that wound healing will not be inhibited and the process of collagen synthesis can run smoothly. Objective: To analyze the effect of ramania leaf extract gel that was applied topically with 5%, 10% and 15% concentration on collagen fibers density in incisional wound of male Wistar rats (Rattus norvegicus) on the 7th and the 14th day. Method: This research is a pure experimental study with a posttest-only control group design, using 24 rats which were divided into 4 groups: the treatment groups given ramania leaf extract gel of 5%, 10%, 15%, and the control group given placebo gel. The application of the extract gel was done once within 24 hours. The collagen level was measured with a spectrophotometer on the 7th and the 14th day. Results: Two-Way ANOVA test results on the 7th and the 14th day of each group showed a significant difference with p=0.000 (p&lt;0.05). The Bonferroni Post-hoc Test showed a significant difference with p&lt;0.05 between the placebo gel group and the groups of ramania leaf extract gel of 5%, 10%, 15% on the 7th and the 14th day. Conclusion: There is an effect of ramania leaf extract gel on collagen fibers density with the most effective concentration of 15%.Keywords: Antioxidant, , Collagen, Ramania Leaf Extract Gel

Clinical effect of simvastatin gel with bone graft in grade II furcation defects: A randomized controlled clinical trial

Aim: To evaluate the effectiveness of 1.2 mg/mL simvastatin (SMV) gel with hydroxyapatite (HA) bone graft in the surgical treatment of mandibular Grade II furcation defects compared with HA bone graft, SMV, and placebo after open-flap debridement (OFD). Materials and Methods: The present study was a single-center, triple-blind randomized controlled clinical trial wherein 23 mandibular grade II furcation defects from 15 chronic periodontitis patients were randomly assigned for treatment with either placebo gel (group 1; n = 5), HA (group 2; n = 6), SMV (group 3; n = 6), and SMV + HA (group 4; n = 6). Clinical parameters at the furcation defect site, such as horizontal and vertical probing depth (HPD and VPD), vertical clinical attachment level (VCAL), radiologic parameters, such as vertical defect depth in intraoral periapical radiograph (IOPA), vertical and horizontal defect depth, and volume of defect in cone-beam computed tomography (CBCT) were recorded at baseline, 3, and 6 months postoperatively and analyzed using SPSS software. For intragroup comparison, paired t test and Wilcoxon test were used, and for intergroup comparison, ANOVA and Kruskal-Wallis test were used. Results: SMV + HA group had improvement in all the clinical parameters when compared to baseline but were not significantly different when compared to other groups. However, statistically significant improvement in HPD was evident in SMV + HA group at 3 months (1.8 ± 1.3; P = 0.019; P < 0.05) when compared to HA group. In CBCT, SMV + HA group had significant improvement in VDD, HDD, and volume of the defect whereas in IOPA, there was no significant findings. Conclusion: Simvastatin with HA is more effective in reducing the horizontal component of grade II furcation defects.

Novel combined topical gel of lidocaine–verapamil–nitroglycerin can dilate the radial artery and reduce radial pain during trans-radial angioplasty

IntroductionRadial approach for coronary angioplasty is accepted by many specialists in medical centers around the world. The use of radial access is associated with fewer vascular complications and the same success rate in comparison with traditional femoral access. Radial artery spasm is one of the main concerns in this method. The small size of the radial artery and high density of alpha-1 adrenergic receptors in this artery can accelerate the spasm. The objects of this study were to evaluate whether the combined topical gel of lidocaine–verapamil–nitroglycerin could dilate the radial artery and reduce patient pain and sympathetic response during radial puncture.MethodsPatients undergoing elective trans-radial angioplasty were randomized to either placebo or therapeutic gel group in single-center, double-blind study. Placebo or therapeutic gel applied 1 cm proximal to the radial styloid process. Radial artery size was measured by ultrasound. Radial pain was reported by the visual analog scale (VAS) and the sympathetic response was assessed by changes in systolic (SBP) and diastolic blood pressure (DBP) and heart rate (HR). The incidence of spasm was defined by the radial artery spasm score.Results60 patients (30 patients in each group) participated in this study. A significant increase in the size of the radial artery was observed in the group receiving therapeutic gel compared to the placebo group (mean diameter, mm: 2.95 ± 0.48 vs. 2.54 ± 0.43, p = 0.001; area, cm2: 0.07 vs. 0.05, p = 0.001). During radial puncture, the radial pain intensity was significantly decreased in patients receiving therapeutic gel (4 (1–5) vs. 2 (1–2), p = 0.003). Radial artery spasm didn’t happen in any group.ConclusionBased on our results, Pre-procedural administration of combined topical gel of verapamil-nitroglycerin-lidocaine significantly increases the size of the radial artery and effectively reduces the radial pain during radial puncture in patients undergoing trans-radial angioplasty.

Interventions for improving oral health in people after stroke.

Interventions for improving oral health in people after stroke.

Efficacy of Timolol in a Novel Intranasal Thermosensitive Gel for Hereditary Hemorrhagic Telangiectasia–Associated Epistaxis

Other than nasal moisturizers, no standard-of-care medical therapy exists for epistaxis in hereditary hemorrhagic telangiectasia (HHT). With epistaxis as the greatest cause of morbidity in patients with HHT, there is a need to identify effective topical therapies. To determine the efficacy and safety of an intranasal timolol thermosensitive gel vs placebo thermosensitive gel in treating HHT-associated epistaxis. This double-blind, placebo-controlled randomized clinical trial was conducted from October 29, 2019, to May 20, 2020, at a tertiary care center. A total of 27 patients with HHT and moderate-to-severe epistaxis were recruited and included in this prespecified analysis: 14 in the timolol group and 13 in the placebo group. Inclusion criteria included (1) age 18 years or older, (2) clinical or genetic diagnosis of HHT, (3) screening Epistaxis Severity Score (ESS) of 4 or greater and 2 or more nosebleeds cumulatively lasting at least 5 minutes per week, (4) stable epistaxis pattern over the preceding 3 months, and (5) no change in epistaxis treatment or nasal hygiene regimen in the preceding month. Exclusion criteria included (1) contraindications to systemic β-blocker administration, (2) use of medications interacting with timolol, (3) use of antiangiogenic medications in the last month before recruitment, and (4) use of anticoagulants, antiplatelets, or fibrinolytic therapies within the last month. Novel thermosensitive intranasal timolol (0.1%) gel vs placebo thermosensitive gel applied twice daily to each nostril for 8 weeks. The primary outcome was the median change in ESS and percentage of participants reaching the minimal clinically important difference in ESS. Secondary outcomes were changes in Clinical Global Impression-Severity and Clinical Global Impression-Improvement scores, Nasal Outcome Score for Epistaxis in Hereditary Hemorrhagic Telangiectasia, and hemoglobin level. Of 27 participants randomized (median [range] age, 55 [20-76] years; 14 women [52%]; 25 White [93%]), a total of 23 patients with HHT completed the primary outcome measure. Within the timolol gel and placebo gel groups, respectively, the median change (range) in ESS was 2.32 (0.22 to 5.97) vs 1.96 (-0.91 to 5.98), and 9 of 11 (82%) vs 9 of 12 (75%) participants experienced a clinically meaningful improvement in ESS. Twenty-two of the 23 participants (96%) reported improvement via the Clinical Global Impression-Improvement score, with 81% vs 58% of participants reporting reduced severity of epistaxis in the timolol vs placebo group, respectively. Of participants completing the Nasal Outcome Score for Epistaxis in HHT at follow-up visit, 7 of 10 (70%) in the timolol group achieved a clinically important difference vs 5 of 10 (50%) in the placebo group. There was no change in hemoglobin level between or within groups. Zero participants in the placebo group and 2 of 13 (15%) in the timolol group withdrew because of adverse events. Thermosensitive gel, alone or in combination with timolol, was highly effective in reducing HHT-associated epistaxis. The timolol group had greater improvement in epistaxis and quality of life than the placebo group, but effect estimates were imprecise, and no definitive conclusions on the superiority of timolol can be drawn. Physicians treating patients with HHT-associated epistaxis should consider a thermosensitive gel (with or without timolol) for their patients. ClinicalTrials.gov Identifier: NCT04139018.

The effects of eugenol nanoemulsion on pain caused by arteriovenous fistula cannulation in hemodialysis patients: A randomized double-blinded controlled cross-over trial

ObjectivesLocal anesthetic and antinociceptive activity of eugenol, as the main ingredient of clove, was determined in previous researches. This study aimed to assess the efficacy of its topical nanoemulsion gel vs. placebo in controlling pain caused by arteriovenous fistula (AVF) needling in patients undergoing hemodialysis (HD). DesignIn this double-blinded cross-over trial, the patients were randomly allocated to eugenol gel 4% (n = 34) and placebo gel (n = 34) groups. For each patient, a tip of finger unit of gel was applied 2 cm around the insertion site of hemodialysis needles. After 10 min, AVF needling was done. AVF needling-related pain was assessed using visual analogue scale (VAS) immediately after the puncture. All patients were tested at three different states: (1) before using any intervention; (2) after using either the eugenol or placebo gel; and (3) after crossing over the groups. ResultsThere was a significant difference between the mean of patients’ pain severity score in the three states (p = 0.001). It was reported as low as 3.29 ± 0.67 in patients who received eugenol nanoemulsion. Also, the highest pain severity score (5.03 ± 0.57) was reported at the no-intervention state. ConclusionsIt seems that topical application of eugenol nanoemulsion may significantly decrease AVF cannulation related pain intensity score in patients undergoing HD. However, further studies with larger sample size and longer intervention period should be done for better judgment on its efficiency and safety.

Treatment of contact burn injury with hypericum perforatum: An experimental study

Aim: Burns are one of the most difficult physical and psychological traumas that people face. Generally, protection and prevention strategies from burns are practiced. The young and the elderly are most likely to be affected tragically. The aim of the present study is to investigate the effect of Hypericum perforatum methanol extractcontaining gel on the healing of burn wounds. Materials and Methods: Forty male rats of the Sprague-Dawley strain were divided into four groups after a 4x4 area of their back was shaved, and an experimental burn was created with the direct contact of an aluminum metal stamp heated in boiling water for 15 seconds. There was no implementation on or treatment of the control group (Group 1). Burn wounds were irrigated with saline solution (Saline group, Group 2), and silver sulphadiazine 1% (Silverdin®) cream (Group 3), Hypericum perforatum methanol extract-containing gel (Group 4), and a placebo gel (Group 5) were applied topically 4 times a day after the contact burn. Histopathological analyses of the burned area were made at 4, 8, and 24 hours. Results: The topical use of Hypericum perforatum methanol extract-containing gel in the experimental contact burns, histologically; resulted in the reduction of collagen discoloration, vascular damage and hair follicle and glandula sebaceous damage while preserving total number of hair follicles, number of vessels and epidermal thickness compared to Silver Sulphadiazine 1% (Silverdin®) cream treatment. Conclusion: Positive effects of topical Hypericum perforatum gel were detected on experimental burns and its use might have beneficial effects on acute burn wounds.

Delayed-Onset Muscle Soreness and Topical Analgesic Alter Corticospinal Excitability of the Biceps Brachii.

The interactive effect of delayed-onset muscle soreness (DOMS) and a topical analgesic on corticospinal excitability was investigated. Thirty-two participants completed Experiments A (no DOMS) and B (DOMS). For each experiment, participants were randomly assigned to two groups: 1) topical analgesic gel (topical analgesic, n = 8), or 2) placebo gel (placebo, n = 8) group. Before the application of gel (pregel), as well as 5, 15, 30, and 45 min postgel, motor-evoked potential (MEP) area, latency, and silent period, as well as cervicomedullary MEP and maximal compound motor unit action potential areas and latencies were measured. In addition, pressure-pain threshold (PPT) was measured pre-DOMS and at the same timepoints in experiment B. In experiment A, neither group showed a significant change for any outcome measure. In experiment B, both groups exhibited a significant decrease in PPT from pre-DOMS to pregel. After the application of topical analgesic, but not placebo, there was a significant increase in PPT at 45 min postgel, respectively, compared with pregel and a main effect of time for the silent period to increase compared with pregel. Participants with DOMS had reduced MEP and cervicomedullary MEP areas and increased corticospinal silent periods compared with those who did not have DOMS. These findings suggest that DOMS reduced corticospinal excitability and after the administration of menthol-based topical analgesic, there was a reduction in pain, which was accompanied by increased corticospinal inhibition.

Effect of Testosterone on NatriureticPeptide Levels.

Circulating natriuretic peptide (NP) levels are markedly lower in healthy men than women. A relative NP deficiency in men could contribute to their higher risk of hypertension and cardiovascular disease. Epidemiological studies suggest testosterone may contribute to sex-specific NP differences. This study aimed to determine the effect of testosterone administration on NP levels using a randomized, placebo-controlled design. One hundred and fifty-one healthy men (20 to 50 years of age) received goserelin acetate to suppress endogenous production of gonadal steroids, and anastrazole to suppress conversion of testosterone to estradiol. Subjects were randomized to placebo gel or 4 different doses of testosterone (1%) gel for 12weeks. Serum N-terminal-pro-B-type natriuretic peptide (NT-proBNP) and total testosterone levels were measured at baseline and follow-up. Men who did not receive testosterone replacement (placebo gel group) after suppression of endogenous gonadal steroid production experienced a profound decrease in serum testosterone (median 540 to 36ng/dl; p<0.0001). This was accompanied by an increase in median NT-proBNP (+8 pg/ml; p=0.02). Each 1-g increase intestosterone dose was associated with a 4.3% lower NT-proBNP at follow-up (95% confidence interval:-7.9% to-0.45%; p=0.029). An individual whose serum testosterone decreased by 500ng/dl had a 26% higher predicted follow-up NT-proBNP than someone whose serum testosterone remained constant. Suppression of testosterone production in men led to increases in circulating NT-proBNP, whichwereattenuated by testosterone replacement. Inhibition of NP production by testosterone may partly explain thelower NPlevels in men. (Dose-Response of Gonadal Steroids and Bone Turnover in Men; NCT00114114).

Self-administered vaginal lidocaine gel for pain management with intrauterine device insertion: a blinded, randomized controlled trial

A major barrier to intrauterine device use is fear of pain during insertion. Trials exploring analgesic interventions for intrauterine device insertion have yielded mixed results, and no standardized pain management guidelines currently exist for this procedure. In an abortion-related study, self-administered lidocaine gel over a prolonged time interval showed promise as a method of pain control. The objective of the study was to assess pain control with intrauterine device insertion after patient-administered lidocaine gel compared with placebo. We conducted a randomized, blinded trial of women undergoing levonorgestrel or copper intrauterine device insertion in an outpatient gynecology clinic between July 2016 and April 2017. Participants self-administered either 20 mL of 2% lidocaine gel or placebo gel vaginally at least 15 minutes prior to intrauterine device insertion. No other analgesics were administered. The primary outcome was pain during intrauterine device insertion, measured on a 100-mm visual analog scale (0 being no pain and 100 being worst pain imaginable). Secondary outcomes included anticipated and baseline pain and pain with speculum insertion and tenaculum placement. In a postprocedure questionnaire, participants reported acceptability of vaginal gel and willingness to wait for pain control. Median values were assessed because of the nonnormal distribution of visual analog scale scores using the Mann-Whitney U test. Predictors of intrauterine device insertion pain were assessed using a multiple linear regression. In total, 220 women were randomized and 215 were included in analysis (108 in lidocaine gel, 107 in placebo gel groups). Median (range) time from gel administration to speculum insertion was 21 (14-74) and 20 (12-43) minutes in the lidocaine and placebo groups, respectively (P= .13). The median pain scores during intrauterine device insertion were not significantly different: 65 (1-99) mm in the lidocaine group and 59 (5-100) mm in the placebo group (P= .09). Among secondary outcome time points, only median pain scores at speculum insertion were significantly different between the lidocaine and placebo groups (7 [0-81] mm vs 11 [0-80] mm, respectively; P= .046). Anticipated pain and menstrual pain were both predictors of pain with intrauterine device insertion. The majority of women in both groups found the amount of vaginal leakage following gel insertion to be acceptable (>80%). Ninety-two percent of participants (n= 194) stated they would be willing to wait before intrauterine device placement for a potential analgesic effect. Self-administered lidocaine gel at least 15 minutes before intrauterine device insertion does not appear to reduce pain compared with placebo but may help with speculum insertion. We found that women are willing to extend visit time to gain pain control. Self-administration of local anesthetic is acceptable to patients and should be considered in future research.

Topical Ketoprofen Versus Placebo in Children Presenting With Ankle Sprain to the Emergency Department: A Randomized Controlled Study.

Despite the favorable data concerning topical agents use in outpatient clinics, they are not commonly in emergency departments (EDs). The present study aimed to compare the effect of 2.5% topical ketoprofen (gel form) to placebo in children presenting with ankle sprain to the ED. Children between 7 and 18 years old presenting with ankle sprain composed the study population. Study patients were randomized into 2 study arms: 2.5% ketoprofen gel and placebo administered in a 5-cm area locally. Pain improvements at 15 and 30 minutes were measured by visual analog scale. Median pain reductions at 15 minutes for ketoprofen and placebo groups were 27.5 (16-39) and 5 (4-10), respectively. Median changes in pain intensity at 30 minutes for ketoprofen and placebo gel groups were 48 (43-52) and 9 (6-16), respectively. When compared 2 arms for the pain improvement at 15 and 30 minutes, the differences between 2 study drugs were 20 (13-28) and 35 (29-41), respectively. There were 7 (12.7%) rescue drug needs in the placebo group and 1 (1.7%) in the ketoprofen group (difference, 10.9%; 95% confidence interval, -6% to 7%; P = 0.83). There were no adverse effects in either group. Ketoprofen gel is superior to placebo in ceasing pain in children presenting with ankle sprain to the ED with a high safety profile.

Effect of in-situ application of simvastatin gel in surgical management of osseous defects in chronic periodontitis–A randomized clinical trial

BackgroundThe present randomized controlled clinical study was designed to investigate the effect of in situ application of 1.2mg Simvastatin (SV) gel in the surgical management of Intrabony defects in chronic periodontitis patients. Methodology20 patients contributing 40 sites were categorized into two treatment groups: Open flap debridement plus 1.2mg SV gel (Group 1) and Open flap debridement plus Placebo gel (Group 2). Gingival index (GI), Plaque index (PI), Pocket depth (PD) and clinical attachment level (CAL) were recorded at baseline, 3 months, 6 months and 9 months. At baseline and at the end of 6 and 9 months Radiographic evaluation of Intrabony defect fill was done using Image j software. ResultsSignificant reduction of GI, PD and gain in CAL was observed at the end of 9 months in both groups. Amount of bone fill and percentage of original defect fill in Group 1 was statistically highly significant than Group 2 at the end of 6 and 9 months. ConclusionHigher amount of decrease in GI and PD along with more amount of CAL gain was observed in treatment group than control group. Radiological assessment confirmed that significant intrabony defect fill and percentage fill of original defect in treatment group than controlled group.