mL Of Placebo Research Articles

Safety and Efficacy of Vocacapsaicin for Management of Postsurgical Pain: A Randomized Clinical Trial.

Nonopioid management of postsurgical pain remains a major unmet need. Few studies have evaluated transient receptor potential vanilloid subfamily member 1 agonists for analgesia after surgery. This study examines intraoperative vocacapsaicin, a novel prodrug of the transient receptor potential vanilloid subfamily member 1 agonist capsaicin, in a validated model of postsurgical pain. This was a triple-blinded, randomized, placebo-controlled, dose-ranging trial in patients undergoing bunionectomy. Patients were randomized 1:1:1:1 to surgical site administration of 14 ml of placebo or one of three vocacapsaicin concentrations: 0.30, 0.15, or 0.05 mg/ml. The prespecified primary endpoint was the area-under-the-curve of the numerical rating scale pain score at rest through 96 h for the 0.30 mg/ml group. Prespecified ordered, secondary endpoints for the 0.30 mg/ml group included the percentage of patients who did not require opioids from 0 to 96 h, total opioid consumption through 96 h, and the area-under-the-curve of the numerical rating scale pain score for the first week. The 147 patients were randomized. During the first 96 h, vocacapsaicin (0.30 mg/ml) reduced pain at rest by 33% versus placebo (primary endpoint, 95% CI [10%, 52%], effect size [Cohen's d] = 0.61, P = 0.005). Of patients receiving vocacapsaicin (0.30 mg/ml), 26% did not require postoperative opioids for analgesia (P = 0.025) versus 5% of patients receiving placebo. Vocacapsaicin (0.30 mg/ml) reduced opioid consumption over the first 96 h by 50% versus placebo (95% CI [26%, 67%], effect size = 0.76, P = 0.002). Vocacapsaicin (0.30 mg/ml) reduced pain over the first week by 37% versus placebo (95% CI [12%, 57%], effect size = 0.62, P = 0.004). The treatment effect persisted for at least 2 weeks. All study endpoints showed an administered concentration-versus-response relationship. Vocacapsaicin was well tolerated with no differences between groups in any safety parameter. A single, local administration of vocacapsaicin during surgery reduced pain and opioid consumption for at least 96 h after surgery compared to control.

Impact of Flaxseed Oil Supplementation on Tobacco Dependence, Craving, and Haematological Parameters in Tobacco-Dependent Subjects.

Background Tobacco is prevalently used in smoking or smokeless forms and remains a major public health concern worldwide, with its adverse effects on overall health. Omega-3 fatty acid (FA) has shown its promising effects in various health conditions. Objective The purpose of this study was to evaluate the effect of flaxseed oil (omega-3 supplementation) on tobacco dependence, craving, withdrawal symptoms, and haematological parameters in tobacco users. Methods In this randomised, single-blind, placebo-controlled study, 104 tobacco users (54 in the omega-3 group and 50 in the placebo group) were supplemented with 10 ml of food-grade flaxseed oil and 10 ml of placebo for six months, respectively. Their demographics, frequency of daily tobacco use, tobacco dependence, tobacco craving, tobacco withdrawal symptoms, and complete blood count (CBC) were assessed at baseline (before intervention) and after a six-month intervention. Results The demographic characteristics of the two groups were similar except for gender at baseline. There were 50 males and four females in the omega-3 group, while there were 42 males and eight females in the placebo group. After a six-month flaxseed oil intervention, BMI values showed a significant reduction (p = 0.0081) in the omega-3 group when compared to baseline; however, CBC parameters did not show any significant changes when comparing baseline to follow-up values. On the contrary, haemoglobin and red blood cells (RBCs) showed significant changes when comparing the follow-ups of the omega-3 group with the placebo group, indicating p = 0.0016 and p = 0.0163, respectively. Also, omega-3 effectively decreased daily tobacco use frequency (p<0.0001), tobacco dependence (p<0.0001), and craving (p<0.0001). Conclusion Supplementation of 10 ml of flaxseed oil per day (omega-3 FA) for six months significantly reduced tobacco dependence and cravings. Additionally, the flaxseed oil supplementation effectively reduced the frequency of daily tobacco intake and modulated tobacco withdrawal symptoms. Thus, our results suggest that flaxseed oil supplementation is a useful adjunct for tobacco users who intend to quit tobacco use.

Effect of patisiran on stroke volume in hereditary transthyretin-mediated amyloidosis: insights from pressure-volume analysis of the APOLLO study.

Transthyretin-mediated (ATTR) amyloidosis is caused by deposition of transthyretin protein fibrils in the heart, nerves, and other organs. Patisiran, an RNA interference therapeutic that inhibits hepatic synthesis of transthyretin, was approved for the treatment of hereditary ATTR amyloidosis with polyneuropathy based on the phase 3 APOLLO study. We use left ventricular (LV) stroke volume (SV) to quantify LV function overtime and non-invasive pressure-volume techniques to delineate the effects of patisiran on LV mechanics in the pre-specified cardiac subpopulation of the APOLLO study. Left ventricular SV was assessed by transthoracic echocardiography at baseline, and after 9 and 18 months of therapy. To determine the mechanisms underlying changes in LV SV, non-invasive pressure-volume parameters, including the end-systolic and end-diastolic pressure-volume relationship, were derived using single beat techniques. At baseline, the mean SV was 51 ± 14ml. At 9months, the least-squares mean change in SV was -0.3 ± 1.2ml for patisiran and -5.4 ± 1.9ml for placebo (p= 0.021). At 18 months, the least-squares mean change in SV was -1.7 ± 1.3ml for patisiran and - 8.1 ± 2.3ml for placebo (p= 0.016). Decline in LV SV was driven by diminished LV capacitance in placebo relative to patisiran. Patisiran may delay progression of LV chamber dysfunction starting at 9months of therapy. These data elucidate the mechanisms by which transthyretin-reducing therapies modulate progression of cardiac disease and need to be confirmed in ongoing phase 3 trials.

Substantivity of mouth-rinse formulations containing cetylpyridinium chloride and O-cymen-5-ol: a randomized-crossover trial

BackgroundThe efficacy of mouth-rinses strongly depends upon their substantivity. The use of natural and non-toxic products that avoid secondary effects is gaining interest in preventive dentistry. The purpose of this study was to evaluate the substantivity of two formulations of mouth-washing solutions based on cetylpyridinium (CPC) and O-cymen-5-ol.MethodsThis was a randomized, double-blind, crossover trial conducted at the Faculty of Medicine and Health Sciences of the University of Barcelona. Bacterial re-colonization was followed by live/dead (SYTOTM9 + propidium iodide) bacterial staining and measured by confocal laser scanning microscopy and fluorometry. Unstimulated saliva samples were collected from 16 healthy individuals at baseline saliva and then, at 15 min, 30 min and 1, 2, 3, and 4 h after the following mouth-rinses: (i) a single, 1-min mouth-rinse with 15 ml of placebo (negative control); (ii) a single, 1-min mouth-rinse with 15 ml of CPC (0.05%) ; (iii) a single, 1-min mouth-rinse with 15 ml of O-cymen-5-ol (0.09%); (iv) a single, 1-min mouth-rinse with 15 ml of CPC (0.05%) + O-cymen-5-ol (0.09%).ResultsProportion of dead bacteria was significantly higher for all mouthrinses during the first 15 min compared to baseline (CPC = 48.0 ± 13.9; 95% CI 40.98–56.99; p < 0.001, O-cymen-5-ol = 79.8 ± 21.0; 95% CI 67.71–91.90; p < 0.05, CPC + O-cymen-5-ol = 49.4 ± 14; 95% CI 40.98–56.99; p < 0.001 by fluorometry and 54.8 ± 23.0; 95% CI 41.50–68.06; p < 0.001, 76.3 ± 17.1; 95% CI 66.36–86.14; p < 0.001, 47.4 ± 11.9; 95% CI 40.49–54.30; p < 0.001 by confocal laser scanning microscopy, respectively). Nevertheless, after 4 h, CPC + O-cymen-5-ol was the only one that obtained significant values as measured by the two quantification methods used (80.3 ± 22.8; 95% CI 67.15–93.50; p < 0.05 and 81.4 ± 13.8; 95% CI 73.45–89.43; p < 0.05). The combined use of CPC + O-cymen-5-ol increased the substantivity of the mouthrinse with respect to mouthrinses prepared with either of the two active products alone.ConclusionThe synergistic interaction of CPC and O-cymen-5-ol prolongs their substantivity. The resulting formulation may be as effective as other antimicrobials, such as triclosan or chlorhexidine, but without their undesirable secondary effects. Thus, mouthrinsing products based on Combinations of CPC and O-cymen-5-ol may replace in the near future Triclosan and Chlorhexidine—based mouthrinses.

Effects of Early Empagliflozin Initiation on Diuresis and Kidney Function in Patients With Acute Decompensated Heart Failure (EMPAG-HF).

Effective diuretic regimens using loop diuretics in patients with acute decompensated heart failure are often limited by the development of worsening kidney function. Sodium-glucose cotransporter-2 inhibitors induce glucosuria and sodium excretion with nephroprotective effects in patients with stable heart failure but their role in acute decompensated heart failure is unclear. In this single-center, prospective, double-blind, placebo-controlled, randomized study, we randomly assigned patients with acute decompensated heart failure to empagliflozin 25 mg daily or placebo in addition to standard decongestive treatments that included loop diuretics. The primary end point was cumulative urine output over 5 days. Secondary end points included diuretic efficiency, dynamics in markers of kidney function and injury, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). Sixty patients were randomized within 12 hours of hospitalization for acute decompensated heart failure. Addition of empagliflozin daily to standard medical treatment of acute decompensated heart failure resulted in a 25% increase in cumulative urine output over 5 days (median 10.8 versus 8.7 L mL in placebo, group difference estimation 2.2 L [95% CI, 8.4 to 3.6]; P=0.003). Empagliflozin increased diuretic efficiency compared with placebo (14.1 mL urine per milligram furosemide equivalent [95% CI, 0.6-27.7]; P=0.041) without affecting markers of renal function (estimated glomerular filtration rate, 51±19 versus 54±17 mL/min per 1.73 m²; P=0.599) or injury (total urinary protein, 492±845 versus 503±847 mg/g creatinine; P=0.975; and urinary α1-microglobulin, 55.4±38.6 versus 31.3±33.6 mg/g creatinine; P=0.066) with more pronounced decrease in NT-proBNP in the empagliflozin group compared with placebo (-1861 versus -727.2 pg/mL after 5 days; quotient in slope, 0.89 [95% CI, 0.83-0.95]; P<0.001). There were no differences in the incidence of safety events between groups. Early addition of empagliflozin to standard diuretic therapy increases urine output without affecting renal function in patients with acute decompensated heart failure. URL: https://www. gov; Unique identifier: NCT04049045.

Randomized controlled trial assessing the impact of a combined treatment of insulin glargine and propylene glycol on the resolution of hyperketonemia and milk production in postpartum dairy cows

Multiple treatments for hyperketonemia have been studied, and although propylene glycol has been the most constantly reported as successful in mitigating the effects of this condition, a recent study showed that a subpopulation of cows affected by hyperketonemia and hypoglycemia could benefit from a combined treatment of propylene glycol and insulin glargine. The objective of the present study was to assess the effect of this combination on the time-to-hyperketonemia resolution, and on milk production following the initial treatment. A randomized controlled trial was conducted on 2 commercial farms on which postpartum exams were conducted twice a week. Cows naturally affected by both hyperketonemia [β-hydroxybutyrate (BHB) ≥ 1.4 mmol/L] and hypoglycemia (glucose <2.2 mmol/L) were enrolled and randomly assigned to receive 2 mL of placebo (physiological saline) subcutaneously (PBO), or to receive 2 mL of insulin glargine (200 IU) subcutaneously (INS). Cows in both groups also received 300 g of propylene glycol orally for 3 d. Time-to-hyperketonemia resolution (return to BHB <1.4 mmol/L) and daily milk production following the initial treatment were compared between groups using Cox proportional hazard and mixed linear regression models, respectively. A total of 248 cows between 1 and 30 d in milk (median = 16) were enrolled in the trial from January 2018 to February 2022. Cows were of first (32.3%; n = 80/248), second (32.3%; n = 80/248), or third or greater (35.4%; n = 88/248) parity. The overall time-to-hyperketonemia resolution was not different between treatments, but there was a 2-way interaction between treatment group and parity. Primiparous cows had a shorter time-to-resolution in the INS group than in the PBO group; no difference was observed between treatment groups for older cows. The overall milk production of cows in the INS group was 3.4 kg higher than cows in the PBO group during the 14 d after enrollment. There was a 2-way interaction between treatment group and parity. Primiparous cows in the INS group produced 5.3 kg more milk daily than primiparous cows in the PBO group; no effect of treatment was found for older cows. These results suggest that cows affected simultaneously by hyperketonemia and hypoglycemia benefited from a combined treatment of propylene glycol and insulin glargine to improve subsequent milk production and that the effect primarily came from the positive effect in primiparous cows. Time-to-hyperketonemia resolution was also improved in primiparous cows but not in older cows.

A Randomized Controlled Pilot Study of Topical Ropivacaine for Prevention of Post-POEM Pain.

Background and AimsAlthough usually mild to moderate in severity, postoperative pain after peroral endoscopic myotomy (POEM) is common. There are no studies that have addressed minimizing postoperative pain in patients undergoing POEM for achalasia. We hypothesized that intraoperative topical intra-tunnel irrigation with ropivacaine would result in a significant reduction in pain scores in the postoperative period.MethodsA double-blind, randomized, placebo-controlled trial was conducted at the Kingston Health Sciences Center. Patients received either 30 mL of 0.2% ropivacaine or 30 mL of placebo irrigated topically into the POEM tunnel after completing the myotomy and prior to closing the mucosal incision. The primary outcome was pain post-POEM at 6 h assessed by the Numeric Rating Scale (NRS). Secondary objectives included assessing pain score at 0.5, 1, 2, 4 h post-POEM and on discharge, Quality of Recovery (QoR-15) scores at discharge, narcotic requirement, adverse events, and patients’ willingness to have the procedure done on an outpatient basis.ResultsA total of 20 patients were enrolled. For the primary outcome of pain post-POEM at 6 h, the NRS was 1.1 in the placebo group and 2.4 in the ropivacaine group (95% CI of the difference: −3.2 to 0.6, P = 0.171). No statistical difference was seen in the pain scores. Overall usage of post-procedural narcotics was low with no differences between the two groups. Fifty percent of patients in both groups were willing to have the procedure done as an outpatient.ConclusionThe addition of intra-procedural tunnel irrigation with 30 mL 0.2% ropivacaine did not lead to reduced post-POEM pain.

Inmunocastración con Vacunación en Contra del Factor Liberador de Gonadotropinas (GnRF) Sobre el Comportamiento Productivo de Carnerillos

The objective of this study was to investigate the immunocastration using against gonadotropin-releasing factor (GnRF) with Bopriva® (Zoetis) on the performance of production variables, meat quality, docility, and scrotal circumference in young rams, from Sheep production center “Tupac Amaru”, Junin region, Perú. A total of 60 animals were divided into four treatments: T1, T2, and T3 with 0.50 mL, 0.75 mL, and 1.0 mL of doses with Bopriva®, respectively, and T4 (control - 1.0 mL of placebo (distilled water)), with fifteen animals in each. The variables were measured every 15 days for three months (September to November 2018). Datasets were assessed by one-way ANOVA and subsequent posthoc Tukey´s test to detect significant differences among treatments. The results indicated differences found between treatments with the immunocastration compared with non-castrated animals for final weight, carcass weight and performance, scrotal circumference, and docility. Growth performance and meat quality characteristics were not adversely affected by immunocastration. Likewise, immunocastration with Bopriva proved to be effective to stop scrotal development and consequently reduces the sexual and aggressive behavior of young rams. The dose of 0.5 mL seems to be adequate due showed better performance for most variables compared to other treatments

Effectiveness of Pre-Procedural Rinsing with Essential Oils-Based Mouthrinse to Reduce Aerosol Contamination of Periodontitis Patients

This research aims to evaluate the effectiveness of pre-procedural rinsing using essential oils-mouthwash (Listerine®) in reducing bioaerosol contamination in a dental clinic. Thirty (30) subjects who consisted of those receiving treatment for periodontitis problems were randomly assigned to rinse with either 20 mL of Listerine® or 20 mL of placebo as control rinse. Every subject was instructed to gargle using the rinse for 1 min. Microbial samples of environmental air and saliva were collected before and after the rinse. All samples were further analyzed for total plate counts to measure the microbial level. Rinsing using Listerine® showed significant reduction in the level of microbial load in saliva compared to the control mouthrinses. Analysis done at three defined distance intervals from the operating site showed the level of bioaerosol contamination was highest at distance nearest to the treatment point of 1 ft. Based on counts of cfu, there was higher presence of microbial contaminant in bioaerosols of the control-rinsed group compared to the test-rinsed group using Listerine®. Therefore, it can be concluded that rinsing using Listerine® was effective towards reducing the microorganisms in saliva and oral cavity in general.

Intrauterine Instillation of Tranexamic Acid in Hysteroscopic Myomectomy: A Double-Blind, Placebo-Controlled, Parallel-Group Randomized Clinical Trial

To evaluate the hemostatic effect of intrauterine instillation of tranexamic acid (TXA) with the distention medium during hysteroscopic myomectomy. Prospective, parallel-group, double-blind, placebo-controlled randomized clinical trial. Early Cancer Detection Unit in Ain Shams University Maternity Hospital, Cairo, Egypt. Eighty women with type 0 or I submucous myoma undergoing hysteroscopic myomectomy using unipolar resectoscope. The participants were randomly assigned to receive either 1 g of TXA for every 1000 mL of the distending medium (intervention group) or 10 mL of placebo (10 mL of 1.5% glycine) in the same form inside every 1000 mL of the distention medium. The primary outcome was a change in hemoglobin level 24 hours after surgery compared with preoperative values, and the secondary outcomes were the surgeon's rating of intraoperative bleeding and the quality of operative view, the duration of surgery, the volume of injected media, intraoperative complications, and the completion of myomectomy in 1 procedure. The mean difference in hemoglobin level was 1.11 ±.58 g/dL in the TXA group and 1.46 ± 0.61 g/dL in the placebo group (p = .015). The quality of hysteroscopic view was better in the TXA group (p = .001), with good operative view in 23 (60.5%) cases in TXA vs 8 (20.5%) in the placebo group. The surgeon's rating of bleeding as excessive was reported in 1 (2.6%) case in the TXA group and in 9 (23.1%) cases in the placebo group. There was no difference between the groups regarding the duration of surgery, the volume of injected media, completion of myoma resection in 1 session, and intraoperative complications. Three cases of uterine perforation with the thermal loop were reported, and all were associated with poor operative field in the placebo group. Intrauterine instillation of TXA with the distention medium during hysteroscopic myomectomy resulted in a statistically significant decrease in hemoglobin level 24 hours after surgery, albeit with minimal clinical significance. TXA resulted in better visualization of the field throughout the procedure.

Ingesting a Bitter Solution: The Sweet Touch to Increasing Short-Term Cycling Performance

Purpose: The authors investigated the potential benefit of ingesting 2mM of quinine (bitter tastant) on a 3000-m cycling time-trial (TT) performance. Methods: Nine well-trained male cyclists (maximal aerobic power: 386 [38]W) performed a maximal incremental cycling ergometer test, three 3000-m familiarization TTs, and four 3000-m intervention TTs (∼4min) on consecutive days. The 4 interventions were (1)25mL of placebo, (2)a 25-mL sweet solution, and (3) and (4)repeat 25mL of 2-mM quinine solutions (Bitter1 and Bitter2), 30 s before each trial. Participants self-selected their gears and were only aware of distance covered. Results: Overall mean power output for the full 3000m was similar for all 4 conditions: placebo, 348 (45)W; sweet, 355 (47)W; Bitter1, 354 (47)W; and Bitter2, 355 (48)W. However, quinine administration in Bitter1 and Bitter2 increased power output during the first kilometer by 15 ± 11W and 21 ± 10W (mean ± 90% confidence limits), respectively, over placebo, followed by a decay of 34 ± 32W during Bitter1 and Bitter2 during the second kilometer. Bitter2 also induced a 11 ± 13-W increase during the first kilometer compared with the sweet condition. Conclusions: Ingesting 2mM of quinine can improve cycling performance during the first one-third of a 3000-m TT and could be used for sporting events lasting ∼80s to potentially improve overall performance.

Effect of preoperative bicarbonate infusion on maternal and perinatal outcomes of obstructed labour in Mbale Regional Referral Hospital: a study protocol for a randomised controlled trial

IntroductionTo improve maternal and fetal outcomes among patients with obstructed labour (OL) in low-resource settings, the associated electrolyte and metabolic derangements must be adequately corrected. Oral fluid intake during labour...

Comparison of Postoperative Analgesia Following Epidural Bupivacaine and Epidural Bupivacaine with Verapamil in Orthopaedic Lower Limb Surgeries

Comparison of Postoperative Analgesia Following Epidural Bupivacaine and Epidural Bupivacaine with Verapamil in Orthopaedic Lower Limb Surgeries

Liposomal bupivacaine efficacy for postoperative pain following posterior vaginal surgery: a randomized, double-blind, placebo-controlled trial

Effective postoperative pain management is a crucial component of recovery following surgery. Narcotics are a cornerstone of postoperative analgesia, but can require a redosing requirement, encompass a lengthy list of side effects and adverse reaction risks, as well as carry a dependency potential. The national focus on decreasing opioid use has directly impacted postoperative pain management. Previous studies have reported the beneficial use of a single intraoperative injection of extended-release liposomal bupivacaine in postoperative pain management, however the same results have not been extensively studied in the urogynecology literature. We sought to evaluate cumulative postoperative vaginalpain on days 1 and 3 after posterior vaginal wall surgery comparing studymedication (extended-release liposomal bupivacaine) to placebo (saline). Secondary aims were to evaluate vaginal pain on postoperative day 7 and total morphine-equivalent narcotic usage on days 1, 3, and7. This is a randomized, double-blinded, placebo-controlled trial with 100 subjects recruited from Walter Reed National Military Medical Center urogynecology clinic. All subjects were age >18 years and scheduled for surgery involving the posterior vaginal wall or muscularis (including posterior colporrhaphy, colpocleisis, sphincteroplasty, perineorrhaphy), excluding those with regular narcotic usage or concurrent pain management requiring the use of epidural anesthesia. A sample size of 96 patients was calculated. Subjects were randomized to receive either 20 mL of extended-release liposomal bupivacaine (Exparel) (Pacira Pharmaceuticals Inc, Parsippany, NJ) or 20 mL of placebo (saline) at the end of surgery. Concealed syringes were used and injected immediately postoperative into the lateral vaginal wall/levator muscle area and perineal body. In-house morphine-equivalent narcotic usage was recorded along with the postoperative day 1 pain scores. Patients were contacted by telephone on postoperative days 3 and 7. Vaginal pain scores were evaluated using the Defense and Veterans Pain Rating Scale, cumulatively and on days 1, 3, and 7. Overall morphine-equivalent narcotics were compared between the 2 groups. From October 2014 through August 2017, 100 patients were enrolled and completed the study; 49 (49%) of the patients were randomized to the study group and 51 (51%) were in the placebo group. There was no significant difference between vaginal pain scores between the study group and the placebo group (postoperative day 1: study medication median score 1 [interquartile range 0-3], placebo median score 1 [interquartile range 0-3] [P= .59]; postoperative day 3: study medication median score 2 [interquartile range 0-3], placebo median score 1 [interquartile range 0-3] [P= .20]; postoperative day 7: study medication median score 3 [interquartile range 1-4], placebo median score 1.5 [interquartile range 0-3] [P= .06]). Cumulative pain scores postoperative day 1-7 were also not significant (study medication median score 6 [interquartile range 1-10], placebo median score 4 [interquartile range 1-8] [P= .14]). Multivariate model for the presence of vaginal pain was calculated and after controlling for body mass index, age, and combined laparoscopy surgery, there was no significant difference between the study and the placebo groups (P= .62). There was no statistically significant difference in morphine equivalents for the 2 groups: study medication 112.5 (interquartile range 45-207) and placebo 101.5 (interquartile range 37.5-195), P= .81. The use of extended-release liposomal bupivacaine in posterior vaginal wall surgeries, injected into the lateral posterior vaginal wall and perineal body, does not provide a significant decrease in postoperative pain or decrease narcotic medication usage when compared to saline.

The Benefit of Fentanyl in Effective Sedation and Quality of Upper Endoscopy: A Double-Blinded Randomized Trial of Fentanyl Added to Midazolam Versus Midazolam Alone for Sedation.

AimsOur goals were to compare the effect of adding fentanyl to midazolam in a double-blinded, randomized, placebo-controlled trial and determine if fentanyl enhances sedation, increases adverse events or effects time of the procedure or discharge.MethodsPatients 18 to 65 years scheduled for outpatient upper endoscopy were eligible for the study. Patients were randomized to receive either 100 mcg/2 mL of Fentanyl or 2 mL of placebo IV with a double-blinded protocol. All patients received 2 mg of intravenous midazolam initially. Additional midazolam could be given to achieve adequate sedation.ResultsThere were 68 patients randomized to the Fentanyl group and 69 patients to the placebo group. The mean dose of midazolam was 4.0 mg for the Fentanyl group and 5.2 mg for placebo group (P=0.003). Both endoscopist and nurse independently rated sedation to be better in the fentanyl group (P=0001). The patient did not perceive any difference in sedation (P=0.4). Procedure time was significantly shorter in the Fentanyl group (8.5 versus 11.1 minutes, P=0.001), with no difference in the discharge time. There was significantly less retching observed in patients in the fentanyl group (P<0.001). There were no major complications.ConclusionsEndoscopists and nurses found adding fentanyl significantly improved sedation, led to a shorter procedure time, and allowed for less midazolam to be used per case. It did not affect the patient experience of sedation and was safe. Fentanyl use for routine outpatient upper endoscopy should be considered as a safe option to improve procedural sedation.NCT:01514695 (www.clinicaltrials.gov)Accepted as an abstract for the Canadian Digestive Diseases Week meeting in February 2014.

Efficacy and tolerance of early administration of tranexamic acid in patients with cirrhosis presenting with acute upper gastrointestinal bleeding: a study protocol for a multicentre, randomised, double-blind, placebo-controlled trial (the EXARHOSE study)

IntroductionThe management of acute upper gastrointestinal bleeding (UGIB) is challenging in patients with cirrhosis, as it is responsible for severe complications and high mortality rates. Tranexamic acid (TXA) may help...

Current role of low molecular weight heparin in the treatment of acute ischemic stroke

Background: Nevertheless, several studies of LMWH in acute ischemic stroke have been neutral with regard to their primary outcomes, and it remains unclear whether these drugs should be used routinely or not. Our present trial endeavors to study the efficacy of LMWH (low and high dose dalteparin) in patients with progressive ischemic stroke in terms of morbidity and mortality as compared to control group and to compare it with AS+CLOP, with respect to these event rates, at the end of treatment.Methods: Our study was performed on 38 patients of acute ischemic stroke admitted to LLR and associated Hospitals, G. S. V. M. Medical College, Kanpur and who were assigned randomly to any of the four treatment groups (0.4ml dalteparin, 0.8ml of dalteparin, O ml of placebo and aspirin +clopidogrel 150+75 mg). The standard error of proportion method and Chi square test was applied.Results: 70% of patients in group I, 62.5% in Group II and 60% Group III presented with stroke in evolution at presentation as compared to only 30% in the placebo group. 75% of patients in group I, 66.66% in group II, 50% in Group III and 33.34% in group IV had a complete recovery. 25% of patients in Group-I, 33.34% in Group-II, 50% in Group III and 66.66% in Group-IV had an incomplete recovery.Conclusions: There is no significant reduction in the mortality and morbidity amongst LMWH groups at the end of treatment and end of trial as compared to the AS+CLOP, or placebo group or even amongst the low and high dose LMWH groups.

A Randomized Double-Blind Trial Comparing the Effect on Pain of an Oral Sucrose Solution vs. Placebo in Children 1 to 3 Months Old Undergoing Simple Venipuncture

BackgroundFew clinical trials evaluating the efficacy of oral sweet solutions for procedures in the emergency department (ED) have been published. ObjectivesTo compare the efficacy of an oral sucrose solution vs. a placebo in reducing pain in infants undergoing venipuncture without cannulation. MethodsA randomized, double-blinded clinical trial was conducted in a pediatric ED. Infants 1 to 3 months old were randomly allocated to receive 2 mL of 88% sucrose or 2 mL of placebo, 2 min prior to venipuncture. The outcome measures were the difference in pain levels as assessed by the Face, Legs, Activity, Cry and Consolability Pain Scale (FLACC) and Neonatal Infant Pain Scale (NIPS) scores, crying time, and variations in heart rate. ResultsEighty-two participants were recruited. Data were analyzed for 38 patients from each group (excluding protocol deviations). The mean difference in FLACC scores 1 min post venipuncture compared with baseline was 2.84 ± .64 (sucrose) vs. 2.71 ± .62 (placebo) (p = 0.98). For the NIPS score, it was 2.32 ± .47 (sucrose) vs. 1.63 ± .49 (placebo) (p = 0.60). The difference in the median crying time was not statistically significant between the two groups: 63.0 ± 3 (sucrose) vs. 48.5 ± 5 s (placebo) (p = 0.17). No significant difference was found in participants' heart rates 1 min post venipuncture compared with baseline: 33 ± 6 (sucrose) vs. 24 ± 5 beats per minute (placebo) (p = 0.44). ConclusionsIn infants 1 to 3 months of age undergoing simple venipuncture, administration of an oral sweet solution did not statistically decrease pain scores, and participants' heart rate variations and crying time were not significantly changed.

Analgesic Effects of Intravenous Acetaminophen vs Placebo for Endoscopic Sinus Surgery and Postoperative Pain

Intravenous acetaminophen is a commonly prescribed analgesic for the prevention and treatment of postsurgical pain. Its efficacy in the context of endoscopic sinus surgery (ESS) has yielded mixed results. To compare the efficacy of perioperative intravenous acetaminophen (IVAPAP) with that of placebo in improving early postoperative pain after endoscopic sinus surgery (ESS). A prospective, randomized clinical trial including 62 patients undergoing ESS for chronic rhinosinusitis in a single tertiary referral hospital. Participants were randomized to receive 1 g of IVAPAP or 100 mL of placebo consisting of saline infusions immediately before the start of surgery and 4 hours after the initial dose. The primary outcome was postoperative pain measured by visual analog scale (VAS) scores up to 24 hours after surgery by blinded observers. Secondary endpoints included postoperative opioid (intravenous and oral) use and adverse events in the 24-hour postoperative period. Of the 62 enrolled adult participants, 60 were randomized (31 to IVAPAP intervention and 29 to placebo). The mean (SD) age of participants was 53.7 (14.7) years and 35 (58%) of the participants were men and 25 (42%) were women. Within the first hour, mean pain scores were reduced in the IVAPAP group compared with the control group, reaching a maximum difference of 7.7 mm on a VAS scale favoring the treatment group with a true difference possibly as high as 22 mm, and the data are compatible with a clinically meaningful difference. At 12- and 24-hours, average pain scores were less in the placebo group and the data are compatible with a clinically meaningful difference of 5.8 (-5.2 to 16.8) and 8.2 (-1.9 to 18.4), respectively, favoring the placebo group. However, at all time points the CIs included the null value and were wide, thus preventing definitive conclusions. Inspection of the secondary outcomes favored IVAPAP, but the wide range of the CIs and inclusion of the null value prevent definitive conclusions. The results of this study are inconclusive. The data suggest that perioperative intravenous acetaminophen may reduce immediate postoperative pain and opioid requirements compared with placebo and these differences could be clinically meaningful. Unfortunately, the imprecision of the estimates prevents definitive conclusion. Use of IVAPAP does not seem to increase adverse events. clinicaltrials.gov Identifier: NCT01608308.

No Effect of Acute Beetroot Juice Supplementation on Moderate and Vigorous Intensity Aerobic Exercise

Nitric oxide (NO) plays a critical role in regulating blood flow to skeletal muscle. NO production in humans is 1) oxygen-dependent via NO-synthases that convert L-arginine to NO and 2) oxygen-independent via the nitrate-nitrite-NO pathway. The latter pathway is largely dependent on the intake of nitrate-rich foods, such as beetroot and beetroot juice supplements (BR). Consumption of BR has been shown to lower resting blood pressure and the volume of oxygen (VO2) required to perform submaximal aerobic exercise. PURPOSE: The purpose of the present study was to investigate the acute effect of a low dose of BR compared to placebo (PL) during moderate and vigorous intensity aerobic exercise. METHODS: Ten female division-3 collegiate club-level volleyball players (mean ± SD: age = 19.3 ± 1.3 yr, VO2peak = 37.4 ± 3.3 ml·kg-1·min-1) completed three exercise trials consisting of an initial graded test to exhaustion and two performance trials on a motorized treadmill. For the performance trials, participants consumed either 60 mL of BR or PL, three hours prior to five minutes of walking/jogging at 45%, 65%, and 85% of volume of oxygen uptake reserve (VO2R). RESULTS: Separate two-way repeated measures ANOVAs were run to determine the effect of treatment (BR or PL) and exercise intensity (45%, 65%, and 85% VO2R) on VO2, heart rate (HR), and rating of perceived exertion (RPE). Paired samples t-tests were run to compare differences between resting systolic (SBP) and diastolic blood pressure (DBP) between treatments. All data are reported mean ± standard deviation with statistical significance accepted at p < 0.05. There were no statistically significant interactions between treatment and exercise intensity for VO2, HR, or RPE. The main effect of treatment was not statistically significantly different for VO2 (BR: 19.9 ± 6.6 vs. PL: 20.4 ± 6.5 ml·kg-1·min-1; p = .360), HR (BR: 131.3 ± 25.8 vs. PL: 135.4 ± 25.3 beats·min-1; p = .172), or RPE (BR: 9.8 ± 2.2 vs. PL: 9.9 ± 2.4; p = .504). There were no statistically significant differences in resting SBP (BR: 110.6 ± 6.8 vs. PL: 112.7 ± 8.0; p = .166) or DBP (BR: 70.8 ± 5.5 vs. PL: 73.3 ± 6.6; p = .275) between treatments. CONCLUSIONS: These results suggest that a low dose of BR taken three hours prior to moderate and vigorous intensity aerobic exercise has no effect on VO2, HR, RPE, or resting SBP and DBP.