Double-blind Placebo-controlled Study Research Articles

Objective randomised blinded investigation of therapeutic ablation versus cardioversion for persistent atrial fibrillation- outcomes of the feasibility

Abstract Background Patients with persistent atrial fibrillation (pers.AF) commonly undergo catheter ablation (CA) for symptom relief and improved quality of life(QoL). However,the benefits of CA compared to DC cardioversion (DCCV) or medical therapy lack substantial evidence from blinded randomized trials. Purpose Conducting such a large-scale trial presents substantial challenges in terms of recruitment, maintaining blinding, and implementation.To address this, we conducted a pilot study prior to a definitive larger study. Methods This feasibility trial is a single-centre, prospective, randomised, double-blinded placebo control study. Patients with early pers AF (<2 years) eligible for pulmonary vein isolation (PVI) or DCCV were enrolled. Twenty patients were recruited, accounting for 10% of the proposed larger trial based on power calculation. The intervention arm (PVI + DCCV) and placebo arm (Placebo + DCCV) were randomised in a 1:1 manner after ultrasound-guided vascular access with local anaesthetic and deep sedation (Midazolam + opioid). All procedures were performed as day cases on uninterrupted oral anticoagulation. Phrenic nerve pacing was performed in the Placebo group, mimicking lab interactions and fluoroscopy system movements. Implantable loop monitors were inserted immediately after heparin reversal and groin sheath removal. A 6-week(wk) blanking period was observed post-procedure. Blinding was assessed using Bang's blinding index (BI) for both patients and medical staff and a successful blinding is considered BI between -0.2 to 0.2. Health-related quality of life (HRQoL) was evaluated using SF12, EQ5D-5L, and AF PROMS. The study obtained ethical approval (REC ref 19/LO/0775),adhered to the principles of the Declaration of Helsinki,and obtained written informed consent from all participants. Results A remarkable 92% of patients approached, expressed a willingness to participate in the study. Procedure time and time to discharge were similar between groups. The study successfully achieved blinding among the patients at day0 (BI = PVI-0.2 vs placebo- 0) and was maintained throughout the 6-wk and 3M follow-up, among the patients as well as clinical staff. HRQoL improved in the active group in terms of AF PROMS [Improved difference from baseline PVI 23 (±22); vs Placebo 2 (±10), p=<0.001 and SF-12 mental component (MCS) at 12M (PVI 11.8 (±11) vs placebo 8.54(±11.5), p= 0.017). Over a follow up period of 12M, there was a trend towards greater recurrence (60% vs 30%; p=0.07) and repeat procedures (70% vs 40%; p=0.4) in the placebo group. Conclusion: Performing a blinded placebo-controlled interventional study to assess the efficacy of PVI is feasible and high recruitment rates are achievable. CA appears to result in better arrhythmic and QoL outcomes;a full-scale follow-on study will assess the true efficacy of CA in patients with early pers.AF and allow consideration of whether there is a role for DCCV in many patients.

Laparoscopic-Guided Transversus Abdominis Plane (TAP) Block Combined with Port-Site Infiltration (PSI) for Laparoscopic Sleeve Gastrectomy in an ERABS Pathway: A Randomized, Prospective, Double-Blind, Placebo-Controlled Trial.

Patients undergoing laparoscopic sleeve gastrectomy (LSG) commonly experience moderate to severe postoperative pain. We conducted a randomized, prospective double-blind placebo-controlled study to evaluate the analgesic effect of laparoscopic-guided TAP (LG-TAP) block after LSG in a high-volume bariatric center, applying an enhanced recovery after bariatric surgery (ERABS) pathway. One hundred ten patients were randomly allocated to receive LG-TAP block with local anesthetic (LA) or saline solution (placebo), both combined with port-site infiltration with LA (LA-PSI). Primary outcome was pain score measured in post-anesthesia care unit (PACU) and at 6, 12, and 24 h after surgery. Secondary outcomes included postoperative nausea and/or vomiting (PONV), analgesic requirement, time to walking, time to flatus, length of hospital stay (LOS), and surgical complications. No significant differences were observed between LG-TAP and placebo groups in postoperative analgesia, with a median (IQR) NRS of 2 (4.75-0) vs. 2 (5.25-0) in PACU, 5.5 (7-3) vs. 6 (7-4) at 6 h, 2 (6-0) vs. 3 (5.25-1.75) at 12 h, and 2 (3.75-0) vs. 1 (2-0) at 24 h; all p > 0.05. A significant difference was found in PONV in PACU (LG-TAP, 46%; placebo, 25%, p-value, 0.019) and at 6 h postoperatively (LG-TAP, 69%, placebo, 41%, p-value, 0.003). No differences were observed as regards other secondary outcomes. Our results suggest that LG-TAP block is not related to more effective postoperative analgesia compared to placebo when LA-PSI is performed.

In the article “Double blind randomized placebocontrolled study of the efficacy and safety of proroxan in the complex therapy of generalized anxiety disorder”

In the article “Double blind randomized placebocontrolled study of the efficacy and safety of proroxan in the complex therapy of generalized anxiety disorder”

Supplementation with selenium and coenzyme Q10 in an elderly Swedish population low in selenium — positive effects on thyroid hormones, cardiovascular mortality, and quality of life

BackgroundSelenium-dependent deiodinases play a central role in thyroid hormone regulation and metabolism. In many European countries, insufficient selenium intake may consequently lead to adverse effects on thyroid function. In this randomised placebo-controlled double-blind study, we examined the effect of supplementation with selenium and coenzyme Q10 on thyroid hormonal status, cardiovascular (CV) mortality and health-related quality of life (Hr-QoL).MethodsFree T3, free T4, reverse T3, and TSH were determined in 414 individuals at baseline, and the effect of selenium yeast (200 µg/day) and coenzyme Q10 (200 mg/day) supplementation on hormone concentrations, CV mortality and Hr-QoL was evaluated after 48 months using Short Form 36 (SF-36). Pre-intervention plasma selenium was low, mean 67 µg/L, corresponding to an estimated intake of 35 µg/day. Changes in concentrations of thyroid hormones following the intervention were assessed using T-tests, repeated measures of variance, and ANCOVA analyses.ResultsIn the total population, the group with the lowest selenium concentration at baseline presented with significantly higher levels of TSH and lower levels of fT3 as compared to subjects with the highest selenium concentration. Supplementation with selenium and coenzyme Q10 for 4 years significantly increased fT3 and rT3, decreased fT4, and diminished the increase in TSH levels compared with placebo treatment (p = 0.03, all). In the placebo group, TSH and fT4 values above the median were associated with an increase in 10-year CV mortality, as compared with the mortality rate among those with TSH and fT4 below the median (p < 0.04, both), with no difference in mortality rate according to TSH and fT4 levels in the active intervention group. Similarly, TSH > median and fT3 < median were associated with a decline in mental Hr-QoL measures vs. TSH < and fT3 > median in the placebo group during 4 years of follow-up, but this was wiped out in the active group.ConclusionsSupplementation with selenium and coenzyme Q10 had a beneficial effect on thyroid hormones with respect to CV mortality and Hr-QoL outcomes. The initial deficient selenium status was associated with an impaired thyroid function and the changes in thyroid hormone levels can be explained by increased activity of deiodinases. We conclude that a substantial part of the elderly study population might suffer from suboptimal thyroidal function with adverse clinical implications due to selenium deficiency.Trial registrationThis study was registered at ClinicalTrials.gov and has the identifier NCT01443780. Since it was not mandatory to register at the time the study began, the study has been registered retrospectively.

The effect of non-pooled multi-donor faecal microbiota transplantation for inducing clinical remission in patients with chronic pouchitis: Results from a multicentre randomised double-blinded placebo-controlled trial (MicroPouch).

To investigate if treatment with non-pooled multi-donor faecal microbiota transplantation (FMT) for four weeks was superior to placebo to induce clinical remission in patients with chronic pouchitis. The study was a randomised double-blinded placebo-controlled study with a 4-week intervention period and 12-month follow-up. Eligible patients with chronic pouchitis were recruited from five Danish hospitals. Participants were randomised to non-pooled multi-donor FMT derived from four faecal donors, or placebo. Treatment was delivered daily by enema for two weeks followed by every second day for two weeks. Disease severity was accessed at inclusion and 30-day follow-up, using the Pouchitis Disease Activity Index (PDAI); PDAI <7 was considered equivalent to clinical remission. Faecal samples from participants and donors were analysed by shotgun metagenomic sequencing. Inclusion was stopped after inclusion of 30 participants who were randomised 1:1 for treatment with FMT or placebo. There was no difference in participants achieving clinical remission between the two groups at 30-day follow-up, relative risk 1.0 (95%CI(0.55;1.81)). Treatment with FMT resulted in a clinically relevant increase in adverse events compared to placebo, incidence rate ratio 1.67 (95%CI(1.10;2.52)); no serious adverse events within either group. Faecal microbiota transplantation statistically significantly increased the similarity of participant faecal microbiome to the faecal donor microbiome at 30-days follow-up (p=0.01), which was not seen after placebo. Non-pooled multi-donor FMT was comparable to placebo in inducing clinical remission in patients with chronic pouchitis but showed a clinically relevant increase in adverse events compared to placebo.

Comparison Between Efficacy of Oral Melatonin and Oral L-theanine in Improving Sleep in Cancer Patients Suffering From Insomnia: A Randomised Double-blinded Placebo-controlled Study

Objectives: The primary objective was to compare the hypnotic efficacy of oral melatonin, oral L-theanine, and placebo in improving sleep in cancer patients with insomnia by the Athens Insomnia Scale (AIS). The secondary objective was to know the prevalence of insomnia in patients with cancer. Materials and Methods: A prospective, double-blinded, placebo-controlled study was conducted after obtaining Institutional Ethics Committee approval. One hundred and twenty patients were randomly assigned to either Group A (melatonin), Group B (L-theanine), or Group C (placebo). They were instructed to take the tablets for 14 consecutive days, two h (hours) before bedtime, and evaluated with AIS on the 1st day, 7th day, and 14th day. Results: There were seven dropouts: Two in Group A, two in Group B, and three in Group C. Significant differences in favour of melatonin treatment were found. There were statistically significant improvements in insomnia in cancer patients on melatonin intake compared to L-theanine. L-theanine had statistically significant improvements in insomnia in comparison to placebo. The mean ± standard deviation AIS on day one in Group A was 14.82 ± 1.29; on day seven was 10.92 ± 1.12; and on day 14 was 5.00 ± 0.70. Similarly, in Group B, the mean ± standard deviation AIS was 15.39 ± 1.03, 13.05 ± 1.06, and 9.55 ± 1.01, and in Group C, the mean AIS was 14.92 ± 1.40, 14.54 ± 1.35 and 13.05 ± 1.61 on the 1st, 7th and 10th day, respectively. There was an improvement in sleep from 1 to 7 days, 7 days to 14 days, and 1 day to 14 days in all the groups (P &lt; 0.005). Conclusion: The hypnotic efficacy of oral melatonin 3 mg was better than oral L-theanine 200 mg in cancer patients having insomnia. Furthermore, L-theanine had a better hypnotic efficacy when compared to a placebo.

Effects of Low-Level Light Therapy on Resting-State Connectivity Following Moderate Traumatic Brain Injury: Secondary Analyses of a Double-blinded Placebo-controlled Study.

Background Low-level light therapy (LLLT) has been shown to modulate recovery in patients with traumatic brain injury (TBI). However, the impact of LLLT on the functional connectivity of the brain when at rest has not been well studied. Purpose To use functional MRI to assess the effect of LLLT on whole-brain resting-state functional connectivity (RSFC) in patients with moderate TBI at acute (within 1 week), subacute (2-3 weeks), and late-subacute (3 months) recovery phases. Materials and Methods This is a secondary analysis of a prospective single-site double-blinded sham-controlled study conducted in patients presenting to the emergency department with moderate TBI from November 2015 to July 2019. Participants were randomized for LLLT and sham treatment. The primary outcome of the study was to assess structural connectivity, and RSFC was collected as the secondary outcome. MRI was used to measure RSFC in 82 brain regions in participants during the three recovery phases. Healthy individuals who did not receive treatment were imaged at a single time point to provide control values. The Pearson correlation coefficient was estimated to assess the connectivity strength for each brain region pair, and estimates of the differences in Fisher z-transformed correlation coefficients (hereafter, z differences) were compared between recovery phases and treatment groups using a linear mixed-effects regression model. These analyses were repeated for all brain region pairs. False discovery rate (FDR)-adjusted P values were computed to account for multiple comparisons. Quantile mixed-effects models were constructed to quantify the association between the Rivermead Postconcussion Symptoms Questionnaire (RPQ) score, recovery phase, and treatment group. Results RSFC was evaluated in 17 LLLT-treated participants (median age, 50 years [IQR, 25-67 years]; nine female), 21 sham-treated participants (median age, 50 years [IQR, 43-59 years]; 11 female), and 23 healthy control participants (median age, 42 years [IQR, 32-54 years]; 13 male). Seven brain region pairs exhibited a greater change in connectivity in LLLT-treated participants than in sham-treated participants between the acute and subacute phases (range of z differences, 0.37 [95% CI: 0.20, 0.53] to 0.45 [95% CI: 0.24, 0.67]; FDR-adjusted P value range, .010-.047). Thirteen different brain region pairs showed an increase in connectivity in sham-treated participants between the subacute and late-subacute phases (range of z differences, 0.17 [95% CI: 0.09, 0.25] to 0.26 [95% CI: 0.14, 0.39]; FDR-adjusted P value range, .020-.047). There was no evidence of a difference in clinical outcomes between LLLT-treated and sham-treated participants (range of differences in medians, -3.54 [95% CI: -12.65, 5.57] to -0.59 [95% CI: -7.31, 8.49]; P value range, .44-.99), as measured according to RPQ scores. Conclusion Despite the small sample size, the change in RSFC from the acute to subacute phases of recovery was greater in LLLT-treated than sham-treated participants, suggesting that acute-phase LLLT may have an impact on resting-state neuronal circuits in the early recovery phase of moderate TBI. ClinicalTrials.gov Identifier: NCT02233413 © RSNA, 2024 Supplemental material is available for this article.

Safety Assessment of Streptococcus salivarius UBSS-01 in Rats and Double-Blind Placebo-Controlled Study in Healthy Individuals.

Streptococcus salivarius is a common, harmless, and prevalent member of the oral microbiota in humans. In the present study, the safety of S. salivarius UBSS-01 was evaluated using in silico methods and preclinical and clinical studies. In an acute toxicity study, rats were administered with 5g/kg (500 × 109CFU) S. salivarius UBSS-01. The changes in phenotypic behaviors and hematological, biochemical, electrolytes, and urine analyses were monitored. No toxicity was observed at 14days post-treatment. The no observable effects limit (NOEL) of S. salivarius UBSS-01 was >5g/kg in rats. In a 28-day repeat dose toxicity study, rats were administered S. salivarius UBSS-01 once daily at doses of 0.1, 0.5, and 1g/kg (10, 50, and 100 billion CFU/kg, respectively) body weight. S. salivarius UBSS-01 did not influence any of the hematology parameters and clinical chemistry parameters in plasma and serum samples after 28-day repeated administration. No structural abnormality was observed in the histological examination of organs. Whole genome analysis revealed the absence of virulence factors or genes that may transmit antibiotic resistance. In the double-blind study with 60 human participants (aged 18-60years), consumption of S. salivarius UBSS-01 for 30days was found to be safe and results were comparable with placebo treatment These findings indicate that S. salivarius UBSS-01 may be safe for human consumption.

Urban indoor gardening enhances immune regulation and diversifies skin microbiota — A placebo-controlled double-blinded intervention study

According to the hygiene and biodiversity hypotheses, frequent exposure to environmental microbiota, especially through soil contact, diversifies commensal microbiota, enhances immune modulation, and ultimately lowers the risk of immune-mediated diseases. Here we test the underlying assumption of the hygiene and biodiversity hypotheses by instructing volunteers to grow edible plants indoors during the winter season when natural exposure to environmental microbiota is low. The one-month randomized, placebo-controlled double-blind trial consisted of two treatments: participants received either microbially diverse growing medium or visually similar but microbially poor growing medium. Skin microbiota and a panel of seven immune markers were analyzed in the beginning of the trial and after one month. The diversity of five bacterial phyla (Bacteroidetes, Planctomycetes, Proteobacteria, Cyanobacteria, and Verrucomicrobia) and one class (Bacteroidia) increased on the skin of participants in the intervention group while no changes were observed in the placebo group. The number of nodes and edges in the co-occurrence networks of the skin bacteria increased on average three times more in the intervention group than in the placebo group. The plasma levels of the immunomodulatory cytokine interleukin 10 (IL-10) increased in the intervention group when compared with the placebo group. A similar trend was observed in the interleukin 17A (IL-17A) levels and in the IL-10:IL-17A ratios. Participants in both groups reported high satisfaction and adherence to the trial. The current study provides evidence in support of the core assumption of the hygiene and biodiversity hypotheses of immune-mediated diseases. Indoor urban gardening offers a meaningful and convenient approach for increasing year-round exposure to environmental microbiota, paving the way for other prophylactic practices that might help prevent immune-mediated diseases.

The potential of infra-low frequency neurofeedback training in peak performance: The first double-blinded placebo-controlled longitudinal study in healthy adults

Infra-low frequency neurofeedback training (ILF-NFT) has shown promise in addressing cognitive and affective distress symptoms across a range of psychiatric disorders. This study tested ILF-NFT's effects in a double-blinded, placebo-controlled longitudinal context in healthy psychology students.Across five weeks, forty-two healthy psychology students (aged 18–35) were randomly allocated into two groups, receiving ten sessions of 30 minutes of active and sham ILF-NFT. Dependent variables were measured before, following, and two months after the intervention and were comprised of: heartrate variability assessments as a measure of stress resilience; digit span, n-back, trail making and go-no-go task measures of executive functioning performance; and SCL-90-R, WHOQOL-Bref, and peak performance measures of subjective self-report. Statistical analysis was performed using an ANCOVA and compared across groups correcting for baseline differences and multiple comparisons.ANCOVA analyses revealed no significant differences across active and placebo groups in any dependent variables, when correcting for multiple comparisons. Thus, the remaining analyses focused on questionnaire correlations. Here, significant correlations were observed between the novel peak performance questionnaire with the SCL-90-R and WHOQOL-Bref, confirming its construct and retest validity.Despite several methodological limitations, including a potential type-2 error, this study highlights limited effects of ILF-NFT in healthy volunteers. Future research should thus focus on clinically driven experimental designs to explore ILF-NFT's potential in psychiatric contexts. Further research utilization of the novel peak performance questionnaire is recommended for measures of peak performance.

Inability to belch syndrome: what the gastroenterologist needs to know.

To review recent publications on the inability to belch syndrome. Five recent retrospective case series indicate that the inability to belch syndrome usually starts in early childhood and is often accompanied by gurgling noises in the chest, pain in the chest or upper abdomen, bloating, and excessive flatulence. Currently, the vast majority of patients who have been identified with inability to belch have self-diagnosed the syndrome on the basis of information available on the internet. A favorable response to injection of botulinum toxin in the cricopharyngeus muscle is regarded as confirmation of the diagnosis. In a mechanistic study in eight patients, absence of reflexogenic relaxation of the upper esophageal sphincter upon rapid gaseous esophageal distension was confirmed to play a pivotal role in the pathogenesis of the syndrome. The inability to belch syndrome, caused by failure of the upper esophageal sphincter to relax when the esophageal body is distended, clearly exists and may not be as rare as thought hitherto. However, overdiagnosis is also likely to occur because the diagnosis is usually made on the basis of symptoms only. The efficacy of botulinum toxin injection in the upper sphincter needs to be assessed in double-blind placebo-controlled studies.

Multi-strain probiotics during pregnancy in women with obesity influence infant gut microbiome development: results from a randomized, double-blind placebo-controlled study

ABSTRACT Probiotics have been described to influence host health and prevent the risk of obesity by gut microbiome (GM) modulation. In a randomized double-blinded placebo-controlled feasibility study, we investigated whether Vivomixx® multi-strain probiotics administered to 50 women with obesity during pregnancy altered the GM composition and perinatal health outcomes of their infants up to 9 months after birth. The mothers and infants were followed up with four visits after birth: at 3 d, and at 3, 6, and 9 months after delivery. The infants were monitored by anthropometric measurements, fecal sample analysis, and questionnaires regarding health and diet. The study setup after birth was feasible, and the women and infants were willing to participate in additional study visits and collection of fecal samples during the 9-month follow-up. In total, 47 newborns were included for microbiome analysis. Maternal prenatal Vivomixx® administration did not alter infant GM diversity nor differential abundance, and the probiotic strains were not vertically transferred. However, the infant GM exhibited a decreased prevalence of the obesity-associated genera, Collinsella, in the probiotic group and of the metabolic health-associated Akkermansia in the placebo group, indicating that indirect community-scale effects of Vivomixx® on the GM of the mothers could be transferred to the infant. Moreover, 3 d after birth, the GM of the infant was influenced by mode of delivery and antibiotics administered during birth. Vaginally delivered infants had increased diversity and relative abundance of the metabolic health-associated Bifidobacterium and Bacteroides while having a decreased relative abundance of Enterococcus compared with infants delivered by cesarean section. Maternal antibiotic administration during birth resulted in a decreased relative abundance of Bifidobacteriumin the GM of the infants. In conclusion, this study observed potential effects on obesity-associated infant GM after maternal probiotic supplementation.

The Efficacy of a Cosmetic Preparation Containing Sheep Colostrum on Mature Skin: A Randomized Placebo-Controlled Double-Blind Study

Colostrum, the first milk produced by mammals, is rich in various bioactive components that provide numerous health benefits to newborns, such as growth factors, hormones, immunoglobulins, cytokines, and enzymes. Topical application of bovine or equine colostrum has been found to improve regeneration, accelerate cutaneous wound healing, and have moisturizing, protective, and anti-aging properties. The aim of this study was to examine the effect of a cosmetic preparation containing sheep colostrum on skin with signs of aging in mature women. Fifty-two women, aged 40–70, were randomized into two groups to receive either colostrum or placebo cream. The participants applied the cream for eight weeks. Skin hydration, TEWL, sebum, erythema, and tone were measured using a standardized Courage + Khazaka electronic GmbH Multi Probe Adapter; skin elasticity was measured with a cutometer, and images were taken by FotoMedicus. The treatment increased skin moisture, reduced TEWL, and improved skin firmness. These findings were confirmed by the subjective survey. The participants reported, inter alia, improved skin softness and less redness and hypersensitivity. Sheep colostrum cream was more effective at improving skin conditions than placebo cream. Colostrum creams can improve certain aspects of skin quality, especially the hydrolipid barrier, and overall rejuvenation.

A randomized placebo-controlled double-blinded study comparing oral and subcutaneous administration of mistletoe extract for the treatment of equine sarcoid disease.

Equine sarcoids (ES) are the most common cutaneous tumors in equids. Systemic treatment options are sparse. Subcutaneous (SC) injections of Viscum album extract (VAE) demonstrate efficacy as a systemic treatment directed against ES. To critically assess the therapeutic efficacy of orally administered VAE. Forty-five ES-affected, privately owned, 3-12 year-old horses. A 3-armed randomized placebo-controlled, double-blinded study was conducted in a double-dummy design. Horses were subjected to oral administration and SC injections of either VAE or placebo (VAE oral/placebo SC, VAE SC/placebo oral, placebo oral/placebo SC) over a 7-month treatment period. Primary endpoint was the change of baseline of a composite index of ES number and ES area after 14 months. Second endpoint was the clinical response. No statistically significant difference in the composite endpoint between the 3 study arms was found. The primary endpoint showed 4 (27%) horses in the VAE oral group with complete ES regression, 3 (21%) in the VAE SC injection group, and 2 (13%) in the placebo group. The clinical response revealed complete or partial regression in 6 horses of the oral VAE group (40%), 4 of the SC injection group (29%), and 4 of the placebo group (25%). Direct comparison of oral VAE and placebo showed an odds ratio, stratified for prognosis of 2.16 (95%-CI: 0.45-10.42) and a P-value of 0.336. Oral administration of VAE is well tolerated. No statistically significant difference in the effectiveness of systemic VAE versus placebo against ES was found.

Subcutaneous injection of lidocaine around ischemic ankle provides safe and effective foot analgesia in patients with critical limb ischemia.

It is often difficult to alleviate foot pain associated with critical limb ischemia (CLI) using common analgesics. Neuraxial block is contraindicated in anticoagulant therapy. This study was designed to determine the response to subcutaneous injection of lidocaine around the network of peripheral nerves around the ankle in patients with CLI pain on anticoagulants and antiplatelets. Sixteen patients with CLI pain in the foot were enrolled in this double-blind placebo-controlled crossover study. Patients were randomized to receive either 2% lidocaine or saline via catheters inserted into the subcutaneous area around the ankle. After recurrence of pain, the patients were crossed over to receive the alternative treatment. Pain was assessed with a numerical rating scale (NRS) before and 15min after injection. Patients used a descriptive scale to grade pain control and were asked to determine the duration of analgesia in each arm of the study. No serious complications including protracted bleeding occurred. Lidocaine significantly decreased the NRS on movement from 10 (6, 10) [median (range)] to 2 (0, 10) (p < .001), and the differences in the Δ change in NRS between lidocaine and placebo were significant (p = .009). Of the 16 patients, 14 patients were very satisfied after lidocaine but only one described the same after saline. The effect of lidocaine and placebo lasted 11 (0, 28) and 1 (0, 22) h, respectively. Subcutaneous injection of lidocaine around the ischemic ankle affectively alleviated pain in patients with CLI without serious adverse effects under anticoagulant therapy.

Impact of curcumin supplementation on exercise performance and muscle damage after a soccer match: a double-blind placebo-controlled cross-over study.

Curcumin ingestion can mitigate muscle damage, soreness, and inflammation following a laboratory-based eccentric exercise. Similar effects were observed in recent field-based studies wherein responses were evaluated after a soccer match. However, various potential confounding factors, such as matching opponent skill levels and daily training conditions, may have influenced the outcomes. In the present study, we investigated whether curcumin intake ameliorates changes in muscle damage markers following a soccer match while controlling for the potential confounding factors. Fifteen collegiate athletes were tested in a randomized, double-blind, cross-over manner. They were recruited from the same college soccer team and thus followed the same daily training regimen and competition levels. Furthermore, athletes positioning during matches were counterbalanced. They consumed either 180mg/day of curcumin or a placebo starting 1h before the match and continuing for 2days after a match (two 45-min plays and a 15-min half-time). Muscle soreness, jump performance (including countermovement jump and rebound jump index), and inflammatory and muscle damage markers (high-sensitive C-reactive protein, serum creatine kinase activity, and urinary N-terminal fragment of titin concentration) were evaluated before and after the match. The washout period between matches was set at 1week. After the match, all markers showed similarity between the placebo and curcumin conditions (all P > 0.208). These findings indicate that ingesting 180mg/day of curcumin may not expedite recovery from muscle damage elicited by soccer matches in collegiate soccer players.

(029) Safety and Efficacy of Botulinum Neurotoxin in the Treatment of Erectile Dysfunction Refractory to Phosphodiesterase Inhibitors: Results of a Randomized Controlled Trial

Abstract Introduction There has been recent interest in the use of botulinum neurotoxin (BoNT) in the field of Andrology, whereby it has been investigated in the treatment of penile retraction and premature ejaculation. Objective To evaluate the safety and efficacy of intracavernosal BoNT-A injection in the treatment of patients with erectile dysfunction (ED) refractory to oral phosphodiesterase inhibitors (PDE5Is). Methods A double-blind randomized placebo-controlled prospective comparative study conducted at one center and involved 70 patients with ED refractory to PDE5Is. At baseline, the following data were collected: erection hardness score (EHS), peak systolic velocity (PSV), end diastolic velocity (EDV), sexual health inventory for men (SHIM), and the sexual encounter profile 2&amp;3 (SEP-2&amp;3) questionnaires. Treatment group (n = 35) received a single ICI of 100 units of BoNT-A in 2 ml of saline and control group (n = 35) received a single ICI of 2 ml of saline. EHS, PSV, and EDV were assessed at 2 weeks post treatment. SHIM, SEP-2, SEP-3, and global assessment questionnaire (GAQ-Q1&amp;Q2) were completed at 2-, 6-, and 12-weeks post treatment. Results Two weeks post treatment, the treatment group showed a statistically significant improvement in the mean EHS, PSV, EDV, and GAQ-Q1 positive responders (p &amp;lt; 0.001) compared to the control group. At 6- and 12-weeks post treatment, the treatment group showed a statistically significant improvement in the SHIM scores, SEP-2, and GAQ-Q1&amp;Q2 positive responders compared to the control group. At 6 weeks, where there was a 5-point improvement in the mean SHIM score of the treatment group (10±5.9 from 5.4±1.7 at baseline) versus no improvement in the placebo group, 18 patients in the treatment group (53%) were able to have an erection hard enough for vaginal penetration versus only one patient in the control group. Conclusions BoNT-A is safe and effective as a potential treatment for ED refractory to PDE5I therapy. Disclosure No.

Topical Diclofenac Versus Oral Ibuprofen Versus Diclofenac + Ibuprofen for Emergency Department Patients With Acute Low Back Pain: A Randomized Study

IntroductionTopical non-steroidal anti-inflammatory drugs (NSAIDs) are useful for a variety of musculoskeletal injuries. It is not known whether topical NSAIDs should be used for patients presenting with acute non-radicular musculoskeletal low back pain (LBP). MethodsWe conducted a randomized, placebo-controlled double-blind study in which ED patients 18-69 years with acute, non-traumatic, non-radicular, musculoskeletal LBP were randomized at the time of discharge to treatment with oral ibuprofen 400mg orally + placebo topical gel, 1% diclofenac topical gel + oral placebo, or ibuprofen 400mg + 1% diclofenac topical gel. We measured outcomes using the Roland Morris Disability Questionnaire (RMDQ), a 24-item yes/no instrument about the impact of back pain on a respondent’s daily activities. The primary outcome was change in RMDQ between ED discharge and two days later. Medication related adverse events were elicited by asking whether the study medications caused any new symptoms. Results3281 patients were screened for participation and 198 were randomized. Overall, 36% of the population were women, the mean age was 40 years (SD 13), and the median RMDQ score at baseline was 18 (25th, 75th percentile: 13, 22) indicating substantial low back related functional impairment. 183 (92%) participants provided primary outcome data. By two days after the ED visit, the ibuprofen + placebo group had improved by 10.1(95%CI 7.5 to 12.7), the diclofenac gel + placebo group by 6.4(95%CI 4.0 to 8.8), and the ibuprofen + diclofenac gel by 8.7(95%CI 6.3 to 11.1). The 95%CI for between group differences were as follows-- ibuprofen versus diclofenac: 3.7 (0.2, 7.2); ibuprofen versus both medications 1.4 (-2.1, 4.9); diclofenac versus both medications -2.3 (-5.7, 1.0). Medication related adverse events were reported by 3/60 (5%) ibuprofen patients, 1/63 (2%) diclofenac patients, and 4/64 (6%) patients who got both. ConclusionsAmong patients with non-traumatic, non-radicular acute musculoskeletal low back pain discharged from an ED, topical diclofenac was probably less efficacious than oral ibuprofen. It demonstrated no additive benefit when co-administered with oral ibuprofen.

Efficacy of Continuous vs. Intermittent Administration of Cefepime in Adult ICU Patients with Gram-Negative Bacilli Bacteremia: A Randomized Double-Blind Clinical Study.

The objective of this study was to compare the continuous infusion of cefepime with the intermittent infusion in patients with sepsis caused by Gram-negative bacilli (GNB). Randomized 1:1 multicenter double-blinded placebo-controlled study with allocation concealment; multicenter study in the intensive care units of Colombia. Patients with sepsis, severe sepsis or septic shock, and GNB-suspected bacteremia. Cefepime was administered for 7 to 14 days over 30 m intermittently every 8 h over 24 h plus continuous saline solution (0.9%) (G1) or 3 g administered continuously plus saline solution every 8 h (0.9%) (G2). The percentage of clinical response at 3, 7, and 14 days, relapse at 28 days, and mortality at discharge were measured. The recruitment was stopped at the suggestion of the Institutional Review Board (IRB) following an FDA alert about cefepime. Thirty-two patients were randomized; 25 received the intervention, and GNB bacteremia was confirmed in 16 (9 G1 and 7 G2). Favorable clinical response in days 3, 7, and 14 was 88.8%, 88.8%, and 77.8% (G1) and was similar for G2 (85.7%). There were no relapses or deaths in G2, while in G1, one relapse and two deaths were observed. The results of this study support the use of cefepime for the treatment of Gram-negative infections in critically ill patients, but we could not demonstrate differences between continuous or intermittent administration because of the small sample size, given the early suspension of the study.

Role of zonisamide in advanced Parkinson’s disease: a randomized placebo-controlled study

BackgroundZonisamide (ZNS) has shown some efficacy in motor symptoms of PD; however, more evidence is lacking, and its effects on nonmotor symptoms (NMSs) and quality of life (QoL) remain to be investigated. This randomized double-blinded placebo-controlled crossover study investigated the effect of ZNS on motor and NMS symptoms and QoL in advanced PD.MethodsPD patients with Hoehn and Yahr stage ≥ 2 (“On” state) and at least 2 h off time daily were randomized to groups: ZNS 25 mg, ZNS 50 mg and placebo. Groups were assessed at baseline and at the 1- and 3-month follow-ups. The primary endpoint was the change in the total MDS-UPDRS III “On”, while the secondary endpoint was the change in the total and parts I and IV MDS-UPDRS, Nonmotor Symptoms Scale and Parkinson’s disease questionnaire-39 at the final assessment.ResultsSixty-nine patients were assessed for efficacy at the 1-month follow-up, and 58 patients were assessed at the 3-month follow-up. The primary endpoint showed significant improvement in the ZNS 25 mg group compared to the placebo group (p = 0.009). At the final assessment, the ZNS 25 mg group showed significant improvement of total and part VI MDS-UPDRS, bradykinesia, tremor and functional impact of fluctuations compared to placebo. There was no change in dyskinesia, NMSs, QoL or side effects except for sedation.ConclusionZNS has a favourable effect on motor symptoms in patients with wearing off as adjunctive therapy with other dopaminergic drugs, with no exacerbation of dyskinesia and a limited impact on NMSs and QoL.Trial registrationClinicaltrials.gov, NCT04182399, in 24/11/2019.