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Minerva Obstetrics and Gynecology Jun 2024Pelvic congestion syndrome (PCS) is associated with chronic pelvic pain (CPP). The efficacy of flavonoids for treating PCS symptoms is still a matter of debate, and...
The effect of a flavonoid mixture containing diosmin, hesperidin and troxerutin in women with congestion syndrome associated to pelvic pain: a color Doppler ultrasonography study.
BACKGROUND
Pelvic congestion syndrome (PCS) is associated with chronic pelvic pain (CPP). The efficacy of flavonoids for treating PCS symptoms is still a matter of debate, and little has been published. The aim of this study was to assess the efficacy of a mixture of diosmin, troxerutin, and hesperidin in improving symptoms of patients with PCS, observing a direct effect on circulation by specific color Doppler ultrasonography (CDU) evaluations.
METHODS
This was a pilot, prospective, independent, cross-over, daily-diary-based trial. Women were evaluated with CDU for 3 times (baseline, 60 days, 120 days). Data about N.=13 women who completed the study were analyzed.
RESULTS
During the treatment, we recorded a significant reduction of intermenstrual and menstrual pain intensity (total points) (P<0.05). The satisfaction after treatment was significantly higher than after placebo (P<0.0001). A significant reduction in the diameter of the major ovarian vein (P=0.004 compared to placebo), associated with an increase in peak systolic velocity (P=0.01) and a corresponding significant increase in the Resistivity Index (P<0.0001) were recorded during treatment.
CONCLUSIONS
The use of a mixture of diosmin, troxerutin and hesperidin in women with PCS can significantly help to manage typical symptoms of pelvic pain and it is associated with an evident Doppler effect on pelvic microcirculation.
Topics: Humans; Female; Hydroxyethylrutoside; Diosmin; Hesperidin; Pelvic Pain; Adult; Prospective Studies; Ultrasonography, Doppler, Color; Cross-Over Studies; Pilot Projects; Syndrome; Young Adult; Treatment Outcome; Ovary; Drug Combinations
PubMed: 38939979
DOI: 10.23736/S2724-606X.24.05432-0 -
Journal of Arrhythmia Jun 2024Atrial fibrillation (AF) is the most frequent arrhythmia after cardiac surgery causing a range of clinical symptoms and treatments that develop in around one-third of...
Evaluation of the effect of small single intravenous dose of amiodarone on the prevention of arrhythmias in patients who underwent coronary artery bypass graft surgery: A randomized controlled trial.
BACKGROUND
Atrial fibrillation (AF) is the most frequent arrhythmia after cardiac surgery causing a range of clinical symptoms and treatments that develop in around one-third of coronary artery bypass surgery patients. We aimed to evaluate the effect of Amiodarone in preventing arrhythmia in patients undergoing coronary artery bypass surgery.
METHOD
In this double-blind randomized clinical trial, 60 patients candidate for coronary artery bypass surgery above the age of 18 were included and randomly divided into two groups of intervention, receiving an infusion of Amiodarone (3 mg/kg) 10 min (in 100 cc Normal saline) before declamping of the aorta, and a control group, receiving 100 cc of saline 10 min before declamping of the aorta. The patient's demographic, clinical features, and hospital and clinical course were recorded.
RESULTS
After undergoing operation, 22 (36.67%) of patients were developed arrhythmia. The Amiodarone group demonstrated significantly lower reperfusion ventricular fibrillation (RVF) rates (26.7% vs. 70%; = .001) and AF occurrence (13.3% vs. 60%; < .001) during the initial 24 h after surgery compared to the placebo group. There was no significant difference between the two groups regarding the need for D/C shock after removing the aortic clamp. ( = .117) Furthermore, the intensive care unit stay among the amiodaron group was significantly lower than the control group (2.43 vs. 3.07 days; = .013).
CONCLUSION
The predictive properties in the administration of single intravenous low-dose Amiodarone 10 min before the declamping of the aorta can significantly lower the rates of RVF and AF after coronary artery bypass grafting, while also decreasing hospitalization duration.
PubMed: 38939762
DOI: 10.1002/joa3.12986 -
ESC Heart Failure Jun 2024Acute myocarditis, although a rare disease, can be associated with sudden cardiac death or the need for transplantation in both children and young adults. To date, there...
AIMS
Acute myocarditis, although a rare disease, can be associated with sudden cardiac death or the need for transplantation in both children and young adults. To date, there is no definitive evidence to support the routine use of immunosuppressive therapy or treatment targeting inflammation in patients with myocarditis. Animal models of cardiovascular (CV), as well as neurological diseases, have demonstrated that cannabidiol has significant anti-inflammatory properties and may represent a promising therapy in acute myocarditis. This efficacy has been shown in a murine model of autoimmune myocarditis as well as in in vitro and in vivo models of heart failure (HF).
METHODS AND RESULTS
We present the rationale and design of the ARCHER Trial, an international multicentre, double-blind, randomized, placebo-controlled, phase II study examining the safety and efficacy of a pharmaceutically produced cannabidiol formulation, in patients with mild to moderate acute myocarditis. Eligible patients are those with acute myocarditis, randomized within 10 days of the diagnostic cardiac MRI (CMR), which has met defined diagnostic criteria for myocarditis. Oral treatment (cannabidiol or placebo) is titrated from 2.5 mg/kg of body weight up to 10 mg/kg of body weight b.i.d. (or highest tolerated dose) and taken for 12 weeks in addition to standard of care therapy for HF. The primary endpoints are defined as changes in global longitudinal strain (GLS) and extra cellular volume (ECV), measured by CMR at 12 weeks. Assuming 80% power, a 5% alpha risk and 25% missing CMR follow-up data at Week 12, 100 patients are required to demonstrate the desired treatment effect of 18%. The change in left ventricular ejection fraction (LVEF) from baseline to Week 12 was selected as the secondary endpoint. Additional exploratory endpoints include changes in hs-troponin, NT-proBNP, markers of inflammation and endothelial function during the 12-week treatment period. The trial is ongoing but is now more than 50% recruited. As enrolment in the trial continues, no interim data are available for inclusion in this Design paper.
CONCLUSIONS
The ongoing ARCHER Trial is an international, multicentre, double-blind, randomized, placebo-controlled phase II study, designed to determine the effect of a pharmaceutically produced cannabidiol formulation on CMR parameters in patients presenting with acute myocarditis. Enrolment of 100 patients is expected to conclude in Q3 2024. Study results will be available in early 2025.
PubMed: 38937900
DOI: 10.1002/ehf2.14889 -
The Journal of Pharmacology and... Jun 2024Endocannabinoids, which are present throughout the central nervous system (CNS), can activate CB1 and CB2 receptors. CB1 and CB2 agonists exhibit broad...
Endocannabinoids, which are present throughout the central nervous system (CNS), can activate CB1 and CB2 receptors. CB1 and CB2 agonists exhibit broad anti-inflammatory properties, suggesting their potential to treat inflammatory diseases. However, careful evaluation of abuse potential is necessary. This study evaluated the abuse potential of lenabasum, a selective CB2 receptor agonist in participants (n=56) endorsing recreational cannabis use. Three doses of lenabasum (20, 60, and 120mg) were compared to placebo, and nabilone (3 and 6mg). The primary endpoint was the peak effect (Emax) on a bipolar Drug Liking visual analog scale (VAS). Secondary VAS and pharmacokinetic (PK) endpoints and adverse events were assessed. : Lenabasum was safe and well tolerated. Compared to placebo, a 20mg dose of lenabasum did not increase ratings of Drug Liking and had no distinguishable effect on other VAS endpoints. Dose-dependent increases in ratings of Drug Liking were observed with 60 and 120mg lenabasum. Drug Liking and all other VAS outcomes were greatest for nabilone 3mg and 6mg, which is a currently FDA-approved medication. : At a target therapeutic dose (20mg), lenabasum did not elicit subjective ratings of Drug Liking. However, supratherapeutic doses of lenabasum (60 and 120mg) did elicit subjective ratings of Drug Liking compared to placebo. Although both doses of lenabasum were associated with lower ratings of Drug Liking compared to 3mg and 6mg of nabilone, suggesting that lenabasum does have abuse potential and should be used cautiously in clinical settings. This work provides evidence that in people with a history of recreational cannabis use, lenabasum was safe and well-tolerated, although it did demonstrate abuse potential. This work supports further development of lenabasum for potential therapeutic indications.
PubMed: 38936978
DOI: 10.1124/jpet.124.002129 -
BMJ Supportive & Palliative Care Jun 2024Chemotherapy-induced peripheral neuropathy (CIPN) affects patients' quality of life and treatment effectiveness. Gabapentinoids, like gabapentin and pregabalin, are...
INTRODUCTION
Chemotherapy-induced peripheral neuropathy (CIPN) affects patients' quality of life and treatment effectiveness. Gabapentinoids, like gabapentin and pregabalin, are often used for CIPN treatment, but their efficacy and safety remain uncertain. This study reviews and analyses randomised controlled trial data on this topic.
MATERIALS/METHODS
We searched PubMed, Embase and Cochrane CENTRAL until 29 August 2022 for studies on gabapentinoid use in CIPN. Meta-analysis was performed using RevMan V.5.4 and the Metafor package in R. Outcomes included pain scores, quality of life and adverse drug events.
RESULTS
For the prevention setting, our meta-analysis shows that pregabalin did not significantly improve average pain (standardised mean difference (SMD) -0.14, 95% CI -0.51 to 0.23; I=26% (95% CI 0% to >98%)) or quality of life (mean difference (MD) 2.5, 95% CI -4.67 to 9.67; p=0.49) in preventing CIPN compared with placebo. However, it showed a potential trend towards reducing the worst pain (SMD -0.28, 95% CI -0.57 to 0.01; I=0% (95% CI 0% to 98%; p=0.06)). For the treatment setting, some studies have shown a potential therapeutic effect of gabapentinoids. However, the results are not consistent between studies. Given the studies' heterogeneity, a meta-analysis in treatment setting was not performed.
CONCLUSION
There is limited evidence to support the use of gabapentinoids in CIPN. In prevention setting, gabapentinoids do not significantly prevent CIPN. In treatment setting, studies have been inconsistent in their conclusions, lacking definitive benefits over placebo. More comprehensive and higher quality research is needed in the future.
PROSPERO REGISTRATION NUMBER
CRD42022361193.
PubMed: 38936970
DOI: 10.1136/spcare-2023-004362 -
Behavioural Brain Research Jun 2024The tendency to show the renewal effect of extinction appears as an intra-individually stable, reproducible processing strategy associated with differential patterns of...
The tendency to show the renewal effect of extinction appears as an intra-individually stable, reproducible processing strategy associated with differential patterns of BOLD activation in hippocampus, iFG and vmPFC, as well as differential resting-state functional connectivity between prefrontal regions and the dorsal attention network. Also, pharmacological modulations of the noradrenergic system that influence attentional processing have partially different effects upon individuals with (REN) and without (NoREN) a propensity for renewal. However, it is as yet unknown whether REN and NoREN individuals differ regarding microstructural properties in attention-related white matter (WM) regions, and whether such differences are related to noradrenergic processing. In this diffusion tensor imaging (DTI) analysis we investigated the relation between microstructural properties of attention-related WM tracts and ABA renewal propensity, under conditions of noradrenergic stimulation by means of the noradrenergic reuptake inhibitor atomoxetine, compared to placebo. Fractional anisotropy (FA) was higher in participants with noradrenergic stimulation (ATO) compared to placebo (PLAC), the effect was predominantly left-lateralized and based on the comparison of ATO REN and PLAC REN participants. In REN participants of both treatment groups, FA in several WM tracts showed a positive correlation with the ABA renewal level, suggesting higher renewal levels were associated with higher microstructural integrity. These findings point towards a relation between microstructural properties of attention-related WM tracts and the propensity for renewal that is not specifically dependent on noradrenergic processing.
PubMed: 38936425
DOI: 10.1016/j.bbr.2024.115125 -
Animal : An International Journal of... May 2024No single enteric CH mitigating strategy has been consistently effective or is readily applicable to ruminants in grassland systems. When CH mitigating strategies are...
No single enteric CH mitigating strategy has been consistently effective or is readily applicable to ruminants in grassland systems. When CH mitigating strategies are effective under grazing conditions, mitigation is mild to moderate at best. A study was conducted to evaluate the potential of combining two CH mitigation strategies deemed feasible to apply in grazing dairy cows, the methanogenesis inhibitor 3-nitrooxypropanol additive (3-NOP) and cottonseed supplementation (CTS), seeking to enhance their individual CH mitigating potential. Forty-eight dairy cows were evaluated in a continuous grazing study and supplemented with either a starch-based concentrate (STA) or one that contained cottonseeds (1.75 kg DM/d; CTS), and with either 19 g/d of 10% 3-NOP (Bovaer®) or the additive's carrier (placebo), in a 2 × 2 factorial arrangement of treatments. Treatments were supplied mixed with a concentrate supplement (5 kg/d as fed) and offered in two equal rations at milking. Methane emissions were measured on weeks 4 and 8 using the sulphur hexafluoride tracer gas technique over a 5-d period. The 3-NOP and CTS treatments tended to interact on absolute CH such that 3-NOP decreased CH by 13.4% with STA, but there was no mitigation with 3-NOP and CTS. Treatment interactions were also obtained for CH yield, where 3-NOP tended to decrease CH when supplied with STA, and tended to increase it with CTS. The increase in CH yield with the CTS diet was driven by a numerical decrease in DM intake. Methane intensity was not affected by the 3-NOP or CTS treatments. Total volatile fatty acids in ruminal fluid were not affected by 3-NOP supplementation, but a reduction in acetate and an increase in propionate proportion occurred, resulting in decreased acetate: propionate. The 3-NOP additive decreased grass intake; however, energy-corrected milk yield and milk composition were largely unaffected. Milk urea increased with 3-NOP supplementation. Combining twice daily supplementation of 3-NOP and CTS did not enhance their CH mitigation potential when fed to grazing dairy cows. The relatively low inhibition of CH production by 3-NOP compared to studies with total mixed rations may result from the mode of delivery (pulse dosed twice daily) and time gap caused by experimental handling and moving of animals to pasture after 3-NOP supplementation in the milking parlour, which could have impaired the synchrony between the additive presence in the rumen and grass intake in paddocks.
PubMed: 38935983
DOI: 10.1016/j.animal.2024.101203 -
Endocrine Jun 2024We recently demonstrated an additional oxytocin (OT) deficiency in patients with arginine vasopressin (AVP) deficiency (central diabetes insipidus) by using...
PURPOSE
We recently demonstrated an additional oxytocin (OT) deficiency in patients with arginine vasopressin (AVP) deficiency (central diabetes insipidus) by using 3,4-methylenedioxy-methamphetamine (MDMA) as a novel provocation test. However, the implication of the MDMA provocation test in clinical practice might be challenging. Glucagon effectively stimulates vasopressinergic neurons with a strong increase in plasma copeptin. We therefore hypothesized that this provocation test might also stimulate OT.
METHODS
This is a predefined secondary analysis of a prospective double-blind, randomised, placebo-controlled cross-over trial involving ten patients with AVP deficiency and ten sex- and body-mass index-matched healthy participants at the University Hospital Basel, Switzerland. Each participant underwent the glucagon test (s.c. injection of 1 mg glucagon) and placebo test (s.c. injection of 0.9% normal saline). Plasma OT levels were measured at baseline, 60, 120 and 180 min after injection. The primary objective was to determine whether glucagon stimulates OT and whether OT levels differ between patients with AVP deficiency and healthy participants. The primary outcome (maximum change in OT within 180 min) was compared between groups and conditions using a linear mixed effects model.
RESULTS
In healthy participants, the median OT at baseline was 82.7 pg/ml [62.3-94.3] and slightly increased to a maximum of 93.3 pg/ml [87.2-121.1] after injection of glucagon, resulting in a change increase of 24.9 pg/ml [5.1-27.8]. Similarly, in patients with AVP deficiency, the median OT at baseline was 73.9 pg/ml [65.3-81.6] and slightly increased after glucagon injection to 114.9 pg/ml [70.9-140.9], resulting in a change increase of 36.8 pg/ml [-2.2 to 51.2]. The results from the mixed model showed no effect between glucagon compared to placebo on OT (difference: -0.5 pg/ml; 95%-CI [-25, 24]; p = 0.97) and no significant treatment-by-group interaction effect between patients compared to healthy participants (interaction: 28 pg/ml; 95%-CI [-7, 62]; p = 0.13).
CONCLUSION
We found no effect of glucagon on plasma OT levels and no difference between patients with AVP deficiency and healthy participants.
PubMed: 38935296
DOI: 10.1007/s12020-024-03920-2 -
Probiotics and Antimicrobial Proteins Jun 2024As the population ages, cognitive decline becomes more common. Strategies targeting the gut-brain axis using probiotics are emerging to achieve improvements in...
Cognitive and Emotional Effect of a Multi-species Probiotic Containing Lactobacillus rhamnosus and Bifidobacterium lactis in Healthy Older Adults: A Double-Blind Randomized Placebo-Controlled Crossover Trial.
As the population ages, cognitive decline becomes more common. Strategies targeting the gut-brain axis using probiotics are emerging to achieve improvements in neuropsychiatric and neurological disorders. However, the beneficial role of probiotics on brain function in healthy older adults remains unclear. Our aim was to evaluate a multi-species probiotic formulation as a therapeutic approach to reduce emotional and cognitive decline associated with aging in healthy adults. A randomized double-blind placebo-controlled crossover trial was conducted. The study involved a 10-week intervention where participants consumed the assigned probiotic product daily, followed by a 4-week washout period before the second condition started. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) and the Psychological Experiments Construction Language Test Battery. At the emotional level, the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI) were used. Thirty-three participants, recruited between July 2020 and April 2022, ingested a multispecies probiotic (Lactobacillus rhamnosus and Bifidobacterium lactis). After the intervention, noticeable enhancements were observed in cognitive function (mean difference 1.90, 95% CI 1.09 to 2.70, p < 0.005), memory (mean difference 4.60, 95% CI 2.91 to 6.29, p < 0.005) by MMSE and digit task, and depressive symptoms (mean difference 4.09, 95% CI 1.70 to 6.48, p < 0.005) by BDI. Furthermore, there were significant improvements observed in planning and problem-solving skills, selective attention, cognitive flexibility, impulsivity, and inhibitory ability. Probiotics administration improved cognitive and emotional function in older adults. Limited research supports this, requiring more scientific evidence for probiotics as an effective therapy for cognitive decline. This study has been prospectively registered at ClinicalTrials.gov (NCT04828421; 2020/July/17).
PubMed: 38935259
DOI: 10.1007/s12602-024-10315-2 -
International Journal of Surgery... Jun 2024The efficacy and necessity of prophylactic antibiotics in clean and clean-contaminated surgery remains controversial.
BACKGROUND
The efficacy and necessity of prophylactic antibiotics in clean and clean-contaminated surgery remains controversial.
METHODS
The studies were screened and extracted using databases including PubMed, Embase, Cochrane Library, Web of Science, and Clinical Trials.gov according to predefined eligibility criteria. Randomized controlled trials (RCTs) comparing the effect of preoperative and postoperative prophylactic antibiotic use on the incidence of surgical site infections (SSIs) in patients undergoing any clean or clean-contaminated surgery.
RESULTS
A total of 16,189 participants in 48 RCTs were included in the primary meta-analysis following the eligibility criteria. The pooled odds ratio (OR) for SSI with antibiotic prophylaxis versus placebo was 0.60 (95% CI: 0.53-0.68). The pooled OR among gastrointestinal, oncology, orthopedics, neurosurgery, oral, and urology surgery was 3.06 (95% CI: 1.05-8.91), 1.16 (95% CI: 0.89-1.50), 2.04 (95% CI: 1.09-3.81), 3.05 (95% CI: 1.25-7.47), 3.55 (95% CI: 1.78-7.06), and 2.26 (95% CI: 1.12-4.55), respectively. Furthermore, the summary mean difference (MD) for patients' length of hospitalization was -0.91 (95% CI: -1.61, -0.16). The results of sensitivity analyses for all combined effect sizes showed good stability.
CONCLUSION
Antibiotics are both effective, safe, and necessary in preventing surgical wound infections in clean and clean-contaminated procedures, attributed to their reduction in the incidence of surgical site infections as well as the length of patient hospitalization.
PubMed: 38935088
DOI: 10.1097/JS9.0000000000001882