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Medicina (Kaunas, Lithuania) May 2024: Increasing evidence supporting the clinical effectiveness of cooled radiofrequency ablation (RFA) therapy for genicular nerves in patients with chronic knee... (Randomized Controlled Trial)
Randomized Controlled Trial
Effectiveness of the Cooled Radiofrequency Ablation of Genicular Nerves in Patients with Chronic Knee Pain Due to Osteoarthritis: A Double-Blind, Randomized, Controlled Study.
: Increasing evidence supporting the clinical effectiveness of cooled radiofrequency ablation (RFA) therapy for genicular nerves in patients with chronic knee osteoarthritis (OA) exists. However, no study has been conducted to eliminate the potential influence of a placebo effect associated with this procedure. Therefore, we evaluated the efficacy of cooled RFA compared with a sham procedure in patients with painful knees due to OA. : In this double-blind, randomized, controlled study, participants were randomly assigned to receive cooled RFA of the knee (cooled RFA group, n = 20) or a sham procedure (sham group, n = 20). The primary outcome was the proportion of successful responders at the three-month follow-up. The secondary outcomes were successful responders at one and six months; pain intensity of the knee; functional status; medication; and satisfaction at one, three, and six months after the procedures. : For the primary outcome, the successful responder rate was significantly higher in the cooled RFA group (76.5%) than in the sham group (33.3%) ( = 0.018). For the secondary outcome, more successful responders were observed in the cooled RFA group than in the sham group at one and six months after the procedure ( = 0.041 and 0.007, respectively). The decreased knee pain intensity was maintained throughout the six-month follow-up period in the cooled RFA group. No differences were observed in functional status, medication change, or satisfaction in both groups. : The cooled RFA of genicular nerves offers significant pain relief and surpasses the effects attributable to a placebo.
Topics: Humans; Double-Blind Method; Osteoarthritis, Knee; Female; Male; Radiofrequency Ablation; Middle Aged; Aged; Treatment Outcome; Chronic Pain; Pain Measurement; Knee Joint
PubMed: 38929474
DOI: 10.3390/medicina60060857 -
International Journal of Environmental... May 2024The intake of specific collagen peptides (SCPs) has been shown to decrease activity-related knee pain in young, physically active adults. This trial investigated the... (Randomized Controlled Trial)
Randomized Controlled Trial
The intake of specific collagen peptides (SCPs) has been shown to decrease activity-related knee pain in young, physically active adults. This trial investigated the effect of a 12-week SCP supplementation in a wider age range of healthy men and women over 18 years with functional knee and hip pain during daily activities. A total of 182 participants were randomly assigned to receive either 5 g of specific collagen peptides (CP-G) or a placebo (P-G). Pain at rest and during various daily activities were assessed at baseline and after 12 weeks by a physician and participants using a 10-point numeric rating scale (NRS). The intake of 5 g SCP over 12 weeks significantly reduced pain at rest ( = 0.018) and during walking ( = 0.032) according to the physician's evaluation. Participants in the CP-G also reported significantly less pain when climbing stairs ( = 0.040) and when kneeling down ( < 0.001) compared to the P-G. Additionally, after 12 weeks, restrictions when squatting were significantly lower in the CP-G compared with the P-G ( = 0.014). The daily intake of 5 g of SCP seems to benefit healthy adults with hip and knee joint discomforts by reducing pain during daily activities.
Topics: Humans; Male; Female; Adult; Collagen; Middle Aged; Activities of Daily Living; Young Adult; Double-Blind Method; Knee Joint; Peptides; Lower Extremity; Aged; Hip Joint; Dietary Supplements
PubMed: 38928934
DOI: 10.3390/ijerph21060687 -
BMC Veterinary Research Jun 2024The present study was performed to characterize and compare the perfusion of vaginal and uterine arteries after challenging the reproductive tract of dairy cows via...
AIM
The present study was performed to characterize and compare the perfusion of vaginal and uterine arteries after challenging the reproductive tract of dairy cows via natural mating, artificial insemination (AI), or intravaginal deposition (vaginal fundus) of different biological fluids or a placebo.
MATERIALS AND METHODS
In a double-blind study, six German Holstein cows were administered PGF during dioestrus and 48 h later treated with GnRH. Intravaginal or intrauterine treatments were carried out 12 h after GnRH was administered. Animals served as their controls, using a cross-over design with an interval of 14 days between experiments. The experimental animals were allocated to receive the following treatments: natural mating (N), intrauterine artificial insemination (A), intravaginal deposition (vaginal fundus) of 6 mL raw semen (R) or 6 mL seminal plasma (S), and compared to their controls [control 1: 6 mL placebo (P: physiological saline); control 2: no treatment (C)). Corresponding time intervals were chosen for the untreated control oestrus. Blood flow volume (BFV) in the uterine (u) and vaginal (v) arteries ipsilateral to the ovary bearing the preovulatory follicle was determined using transrectal Doppler sonography.
RESULTS
All animals exhibited oestrus and ovulated between 30 and 36 h after GnRH. Transient increases (P < 0.05) in vaginal blood flow occurred between 3 and 12 h following mating as well as 3 to 9 h after deposition of raw semen and seminal plasma, respectively. The most distinct increases (199%) in vBFV occurred 6 h after mating compared to values immediately before mating (= time 0 h). Neither AI nor deposition of a placebo into the vagina affected vBFV (P > 0.05). Only mating and deposition of either raw semen, seminal plasma or AI increased uBFV (P < 0.003). The greatest rise in uBFV occurred after natural mating. Maximum uBFV values were detected 9 h after mating when values were 79% greater (P < 0.05) than at 0 h.
CONCLUSIONS
The natural mating, deposition of raw semen or seminal plasma and conventional AI affect vaginal and/or uterine blood flow to different degrees. The factors responsible for these alterations in blood flow and their effects on fertility remain to be clarified in future studies.
Topics: Animals; Insemination, Artificial; Female; Semen; Cattle; Vagina; Uterus; Male; Administration, Intravaginal; Double-Blind Method; Gonadotropin-Releasing Hormone; Cross-Over Studies; Regional Blood Flow
PubMed: 38926710
DOI: 10.1186/s12917-024-03919-x -
Scientific Reports Jun 2024To compare the efficacy and safety of the proposed aflibercept biosimilar SCD411 and reference aflibercept in patients with neovascular age-related macular degeneration,... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
To compare the efficacy and safety of the proposed aflibercept biosimilar SCD411 and reference aflibercept in patients with neovascular age-related macular degeneration, this randomized, double-masked, parallel-group, multicenter study was conducted in 14 countries from 13 August 2020 to 8 September 2022. Patients with neovascular age-related macular degeneration. With subfoveal, juxtafoveal, or extrafoveal choroidal neovascularization were aged 50 years or older. Intravitreal injection of SCD411 or aflibercept (2.0 mg) were administered every 4 weeks for the first three injections and every 8 weeks until week 48. The primary efficacy endpoint was the change in best-corrected visual acuity from baseline to week 8 with an adjusted equivalence margin of ± 3.0 letters. Patients were randomly assigned to receive either SCD411 (n = 288) or reference aflibercept (n = 288). A total of 566 participants (98.3%) completed week 8 of the study. The least-squares mean difference of change in best-corrected visual acuity from baseline to week 8 (SCD411-aflibercept) was - 0.4 letters (90% confidence interval = - 1.6 to 0.9). The incidence of ocular (69 of 287 [24.0%] vs. 71 of 286 [24.8%]) and serious ocular (5 of 287 [1.7%] vs. 3 of 286 [1.0%]) treatment-emergent adverse effects were similar between the SCD411 and aflibercept groups. Immunogenicity analysis revealed a low incidence of neutralizing antibody formation in both groups. In conclusion, SCD411 has equivalent efficacy compared with reference aflibercept in patients with neovascular age-related macular degeneration and has a comparable safety profile. The results support the potential use of SCD411 for the treatment of neovascular age-related macular degeneration.
Topics: Humans; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Male; Female; Aged; Visual Acuity; Intravitreal Injections; Treatment Outcome; Macular Degeneration; Middle Aged; Double-Blind Method; Aged, 80 and over; Choroidal Neovascularization; Biosimilar Pharmaceuticals; Angiogenesis Inhibitors
PubMed: 38926553
DOI: 10.1038/s41598-024-65815-6 -
BMJ Open Jun 2024The prevalence of major depressive disorder (MDD) is on the rise globally, and the use of antidepressant medications for its treatment does not usually result in full... (Randomized Controlled Trial)
Randomized Controlled Trial
Study protocol on the efficacy of exergames-acceptance and commitment therapy program for the treatment of major depressive disorder: comparison with acceptance and commitment therapy alone and treatment-as-usual in a multicentre randomised controlled trial.
BACKGROUND
The prevalence of major depressive disorder (MDD) is on the rise globally, and the use of antidepressant medications for its treatment does not usually result in full remission. However, the combination of physical exercise and psychotherapy for the treatment of MDD increase the rate of full remission among patients. This three-armed, parallel-group, double-blinded randomised controlled trial (RCT) aims to assess and compare the effects between the combination of exergame and acceptance and commitment therapy (e-ACT) programme, ACT only and treatment-as-usual (TAU) control groups on the severity of depression and anxiety symptoms, the degree of experiential avoidance and quality of life (QoL) and the serum levels of depression biomarkers (such as brain-derived neurotrophic factor, C-reactive protein and vascular endothelial growth factor) among patients with MDD across three time points.
METHODS AND ANALYSIS
This RCT will recruit 126 patients with MDD who will be randomised using stratified permuted block randomisation into three groups, which are the combined e-ACT programme, ACT-only and TAU control groups in a 1:1:1 allocation ratio. The participants in the e-ACT and ACT-only intervention groups will undergo once a week intervention sessions for 8 weeks. Assessments will be carried out through three time points, such as the pre-intervention assessment (t), assessment immediately after completion of the intervention at 8 weeks (t) and assessment at 24 weeks after completion of the intervention (t). During each assessment, the primary outcome to be assessed includes the severity of depression symptoms, while the secondary outcomes to be assessed are the severity of anxiety symptoms, experiential avoidance, QoL and depression biomarkers.
ETHICS AND DISSEMINATION
Approval of this study was obtained from the Human Research Ethics Committee of Universiti Sains Malaysia (USM/JEPeM/PP/23050420). The findings of the study will be published in academic peer-reviewed journals.
TRIAL REGISTRATION NUMBER
NCT05812001 (ClinicalTrials.gov). Registered on 12 April 2023.
Topics: Humans; Depressive Disorder, Major; Quality of Life; Acceptance and Commitment Therapy; Adult; Double-Blind Method; Male; Female; Video Games; Randomized Controlled Trials as Topic; Middle Aged; Treatment Outcome; Multicenter Studies as Topic; Exercise Therapy; Brain-Derived Neurotrophic Factor; Biomarkers
PubMed: 38926142
DOI: 10.1136/bmjopen-2023-080315 -
BMJ (Clinical Research Ed.) Jun 2024To assess the efficacy and safety of colchicine versus placebo on reducing the risk of subsequent stroke after high risk non-cardioembolic ischaemic stroke or transient... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
To assess the efficacy and safety of colchicine versus placebo on reducing the risk of subsequent stroke after high risk non-cardioembolic ischaemic stroke or transient ischaemic attack within the first three months of symptom onset (CHANCE-3).
DESIGN
Multicentre, double blind, randomised, placebo controlled trial.
SETTING
244 hospitals in China between 11 August 2022 and 13 April 2023.
PARTICIPANTS
8343 patients aged 40 years of age or older with a minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L were enrolled.
INTERVENTIONS
Patients were randomly assigned 1:1 within 24 h of symptom onset to receive colchicine (0.5 mg twice daily on days 1-3, followed by 0.5 mg daily thereafter) or placebo for 90 days.
MAIN OUTCOME MEASURES
The primary efficacy outcome was any new stroke within 90 days after randomisation. The primary safety outcome was any serious adverse event during the treatment period. All efficacy and safety analyses were by intention to treat.
RESULTS
4176 patients were assigned to the colchicine group and 4167 were assigned to the placebo group. Stroke occurred within 90 days in 264 patients (6.3%) in the colchicine group and 270 patients (6.5%) in the placebo group (hazard ratio 0.98 (95% confidence interval 0.83 to 1.16); P=0.79). Any serious adverse event was observed in 91 (2.2%) patients in the colchicine group and 88 (2.1%) in the placebo group (P=0.83).
CONCLUSIONS
The study did not provide evidence that low-dose colchicine could reduce the risk of subsequent stroke within 90 days as compared with placebo among patients with acute non-cardioembolic minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT05439356.
Topics: Humans; Colchicine; Male; Female; Double-Blind Method; Middle Aged; Ischemic Attack, Transient; Aged; Ischemic Stroke; Treatment Outcome; China; C-Reactive Protein; Adult
PubMed: 38925803
DOI: 10.1136/bmj-2023-079061 -
BMJ Open Jun 2024Acute-on-chronic liver failure (ACLF) is a prevalent and life-threatening liver disease with high short-term mortality. Although recent clinical trials on the use of...
Human umbilical cord mesenchymal stem cell transplantation for the treatment of acute-on-chronic liver failure: protocol for a multicentre random double-blind placebo-controlled trial.
INTRODUCTION
Acute-on-chronic liver failure (ACLF) is a prevalent and life-threatening liver disease with high short-term mortality. Although recent clinical trials on the use of mesenchymal stem cells (MSCs) for ACLF treatment have shown promising results, multicentre randomised controlled phase II clinical trials remain uncommon. The primary aim of this trial is to assess the safety and efficacy of different MSCs treatment courses for ACLF.
METHODS AND ANALYSIS
This is a multicentre, double-blind, two-stage, randomised and placebo-controlled clinical trial. In the first stage, 150 patients with ACLF will be enrolled and randomly assigned to either a control group (50 cases) or an MSCs treatment group (100 cases). They will receive either a placebo or umbilical cord-derived MSCs (UC-MSCs) treatment three times (at weeks 0, 1 and 2). In the second stage, 28 days after the first UC-MSCs infusion, surviving patients in the MSCs treatment group will be further randomly divided into MSCs-short and MSCs-prolonged groups at a 1:1 ratio. They will receive two additional rounds of placebo or UC-MSCs treatment at weeks 4 and 5. The primary endpoints are the transplant-free survival rate and the incidence of treatment-related adverse events. Secondary endpoints include international normalised ratio, total bilirubin, serum albumin, blood urea nitrogen, model for end-stage liver disease score and Child-Turcotte-Pugh score.
ETHICS AND DISSEMINATION
Ethical approval of this study has been obtained from the Fifth Medical Center of the Chinese PLA General Hospital (KY-2023-3-19-1). All results of the study will be submitted to international journals and international conferences for publication on completion of the study.
TRIAL REGISTRATION NUMBER
NCT05985863.
Topics: Humans; Acute-On-Chronic Liver Failure; Double-Blind Method; Mesenchymal Stem Cell Transplantation; Umbilical Cord; Adult; Female; Male; Randomized Controlled Trials as Topic; Multicenter Studies as Topic; Middle Aged; Treatment Outcome
PubMed: 38925694
DOI: 10.1136/bmjopen-2024-084237 -
The New England Journal of Medicine Jun 2024Benralizumab is an eosinophil-depleting anti-interleukin-5 receptor α monoclonal antibody. The efficacy and safety of benralizumab in patients with eosinophilic... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Benralizumab is an eosinophil-depleting anti-interleukin-5 receptor α monoclonal antibody. The efficacy and safety of benralizumab in patients with eosinophilic esophagitis are unclear.
METHODS
In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial, we assigned patients 12 to 65 years of age with symptomatic and histologically active eosinophilic esophagitis in a 1:1 ratio to receive subcutaneous benralizumab (30 mg) or placebo every 4 weeks. The two primary efficacy end points were histologic response (≤6 eosinophils per high-power field) and the change from baseline in the score on the Dysphagia Symptom Questionnaire (DSQ; range, 0 to 84, with higher scores indicating more frequent or severe dysphagia) at week 24.
RESULTS
A total of 211 patients underwent randomization: 104 were assigned to receive benralizumab, and 107 were assigned to receive placebo. At week 24, more patients had a histologic response with benralizumab than with placebo (87.4% vs. 6.5%; difference, 80.8 percentage points; 95% confidence interval [CI], 72.9 to 88.8; P<0.001). However, the change from baseline in the DSQ score did not differ significantly between the two groups (difference in least-squares means, 3.0 points; 95% CI, -1.4 to 7.4; P = 0.18). There was no substantial between-group difference in the change from baseline in the Eosinophilic Esophagitis Endoscopic Reference Score, which reflects endoscopic abnormalities. Adverse events were reported in 64.1% of the patients in the benralizumab group and in 61.7% of those in the placebo group. No patients discontinued the trial because of adverse events.
CONCLUSIONS
In this trial involving patients 12 to 65 years of age with eosinophilic esophagitis, a histologic response (≤6 eosinophils per high-power field) occurred in significantly more patients in the benralizumab group than in the placebo group. However, treatment with benralizumab did not result in fewer or less severe dysphagia symptoms than placebo. (Funded by AstraZeneca; MESSINA ClinicalTrials.gov number, NCT04543409.).
Topics: Adolescent; Adult; Aged; Child; Female; Humans; Male; Middle Aged; Young Adult; Antibodies, Monoclonal, Humanized; Deglutition Disorders; Double-Blind Method; Eosinophilic Esophagitis; Eosinophils; Interleukin-5 Receptor alpha Subunit; Leukocyte Count
PubMed: 38924732
DOI: 10.1056/NEJMoa2313318 -
The New England Journal of Medicine Jun 2024Dupilumab is a human monoclonal antibody that blocks interleukin-4 and interleukin-13 pathways and has shown efficacy in five different atopic diseases marked by type 2... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Dupilumab is a human monoclonal antibody that blocks interleukin-4 and interleukin-13 pathways and has shown efficacy in five different atopic diseases marked by type 2 inflammation, including eosinophilic esophagitis in adults and adolescents.
METHODS
In this phase 3 trial, we randomly assigned, in a 2:2:1:1 ratio, patients 1 to 11 years of age with active eosinophilic esophagitis who had had no response to proton-pump inhibitors to 16 weeks of a higher-exposure or lower-exposure subcutaneous dupilumab regimen or to placebo (two groups) (Part A). At the end of Part A, eligible patients in each dupilumab group continued the same regimen and those in the placebo groups were assigned to higher-exposure or lower-exposure dupilumab for 36 weeks (Part B). At each level of exposure, dupilumab was administered in one of four doses tiered according to baseline body weight. The primary end point was histologic remission (peak esophageal intraepithelial eosinophil count, ≤6 per high-power field) at week 16. Key secondary end points were tested hierarchically.
RESULTS
In Part A, histologic remission occurred in 25 of the 37 patients (68%) in the higher-exposure group, in 18 of the 31 patients (58%) in the lower-exposure group, and in 1 of the 34 patients (3%) in the placebo group (difference between the higher-exposure regimen and placebo, 65 percentage points [95% confidence interval {CI}, 48 to 81; P<0.001]; difference between the lower-exposure regimen and placebo, 55 percentage points [95% CI, 37 to 73; P<0.001]). The higher-exposure dupilumab regimen led to significant improvements in histologic, endoscopic, and transcriptomic measures as compared with placebo. The improvements in histologic, endoscopic, and transcriptomic measures between baseline and week 52 in all the patients were generally similar to the improvements between baseline and week 16 in the patients who received dupilumab in Part A. In Part A, the incidence of coronavirus disease 2019, nausea, injection-site pain, and headache was at least 10 percentage points higher among the patients who received dupilumab (at either dose) than among those who received placebo. Serious adverse events were reported in 3 patients who received dupilumab during Part A and in 6 patients overall during Part B.
CONCLUSIONS
Dupilumab resulted in histologic remission in a significantly higher percentage of children with eosinophilic esophagitis than placebo. The higher-exposure dupilumab regimen also led to improvements in measures of key secondary end points as compared with placebo. (Funded by Sanofi and Regeneron Pharmaceuticals; EoE KIDS ClinicalTrials.gov number, NCT04394351.).
Topics: Humans; Eosinophilic Esophagitis; Antibodies, Monoclonal, Humanized; Male; Female; Child; Double-Blind Method; Child, Preschool; Infant; Eosinophils; Injections, Subcutaneous; Dose-Response Relationship, Drug; Esophagus; Interleukin-13; Remission Induction; Interleukin-4
PubMed: 38924731
DOI: 10.1056/NEJMoa2312282 -
Neurology Jul 2024Atogepant is an oral, calcitonin gene-related peptide receptor antagonist approved for the preventive treatment of migraine. We evaluated the efficacy of atogepant for... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND OBJECTIVES
Atogepant is an oral, calcitonin gene-related peptide receptor antagonist approved for the preventive treatment of migraine. We evaluated the efficacy of atogepant for the preventive treatment of chronic migraine (CM) in participants with and without acute medication overuse.
METHODS
This subgroup analysis of the phase 3, 12-week, randomized, double-blind, placebo-controlled PROGRESS trial evaluated adults with a ≥1-year history of CM, ≥15 monthly headache days (MHDs), and ≥8 monthly migraine days (MMDs) during the 4-week baseline period. Participants were randomized (1:1:1) to placebo, atogepant 30 mg twice daily (BID), or atogepant 60 mg once daily (QD) for 12 weeks and were analyzed by acute medication overuse status (triptans/ergots for ≥10 days per month, simple analgesics for ≥15 days per month, or combinations of triptans/ergots/simple analgesics for ≥10 days per month). Outcomes included change from baseline in mean MMDs, MHDs, and monthly acute medication use days; ≥50% reduction in mean MMDs across 12 weeks; and patient-reported outcome (PRO) measures.
RESULTS
Of 755 participants in the modified intent-to-treat population, 500 (66.2%) met baseline acute medication overuse criteria (placebo, n = 169 [68.7%]; atogepant 30 mg BID, n = 161 [63.6%]; atogepant 60 mg QD, n = 170 [66.4%]). The least squares mean difference (LSMD) (95% CI) from placebo in MMDs was -2.7 (-4.0 to -1.4) with atogepant 30 mg BID and -1.9 (-3.2 to -0.6) with atogepant 60 mg QD. Mean MHDs (LSMD [95% CI] -2.8 [-4.0 to -1.5] and -2.1 [-3.3 to -0.8]) and mean acute medication use days (LSMD [95% CI] -2.8 [-4.1 to -1.6] and -2.6 [-3.9 to -1.3]) were reduced and a higher proportion of participants achieved ≥50% reduction in MMDs (odds ratio [95% CI] 2.5 [1.5-4.0] and 2.3 [1.4-3.7]) with atogepant 30 mg BID and atogepant 60 mg QD. There was a 52.1%-61.9% reduction in the proportion of atogepant-treated participants meeting acute medication overuse criteria over 12 weeks. Atogepant improved PRO measures. Similar results were observed in the subgroup without acute medication overuse.
DISCUSSION
Atogepant was effective in participants with CM, with and without acute medication overuse, as evidenced by reductions in mean MMDs, MHDs, and acute medication use days; reductions in the proportion of participants meeting acute medication overuse criteria; and improvements in PROs.
TRIAL REGISTRATION INFORMATION
ClinicalTrials.gov NCT03855137. Submitted: February 25, 2019; first patient enrolled: March 11, 2019. clinicaltrials.gov/ct2/show/NCT03855137.
CLASSIFICATION OF EVIDENCE
This study provides Class II evidence that atogepant reduces mean MMDs, MHDs, and monthly acute medication use days in adult patients with or without medication overuse.
Topics: Humans; Migraine Disorders; Double-Blind Method; Male; Female; Adult; Middle Aged; Calcitonin Gene-Related Peptide Receptor Antagonists; Chronic Disease; Treatment Outcome; Analgesics; Tryptamines; Headache Disorders, Secondary
PubMed: 38924724
DOI: 10.1212/WNL.0000000000209584