Open-label Study Research Articles

Duodeno-ileal diversion with self-forming magnets in a sutureless neodymium anastomosis procedure (SNAP) for weight recidivism after sleeve gastrectomy: feasibility and 9-month results.

The sleeve gastrectomy (SG) has become the most common bariatric procedure worldwide. However, insufficient weight loss or weight recidivism is frequent, which may require effective and safe revisional procedures. To determine the technical feasibility and safety of a minimally invasive, duodeno-ileal side-to-side anastomosis using a Sutureless Neodymium Anastomosis Procedure (SNAP) for patients with weight recidivism or inadequate weight loss following SG. This is a prospective, single-arm, open-label pilot study that enrolled patients with obesity to assist in weight reduction following an SG performed > 12months prior. For the SNAP, self-assembling magnets were deployed into the ileum (laparoscopically) and duodenum (per-oral endoscopy). Magnets were coupled under laparoscopic and fluoroscopic guidance to create a compression anastomosis. The primary endpoints were technical feasibility, weight loss, and rate of serious adverse events (SAEs). Successful duodeno-ileal diversions were created with SNAP in 27 participants (mean age: 50.6 ± 9.1, mean BMI: 38.1 ± 4.6kg/m2) with no device-related serious adverse events. Upper endoscopy at 3months confirmed patent, healthy anastomoses in all patients. At 9months, patients (n = 24) experienced 11.9 ± 6.2%, 14.5 ± 10.8%, and 17.0 ± 13.9% TBWL at 3, 6, and 9months, respectively. There were no device-related SAEs. The SNAP is technically feasible and relatively safe, with all patients presenting widely patent anastomosis at 3months. Patients experienced a progressive, clinically meaningful weight loss. Further studies are needed to confirm our findings.

Pharmacokinetics and Safety of Spesolimab in Healthy Chinese Subjects: An Open-Label, Phase I Study.

Generalized pustular psoriasis (GPP) is a rare and potentially life-threatening inflammatory skin disease. Interleukin (IL)-36 signalling may play a central role in GPP pathogenesis. Spesolimab is a humanized anti-IL-36 monoclonal antibody inhibiting the IL-36 signalling pathway. Here, we investigated the pharmacokinetics and safety of spesolimab in healthy Chinese subjects. In this Phase 1, single-dose, parallel-group, open-label study, healthy Chinese subjects aged 18-45years received a single spesolimab dose by intravenous infusion (IV; 450mg, 900mg, or 1200mg) or subcutaneous (SC) administration (300mg or 600mg). Primary endpoints were spesolimab exposure (area under the plasma concentration-time curve and maximum plasma concentration); secondary endpoints were treatment-emergent adverse events (TEAEs) and drug-related adverse events (AEs). Fifty subjects received IV (n = 30) or SC (n = 20) spesolimab (n = 10 per dose group); 60.0% were male, mean ± standard deviation age was 31.5 ± 6.6 and 31.0 ± 6.5years in the IV and SC groups, respectively. Spesolimab exposure increased in a dose-proportional manner in both groups. TEAEs were reported in 83.3% and 80.0% of subjects in the IV and SC groups, the most common TEAE was upper respiratory tract infection (20.0% and 25.0%, respectively). One serious AE of hand fracture was reported in the 900mg IV group that was not considered drug-related. Drug-related AEs were reported in 53.3% and 55.0% of subjects in the IV and SC groups. All laboratory-related AEs were mild and resolved. Spesolimab exposure increased in a dose-proportional manner after a single dose by IV and SC administration. Spesolimab was well tolerated in healthy Chinese subjects. Clinicaltrials.gov registration: NCT04390568.

Pruritus Severity and Serum Phosphate in CKD: A Post Hoc Analysis of Difelikefalin Studies.

Chronic kidney disease-associated pruritus (CKD-aP) has historically been associated with elevated serum phosphate (sP). Difelikefalin is a novel antipruritic agent approved for the treatment of moderate-to-severe CKD-aP in adults undergoing hemodialysis. This post hoc analysis utilized data from Phase 3 difelikefalin studies (KALM-1, KALM-2, and open-label Study 3105) to assess the role of sP in the pathogenesis of CKD-aP, and whether difelikefalin ameliorates CKD-aP in patients with and without elevated sP. Patients with moderate-to-severe CKD-aP undergoing hemodialysis with baseline sP data were included in the analysis (KALM-1 and KALM-2, n=845; Study 3105, n=220). Assessments included correlation between 24-hour Worst Itching Intensity Numerical Rating Scale (WI-NRS) score and sP. In KALM-1 and KALM-2, baseline characteristics in the overall population were similar between patients with sP ≤5.5 and >5.5 mg/dL; no significant correlation was observed between WI-NRS and sP at baseline or at Week 12. In patients receiving placebo, no correlation was observed between WI-NRS and sP at baseline or between their change from baseline to Week 12 (all p<0.05). Clinically meaningful (≥3-point) reductions from baseline to Week 12 in WI-NRS scores were reported by more patients receiving placebo with baseline sP ≤5.5 mg/dL than >5.5 mg/dL; least squares (LS) mean 37.2% versus 27.4% (odds ratio [95% CI], 0.63 [0.41, 0.97]; p=0.04). A greater proportion of patients treated with difelikefalin achieved a ≥3-point WI-NRS reduction from baseline to Week 12 versus placebo, and was similar between sP ≤5.5 and >5.5 mg/dL subgroups (LS means 51.1% vs 57.6% [p=0.20]). No significant relationships between sP and WI-NRS in patients receiving difelikefalin were identified in Study 3105 at any timepoint. No correlation was observed between pruritus severity and sP, or response to placebo or difelikefalin in patients with CKD-aP undergoing HD. Difelikefalin improved itch versus placebo irrespective of baseline sP.

Switching from Dose-Intensified intravenous to SubCutaneoUS infliximab in Inflammatory Bowel Disease (DISCUS-IBD): protocol for a multicentre randomised controlled trial

IntroductionA substantial proportion of patients with inflammatory bowel disease (IBD) on intravenous infliximab require dose intensification. Accessing additional intravenous infliximab is labour-intensive and expensive, depending on insurance and pharmaceutical reimbursement....

Evaluation of a urinary filtration device for kidney stone retrieval: Pibox®

Introduction: There is an unmet need to offer a proper urinary straining device for patients in whom spontaneous expulsion of stones is expected. The objective of this study was to assess the efficacity, duration and ease of use of a new filtration device: the Pibox®.Material and Methods: This was a single-institution, non-randomized open-label study. Consecutive male patients with at least one stone that was susceptible of spontaneous passage, or after shockwave lithotripsy were included. The first 30 consecutive patients (Group 1) used the usual recommended techniques, and the 30 following consecutive patients (Group 2) were given the Pibox®. The patients completed a questionnaire when seen at 1 month follow-up.Results: Sixty men were included between January 2023 and May 2023. Thirteen (43 %) patients retrieved a stone in each group (p=1). Filtration was performed for a median of 5 days in Group 1 and 10 days in Group 2 (p=0.03). Fourteen (46 %) patients were satisfied or very satisfied with their filtration technique without the device versus 18 (60 %) with the Pibox® (p=0.3). Eighteen (60 %) and 21 patients (70 %) would recommend their straining technique to a relative in groups 1 and 2, respectively (p=0.42).Conclusions: The number of straining days was twice longer with the Pibox® device and is in favor of a better observance. The device did not increase the number of stones retrieved by urine filtration, which was high in this pilot study and may have been due to a participation bias.

Study APV20002: Safety and Efficacy Results Through Week 684 for Pediatric Participants Living with HIV-1 Treated with Ritonavir-Boosted Fosamprenavir Oral Solution-Based Antiretroviral Therapy.

APV20002 was a multicenter, international, open-label study that began in 2003 investigating the pharmacokinetics, efficacy, and safety of ritonavir-boosted fosamprenavir (FPV/r) oral solution (OS) in combination with nucleoside reverse transcriptase inhibitor-based antiretroviral therapy (ART) in participants living with HIV-1 aged 4 weeks to <2 years with a primary endpoint at Week 48 (48W). Participants in APV20002 could continue in the study post-48W until FPV OS was locally available in their countries. Children were required to discontinue after reaching >39 kg or if FPV OS had no clinical benefit. Fifty-nine participants were enrolled; 5/59 received a single FPV OS visit for pharmacokinetic determinations. Most (38/54; 70%) were antiretroviral experienced; 39/59 participants had >48 weeks on treatment, 4/39 of whom discontinued after 48 weeks due to an adverse event (AE). At 48W, 88% of participants had HIV-1 RNA <400 copies/mL by Observed analysis; the proportion with HIV-1 RNA <400 copies/mL remained high (84%-100%) through Week 684. The median CD4+ cell count was 1,235 cells/mm3 [n = 51] at baseline, 1,690 cells/mm3 (n = 41) at Week 48, and 1,280 cells/mm3 (n = 21) at Week 180. From baseline to Week 684, 54/59 (92%) participants had ≥1 treatment-emergent AE regardless of causality; 42/59 (71%) had a treatment-emergent grade 2-4 AE, predominantly maximum toxicity: grade 2; 21/59 (36%) and 21/59 (36%) had severe or grade 3/4 AEs. From baseline to Week 684, 14/54 (26%) participants met virologic failure (VF) criteria, 9/14 before 48W. HIV from 1/9 VFs through 48W developed treatment-emergent reduced susceptibility to FPV and 1/9 to lamivudine/emtricitabine. Post-48W, 4/5 participants with VF had phenotype results; all were still susceptible to all study drugs at VF. In conclusion, FPV OS-based ART was efficacious and generally well tolerated in this long-running pediatric study through 684 weeks of treatment, with a safety profile consistent with experience in adults and older children.

Evaluation of the efficacy and safety of rivaroxaban compared to warfarin in patients with left ventricular apical thrombus: a randomized clinical trial

IntroductionThis research is one of the pioneering randomized clinical trials (RCTs) aimed at assessing the effectiveness and safety of rivaroxaban in treating left ventricular thrombus (LVT) in patients who have experienced acute coronary syndrome (ACS).Materials and methodsThis is a randomized, controlled, interventional, open-label study. The patients were randomly divided into warfarin and rivaroxaban groups. We performed transthoracic echocardiography at the start of the study and again after three months to measure the thrombus area in square millimeters. The morphology of the thrombus was categorized into mural and round, and the mobility was classified into immobile, semi-mobile and hypermobile. We also monitored for adverse events including bleeding, systemic embolic occurrences, rehospitalization, and major adverse cardiac events (MACE).ResultsThe study included fifty-two patients in the intention-to-treat analysis, with an equal split between the rivaroxaban and warfarin groups (26 patients each). The average follow-up duration was three months. The thrombus resolution rates in the rivaroxaban (76.9%) and warfarin (69.2%) groups, as well as the thrombus size reduction, did not show statistical significance between groups. All semi-mobile or hypermobile thrombi transformed into immobile and all of the round LVTs changed into a mural in both rivaroxaban and warfarin groups. No significant difference was observed in bleeding complications and rehospitalization between the two groups.ConclusionThe trial demonstrated that rivaroxaban is as effective as warfarin in terms of thrombus resolution rate, reduction in thrombus size, bleeding risk, and rehospitalization rate. Our findings suggest that rivaroxaban is a viable alternative to warfarin for managing left ventricular thrombus.Graphical

Steady-state pharmacokinetics of lamivudine in end-stage kidney failure persons with detectable and undetectable HIV-1 RNA in peritoneal dialysis effluent

BackgroundRenally adjusted lamivudine dosages are effective. However, some of the kidney failure patients managed with lamivudine-containing regimens are failing to suppress HIV in peritoneal dialysis (CAPD) effluent. The steady-state lamivudine pharmacokinetics among these patients was evaluated.MethodsThis overnight open-label pharmacokinetic study enrolled participants living with HIV and managed with CAPD. Lamivudine levels in blood serum and CAPD effluent samples were quantified using liquid chromatography coupled with a mass spectrometer. Pharmacokinetic measures were obtained through non-compartmental analysis.ResultsTwenty-eight participants were recruited with a median antiretroviral (ARV) drug duration of 8 (IQR,4.5–10.5) years and a CAPD duration of 13.3 (IQR,3.3–31.9) months. 14.3% (4/28) had detectable unsuppressed HIV-1 viral load in CAPD effluents. The majority (78,6%,22/28) of participants received a 50 mg dose, while 10.7% (3/28), and another 10.7% (3/28) received 75 mg and 300 mg dosages, respectively. Among those treated with 75 and 300 mg, 66.7% (2/3) and 33.3% (1/3) had detectable HIV-VL in CAPD, respectively. The peritoneal membrane characteristics and CAPD system strengths were variable across the entire study population. Lamivudine exposure was increased in blood serum (50 mg-AUC0-24 h, 651.3 ng/mL; 75 mg-AUC0-24 h, 677.84 ng/mL; 300 mg-AUC0-24 h, 3135.89 ng/mL) compared to CAPD effluents (50 mg-AUC0-24 h, 384.91 ng/mL; 75 mg-AUC0-24 h, 383.24 ng/mL; 300 mg-AUC0-24 h, 2001.60 ng/mL) among the entire study population. The Cmax (50 mg, 41.5 ng/mL; 75 mg, 53.2 ng/mL; 300 mg, 199.1 ng/mL) and Cmin (50 mg, 17.8 ng/mL; 75 mg, 16.4 ng/mL; 300 mg, 76.4 ng/mL) measured in serum were within the therapeutic levels.ConclusionsSteady-state lamivudine pharmacokinetic measures were variable among the entire study population. However, the total lamivudine exposure was within the therapeutic levels.

Efanesoctocog Alfa Prophylaxis for Children with Severe Hemophilia A

BackgroundOnce-weekly efanesoctocog alfa provides high sustained factor VIII activity with superior bleeding prevention as compared with prestudy factor VIII prophylaxis in previously treated patients 12 years of age or older with severe hemophilia A. Data on outcomes of efanesoctocog alfa treatment in children younger than 12 years of age with severe hemophilia A are limited.MethodsWe conducted a phase 3, open-label study involving previously treated patients younger than 12 years of age with severe hemophilia A. Patients received prophylaxis with once-weekly efanesoctocog alfa (50 IU per kilogram of body weight) for 52 weeks. The primary end point was the occurrence of factor VIII inhibitors (neutralizing antibodies against factor VIII). Secondary end points included annualized rates of treated bleeding episodes, bleeding treatment, safety, and pharmacokinetics.ResultsA total of 74 male patients were enrolled (38 with an age of <6 years and 36 with an age of 6 to <12 years). No factor VIII inhibitors developed. Most adverse events were nonserious. No serious adverse events that were assessed by the investigator as being related to efanesoctocog alfa were reported. In the 73 patients treated according to the protocol, the median and model-based mean annualized bleeding rates were 0.00 (interquartile range, 0.00 to 1.02) and 0.61 (95% confidence interval, 0.42 to 0.90), respectively. A total of 47 patients (64%) had no treated bleeding episodes, 65 (88%) had no spontaneous bleeding episodes, and 61 (82%) had no episodes of bleeding into joints. A total of 41 of 43 bleeding episodes (95%) resolved with one injection of efanesoctocog alfa. Mean factor VIII activity at steady state was more than 40 IU per deciliter for 3 days and more than 10 IU per deciliter for almost 7 days after dose administration. The geometric mean terminal half-life was 40.0 hours.ConclusionsIn children with severe hemophilia A, once-weekly prophylaxis with efanesoctocog alfa provided high sustained factor VIII activity in the normal to near-normal range (>40 IU per deciliter) for 3 days and more than 10 IU per deciliter for almost 7 days after administration, leading to effective bleeding prevention. Efanesoctocog alfa was associated with mainly nonserious adverse events. (Funded by Sanofi and Sobi; XTEND-Kids ClinicalTrials.gov number, NCT04759131.)

Dupilumab 200 mg was efficacious in children (6-11 years) with moderate-to-severe asthma for up to 2 years: EXCURSION open-label extension study.

The phase 3 VOYAGE (NCT02948959) and open-label extension EXCURSION (NCT03560466) studies evaluated dupilumab in children (6-11 years) with uncontrolled moderate-to-severe asthma. This post hoc analysis assessed the efficacy and safety of add-on dupilumab 200 mg every 2 weeks (q2w), the largest dose cohort in both studies, in children from VOYAGE who participated in EXCURSION. Annualized rate of severe asthma exacerbations (AERs), change in prebronchodilator percent predicted forced expiratory volume in 1 s (ppFEV1), and treatment-emergent adverse events were assessed in children with moderate-to-severe asthma who received dupilumab 200 mg q2w in VOYAGE and EXCURSION (dupilumab/dupilumab arm) and those who received placebo in VOYAGE and dupilumab 200 mg q2w in EXCURSION (placebo/dupilumab arm). These endpoints were also assessed in children with moderate-to-severe type 2 asthma (defined as blood eosinophil count ≥150 cells/µL or FeNO ≥20 ppb at the parent study baseline [PSBL]). In the overall population, dupilumab reduced AER and improved prebronchodilator ppFEV1 in the dupilumab/dupilumab arm (n = 158) for up to 2 years. Children receiving placebo/dupilumab (n = 85) showed similar reductions after initiation of dupilumab 200 mg q2w in EXCURSION. Similar results were observed for children with type 2 asthma at PSBL. The safety profile was consistent with the known safety profile of dupilumab. In children (6-11 years) with uncontrolled moderate-to-severe type 2 asthma, dupilumab 200 mg reduced exacerbation rates and improved lung function for up to 2 years and showed safety consistent with the known dupilumab safety profile.

A phase 1 open label study to assess the human mass balance and metabolite profile of 14C-fosmanogepix, a novel Gwt-1 inhibitor in healthy male participants.

This study is registered with ClinicalTrials.gov as NCT04804059.

Efficacy of dexamethasone implant in the management of chronic central serous chorioretinopathy without choroidal neovascularization.

To demonstrate the treatment efficacy of intravitreal dexamethasone (DEX) implant in chronic recurrent/persistent central serous chorioretinopathy (CSC). Prospective, non-randomized, open-label study. In this study, subjects with chronic CSC without signs of choroidal neovascularization (CNV) received intravitreal DEX implant therapy. The primary outcome measure was the change in visual acuity. Changes in central macular thickness (CMT) and change in subfoveal choroidal thickness (SFCT) on optical coherence tomography (OCT), incidence of recurrent fluid, and safety of DEX implant were secondary outcome measures. Subjects were followed up for a minimum of 3 months after DEX implantation. In total, 20 eyes of 20 subjects (mean age: 47 ± 9 years) with a median disease duration of 23.5 months were enrolled. With a single injection of DEX implant, a reduction in CMT was noted in 90% of eyes. Complete resolution of subretinal and intraretinal fluid was noted in 55% of eyes within 3 months of injection. A significant improvement in vision (mean Log MAR visual acuity 0.66 ± 0.49 vs. 0.54 ± 0.45; P = 0.020), mean CMT (338 ± 110 microns to 238 ± 73 microns; P < 0.001) and SFCT (514 ± 95 microns to 445 ± 111 microns; P < 0.001) was noted over 3 months. Recurrent fluid was noted in 50% of eyes after a mean follow-up duration of 7 ± 4 months. Elevated intraocular pressure, managed by topical therapy, was noted in six eyes. The consistent improvement in visual acuity, fluid resolution, and reduction in choroidal thickness suggests a possible role for DEX implants in managing chronic CSC. A larger randomized trial is warranted.

Risk Factor Targeted Perioperative Care Reduces Anastomotic Leakage after Colorectal Surgery: The DoubleCheck study.

The DoubleCheck study aimed to introduce pre- and perioperative interventions minimizing exposure to modifiable risk factors and determine its effect on CAL. Colorectal anastomotic leakage (CAL) is a severe complication. In order to predict and prevent its occurrence, the LekCheck study identified intraoperative modifiable risk factors for CAL: anemia, hyperglycemia, hypothermia, incorrect timing of antibiotic prophylaxis, administration of vasopressors and epidural analgesia. This international open-labelled interventional study was performed between September 2021 and December 2023. An enhanced care bundle consisting of anemia correction, glucose measurement, attaining normothermia, antibiotics administration within 60 to 15 minutes preoperatively, refraining from vasopressors and epidural analgesia was introduced. Primary outcome was the occurrence of intraoperative risk factors just prior to the anastomosis creation. Secondary outcomes were CAL and mortality. Univariate and multivariate regression analysis were performed to establish the relationship between the enhanced care bundle, exposure to the six factors and CAL. The historical LekCheck group consisted of 1572 patients versus 902 in the DoubleCheck. The LekCheck group had a mean of 1.84 risk factors versus 1.63 in DoubleCheck ( P <0.001). In the DoubleCheck significantly less patients had ≥3 risk factors ( P <0.001). CAL was significantly lower in the DoubleCheck group (8.6% vs. 6.2%, P =0.039). The reduction of CAL was associated with the enhanced care bundle in multivariate regression analysis (OR 1.521, 95% CI 1.01-2.29, P =0.045). The mortality rate did not differ significantly (1.3%, vs. 0.8%, P =0.237). The DoubleCheck study showed that optimization of modifiable risk factors reduced CAL in colorectal surgery.

Transrectal Drainage Tube Use for Preventing Post-endoscopic Submucosal Dissection Coagulation Syndrome in Patients with Colorectal Lesions: A Multicenter Randomized Controlled Clinical Trial.

Post-endoscopic submucosal dissection (ESD) coagulation syndrome (PECS) prevention is one of the common postoperative complications of colorectal ESD. Considering the increasing incidence of PECS, it is critical to investigate various prevention To evaluate the efficacy of transrectal drainage tubes (TDTs) in PECS prevention in patients following colorectal ESD. From July 2022 to July 2023, a multicenter, randomized controlled clinical trial was conducted in 3 hospitals in China. Patients with superficial colorectal lesions ≥20 mm who had undergone ESD for a single lesion were enrolled. Initially, 229 patients were included in the study and 5 were excluded. 224 were randomly assigned to the TDT and non-TDT group in the end. This open-label study utilized a parallel design with a 1:1 allocation ratio, and endoscopists and patients were not blind to the randomization. And a 24Fr drainage tube was inserted approximately 10-15 cm above the anus after the ESD under the endoscopy and tightly attached to a drainage bag. The TDTs were removed in 1 to 3 days following the ESD. A total of 229 eligible patients were enrolled in this study and 5 patients were excluded. Ultimately, 224 patients were assigned to the TDT group(n=112) and non-TDT group(n=112). The median age for the patients was 63.45(IQR 57-71; 59 men [52.68%]) in the TDT group and 60.95(IQR 54-68; 60 men [53.57%]) in the non-TDT group. Intention-to-treat analysis showed patients in the TDT group had a lower incidence of PECS than patients in the non-TDT group (7 [6.25%] vs 20 [17.86%]; relative risk, 0.350; 95% CI,0.154-0.795; P =0.008). In the subgroup analysis, TDTs were found to prevent PECS in patients of the female gender(odd ratio, 0.097; 95% CI, 0.021-0.449; P =0.001), tumor size ＜4cm(odd ratio, 0.203; 95% CI, 0.056-0.728; P = 0.011), tumor located in the left-sided colorectum (odd ratio, 0. 339 95% CI, 0.120-0.957; P = 0.035) and shorter procedure time(＜45 mins) (odd ratio, 0.316; 95% CI, 0.113-0.879; P =0.023). The tube fell off in 1 case (0.89%) accidentally ahead of time. No TDT-related complication was observed. The results from this randomized clinical study indicate that the application of TDTs effectively reduced the incidence of PECS in patients after colorectal ESD (chictr.org.cn Identifier: ChiCTR2200062164).

Dupilumab in Adults With Moderate to Severe Atopic Dermatitis

Moderate to severe atopic dermatitis (AD) is a chronic inflammatory skin disease that often requires continuous long-term systemic management. Long-term safety and efficacy data for treatment options are critically important. To assess the safety and efficacy of dupilumab treatment for up to 5 years in adults with moderate to severe AD. The 5-year LIBERTY AD open-label extension study was conducted from September 2013 to June 2022 at 550 sites in 28 countries. The study enrolled adult patients with moderate to severe AD who had participated in previous dupilumab clinical trials. Data were analyzed from August 2022 to February 2023. At enrollment, patients initiated a regimen of subcutaneous dupilumab, 200 mg, weekly (400-mg loading dose). The regimen was amended in June 2014 to dupilumab, 300 mg, weekly (600-mg loading dose) based on a dose-ranging study and again in November 2019 to dupilumab, 300 mg, every 2 weeks to align with the regulatory regimen approvals. The primary end points were the incidence and rate of treatment-emergent adverse events (TEAEs). Key secondary end points included incidence and rate of serious TEAEs and adverse events of special interest, proportion of patients achieving an Investigator's Global Assessment (IGA) score of 0 or 1 (clear or almost clear), and proportion of patients with 75% or more improvement in the Eczema Area and Severity Index (EASI) from the parent study baseline. A total of 2677 patients were enrolled and treated in the open-label extension study; 1611 (60.2%) were male, and the mean (SD) age was 39.2 (13.4) years. A total of 334 patients (12.5%) completed treatment up to week 260. The most common reasons for withdrawal were due to regulatory approval of dupilumab in compliance with the study protocol (810 of 1380 [58.7%]), patient withdrawal (248 of 1380 [18.0%]), and adverse events (116 of 1380 [8.4%]). Exposure-adjusted rates of TEAEs were generally stable or declined throughout the study. Common TEAEs (incidence of 5% or greater) included nasopharyngitis, worsening AD, upper respiratory tract infection, conjunctivitis, conjunctivitis allergic, headache, oral herpes, and injection-site reaction. At week 260, 220 of 326 patients (67.5%) achieved an IGA score of 0 or 1 and 288 of 324 (88.9%) achieved 75% or greater improvement in the EASI. The mean (SD) EASI score was 16.39 (14.60) at baseline and 2.75 (5.62) at end of study. In this study, there was sustained safety and efficacy of continuous long-term dupilumab treatment for adults with moderate to severe AD.

Safety of Rimegepant in Adults with Migraine and Cardiovascular Risk Factors: Analysis of a Multicenter, Long-Term, Open-Label Study.

Cardiovascular (CV) risk factors can limit treatment options for migraine. Rimegepant is an orally administered small-molecule calcitonin gene-related peptide receptor antagonist that does not induce vasoconstriction. The aim of these post hoc subgroup analyses was to assess the safety of rimegepant according to CV risk. In a multicenter, long-term, open-label, phase II/III safety study, participants with a history of 2-14 migraine attacks per month of moderate or severe pain intensity self-administered rimegepant 75 mg, orally, to treat migraine up to once daily for up to 52 weeks. Uncontrolled, unstable, or recently diagnosed CV disease was part of the exclusion criteria. Safety was assessed across subgroups according to number of CV risk factors (0, 1, or ≥ 2) and Framingham Risk Score (< 10% or ≥ 10%). Of 1800 treated participants, 28.8% had one CV risk factor and 12.1% had ≥ 2 CV risk factors; 7.0% had Framingham Risk Score ≥ 10%. Across the subgroups with 0, 1, and ≥ 2 CV risk factors and Framingham Risk Score < 10% and ≥ 10%, respectively, proportions of participants reporting adverse events (AEs; 59.6%, 61.4%, 62.2%, 59.9%, 67.5%) and serious AEs (2.7%, 2.5%, 2.3%, 2.6%, 2.4%) were consistent, and AEs leading to study drug discontinuation were low (1.9%, 3.1%, 5.5%, 2.5%, 4.8%). Rimegepant showed favorable safety and tolerability in adults with migraine and CV risk factors, including those with moderate to high CV risk. ClinicalTrials.gov NCT03266588.

Comparative study between the efficacy of prabotulinum toxin-A versus onabotulinum toxin-A for the treatment of upper facial expression lines.

Botulinum Toxin (BoNTA) is the most used nonsurgical aesthetic procedure to treat facial expression lines. This study compared the efficacy of Prabotulinum toxin-A, a novel BoNTA that originates from Clostridium botulinum Hall-A, with onabotulinum toxin-A in treating facial expression lines using the Facial Wrinkle Scale (FWS) and FACE-Q questionnaires. This was an experimental, comparative, longitudinal, open-label, and prospective study. Patients aged between 25 and 40 years with upper-third facial expression lines were included. Follow-ups were made at three, seven, 30, and 120 days. A total of 26 patients were included: 20 female, and six males, with a mean age of 28.26 years. An average of 31.00 IU and 31.38 IU were administered to the onabotulinum and prabotulinum groups, respectively. The prabotulinum group demonstrated superiority in FWS and Face-Q scores between the first and third days (p ≤ 0.001, p < 0.001, respectively), which continued on day 7. By day 30, there were no differences in the scores of the two questionnaires. Prabotulinum toxin-A is a safe and effective treatment for upper-third facial wrinkles. On day three and seven, the results suggest that prabotulinum toxin-A has a quicker onset of action than onabotulinum toxin-A. On days 30 and 120, both groups showed similar FWS and Face-Q scores.

Respiratory physiological exploration during self-induced cognitive trance

Background and methodsLittle is known about self-induced cognitive trance (SICT) on respiratory function. The aims of this prospective, single-center, non-randomized, open-label study of healthy volunteers, were to characterize spirometry changes during SICT, confirm the safety of this technique, and investigate the potential clinical benefits of SICT. ResultsNine people participated. There were no significant difference in FEV1 FVC or FEF 25–75 before, during, and after SICT. There were significant improvements in grip strength during SICT (+2.2 kg/5.7 %, p<0.05) and in self-efficacy score related to physical activity at the end of the trance. One participant had a significant worsening of FEV1 during SICT in the context of a recent upper airway infection. ConclusionSICT does not significantly modify spirometry data in healthy volunteers and can improve self-efficacy related to physical activity. SICT should probably be performed with caution during upper airway infections.

Vitamin D deficiency and effect of treatment on seizure frequency and quality of life parameters in patients with drug-resistant epilepsy: A randomized clinical trial.

This study was undertaken to assess the effect of treatment of vitamin D deficiency in drug-resistant epilepsy. We conducted a multicenter, double-blind, placebo-controlled, randomized clinical trial, including patients aged ≥15 years with drug-resistant focal or generalized epilepsy. Patients with 25-hydroxyvitamin D (25[OH]D) < 30 ng/mL were randomized to an experimental group (EG) receiving vitamin D3 (cholecalciferol, 100 000 IU, five doses in 3 months) or a control group (CG) receiving matched placebo. During the open-label study, EG patients received 100 000 IU/month for 6 months, whereas CG patients received five doses in 3 months then 1/month for 3 months. Monitoring included seizure frequency (SF), 25(OH)D, calcium, albumin, creatinine assays, and standardized scales for fatigue, anxiety-depression, and quality of life (Modified Fatigue Impact Scale [M-FIS], Hospital Anxiety and Depression Scale, Quality of Life in Epilepsy [QOLIE-31]) at 3, 6, and 12 months. The primary efficacy outcome was the percentage of SF reduction compared to the reference period and CG at 3 months. Secondary outcomes were SF and bilateral tonic-clonic seizure (BTCS) reduction, scale score changes, and correlations with 25(OH)D during the follow-up. Eighty-eight patients were enrolled in the study (56 females, aged 17-74 years), with median baseline SF per 3 months = 16.5 and ≥2 antiseizure medications in 88.6%. In 75 patients (85%), 25(OH)D was <30 ng/mL; 40 of them were randomly assigned to EG and 34 to CG. After the 3-month blinded period, SF reduction did not significantly differ between groups. However, during the open-label period, SF significantly decreased (30% median SF reduction, 33% responder rate at 12 months). BTCSs were reduced by 52%. M-FIS and QOLIE-31 scores were significantly improved at the whole group level. SF reduction correlated with 25(OH)D > 30 ng/mL for >6 months. Despite no proven effect after the 3-month blinded period, the open-label study suggests that long-term vitamin D3 supplementation with optimal 25(OH)D may reduce SF and BTCSs, with a positive effect on fatigue and quality of life. These findings need to be confirmed by further long-term studies. ClinicalTrials.gov identifier: NCT03475225 (03-22-2018).

Reduced protein carbonylation on hormone therapy is associated with improved fibrinolysis in postmenopausal women: the impact of PAI-1 and TAFI activity.

Hormone therapy (HT) has been reported to reduce protein carbonylation (PC) in postmenopausal women, in whom fibrinolysis is impaired. We investigated whether PC affects fibrinolysis and if HT modulates this effect. We enrolled 150 women aged 55.5 ± 4.7years in a randomized interventional open-label study, including 50 on standard oral HT, 50 on ultra-low-dose HT, and 50 controls. PC, along with global fibrinolysis (clot lysis time, CLT), fibrinolysis proteins, and prothrombotic markers were determined at baseline and at 24weeks. Patients with the baseline top quartile PC (> 2.07nM/mg protein) had 10.3% longer CLT, higher activity (but not antigen) of TAFI (+ 19.9%) and PAI-1 (+ 68.1%) compared to the remainder. No differences were observed in thrombin generation, factor VIII, plasminogen or α2-antiplasmin. On-treatment PC decreased by 16.4% (p < 0.0001), without differences related to the type of HT, compared to baseline and by 30% compared to controls, in whom PC and fibrinolysis markers remained unchanged. Patients with PC > 2.07nM/mg had shortened CLT during HT compared to baseline, along with lower PAI-1 (-69%) and TAFI (-26%) activity. In this subgroup CLT was 5.8% shorter compared to controls with the highest PC. In postmenopausal women with increased PC, HT was accompanied by PC reduction and faster clot lysis together with decreased PAI-1 and TAFI activity.