Safety and effectiveness of ulotaront (SEP-363856) in schizophrenia: results of a 6-month, open-label extension study

Ulotaront, a trace amine-associated receptor 1 (TAAR1) and serotonin 5-HT1A receptors agonist, has demonstrated efficacy in the treatment of patients with an acute exacerbation of schizophrenia in a 4-week, double-blind, placebo-controlled study. The aim of this 26-week open-label extension study was to evaluate the safety and effectiveness of ulotaront (25/50/75 mg/d) in patients who completed the initial 4-week study. Of the 193 4-week completers, 157 patients (81.3%) continued into the open-label extension study; 66.9% were completers. Among all extension phase patients, treatment with ulotaront was associated with minimal changes in body weight (mean [SD] change from double-blind baseline: −0.3 [3.7] kg), cholesterol (median change, −2.0 mg/dL), triglycerides (median, −5.0 mg/dL), and prolactin (female, median, −3.4 ng/mL; male, median, −2.7 ng/mL). Movement disorder scales showed no extrapyramidal effects. Twenty-six weeks of extension phase treatment was associated with a mean (95% CI) observed change from open-label baseline in the PANSS total score of −22.6 (−25.6, −19.6; effect size, 1.46), and a mean (95% CI) change in the CGI-Severity score of −1.0 (−1.2, −0.8; effect size, 1.07). Long-term treatment with the TAAR1 agonist ulotaront, in the daily dose range of 25–75 mg, was characterized by a relatively high completion rate, an adverse event profile notable for the absence of extrapyramidal-related adverse effects, a low liability for adverse weight and metabolic effects, and no effect on prolactin levels. Additional studies are needed to further confirm the long-term efficacy and safety of ulotaront.

Safety and efficacy of thalidomide in patients with transfusion-dependent β-thalassemia: a randomized clinical trial

Thalidomide induces γ-globin expression in erythroid progenitor cells, but its efficacy on patients with transfusion-dependent β-thalassemia (TDT) remains unclear. In this phase 2, multi-center, randomized, double-blind clinical trial, we aimed to determine the safety and efficacy of thalidomide in TDT patients. A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks, followed by an extension phase of at least 36 weeks. The primary endpoint was the change of hemoglobin (Hb) level in the patients. The secondary endpoints included the red blood cell (RBC) units transfused and adverse effects. In the placebo-controlled period, Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0 (range, 2.5 to 37.5) g/L, whereas Hb in patients treated with placebo did not significantly change. Within the 12 weeks, the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4 ± 5.0 U and 10.3 ± 6.4 U, respectively (P < 0.001). Adverse events of drowsiness, dizziness, fatigue, pyrexia, sore throat, and rash were more common with thalidomide than placebo. In the extension phase, treatment with thalidomide for 24 weeks resulted in a sustainable increase in Hb concentrations which reached 104.9 ± 19.0 g/L, without blood transfusion. Significant increase in Hb concentration and reduction in RBC transfusions were associated with non β0/β0 and HBS1L-MYB (rs9399137 C/T, C/C; rs4895441 A/G, G/G) genotypes. These results demonstrated that thalidomide is effective in patients with TDT.

Differences in the Flexion and Extension Phases during Kneeling Investigated by Kinematic and Contact Point Analyses: A Cross-sectional Study

Background: Kneeling is necessary for certain religious and ceremonial occasions, crouching work, and gardening, which many people take part in worldwide. However, there have been few reports regarding kneeling activities. The purpose of this study was to clarify the kinematics of kneeling.Methods: The subjects were 15 healthy young males. Kneeling activity was analysed within a knee flexion angle from 100° to maximum flexion (maxflex, mean ± SD = 161.3 ± 3.2°). The kinematic and contact point (CP) analyses were performed using a 2D/3D registration method, in which a 3D bone model created from computed tomography images was matched to knee lateral fluoroscopic images and analysed on a personal computer.Results: In the kinematic analysis, the femur translated 37.5 mm posteriorly and rotated 19.8° externally relative to the tibia during the knee flexion phase. During the knee extension phase, the femur translated 36.4 mm anteriorly, which was almost the same amount as in the knee flexion phase. However, the femur rotated only 7.4° internally during the knee extension phase. In the CP analysis, the amount of anterior translation of the CP in the knee extension phase was greater in the medial CP and smaller in the lateral CP than that of posterior translation in the knee flexion phase.Conclusions: In kneeling, there was a difference in the rotational kinematics between the flexion phase and the extension phase. The kinematic difference between the flexion and extension phases may have some effect on the meniscus and articular cartilage.

Implementation of a zero fluoroscopic workflow using a simplified intracardiac echocardiography guided method for catheter ablation of atrial fibrillation, including repeat procedures

Objective Pulmonary vein isolation (PVI) is the cornerstone of the interventional treatment of atrial fibrillation (AF). Traditionally, during these procedures the catheters are guided by fluoroscopy, which poses a risk to the patient and staff by ionizing radiation. Our aim was to describe our experience in the implementation of an intracardiac echocardiography (ICE) guided zero fluoroscopic (ZF) ablation approach to our routine clinical practice. Methods We developed a simplified ICE guided technique to perform ablation procedures for AF, with the aid of a 3D electroanatomical mapping system. The workflow was implemented in two phases: (1) the Introductory phase, where the first 16 ZF PVIs were compared with 16 cases performed with fluoroscopy and (2) the Extension phase, where 71 consecutive patients (including repeat procedures) with ZF approach were included. Standard PVI (and redoPVI) procedures were performed, data on feasibility of the ZF approach, complications, acute and 1-year success rates were collected. Results In the Introductory phase, 94% of the procedures could be performed with complete ZF with a median procedure time of 77.5 (73.5–83) minutes. In one case fluoroscopy was used to guide the ICE catheter to the atrium. There was no difference in the complication, acute and 1-year success rates, compared with fluoroscopy guided procedures. In the Extension phase, 97% of the procedures could be completed with complete ZF. In one case fluoroscopy was used to guide the transseptal puncture and in another to position the ICE catheter. Acute success of PVI was achieved in all cases, 64.4% patients were arrhythmia free at 1-year. Acute major complications were observed in 4 cases, all of these occurred in the redo PVI group and consisted of 2 tamponades, 1 transient ischemic attack and 1 pseudoaneurysm at the puncture site. The procedures were carried out by all members of the electrophysiology unit in the Extension phase, including less experienced operators and electrophysiology fellows (3 physicians) under the supervision of the senior electrophysiologist. Consequently, procedure times became longer [90 (75–105) vs 77.5 (73.5–85) min, p = 0.014]. Conclusions According to our results, a ZF workflow of AF ablations can be successfully implemented into the routine practice of an electrophysiology laboratory, without compromising safety and effectivity.