Safety analysis of a live attenuated mumps vaccine in healthy adolescents in China: A phase 4, observational, open-label trial.

Mumps is an acute infectious disease, which was well controlled in the past, but recently it has resurged in some areas. This study aimed to evaluate the safety profile of the live attenuated mumps vaccine after large-scale vaccination. We conducted an observational, open-label phase 4 trial in Shaanxi, China from October 2020 to March 2021. Eligible participants were freshmen of junior high school who were not above 14 years old. Adverse events following immunization (AEFI) monitoring was carried out by active and passive surveillance. Safety follow-ups were conducted during the study participation. Overall, 10057 subjects were enrolled in the active surveillance analysis. A total of 214 subjects reported adverse reactions with an incidence of 2.13% (214/10057). Most adverse reactions were grade 1, and the incidence of grade 1 adverse reactions was 1.44% (145/10057); 0.60% for grade 2 (60/10057); and 0.09% for grade 3 (9/10057). The majority of adverse reactions were solicited (1.73%, 174/10057). Injection-site pain was the most frequently reported local adverse reaction (0.71%, 71/10057), followed by redness (0.29%, 29/10057). The most common systemic adverse reactions were nausea (0.19%, 19/10057) and fever (0.16%, 16/10057). For passive AEFI surveillance, 57 AEFI cases were reported, with an incidence of 19.28/100000 (57/287608). And most AEFI cases were common adverse reactions (66.67%, 38/57). In total, the live attenuated mumps vaccine evaluated in this trial has a favorable safety profile and can be used for large-scale inoculation.

The Correlation between Serum Sclerostin Level and Arterial Stiffness in Peritoneal Dialysis Patients.

Objective: To study the correlation between serum sclerostin (SO) and arterial stiffness in peritoneal dialysis (PD) patients. Methods: The study included 50 Parkinson's disease (PD) patients on continuous ambulatory peritoneal dialysis (CAPD) for more than 6 months at the nephrology department of our hospital. Without regard for age, the eligible patients were assigned to a low PWV group and a high PWV group with brachial-ankle pulse wave velocity (Ba PWV) of 1400 cm/s as the cutoff value. Patient characteristics such as age, gender, height, weight, BMI, smoking history, dialysis age, systolic blood pressure (SBP), diastolic blood pressure (DBP), urea clearance index (Kt/V), residual renal function (RRF), and diabetes mellitus (DM) were analyzed. Biochemical indices for analysis include hemoglobin (Hb), albumin (ALB), total cholesterol (TC), urea nitrogen (BUN), creatinine (CREA), triglyceride (TG), uric acid (UA), parathyroid hormone (PTH), blood phosphorus(P), fasting blood glucose (GLU), corrective calcium (Ca), calcium-phosphorus product, low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), SO, and arterial stiffness. Results: There were 9 males and 16 females in the low PWV group and 12 males and 13 females in the high PWV group. Statistical significance was absent in patient characteristics despite more males in the high PWV group (P=0.055). The low PWV group had significantly lower mean age, SBP, SO, and PWV level, fewer diabetic patients, and higher CREA than the control group. Analysis of PWV-related factors showed that PWV was positively correlated with age, P, Ca, GLU, SBP, PTH, and SO while negatively correlated with CREA. Multiple stepwise regression analysis showed that age, SO, and SBP demonstrated great potential to predict PWV (P < 0.05). Conclusion: The degree of vascular sclerosis is highly correlated with SO level in Parkinson's disease patients, which might provide a theoretical basis for the evaluation of cardiovascular illness in Parkinson's disease patients. High serum sclerostin level is a risk factor for deteriorated arterial stiffness. Given the limited sample size, the relevant results require further validation by expanding the sample size.

Immunogenicity and safety of an inactivated enterovirus 71 vaccine co-administered with measles-mumps-rubella vaccine and live-attenuated Japanese encephalitis vaccine: a phase 4, single-center, randomized controlled trial.

Co-administration of vaccines could be an efficient strategy to increase vaccination uptake and reduce the number of clinic visits. This randomized controlled study aimed to evaluate the immunogenicity and safety of enterovirus 71 (EV71) vaccine co-administered with measles-mumps-rubella (MMR) vaccine and live-attenuated Japanese encephalitis vaccine (LA-JEV). A total of 372 healthy infants were randomly assigned in a 1:1:1 ratio to receive simultaneous administration of EV71 vaccine (dose 1) and MMR on d 0 and EV71 vaccine (dose 2) and LA-JEV on d 30 (Group 1); administration of MMR and LA-JEV on d 0 and 30, respectively (Group 2); or administration of doses 1 and 2 of EV71 vaccine on d 0 and 30, respectively (Group 3). The non-inferiority analysis of the seroconversion for EV71 neutralizing antibody after vaccination was the primary outcome. According to per protocol set, antibody response against EV71, measles, mumps, rubella, and Japanese encephalitis (JE) virus was similar regardless of administration schedule. After vaccination, the seroconversion rate of EV71 neutralizing antibody in Group 1 (107 [97.27%] of 110) was non-inferior to that in Group 3 (109 [97.32%] of 112; difference - 0.05% [95% CI - 5.38 to 5.21]). The incidences of adverse reactions were 62.60% (77/123) in Group 1, 54.84% (68/124) in Group 2, and 37.70% (46/122) in Group 3, and most of them were mild to moderate in severity. No vaccine-related serious adverse events were reported. In total, the co-administration of combined EV71 vaccine with MMR and LA-JEV showed no interference with antibody response and demonstrated good safety profiles.

Evaluation of alpha7 nicotinic acetylcholine receptor agonists and positive allosteric modulators using the parallel oocyte electrophysiology test station.

Neuronal acetylcholine receptors (nAChRs) of the alpha7 subtype are ligand-gated ion channels that are widely distributed throughout the central nervous system and considered as attractive targets for the treatment of various neuropsychiatric and neurodegenerative diseases. Both agonists and positive allosteric modulators (PAMs) are being developed as means to enhance the function of alpha7 nAChRs. The in vitro characterization of alpha7 ligands, including agonists and PAMs, relies on multiple technologies, but only electrophysiological measurements assess the channel activity directly. Traditional electrophysiological approaches utilizing two-electrode voltage clamp or patch clamp in isolated cells have very low throughput to significantly impact drug discovery. Abbott (Abbott Park, IL) has developed a two-electrode voltage clamp-based system, the Parallel Oocyte Electrophysiology Test Station (POETs()), that allows for the investigation of ligand-gated ion channels such as alpha7 nAChRs in a higher-throughput manner. We describe the utility of this technology in the discovery of selective alpha7 agonists and PAMs. With alpha7 agonists, POETs experiments involved both single- and multiple-point concentration-response testing revealing diverse activation profiles (zero efficacy desensitizing, partial, and full agonists). In the characterization of alpha7 PAMs, POETs testing has served as a reliable primary or secondary screen identifying compounds that fall into distinct functional types depending on the manner in which current potentiation occurred. Type I PAMs (eg, genistein, NS1738, and 5-hydroxyindole) increase predominantly the peak amplitude response, type II PAMs affect the peak current and current decay (eg, PNU-120,596 and 4-(naphthalen-1-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-8-sulfonamide), and anothertype slowing the current decay kinetics in the absence of increases in the peak current. In summary, POETs technology allows for significant impact on higher throughput in the testing of alpha7 agonists and PAMs and for identification of compounds with unique profiles that could prove valuable in identifying an optimum in vitro profile in the development of therapeutics for which the alpha7 subtype is considered.