Effect of High-Fat Food on the Pharmacokinetic Profile and Safety of SAF-189s, an ALK/ROS1 Inhibitor, in Healthy Chinese Adults.

Background And Objectives: This study was conducted to investigate the effect of high-fat meals on the pharmacokinetics (PK) and safety profile of SAF-189s, a novel ALK/ROS1 inhibitor.

Methods: This was a single-center, phase I, open-label, crossover study in which healthy adults (≥18 years) were randomized (1:1) to two sequences of SAF-189s administration (fasted-fed or fed-fasted) separated by a 14-day washout. After a ≥10-h overnight fast, volunteers received SAF-189s 160 mg orally in a fasted state or 30 min after a high-fat, high-calorie meal.

Effect of Food (Low and High Fat) on Pharmacokinetics of FCN-159, a Selective MEK Inhibitor, in Healthy Chinese Males.

Introduction: FCN-159 is a novel, oral, potent, selective MEK1/2 inhibitor in clinical development for the treatment of NRAS-mutant advanced melanoma and neurofibromatosis type 1. We investigated the effect of food on the pharmacokinetics (PK), safety, and tolerability of FCN-159.

Methods: In this single-center, open-label, phase 1 study with a three-period, three-sequence, crossover design, healthy Chinese male subjects (n = 24) were randomized (1:1:1) to receive a single, oral 8 mg dose of FCN-159 in the fasted state (overnight, > 10 h), and with a low-fat and a high-fat meal, separated by a 10-day washout.

Immunogenicity and safety of BNT162b2 mRNA vaccine in Chinese adults: A phase 2 randomised clinical trial.

Background: BNT162b2, an mRNA vaccine against COVID-19, is being utilised worldwide, but immunogenicity and safety data in Chinese individuals are limited.

Methods: This phase 2, randomised, double-blind, placebo-controlled trial included healthy or medically stable individuals aged 18-85 years enrolled at two clinical sites in China. Participants were stratified by age (≤55 or >55 years) and randomly assigned (3:1) by an independent randomisation professional to receive two doses of intramuscular BNT162b2 30 μg or placebo, administered 21 days apart.

Immune Persistence and Safety After SARS-CoV-2 BNT162b1 mRNA Vaccination in Chinese Adults: A Randomized, Placebo-Controlled, Double-Blind Phase 1 Trial.

Introduction: BNT162b1 is a lipid nanoparticle-formulated, nucleoside-modified mRNA SARS-CoV-2 vaccine. Here, we report safety and immune persistence data following a primary two-dose vaccination schedule administered 21 days apart.

Methods: Immune persistence was determined at month 3 in 72 younger participants (aged 18-55 years) and at month 6 in 70 younger and 69 older participants (aged 65-85 years).

A Biomarker-enriched, Randomized Phase II Trial of Adavosertib (AZD1775) Plus Paclitaxel and Carboplatin for Women with Platinum-sensitive -mutant Ovarian Cancer.

Purpose: Preclinical studies show that adavosertib, a WEE1 kinase inhibitor, sensitizes -mutant cells to chemotherapy. We hypothesized that adavosertib, plus chemotherapy, would enhance efficacy versus placebo in -mutated ovarian cancer.

Patients And Methods: Following safety run-in, this double-blind phase II trial (NCT01357161) randomized women with -mutated, platinum-sensitive ovarian cancer to oral adavosertib (225 mg twice daily for 2.

Patient-reported outcomes in individuals with hepatitis C virus infection treated with elbasvir/grazoprevir.

Purpose: People chronically infected with hepatitis C virus (HCV) have diminished patient-reported outcomes (PROs). This study aimed to compare the impact of elbasvir/grazoprevir (EBR/GZR) treatment versus sofosbuvir with pegylated interferon and ribavirin (SOF/PR) on changes in PROs: 1) during the treatment period and 2) at posttreatment follow-up.

Patients And Methods: PRO data collected during the Phase III C-EDGE Head-2-Head (H2H) open-label study was analyzed.

Association of the characteristics of B- and T-cell repertoires with papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Complementarity-determining region 3 (CDR3) of B-cell receptors (BCRs) and T-cell receptors are the major site of antigen recognition, which determines a unique clone type, and are considered to be the representative of the disease. In the present study, high-throughput sequencing was used to analyze the association of characteristics of the BCR immunoglobulin heavy chain (IGH) and the T-cell receptor β chain (TRB) CDR3 genes in PTC and corresponding pericarcinous tissues from patients.

Integrated analysis of B‑cell and T‑cell receptors by high‑throughput sequencing reveals conserved repertoires in IgA nephropathy.

Immunoglobulin A nephropathy (IgAN) is a type of glomerular disorder associated with immune dysregulation, and understanding B‑/T‑cell receptors (BCRs/TCRs) may be valuable for the development of specific immunotherapeutic interventions. In the present study, B and T cells were isolated from IgAN patients and healthy controls, and the composition of the BCR/TCR complementarity‑determining region (CDR)3 was analyzed by multiplex polymerase chain reaction, high‑throughput sequencing and bioinformatics. The present results revealed that the BCR/TCR CDR3 clones were expressed at very low frequencies, and the composition of clone types in patients with IgAN was skewed; the majority of clones were unique, and only 12 BCR and 228 TCR CDR3 clones were public ones, of which 16 were expressed at a significantly higher frequency in patients with IgAN (P<0.

Immunogenicity and safety evaluation of bivalent types 1 and 3 oral poliovirus vaccine by comparing different poliomyelitis vaccination schedules in China: A randomized controlled non-inferiority clinical trial.

Background: The type 2 component of the oral poliovirus vaccine is targeted for global withdrawal through a switch from the trivalent oral poliovirus vaccine (tOPV) to a bivalent oral poliovirus vaccine (bOPV). The switch is intended to prevent paralytic polio caused by circulating vaccine-derived poliovirus type 2. We aimed to assess the immunogenicity and safety profile of 6 vaccination schedules with different sequential doses of inactivated poliovirus vaccine (IPV), tOPV, or bOPV.

A nested group sequential framework for regional evaluation in global drug development program.

The primary objective of a multiregional clinical trial (MRCT) is to assess the efficacy of all participating regions and evaluate the probability of applying the overall results to a specific region. The consistency assessment of the target region with the overall results is the most common way of evaluating the efficacy in a specific region. Recently, Huang et al.

Elbasvir/Grazoprevir for Patients With Hepatitis C Virus Infection and Inherited Blood Disorders: A Phase III Study.

Unlabelled: Direct-acting antiviral agents have not been studied exclusively in patients with inherited blood disorders and hepatitis C virus (HCV) infection. The objective of the randomized, placebo-controlled, phase III C-EDGE IBLD study was to assess the safety and efficacy of elbasvir/grazoprevir (EBR/GZR) in patients with inherited bleeding disorders and HCV infection. One hundred fifty-nine adults with HCV infection and sickle cell anemia, thalassemia, or hemophilia A/B or von Willebrand disease were enrolled at 31 study sites in the United States, Europe, Australia, Canada, Israel, and Thailand.

Flavivirus NS1 protein in infected host sera enhances viral acquisition by mosquitoes.

The arbovirus life cycle involves viral transfer between a vertebrate host and an arthropod vector, and acquisition of virus from an infected mammalian host by a vector is an essential step in this process. Here, we report that flavivirus nonstructural protein-1 (NS1), which is abundantly secreted into the serum of an infected host, plays a critical role in flavivirus acquisition by mosquitoes. The presence of dengue virus (DENV) and Japanese encephalitis virus NS1s in the blood of infected interferon-α and γ receptor-deficient mice (AG6) facilitated virus acquisition by their native mosquito vectors because the protein enabled the virus to overcome the immune barrier of the mosquito midgut.

Efficacy and safety of elbasvir/grazoprevir and sofosbuvir/pegylated interferon/ribavirin: A phase III randomized controlled trial.

Background & Aims: Direct-acting antiviral agents have improved treatment outcomes for patients with hepatitis C virus (HCV) infection; however, head-to-head comparisons are limited. The C-EDGE Head-2-Head Study compared the safety and efficacy of elbasvir/grazoprevir (EBR/GZR) with sofosbuvir plus pegylated interferon/ribavirin (SOF/PR) in patients with HCV infection.

Methods: This was a randomized, open-label, phase III trial.

Frequent emergency department use among released prisoners with human immunodeficiency virus: characterization including a novel multimorbidity index.

Objectives: The objective was to characterize the medical, social, and psychiatric correlates of frequent emergency department (ED) use among released prisoners with human immunodeficiency virus (HIV).

Methods: Data on all ED visits by 151 released prisoners with HIV on antiretroviral therapy (ART) were prospectively collected for 12 months. Correlates of frequent ED use, defined as having two or more ED visits postrelease, were described using univariate and multivariate models and generated medical, psychiatric, and social multimorbidity indices.

Emergency department use by released prisoners with HIV: an observational longitudinal study.

Background: Many people living with HIV access healthcare systems through the emergency department (ED), and increased ED use may be indicative of disenfranchisement with primary HIV care, under-managed comorbid disease, or coincide with use of other healthcare resources. The goal of this study was to investigate ED use by HIV-infected prisoners transitioning to communities.

Methods: We evaluated ED use by 151 HIV-infected released prisoners who were enrolled in a randomized controlled trial of directly administered versus self-administered antiretroviral therapy in Connecticut.

Retention on buprenorphine is associated with high levels of maximal viral suppression among HIV-infected opioid dependent released prisoners.

Introduction: HIV-infected prisoners lose viral suppression within the 12 weeks after release to the community. This prospective study evaluates the use of buprenorphine/naloxone (BPN/NLX) as a method to reduce relapse to opioid use and sustain viral suppression among released HIV-infected prisoners meeting criteria for opioid dependence (OD).

Methods: From 2005-2010, 94 subjects meeting DSM-IV criteria for OD were recruited from a 24-week prospective trial of directly administered antiretroviral therapy (DAART) for released HIV-infected prisoners; 50 (53%) selected BPN/NLX and were eligible to receive it for 6 months; the remaining 44 (47%) selected no BPN/NLX therapy.

Rationale, study design and sample characteristics of a randomized controlled trial of directly administered antiretroviral therapy for HIV-infected prisoners transitioning to the community - a potential conduit to improved HIV treatment outcomes.

Background: HIV-infected prisoners experience poor HIV treatment outcomes post-release. Directly administered antiretroviral therapy (DAART) is a CDC-designated, evidence-based adherence intervention for drug users, yet untested among released prisoners.

Methods: Sentenced HIV-infected prisoners on antiretroviral therapy (ART) and returning to New Haven or Hartford, Connecticut were recruited and randomized 2:1 to a prospective controlled trial (RCT) of 6 months of DAART versus self-administered therapy (SAT); all subjects received case management services.

Ageing, the urban-rural gap and disability trends: 19 years of experience in China - 1987 to 2006.

Background: As the age of a population increases, so too does the rate of disability. In addition, disability is likely to be more common in rural compared with urban areas. The present study aimed to examine the influence of rapid population changes in terms of age and rural/urban residence on the prevalence of disability.

[Development of an indicator system for recognizing the sub-health status and study on the related reliability and validity].

Objective: To establish a subjective indicator system for the evaluation of sub-health status and study on its reliability and validity.

Methods: Based on the basic features of general malice and losing ability of workforce, the indicator system for sub-health status evaluation was developed according to the chronic stress on human body' s main systems. The items were adjusted according to the experience from experts and the results of the pilot study.

Development and evaluation of a questionnaire for measuring suboptimal health status in urban Chinese.

Background: Suboptimal health status (SHS) is characterized by ambiguous health complaints, general weakness, and lack of vitality, and has become a new public health challenge in China. It is believed to be a subclinical, reversible stage of chronic disease. Studies of intervention and prognosis for SHS are expected to become increasingly important.