Early transition from insulin to sulfonylureas in neonatal diabetes and follow-up: experience from China

Background: Sulfonylurea therapy can improve glycemic control and ameliorate neurodevelopmental outcomes in patients suffering from neonatal diabetes mellitus (NDM) with KCNJ11 or ABCC8 mutations. As genetic testing results are often delayed, it remains controversial whether sulfonylurea treatment should be attempted immediately at diagnosis or doctors should await genetic confirmation. Objective: This study aimed to investigate the effectiveness and safety of sulfonylurea therapy in Chinese NDM patients during infancy before genetic testing results were available. Methods: The medical records of NDM patients with their follow‐up details were reviewed and molecular genetic analysis was performed. Sulfonylurea transfer regimens were applied in patients diagnosed after May 2010, and glycemic status and side effects were evaluated in each patient. Results: There were 23 NDM patients from 22 unrelated families, 10 had KCNJ11 mutations, 3 harbored ABCC8 mutations, 1 had INS mutations, 4 had chromosome 6q24 abnormalities, 1 had a deletion at chromosome 1p36.23p36.12, and 4 had no genetic abnormality identified. Sixteen NDM infants were treated with glyburide at an average age of 49 days (range 14‐120 days) before genetic confirmation. A total of 11 of 16 (69%) were able to successfully switch to glyburide with a more stable glucose profile. The responsive glyburide dose was 0.51 ± 0.16 mg/kg/d (0.3‐0.8 mg/kg/d), while the maintenance dose was 0.30 ± 0.07 mg/kg/d (0.2‐0.4 mg/kg/d). No serious adverse events were reported. Conclusions: Molecular genetic diagnosis is recommended in all patients with NDM. However, if genetic testing results are delayed, sulfonylurea therapy should be considered before such results are received, even in infants with newly diagnosed NDM

Efficacy and safety of molnupiravir in patients with Omicron variant vaccine breakthrough COVID-19 infection: a randomized, controlled trial

Introduction: Randomized, controlled trials of molnupiravir in real-world use during the Omicron wave are scarce. The frequency of hospitalization and death is low, so further research is needed to confirm the virological efficacy of molnupiravir.Methods: A single-center, randomized, controlled clinical trial was conducted, and 111 hospitalized coronavirus disease 2019 (COVID-19) patients were randomly assigned at a ratio of 1:1. Fifty-three patients in the molnupiravir group were administered 800 mg of molnupiravir twice daily for 5 days in addition to the standard therapy, and 58 patients in the control group only received the standard therapy in accordance with local guidelines. The antiviral effect and adverse events were evaluated during the follow-up.Results: The median viral clearance time in the molnupiravir group was significantly shorter than that in the control group (p = 0.003). Furthermore, patients who started molnupiravir therapy within 3 days had significantly shorter viral clearance time than the controls (p = 0.003). In the vaccinated subgroup, molnupiravir therapy was also associated with a shorter viral clearance time (p = 0.003). A total of three adverse events, which were minor, were reported in the molnupiravir group. One of the patients had mild liver function abnormalities, and all of them were resolved without intervention. However, the remission time was similar between the two tested groups.Conclusion: Molnupiravir exhibited good viral replication inhibitor efficacy in patients with Omicron variant vaccine breakthrough COVID-19 infection.Clinical Trial Registration: [https://www.chictr.org.cn/], identifier [ChiCTR2200059796]

Safety and efficacy of lentinan nasal drops in patients infected with the variant of COVID-19: a randomized, placebo-controlled trial

Objective: Lentinan has antiviral, anti-tumor, immunomodulatory, stimulating interferon production, and other pharmacological effects. Previous animal experiments have shown that lentinan nasal drops can assist [Corona Virus Disease 2019) COVID-19] vaccine to induce high levels of neutralizing antibodies and can effectively resist the invasion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to evaluate the safety and efficacy of lentinan nasal drops in patients infected with Omicron (SARS-CoV-2 variant) through a dose-escalation study and a placebo-controlled trial.Methods: A randomized, placebo-controlled trial. The study was divided into two phases: Phase I: a dose escalation trial in which 24 COVID-19 patients were enrolled, that is, 12 in the escalation dose group (50, 75, and 100 µg/day) and 12 in the standard treatment group. The aim was to evaluate the safety and tolerance of lentinan nasal drops. The second stage was a placebo-controlled study. The optimal dose group of the first stage was used as the therapeutic dose, and the sample size was expanded to verify the anti-COVID-19 efficacy of lentinan nasal drops.Results: In the dose-increasing study, lentinan nasal drops showed good safety, and no serious adverse reactions occurred. The virus shedding time of the 100 µg dose group was significantly shorter than that in the control group (7.75 ± 1.71 VS 13.41 ± 3.8 days) (p = 0.01), and the 100 µg/day lentinan nasal drops were tolerated well. The results of the placebo-controlled study showed that compared with that in the placebo group, the time for COVID-19 antigen to turn negative was significantly shorter in the 100 µg lentinan nasal drop group (p = 0.0298), but no significant difference was observed in symptom improvement between the two groups. In the placebo-controlled study, two patients experienced mild nasal discomfort with nasal drops, but the symptoms relieved themselves.Conclusion: Lentinan nasal drops are tolerated well and can shorten the time of virus clearance

Nurse educators perceptions of simulation teaching in Chinese context: benefits and barriers

Background Although simulated teaching was introduced to China in the 1990s, it remains underused in nursing education. Determining how Chinese nurse educators feel about using simulation in their institutions is very important for faculty training and has the potential to influence simulation implementation. Method This cross-sectional descriptive study was undertaken to identify the nurse educators’ experiences in the use of simulation from various regions of China. One hundred and thirty-six nurse educators provided demographic data and information about simulation implementation within their institutions and explored the perceived barriers and benefits of simulation usage. Results The survey data shows that 108 participants have used simulation in their work, but less than 92 (67.6%) of the respondents had used this teaching strategy more than ten times in last year. The study identified four factors hindering nurse faculty from simulation adoption: (1) concerns with student readiness; (2) the need for faculty team-building for simulation teaching; (3) lack of adequate simulation resources; and (4) thoughtful integration of simulation into nursing curricula. Conclusions Study data suggest that faculty training programs for simulation should be based on the nurse educators’ training needs, including systematically designed training topics, and the provision of hands-on learning simulation activities with expert feedback to help nurse educators achieve the competencies required for effective simulation-based education

Family-clinician shared decision making in intensive care units : cluster randomized trial in China

We thank the China Medical Board, which financially supported our study.Objective To investigate if a Family-Clinician Shared Decision-Making (FCSDM) intervention benefits patients, families and intensive care units (ICUs) clinicians.  Methods Six ICUs in China were allocated to intervention or usual care. 548 patients with critical illness, 548 family members and 387 ICU clinicians were included into the study. Structured FCSDM family meetings were held in the intervention group. Scales of SSDM, HADS, QoL2 and CSACD were used to assess families’ satisfaction and distress, patients’ quality of life, and clinicians’ collaboration respectively.  Results Comparing the intervention group with the control group at post-intervention, there were significant differences in the families’ satisfaction (P =0.0001), depression level (P =0.005), and patients’ quality of life (P =0.0007). The clinicians’ mean CSCAD score was more positive in the intervention group than controls (P < 0.05). There was no significant between-group differences on ICU daily medical cost, but the intervention group demonstrated shorter number of days’ stay in ICU (P=0.0004).  Conclusion The FCSDM intervention improved families’ satisfaction and depression, shortened patients’ duration of ICU stay, and enhanced ICU clinicians’ collaboration.  Practice implications Further improvement and promotion of the FCSDM model are needed to provide more evidence to this field in China.Publisher PDFPeer reviewe

Safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of aficamten in healthy Chinese participants: a randomized, double-blind, placebo-controlled, phase 1 study

Objectives: Aficamten is a selective, small-molecule allosteric inhibitor of cardiac sarcomere being developed as a chronic oral treatment for patients with symptomatic obstructive hypertrophic cardiomyopathy. This was the first-in-Chinese study aiming to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of aficamten in healthy adults.Methods: This double-blind, randomized, placebo-controlled, phase 1 study was conducted in 28 healthy male and female Chinese participants after single ascending dose (SAD) and multi-dose (MD) administrations of aficamten. In the SAD cohort, 16 participants were randomized to receive a single oral dose of aficamten: 10 mg, 20 mg, or placebo. In the MD cohort, 12 participants were randomized to receive multiple doses of aficamten: 5 mg or placebo once daily for 14 days. Safety was monitored throughout the study with electrocardiograms, echocardiograms, clinical laboratory tests, and reporting of adverse events (AEs). Pharmacokinetic profiles of aficamten and metabolites, as well as CYP2D6 genetic impact, were evaluated.Results: A total of 35 treatment-emergent AEs were reported by 14 (50%) participants with mild severity. There were no serious AEs or adverse decreases in left ventricular ejection fraction below 50% during the study. Aficamten was dose-proportional over the dose range of 5–20 mg and accumulated in the MD cohort.Conclusion: Aficamten was safe and well-tolerated in the healthy Chinese adult participants. The pharmacokinetics of aficamten in the Chinese population was comparable to those previously found in Western participants. These phase 1 data support the progression of aficamten into future clinical studies in Chinese patients.Clinical Trial registration:https://clinicaltrials.gov, identifier: NCT04783766

A Novel High-Throughput Vaccinia Virus Neutralization Assay and Preexisting Immunity in Populations from Different Geographic Regions in China

Background: Pre-existing immunity to Vaccinia Tian Tan virus (VTT) resulting from a large vaccination campaign against smallpox prior to the early 1980s in China, has been a major issue for application of VTT-vector based vaccines. It is essential to establish a sensitive and high-throughput neutralization assay to understand the epidemiology of Vaccinia-specific immunity in current populations in China. Methodology/Principal Findings: A new anti-Vaccinia virus (VACV) neutralization assay that used the attenuated replication-competent VTT carrying the firefly luciferase gene of Photinus pyralis (rTV-Fluc) was established and standardized for critical parameters that included the choice of cell line, viral infection dose, and the infection time. The current study evaluated the maintenance of virus-specific immunity after smallpox vaccination by conducting a non-randomized, crosssectional analysis of antiviral antibody-mediated immune responses in volunteers examined 30–55 years after vaccination. The rTV-Fluc neutralization assay was able to detect neutralizing antibodies (NAbs) against Vaccinia virus without the ability to differentiate strains of Vaccinia virus. We showed that the neutralizing titers measured by our assay were similar to those obtained by the traditional plaque reduction neutralization test (PRNT). Using this assay, we found a low prevalence of NAb to VTT (7.6%) in individuals born before 1980 from Beijing and Anhui provinces in China, and when present, anti-VTT NAb titers were low. No NAbs were detected in all 222 samples from individuals born after 1980. There was no significan

Impact of Spontaneously Adsorbed Hydroxide Ions on Emulsification via Solvent Shifting

In this study, the influence of interfacial OH ions on spontaneous emulsification of a hexadecane–acetone–water system via the Ouzo effect (solvent shifting) was investigated. It was found that although there is no surfactant utilized in the solvent shifting method, the resulting emulsion droplets are negatively charged in a wide pH range (pH > ∼2.4) due to the spontaneous adsorption of OH ions. The OH ions remarkably affect the size, size distribution, and stability of the emulsions. The emulsion droplets obtained in the absence of OH ions are large and have a wide size distribution. Coalescence of the emulsion droplets and phase separation are prone to take place. At high OH^– concentration, the resulting emulsion droplets have a small size, a narrow size distribution, and excellent colloid stability. The results suggest that the spontaneous OH^– adsorption affects the nucleation process during the emulsification and the stability of the obtained emulsions during storage