Predicting pediatric off-label drug use in Chinese hospitals: an application of the theory of planned behavior

The use of drugs is authorized according to guarantees given by drug makers concerning the clinical effectiveness of the drug under the condition that the drug administration follows specific guidelines. These guidelines are indicated in the drug package inserts reflecting knowledge from clinical trials. However, pediatric drugs are rarely included in the study of clinical trials as a result of special physiological and psychological characteristics of users. This leads to a lack of data relating to safety and effectiveness of pediatric marketed drug user groups. Thus, doctors often opt for off-label use of drugs, meaning, they prescribe, use administration route or dose beyond package insert issued by authority. Such off-label use is considered inevitable due to treatment of children diseases. Many countries have made explicit laws, regulations or rules on off-label drug use. In China, off-label drug use has become more common, but not conforming to regulations. In addition, there was no clear stipulation on off-label drug use, especially pediatric off-label drug use. As a result, doctors' medical orders, drug dispensing and distribution of pharmacists, and drug user groups were at greatest risks, laying hidden dangers for doctor-patient disputes. This implies, it is important to generate a behavioral model that allows for the prediction of off-label drug use in pediatrics. Objective: From the perspective of the Theory of Planned Behavior, this research aims to generate a predictive model of off-label drug use in Chinese hospitals. This model adds to extant state-of-art on behavioral models in off-label pediatric use, and it also intends to help normalize doctors' off-label drug use, prevent and treat drug abuse, and ensure the interests of patients and treatment demands. Methods: The present research included objective analysis on pediatric drug information of commonly used pediatric drugs package inserts and subjective analysis on behavior and cognition of pediatricians to model effects on off-label prescription. Results: Findings show pediatricians use of information concerning children's commonly-used drugs in China varied with different subpopulations and drugs. Doctors with different titles have issued off-label prescription in different frequencies. The explanatory model has predictive power on behavioral intention and off-label behavior. It was recommended that permission on issuance of off-label prescription should be limited. As for treatment of common diseases and rare, refractory diseases, different levels of off-label drug uses should be formulated for generic drugs and high-risk drugs. Conclusion: There were subjective and objective reasons of pediatric off-label drug use in China, relating to lack of drug information and prescription behavior of doctors. The theory of planned behavior can be used to predict the behavior of pediatricians in off-label drug use. Countermeasure and suggestion for normalization of off-label drug use was proposed to provide reference and basis for normalizing clinical pediatric off-label drug use. China's pediatric off-label drug use can and should be implemented in terms of academics, management, operation, and technologyA utilização de fármacos é autorizada mediante garantias dadas pelas farmacêuticas no que respeita à eficácia clínica sob a condição de que os fármacos sejam administrados de acordo com orientações específicas. Estas orientações estão indicadas nos folhetos informativos refletindo o conhecimento dos ensaios clínicos. Contudo, os fármacos pediátricos são raramente incluídos nos ensaios clínicos devido às características fisiológicas e psicológicas especiais dos utilizadores. Isto leva a uma falta de informação relativa à segurança e eficácia de fármacos comercializados para este grupo de utilizadores. Assim, os médicos frequentemente optam por uma utilização off-label, o que significa que prescrevem, administram ou doseiam para além do indicado nos folhetos informativos aprovados pelas autoridades. Tal uso off-label é considerado inevitável devido ao tratamento de doenças pediátricas. Na China, a utilização off-label de medicamentos tornou-se comum, mas não em conformidade com o regulamentado. Como resultado, as prescrições médicas, distribuição e dispensa pelos farmacêuticos face a grupos de utilizadores podem criar riscos traduzindo-se em disputas médico-paciente. Tal implica que é importante gerar um modelo comportamental que permita prever o uso off-label de medicamentos no contexto pediátrico. Objectivo: Utilizando a teoria do comportamento planeado, pretende a presente investigação gerar um modelo preditivo da utilização off-label de medicamentos em contexto hospitalar na China. Este modelo acresce ao estado da arte dos modelos comportamentais na utilização off-label pediátrica e também procura ajudar a normalizar o uso off-label de medicamentos por parte dos médicos, a prevenir e tratar o abuso medicamentoso, e a garantir o interesse dos pacientes e as exigências terapêuticas. Método: O estudo presente compreende a investigação objetiva de folhetos informativos de fármacos comummente usados em pediatria bem como investigação subjetiva sobre o comportamento e cognições dos pediatras relativos à prescrição off-label. Resultados: A utilização de informação relativa à administração pediátrica de fármacos comuns na China varia de acordo com as diferentes subpopulações pediátricas e o tipo de fármaco. Os médicos com variadas categorias profissionais têm prescrito off-label com frequência diversa. Foi recomendado que a permissão para prescrever off-label seja limitada. Para o tratamento de doenças comuns e raras, devem ser formulados diferentes níveis de prescrição off-label diferenciando os fármacos de baixo e alto risco. Conclusão: Há motivos subjetivos e objetivos para que ocorra uso off-label de medicamentos na China, que se relacionam com a falta de informação farmacológica e o comportamento de prescrição dos médicos. A teoria do comportamento planeado pode ser mobilizada para prever o comportamento dos pediatras relativo aos usos off-label. São propostas medidas corretivas e sugestões para a normalização do uso off-label para facultar uma referência e a base para normalizar o uso clínico pediátrico off-label de fármacos. A utilização off-label de fármacos na China pode e deve ser implementada com base no conhecimento científico, gestão, operação e tecnologia

Urinary screening of elementary school students in Taicang, China

AbstractBackground: Chronic kidney disease in children is a severe progressive disease that influences the growth, development, and life quality of patients. This study aimed to explore the detection rate of proteinuria and hematuria in elementary school students in Taicang, China.Materials and methods: From 2015 to 2019, urine specimens were selected from 11,753 pupils in Taicang. The samples were tested for proteinuria and hematuria by applying single urine tests and urine sediment microscopic examinations. The observation results were divided into three groups: hematuria, proteinuria, and co-existing hematuria and proteinuria. In addition, kidney biopsies were carried out.Results: The positive rate of urinary abnormalities was 0.842% (99 cases), of which there were 51 cases (0.433%) of proteinuria, 42 cases (0.357%) of hematuria, and six cases (0.051%) of co-existing proteinuria and hematuria. In terms of gender, of the 99 cases, 63 were female students (1.142%) and 36 were male students (0.577%). Additionally, the age distribution results indicated that the prevalence of urine abnormalities in each age group from age 7 to age 13 were 11.11%, 12.12%, 12.12%, 16.16%, 29.29%, 18.18% and 3.03%, respectively. Furthermore, one immunoglobin A nephropathy case was certified by renal biopsy assay in the follow-up at six months.Conclusions: The urine screening revealed that abnormal proteinuria was the main form of urinary abnormalities in elementary school students from Taicang. Urine screening is necessary for early detection and intervention of kidney disease. [Ethiop. J. Health Dev. 2021; 35(2):91-96] Key words: Urine screening, Taicang, elementary school student, proteinuria, hematuri

Effective inhibition of HCMV UL49 gene expression and viral replication by oligonucleotide external guide sequences and RNase P

Abstract Background Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that typically causes asymptomatic infections in healthy individuals but may lead to serious complications in newborns and immunodeficient individuals. The emergence of drug-resistant strains of HCMV has posed a need for the development of new drugs and treatment strategies. Antisense molecules are promising gene-targeting agents for specific regulation of gene expression. External guide sequences (EGSs) are oligonucleotides that consist of a sequence complementary to a target mRNA and recruit intracellular RNase P for specific degradation of the target RNA. The UL49-deletion BAC of HCMV was significantly defective in growth in human foreskin fibroblasts. Therefore, UL49 gene may serve as a potential target for novel drug development to combat HCMV infection. In this study, DNA-based EGS molecules were synthesized to target the UL49 mRNA of human cytomegalovirus (HCMV). Results By cleavage activity assessing in vitro, the EGS aimed to the cleavage site 324 nt downstream from the translational initiation codon of UL49 mRNA (i.e. EGS324) was confirmed be efficient to direct human RNase P to cleave the target mRNA sequence. When EGS324 was exogenously administered into HCMV-infected human foreskin fibroblasts (HFFs), a significant reduction of ~76% in the mRNA and ~80% in the protein expression of UL49 gene, comparing with the cells transfected with control EGSs. Furthermore, a reduction of about 330-fold in HCMV growth were observed in HCMV-infected HFFs treated with the EGS. Conclusions These results indicated that UL49 gene was essential for replication of HCMV. Moreover, our study provides evidence that exogenous administration of a DNA-based EGS can be used as a potential therapeutic approach for inhibiting gene expression and replication of a human virus.</p

Fast and accurate 3-D ray tracing using bilinear traveltime interpolation and the wave front group marching

National Natural Science Foundation of China [41074077, 40774065]P>We propose a new ray tracing technique in a 3-D heterogeneous isotropic media based on bilinear traveltime interpolation and the wave front group marching. In this technique, the media is discretized into a series of rectangular cells. There are two steps to be carried out: one is a forward step where wave front expansion is evolved from sources to whole computational domain and the subsequent one is a backward step where ray paths are calculated for any source-receiver configuration as desired. In the forward step, we derive a closed-form expression to calculate traveltime at an arbitrary point in a cell using a bilinear interpolation of the known traveltimes on the cell's surface. Then the group marching method (GMM), a fast wave front advancing method, is applied to expand the wave front from the source to all girds. In the backward step, ray paths starting from receivers are traced by finding the intersection points of potential ray propagation vectors with the surfaces of relevant cells. In this step, the same TI scheme is used to compute the candidate intersection points on all surfaces of each relevant cell. In this process, the point with the minimum traveltime is selected as a ray point from which the similar step is continued until sources. A number of numerical experiments demonstrate that our 3-D ray tracing technique is able to achieve very accurate computation of traveltimes and ray paths and meanwhile take much less computer time in comparison with the existing popular ones like the finite-difference-based GMM method, which is combined with the maximum gradient ray tracing, and the shortest path method

S1P/S1PR signaling pathway advancements in autoimmune diseases

Sphingosine-1-phosphate (S1P) is a versatile sphingolipid that is generated through the phosphorylation of sphingosine by sphingosine kinase (SPHK). S1P exerts its functional effects by binding to the G protein-coupled S1P receptor (S1PR). This lipid mediator plays a pivotal role in various cellular activities. The S1P/S1PR signaling pathway is implicated in the pathogenesis of immune-mediated diseases, significantly contributing to the functioning of the immune system. It plays a crucial role in diverse physiological and pathophysiological processes, including cell survival, proliferation, migration, immune cell recruitment, synthesis of inflammatory mediators, and the formation of lymphatic and blood vessels. However, the full extent of the involvement of this signaling pathway in the development of autoimmune diseases remains to be fully elucidated. Therefore, this study aims to comprehensively review recent research on the S1P/S1PR axis in diseases related to autoimmunity

Protective effects of ferulic acid against ionizing radiation-induced oxidative damage in rat lens through activating Nrf2 signal pathway

AIM: To examine the protection of ferulic acid (FA) against ionizing radiation (IR)-induced lens injury in rats, as well as the underlying mechanisms. METHODS: FA (50 mg/kg) was administered to rats for 4 consecutive days before they were given 10 Gy γ-radiation, as well as for 3 consecutive days afterward. Two weeks after radiation, the eye tissues were collected. Histological alterations were evaluated by hematoxylin-eosin staining. Enzyme linked immunosorbent assay (ELISA) was utilized to assess the activities of glutathione reductase (GR) and superoxide dismutase (SOD), as well as the levels of glutathione (GSH) and malondialdehyde (MDA) in the lenses. The protein and mRNA levels of Bcl-2, caspase-3, Bax, heme oxygenase-1 (HO-1), and glutamate-cysteine ligase catalytic subunit (GCLC) were quantified using Western blot and quantitative reverse transcription polymerase chain reaction, respectively. With nuclear extracts, the nuclear factor erythroid-2 related factor (Nrf2) protein expressions in the nuclei were also measured. RESULTS: Rats exposed to IR showed lens histological alterations which could be alleviated by FA. FA treatment reversed apoptosis-related markers in IR-induced lens, as evidenced by lower levels of Bax and caspase-3 and higher level of Bcl-2. Furthermore, IR induced oxidative damage manifested by decreased GSH level, increased MDA level, and decreased SOD and GR activities. FA boosted nuclear translocation of Nrf2 and increased the expressions of HO-1 and GCLC to inhibit oxidative stress, as evidenced by an increase in GSH, a decrease in MDA, and an increase in GR and SOD activities. CONCLUSION: FA may work well in preventing and treating IR-induced cataract through promoting the Nrf2 signal pathway to attenuate oxidative damage and cell apoptosis

Effects of two ecological earthworm species on atrazine degradation performance and bacterial community structure in red soil

Vermicomposting is an effective and environmentally friendly approach for eliminating soil organic contamination. Atrazine is one of the most commonly applied triazinic herbicides and frequently detected in agricultural soils. This study investigated the roles and mechanisms of two earthworm species (epigeic Eisenia foetida and endogeic Amynthas robustus) in microbial degradation of atrazine. Both earthworms accelerated atrazine degradation performance from 39.0% in sterile soils to 94.9%–95.7%, via neutralizing soil pH, consuming soil humus, altering bacterial community structure, enriching indigenous atrazine degraders and excreting the intestinal atrazine-degrading bacteria. Rhodoplanes and Kaistobacter were identified as soil indigenous degraders for atrazine mineralization and stimulated by both earthworm species. A. robustus excreted the intestinal Cupriavidus and Pseudomonas, whereas Flavobacterium was released by E. foetida. This study provides a comprehensive understanding of the distinct effects of two earthworm species on soil microbial community and atrazine degradation, offering technical supports to apply vermicomposting in effective soil bioremediation