Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 314
Filtrar
1.
Br J Clin Pharmacol ; 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34729817

RESUMO

OBJECTIVES: A lot of medication risks related to high-dose methotrexate (HDMTX) therapy still remain to be identified and standardized. This study aims to establish an evidence-based practice guideline for individualized medication of HDMTX. METHODS: The practice guideline was launched by the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society. The guideline was developed following the WHO handbook for guideline development and the methodology of evidence-based medicine (EBM). The guideline was initially registered in the International Practice Guidelines Registry Platform (IPGRP-2017CN021). Systematic reviews were conducted to synthesis available evidence. A multicenter cross-sectional study was conducted by questionnaires to evaluate patients' perception and willingness on individualized medication of HDMTX. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to rate the quality of evidence and to grade the strength of recommendations. RESULTS: Multidisciplinary working groups were included in this guideline, including clinicians, pharmacists, methodologists, pharmacologists and pharmacoeconomic specialists. A total of 124 patients were involved to integrate patient values and preferences. Finally, the guideline presents 28 recommendations, regarding evaluation prior to administration (renal function, liver function, pleural effusion, comedications, genetic testing), pre-treatment and routine dosing regimen, therapeutic drug monitoring (necessity, method, timing, target concentration), leucovorin rescue (initial timing, dosage regimen and optimization), management of toxicities. Of them, 12 are strong recommendations. CONCLUSIONS: We developed an evidence-based practice guideline with respect to HDMTX medication using a rigorous and multidisciplinary approach. This guideline provides comprehensive and practical recommendations involving the whole process of HDMTX administration to health care providers.

2.
Front Pharmacol ; 12: 741724, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34759821

RESUMO

Background: Pharmacist's direct intervention or participation in multidisciplinary management teams can improve the clinical outcome and quality of life of patients. We aimed to determine the effectiveness of pharmacist-led interventions on the inappropriate use of stress ulcer prophylaxis (SUP) pharmacotherapy in intensive care units (ICUs). Methods: A systematic review was performed for relevant studies using searched PubMed, EMBASE (Ovid), the Cochrane Library, Cochrane Central Register of Controlled Trials (CENTRAL), and four Chinese databases from the establishment of databases to 12 March 2020. We conducted a descriptive analysis of participants, the intervention content and delivery, and the effects on inappropriate medication rates. Results: From 529 records, 8 studies from 9 articles were included in the systematic review. The time of appropriateness judgment and the criteria of "appropriate" varied from included studies. Pharmacist interventions mainly included clarifying indications for SUP pharmacotherapy, education and awareness campaign, reviewed patients on SUP pharmacotherapy during rounds, and adjustments of drug use. Five (62.5%) studies found a significant intervention effect during hospitalization, while 2 (25%) studies at ICU transfer and 2 (25%) studies at hospital discharge. 4 (50%) studies identified the complications related to SUP pharmacotherapy and found no significant difference. 4 (50%) studies declared the pharmacist-led interventions were associated with cost savings. Conclusion: Pharmacist-led intervention is associated with a decrease in inappropriate use of SUP pharmacotherapy during hospitalization, at ICU transferred and hospital discharged, and a lot of medical cost savings. Further research is needed to determine whether pharmacist-led intervention is cost-effective.

3.
Vaccine ; 39(48): 7001-7011, 2021 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-34750014

RESUMO

COVID-19 pandemic has severely impacted the public health and social economy worldwide. A safe, effective, and affordable vaccine against SARS-CoV-2 infections/diseases is urgently needed. We have been developing a recombinant vaccine based on a prefusion-stabilized spike trimer of SARS-CoV-2 and formulated with aluminium hydroxide and CpG 7909. The spike protein was expressed in Chinese hamster ovary (CHO) cells, purified, and prepared as a stable formulation with the dual adjuvant. Immunogenicity studies showed that candidate vaccines elicited robust neutralizing antibody responses and substantial CD4+ T cell responses in both mice and non-human primates. And vaccine-induced neutralizing antibodies persisted at high level for at least 6 months. Challenge studies demonstrated that candidate vaccine reduced the viral loads and inflammation in the lungs of SARS-CoV-2 infected golden Syrian hamsters significantly. In addition, the vaccine-induced antibodies showed cross-neutralization activity against B.1.1.7 and B.1.351 variants. These data suggest candidate vaccine is efficacious in preventing SARS-CoV-2 infections and associated pneumonia, thereby justifying ongoing phase I/II clinical studies in China (NCT04982068 and NCT04990544).


Assuntos
Vacinas contra COVID-19 , COVID-19 , Compostos de Alúmen , Hidróxido de Alumínio , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , Células CHO , Cricetinae , Cricetulus , Humanos , Camundongos , Pandemias , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/genética
4.
Front Pharmacol ; 12: 694381, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616294

RESUMO

Background: As a third-generation antiseizure medication (ASM), lacosamide (LCM) is recommended worldwide for patients with epilepsy. We aimed to provide more conclusive evidence for the safety and tolerability of LCM in patients with epilepsy. Methods: A systematic search was performed on MEDLINE, Embase, Cochrane Library, CBM, CNKI, IDB, VIP Database, and Wanfang Database from inception to 2021 March, and all studies assessing the safety of LCM were included. A meta-analysis was performed for safety data of LCM. Results: Eighty-three studies involving 12268 populations (11 randomized clinical trials (RCTs), 16 cohort studies, 53 case series, and 3 case reports) were included in our study. Meta-analysis of the total incidence of adverse events (AEs) of LCM was 38.7% [95% CI (35.1%, 45.8%); n=75 studies]. Incidence of withdrawal due to AEs was 10.8% [95% CI (9.1%, 12.6%); n=56 studies], and incidence of serious adverse events (SAEs) was 6.5% [95% CI (4.0%, 8.9%); n=13 studies]. Most AEs were in the nervous system and digestive system. The most common AEs were sedation (15.8%), dizziness (15.7%), fatigue (9.4%), and nausea/vomiting (9.3%). For children, the total incidence of AEs of LCM was 32.8% [95% CI (21.6%, 44.0%); n=16 studies], and the most common AEs were dizziness (8.6%), nausea/vomiting (8.6%), and somnolence (6.8%). Conclusion: Lacosamide is generally safe and well tolerated in patients with epilepsy. Common AEs were sedation, dizziness, and fatigue. It is necessary to pay more attention to the prevention and management of these AEs and conduct more large-scale and high-quality studies to update safety data.

5.
Front Cell Dev Biol ; 9: 741183, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631718

RESUMO

Exosomes are membranous lipid vesicles fused with intracellular multicellular bodies and then released into the extracellular environment. They contain various bioactive substances, including proteins, mRNA, miRNAs, lncRNAs, circRNAs, lipids, transcription factors, and cytokine receptors. Under certain conditions, bone marrow mesenchymal stem cells (BMSCs) can differentiate into osteoblasts, chondrocytes, adipocytes, and biological functions. This study provides a theoretical basis for the application of exosomes derived from bone marrow mesenchymal stem cells (BMSC-Exos) in osteology, exploring different sources of exosomes to improve bone microenvironment and resist bone metastasis. We also provided new ideas for the prevention and rehabilitation of human diseases by exosomes.

6.
Ir J Med Sci ; 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635968

RESUMO

OBJECTIVE: We aimed to investigate the relationship among epidermal growth factor-like protein-7 (EGFL7), integrin subunit beta 3 (ITGB3), and Kruppel-like factor 2 (KLF2) expressions and their clinical implication in multiple myeloma (MM). METHODS: This prospective study enrolled 72 de novo symptomatic MM patients and 30 controls, and then collected their bone marrow plasma cell samples. Subsequently, the EGFL7, ITGB3, and KLF2 expressions were carried out by reverse transcription quantitative polymerase chain reaction. RESULTS: EGFL7, ITGB3, and KLF2 expressions were increased in MM patients compared to controls. Besides, EGFL7, ITGB3, and KLF2 inter-correlated with each other in MM patients but not in controls. In MM patients, EGFL7 and ITGB3 (but not KLF2) expressions were positively correlated with ISS stage, while ITGB3 and KLF2 (but not EGFL7) expressions were correlated with increased R-ISS stage. Interestingly, ITGB3 and KLF2 were decreased in induction-treatment complete remission (CR) MM patients compared to non-CR MM patients, while EGFL7 only showed a trend but without statistical significance. Furthermore, ITGB3 high expression was correlated with worse progression-free survival (PFS) and overall survival (OS), while EGFL7 and KLF2 high expressions only associated with pejorative PFS but not OS. CONCLUSION: EGFL7, ITGB3, and KLF2 may serve as potential prognostic indicators in MM patients.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34655114

RESUMO

BACKGROUND: Case-based payment has extensively been adopted to replace the fee-for-service payment in China. This paper aims to assess the impacts of case-based payment reform on the providers' behaviour using cataract surgery as an example. METHODS: A total of 400 cataract inpatients were sampled in a tertiary hospital. Data analysis consisted of descriptive statistics, Wilcoxon rank-sum test and Chi-square test. RESULTS: The number of routine preoperative laboratory tests and drugs significantly declined after the case-based payment reform (p < 0.001). Healthcare providers significantly reduced the use frequency of systemic glucocorticoids (GCs) and antibiotics, adjuvant drugs, multiple antibiotic eye drops, generic drugs in cataract surgery after reform (p < 0.001), and they reduced non-ophthalmic medications after reform (p < 0.01). Notably, all patients were prescribed GC eye drops, antibiotic eye drops, and original drugs in both groups. Moreover, the preoperative, postoperative, and total length of stay (LOS) declined after the reform (p < 0.001). Nonetheless, no significant difference was noted in the care quality between the two group. CONCLUSION: The case-based payment reform decreased the intensity of care by reducing unnecessary drugs and retaining necessary drugs on cataract surgery. Besides, the LOS was shortened. Further, an impaired care quality was not witnessed, however, cost-shifting warrants further attention.

8.
Cancer Cell Int ; 21(1): 572, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34715859

RESUMO

BACKGROUND: Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death worldwide, and cancer stem cell is responsible for the poor clinical outcome of NSCLC. Previous reports indicated that long noncoding RNAs (lncRNAs) play important roles in maintaining cancer stemness, however, the underlying mechanisms remain unclear. This study investigates the role of ASAP1 Intronic Transcript 1 (ASAP1-IT1) in cancer cell stemness of NSCLC. METHODS: The expression of ASAP1-IT1, microRNA-509-3p (miR-509-3p) and apoptosis-/stemness-related genes was analyzed by qRT-PCR in NSCLC tissues, cancer cells and spheres of cancer stem cells. Knockdown of ASAP1-IT1 or overexpression of miR-509-3p in NSCLC cells by infection or transfection of respective plasmids. Sphere formation and colony formation were used to detect NSCLC stem cell-like properties and tumor growth in vitro. Luciferase reporter assays, RNA immunoprecitation (RIP) and qRT-PCR assays were used to analyze the interaction between lncRNA and miRNA. The expression of expression of regulated genes of ASAP1-IT1/miR-509-3p axis was evaluated by qRT-PCR and Western blot. The NSCLC xenograft mouse model was used to validate the role of ASAP1-IT1 in NSCLC stemness and tumor growth in vivo. RESULTS: ASAP1-IT1 was up-regulated in NSCLC tissues, cancer cells, and in spheres of A549-derived cancer stem cells. Downregulation of ASAP1-IT1 or overexpression of miR-509-3p significantly decreased cell colony formation and stem cell-like properties of A549-dereived stem cells with decreased expression of stem cell biomarkers SOX2, CD34, and CD133, and suppressing the expression of cell growth-related genes, Cyclin A1, Cyclin B1, and PCNA. Furthermore, knockdown of ASAP1-IT1 or overexpression of miR-509-3p repressed tumor growth in nude mice via reducing expression of tumorigenic genes. ASAP1-IT1 was found to interact with miR-509-3p. Moreover, overexpression of ASAP1-IT1 blocked the inhibition by miR-509-3p on stem cell-like properties and cell growth of A549-dereived stem cells both in vitro and in vivo. Finally, the level of YAP1 was regulated by ASAP1-IT1 and miR-509-3p. CONCLUSIONS: YAP1-involved ASAP1-IT1/miR-509-3p axis promoted NSCLC progression by regulating cancer cell stemness, and targeting this signaling pathway could be is a promising therapeutic strategy to overcome NSCLC stemness.

9.
Rice (N Y) ; 14(1): 87, 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34674053

RESUMO

microRNAs act as fine-tuners in the regulation of plant growth and resistance against biotic and abiotic stress. Here we demonstrate that rice miR1432 fine-tunes yield and blast disease resistance via different modules. Overexpression of miR1432 leads to compromised resistance and decreased yield, whereas blocking miR1432 using a target mimic of miR1432 results in enhanced resistance and yield. miR1432 suppresses the expression of LOC_Os03g59790, which encodes an EF-hand family protein 1 (OsEFH1). Overexpression of OsEFH1 leads to enhanced rice resistance but decreased grain yield. Further study revealed that miR1432 and OsEFH1 are differentially responsive to chitin, a fungus-derived pathogen/microbe-associated molecular pattern (PAMP/MAMP). Consistently, blocking miR1432 or overexpression of OsEFH1 improves chitin-triggered immunity responses. In contrast, overexpression of ACOT, another target gene regulating rice yield traits, has no significant effects on rice blast disease resistance. Altogether, these results indicate that miR1432 balances yield and resistance via different target genes, and blocking miR1432 can simultaneously improve yield and resistance.

10.
PLoS One ; 16(10): e0258483, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34710109

RESUMO

This study investigates the degradation of nifedipine (NIF) by using a novel and highly efficient ultraviolet light combined with hydrogen peroxide (UV/H2O2). The degradation rate and degradation kinetics of NIF first increased and then remained constant as the H2O2 dose increased, and the quasi-percolation threshold was an H2O2 dose of 0.378 mmol/L. An increase in the initial pH and divalent anions (SO42- and CO32-) resulted in a linear decrease of NIF (the R2 of the initial pH, SO42- and CO32- was 0.6884, 0.9939 and 0.8589, respectively). The effect of monovalent anions was complex; Cl- and NO3- had opposite effects: low Cl- or high NO3- promoted degradation, and high Cl- or low NO3- inhibited the degradation of NIF. The degradation rate and kinetics constant of NIF via UV/H2O2 were 99.94% and 1.45569 min-1, respectively, and the NIF concentration = 5 mg/L, pH = 7, the H2O2 dose = 0.52 mmol/L, T = 20 ℃ and the reaction time = 5 min. The ·OH was the primary key reactive oxygen species (ROS) and ·O2- was the secondary key ROS. There were 11 intermediate products (P345, P329, P329-2, P315, P301, P274, P271, P241, P200, P181 and P158) and 2 degradation pathways (dehydrogenation of NIF → P345 → P274 and dehydration of NIF → P329 → P315).


Assuntos
Raios Ultravioleta , Peróxido de Hidrogênio , Cinética , Nifedipino
11.
Front Pharmacol ; 12: 698907, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34489695

RESUMO

Introduction: Drug-related problems (DRPs) are not only detrimental to patients' physical health and quality of life but also lead to a serious waste of health care resources. The condition of DRPs might be more severe for patients in primary health care institutions. Objective: This systematic review aims to comprehensively review the characteristics of DRPs for patients in primary health care institutions, which might help find effective strategies to identify, prevent, and intervene with DRPs in the future. Methods: We searched three English databases (Embase, The Cochrane Library, and PubMed) and four Chinese databases (CNKI, CBM, VIP, and Wanfang). Two of the researchers independently conducted literature screening, quality evaluation, and data extraction. Qualitative and quantitative methods were combined to analyze the data. Results: From the 3,368 articles screened, 27 met the inclusion criteria and were included in this review. The median (inter-quartile range, IQR) of the incidences of DRPs was 70.04% (59%), and the median (IQR) of the average number of DRPs per patient was 3.4 (2.8). The most common type of DRPs was "treatment safety." The causes of DRPs were mainly in the prescribing section, including "drug selection" and "dose selection", while patients' poor adherence in the use section was also an important cause of DRPs. Risk factors such as the number of medicines, age, and disease condition were positively associated with the occurrence of DRPs. In addition, the medians (IQR) of the rate of accepted interventions, implemented interventions, and solved DRPs were 78.8% (22.3%), 64.15% (16.85%), and 76.99% (26.09%), respectively. Conclusion: This systematic review showed that the condition of DRPs in primary health care institutions was serious. In pharmaceutical practice, the patients with risk factors of DRPs should be monitored more closely. Pharmacists could play important roles in the identification and intervention of DRPs, and more effective intervention strategies need to be established in the future.

12.
Front Mol Biosci ; 8: 727347, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34527704

RESUMO

[This corrects the article DOI: 10.3389/fmolb.2021.682594.].

13.
Transl Psychiatry ; 11(1): 478, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34531367

RESUMO

The role of diet in depression is becoming increasingly acknowledged. This umbrella review aimed to summarize comprehensively the current evidence reporting the effects of dietary factors on the prevention and treatment of depression. PubMed, Embase, and the Cochrane Library were searched up to June 2021 to identify relevant meta-analyses of prospective studies. Twenty-eight meta-analyses, with 40 summary estimates on dietary patterns (n = 8), food and beverages (n = 19), and nutrients (n = 13) were eligible. The methodological quality of most meta-analyses was low (50.0%) or very low (25.0%). Quality of evidence was moderate for inverse associations for depression incidence with healthy diet [risk ratio (RR): 0.74, 95% confidential interval (CI), 0.48-0.99, I2 = 89.8%], fish (RR: 0.88, 95% CI, 0.79-0.97, I2 = 0.0%), coffee (RR: 0.89, 95% CI, 0.84-0.94, I2 = 32.9%), dietary zinc (RR: 0.66, 95% CI 0.50-0.82, I2 = 13.9%), light to moderate alcohol (<40 g/day, RR: 0.77, 95% CI, 0.74-0.83, I2 = 20.5%), as well as for positive association with sugar-sweetened beverages (RR: 1.05, 95% CI, 1.01-1.09, I2 = 0.0%). For depression treatment, moderate-quality evidence was identified for the effects of probiotic [standardized mean difference (SMD): -0.31, 95% CI, -0.56 to -0.07, I2 = 48.2%], omega-3 polyunsaturated fatty acid (SMD: -0.28, 95% CI, -0.47 to -0.09, I2 = 75.0%) and acetyl-L-carnitine (SMD: -1.10, 95% CI, -1.65 to -0.56, I2 = 86.0%) supplementations. Overall, the associations between dietary factors and depression had been extensively evaluated, but none of them were rated as high quality of evidence, suggesting further studies are likely to change the summary estimates. Thus, more well-designed research investigating more detailed dietary factors in association with depression is warranted.


Assuntos
Depressão , Ácidos Graxos Ômega-3 , Animais , Depressão/prevenção & controle , Dieta , Incidência , Metanálise como Assunto , Estudos Prospectivos
14.
Front Med (Lausanne) ; 8: 685544, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34485329

RESUMO

Background: While some contacts of COVID-19 cases become symptomatic and radiographically abnormal, their SARS-CoV-2 RNA tests remain negative throughout the disease course. This prospective population-based cohort study aimed to explore their characteristics and significances. Methods: From January 22, 2020, when the first COVID-19 case was identified in Hefei, China, until July 3, a total of 14,839 people in Feidong, Hefei, with a population of ~1,081,000 underwent SARS-CoV-2 RNA testing, where 36 cases (0.2%) with confirmed COVID-19 infection (Group 1) and 27 close contacts (0.2%) testing negative for SARS-CoV-2 RNA but having both positive COVID-19 exposure histories and CT findings (Group 2) from eight clusters were prospectively identified. Another 62 non-COVID-19 pneumonia cases without any exposure history (Group 3) were enrolled, and characteristics of the three groups were described and compared. We further described a cluster with an unusual transmission pattern. Results: Fever was more common in Group 2 than Groups 1 and 3. Frequency of diarrhea in Group 1 was higher than in Groups 2 and 3. Median leucocyte, neutrophil, monocyte, and eosinophil counts were all lower in Groups 1 and 2 than in Group 3. Median D-dimer level was lower in Group 1 than in Groups 2 and 3. Total protein and albumin levels were higher in Groups 1 and 2 than in Group 3. C-reactive protein level was lower and erythrocyte sedimentation rate slower in Groups 1 and 2 than in Group 3. Combination antibacterial therapy and levofloxacin were more often used in Group 3 than in Groups 1 and 2. Lopinavir/ritonavir was more often administered in Groups 1 and 2 than in Group 3. Group 1 received more often corticosteroids than Groups 2 and 3. Group 2 received less often oxygen therapy than Groups 1 and 3. Median duration from illness onset to discharge was longer in Group 1 (27 d) than Groups 2 and 3 (both 17 d). Among contacts of a confirmed COVID-19 patient, only one had a positive virus RNA test but remained asymptomatic and had negative CT findings, and three had negative virus RNA tests but had symptoms and positive CT findings, one of whom transmitted COVID-19 to another asymptomatic laboratory-confirmed patient who had no other exposures. Conclusions: Among close contacts of confirmed COVID-19 cases, some present with positive symptoms and CT findings but test negative for SARS-CoV-2 RNA using common respiratory (throat swab and sputum) specimens; they have features more similar to confirmed COVID-19 cases than non-COVID-19 pneumonia cases and might have transmitted SARS-CoV-2 to others. Such cases might add to the complexity and difficulty of COVID-19 control. Our hypothesis-generating study might suggest that SARS-CoV-2 RNA testing by rRT-PCR assays of common respiratory (throat swab and sputum) specimens alone, the widely accepted "golden standard" for diagnosing COVID-19, might be sometimes insufficient, and that further studies with some further procedures (e.g., testing via bronchoalveolar lavage or specific antibodies) would be warranted for Group 2-like patients, namely, the SARS-CoV-2 RNA-negative (tested using common respiratory specimens), radiographically positive, symptomatic contacts of COVID-19 cases, to further reveal their nature.

15.
Stem Cells Int ; 2021: 2130727, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34367292

RESUMO

Intervertebral disc (IVD) degeneration is considered to be the primary reason for low back pain (LBP), which has become more prevalent from 21 century, causing an enormous economic burden for society. However, in spite of remarkable improvements in the basic research of IVD degeneration (IVDD), the effects of clinical treatments of IVDD are still leaving much to be desired. Accumulating evidence has proposed the existence of endogenous stem/progenitor cells in the IVD that possess the ability of proliferation and differentiation. However, few studies have reported the biological properties and potential application of IVD progenitor cells in detail. Even so, these stem/progenitor cells have been consumed as a promising cell source for the regeneration of damaged IVD. In this review, we will first introduce IVD, describe its physiology and stem/progenitor cell niche, and characterize IVDSPCs between homeostasis and IVD degeneration. We will then summarize recent studies on endogenous IVDSPC-based IVD regeneration and exogenous cell-based therapy for IVDD. Finally, we will discuss the potential applications and future developments of IVDSPC-based repair of IVD degeneration.

16.
Front Pharmacol ; 12: 691606, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34421594

RESUMO

Background: Accessibility of medicines for children is a matter of global concern. Medicines prescribed for children are often off-label. To formulate appropriate policies and undertake necessary interventions to improve access to medicines for children, it is necessary to evaluate the accessibility of medicines for children. However, there is no systematic review of the medicine accessibility for children. Methods: Relevant studies were identified through searching Pubmed, Embase, CNKI, Wanfang, VIP, World Health Organization website, and Health Action International website. Besides, the references of included studies as a supplementary search were read. We extracted the basic information of articles (the first author, published year, the name of journal, research institution, etc.), the basic study characteristics (survey area, survey time, survey method, survey medicine lists, the number of medicine outlets surveyed, etc.), and the study results (the current situation of the accessibility of medicines for children, including the availability, price, and affordability of medicines for children, etc.). Two reviewers independently selected studies and extracted the data. Descriptive analysis methods to analyze the current situation of the accessibility of children's medicines were used. Results: A total of 18 multicenter cross-sectional studies were included in this systematic review, which were from low-income and middle-income countries. Seventeen studies (17/18, 94.4%) used the WHO/Health Action International (HAI) medicine price methodology to investigate the accessibility of medicines for children. Fifteen studies (15/18, 83.3%) were selected to investigate medicines based on the WHO Model List of Essential Medicines for Children (WHO EMLc). In the public sectors, the availability of originator brands (OBs) ranged from 0 to 52.0%, with a median of 24.2%, and the availability of lowest-priced generics (LPGs) ranged from 17.0 to 72.6%, with a median of 38.1%. In the private sectors, the availability of OBs ranged from 8.9 to 80%, with a median of 21.2%. The availability of LPGs ranged from 20.6 to 72.2%, with a median of 35.9%. In most regions, the availability of OBs in the private sectors was higher than in the public sectors. Collectively, in the price of medicines for children, the median price ratio (MPR) of the OBs in the public sectors and private sectors were much higher than that of the LPGs. And the affordability of the LPGs in the public sectors and private sectors was higher than that of originator brands (OBs). Conclusion: The availability of medicines for children is low in both the public sectors and private sectors in low-income and middle-income countries. The MPR of originator brands (OBs) is higher than that of lowest-priced generics (LPGs), and the most lowest-priced generics (LPGs) have better affordability.

17.
Risk Manag Healthc Policy ; 14: 3473-3482, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34456594

RESUMO

Objective: To give recommendations for the development of primary care clinical practice guideline (CPG) to improve applicability and feasibility of primary care CPGs in China. Design: A two-round Delphi survey. Methods: A two-round Delphi survey including guideline development methodologists and clinical practitioners from six countries was conducted. In round one, participants were asked to raise special considerations for the development of primary care CPGs through open-ended questions. In round two, participants were asked to rate the level of agreement on each recommendation item generated by round one and to raise additional recommendations. Opinions from participants were reviewed by thematic analysis. Integrated results from the Delphi survey were validated by participants. Results: The necessity of developing recommendations for the development of primary care CPGs were consistently recognized by participants. The main recommendations of guideline development were generated as follows: (1) considering the context of primary care institutions and the applicability of existing guidelines for primary care in planning guideline; (2) involving primary care practitioners and patients in guideline groups; (3) considering the variation of health-care resources between primary care settings when developing recommendations; (4) presenting the difference of recommendations between primary care CPG and general CPG; (5) implementing more active education and training; and (6) considering the changing of primary care medical resource when updating guideline. Conclusion: In this study, we present recommendations to inform the development of clinical practice guidelines in primary care settings. Next steps will include merging these recommendations with general guideline development methods to inform the development of guidelines for primary care.

18.
J Clin Lab Anal ; 35(9): e23910, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34390275

RESUMO

BACKGROUND: PHD finger protein 19 (PHF19), also known as polycomb-like protein 3 (PCL3), promotes the progression of multiple myeloma (MM) and drug resistance; however, its role in the management of MM remains unclear. Therefore, we aimed to elucidate the correlation between PHF19 expression and treatment response, disease progression, and survival of patients with MM. METHODS: Plasma cells derived from the bone marrow of 101 patients with de novo MM were collected prior to induction therapy, as were plasma cells derived from the bone marrow of 30 healthy donors. PHF19 expression in plasma cells was analyzed using quantitative reverse transcription polymerase chain reaction. Furthermore, the response to induction therapy, progression-free survival (PFS), and overall survival (OS) were assessed. RESULTS: PHF19 expression tends to be upregulated more often in MM patients than in healthy donors (p < 0.001) and can accurately predict MM risk (area under curve [AUC], 0.916; 95% confidence interval [CI], 0.869-0.962). Furthermore, elevated PHF19 expression was correlated with higher International Staging System (ISS) (p = 0.036) and revised ISS stages (p = 0.035). In addition, MM patients who achieved complete response (CR) exhibited reduced PHF19 compared to those who did not (p = 0.028). Moreover, increased PHF19 expression was correlated with unfavorable PFS (p = 0.006) and OS (p = 0.027) rates. Furthermore, the results of multivariate Cox analysis also revealed that PHF19 high expression was independently associated with a reduced PFS rate (hazard ratio: 2.025, p = 0.028). CONCLUSION: Increased PHF19 expression is correlated with poor induction therapy response and unfavorable long-term prognosis of MM.

19.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(4): 1011-1018, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34362476

RESUMO

OBJECTIVE: To the clinical characteristics and prognostic value of the patients with complete deletion of TET_JBP domain (ΔJBP) in TET2 acute myeloid leukemia (AML). METHODS: Next Generation Sequencing technology was used to determine the mutations of 34 AML-related genes (including TET2 gene). The I-TASSER tool was used to predict the tertiary structure of the full-length TET2 protein and TET_JBP structure deletion. RESULTS: Among 38 AML patients with TET2 mutations, 22(57.9%) showed truncation mutations, of which 16 (72.7%) produced TET2ΔJBP truncation mutants. Protein structure prediction showed that the deletion of TET_JBP domain lead to the significant changes of tertiary structure in TET2 protein. Compared with the patients in non-ΔJBP group, the age of patients in ΔJBP group were older (63 vs 54 years old, P=0.047), and the occurrence rate of CEBPA double mutation (CEBPAdm) were more frequency (31.3% vs 0, P=0.009), the complete remission (CR) rate after induction chemotherapy(37.5% vs 81.8%, P=0.008) were lower, the median EFS (5 vs 19 months, P=0.000) and median OS (16 vs 22 months, P=0.041) were shorter. Univariate analysis showed that platelets <50×109/L (P=0.004) and CEBPAdm (P=0.001) were related to the shorter OS of the patients. Further COX multivariate analysis showed that CEBPAdm is an independent prognostic factors of OS in TET2ΔJBP patients (P=0.010). In addition, ΔJBP patients with CEBPAdm showed lower hemoglobin levels (62 vs 75g/L, P=0.030) and lower median OS (9 months vs 18 months, P=0.000) than the patients without CEBPAdm. CONCLUSION: AML patients with TET2ΔJBP truncation mutant shows lower CR rate, shorter EFS and OS after induction chemotherapy, which may be related to the poor prognosis, and co-mutation with CEBPAdm, which is the independent prognostic factors of OS in AML patients with TET2ΔJBP.


Assuntos
Leucemia Mieloide Aguda , Proteínas de Ligação a DNA/genética , Humanos , Quimioterapia de Indução , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Pessoa de Meia-Idade , Mutação , Prognóstico , Proteínas Proto-Oncogênicas/genética , Indução de Remissão
20.
Pharmacol Res ; 172: 105808, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34389457

RESUMO

BACKGROUND: We aimed to evaluate comparative safety and tolerability of the approved PARP inhibitors in people with cancer. METHODS: Eligible studies included randomized controlled trials comparing an approved PARP inhibitor (fluzoparib, olaparib, rucaparib, niraparib, or talazoparib) with placebo or chemotherapy in cancer patients. Outcomes of interest included: serious adverse event (SAE), discontinuation due to adverse event (AE), interruption of treatment due to AE, dose reduction due to AE, and specific grade 1-5 AEs. RESULTS: Ten trials including 3763 participants and six treatments (olaparib, rucaparib, niraparib, talazoparib, placebo, and protocol-specified single agent chemotherapy) were identified. SAE and discontinuation of treatment did not differ significantly among the four approved PARP inhibitors. Regarding interruption of treatment and dose reduction due to AE, statistically significant differences and statistically non-significant trend were observed. Talazoparib is associated with a higher risk of interruption of treatment and dose reduction (excluding rucaparib) due to AE as compared with the other drugs. Niraparib showed a trend of lower risk of AE related dose reduction as compared with the other drugs. Furthermore, there were significant differences in specific grade 1-5 AE among the four drugs. CONCLUSION: The safety profile of the four approved PARP inhibitors is comparable in terms of SAE and AE-related discontinuation of treatment. Statistically significant differences in the AEs spectrum and AEs related dose interruption and dose reduction demonstrated the prompt identification of AE and dose personalization seem mandatory to obtain maximal benefit from PARP inhibitors.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...