Asp

Asp
  • 文章类型: Journal Article
    生物仿制药提供了节省成本和扩大获取生物产品的潜力;然而,人们对生物仿制药的摄取率感到担忧。我们评估了生物仿制药和发起人定价之间的关系,覆盖范围,通过描述分为两类的四个案例研究和市场份额:(1)唯一优先覆盖策略(即,目标是首选发起人产品;非首选生物仿制药),定义为发起人产品的平均销售价格(ASP)大幅降低(到2022年引入生物仿制药竞争后净价下降至少50%)和(2)非唯一优先覆盖战略(即,目标是让发起人产品与生物类似产品一起优先使用),定义为鼻祖产品的ASP适度降低(净价至少没有下降其生物仿制药竞争前价值的50%)。我们发现,相对于具有非唯一优先覆盖策略的发起人,具有唯一优先覆盖策略的发起人保持了处方集偏好和市场份额。不管策略如何,在引入生物仿制药之后的几年中,所有四个产品系列(原始产品和生物仿制药)的市场加权ASP显着下降,这表明,单独的生物仿制药吸收可能并不能完全衡量生物仿制药市场是否促进竞争和降低价格。
    Biosimilars offer the potential for cost savings and expanded access to biologic products; however, there are concerns regarding the rate of biosimilar uptake. We assessed the relationship between biosimilar and originator pricing, coverage, and market share by describing four case studies that fall into two categories: (1) sole preferred coverage strategy (ie, aim is to have originator product preferred; biosimilar(s) non-preferred), defined as steep average sales price (ASP) reductions for originator products (decline in net prices by at least 50% following the introduction of biosimilar competition by 2022) and (2) non-sole preferred coverage strategy (ie, aim is to have originator product preferred alongside biosimilar products), defined as moderate ASP reductions for originator products with (net prices did not decline by at least 50% of its pre-biosimilar competition value). We found that originators with sole preferred coverage strategies maintained formulary preference and market share relative to originators with non-sole preferred coverage strategies. Regardless of strategy, the market-weighted ASP for all four product families (originator and biosimilars) declined significantly in the years following the introduction of biosimilars, suggesting that biosimilar uptake alone may not be a complete measure of whether the biosimilar market is facilitating competition and lowering prices.
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  • 文章类型: Journal Article
    HIV-1具有编码ASP蛋白的反义基因重叠env。ASP功能仍然未知,但它与感染细胞的病毒包膜和膜中的gp120有关,使其成为免疫反应的潜在目标。尽管如此,针对ASP的免疫反应模式描述不充分,并且可能受到env基因的高遗传变异性的影响。为了探索这个,我们分析了100kHIV-1ASP序列从LosAlamosHIV序列数据库使用系统发育,香农熵(Hs),和徽标工具,以研究来自巴西最普遍的HIV-1亚型的全球和巴西序列中的ASP变异性(B,C,和F1)。在计算机上获得的数据通过在纤维素膜上的点合成指导了15聚体重叠肽的设计和合成。筛选肽阵列以评估来自HIV控制者和患有急性或近期HIV感染的个体的汇集血浆样品中的IgG和IgM应答。排除对准精度低的区域,在数据集中确定了几个变异性较高的位点(Hs>1.5)(全球序列为25个,巴西序列为20)。在Hs<1.5的位点中,序列标识允许鉴定具有亚型特异性签名的23个其他位点。总之,在鉴定的48个可变位点中频率>20%的氨基酸变异包括在92个肽中,分为15套,表示接近全长的ASP。在免疫筛查过程中,在三组中观察到最强的反应,一个在蛋白质的中间,一个在蛋白质的C末端。虽然一些集合呈现与IgG和IgM靶标之间的表位置换潜在相关的变异,并且亚型特异性特征似乎影响一些肽的应答水平。尽管存在B/C/F1特征,但仍观察到某些组的交叉反应性信号。我们的数据提供了IgG和IgM应答优先靶向的ASP区域的图谱。尽管ASP中的B/C/F1子类型签名,IgM和IgG优先靶向的某些区域的氨基酸变异并未对针对免疫原性较高区域的应答产生负面影响.
    HIV-1 has an antisense gene overlapping env that encodes the ASP protein. ASP functions are still unknown, but it has been associated with gp120 in the viral envelope and membrane of infected cells, making it a potential target for immune response. Despite this, immune response patterns against ASP are poorly described and can be influenced by the high genetic variability of the env gene. To explore this, we analyzed 100k HIV-1 ASP sequences from the Los Alamos HIV sequence database using phylogenetic, Shannon entropy (Hs), and logo tools to study ASP variability in worldwide and Brazilian sequences from the most prevalent HIV-1 subtypes in Brazil (B, C, and F1). Data obtained in silico guided the design and synthesis of 15-mer overlapping peptides through spot synthesis on cellulose membranes. Peptide arrays were screened to assess IgG and IgM responses in pooled plasma samples from HIV controllers and individuals with acute or recent HIV infection. Excluding regions with low alignment accuracy, several sites with higher variability (Hs > 1.5) were identified among the datasets (25 for worldwide sequences, 20 for Brazilian sequences). Among sites with Hs < 1.5, sequence logos allowed the identification of 23 other sites with subtype-specific signatures. Altogether, amino acid variations with frequencies > 20% in the 48 variable sites identified were included in 92 peptides, divided into 15 sets, representing near full-length ASP. During the immune screening, the strongest responses were observed in three sets, one in the middle and one at the C-terminus of the protein. While some sets presented variations potentially associated with epitope displacement between IgG and IgM targets and subtype-specific signatures appeared to impact the level of response for some peptides, signals of cross-reactivity were observed for some sets despite the presence of B/C/F1 signatures. Our data provides a map of ASP regions preferentially targeted by IgG and IgM responses. Despite B/C/F1 subtype signatures in ASP, the amino acid variation in some areas preferentially targeted by IgM and IgG did not negatively impact the response against regions with higher immunogenicity.
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  • 文章类型: Journal Article
    较早的报道表明,尽管缺乏直接证据表明COVID-19患者具有抗病毒病原体的活性,但其抗生素使用率很高。据报道,2020年与2019年相比,抗生素消费趋势不同。
    这项研究的目的是评估在存在积极的抗生素管理计划的情况下,COVID-19大流行对抗生素消费的影响。
    这项研究代表了对常用抗生素消费的五年评估,以DDDs/100-BedDays为单位。我们使用非参数Friedman和Friedman检验对数据进行了分析,以比较COVID-19在随后的三波波中和之前的抗生素消耗量。
    通过DDDs/100-BD的抗生素消费表明,与新冠肺炎之前相比,新冠肺炎期间大多数抗生素的抗生素消费中位数有所下降,这对美罗培南和环丙沙星很重要,除了科霉素略有增加。与COVID前期相比,第二波和第三波期间亚胺培南和美罗培南的消费量显着减少。多年来,2018年至2019年期间观察到显著下降(p=<.001),2018年和2020年(p=0.008),2018年和2022年(p=0.002)。
    抗生素消费的减少归因于ASP的强大影响,以及在COVID-19大流行期间人们不愿去医院。其他相关的COVID-19预防措施,如物理距离,良好的手部卫生,口罩,这导致了继发细菌感染的预防,这有助于在大流行期间减少抗生素的使用。
    UNASSIGNED: Earlier reports suggested high rates of antibiotic utilization among COVID-19 patients despite the lack of direct evidence of their activity against viral pathogens. Different trends in antibiotic consumption during 2020 compared to 2019 have been reported.
    UNASSIGNED: The objective of this study is to assess the impact of COVID-19 pandemic on antibiotic consumption in the presence of active Antibiotic Stewardship Program.
    UNASSIGNED: This study represented a five years assessment of the consumption of the commonly prescribed antibiotics measured as DDDs/100-Bed Days. We analyzed the data by using nonparametric Friedman and Friedman tests to compare the antibiotic consumption before and during the three subsequent waves of COVID-19.
    UNASSIGNED: Antibiotic consumption through the DDDs/100-BD has shown reduction in the median of antibiotics consumption of most antibiotics during the period of COVID-19 as compared to the pre-COVID-19 period, which was significant for meropenem and ciprofloxacin, except colomycin that slightly increased. Significant reduction in the consumption of imipenem and meropenem during the second and third waves as compared to the pre-COVID period. Throughout the years, significant reductions were observed between 2018 and 2019 (p=<.001), 2018 and 2020 (p=0.008), and 2018 and 2022 (p=0.002).
    UNASSIGNED: The reduction in antibiotic consumption is attributed to the strong influence if the ASP and the reluctance of people to visit hospitals during the COVID-19 pandemic. Other related COVID-19 precautions such as physical distance, good hand hygiene, facemasks, that resulted in the prevention of secondary bacterial infections have contributed to the reduction in antibiotic utilization during the pandemic.
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  • 文章类型: Journal Article
    非人类灵长类动物物种目前面临着人为的压力,并将继续在现代景观中面对它们。这些压力需要灵长类动物栖息地国家的保护项目来帮助保护,保存,和保护。虽然有几个灵长类动物保护项目的例子,启动一项倡议可能是一项艰巨的任务。美国灵长类动物学会(ASP)保护委员会主办了一次视频网络研讨会,介绍了开发的第一步,运行和继续灵长类动物保护计划。ChristopherShaffer博士,RahayuOktaviani,JillPruetz博士介绍了他们建立野生灵长类动物保护项目的早期项目经验,以教育世界各地的灵长类动物学家。演讲的主题包括建立社区,在当地工作,影响当地并为未来做准备。
    Nonhuman primate species currently face human-induced pressures and will continue to face them in the modern landscape. These pressures require conservation projects in primate habitat countries to aid in protection, preservation, and conservation. Though there are several examples of primate conservation projects, starting up an initiative can be a daunting task. The American Society of Primatology (ASP) Conservation Committee hosted a video webinar presenting on the first steps of developing, running and continuing a primate conservation program. Dr. Christopher Shaffer, Rahayu Oktaviani, and Dr. Jill Pruetz presented their early program experiences establishing wild primate conservation projects to educate primatologists around the world. The running themes of the presentations included establishing community, working locally, impacting locally and preparing for the future.
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  • 文章类型: Letter
    不断升级的抗菌素耐药性(AMR)挑战对全球健康构成了相当大的关注。特别影响低收入和中等收入国家(LMICs)。本文强调了通过采用全球抗菌药物管理认证计划(GAMSAS)解决LMIC中AMR的至关重要性。GAMSAS被描述为抗菌药物管理的整体和可持续战略,超越认证,包括教育项目,能力增强,改进监控,并支持AMS政策研究。在承认该计划在全球范围内得到采纳的同时,这篇文章强调了其在LMICs中采用的初步阶段,特别是在撒哈拉以南非洲等高AMR负担地区。这篇文章强调了LMICs整合GAMSAS的必要性,强调其在优化抗菌药物使用和患者健康结果方面的重要性。它主张采取包罗万象的方法,利用国际合作和持续的金融支持,对于在这些关键领域有效部署和持久成功的抗菌管理工作至关重要。
    The escalating challenge of antimicrobial resistance (AMR) poses a considerable concern for global health, particularly impacting low- and middle-income countries (LMICs). This article highlights the critical importance of tackling AMR in LMICs by adopting the Global Antimicrobial Stewardship Accreditation Scheme (GAMSAS). GAMSAS is portrayed as a holistic and sustainable strategy for antimicrobial stewardship, extending beyond accreditation to include educational programs, capacity enhancement, improved surveillance, and support for AMS policy research. While acknowledging the global uptake of the scheme, the article highlights its preliminary phase of adoption in LMICs, particularly in high-AMR burden regions like Sub-Saharan Africa. The piece stresses the imperative for LMICs to integrate GAMSAS, underscoring its significance in optimizing antimicrobial usage and patient health outcomes. It advocates for an all-encompassing approach that leverages international cooperation and sustained financial backing, crucial for the effective deployment and enduring success of antimicrobial stewardship efforts in these key areas.
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  • 文章类型: Journal Article
    简介:不断增长的抗菌素耐药性(AMR)和现有抗菌素的功效下降已成为重大的公共卫生问题。抗菌药物管理计划(ASP)确保适当使用抗菌药物,并通过各种干预措施减轻耐药性流行。ASP的核心组件之一是教育医护人员(HW)。因此,本研究旨在确定以药剂师为主导的针对知识的教育干预的影响,态度,以及旁遮普邦二级保健医院医疗保健专业人员合理使用抗生素的做法。方法:这是一个单中心,以问卷调查为基础,在6个月的时间内进行的干预前研究.使用SPSS版本26进行数据分析。结果:关于介入前的知识,态度,受访者的实践(KAP)得分,90.3%有良好的知识得分,81.5%持积极态度,72.3%的HWs(不包括医生)有良好的实践评分。此外,74.6%的医生有良好的实践评分。教育干预后,知识有了很大的提高,态度,和受访者HWs的实践(p值<0.001)。此外,在干预前和干预后阶段,男性的知识得分高于女性(p值<0.05),医生在干预前和干预后阶段的知识得分与护士不同。结论:将教育计划视为ASP的支柱,必须在HW正在进行的教育计划中继续努力,以提高HW中对ASP的认识和坚持。
    Introduction: Growing antimicrobial resistance (AMR) and decreasing efficacy of the available antimicrobials have become a significant public health concern. The antimicrobial stewardship program (ASP) ensures the appropriate use of antimicrobials and mitigates resistance prevalence through various interventions. One of the core components of the ASP is to educate healthcare workers (HWs). Therefore, this study aims to identify the impact of a pharmacist-led educational intervention targeting knowledge, attitude, and practices regarding rational antibiotic use among healthcare professionals in a secondary care hospital in Punjab. Methods: This is a single-center, questionnaire-based, pre-post interventional study conducted over a six-month time period. Data analysis was conducted using SPSS version 26. Results: Regarding the pre-interventional knowledge, attitude, and practice (KAP) score of the respondents, 90.3% had a good knowledge score, 81.5% had a positive attitude, and 72.3% of HWs (excluding doctors) had a good practice score. Additionally, 74.6% of the doctors had a good practice score. After educational intervention, there was a significant improvement in the knowledge, attitude, and practice of the respondent HWs (p-value <0.001). Furthermore, males have higher knowledge scores compared to females in the pre- and post-intervention stages (p-value <0.05), and doctors differ from nurses regarding knowledge scores in both pre- and post-intervention stages. Conclusion: Considering educational programs as the backbone of the ASP, it is imperative to sustain efforts in the ongoing educational programs of HWs to foster high awareness and adherence to the ASP among HWs.
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  • 文章类型: Review
    脂肪组织,作为一个内分泌器官,分泌几种脂肪细胞衍生的激素,称为“脂肪因子”,与调节能量止血有关。大量证据表明,白色脂肪组织来源的脂肪因子介导肥胖相关的外源性因素(如饮食和生活方式)和具有肥胖后果(心脏代谢紊乱)的各种生物事件(如绝经前和绝经后状态)之间的联系。肥胖相关疾病的关键病因之一是脂肪因子途径的功能障碍。酰化刺激蛋白(ASP)是一种脂肪因子,其通过增强葡萄糖和脂肪酸摄取来刺激脂肪组织中的甘油三酯合成和储存。ASP通过其受体C5L2起作用。这篇综述的主要目的是通过研究肥胖的多个决定因素之间的不同反应和受体相互作用,来解决文献中有关ASP的现有空白。这些决定因素包括饮食组成,代谢紊乱,器官受累,性和性激素水平。此外,这篇文章探讨了更广泛的范式转变,从仅仅关注脂肪组织质量,这导致了肥胖,考虑脂肪组织功能的更广泛含义。此外,我们提出了一个关于从这篇综述中获得的见解的临床相关性的关键问题,在针对ASP的潜在治疗干预措施和预防肥胖相关疾病的背景下,强调ASP-C5L2相互作用作为药理学靶标的潜力。总之,这些发现证实了肥胖是一种低度炎症状态,具有多器官受累和性别差异,证明免疫和代谢反应决定因素之间的动态相互作用。
    Adipose tissue, as an endocrine organ, secretes several adipocyte-derived hormones named \'adipokines\' that are implicated in regulating energy haemostasis. Substantial evidence shows that white adipose tissue-derived adipokines mediate the link between obesity-related exogenous factors (like diet and lifestyle) and various biological events (such as pre- and postmenopausal status) that have obesity consequences (cardiometabolic disorders). One of the critical aetiological factors for obesity-related diseases is the dysfunction of adipokine pathways. Acylation-stimulating protein (ASP) is an adipokine that stimulates triglyceride synthesis and storage in adipose tissue by enhancing glucose and fatty acid uptake. ASP acts via its receptor C5L2. The primary objective of this review is to address the existing gap in the literature regarding ASP by investigating its diverse responses and receptor interactions across multiple determinants of obesity. These determinants include diet composition, metabolic disorders, organ involvement, sex and sex hormone levels. Furthermore, this article explores the broader paradigm shift from solely focusing on adipose tissue mass, which contributes to obesity, to considering the broader implications of adipose tissue function. Additionally, we raise a critical question concerning the clinical relevance of the insights gained from this review, both in terms of potential therapeutic interventions targeting ASP and in the context of preventing obesity-related conditions, highlighting the potential of the ASP-C5L2 interaction as a pharmacological target. In conclusion, these findings validate that obesity is a low-grade inflammatory status with multiorgan involvement and sex differences, demonstrating dynamic interactions between immune and metabolic response determinants.
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  • 文章类型: Journal Article
    本文介绍了一个全面的框架,阐明了数据驱动的抗菌管理计划(ASP)的微观基础,特别关注资源受限的设置。这种设置需要利用可用资源和多个利益相关者之间的参与。微基础被概念化为相互关联的组件:输入,process,输出,和结果。总的来说,这些组件提供了一个全面的框架,用于了解资源受限环境中数据驱动的ASP的开发和实施。它强调了在评估微生物时同时考虑社会和物质维度的重要性,临床,和社会影响。通过协调技术,实践,值,和行为,这个框架为发展提供了宝贵的见解,实施,以及针对资源受限环境量身定制的ASP评估。
    This paper introduces a comprehensive framework that elucidates the microfoundations of data-driven antimicrobial stewardship programs (ASPs), specifically focusing on resource-constrained settings. Such settings necessitate the utilization of available resources and engagement among multiple stakeholders. The microfoundations are conceptualized as interlinked components: input, process, output, and outcome. Collectively, these components provide a comprehensive framework for understanding the development and implementation of data-driven ASPs in resource-constrained settings. It underscores the importance of considering both the social and material dimensions when evaluating microbiological, clinical, and social impacts. By harmonizing technology, practices, values, and behaviors, this framework offers valuable insights for the development, implementation, and assessment of ASPs tailored to resource-constrained environments.
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  • 文章类型: Journal Article
    在不断增长的植物种群中,压力的影响是影响其生理的扰动问题,生物化学,产量损失和发育生长。蛋白质-L-异天冬氨酸-O-甲基转移酶(PIMT)是一种广泛分布的蛋白质修复酶,可在压力环境或衰老下起作用。应激可介导将结合蛋白的天冬氨酸(Asp)残基转化为异天冬氨酸(iso-Asp)的损伤。这种自发和有害的转化发生在应激和老化的升高状态。Iso-Asp形成与蛋白质失活和受损的细胞存活相关。PIMT可以将iso-Asp转换回Asp,从而修复并促进细胞存活。目前的工作描述了隔离,克隆,番木瓜(Cppimt)和蓖麻(Rcpimt)PIMT基因的测序和表达使用基因特异性引物,从它们各自的cDNA中扩增这两个pimt,并随后克隆到原核表达载体pProEXHTa中。使用大肠杆菌细胞的BL21(DE3)菌株作为表达宿主。用不同浓度的IPTG和在不同时间点研究了两种PIMT的表达动力学。最后,与具有空载体对照的对应物相比,针对不同的应激评估补充了PIMT的BL21(DE3)细胞。
    In growing plant population, effect of stress is a perturb issue affecting its physiological, biochemical, yield loss and developmental growth. Protein-L-isoaspartate-O-methyltransferase (PIMT) is a broadly distributed protein repair enzyme which actuate under stressful environment or aging. Stress can mediate damage converting protein bound aspartate (Asp) residues to isoaspartate (iso-Asp). This spontaneous and deleterious conversion occurs at an elevated state of stress and aging. Iso-Asp formation is associated with protein inactivation and compromised cellular survival. PIMT can convert iso-Asp back to Asp, thus repairing and contributing to cellular survival. The present work describes the isolation, cloning, sequencing and expression of PIMT genes of Carica papaya (Cp pimt) and Ricinus communis (Rc pimt) Using gene specific primers, both the pimts were amplified from their respective cDNAs and subsequently cloned in prokaryotic expression vector pProEXHTa. BL21(DE3) strain of E. coli cells were used as expression host. The expression kinetics of both the PIMTs were studied with various concentrations of IPTG and at different time points. Finally, the PIMT supplemented BL21(DE3) cells were evaluated against different stresses in comparison to their counterparts with the empty vector control.
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  • 文章类型: Journal Article
    背景:由于不合理的抗生素使用和缺乏有效的抗菌药物管理计划(ASP),抗菌药物耐药性(AMR)的增长使常见感染危及生命。
    目的:为了调查意识,医生对ASP的看法和做法,孟加拉国三级保健医院的AMR和抗生素处方。
    方法:这项基于医院的横断面调查于2020年9月至2021年1月在孟加拉国的11家三级医院进行。通过面对面访谈进行半结构化问卷进行数据收集。使用STATA版本13进行描述性和多变量分析。
    结果:总计,559名医生参加了这项调查。总的来说,40.6%[95%置信区间(CI)36.5-44.8]的医生报告知道ASP,与私立医院相比,公立医院的这一数字更高(43.8%对27.1%)。所有研究医院都没有任何ASP计划。超过一半(55.1%)的参与者愿意接受ASP对抗生素选择的反馈。只有30.9%的受访者表示,他们在开抗生素之前等待微生物测试的结果,尽管挑战包括经验性使用广谱抗生素,延迟的实验室结果和耐药患者的存在。相比之下,了解ASP的医师有33%(调整后比值比0.67,95%CI0.45-0.98;P=0.033)的患者在开抗生素前等待实验室检查结果的可能性较小.然而,42.5%的医生在处方时认为患者购买抗生素的承受能力。
    结论:发现医师对ASP的基本知识和合理的抗生素处方达不到标准。特定上下文和集成的ASP活动,指南的可用性和使用,在孟加拉国,需要改进的实验室设施来对抗AMR。
    BACKGROUND: The concerning growth of antimicrobial resistance (AMR) renders common infections life-threatening due to irrational antibiotic use and a lack of effective antimicrobial stewardship programmes (ASPs).
    OBJECTIVE: To investigate the awareness, perceptions and practices of physicians regarding ASPs, AMR and antibiotic prescribing in tertiary care hospitals in Bangladesh.
    METHODS: This hospital-based cross-sectional survey was conducted in 11 tertiary care hospitals across Bangladesh between September 2020 and January 2021. A semi-structured questionnaire was administered through face-to-face interviews for data collection. Descriptive and multi-variate analyses were performed using STATA Version 13.
    RESULTS: In total, 559 physicians were enrolled in this survey. Overall, 40.6% [95% confidence interval (CI) 36.5-44.8] of physicians reported being aware of ASPs, and this figure was higher in public hospitals compared with private hospitals (43.8% vs 27.1%). None of the study hospitals had any ASP initiatives. More than half (55.1%) of the participants were willing to receive feedback from an ASP on their antibiotic selection. Only 30.9% of respondents stated that they wait for the findings of microbiological tests before prescribing antibiotics, although challenges included empiric use of broad-spectrum antibiotics, delayed laboratory results and the existence of drug-resistant patients. In contrast, physicians aware of ASPs were 33% (adjusted odds ratio 0.67, 95% CI 0.45-0.98; P=0.033) less likely to wait for laboratory results before prescribing antibiotics. However, 42.5% of physicians considered patient affordability of purchasing antibiotics when prescribing.
    CONCLUSIONS: Physicians\' fundamental knowledge of ASPs and rational antibiotic prescription were found to fall short of the standard. Context-specific and integrated ASP activities, availability and use of guidelines, and improved laboratory facilities are required to battle AMR in Bangladesh.
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