甲状腺功能亢进症治疗中护理干预的应用效果分析

目的 探讨针对性护理在甲状腺功能亢进症治疗中的临床应用效果.方法 收集2015年4月至2016年6月入院的80例甲状腺功能亢进症患者随机分为两组,对照组患者给予入院指导、治疗期间注意事项、健康宣教、施药操作与床边护理等传统护理,实验组患者则在传统护理的基础上加施服药前准备、心理干预、饮食干预、行为干预等针对性护理,比较两组患者干预前后心理状态、甲状腺激素、肝功能水平与护理满意度.结果 实验组患者干预后SAS[(45.27±5.48)]与SDS评分[(44.11±5.09)]组间比较均显著低于对照组[(51.36±5.75),(50.05±4.87)];实验组患者干预后TSH水平[(4.45±1.08)mU/L组间比较显著高于对照组[(2.36±0.93) mU/L],TT3[(2.25±0.82) nmol/L]、Tr4[(95.45±12.77)nmol/L]、FT3[(4.85±0.94) pmol/L]、FT4[(10.74±2.65) pmol/L]、ALT[(24.86±5.74) U/L]、ALP[(24.30±6.79) U/L]、AST[(24.26±6.17) U/L]与r-GT水平[(22.45±6.81) U/L]组间比较均显著低于对照组[(4.03±0.88) nmol/L,(130.57±14.81) nmol/L,(7.87±1.07) pmol/L,(20.40±3.72)pmol/L,(31.47±6.16) U/L,(33.52±7.57) U/L,(32.75±7.27) U/L,(33.38±7.28) U/L],差异有统计学意义(P＜ 0.01);实验组患者护理满意度明显优于对照组,差异有统计学意义(P＜0.05).结论 针对性护理在甲状腺功能亢进症治疗中的临床应用效果显著,可提高满意度,具有借鉴意义.     

医学模式的转变促进健康观念的更新

健康是人类追求的永恒目标。随着社会的发展,生物医学模式向生物心理社会医学模式转变,“没有疾病就是健康”的观念已过于陈腐,人们对健康的理解已从“没有疾病”发展到包括生理、心理、社会的完满状态,健康的涵义更为深化,健康观念得到更新。     

Prediction of ARA/PPI Drug-Drug Interactions at the Drug Discovery and Development Interface

Advances in understanding of human disease have prompted the U.S. Food and Drug Administration to classify certain molecules as “break-through therapies,” providing an accelerated review that may potentially enhance the quality of patient lives. With this designation come compressed timelines to develop drug products, which are not only suitable for clinic trials but can also be approved and brought to the market rapidly. Early risk identification for decreased oral absorption due to drug-drug interactions with proton pump inhibitors (PPIs) or acid-reducing agents (ARAs) is paramount to an effective drug product development strategy. An early ARA/PPI drug-drug interaction (DDI) risk identification strategy has been developed using physiologically based absorption modeling that readily integrates ADMET predictor generated in silico estimates or measured in vitro solubility, permeability, and ionization constants. Observed or predicted pH-solubility profile data along with pKas and drug dosing parameters were used to calculate a fraction of drug absorbed ratio in absence and presence of ARAs/PPIs. An integrated physiologically based pharmacokinetic absorption model using GastroPlus? with pKa values fitted to measured pH-solubility profile data along with measured permeability data correctly identified the observed ARA/PPI DDI for 78% (16/22) of the clinical studies. Formulation strategies for compounds with an anticipated pH-mediated DDI risk are presented.     

In Vitro and In Vivo Correlation of Hepatic Fraction of Metabolism by P450 in Dogs

1-Aminobenzotriazole (ABT) has been widely used as a nonspecific mechanism-based inhibitor of cytochrome P450 (P450) enzymes. It is extensively used in preclinical studies to determine the relative contribution of oxidative metabolism mediated by P450 in vitro and in vivo. The aim of present study was to understand the translation of fraction metabolized by P450 in dog hepatocytes to in vivo using ABT, for canagliflozin, known to be cleared by P450-mediated oxidation and UDP-glucuronosyltransferases–mediated glucuronidation, and 3 drug discovery project compounds mainly cleared by hepatic metabolism. In a dog hepatocyte, intrinsic clearance assay with and without preincubation of ABT, 3 Lilly compounds exhibited a wide range of fraction metabolized by P450. Subsequent metabolite profiling in dog hepatocytes demonstrated a combination of metabolism by P450 and UDP-glucuronosyltransferases. In vivo, dogs were pretreated with 50 mg/kg ABT or vehicle at 2 h before intravenous administration of canagliflozin and Lilly compounds. The areas under the concentration-time curve (AUC) were compared for the ABT-pretreated and vehicle-pretreated groups. The measured AUC_ABT/AUC_veh ratios were correlated to fraction of metabolism by P450 in dog hepatocytes, suggesting that in vitro ABT inhibition in hepatocytes is useful to rank order compounds for in vivo fraction of metabolism assessment.     

Design,synthesis and pharmacological evaluation of 4-(3-chloro-4-(3-cyclopropylthioureido)-2-fluorophenoxy)-7-methoxyquinoline-6-carboxamide (WXFL-152): a novel triple angiokinase inhibitor for cancer therapy

Angiokinases, such as vascular endothelial-, fibroblast- and platelet-derived growth factor receptors (VEGFRs, FGFRs and PDGFRs) play crucial roles in tumor angiogenesis. Anti-angiogenesis therapy using multi-angiokinase inhibitor has achieved great success in recent years. In this study, we presented the design, synthesis, target identification, molecular mechanism, pharmacodynamics (PD) and pharmacokinetics (PK) research of a novel triple-angiokinase inhibitor WXFL-152. WXFL-152, identified from a series of 4-oxyquinoline derivatives based on a structure–activity relationship study, inhibited the proliferation of vascular endothelial cells (ECs) and pericytes by blocking the angiokinase signals VEGF/VEGFR2, FGF/FGFRs and PDGF/PDGFRβ simultaneously in vitro. Significant anticancer effects of WXFL-152 were confirmed in multiple preclinical tumor xenograft models, including a patient-derived tumor xenograft (PDX) model. Pharmacokinetic studies of WXFL-152 demonstrated high favourable bioavailability with single-dose and continuous multi-dose by oral administration in rats and beagles. In conclusion, WXFL-152, which is currently in phase Ib clinical trials, is a novel and effective triple-angiokinase inhibitor with clear PD and PK in tumor therapy.     

Valuation of EuroQol Five-Dimensional Questionnaire,Youth Version (EQ-5D-Y) and EuroQol Five-Dimensional Questionnaire,Three-Level Version (EQ-5D-3L) Health States: The Impact of Wording and Perspective

Background

Valuations of health states were affected by the wording of the two instruments (EQ-5D-3L and EQ-5D-Y) and by the perspective taken (child or adult).

European health inequality through the ‘Great Recession’: social policy matters

This paper investigates the association between the Great Recession and educational inequalities in self‐rated general health in 25 European countries. We investigate four different indicators related to economic recession: GDP; unemployment; austerity and a ‘crisis’ indicator signifying severe simultaneous drops in GDP and welfare generosity. We also assess the extent to which health inequality changes can be attributed to changes in the economic conditions and social capital in the European populations. The paper uses data from the European Social Survey (2002–2014). The analyses include both cross‐sectional and lagged associations using multilevel linear regression models with country fixed effects. This approach allows us to identify health inequality changes net of all time‐invariant differences between countries. GDP drops and increasing unemployment were associated with decreasing health inequalities. Austerity, however, was related to increasing health inequalities, an association that grew stronger with time. The strongest increase in health inequality was found for the more robust ‘crisis’ indicator. Changes in trust, social relationships and in the experience of economic hardship of the populations accounted for much of the increase in health inequality. The paper concludes that social policy has an important role in the development of health inequalities, particularly during times of economic crisis.     

产前心理干预对初产妇心理状态及分娩方式影响的meta分析

目的:评价产前心理干预对初产妇心理状态及分娩方式影响。方法:通过计算机检索CNKI、Wan Fang、CBM及VIP建库以来至2019年1月国内产前心理干预对初产妇心理状态及分娩方式影响的相关文献。由2名评价者独立检索筛选评价文献后,采用RevMan 5.3软件分析。结果:最终纳入9项RCT研究,包括1136例初产妇。meta分析结果显示:心理护理可以减轻初产妇的焦虑[MD=-1.41,95%CI(-1.54,-1.27),P<0.00001]、抑郁情绪[MD=-1.37,95%CI(-1.50,-1.23),P<0.00001],提高自然分娩率[OR=3.09,95%CI(2.32,4.13),P<0.00001],减少剖宫产率[OR=0.34,95%CI(0.26,0.44),P<0.00001]。结论:初产妇开展产前心理干预,能缓解初产妇焦虑抑郁情绪,有效提高自然分娩率。     

Innovation in Chemistry,Manufacturing, and Controls—A Regulatory Perspective From Industry

This review describes the landscape of novel modalities such as cell and gene therapies, viruses, other novel biologics, oligomers, and emerging technologies, including modern analytics. We summarize the regulatory history and recent landmark developments in some major markets and examine specific chemistry, manufacturing, and controls (CMC) challenges, including suggestions for exploration of potential science-based approaches in support of regulatory strategy development from an industry perspective. In addition, we evaluate the economic factors contributing to patient access to innovation and discuss the impact of regulation. There is a desperate need for a consistent form of regulation where global approaches to regulatory strategies can be harmonized, and specific CMC challenges can be dealt with using the appropriate science and risk-based tools. Although these tools are well described in current guidance documents, the specifics of applicability to complex novel modalities can still result in differing regulatory advice and outcomes. The future goals for efficiently regulating innovative modalities and technologies could be aided by more regulatory harmonization, regulatory education, and industry cooperation through consortia, enabling industry to supply key information to regulators in a transparent yet well-defined manner, and utilizing mutually understood risk-benefit analyses to produce drugs with appropriate safety, efficacy, and quality characteristics.     

Evaluation of log-rank tests for infrequent observations from a multi-state process, with application to HPV vaccine efficacy

Genital infection by human papillomavirus (HPV) is a common sexually transmitted disease, with over 25 per cent prevalence among young women in the US. Infections are usually without symptoms and transient (or reversible), but a small proportion of infections persist and are believed to be responsible for nearly all cervical cancers and precursor lesions such as cervical intraepithelial neoplasia (CIN). Therefore, successful vaccines against persistent HPV infections could have a great impact in preventing cervical cancers. In trials being planned, ongoing, and recently completed, a log-rank or a similar test may be employed to assess a vaccine effect in comparison to placebo, with an infection 'event' defined to capture persistent but not transient infections. However, it is not clear how best to define such an event, because (1) diagnostic tests cannot distinguish a persistent from a transient infection, (2) participants are only examined periodically, and (3) there can be misclassification errors in the detection of infections. This paper evaluates several definitions of persistent infection that are based on periodically observed infection statuses by postulating a multi-state model for persistent and transient infections. The type I error and the power of tests on vaccine efficacy based on these operational definitions are then examined under various scenarios of how a vaccine might affect the infection-disease process. We find that none of the candidates performs satisfactorily, thus raising concerns that clinical trials based only on infection endpoints will not be reliable.