The cost-effectiveness of trivalent and quadrivalent influenza vaccination in communities in South Africa,Vietnam and Australia

BackgroundTo inform national healthcare authorities whether quadrivalent influenza vaccines (QIVs) provide better value for money than trivalent influenza vaccines (TIVs), we assessed the cost-effectiveness of TIV and QIV in low-and-middle income communities based in South Africa and Vietnam and contrasted these findings with those from a high-income community in Australia.MethodsIndividual based dynamic simulation models were interfaced with a health economic analysis model to estimate the cost-effectiveness of vaccinating 15% of the population with QIV or TIV in each community over the period 2003–2013. Vaccination was prioritized for HIV-infected individuals, before elderly aged 65+ years and young children. Country or region-specific data on influenza-strain circulation, clinical outcomes and costs were obtained from published sources. The societal perspective was used and outcomes were expressed in International$ (I$) per quality-adjusted life-year (QALY) gained.ResultsWhen compared with TIV, we found that QIV would provide a greater reduction in influenza-related morbidity in communities in South Africa and Vietnam as compared with Australia. The incremental cost-effectiveness ratio of QIV versus TIV was estimated at I$4183/QALY in South Africa, I$1505/QALY in Vietnam and I$80,966/QALY in Australia.ConclusionsThe cost-effectiveness of QIV varied between communities due to differences in influenza epidemiology, comorbidities, and unit costs. Whether TIV or QIV is the most cost-effective alternative heavily depends on influenza B burden among subpopulations targeted for vaccination in addition to country-specific willingness-to-pay thresholds and budgetary impact.     

Haemophilus influenzae-protein D specific antibody correlate with protection against acute otitis media in young children

BackgroundHaemophilus influenzae (Hi) causes respiratory infections and pathogenesis of this microbe begins in the human nasopharynx (NP). The objective of this study was to assess the correlation of NP colonization-induced serum antibody levels to Hi protein D with risk of acute otitis media (AOM) in children <2 yr.Methods455 sera from 213 children (age 6–24 months old) were collected when they were colonized with Hi and when the children developed AOM. Presence of Hi during AOM was confirmed by culture of middle ear fluid. Quantitative ELISA was used to determine serum IgG against protein D antigen.ResultsAsymptomatic Hi NP colonization reduced the risk of future AOM infections. Higher serum IgG titers against Hi protein D were correlated with reduced future AOM risk.ConclusionColonization by Hi reduces future AOM risk. Higher antibody levels against protein D correlates with lower risk of AOM caused by Hi.     

贵州省实施乙型肝炎疫苗免疫策略的成本-效果分析

目的 分析贵州省实施乙型肝炎疫苗(Hepatitis B vaccine,HepB)免疫策略的成本-效果。方法 根据贵州省HepB接种情况,1992年、2006年、2014年贵州省乙肝血清流行病学调查结果,计算全省不同时期HepB接种投入以及接种HepB的成本效果比值(Cost-Effectiveness Ratio,CER)。结果 贵州省1999-2016年共接种HepB 25951786剂次。全省推广使用HepB、纳入免疫规划并联合查漏补种免疫策略18年,共减少HBsAg携带者3195730例,减少慢性乙肝319573例,减少肝硬化31957例,减少肝癌3196例。1999-2016年贵州省实施HepB免疫策略总投入成本675亿元,18年间接种HepB每减少1例HBsAg携带者、慢性乙肝、肝硬化及肝癌病例需投入的成本为19013元,其中,推广使用HepB疫苗时期(1999-2002年)、纳入免疫规划并联合HepB查漏补种时期(2003-2010年)以及后HepB常规免疫时期(2011-2016年)接种HepB每减少1例HBsAg携带者、慢性乙肝、肝硬化及肝癌病例需投入的成本分别为57979元、7809元和35912元。结论 接种HepB对降低贵州省接种人群乙肝发病水平具有良好的成本-效果,2003-2010年将HepB纳入免疫规划并联合查漏补种免疫策略的成本效果最好。     

2016—2018年中国医科大学附属第一医院门诊药房麻醉药品的使用情况分析

目的 分析2016—2018年中国医科大学附属第一医院门诊药房麻醉药品的使用情况和变化趋势,为临床合理使用麻醉药品提供参考。方法 对2016—2018年中国医科大学附属第一医院门诊药房麻醉药品的使用数量、销售金额、用药频度（DDDs）、日均费用（DDC）以及排序比（B/A）进行统计学分析。结果 2016—2018年门诊药房麻醉药品消耗量持续增长,麻醉药品的销售金额排名稳定,盐酸羟考酮缓释片（10、40 mg）的销售金额排名分别位列前两位。各药品的DDDs排名变化不明显,芬太尼透皮贴剂（4.2 mg）的DDDs连续3年排名第1位。DDC持续下降,DDC值最高的为盐酸羟考酮缓释片（40 mg）,最低的为盐酸布桂嗪片。B/A最低的为盐酸羟考酮缓释片（10 mg）,最高的为芬太尼透皮贴剂（4.2 mg）,其他麻醉药品的B/A值都在1左右。结论 中国医科大学附属第一医院门诊药房麻醉药品的使用基本合理。     

2015—2017年青岛市城阳区人民医院住院患者中药注射剂的使用合理性分析

目的 了解2015—2017年青岛市城阳区人民医院住院患者中药注射剂的使用情况,为临床合理使用提供参考。方法 对2015—2017年青岛市城阳区人民医院住院患者中药注射剂的销售金额、用药频度（DDDs）、日均费用（DDC）和药品排序比（B/A）以及不合理使用情况等进行统计分析。结果 2015—2017年中药注射剂的销售总金额呈逐年下降趋势;理血剂的销售金额连续3年排名第1位;注射用血栓通的销售金额和DDDs一直位列第1位,呈逐年下降趋势;大部分中药注射剂的DDC基本稳定,排序完全不变。大部分中药注射剂的使用越来越合理,B/A不断接近1.0。结论 2015—2017年青岛市城阳区人民医院中药注射剂使用率大幅下降,合理使用率明显提高,专项点评效果显著,但仍存在不合理使用情况,需要进一步进行干预。     

Proposal of a Parameter for OATP1B1 Inhibition Screening at the Early Drug Discovery Stage

It is known that potent inhibition of organic-anion-transporting polypeptide (OATP)1B1 increases exposure to statins, leading to severe adverse effects. The aim of this study was to propose a parameter and its criteria in OATP1B1 inhibition assay at the early drug discovery stage to avoid compounds with the risk of statin-related adverse effects. According to drug label information, most compounds classified as “contraindicated” or “should be avoided” when administered concomitantly with statins increased their AUCs more than 4-fold. Generally, R values where R = 1 + plasma unbound fraction (fu) × maximum inhibitor concentration at the inlet to the liver/IC₅₀ are used to evaluate the extent of clinical drug interaction. However, clinical doses and C_max cannot be determined at the screening stage. Therefore, we estimated the correlations between change in AUC of statins concomitantly administered with OATP1B1 inhibitors and various parameters including fu/IC₅₀. Cyclosporin A, rifampicin, and telaprevir increased the AUC of statins more than 4-fold and fu/IC₅₀ of these compounds was >0.1 L/μmol. On the other hand, fu/IC₅₀ of other compounds was ≤0.03 L/μmol. This study indicates that fu/IC₅₀ is a useful parameter to avoid compounds that seriously affect statin potency through interaction with OATP1B1 at the screening stage.     

Bennett acceptance ratio method to calculate the binding free energy of BACE1 inhibitors: Theoretical model and design of new ligands of the enzyme

In recent years, the design, development, and evaluation of several inhibitors of the BACE1 enzyme, as part of Alzheimer's treatment, have gathered the scientific community's interest. Here, a linear regression model was built using binding free energy calculations through the Bennett acceptance ratio method for 20 known inhibitors of the BACE1 enzyme, with a Pearson coefficient of R = 0.88 and R² = 0.78. The validation of this model was verified employing eight additional random inhibitors, which also gave a linear correlation with R = 0.97 and R² = 0.93. Furthermore, this linear regression model was also used for proposing the structure of four potential BACE1 inhibitors, and the most active of them gave a theoretical K_d = 10 nM. However, these molecules have not been synthesized yet. Our team used a total time of more than 800 ns for the Molecular Dynamics to carry out this study, and all the software used were freely available.     

Ionized magnesium and calcium concentration and their ratio in equine plasma samples as determined by a regulatory laboratory compared to a clinical reference laboratory

Magnesium sulfate (MgSO₄) was administered to calm competition horses. We evaluated the impact of regulatory requirements for the handling of blood samples on plasma ionized magnesium (iMg), ionized calcium (iCa), the iMg to iCa ratio, and pH. We hypothesized that iCa, iMg. and iMg/iCa would be similar among storage and collection methods. Four blood samples were collected from each of 50 horses on the same day: Group 1 – collection in a heparinized syringe and processed within hours in a clinical laboratory; Group 2 – collection into a plasma separator tube (PST) centrifuged just prior to analysis, and plasma processed as in (1); Group 3 – collection into a PST, refrigerated, shipped via overnight carrier to the United States Equestrian Federation (USEF) Equine Drug Testing and Research laboratory, centrifuged just prior to analysis, and plasma processed; and Group 4 – as in Group 3, but stored frozen at ?80°C for 90 days, thawed, and plasma processed as in Group 3. Results for iMg/iCa are unit‐less, adjusted iMg for potential influence of plasma protein and iCa, and highly correlated with iMg pH (r = ?.933; P < 0.01). Samples processed immediately in a clinical reference laboratory had the greatest iMg/iCa. Both iMg/iCa and pH predictably decreased after freezing (P < 0.001). These data suggest that the iMg/iCa mirrors alterations in iMg regardless of storage and collection methods. This understanding can facilitate the development of a regulatory threshold for the control of the nefarious use of magnesium sulfate in competing horses, and an understanding of potential changes to iMg/iCa with storage of B samples.     

Development and validation of a method to confirm the exogenous origin of prednisone and prednisolone by GC‐C‐IRMS

Prednisone and prednisolone are two anti‐inflammatory steroidal drugs listed by the World Anti‐Doping Agency (WADA) within the class of glucocorticoids, which are prohibited “in competition” and when administered systemically. Their presence in collected urine samples may be attributed, if no exogenous administration has occurred, to an in situ microbial formation from endogenous steroids. In this work, a gas chromatography coupled to carbon isotope ratio mass spectrometry (GC‐C‐IRMS) method was developed and validated to distinguish an exogenous origin from an endogenous one. Eight prednisone/prednisolone pharmaceutical preparations commercially available in Italy were analysed to establish an exogenous δ¹³C value reference range (?28.96 ± 0.39‰). No more than 25 mL of urine was processed and no derivatization nor intentional steroids structure modifications were performed before the GC‐C‐IRMS analysis. A first HPLC purification step was set up to isolate the three endogenous reference compounds (ERCs) selected (tetrahydro‐11‐deoxycortisol (THS), pregnanediol (PD), and pregnanetriol (PT)), while a second LC purification was necessary to separate prednisone from prednisolone. In the GC‐C‐IRMS analysis, two different GC run methods were set up to guarantee better sensitivity and selectivity for each compound. Both prednisone and prednisolone showed signals (m/z 44) with amplitudes within the method linearity range to a lower urinary concentration of 20 ng/mL (< WADA reporting level, 30 ng/mL). The method was fully validated according to WADA requirements. As a proof of concept, urine samples collected from two excretion studies in healthy male volunteers, after a prednisone or prednisolone administration, were analysed by the proposed method, demonstrating its applicability for the analysis of real samples.