Identification of factors driving differences in cost effectiveness of first-line pharmacological therapy for uncomplicated hypertension

BACKGROUND:

Published practice guidelines and economic evaluations have come to different conclusions regarding optimal pharmacotherapy for the treatment of uncomplicated hypertension. The drivers of these disparities are not clear. Greater understanding is needed for clinicians, researchers and policy makers to determine the most effective and sustainable strategies.

OBJECTIVES:

To identify how cost and cost-effectiveness considerations are used to generate recommendations by major hypertension guidelines, and determine key drivers of cost-effectiveness conclusions in available economic evaluations.

METHODS:

A systematic search and narrative review of major hypertension guidelines and health technology assessments of first-line antihypertensive therapy were performed.

RESULTS:

Of the eight guidelines identified, formal cost-effectiveness analysis was rarely integrated in the formulation of recommendations. When guidelines considered costs, recommendations remained incongruent. Two economic evaluations were identified (United Kingdom and Canada); however, these differed in their conclusion of the most cost-effective agent and attractiveness of calcium channel blockers. Review of these economic evaluations suggests that cost-effectiveness conclusions are strongly influenced by relative costs of drug classes; when relative differences in drug costs are lower, the impact on associated conditions such as heart failure and diabetes influences cost-effectiveness conclusions.

CONCLUSION:

In the setting of finite health care resources and significant budget impact due to high population prevalence, cost effectiveness is an important consideration in the treatment of uncomplicated hypertension. Identification of key drivers of cost effectiveness will assist interpretation and conduct of current and future economic evaluations.     

人外周血树突状细胞的分离与鉴定

目的:体外分离培养并鉴定人外周血树突状细胞,并观察其抗原呈递功能。方法:实验于2005-05/2006-11在南方医科大学南方医院肿瘤中心生物治疗实验室完成。从人类白细胞抗原A2表达阳性的健康人外周血中分离获得单个核细胞。培养5h后洗涤贴壁细胞,加入含有10%人AB血清的RPMI1640培养基,及重组人粒细胞-巨噬细胞集落刺激因子和重组人白细胞介素4,于培养的第1,3,6天对树突状细胞的形态、表型进行分析,并定期检测树突状细胞的纯度与得率。抽取与以上树突状细胞不同来源的其他健康人外周血。经淋巴细胞分离液分离后,获取非贴壁细胞,用含10%人AB血清的1640培养基重悬,加入白细胞介素2继续孵育6d,作为同种异体T淋巴细胞。将树突状细胞分为两组,一组按常规方法培养6d,另一组在培养至第5天时加入黑色素瘤抗原基因A3编码的多肽继续培养24h。在经紫外线处理后的96孔板中,分别加入树突状细胞悬液1×104,5×103,2×103,1×103细胞/每孔,以自身T淋巴细胞作为对照,每孔设3个复孔,分别加入1×105淋巴细胞/每孔。评价树突状细胞刺激T淋巴细胞增殖的能力。结果:①单个核细胞体外培养至第6天,可获得大量、90.81%高纯度的树突状细胞,能够较高地表达21.8?1a、99.0%HLA-DR、63.4?80、18.9?83和80.6?86。②将诱导培养6d获得的两组树突状细胞作为刺激细胞,以不同的浓度与同种异体淋巴细胞混合,均可产生增殖反应;经过黑色素瘤抗原基因A3编码的多肽处理的各种比例的树突状细胞,较相应未经黑色素瘤抗原基因A3编码的多肽处理的树突状细胞激发淋巴细胞增殖的能力明显增强,浓度相对较高的树突状细胞刺激效果最明显,能够强烈地激发同种混合淋巴细胞增殖。结论:得到了一群较高程度表达CD83、CD86和HLA-DR分子、体外可强烈激发同种异体T淋巴细胞增殖的树突状细胞群。     

Effects of human neutrophil elastase (HNE) on neutrophil function in vitro and in inflamed microvessels

The primary objective of this study was to test the hypothesis that human neutrophil elastase (HNE) affects neutrophil infiltration (adhesion and emigration) into inflamed vessels. To determine whether HNE contributes to neutrophil adhesion in vivo, intravital microscopy was used to study neutrophil-endothelial cell interactions in single inflamed postcapillary venules. Superfusion of platelet-activating factor (PAF) (100 nmol/L) onto the mesentery caused an increase in neutrophil-neutrophil interactions, neutrophil adhesion to postcapillary venules, and cellular emigration out of the vasculature. Both L658 758 (an elastase-specific inhibitor), and Eglin C (an elastase and cathepsin G inhibitor) significantly attenuated all of these parameters in vivo. To further characterize the mechanism(s) involved, various in vitro parameters were assessed. HNE, but not trypsin, caused a dose-dependent (0.01 to 1.0 microgram/mL) increase in the expression of the beta subunit (CD18) of the CD11/CD18 adhesive glycoprotein complex on neutrophils. An HNE-dependent increase in CD11b expression was also observed; however, HNE did not affect the expression of other neutrophil adhesion molecules (L-selectin), superoxide production, or degranulation. PAF-enhanced CD18 expression on neutrophils and neutrophil migration were both abolished by L658 758 but PAF-induced neutrophil adhesion to endothelial monolayers was not affected by the antiproteinase. The in vitro data suggest that the antiproteinases do not directly prevent neutrophil adhesion in vivo but may be important in other CD18-dependent events such as neutrophil- neutrophil interaction or neutrophil infiltration (chemotaxis). These results translate into an important, rate-limiting role for elastase in the process of leukocyte infiltration and accumulation in inflamed microvessels.     

Choice of pretransplant treatment and timing of transplants for chronic myelogenous leukemia in chronic phase [see comments]

We analyzed the outcome of 450 HLA-identical sibling bone marrow transplants for chronic myelogenous leukemia (CML) in chronic phase performed between 1985 and 1990 and reported to the International Bone Marrow Transplant Registry (IBMTR). All patients received either hydroxyurea (n = 292) or busulfan (n = 158) to treat their CML before transplant. The median interval between diagnosis and transplant was 10 months (range, 1 to 191). Patients treated with hydroxyurea had a higher probability (95% confidence interval) of leukemia-free survival (LFS) at 3 years than those treated with busulfan (61% [51% to 70%] v 45% [36% to 55%], P < .0003). Probability of LFS was also higher in patients transplanted within 1 year of diagnosis (61% [53 to 68%] v 47% [38% to 57%], P < .001). After adjustment for patient and transplant covariables in a multivariate analysis, prior chemotherapy and duration of disease pretransplant were independently associated with LFS. These data support the use of hydroxyurea rather than busulfan and transplant within 1 year of diagnosis for patients with CML and an HLA-identical sibling.