Patient perspectives on de‐simplifying their single‐tablet co‐formulated antiretroviral therapy for societal cost savings

Objectives

The incremental costs of expanding antiretroviral (ARV) drug treatment to all HIV‐infected patients are substantial, so cost‐saving initiatives are important. Our objectives were to determine the acceptability and financial impact of de‐simplifying (i.e. switching) more expensive single‐tablet formulations (STFs) to less expensive generic‐based multi‐tablet components. We determined physician and patient perceptions and acceptance of STF de‐simplification within the context of a publicly funded ARV budget.

Methods

Programme costs were calculated for patients on ARVs followed at the Southern Alberta Clinic, Canada during 2016 (Cdn$). We focused on patients receiving Triumeq® and determined the savings if patients de‐simplified to eligible generic co‐formulations. We surveyed all prescribing physicians and a convenience sample of patients taking Triumeq® to see if, for budgetary purposes, they felt that de‐simplification would be acceptable.

Results

Of 1780 patients receiving ARVs, 62% (n = 1038) were on STF; 58% (n = 607) of patients on STF were on Triumeq®. The total annual cost of ARVs was $26 222 760. The cost for Triumeq® was $8 292 600. If every patient on Triumeq® switched to generic abacavir/lamivudine and Tivicay® (dolutegravir), total costs would decrease by $4 325 040. All physicians (n = 13) felt that de‐simplifying could be safely achieved. Forty‐eight per cent of 221 patients surveyed were agreeable to de‐simplifying for altruistic reasons, 27% said no, and 25% said maybe.

Conclusions

De‐simplifying Triumeq® generates large cost savings. Additional savings could be achieved by de‐simplifying other STFs. Both physicians and patients agreed that selective de‐simplification was acceptable; however, it may not be acceptable to every patient. Monitoring the medical and cost impacts of de‐simplification strategies seems warranted.

     

部分脱乙酰甲壳质生物套管小间隙桥接修复周围神经损伤:免疫组织化学观察

目的:神经断端保留小间隙的静脉桥接模拟神经外膜形成神经再生室,为周围神经再生创造了良好的生理环境,从而保证神经束的良好对合。实验采用部分脱乙酰甲壳质作为套管材料,用小间隙桥接方法修复坐骨神经损伤,观察套管内的神经再生情况,并与传统外膜缝合法进行比较。方法:实验于2001-01/2002-10在北京大学人民医院创伤骨科实验室完成。①主要材料:实验所用中空圆柱形套管为北京大学人民医院与中国纺织科学院共同发明的一种部分脱乙酰甲壳质生物套管(专利号:01136314.2)。实验中所用套管尺寸为:管长4 mm,壁厚0.1 mm,内径1.5 mm。②实验动物:健康成年雄性SD大鼠20只,随机分成2大组,每组10只,每一大组全部10只动物的左腿坐骨神经为一组,右腿坐骨神经为另一组,每组10根坐骨神经。另取5只同样大鼠双侧坐骨神经未做处理作为正常对照组。③实验方法:外膜原位缝合组:切断坐骨神经,显微镜下神经外膜原位缝合;生物套管小间隙原位桥接组:切断坐骨神经,显微镜下小间隙套管桥接;断端旋转180°外膜缝合组:切断坐骨神经,显微镜下远端旋转180°后,神经外膜缝合;断端旋转180°生物套管小间隙桥接组:切断坐骨神经,显微镜下远端旋转180°后,小间隙套管桥接。④实验评估:术后第7,14,21,28,42天取坐骨神经,进行免疫组织化学染色及观察。结果:再生神经延套管中央走行,7 d时已有部分纤维通过2 mm间隙,14 d时有髓纤维数量明显多于近端。21 d后,套管组与原位外膜组新生有髓神经纤维数相近。再生纤维胞核数量较多,髓鞘纤细。套管结构完整。结论:此种部分脱乙酰甲壳质生物套管内的再生神经连续、整齐,髓鞘完整,其神经再生情况好于传统外膜缝合法。     

Increasing sexually transmitted infection rates in young men having sex with men in the Netherlands, 2006–2012

Background

Men having sex with men (MSM) remain the largest high-risk group involved in on-going transmission of sexually transmitted infections (STI), including HIV, in the Netherlands. As risk behaviour may change with age, it is important to explore potential heterogeneity in risks by age. To improve our understanding of this epidemic, we analysed the prevalence of and risk factors for selected STI in MSM attending STI clinics in the Netherlands by age group.

Methods

Analysis of data from the national STI surveillance system for the period 2006–2012. Selected STI were chlamydia, gonorrhoea, infectious syphilis and/or a new HIV infection. Logistic regression was used to identify factors associated with these selected STI and with overall STI positivity. Analyses were done separately for MSM aged younger than 25 years and MSM aged 25 years and older.

Results

In young MSM a significant increase in positivity rate was seen over time (p?<?0.01), mainly driven by increasing gonorrhoea diagnoses, while in MSM aged 25 and older a significant decrease was observed (p?<?0.01). In multivariate analyses for young MSM, those who were involved in commercial sex were at higher risk (OR: 1.5, 95% CI: 1.2-1.9). For MSM aged 25 years and older this was not the case. Having a previous negative HIV test was protective among older MSM compared to those not tested for HIV before (OR: 0.8, 95% CI: 0.8-0.8), but not among younger MSM.

Conclusions

MSM visiting STI clinics remain a high-risk group for STI infections and transmission, but are not a homogenous group. While in MSM aged older than 25 years, STI positivity rate is decreasing, positivity rate in young MSM increased over time. Therefore specific attention needs to be paid towards targeted counselling and reaching particular MSM sub-groups, taken into account different behavioural profiles.

     

Oxidative metabolism of the human eosinophil

We have compared the oxidative metabolism of human eosinophils (80%-90% purity) to that of neutrophils. Hexose monophosphate (HMP) shunt activity of eosinophils was higher than that of neutrophils under either resting or phagocytizing conditions. Eosinophil HMP shunt activity also was stimulated by phorbol myristate acetate, a membrane- active agent. Eosinophils showed a marked incorporation of 125I into trichloroacetic acid-insoluble material under resting conditions, which increased markedly during phagocytosis. Eosinophils likewise showed a greater reduction of nitroblue tetrazolium dye during phagocytosis than did neutrophils. Measurement of other parameters of oxidative metabolism indicated that eosinophils generated superoxide anion following phagocytosis and also elicited a burst of chemiluminescence similar to that observed during phagocytosis by neutrophils. Measurement of NADPH oxidase activity demonstrated that this enzyme was 3-6 times more active in fractions isolated from eosinophils than in corresponding fractions isolated from neutrophils; this was observed over a range of substrate concentrations. The eosinophil enzyme sedimented differently than the neutrophil enzyme with differential centrifugation; neither showed sedimentation characteristics of peroxidase. These data indicate that eosinophils possess a similar, although in some ways more potent, oxidative burst than neutrophils and are consistent with a role for NADPH oxidase in the initiation of that burst.     

从兔股骨头中提取总RNA的方法特点

目的:建立一种高效、快速的骨组织总RNA提取方法。方法:实验于2005-01/2006-01在昆明医学院实验动物中心和中国科学院昆明动物研究所中科院细胞与分子进化重点实验室完成。取健康新西兰大白兔1只,截取其股骨头,迅速置于液氮罐中保存,于研钵中研磨,使骨组织始终保存于液氮中,继续研磨,如此重复3次,然后利用Trizol使骨细胞结构迅速破坏,将粉末转入离心管,室温静置5min。随后加入氯仿等有机溶剂处理、离心,使RNA与细胞DNA、蛋白质及其他成分分离从而得到总RNA。最后鉴定RNA的质量、纯度及产率,取2μL提取出的RNA在体积分数为0.008的甲醛变性琼脂糖凝胶上进行电泳,主要观察RNA的28S、18S及5S三个条带是否清晰,有无降解和DNA污染。以99μLDEPC水稀释1μLRNA样品,紫外分光光度计测量其吸光度(A)值,A260/A280之比值表示RNA的纯度,同时根据吸光度值计算其质量浓度。结果:①对提取的兔股骨头RNA进行琼脂糖凝胶电泳,可显示清晰的28S、18S两个条带,5S条带亦可见,表明了RNA是完整的。②用紫外分光光度法测定兔股骨头中提取出的RNAA260/A280,结果表明由本法提取的RNA纯度高,无DNA和蛋白质的污染。③经紫外分光光度计吸收定量,每毫克兔股骨头组织能提取1.0～1.2μg的总RNA。结论:本法提取骨组织总RNA方便、快捷,质量高,可用于骨组织的分子生物学研究。     

间硝苯地平对血管紧张素Ⅱ促进血管平滑肌细胞增殖和蛋白质合成的影响

以培养血管平滑肌细胞(vascularsmcothmusclecell,VSMC)为模型,观察了间硝苯地平(m-nifedipine,m-Nif)对血管紧张素Ⅱ(angiotensinⅡ,ANGⅡ)促进VSMC增殖和蛋白质合成的影响。结果表明,m-Nif抑制ANGⅡ(100nmol·L^-1)引起VSMC[³H]thymidine和[³H]leucine参入,并呈剂量依赖性。m-Nif(2×10^-6mol·L^-1)可抑制ANGⅡ对VSMC的刺激、DNA及蛋白质合成速率,分别降低了46%,58%,53%。提示m-Nif可抑制ANGⅡ对VSMC增殖和蛋白合成的促进作用。     

Ultrasonic detection of myocardial infarction by amplitude analysis.

Myocardial infarctions were produced in dogs by occluding the left anterior descending artery; the dogs were killed at varying times, from 30 minutes to 8 days. Prior to sacrifice, Thioflavin S was injected intravenously. The excised heart was scanned by a B-scanner interfaced with a computer that permitted quantification of signal amplitude. The heart was sectioned, photographed, and studied pathologically. Infarcted myocardium showed high ultrasonic reflectivity with average amplitudes 1.4--2.6 times that of normal muscle. Perfusion-histomorphologic evidence of infarction correlated best in infarcts of 24 hours or less; older infarcts were generally underestimated. Tissue changes, sources of false-positive and false-negative findings, signal processing, and potential clinical utility are discussed.     

Annotation: The similarities and differences between autistic disorder and Asperger's disorder: a review of the empirical evidence

Background:  The ongoing controversy over the distinction between autistic disorder and Asperger's disorder is important to resolve because of the implications regarding an understanding of the aetiology and prognosis, and the diagnostic and clinical practices relating to these conditions. This paper provides a critical evaluation of current published research evidence.
Method:  Databases, such as PsychINFO and Medline, as well as book chapters, reference lists from relevant articles, and recent editions of key journals were searched for all relevant studies (until 2002) which incorporated participants diagnosed with high-functioning autism and Asperger's disorder using either cluster analysis or comparative approaches to examine similarities and differences between these groups. Keywords used in the searches included autistic disorder, Asperger's disorder, autism, high-functioning autism, and pervasive developmental disorder.
Results:  On the basis of the available evidence, there seem to be few qualitative differences between autistic disorder and Asperger's disorder.
Conclusion:  There is currently insufficient evidence to establish the validity of Asperger's disorder as a syndrome distinct from high-functioning autism. The findings are consistent with the view that these disorders belong on an autism spectrum.