Quantifying the risks and benefits of efavirenz use in HIV‐infected women of childbearing age in the USA

Objectives

The aim of the study was to quantify the benefits (life expectancy gains) and risks (efavirenz‐related teratogenicity) associated with using efavirenz in HIV‐infected women of childbearing age in the USA.

Methods

We used data from the Women's Interagency HIV Study in an HIV disease simulation model to estimate life expectancy in women who receive an efavirenz‐based initial antiretroviral regimen compared with those who delay efavirenz use and receive a boosted protease inhibitor‐based initial regimen. To estimate excess risk of teratogenic events with and without efavirenz exposure per 100 000 women, we incorporated literature‐based rates of pregnancy, live births, and teratogenic events into a decision analytic model. We assumed a teratogenicity risk of 2.90 events/100 live births in women exposed to efavirenz during pregnancy and 2.68/100 live births in unexposed women.

Results

Survival for HIV‐infected women who received an efavirenz‐based initial antiretroviral therapy (ART) regimen was 0.89 years greater than for women receiving non‐efavirenz‐based initial therapy (28.91 vs. 28.02 years). The rate of teratogenic events was 77.26/100 000 exposed women, compared with 72.46/100 000 unexposed women. Survival estimates were sensitive to variations in treatment efficacy and AIDS‐related mortality. Estimates of excess teratogenic events were most sensitive to pregnancy rates and number of teratogenic events/100 live births in efavirenz‐exposed women.

Conclusions

Use of non‐efavirenz‐based initial ART in HIV‐infected women of childbearing age may reduce life expectancy gains from antiretroviral treatment, but may also prevent teratogenic events. Decision‐making regarding efavirenz use presents a trade‐off between these two risks; this study can inform discussions between patients and health care providers.     

Nitrite directly vasodilates hypoxic vasculature via nitric oxide-dependent and -independent pathways

Background and purpose:

It is postulated that nitrite requires reduction to nitric oxide in order to exert its relaxant effect upon isolated hypoxic vessels. Herein, we evaluate the relative contribution of nitric oxide and characterize the downstream mechanisms of nitrite-induced vasorelaxation.

Experimental approach:

Aortic rings were treated with pharmacological agents and exposed to hypoxia (<1% O₂). Following pre-constriction, nitrite (10 µM final) was added to appropriate baths; isometric tension was recorded throughout.

Key results:

Nitrite (under hypoxic conditions at physiological pH) is capable of exerting physiological effects that cannot be completely inhibited by the inhibitor of soluble guanylate cyclase (sGC), 1H [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one or a nitric oxide scavenger (carboxy-2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide). Simultaneous blockade of both sGC and cyclooxygenase (COX) completely inhibited the response to nitrite. With regard to the nitric oxide-dependent component, we confirm that aldehyde oxidase, but not xanthine oxidase or endothelial nitric oxide synthase, was important for the actions of nitrite in our model.

Conclusions and implications:

Nitric oxide generated from nitrite is not exclusively responsible for the physiological actions observed in isolated hypoxic vessels. Nitrite operates via different pathways dependent on the presence or absence of endothelium to produce vasorelaxation. In intact vessels, both sGC and COX enzymes appear to be important. Irrespective of this difference in relaxation mechanism, nitrite is capable of producing the same maximum relaxation, regardless of the presence of endothelium. Having investigated possible nitrite reduction sites, we confirm that aldehyde oxidase is important for the actions of nitrite.     

模拟教学法可改善成人糖尿病患者的血糖控制

初级保健医师(primary care physicians,PCPs)对继续医学教育的需求很大.为了评估以病例为基础的模拟教学法是否可以提高初级保健医师对糖尿病的诊疗水平,美国明尼苏达州健康合作者研究基金会和医疗集团进行了相关的研究. 研究选择了美国明尼苏达州健康合作者研究基金会和医疗集团旗下的11个诊所的41名初级保健医师,随机分为参与模拟教学组和不参与模拟教学组.在模拟教学组中,给每位初级保健医师派发了1 2个2型糖尿病的模拟病例,这些病例都是针对研究人员在电子病历中观察到的初级保健医师诊疗水平的不足之处所专门设计的,每个模拟病例都需要初级保健医师在15分钟内完成诊疗过程.     

Congenital left atrial appendage ostial stenosis in an extremely premature infant diagnosed by transthoracic echocardiography

Congenital left atrial appendage ostial stenosis is a very rare congenital cardiac condition. We present the case of an extremely premature infant with congenital left atrial appendage ostial stenosis diagnosed by transthoracic echocardiographic imaging.     

A failure in the medication delivery system—how disclosure and systems investigation improve patient safety

A recent medication error at Vanderbilt University Medical Center contributed to the death of a patient. The ensuing criminal indictment of the administering nurse has shaken the medical community. This has led to clinical staff questioning whether they can disclose patient safety incidents without fear of criminal prosecution. However, because of the publicity of this case, hospitals can benefit from the lessons learned and mitigate the risk of this and similar events at their facilities. To uncover the most impactful and relevant safety recommendations, the Vanderbilt case is examined from a systems investigation perspective using the available public information gathered from media reports, the Tennessee Bureau of Investigation report, and Vanderbilt's corrective action plan submitted to CMS. We present an example of how hospitals can benefit from disclosure: Henry Ford Health used the Vanderbilt case study as part of its medication safety continuous improvement initiatives, which are underpinned by available medication safety recommendations from the Institute for Safe Medication Practices. Using this experience and the lessons learned from the Vanderbilt case, a proactive action plan is presented for hospitals nationwide to prevent the recurrence of this medication error. Without disclosure, these analyses and safety recommendations would not have been possible.