In vitro and in vivo evaluation of drug–drug interaction between dabigatran and proton pump inhibitors

To quantify the drug–drug interactions between dabigatran etexilate (DE) and proton pump inhibitors (PPI) and in particular the role of P‐gp activity modulation. In the first part of the study, efflux ratios of DE were evaluated using the caco‐2 cell line in the presence of pantoprazole, omeprazole, rabeprazole, lansoprazole and ciclosporin A (positive control). The two PPI that reduced the efflux ratio of dabigatran to the greatest and least extent, respectively, were used during the second part of the study, comprising a single‐centre, randomised, open‐label study with an incomplete Latin square design. Nine healthy volunteers received DE (150 mg) alone, DE (150 mg) with the first PPI and DE (150 mg) with the second PPI in randomised sequence. Dabigatran plasma concentration and thrombin time were measured in blood samples withdrawn at 11 time points after each treatment. Models were built using a nonlinear mixed‐effect modelling approach. Omeprazole and rabeprazole were the two PPI that reduced the efflux ratio of DE least and most, respectively. The PK model was based on an inverse Gaussian absorption process with one compartment. The relationship between dabigatran concentration and thrombin time was considered linear. Some PK profiles had dramatically low concentration values due to poor absorption. These profiles were clustered using a between subject model mixture with interoccasion variability. The concomitant administration of PPI did not significantly change dabigatran pharmacokinetics. DE is subject to high absorption variability, precluding evaluation of the effect of PPI on its pharmacokinetics.     

“Getting tested is almost like going to the Salem witch trials”: discordant discourses between Western public health messages and sociocultural expectations surrounding HIV testing among East African immigrant women

Washington, DC, has the highest AIDS diagnosis rate in the USA, and Black women are disproportionately affected. Although HIV testing is the first entryway into vital treatment services, evidence reveals that foreign-born blacks have a lower rate of recent HIV testing than US-born blacks. To date, however, there are no studies that examine the culture-specific perceptions of HIV testing among East African immigrant women (who comprise a large share of Black Africans in DC) to better understand their potential barriers to testing. Adopting the PEN-3 cultural model as our theoretical framework, the main objective of this study was to examine East African women's HIV testing perceptions and partner communication norms. Between October 2012 and March 2013, trained interviewers conducted a total of 25 interviews with East African women in the Washington, DC, metropolitan area. For triangulation purposes, data collection consisted of both in-depth, semi-structured interviews and cognitive interviews, in which participants were administered a quantitative survey and assessed on how they interpreted items. Qualitative thematic analysis revealed a systematic pattern of discordant responses across participants. While they were aware of messages related to Western public health discourse surrounding HIV testing (e.g., Everyone should get tested for HIV; One should talk to one's spouse about HIV testing), divergent sociocultural expectations rooted in cultural and religious beliefs prevailed (e.g., Getting an HIV test brings shame to the person who got tested and to one's family; it implies one is engaging in immoral behavior; One should not talk with one's spouse about HIV testing; doing so breaks cultural norms). Implications of using a culture-centered model to examine the role of sociocultural expectations in HIV prevention research and to develop culturally responsive prevention strategies are discussed.     

Acute toxicity when concentration varies with time: A case study with carbon monoxide inhalation by rats

Exposure to time-varying concentrations of toxic compounds is the norm in both occupational settings and daily human life, but little has been done to investigate the impact of variations in concentration on toxic outcomes; this case study with carbon monoxide helps fill that gap. Median acute lethality of 10-, 20-, 40-, and 60-min continuous exposures of rats to carbon monoxide was well described by the toxic load model (k = Cⁿ × t; k is constant, C = test concentration, n = toxic load exponent, and t = exposure duration) with n = 1.74. Dose response-relationships for 1-h exposures including a recovery period between 10- or 20-min pulses showed greater similarity (in both median lethality and steepness of dose-response curve) to continuous exposures with equivalent pulse duration and concentration, rather than a 60-min exposure with equivalent time-weighted average concentrations or toxic load. When pulses were of unequal concentration (3:1 ratio), only the high concentration pulse contributed to lethality. These findings show that fluctuations or interruptions in exposure over a short time scale (60 min or less) can have a substantial impact on outcomes (when n > 1), and thus high-resolution monitoring data are needed to aid interpretation of resulting outcomes.     

Operationalizing Pain Treatment in the Biopsychosocial Model: Take a Daily “SWEM”—Socialize,Work, Exercise,Meditate

In the United States, chronic pain is often poorly treated at an exceedingly high cost. The use of the biomedical model to manage pain is frequently ineffective, and evidence suggests that the biopsychosocial (BPS) model is a better choice. A problem with the BPS model is that it has not been operationalized in terms of patient behavior. This commentary addresses that issue by suggesting that people with chronic pain and illness participate daily in four self-management health behaviors: socialize, work, exercise, and meditation, and discusses evidence that supports these recommendations. These self-management behaviors may decrease pain and thus reduce the need for pain medications and other medical interventions. Additional topics include patient adherence and health coaching.     

护理安全管理模式应用于介入治疗中的临床观察

目的探讨护理安全管理模式在介入治疗中的应用效果。方法通过对我院介入室的护理安全隐患进行分析,并针对性开展护理安全管理模式。选取2013年8月~12月130例介入患者作为对照组,采用常规护理。选取2014年1月~4月开展安全管理后130例介入患者作为研究组,在常规护理的基础上实施护理安全管理。比较两组护理质量及患者满意度。结果两组护理干预后护理质量评分比较,有显著性差异(P0.01)。研究组患者对护理人员的满意度高于对照组(94.6%vs80.7%),有显著性差异(P0.01)。结论通过实施护理安全管理后,能及早解决护理安全隐患,做到防微杜渐,使护理质量及患者满意度明显提高。     

基于回转器理论的电流模式控制型DC-DC变流器统一大信号模型

随着新能源技术的大力发展，直流分布式系统以其独特的优势得到了越来越广泛的关注，逐渐成为业界的研究热点。虽然系统中每个模块都能够单独稳定运行，但由于模块之间复杂的相互作用，系统的稳定性特别是在大信号扰动下的暂态稳定性情况仍是令人困扰的一大难题，且目前该领域的理论研究成果相对缺乏。简单、有效、统一的大信号模型是进行大信号稳定性理论分析的基础。由于电流模式控制方法应用较为广泛，故本文基于回转器理论提出了一种适用于电流模式控制型DC-DC变流器的统一大信号模型。该模型实现了降阶，表达式简单，且仅需修改其中一个模型参数值即可实现对不同拓扑变流器的建模分析，为理论分析系统的大信号稳定性奠定了良好的基础，也为解析形式大信号稳定性判据的提出提供了可能。仿真和实验分别基于Buck、Boost及Buck-Boost变流器对该模型的有效性进行了验证。同时，为验证该大信号模型的完备性，对其稳态工作点附近的小信号特性也进行了分析，并与目前公认的比较精确的电流模式控制小信号模型进行了对比，得到了较好的结果。     

Buck变流器级联系统直流母线电压补偿控制策略

在直流分布式电源系统的设计过程中，稳定性设计是最核心但最复杂的部分。随着系统规模日益庞大，若想将其作为整体进行稳定性设计几乎是不可能的。由于级联是分布式结构中最基本的连接形式，故深入研究、改善级联系统的稳定性对于确保整个系统的稳定运行非常重要。除优化设计变流器参数外，增加母线补偿装置(VBC)也是改善级联系统直流母线电压稳定性的一种有效途径，目前针对DC-DC级联系统母线补偿策略及补偿容量的研究已取得了一定的成果，其中一些研究还可以应用于大信号扰动的场合。但总体而言仍有进一步探索和发展的空间。本文从大信号的研究角度出发，基于混合势函数理论和回转器大信号模型，提出了一种直流母线电压补偿控制策略。该控制策略可根据级联系统中源、负载变流器的具体特性参数进行有针对性的补偿；同时，该策略由混合势函数理论的稳定性定理推导得出，从理论上保证了加入VBC后整个系统在大信号扰动下的稳定性。仿真和实验以峰值电流模式控制型Buck变流器级联系统为例对该补偿控制策略的有效性和补偿效果进行了验证。