Problem‐maintaining circles: Case illustrations of formulations that truly guide therapy

The cognitive behaviour therapy (CBT) emphasis on treatment relevance in assessment, and on evidence‐based intervention, has led to an increasing focus on problem maintenance factors (vs. precipitants) in both its models of psychopathology and in its individual case formulations. This article describes the reasons for this growing focus, and presents a generic CBT model based on the functional analysis of “problem‐maintaining circles” (PMCs) of causes. Some samples of the profuse literature implicating PMCs in many psychological disorders are presented, and the utility of PMC‐based functional analysis, case formulation, or modelling of psychopathology is advanced, not only as a guide to selection of therapeutic interventions, but as an alternative to standard psychiatric diagnosis. A sampling of a taxonomy of such PMCs is presented. And finally, the clinical application of PMC‐based functional analysis, case formulation, and treatment selection is illustrated in five case illustrations drawn from a recent clinical caseload.     

Reliable and reproducible LightCycler qPCR for HIV-1 DNA 2-LTR circles

Highly active anti-retroviral therapy (HAART) has reduced the plasma load of HIV-1 to undetectable levels. It has however failed to eliminate the virus from other body compartments. Current methods for monitoring persistent viral replication in HIV-1+ patients require a large amount of blood and/or repeated tissue biopsies. Furthermore, some of the viral reservoirs, such as brain and eye, are inaccessible for sampling. The detection of episomal HIV-1 DNA 2-LTR circles in CD4+ cells is indicative of recent, acute infection events. This paper describes a reliable and reproducible LightCycler-based assay for the quantitative measurement of HIV-1 DNA 2-LTR circles in human peripheral blood mononuclear (PBMN) cells. It details the modifications to the DNA extraction procedure and to the LightCycler PCR procedure that were required to achieve this. This new surrogate marker of persistent viral replication can now be reliably, reproducibly and robustly used to study the clinical progress of large numbers of patients whose plasma HIV-1 RNA has been reduced to undetectable levels by anti-retroviral drugs.     

品管圈在优质护理病房降低呼叫器使用频率的应用研究

目的：：探讨品管圈在优质护理病房降低呼叫器使用频率的应用价值。方法：成立品管圈活动小组,分析优质护理病房中呼叫器因治疗原因使用所占的比率,并采取相应措施以降低其比率。结果：优质护理病房中呼叫器因治疗原因用所占的比率从79.66%降低到54.58%(P<0.01)。结论：品管圈方法的应用能有效降低优质护理病房中呼叫器因治疗原因使用的频率,可以加强护士主动巡视病房的意识,增强工作责任感和满足感,发挥其积极性、创造性、主动性,提高护理质量。     

应用品管圈降低老年患者拔针后血肿发生率

目的:探讨应用品管圈降低老年患者拔针后血肿发生率的临床疗效。方法:本研究选择的对象为2014年2月至2014年8月来门诊接受输液治疗的1 246例老年患者,根据对输液患者在拔针过程中所采取的护理方案的不同将其随机分为对照组与观察组,每组患者623例,其中对照组患者在拔针过程中采用常规的管理方法;观察组在拔针过程中采用品管圈的管理方法。观察指标为两组患者拔针后的不良反应发生率。结果:对照组患者拔针后不良反应的发生率为15.57%,观察组患者拔针后的不良反应发生率为6.74%,观察组的不良反应发生率显著低于对照组患者,两组进行比较差异有统计学意义(P<0.05)。结论:相比于常规的管理方法,采用品管圈的管理方法在护理老年患者拔针后可以有效降低血肿的发生率,降低不良反应发生率,值得对品管圈的管理方法进行进一步的深入研究。     

焦点循环管理法在提升门诊处方合理率中的应用

目的 提高门诊处方的合理率,保证病人用药安全。方法 利用焦点循环管理法(FOCUS-PDCA)对湖北医药学院附属东风医院2015年1月(干预前)和6月(干预后)的门诊处方进行回顾性评价,采用FOCUS对存在的问题进行整理分析,制订解决方案,采用PDCA法进行实施。结果 门诊处方不合格率由17.34%(366/2 110)下降到6.68%(115/1 700),与干预前对比,处方合理率明显得到提升(P＜0.05),通过FOCUS-PDCA管理模式,成员的责任心、沟通交流、解决问题的能力都得到了极大的提升。结论 FOCUS-PDCA可以有效的提高门诊处方的合理率,提升药学服务质量。     

Complex decay dynamics of HIV virions,intact and defective proviruses,and 2LTR circles following initiation of antiretroviral therapy

In persons living with HIV-1 (PLWH) who start antiretroviral therapy (ART), plasma virus decays in a biphasic fashion to below the detection limit. The first phase reflects the short half-life (<1 d) of cells that produce most of the plasma virus. The second phase represents the slower turnover (t_1/2 = 14 d) of another infected cell population, whose identity is unclear. Using the intact proviral DNA assay (IPDA) to distinguish intact and defective proviruses, we analyzed viral decay in 17 PLWH initiating ART. Circulating CD4⁺ T cells with intact proviruses include few of the rapidly decaying first-phase cells. Instead, this population initially decays more slowly (t_1/2 = 12.9 d) in a process that largely represents death or exit from the circulation rather than transition to latency. This more protracted decay potentially allows for immune selection. After ∼3 mo, the decay slope changes, and CD4⁺ T cells with intact proviruses decay with a half-life of 19 mo, which is still shorter than that of the latently infected cells that persist on long-term ART. Two-long-terminal repeat (2LTR) circles decay with fast and slow phases paralleling intact proviruses, a finding that precludes their use as a simple marker of ongoing viral replication. Proviruses with defects at the 5′ or 3′ end of the genome show equivalent monophasic decay at rates that vary among individuals. Understanding these complex early decay processes is important for correct use of reservoir assays and may provide insights into properties of surviving cells that can constitute the stable latent reservoir.

For persons living with HIV-1 (PLWH), lifelong adherence to antiretroviral therapy (ART) is critical for maintaining suppression of viral replication and forestalling the development of fatal immunodeficiency. Following initiation of ART, plasma virus levels decay rapidly to below the limit of detection of clinical assays (1–6). Because antiretroviral drugs block new infection of susceptible cells, but not virus production by cells that have an integrated viral genome, this decay must reflect the loss of productively infected cells, cells that were infected prior to the initiation of ART. Productively infected cells could die from viral cytopathic effects, cytolytic host effector mechanisms, or virus-independent T cell turnover. In principle, the decay of plasma virus could also be explained by transition to a nonproductive or latent state of infection. Importantly, the decay is biphasic, indicating the presence of two populations of productively infected cells with different half-lives. Most of the plasma virus is produced by cells that decay very rapidly, with a half-life of less than 1 d. Perelson et al. (4) showed that after most of these cells have decayed, the slope changes, reflecting the slower elimination of a second population of productively infected cells. This population decays with a variable half-life (mean ∼ 2 wk). Although this biphasic decay is a consistent feature of the response to ART, there is still uncertainty about the nature, anatomic location, and fate of the cells responsible for virus production during the first and second phases of decay (referred to here as first- and second-phase cells, respectively). The differences between these two populations have never been elucidated.The first and second phases of decay bring viremia down to below the limit of detection of clinical assays (typically 20 to 50 copies of HIV-1 RNA per mL of plasma) within months of ART initiation, initially raising hope for eradication. However, a latent form of the virus persists in resting memory CD4⁺ T cells (7–14). Initial studies used a quantitative viral outgrowth assay (QVOA) to demonstrate that latently infected resting CD4⁺ T cells purified from PLWH on long-term suppressive ART could be induced to produce replication-competent virus by global T cell activation (8, 9). Longitudinal studies using the QVOA demonstrated that the half-life of the latent reservoir in resting CD4⁺ T cells is 44 mo in PLWH who are adherent to ART. This half-life is long enough to guarantee lifetime persistence of HIV-1 despite ART (12–14). Strategies targeting the latent reservoir in resting CD4⁺ T cells are a major focus of HIV cure research (15–17). In addition to resting CD4⁺ T cells, other cell types may contribute to HIV-1 persistence (18–20).Prior to and immediately following initiation of ART, the frequency of latently infected cells detected by QVOA is substantially higher than frequencies observed in PLWH on long-term ART (21). In principle, several different types of decay processes occurring over the first 6 to 12 mo of treatment could reduce the frequency of latently infected cells to the more stable frequencies observed in PLWH on long-term ART. Early studies by Jerome Zack and Mario Stevenson demonstrated that infected resting CD4⁺ T cells could harbor linear, unintegrated HIV-1 DNA in a state of preintegration latency (22, 23). Following cellular activation, linear unintegrated HIV-1 DNA can be integrated and transcribed, allowing production of virus (22, 23). The half-life of linear, unintegrated forms of the viral genome is not clear, with some studies suggesting that these forms are labile (22, 24–26). Some reverse-transcribed viral genomes can undergo homology-dependent or end-to-end ligation, generating one-long-terminal repeat or two-long-terminal repeat (2LTR) circles, respectively (reviewed in ref. 27). The stability of these forms is also controversial, but they are clearly replication-defective (27–31). Following integration of linear viral cDNA, decay dynamics depend on dynamics of the infected host cells, which can be eliminated by viral cytopathic effects, immune cytolytic effector mechanisms, and normal contraction-phase death of previously activated CD4⁺ T cells (32, 33).While the QVOA provides a definitive minimal estimate of the frequency of latently infected cells, it underestimates reservoir size because not all proviruses in resting CD4⁺ T cells are induced upon one round of maximum T cell activation (34–36). Many replication-competent proviruses require multiple rounds of stimulation for induction. As an alternative to the QVOA, many studies use PCR-based assays to measure proviral DNA. However, the vast majority of HIV-1 proviruses are defective due to apolipoprotein B messenger RNA editing enzyme, catalytic polypeptide-like (APOBEC)-mediated hypermutation or large internal deletions (34, 37–39). PCR-based assays do not distinguish between defective and intact proviruses (40, 41). Although infected cell dynamics have been explored using PCR-based assays (42), the results likely reflect the dynamics of defective proviruses (41). The recently developed intact proviral DNA assay (IPDA) uses two carefully chosen amplicons to probe informative regions of individual proviruses to provide better discrimination between intact and defective proviruses (41, 43). This assay has proven useful in evaluating the long-term dynamics of cells with intact and defective proviruses, demonstrating differences in decay rates that may reflect some vulnerability of cells with intact proviruses to immune effector mechanisms (41, 44, 45).In this study, we use the IPDA to explore the decay of intact and defective proviruses at early time points following initiation of ART. We identify decay processes occurring over intermediate time scales, but with pronounced differences between intact and defective proviruses. Of particular importance is the second-phase decay because infected cells that survive second-phase decay may down-regulate HIV-1 gene expression and enter the stable latent reservoir. Our findings also provide insight into mechanisms for the elimination of the cells with intact viral genomes and into the proper use of assays for the latent reservoir.     

品管圈活动提高阿尔茨海默病患者手指精细功能锻炼的应用效果

目的：探讨品管圈(quality control circle,QCC)活动提高阿尔茨海默病患者手指精细功能锻炼的应用效果。方法：成立QCC活动小组,选定“提高阿尔茨海默病患者手指精细功能锻炼的达标率”为本次活动的主题,拟订活动计划,设定改进目标,运用鱼骨图、流程图等管理工具,找出真因,同时通过真因验证,确定真因,并将真因验证结果进行对策拟定,根据“戴明循环”(plan-do-check action cycle,PDCA)组织实施。结果：QCC活动实施后,阿尔茨海默病患者手指精细功能锻炼的达标率从5.9%提高到61.0%,差异有统计学意义(P<0.001)。结论：QCC活动的开展提高阿尔茨海默病患者手指精细功能锻炼达标率,并且提高了QCC成员多方面的能力。     

品质管理圈活动在减少维持性透析患者急诊透析次数中的应用

目的探讨品质管理圈（品管圈）活动在减少维持性透析患者急诊透析次数中的应用效果。方法2012年12月起血液透析中心8名护理人员和1名医生自愿组成1个品管圈,通过评价选定＂减少维持性透析患者急诊透析次数＂为活动主题。通过问卷调查、访谈、比较研究等方法对维持性透析患者发生急诊透析情况进行分析,制定相关的对策并实施。比较改善前（2013年2月3日-5月3日）与改善后（2013年7月2日-10月2日）急诊透析情况。结果通过品管圈活动,维持性透析患者急诊透析次数由改善前的平均11.7例次/月减少至改善后的5.3例次/月,超出了预期目标。同时圈员在解决问题能力、责任心、沟通协调能力、自信心、积极性以及品管圈手法应用各方面都得到了不同程度的提高。结论品管圈活动不仅可以减少维持性透析患者急诊透析的次数,同时也可提高圈员间的团队凝聚力、和谐度及质量管理能力。