A randomized controlled trial of a physiology-guided percutaneous coronary intervention optimization strategy: Rationale and design of the TARGET FFR study

Post-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) ≥0.90 confers an improved cardiac prognosis. There are currently limited data available to determine how often it is possible to improve an angiographically acceptable but physiologically suboptimal result. A physiology-guided optimization strategy can achieve a clinically meaningful increase in the proportion of patients achieving a final post-PCI FFR ≥0.90 compared to standard care. Following angiographically successful PCI procedures, 260 patients will be randomized (1:1) to receive either a physiology-guided incremental optimization strategy (intervention group) or blinded post-PCI coronary physiology measurements (control group). Patients undergoing successful, standard-of-care PCI for either stable angina or non-ST-segment-elevation myocardial infarction who meet the study's inclusion and exclusion criteria will be eligible for randomization. The primary endpoint is defined as the proportion of patients with a final post-PCI FFR result ≥0.90. Secondary endpoints include change from baseline in Seattle Angina Questionnaire and EQ-5D-5L scores at 3 months and the rate of target vessel failure and its components (cardiac death, myocardial infarction, stent thrombosis, unplanned rehospitalization with target vessel revascularization) at 3 months and 1 year. 260 individual patients were successfully randomized between March 2018 and November 2019. Key baseline demographics of the study population are reported within. TARGET FFR is an investigator-initiated, prospective, single-center, randomized controlled trial of an FFR-guided PCI optimization strategy. The study has completed recruitment and is now in clinical follow-up. It is anticipated that primary results will be presented in Autumn 2020. ClinicalTrials.gov Identifier: NCT03259815. [Correction added on Apr 3 2020, after first online publication: Clinical Trials identifier added.]     

Effects of behavioural interventions on postpartum retention and adherence among women with HIV on lifelong ART: the results of a cluster randomized trial in Kenya (the MOTIVATE trial)

Introduction Retention in HIV care and adherence to antiretroviral therapy (ART) during pregnancy and postpartum for women living with HIV (WLWH) are necessary to optimize health outcomes for women and infants. The objective of this study was to evaluate the impact of two evidenced‐based behavioural interventions on postpartum adherence and retention in WLWH in Kenya.MethodsThe Mother‐Infant Visit Adherence and Treatment Engagement (MOTIVATE) study was a cluster‐randomized trial enrolling pregnant WLWH from December 2015 to August 2017. Twenty‐four health facilities in southwestern Kenya were randomized to: (1) standard care (control), (2) text‐messaging, (3) community‐based mentor mothers (cMM) or (4) text‐messaging and cMM. Primary outcomes included retention in care and ART adherence at 12 months postpartum. Analyses utilized generalized estimating equations and competing risks regression. Per‐protocol analyses examined differences in postpartum retention for women with high versus low levels of exposure to the interventions.Results We enrolled 1331 pregnant WLWH (mean age 28 years). At 12 months postpartum, 1140 (85.6%) women were retained in care, 96 women (7.2%) were lost‐to‐follow‐up (LTFU) and 95 (7.1%) were discontinued from the study. In intention‐to‐treat analyses, the relative risk of being retained at 12‐months postpartum was not significantly higher in the intervention arms versus the control arm. In time‐to‐event analysis, the cMM and text arm had significantly lower rates of LTFU (hazard ratio 0.44, p = 0.019). In per‐protocol analysis, the relative risk of 12‐month postpartum retention was 24–29% higher for women receiving at least 80% of the expected intervention compared to the control arm; text message only risk ratio (RR) 1.24 (95% confidence interval [CI] 1.16–1.32, p<0.001), cMM only RR 1.29 (95% CI 1.21–1.37, p<0.001) and cMM plus text RR 1.29 (1.21–1.37, p<0.001). Women LTFU were younger (p<0.001), less likely to be married (p<0.001) and more likely to be newly diagnosed with HIV during pregnancy (p<0.001). Self‐reported ART adherence did not vary by study arm.ConclusionsBehavioural interventions using peer support and text messages did not appear to improve 12‐month postpartum retention and adherence in intention‐to‐treat analyses. Higher levels of exposure to the interventions may be necessary to achieve the desired effects.     

清开灵与利巴韦林治疗小儿呼吸道合胞病毒肺炎的比较：单盲、随机、平行对照试验

目的:比较清开灵与利巴韦林对呼吸道合胞病毒肺炎患儿治疗效果的差异。方法:选择2005-02/2006-04在北京儿童医院分中心治疗的小儿呼吸道合胞病毒肺炎97例,患儿法定监护人知情同意。采用单盲、随机、平行对照试验的原则,按区组随机化方法分为2组,清开灵注射液组49例,利巴韦林组48例。①清开灵注射液组:清开灵注射液静脉滴注加口服中成药。②利巴韦林组:利巴韦林注射液静脉滴注加口服复方愈创木酚磺酸钾口服液。两组疗程均为10d,比较两组患儿的疗效。结果:清开灵注射液组脱落3例,利巴韦林组脱落1例,进入结果分析清开灵注射液组46例,利巴韦林组47例。①清开灵注射液组发热患儿体温恢复正常时间比利巴韦林组短[(2.72±1.86)d,(6.29±2.41)d(P<0.01)]。②清开灵注射液组患儿咳嗽、痰壅、气促症状积分改善方面优于利巴韦林组(P<0.05～0.01)。③清开灵注射液组的呼吸道合胞病毒转阴时间明显优于利巴韦林组。④咳嗽、痰壅、病毒转阴时间、气促均进入Logistic模型,其中前两个症状的回归系数绝对值较大。结论:清开灵注射液治疗小儿呼吸道合胞病毒肺炎在退热、止咳平喘、呼吸道合胞病毒转阴时间等方面均具有明显优势,咳嗽、痰壅这两个症状更能反映清开灵注射液的疗效优于利巴韦林。     

国内六大行政区域六城市中老年人群膝关节骨性关节炎患病危险因素比较

目的：了解中国不同地区间中老年人群膝关节骨性关节炎患病危险因素。方法：调查时间为2005—07／08。①从中国六大行政区（西北，华北，华东。中南，东北，西南）选出六城市（西安，石家庄，上海。广州，哈尔滨市，成都），用分层多阶段整群抽样方法，抽取6218名40岁及以上具有正式户口常住男女人群进行膝关节骨性关节炎的流行病学问卷调查（包括一般情况、现病史、既往史、体格检查、X射线片检查情况和疾病诊断6个方面，共计94个问题141个变量指标），并对其中4808名有症状者进行X射线平片膝正侧位投照。②膝关节骨性关节炎诊断标准为临床症状阳性加X射线Kellgren ＆ Lawrence分级二级及以上者。③计算患病率，并采用Epilnf06．0和SPSS 10．0软件对其中83个变量进行多因素非条件Logistfc回归分析，表示疾病与暴露因素之间联系强度的指标用比值比（OR），若OR〉1，说明疾病发生危险性增加，与暴露因素呈正关联；若OR〈1，说明疾病发生危险性减少，与暴露因素呈负关联。 结果：①六城市膝关节骨性关节炎总患病率为15．6％，其中西安7．7％，石家庄11．2％，上海9．8％。广州30．5％，哈尔滨16．9％，成都17．5％，各城市患病率比较差异显著（P〈0．01）。②Logistic回归分析膝关节骨性关节炎在大部分城市有共同的危险因素如年龄大（OR=1．032—1．181），使用蹲坑排便年限长（OR=1．021-1．077），体质量高（OR=1．048—1．073），和开始饮酒年龄大（OR=1．008～1．028）；而从事专职体育运动（OR=1．651，西安），骨质疏松病史（OR=3．311，石家庄），吸烟（OR=2．654，石家庄），类风湿关节炎病史（OR=4．964，上海），文化程度高（OR=2．593，上海），女性（OR=2．510，广州），姐妹骨关节炎史（OR=13．251，哈尔滨），母亲骨关节炎史（OR=5．683，成都）等危险因素分别在不同地区出现． 结论：年龄大、使用蹲坑排便年限长、体质量高和开始饮酒年龄大是中国六地区膝关节骨性关节炎患病的共同危险因素，同时，不同地区主要危险因素又有一定差异。     

自体骨髓单个核细胞经介入途径移植治疗股骨头坏死54例：12个月疗效随访

目的:观察经介入途径移植自体骨髓单个核细胞在股骨头坏死治疗中的应用,并评价其疗效。方法:选择2004-07/2005-11在解放军四六三院细胞治疗中心住院的,具有完整随访资料的股骨头坏死确诊患者共54例91髋。纳入确诊股骨头坏死,有关节疼痛、功能障碍等症状患者,性别、年龄不限;排除有严重心力衰竭、严重肾功能异常等不能耐受手术者。符合纳入标准54例,男45例,女9例,12～68岁。按ARCO分期Ⅱ期42髋,Ⅲ期47髋,Ⅳ期2髋。实验对象对治疗的相关内容知情同意并签知情同意。干预措施:抽取患者髂后上嵴骨髓进行单个核细胞悬液的制备。在DSA监视下将采集的单个核细胞混悬液经股动脉行Seldinger法穿刺,穿刺成功后,置入4F动脉鞘,经动脉鞘置入Cobra导管,将导管超选择至闭孔动脉及旋股内外侧动脉,平均注入单个核细胞悬液。术后定期随访症状变化情况,1年后复查X射线或CT,随访疼痛、关节活动度等情况。实验评估:①疼痛指数:无疼痛症状为3分,Harris髋关节评分疼痛分级A级;时有隐痛2分,Harris髋关节评分疼痛B级;轻度疼痛为1分,Harris髋关节评分疼痛C级;中度疼痛为0分,Harris髋关节评分疼痛D级。②功能指数:髋关节屈、伸、展、收、旋转度评分达Harris髋关节活动范围评分4～5分为3分;3～4分为2分;2～3分为1分;小于2分为0分。③X射线平片指数:股骨头形态无变化,应力骨小梁清晰,坏死区明显缩小为3分;坏死区略缩小为2分;治疗前后无明显变化为1分;坏死区扩大为0分。④血管指数:治疗后旋股内、外侧动脉及其分支增粗、增多,延长1cm以上者3分;1～0.5cm者2分;小于0.5cm者1分,无变化者0分。结果:54例患者均完成疼痛症状、关节功能及影像学随访1年。①术后12个月复查疼痛消失9髋,缓解61髋,无缓解21髋,缓解率为76.9%。②关节功能缓解33髋,无缓解58髋,缓解率为36.3%。③1年后X射线平片或CT、MRI示股骨头区可见不同程度的股骨头坏死区骨质密度改变,坏死区有吸收、缩小,股骨头形态变圆滑规整,改善28髋,无缓解或加重63髋,缓解率为30.1%。④12例24髋完成术后12个月复查股骨头供血动脉数字减影血管造影,好转18髋,好转率为72.2%。结论:经介入途径移植自体骨髓单个核细胞治疗股骨头坏死损伤小,可缓解临床相关症状。     

Results from a randomized trial of a web-based,tailored decision aid for women at high risk for breast cancer

Objective

To assess the impact of Guide to Decide (GtD), a web-based, personally-tailored decision aid designed to inform women's decisions about prophylactic tamoxifen and raloxifene use.

Methods

Postmenopausal women, age 46–74, with BCRAT 5-year risk ≥1.66% and no prior history of breast cancer were randomized to one of three study arms:intervention (n = 690), Time 1 control (n = 160), or 3-month control (n = 162). Intervention participants viewed GtD prior to completing a post-test and 3 month follow-up assessment. Controls did not. We assessed the impact of GtD on women's decisional conflict levels and treatment decision behavior at post-test and at 3 months, respectively.

Results

Intervention participants had significantly lower decisional conflict levels at post-test (p < 0.001) and significantly higher odds of making a decision about whether or not to take prophylactic tamoxifen or raloxifene at 3-month follow-up (p < 0.001) compared to control participants.

Conclusion

GtD lowered decisional conflict and helped women at high risk of breast cancer decide whether to take prophylactic tamoxifen or raloxifene to reduce their cancer risk.

Practice implications

Web-based, tailored decision aids should be used more routinely to facilitate informed medical decisions, reduce patients’ decisional conflict, and empower patients to choose the treatment strategy that best reflects their own values.     

Mapping Canadian Data Assets to Generate Real-World Evidence: Lessons Learned from Canadian Real-World Evidence for Value of Cancer Drugs (CanREValue) Collaboration’s RWE Data Working Group

Canadian provinces routinely collect patient-level data for administrative purposes. These real-world data (RWD) can be used to generate real-world evidence (RWE) to inform clinical care and healthcare policy. The CanREValue Collaboration is developing a framework for the use of RWE in cancer drug funding decisions. A Data Working Group (WG) was established to identify data assets across Canada for generating RWE of oncology drugs. The mapping exercise was conducted using an iterative scan with informant surveys and teleconference. Data experts from ten provinces convened for a total of three teleconferences and two in-person meetings from March 2018 to September 2019. Following each meeting, surveys were developed and shared with the data experts which focused on identifying databases and data elements, as well as a feasibility assessment of conducting RWE studies using existing data elements and resources. Survey responses were compiled into an interim data report, which was used for public stakeholder consultation. The feedback from the public consultation was used to update the interim data report. We found that databases required to conduct real-world studies are often held by multiple different data custodians. Ninety-seven databases were identified across Canada. Provinces held on average 9 distinct databases (range: 8–11). An Essential RWD Table was compiled that contains data elements that are necessary, at a minimal, to conduct an RWE study. An Expanded RWD Table that contains a more comprehensive list of potentially relevant data elements was also compiled and the availabilities of these data elements were mapped. While most provinces have data on patient demographics (e.g., age, sex) and cancer-related variables (e.g., morphology, topography), the availability and linkability of data on cancer treatment, clinical characteristics (e.g., morphology and topography), and drug costs vary among provinces. Based on current resources, data availability, and access processes, data experts in most provinces noted that more than 12 months would be required to complete an RWE study. The CanREValue Collaboration’s Data WG identified key data holdings, access considerations, as well as gaps in oncology treatment-specific data. This data catalogue can be used to facilitate future oncology-specific RWE analyses across Canada.