Utility of the 3‐Vessel and 3‐Vessel and Trachea Views in Prenatal Diagnosis of a Pulmonary Artery Sling

A pulmonary artery (PA) sling is a very rare congenital cardiovascular anomaly, and only a few studies have reported PA slings in fetuses. The relationship of the PA, aorta, ductus arteriosus, and trachea can be evaluated in the 3‐vessel and 3‐vessel and trachea views during fetal echocardiography. A PA sling can be detected by abnormal positioning of the left PA in relation to the trachea when sweeping from the 3‐vessel view cranially to the 3‐vessel and trachea view. Here we report 3 cases of fetal PA slings and their follow‐ups. Two cases were confirmed by postnatal echocardiography, and the other case was confirmed by a cardiovascular cast after pregnancy termination. We emphasize that the 3‐vessel and 3‐vessel and trachea views are of crucial importance in the prenatal diagnosis of a PA sling.     

Midazolam exposure in the paediatric intensive care unit predicts acute post-traumatic stress symptoms in children

BackgroundClinically significant post-traumatic stress symptoms (PTSS) have been reported in up to a quarter of paediatric intensive care unit (PICU) survivors. Ongoing PTSS negatively impacts children's psychological development and physical recovery. However, few data regarding associations between potentially modifiable PICU treatment factors, such as analgosedatives and invasive procedures, and children's PTSS have been reported.ObjectivesWe sought to investigate the medical treatment factors associated with children's PTSS after PICU discharge.MethodsA prospective longitudinal cohort study was conducted in two Australian tertiary referral PICUs. Children aged 2-16 y admitted to the PICU between June 2008 and January 2011 for >8 h and <28 d were eligible for participation. Biometric and clinical data were obtained from medical records. Parents reported their child's PTSS using the Trauma Symptom Checklist for Young Children at 1, 3, 6, and 12 months after discharge. Logistic regression was used to assess potential associations between medical treatment and PTSS.ResultsA total of 265 children and their parents participated in the study. In the 12-month period following PICU discharge, 24% of children exhibited clinically elevated PTSS. Median risk of death (Paediatric Index of Mortality 2 [PIM2]) score was significantly higher in the PTSS group (0.31 [IQR 0.14–1.09] v 0.67 [IQR 0.20–1.18]; p = 0.014). Intubation and PICU and hospital length of stay were also significantly associated with PTSS at 1 month, as were midazolam, propofol, and morphine. After controlling for gender, reason for admission, and PIM2 score, only midazolam was significantly and independently associated with PTSS and only at 1 month (adjusted odds ration (aOR) 3.63, 95% CI 1.18, 11.12, p = 0.024). No significant relationship was observed between the use of medications and PTSS after 1 month.ConclusionsElevated PTSS were evident in one quarter (24%) of children during the 12 months after PICU discharge. One month after discharge, elevated PTSS were most likely to occur in children who had received midazolam therapy.     

Evaluation of Eye Movement Desensitization and Reprocessing in the management of tinnitus. An observational study

ObjectivesTinnitus can induce disabling psychological suffering, requiring an integrative multimodal approach, combining neuromodulation and psychotherapeutic methods. We sought to evaluate the therapeutic efficacy and acceptability of Eye Movement Desensitization and Reprocessing (EMDR) in tinnitus.Materials and methodsThis was a single-center prospective non-comparative study. Inclusion criteria comprised: adult patient, with chronic tinnitus, Tinnitus Handicap Inventory (THI) score > 17, causing psychological distress motivating active treatment after ineffective “classic” treatment (combining advice, sound therapy and first-line drug treatment), and agreement to EMDR therapy. Therapeutic efficacy was defined by a decrease in THI or Visual Analog Scale (VAS) scores. Treatment acceptability was defined by the rate of included patients who completed therapy.ResultsThirty-eight patients were included. There was a significant reduction of 53.5% in THI score in 78.9% of patients (P < 0.0001; 64.8 ± 20.8 before versus 31.8 ± 24.7 after treatment), and of 51% in VAS score in 76.3% of patients (P < 0.0001; 7.24 ± 2.12 before versus 3.58 ± 2.03 after treatment). The treatment acceptability was 86.8%.ConclusionEMDR appeared to be an effective alternative that was acceptable to the majority of patients, after failure of “classic” first-line treatment, improving quality of life in tinnitus patients and thus relieving disability.     

Differences in Evidentiary Requirements Between European Medicines Agency and European Health Technology Assessment of Oncology Drugs—Can Alignment Be Enhanced?

ObjectivesNational health technology assessments (HTAs) across Europe show differences in evidentiary requirements from assessments by the European Medicines Agency (EMA), affecting time to patient access for drugs after marketing authorization. This article analyzes the differences between EMA and HTA bodies’ evidentiary requirements for oncology drugs and provides recommendations on potential further alignment to minimize and optimally manage the remaining differences.MethodsInterviews were performed with representatives and drug assessment experts from EMA and HTA bodies to identify evidentiary requirements for several subdomains and collect recommendations for potentially more efficiently addressing differences. A comparative analysis of acceptability of the evidence by EMA and the HTA bodies and for potential further alignment between both authorities was conducted.ResultsAcceptability of available evidence was higher for EMA than HTA bodies. HTA bodies and EMA were aligned on evidentiary requirements in most cases. The subdomains showing notable differences concerned the acceptance of limitation of the target population and extrapolation of target populations, progression-free survival and (other) surrogate endpoints as outcomes, cross-over designs, short trial duration, and clinical relevance of the effect size. Recommendations for reducing or optimally managing differences included joint early dialogues, joint relative effectiveness assessments, and the use of managed entry agreements.ConclusionsDifferences between assessments of EMA and HTA bodies were identified in important areas of evidentiary requirements. Increased alignment between EMA and HTA bodies is suggested and recommendations for realization are discussed.     

Trade-offs between acquired and innate immune defenses in humans

Immune defenses provide resistance against infectious disease that is critical to survival. But immune defenses are costly, and limited resources allocated to immunity are not available for other physiological or developmental processes. We propose a framework for explaining variation in patterns of investment in two important subsystems of anti-pathogen defense: innate (non-specific) and acquired (specific) immunity. The developmental costs of acquired immunity are high, but the costs of maintenance and activation are relatively low. Innate immunity imposes lower upfront developmental costs, but higher operating costs. Innate defenses are mobilized quickly and are effective against novel pathogens. Acquired responses are less effective against novel exposures, but more effective against secondary exposures due to immunological memory. Based on their distinct profiles of costs and effectiveness, we propose that the balance of investment in innate versus acquired immunity is variable, and that this balance is optimized in response to local ecological conditions early in development. Nutritional abundance, high pathogen exposure and low signals of extrinsic mortality risk during sensitive periods of immune development should all favor relatively higher levels of investment in acquired immunity. Undernutrition, low pathogen exposure, and high mortality risk should favor innate immune defenses. The hypothesis provides a framework for organizing prior empirical research on the impact of developmental environments on innate and acquired immunity, and suggests promising directions for future research in human ecological immunology.     

亚慢性硝酸钇暴露对雌性大鼠学习记忆能力的影响

目的：观察稀土化合物硝酸钇[Y（NO₃）₃]亚慢性（90 d）暴露对大鼠学习记忆能力的影响，并探究其可能的机制，为全面评估稀土元素钇的健康风险提供科学依据。方法：选用刚离乳（PND21）SD雌性大鼠，根据质量随机分为4组，分别为对照组（ddH₂O），Y（NO₃）₃低剂量组[10 mg/（kg·d）]、中剂量组[40 mg/（kg·d）]和高剂量组[160 mg/（kg·d）]，每组15只。连续灌胃受试物90 d后进行旷场实验、高架十字迷宫实验、转棒实验、Morris水迷宫实验。水迷宫检测后，每组取5只雌鼠心脏原位灌注，进行脑组织病理学检查。每组剩余10只雌鼠摘取脑组织，紫外分光光度计检测雌鼠大脑皮质和海马中谷氨酸（Glu）的含量；Western blot检测海马组织中N-甲基-D-天冬氨酸（NMDA）受体蛋白表达情况。结果：与对照组相比，硝酸钇90 d暴露后，转棒实验中160 mg/（kg·d）剂量组大鼠在棒时间、在棒圈数、掉落速度明显升高（P<0.05）。在Morris水迷宫定位航向实验第4天时，40、160 mg/（kg·d）剂量组大鼠逃避潜伏期明显降低（P<0.05）；Morris水迷宫空间探索实验中，40 mg/（kg·d）剂量组大鼠穿越平台次数、目标象限游泳时间明显增加（P<0.05）；160 mg/（kg·d）剂量组穿越平台次数、进入目标象限次数、目标象限游泳时间明显增加（P<0.05）；160 mg/（kg·d）剂量组大鼠东北、东南、西南象限的逃避潜伏期明显低于西北象限的逃避潜伏期（P<0.05）。160 mg/（kg·d）剂量组大鼠海马中Glu含量和NMDA受体NR1含量均明显低于对照组（P<0.05）。40和160 mg/（kg·d）剂量组大鼠海马中NMDA受体NR2A含量明显低于对照组（P<0.05）。结论：硝酸钇亚慢性（90 d）暴露可以引起雌性大鼠空间学习记忆能力增强；硝酸钇可能通过降低海马组织神经元细胞外Glu含量，抑制NMDA受体激活，增强雌性大鼠的空间学习记忆能力。     

美托洛尔用于老年COPD合并冠心病史治疗的临床疗效观察

目的:探讨美托洛尔(β1受体阻滞剂)用于老年COPD合并冠心病史治疗的临床疗效。方法:选取2018年6月—2019年6月在我院接受治疗的60岁以上(包括60岁)COPD合并冠心病史老年患者,分为对照组与观察组。对照组给予接受布地奈德福莫特罗粉吸入剂治疗,观察组在使用布地奈德福莫特罗粉吸入剂治疗的基础上口服琥珀酸美托洛尔缓释片治疗,观察对比两组治疗效果。结果:观察组临床治疗效果优于对照组,观察组住院时长以及并发症的发生率低于对照组(P<0.05),差异具有统计学意义。结论:老年COPD合并冠心病史接受美托洛尔治疗,可有效缩短住院时长、用药效果明显、有效提升用药安全性,值得临床推广。     

Implementation strategies for the first licensed dengue vaccine: A meeting report

Dengue vaccination would enhance the control of dengue, one of the most frequent vector-borne viral diseases globally. CYD-TDV is the first dengue vaccine to be licensed, but global uptake has been hampered due to its use being limited to seropositive persons aged 9 years and above, and the need for a 3-dose schedule. The Partnership for Dengue Control (PDC) organized a meeting with key opinion leaders and stakeholders to deliberate on implementation strategies for the use of CYD-TDV. New data have emerged that support the shortening of the primary schedule from a 3 to 2 dose schedule, extending the age range below 9 to 6 years of age, and expanding the indication from endemic populations to also include travelers to endemic areas. Cost-effectiveness may improve with the modified 2-dose regimen and with multiple testing. Strategies to implement a dengue vaccination program have been developed, in particular school-based strategies. A range of delivery scenarios can then be considered, using various settings for each step of the intervention. However, several challenges remain, including communication about limiting the use of this vaccine to seropositive individuals only. Affordability will vary from country to country, as will government commitment and community acceptance. Well-tailored communication strategies that target key stakeholders are expected to make up a significant part of any future dengue vaccination program.