Research on medication use in the neonatal intensive care unit

Introduction: Research on medication use aims at assessing how much of current pharmacotherapy is rational. In neonates, this is hampered by extensive off-label drug use and limited knowledge.

Areas covered: We report on medication use research and have conducted a systematic review of observational studies on medication use to provide an updated overview on characteristics, objectives, methods, and patterns in hospitalized neonates. Moreover, a review on aspects of medication use for opioids, anti-epileptics, gastric acid-related disorders and respiratory stimulants with emphasis on trends and impact of interventions is presented, illustrating how research on medication use can contribute to improved neonatal pharmacotherapy and more focused research. Medication use reports describe patterns and provide signals on irrational use, benchmarking, or can guide research priorities. Moreover, this may generate information on how neonatal health topics and their pharmacotherapy are handled over time or across regions.

Expert opinion: Research on medicine utilization is relevant, since it will inform us on aspects like trends, variability, or about the impact and pattern of implementation of guidelines in neonates. Further progress necessitates to merge datasets on medication use with clinical characteristics, and perinatal drug use remains an area in need of additional research.     

The infantile cutaneous microbiome: A review

Recent focus on the neonatal intestinal microbiome has advanced our knowledge of the complex interplay between the intestinal barrier, the developing immune system, and commensal and pathogenic organisms. Despite the parallel role of the infant skin in serving as both a barrier and an interface for priming the immune system, large gaps exist in our understanding of the infantile cutaneous microbiome. The skin microbiome changes and matures throughout infancy, becoming more diverse and developing the site specificity known to exist in adults. Delivery method initially determines the composition of the cutaneous microbiome, though this impact appears transient. Cutaneous microbes play a critical role in immune system development, particularly during the neonatal period, and microbes and immune cells have closely intertwined, reciprocal effects. The unique structure of newborn skin influences cutaneous microbial colonization and the development of dermatologic pathology. The development of the infantile skin barrier and cutaneous microbiome contributes to future skin pathology. Atopic dermatitis flares and seborrheic dermatitis have been linked to dysbiosis, while erythema toxicum neonatorum is an immune response to the establishment of normal bacterial skin flora. Physicians who care for infants should be aware of the impact of the infantile skin microbiome and its role in the development of pathology. A better understanding of the origin and evolution of the skin microbiome will lead to more effective prevention and treatment of pediatric skin disease.     

N-乙酰-5-羟色胺对视网膜缺血-再灌注损伤大鼠视网膜 Fas、FasL 蛋白表达的影响

目的　探讨N-乙酰-5-羟色胺（N-acetylserotonin，NAS）对视网膜缺血-再灌注损伤（retina ischemia-reperfusion injury，RIRI）大鼠视网膜Fas、FasL蛋白表达的影响。方法　取健康成年Sprague Dawley大鼠54只，将大鼠随机分为正常组（6只）、RIRI组（24只）与NAS组（24只）；采用高眼压法建立大鼠RIRI模型，依据造模后不同时间点将RIRI组与NAS组大鼠又分为6 h、12 h、24 h及72 h四个亚组。NAS组于造模前30 min腹腔注射NAS（5 mg·kg^-1），RIRI组腹腔注射等剂量的生理盐水。通过HE染色在光学显微镜下观察各组大鼠视网膜形态学变化，并记录各组大鼠视网膜厚度及视网膜神经节细胞数，采用免疫组织化学染色法检测NAS对RIRI大鼠视网膜Fas、FasL蛋白表达的影响。结果　HE染色显示，正常组大鼠视网膜各层细胞分界清晰，形态正常，神经细胞排列整齐；RIRI组大鼠再灌注后6 h视网膜各层出现水肿，以神经节细胞层及内核层较显著，神经节细胞数较正常组减少；随后视网膜水肿进一步加重，神经节细胞继续减少；NAS组大鼠在再灌注后6 h、12 h、24 h 视网膜水肿程度较 RIRI组轻，NAS组在再灌注后72 h视网膜厚度较 RIRI组厚，NAS组各时间点神经节细胞数均较 RIRI组多，差异均有统计学意义（均为P＜0.05）。免疫组织化学染色显示，正常组几乎未见 Fas⁺细胞。再灌注后6 h，RIRI组视网膜神经节细胞及内核层开始出现少量 Fas⁺细胞；再灌注后12 h，RIRI组视网膜 Fas⁺细胞表达逐渐增多；再灌注后24 h视网膜Fas⁺细胞数达到高峰，棕色阳性染色细胞分布在视网膜神经节细胞层、内丛状层、内核层及神经纤维层；再灌注后 72 h 视网膜 Fas⁺细胞较再灌注后 24 h 减少。NAS组在再灌注后6 h、12 h、24 h、72 h 视网膜 Fas⁺细胞数均较 RIRI组各时间点减少，再灌注后24 h，Fas⁺细胞数达较高水平，随后下降，差异均有统计学意义（均为P＜0.05）。正常组视网膜可见 FasL 全层低表达。RIRI组再灌注后 6 h，视网膜神经节细胞层和神经纤维层存在少量 FasL⁺细胞；再灌注后12 h FasL蛋白表达逐渐增多；再灌注后24 h FasL⁺细胞数达高峰，可见深棕色的细胞膜及细胞质染色细胞分布在视网膜神经节细胞层、内丛状层、内核层及神经纤维层；再灌注后72 h FasL蛋白的阳性表达逐渐减少。NAS组再灌注后6 h、12 h、24 h、72 h 视网膜FasL⁺细胞数均少于 RIRI组各时间点阳性细胞数，差异均有统计学意义（均为P＜0.05）。结论　NAS可通过抑制RIRI大鼠视网膜细胞Fas、FasL蛋白的表达，减轻缺血再灌注对大鼠视网膜细胞造成的损伤。     

Time-Driven Activity-Based Cost Comparison of Three Imaging Pathways for Suspected Midgut Volvulus in Children

ObjectiveTo use time-driven activity-based costing to compare the costs of pathways for evaluating suspected pediatric midgut volvulus using either fluoroscopic upper gastrointestinal examination (UGI) or focused abdominal ultrasound (US).MethodsProcess maps were created through patient shadowing, medical record review, and frontline staff interviews. Using time-driven activity-based costing methodology, practical capacity cost rates were calculated for personnel, equipment, and facility costs. Supply costs were included at institutional purchase prices. The cost of each process substep was determined by multiplying step-specific capacity costs by the median time required for each step, and substep costs were summed to generate total pathway cost. Multivariate sensitivity analyses were performed applying minimum and maximum labor costs. Assuming UGI would be used to troubleshoot nondiagnostic US, a break-even analysis was performed to determine the cost impact of varying frequencies of UGI on the total cost of the US-based pathway.ResultsProcess maps were created from 105 (48 girls, 57 boys) patient encounters. Base case pathway times were 90 min (UGI) and 55 min (US). Base case cost for UGI was $282.74 (range: $170.86-$800.82) when performed by a radiology practitioner assistant and $545.66 (range: $260.97-$1,974.06) when performed by a radiologist. Base case cost for US was $155.67 (range: $122.94-$432.29) when performed by a sonographer and $242.64 (range: $147.46-$1,330.05) when performed by a radiologist. For a US-based pathway, the total cost break-even pathway mix (percent UGI required for troubleshooting) was 57%.ConclusionUS can be a faster and less costly alternative to UGI in pediatric patients with suspected midgut volvulus.     

新生儿重症监护病房中重症肺炎多种菌感染相关因素分析

目的分析新生儿重症监护病房(NICU)中重症肺炎新生儿多种菌感染危险因素。方法回顾分析2014年1月至2019年5月收入NICU的1 057例重症细菌肺炎新生儿的临床资料,分析其多种菌感染的危险因素。结果单因素分析显示,胎龄(37周)、出生体质量(2 500 g)、发病日龄(7 d)、羊水污染(Ⅱ、Ⅲ度)、感染类型(医院感染)、住院时间(≥14天)、机械通气、Apagar评分(7分)、胎膜早破、抗菌药物使用天数(≥10天)、更换抗菌药物(≥3种)、联合使用抗菌药物(≥3种)12个因素是NICU中重症肺炎新生儿多种菌感染的危险因素,差异有统计学意义(P均0.05)。多因素分析显示,更换抗菌药物(≥3种)、Apagar评分(7分)、感染类型(医院感染)、机械通气、羊水污染(Ⅱ、Ⅲ度)是NICU中重症肺炎新生儿多种菌感染的独立危险因素(P0.05)。结论临床应针对主要危险因素采取综合防控措施,减少NICU新生儿重症肺炎多种菌感染。     

Measurement of xenon diffusing capacity in the rat lung by hyperpolarized 129Xe MRI and dynamic spectroscopy in a single breath-hold.

We used the dual capability of hyperpolarized 129Xe for spectroscopy and imaging to develop new measures of xenon diffusing capacity in the rat lung that (analogously to the diffusing capacity of carbon monoxide or DLCO) are calculated as a product of total lung volume and gas transfer rate constants divided by the pressure gradient. Under conditions of known constant pressure breath-hold, the volume is measured by hyperpolarized 129Xe MRI, and the transfer rate is measured by dynamic spectroscopy. The new quantities (xenon diffusing capacity in lung parenchyma (DLXeLP)), xenon diffusing capacity in RBCs (DLXeRBC), and total lung xenon diffusing capacity (DLXe)) were measured in six normal rats and six rats with lung inflammation induced by instillation of fungal spores of Stachybotrys chartarum. DLXeLP, DLXeRBC, and DLXe were 56 +/- 10 ml/min/mmHg, 64 +/- 35 ml/min/mmHg, and 29 +/- 9 ml/min/mmHg, respectively, for normal rats, and 27 +/- 9 ml/min/mmHg, 42 +/- 27 ml/min/mmHg, and 16 +/- 7 ml/min/mmHg, respectively, for diseased rats. Lung volumes and gas transfer times for LP (TtrLP) were 16 +/- 2 ml and 22 +/- 3 ms, respectively, for normal rats and 12 +/- 2 ml and 35 +/- 8 ms, respectively, for diseased rats. Xenon diffusing capacities may be useful for measuring changes in gas exchange associated with inflammation and other lung diseases.     

脑心通对脑缺血再灌注损伤细胞外信号调节激酶活化的影响

目的:观察大鼠局灶性脑缺血/再灌注((ischemia/reperfusion,I/R)后信号转导介质细胞外信号调节激酶(extracellular signal-regulated kinase,ERK)的活化情况以及脑心通对其影响。方法:雄性成年Wistar大鼠90只,随机分成3组:假手术组、对照组和脑心通组(每组30只),分别于缺血前6日每日用生理盐水4mL、生理盐水4mL和脑心通0.48g/kg(脑心通用4mL生理盐水溶解)灌胃。采用线栓法致大脑中动脉栓塞(middle cerebral artery occlusion,MCAO)模型,在脑缺血再灌注后的3h、6h、24h、48h和72h分别处死大鼠(各组每个时间点6只),将脑组织进行免疫组织化学、TTC染色,TUNEL法观察细胞凋亡。结果:脑缺血诱导ERK活化,第6h达高峰,并持续到72h。脑心通组ERKs活化明显较对照组增强,而且各时间点ERK免疫反应阳性细胞数脑心通组显著较对照组增多(P<0.01)。脑心通组TTC染色梗死体积及凋亡细胞数较对照组明显较少(P<0.01)。结论:局灶性脑缺血再灌注可诱导缺血脑细胞部分ERK活化,脑心通干预可使缺血大脑海马ERK活化增强,减轻细胞的缺血性损伤。