Did pediatric drug development advance epilepsy treatment in young patients?It is time for new research goals

Modern drugs have changed epilepsy,which affects people of all ages.However,for young people with epilepsy,the framework of drug development has stalled.In the wake of the thalidomide catastrophe,the misconception emerged that for people<18 years of age drugs,including antiseizure medications(ASMs),need separate proof of efficacy and safety,overall called"pediatric drug development".For ASMs,this has changed to some degree.Authorities now accept that ASMs are effective in<18 years as well,but they still require"extrapolation of efficacy,"as if minors were another species.As a result,some of the pediatric clinical epilepsy research over the past decades was unnecessary.Even more importantly,this has hampered research on meaningful research goals.We do not need to confirm that ASMs work before as they do after the 18th birthday.Instead,we need to learn how to prevent brain damage in young patients by preventing seizures and optimize ASMs’uses.Herein we discuss how to proceed in this endeavor.

Nested case-control study of multiple serological indexes and Brighton pediatric early warming score in predicting death of children with sepsis

BACKGROUND Currently, it is difficult to predict the complications of children at the early stage of sepsis. Brighton pediatric early warning score(PEWS) is a disease risk assessment system that is simple and easy to operate, which has good sensitivity and specificity in disease recognition among children. Because detection indicators vary widely in children, a single indicator is difficult to assess the posttreatment status of children with sepsis.AIM To investigate the relationship between serological markers, Brighton PEWS, and death in children with sepsis after treatment.METHODS A total of 205 children diagnosed with sepsis at our hospital were enrolled. The baseline data, serum scores, and PEWS scores were recorded. In the nested casecontrol study, children who died during the study period were included in an observation group. According to the matching principle, the children who were not dead in the same cohort were included in a control group. The influencing factors of death in children with sepsis after treatment and the value of each evaluation index in predicting the prognosis of children were analyzed.RESULTS A total of 96 children were enrolled in the study, including 48 each in the observation group and the control group. Multivariate logistic regression analysis indicated that antibacterial treatments within 1 h(P = 0.017), shock(P = 0.044),multiple organ dysfunction syndrome(MODS)(P = 0.027), serum procalcitonin(PCT)(P = 0.047), serum albumin(ALB)(P = 0.024), and PEWS(P = 0.012) were independent risk factors for the death of children with sepsis. The area under the curve of the combination of ALB, PCT, and PEWS to predict the death in children with sepsis was the highest(0.908).CONCLUSION Antibacterial treatments within 1 h, shock, MODS, PCT, ALB, and PEWS are independent risk factors for the death of children with sepsis. The predictive accuracy of the combination of PCT, ALB, and PEWS for the prognosis of children with sepsis is the best.

Changes in choroidal thickness in healthy pediatric individuals: a longitudinal study

AIM： To investigate the changes in the choroidal thickness in healthy pediatric children in a longitudinal study, and to determine the ocular and systemic parameters that were significantly correlated with the changes in the choroidal thickness. METHODS： This study included 64 eyes of 34 healthy Japanese children with a mean age（±SD） of 4.4（±0.4）y（range, 3.6-5.8 y） at baseline. Swept-source optical coherence tomography（SS-OCT） was used to record images of the retina and choroid at the baseline and after a mean followup period of about 1.5 y. The 3 D raster scan protocol was used to construct the choroidal thickness map. Mean choroidal thickness was calculated for each of the nine sectors of the Early Treatment Diabetic Retinopathy Study grid. Best-corrected visual acuity, axial length, body height, and weight were also measured. Changes in measurements were defined as the baseline values subtracted from the values at the final visit. A generalized estimating equation was used to eliminate the effect of within-subject intereye correlations. RESULTS： The mean central choroidal thickness was significantly reduced during the follow-up period（baseline, 301.8±8.6 μm; final visit, 286.6±8.0 μm, P〈0.001）. The decrease in the choroidal thickness was greatest in the central sector, followed by the sectors of the inner and outer rings. The inner and outer rings had diameters of 1 to 3 mm and 3 to 6 mm, respectively. The changes in the choroidal thickness in the central, inner ring, and outer ring sectors were significantly and negatively correlated with the age, baseline body height, baseline body weight, and elongation of the axial length. CONCLUSION： These results indicate that the choroidal thickness among preschool-aged Japanese children decreased significantly during the follow-up period. The choroidal thinning is significantly associated with the elongation of axial length. These characteristics should be considered in the evaluation of choroidal thickness in younger children with retinochoroidal disorders.

Ultrastructure of oval cells in children with chronic hepatitis B,with special emphasis on the stage of liver fibrosis:The first pediatric study

AIM:To investigate the ultrastructure of oval cells in children with chronic hepatitis B,with special emphasis on their location in areas of collagen fibroplasia. METHODS:Morphological investigations were conducted on biopsy material obtained from 40 children,aged 3-16 years with chronic hepatitis B. The stage of fibrosis was assessed histologically using the arbitrary semiquantitative numerical scoring system proposed by Ishak et al. The material for ultrastructural investigation was fixed in glutaraldehyde and paraformaldehyde and processed for transmission-electron microscopic analysis. RESULTS:Ultrastructural examination of biopsy specimens obtained from children with chronic hepatitis B showed the presence of two types of oval cells,the hepatic progenitor cells and intermediate hepatic-like cells. These cells were present in the parenchyma and were seen most commonly in areas of intense periportal fibrosis (at least stage 2 according to Ishak et al) and in the vicinity of the limiting plate of the lobule. The activated nonparenchymal hepatic cells,i.e. transformed hepatic stellate cells and Kupffer cells were seen in close proximity to the intermediate hepatic-like cells. CONCLUSION:We found a distinct relationship between the prevalence of oval cells (hepatic progenitor cells and intermediate hepatocyte-like cells) and fibrosis stage in pediatric patients with chronic hepatitis B.

Validation of Peek Acuity application in pediatric screening programs in Paraguay

AIM： To validate the Peek Acuity mobile phone application in pediatric populations and compare its utility, both economic and diagnostic, against conventional screening methods using a pediatric ophthalmologist examination as the gold standard.METHODS： A cohort of 393 subjects from Fernando de la Mora, Paraguay（ages 6-16 y） were enrolled in the study. Subjects were randomly assigned a starting screening modality among： Peek Acuity, a single line of tumbling E optotypes set at 20/40, and Spot Vision Screener. Once completing the first screening modality, the subjects completed the two remaining techniques. Referral criteria were established based on the most current American Association of Pediatric Ophthalmology and Strabismus（AAPOS） recommendations： 20/40 for Peek Acuity and the tumbling E, and refractive error detection for the Spot Vision Screener. Subjects that failed to achieve the cutoff for any of the three screening techniques or subjects that passed the screening but were randomly selected to perform a comprehensive eye exam to determine the false negative rate, were evaluated by a pediatric ophthalmologist. This evaluation was considered the gold standard, and included vision assessment by a Snellen chart, strabismus evaluation, and cycloplegic refraction with dilated fundoscopy.RESULTS： We obtained 48% sensitivity, 83% specificity, 43% positive predictive value, and 86% negative predictive value for Peek Acuity＇s ability to refer compared to evaluation by a pediatric ophthalmologist, failing to achieve a desired sensitivity for implementation. Peek Acuity trended to overestimate the subject＇s visual acuity, providing a higher visual acuity that would not indicate referral for a comprehensive eye examination. However, its high specificity accurately predicted a significant number of children who did not need further evaluation. When comparing the three screening methods, no single screening modality outperformed the others. Peek Acuity represented a technology that was economically feasible compared to other screening modalities in low income settings, due to the prevalence of cell phone use.CONCLUSION： Peek Acuity represents an efficient tool that has potential for implementation in school screenings with different strategies aimed at pediatric populations due to its low cost and high specificity. An increase in sensitivity would improve detection of children with refractive errors.

Risk factors and antibiotic resistance of pneumonia caused by multidrug resistant Acinetobacter baumannii in pediatric intensive care unit

BACKGROUND:With beta-lactam drugs and immunosuppressants widely used,the infection caused by Acinetobacter baumannii(Ab) has become more and more serious with multidrug resistant Acinetobacter baumannii(MDRAb) emerging and worsening rapidly.Compared with other patients,the incidence and multidrug resistance of MDRAb are higher in children in pediatric intensive care unit(PICU) because of immune deficiency,severe basic diseases,prolonged hospitalization and invasive operations.Hence it is significant to study the epidemiology and changes of antibacterial susceptibility in order to reduce the incidence of MDRAb in children.METHODS:A total 115 patients with MDRAb pneumonia and 45 patients with negative MDRAb(NMDRAb) pneumonia who had been treated from January 2009 to August 2011 were studied retrospectively at the PICU of Wuhan Children's Hospital.Clinical data were analyzed with univariate and multivariate Logistic regression.RESULTS:In 176 clinical strains of Acinetobacter baumannii isolated,there were 128 strains of MDRAb,accounting for 72.73%.Drug susceptibility tests showed that the resistance rates of β-lactam antibiotics were more than 70%except for cefoperazone sulbactam.The rates to carbapenems were higher than 90%.They were significantly higher than those of NMDRAb.Amikacin,levofloxacin,ciprofloxacin and minocycline had the lowest drug-resistance rates(<20%).Multivariate Logistic regression revealed that ICU stay,the time of mechanical ventilation,anemia,hypoproteinemia and the use of carbapenems were independent risk factors for MDRAb pneumonia.CONCLUSIONS:MDRAb is an important opportunistic pathogen to pneumonia in PICU,and its drug-resistance is severe.It increases significantly the mortality of patients.It is important to take the effective prevention measures for controlling it.

THE APPLICATION OF GIS IN URBAN PLANNING:ENVIRONMENTAL ZONING STUDY IN THE OLD CITY OF WENZHOU,CHINA

Due to rapid growth of population, urbanization and industrialization, in many cites of the developing world, there is severe contradiction between urban land supply and land demand which resulted in many urban land use conflicting situations and urban environment degrading. This paper is mainly focused on this problem, demonstrating the feasibility and efficiency of environmental study by integrating GIS and environmetal zoning method. Two neighbourhoods of the old city of Wenzhou were chosen as the study area. With the aid of GIS software PC Arc/info as dBate IV, an urhan environmental impact assessment study was carried out based on the data available such as land use map and detailed attribute data of each land planning unit. The main factors taken into consideration include: the type of activity causing environmental stress, the type and strength of environmental impact and the type of receptive area that could be affected.

Development of a Training Textbook for Countermeasures to “Verbal Abuse, Physical Assault, and Harassment in Pediatric Medical Settings”

Background: Recently, abuse, assault, and harassment in pediatric medical settings have become more serious. We extracted typical problems from a nationwide simultaneous survey on abuse in the pediatric medical field and developed a training textbook to simulate or discuss these issues with colleagues. This study aimed to confirm the validity and usability of the contents of this training textbook. Methods: The textbook was mailed to the heads of 51 medical institutions affiliated with the Society of Ambulatory and General Pediatrics of Japan (SAGPJ) and the participants of the SAGPJ online workshop, who were asked to evaluate the textbook using a three-point scale to answer the following questions and provide opinions and impressions about the textbook. Q1. Do you think the whole content and structure of this textbook are useful? Q2. Would you use this textbook as a training textbook for all staff at your facility? A simple tabulation was performed on the evaluation using a three-point scale, while content analysis was performed on the opinions and impressions of the participants. Results: In response to Q1 and Q2, all 63 staff members from 55 facilities answered “3: Yes.” Opinions and impressions on the training textbook included “I think it can be used for workplace training” and “it is useful for exchanging various opinions among staff members and gaining a common opinion.” Conclusion: We developed a training textbook on abuse, assault, and harassment in pediatric medical settings based on a nationwide survey and confirmed the validity and usability of its contents.

Improving First Year Nursing Student’s Test Scores through Pediatric Simulation

Background: Student test scores in the pediatric portion were at a national percentile rank of 30, which was concerning. It was theorized that the main contributor to this dilemma was that the majority of students were not able to have a pediatric clinical experience. Objective: The purpose of this project was to determine if the addition of pediatric simulation scenarios would have an impact on student learning as evidenced by end of level test scores. Method: A convenience sample (n = 100) of first year nursing students attending a university in the western United States participated in this project. This was a mixed methods study. A quasi-experimental design was used to compare test scores of both a non-intervention group and an intervention group of students. A 5 point Likert scale questionnaire was also using post-intervention to assess for changes in perceptions of self-confidence. Results: After implementation of the pediatric focused scenarios, students’ test scores increased to the 95th percentile. This 65 percentile increase is a significant change that suggests that pediatric simulation is effective in improving student exam performance. In addition, 81% of students also reported perceptions of increased levels of self-confidence after implementation of simulation scenarios. Conclusion: The findings suggest that simulation is an effective way to create alternative pediatric clinical experiences which can, in turn, increase student comprehension, test scores, and self-confidence.

Replication of interleukin 23 receptor and autophagy-related 16-like 1 association in adult-and pediatric-onset inflammatory bowel disease in Italy

AIM: To investigate gene variants in a large Italian inflammatory bowel disease (IBD) cohort, and to analyze the correlation of sub-phenotypes (including age at diagnosis) and epistatic interaction with other IBD genes. METHODS: Total of 763 patients with Crohn's disease (CD, 189 diagnosed at age < 19 years), 843 with ulcerative colitis (UC, 179 diagnosed <19 years), 749 healthy controls, and 546 healthy parents (273 trios) were included in the study. The rs2241880 [autophagy-related 16-like 1 (ATG16L1)], rs11209026 and rs7517847 [interleukin 23 receptor (IL23R)], rs2066844, rs2066845, rs2066847 (CARD15), rs1050152 (OCTN1), and rs2631367 (OCTN2) gene variants were genotyped. RESULTS: The frequency of G allele of ATG16L1 SNP (Ala197Thr) was increased in patients with CD compared with controls (59% vs 54% respectively) (OR = 1.25, CI = 1.08-1.45, P = 0.003), but not in UC (55%). The frequency of A and G (minor) alleles of Arg381Gln, rs11209026 and rs7517847 variants of IL23R were reduced significantly in CD (4%, OR = 0.62, CI = 0.45-0.87, P = 0.005; 28%, OR = 0.64, CI = 0.55-0.75, P < 0.01), compared with controls (6% and 38%, respectively). The A allele (but not G) was also reduced signifi cantly in UC (4%, OR = 0.69, CI = 0.5-0.94, P = 0.019). No association was demonstrated with sub-phenotypes and interaction with CARD15 , and OCTN1/2 genes, although both gene variants were associated with pediatric-onset disease. CONCLUSION: The present study confirms the association of IL23R polymorphisms with IBD, and ATG16L1 with CD, in both adult- and pediatric-onset subsets in our study population.

面向流域治理与城镇发展统筹的城市水系统规划协同机制探讨 ——广东东莞生态园实证研究

统筹流域治理与城镇发展是系统解决当前城市发展过程中遇到的水资源短缺、水生态破坏、洪涝灾害频发的关键路径。本文在辨析流域治理与城镇发展统筹面临的主要问题及其辩证关系的基础上,以东莞市中部地区的生态园及其所在的寒溪河流域为研究对象,系统探讨了城市水系统规划在流域治理与城镇发展统筹中的协同作用机制。结果表明,以城镇-流域水系统耦合模型为支撑,城市水系统规划及其协同机制可通过空间、设施等要素的协同,实现保障城市及流域防洪排涝安全、保护水环境和节约水资源的目标,促进流域安全与城镇发展的良性互动。

小儿足部畸形矫正手术后功能恢复的影响因素分析

目的:本研究旨在分析小儿足部畸形矫正手术后功能恢复的关键影响因素,并评估个性化康复计划对提高术后恢复效果的作用。方法:采用前瞻性队列研究设计,选取2023年1月至12月在特定医疗中心接受足部畸形矫正手术的100名小儿患者,随机分为实验组和对照组,每组50名。实验组除了接受常规术后护理外,还实施了包括个性化的物理治疗、营养干预、心理健康干预及家庭支持等在内的综合康复措施。结果:实验组在术后即刻恢复和随访期间的功能恢复评分显著优于对照组,表现在疼痛控制、运动范围、步态分析和独立行走能力等方面。结论:针对小儿足部畸形手术后的个性化康复计划能有效促进功能恢复,减少术后并发症,提升患儿的生活质量。这些发现强调了综合干预在儿童足部畸形手术后康复中的重要性,并为临床提供了更精准的治疗策略。

120例全麻下儿童牙科治疗回顾分析

目的:调查接受牙科全麻(dental general anesthesia,DGA)治疗患儿的牙科治疗状况。方法:选择2017年6月—2019年11月于昆明医科大学附属口腔医院儿童口腔科接受DGA治疗的18岁以下患者,收集患儿基本信息、DGA治疗原因、麻醉及插管方式、诊疗内容、治疗时间及复诊情况。采用SPSS 26.0软件包对数据进行统计学分析。结果:共纳入120例患儿,男性占58.3%,以3~6岁患儿全麻治疗需求最高(85.0%)。恐惧牙科治疗,非药物行为管理无效是低龄儿童选择DGA治疗的首要因素;6岁以上儿童选择DGA最常见的原因为精神智力障碍(38.9%)及患方要求(38.9%)。人均治疗(15.16±3.42)颗牙,每颗牙平均耗时约12.26 min。龋齿充填术、根管治疗术以及乳牙预成冠(包括前牙树脂透明成形冠套和后牙金属预成冠)修复是主要治疗项目。DGA术后1周,98.3%的患儿无不适感。2017—2019年间选择DGA治疗的患者人数呈上升趋势。结论:DGA可快捷、安全、有效解决恐惧牙科治疗、非药物行为管理无效及精神智力障碍儿童的口腔问题,DGA在患者中的接受度呈上升趋势。在经济欠发达地区,需大力推广DGA培训及相关扶持项目,以满足治疗需求。

PICU护士谵妄管理行为意向及影响因素的质性研究

目的 以计划行为理论为框架,深入了解PICU护士谵妄管理行为意向及影响因素,为提高PICU谵妄管理质量提供参考。方法 采用目的抽样法对6所三级甲等医院的16名PICU护士进行半结构式访谈,根据Colaizzi七步分析法对访谈资料进行分析,提取主题。结果 共获得3个主题及8个亚主题,包括行为态度(正性态度,负性态度)、主观规范(自我感知压力增加,团队的影响)及知觉行为控制(谵妄认知及应对技能不足,缺乏相关制度与流程,工作负荷过重,缺乏谵妄管理能力培训)。结论 PICU护士对谵妄管理总体持积极态度,但影响因素较多。应提高护理人员对谵妄的认知,加强相关培训力度,建立多学科团队合作机制,以提高PICU谵妄管理质量。

乡村振兴背景下的研学游基地规划与发展研究——以衢州龙游溪口镇为例

文章首先对乡村文化传承的脉络进行分析,以衢州龙游溪口镇为实际案例,归纳出乡村文化发展的痛点。在此基础上,引入“乡村研学”课题,通过介绍乡村研学发展现状、乡土文化资源等,点明乡村研学重塑乡土文化的重要作用,对乡村研学基地的发展和规划做初步策划。最后,提出以乡村研学为基础的乡村振兴战略,以文化与旅游相结合的产业模式、多元体验的线路项目、不同类型的活动场景来引导乡村振兴,以期将乡村文化与现代功能相结合,重拾乡土特色,为我国乡村研学游可持续发展提供理论依据。