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Vol 14, No 3
Vol 14, No 3 June 2018 ISSN 1708-8569
Personal viewpoint
Review articles
Original articles
Book review
Current status and challenge in clinical work of autism spectrum disorders in China
  Zhi-Wei Zhu, Yan Jin, Ling-Ling Wu, Xiao-Lin Liu
  [Abstract] [Full Text] [PDF]  
Personal viewpoint:
A parent-centered approach to autism diagnosis in early childhood
  Michael E. Mintz
  [Abstract] [Full Text] [PDF]  
Review articles:
Are therapeutic diets an emerging additional choice in autism spectrum disorder management?
  M. Gogou, G. Kolios
Background: A nutritional background has been recognized in the pathophysiology of autism and a series of nutritional interventions have been considered as complementary therapeutic options. As available treatments and interventions are not effective in all individuals, new therapies could broaden management options for these patients. Our aim is to provide current literature data about the effect of therapeutic diets on autism spectrum disorder.
Data sources: A systematic review was conducted by two reviewers independently. Prospective clinical and preclinical studies were considered.
Results: Therapeutic diets that have been used in children with autism include ketogenic and gluten/casein-free diet. We were able to identify 8 studies conducted in animal models of autism demonstrating a beneficial effect on neurophysiological and clinical parameters. Only 1 clinical study was found showing improvement in childhood autism rating scale after implementation
of ketogenic diet. With regard to gluten/casein-free diet, 4 clinical studies were totally found with 2 of them showing a favorable outcome in children with autism. Furthermore, a combination of gluten-free and modified ketogenic diet in a study had a positive effect on social affect scores. No serious adverse events have been reported.
Conclusions: Despite encouraging laboratory data, there is controversy about the real clinical effect of therapeutic diets in patients with autism. More research is needed to provide sounder scientific evidence.
  [Abstract] [Full Text] [PDF]  
Mental health of the male adolescent and young man: the Copenhagen statement
  Timothy R. Rice, Lesha D. Shah, Pilar Trelles, Shih-Ku Lin, Dinne Skjærlund Christensen, Andreas Walther, Leo Sher
Background: Male adolescents and young men benefit when their mental health care is specialized to match their unique gendered and developmental needs. Sensitivity to the social circumstances of this population is important; additionally, the emerging ability to tailor care through knowledge gleaned from the intersection of psychiatry, neurology, and endocrinology informs care.
Data sources: This article summarized the views of six experts in the area of the adolescent and young adult male mental health. These experts were select members of the World Federation of Societies of Biological Psychiatry's Task Force on Men's Mental Health. They convened to present two symposia on the topic of men's mental health at the 13th World Congress of Biological Psychiatry (WCBP) in Copenhagen, Denmark in 2017.
Results: In these works, a special focus is paid to addictive disorders, disruptive behavior disorders, aggression, and brain development. Collectively, the authors present an argument for the merits of a male-specific model of mental health care to advance the overall well-being of this population.
Conclusions: Men' mental health should be recognized as a social issue as much as a medical issue, with special attention paid to problems such as unemployment, familial disruption, and substance abuse. These problems, and especially those of major societal impact including violence and suicide which are much more frequently the product of male youth and men, should have more male-tailored options for service provision that respond to men's mental health needs.
  [Abstract] [Full Text] [PDF]  
Original articles:
Serum proteomic profiling for autism using magnetic bead-assisted matrix-assisted laser desorption ionization time-of-flight mass spectrometry: a pilot study
  Yan-Ni Chen, Hui-Ying Du, Zhuo-Yue Shi, Li He, Yu-Ying He, Duan Wang
Background: The pathogenesis of autism spectrum disorders remains elusive and currently there are no diagnostic or predictive biomarkers in autism available. Proteomic profiling has been used in a wide range of neurodevelopmental disorder studies, which could produce deeper perceptions of the molecular bases behind certain disease and potentially becomes useful in discovering biomarkers in autism spectrum disorders.
Methods: Serum samples were collected from autistic children about 3 years old in age (n = 32) and healthy controls (n = 20) in similar age and gender. The samples were identified specific proteins that are differentially expressed by magnetic bead-based pre-fractionation and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-ToF-MS).
Results: Eight protein peaks were significantly different in autistic children from the healthy controls (P < 0.0001). The two peaks with the most significant differences were 6428 and 7758 Da in size.
Conclusion: According to differences in serum protein profiles between the autistic children and healthy controls, this study identified a set of differentially expressed proteins those are significant for further evaluation and might function as biomarkers in autism.
  [Abstract] [Full Text] [PDF]  
Rasch validation of the Chinese parent每child interaction scale (CPCIS)
  Patrick Ip, Winnie Tso, Nirmala Rao, Frederick Ka Wing Ho, Ko Ling Chan, King Wa Fu, Sophia Ling Li, Winnie Goh, Wilfred Hing-sang Wong, Chun Bong Chow
Background: Proper parent每child interaction is crucial for child development, but an assessment tool in Chinese is currently lacking. This study aimed to develop and validate a parent-reported parent每child interaction scale for Chinese preschool children.
Methods: The Chinese parent-child interaction scale (CPCIS) was designed by an expert panel based on the literature and clinical observations in the Chinese context. The initial CPCIS had 14 parent-child interactive activity items. Psychometric properties of the CPCIS were examined using the Rasch model and confirmatory factor analysis (CFA). Convergent validity was investigated by the associations between CPCIS and family income, maternal education level, and children's school readiness.
Results: The study recruited 567 Chinese parent-child pairs from diverse socioeconomic backgrounds, who completed the CPCIS. Six out of the 14 items in the initial CPCIS were dropped due to suboptimal fit values. The refined 8-item CPCIS was shown to be valid and reliable by Rasch models and CFA. The person separation reliability and Cronbach's 汐 of the CPCIS were 0.81 and 0.82, respectively. The CPCIS scores were positively associated with family's socioeconomic status (2 = 0.05, P < 0.001), maternal education level (2 = 0.08, P < 0.001), and children's school readiness (2 = 0.01, P < 0.01).
Conclusion: CPCIS is an easily administered, valid, and reliable tool for the assessment of parent-child interactions in Chinese families.
  [Abstract] [Full Text] [PDF]  
Hyperthyroxinemia at birth: a cause of idiopathic neonatal
  Irena Ulanovsky, Tatiana Smolkin, Shlomo Almashanu, Tatiana Mashiach, Imad R. Makhoul
Background: Some neonates develop idiopathic hyperbilirubinemia (INHB) requiring phototherapy, yet with no identifiable causes. We searched for an association between abnormal thyroid levels after birth and INHB.
Methods: Of 5188 neonates, 1681 (32.4%) were excluded due to one or more risk factors for hyperbilirubinemia. Total thyroxine (TT4) and thyroid stimulating hormone values were sampled routinely at 40-48 hours of age and measured in the National Newborn Screening Program.
Results: Of the 3507 neonates without known causes for hyperbilirubinemia, 61 (1.7%) developed INHB and received phototherapy. Univariate analyses found no significant association between mode of delivery and INHB (vacuum-delivered neonates were a priori excluded). Nonetheless, in cesarean-delivered (CD) neonates, two variables had significant association with INHB: TT4 ≡ 13 米g/dL and birth at 38-38.6 weeks. In vaginally delivered (VD) born neonates, INHB was associated with weight loss > 7.5% up to 48 hours of age. Multivariate logistic regression analysis showed a strong effect of mode of delivery on possible significant association with INHB. In CD neonates, such variables included: TT4 ≡ 13 米g/dL [P = 0.025, odds ratio (OR) 5.49, 95% confidence interval (CI) 1.23-24.4] and birth at 38-38.6 weeks (P = 0.023, OR 3.44, 95% CI 1.19-9.97). In VD neonates, weight loss > 7.5% (P = 0.019, OR 2.1, 95% CI 1.13-3.83) and 1-min Apgar score < 9 (P < 0.001, OR 3.8, 95% CI 1.83-7.9), but not TT4, showed such an association.
Conclusions: INHB was significantly associated with birth on 38-38.6 week and TT4 (≡ 13 米g/dL) in CD neonates, and with a weight loss > 7.5% in VD neonates. We herein highlight some acknowledged risk factors for neonatal hyperbilirubinemia, and thus minimize the rate of INHB.
  [Abstract] [Full Text] [PDF]  
Cardiac diagnostics before oral propranolol therapy in infantile hemangioma: retrospective evaluation of 234 infants
  Giovanni Frongia, Ji-Oun Byeon, Raoul Arnold, Arianeb Mehrabi, Patrick G邦nther
Background: The indication and extent of cardiac screening before oral propranolol therapy (OPT) in patients with infantile hemangioma (IH) has been challenged. In this study, we evaluated pre-OPT cardiac diagnostics in a pediatric IH cohort in our department.
Methods: Retrospective chart review of infants ≒ 12 months old with IH undergoing OPT. The diagnostics prior to OPT, occurrence of complications, and outcome were recorded.
Results: A total of 234 patients were evaluated. The mean age at the onset of OPT was 4.2 ㊣ 0.3 months, the average duration of OPT was 6.1 ㊣ 0.1 months, and the average follow-up was 12.3 ㊣ 0.7 months. Echocardiograms and electrocardiograms were performed prior to OPT in all patients. One hundred and three (44.0%) echocardiograms revealed pathological findings, 19 (8.1%) of which were minor (including atrial septal defects, pulmonary stenosis, and patent ductus arteriosus). Pathological findings were observed in 17 (7.3%) of electrocardiograms, only one (0.4%) of which was minor (suspected cardiac arrhythmia, subsequently excluded by long-term electrocardiogram analysis). These findings did not contraindicate OPT and no severe adverse events associated with OPT occurred during the follow-up period.
Conclusions: Routine cardiac screening by electrocardiogram and echocardiogram before OPT is debatable and not routinely indicated in children with IH. Further studies are necessary to draw definite conclusions on the reasonable indication and extent of this diagnostic approach.
  [Abstract] [Full Text] [PDF]  
Serial evaluation of myocardial function using the myocardial performance index in Kawasaki disease
  Eun Song Song, Somy Yoon, Joo Hyun Cho, Eun Mi Yang, Hwa Jin Cho, Young Youn Choi, Jae Sook Ma, Gwang Hyeon Eom, Young Kuk Cho
Background: Kawasaki disease (KD) is known as systemic vasculitis, and more than half of the patients with KD have myocarditis, which can induce ventricular dysfunction. In this study, we evaluate left ventricular (LV) dysfunction in patients with KD based on the myocardial performance index (MPI) using pulse Doppler (PD) and tissue Doppler imaging (TDI), from the acute to convalescent phases.
Methods: We retrospectively studied 89 children diagnosed with KD from January 2010 to August 2012. We assessed the presence of coronary artery lesions (CALs) and the LV ejection fraction, PD-MPI, and TDI-MPI at diagnosis, and 2, 14, and 56 days after intravenous immunoglobulin (IVIG) treatment. We enrolled 70 healthy children as a control group.
Results: The ejection fraction in patients with KD at diagnosis (67.3 0.9%) was lower than that in the control group (69.8 ㊣ 0.8%, P = 0.035), and the LV TDI-MPIs for patients with KD at diagnosis (0.49 ㊣ 0.01) and 2 days after IVIG treatment (0.48 ㊣ 0.01) were higher than those in the control group (0.45 ㊣ 0.01, P = 0.002, P = 0.033, respectively). No significant differences were found in the LV dysfunction between the patients with complete and incomplete KD. Septal TDI-MPIs in patients with KD with CAL at diagnosis (0.52 ㊣ 0.02) were higher than those in patients with KD without CAL (0.47 ㊣ 0.01, P = 0.019).
Conclusions: Transient LV dysfunction occurred in patients with complete and incomplete KD in the acute stage. In patients with KD with CAL at diagnosis, the LV dysfunction was more prominent. The PD-MPI and TDI-MPI are useful parameters for assessing LV function in patients with KD.
  [Abstract] [Full Text] [PDF]  
Morbidity and mortality of coagulase-negative staphylococcal sepsis in very-low-birth-weight infants
  Joseph B. Cantey, Kelsey R. Anderson, Ram R. Kalagiri, Lea H. Mallett
Background: Coagulase-negative staphylococci (CoNS) are the most common cause of late-onset sepsis in the neonatal intensive care unit (NICU) and usually require vancomycin treatment. Our objective was to determine whether CoNS are associated with neonatal morbidity and mortality.
Methods: This was a retrospective cohort study of very-low-birth-weight (VLBW, ≒ 1500 g) infants from 1989 to 2015. Exclusion criteria were major congenital anomaly or death within 72 h. CoNS was considered a pathogen if recovered from ≡ 2 cultures, or 1 culture if treated for ≡ 5 days and signs of sepsis were present. Logistic regression was used to examine factors associated with morbidity and mortality.
Results: Of 2242 VLBW infants, 285 (12.7%) had late-onset sepsis. CoNS (125, 44%), Staphylococcus aureus (52, 18%), and Escherichia coli (36, 13%) were the most commonly recovered organisms. In multivariate analysis, CoNS sepsis was not associated with mortality [OR 0.6 (95% CI 0.2-2.6)), but sepsis with other organisms was [OR 4.5 (95% CI 2.6-8.0)]. CoNS sepsis was associated with longer hospitalization but not risk for bronchopulmonary dysplasia, intraventricular hemorrhage, or retinopathy of prematurity.
Conclusion: CoNS sepsis was not associated with mortality or morbidities other than length of stay. These findings support vancomycin-reduction strategies in the NICU.
  [Abstract] [Full Text] [PDF]  
Introducing an antibiotic stewardship program in a pediatric center in China
  Zhi-Gang Zhang, Fei Chen, Jian-Zhong Chen
Background: This study aimed to investigate the effect of antibiotic stewardship programs (ASP) on reducing antimicrobial resistance rate, antibiotics consumption and multi-drug resistance bacterial infections in the pediatric patients.
Methods: This study was carried out in the Pediatric Center of a tertiary hospital of Shandong Province, China. The study duration was separated into two periods according to introduction of ASP (began from April 2011). Before intervention: from April 2009 to March 2011; after intervention: from April 2012 to March 2014. The consumption of antibiotics, defined daily dose (DDD), isolation of multidrug-resistant organisms (MDRO) and resistance rate of antibiotics were analyzed and compared between the two study periods.
Results: Total antibiotics consumption (DDDs) reduced from 56,725 in 2011 to 31,380 in 2014; antibiotic use density (AUD) reduced from 93.8 to 43.5; mean ( SD) antibiotic costs per patient (per quarter) decreased from 637 (㊣ 29) RMB to 462 (㊣ 49) RMB; and the mean total drug consumption (g)/DDD (DDDs) for inpatients decreased from 90.4 (㊣ 3.3) to 56.4 (㊣ 9.5). Multidrug-resistant microorganisms isolation reduced significantly from 463 (20.0) to 216 (6.9%). Resistance rate of general spectrum antibiotics reduced remarkably after intervention. The proportion of patients colonized or infected with Carbapenems-resistant Acinetobacter baumannii was correlated with DDDs of carbapenem.
Conclusions: Implementation of ASP leads to reduced medical expense, decrease of improper and abuse of antibiotics, and reduced antibiotics resistance rate and MDRO isolation. Continuous efforts to improve antibiotic use are required.
  [Abstract] [Full Text] [PDF]  
Oxcarbazepine oral suspension in young pediatric patients with partial seizures and/or generalized tonic每clonic seizures in routine clinical practice in China: a prospective observational study
  Jiong Qin, Yi Wang, Xin-Fang Huang, Yu-Qin Zhang, Fang Fang, Yin-Bo Chen, Zhong-Dong Lin, Yan-Chun Deng, Fei Yin, Li Jiang, Ye Wu, Xiang-Shu Hu
Background: This study aimed to assess efficacy and safety of oxcarbazepine (OXC) oral suspension in pediatric patients aged 2-5 years with partial seizures (PS) and/or generalized tonic-clonic seizures (GTCS) in real-world clinical practice in China.
Methods: This 26-week, prospective, single-arm, multicenter, observational study recruited pediatric patients aged 2-5 years with PS or GTCS suitable for OXC oral suspension treatment based on physicians ' judgments from 11 medical centers in China. Enrolled subjects started OXC oral suspension treatment as monotherapy or in combination with other antiepileptic drugs. Primary efficacy outcome was the percentage of pediatric subjects achieving ≡ 50% seizure frequency reduction at the end of the 26-week treatment. Secondary efficacy-related parameters and safety parameters such as adverse events (AEs) and serious AEs (SAEs) were also monitored during the 26-week treatment period.
Results: Six hundred and six pediatric patients were enrolled and 531 (87.6%) completed the study. After 26 weeks of treatment, 93.3% subjects achieved ≡ 50% seizure frequency reduction, and 81.8% achieved 100% seizure frequency reduction compared to baseline. Among different seizure types, OXC was effective in all subjects with simple PS and in > 90% of subject with other type of seizure present in the study. AEs were observed in 49 (8.1%) subjects. Only three subjects experienced SAE. Rash (n = 18, 2.97%) was the most common AE. Only 17 subjects discontinued due to AEs.
Conclusion: This study, reporting the real-world data, further confirms the efficacy and good safety profile of OXC oral suspension in Chinese pediatric patients aged 2-5 years with PS and/or GTCS.
  [Abstract] [Full Text] [PDF]  
Clinical characteristics of two cohorts of infantile spasms: response to pyridoxine or topiramate monotherapy
  Jiao Xue, Ping Qian, Hui Li, Ye Wu, Hui Xiong, Yue-Hua Zhang, Zhi-Xian Yang
Background: Infantile spasms (IS) was an epileptic disease with varied treatment widely among clinicians. Here, we aimed to compare and analyze the clinical characteristics of IS response to pyridoxine or topiramate monotherapy (TPM control IS).
Methods: The clinical manifestations, treatment processes and outcomes were analyzed in 11 pyridoxine responsive IS and 17 TPM-control IS.
Results: Of the 11 patients with pyridoxine responsive IS, nine were cryptogenic/idiopathic. Age of seizure onset was 5.36 1.48 months. Spasms were controlled within a week in most of the patients. At the last follow-up, EEG returned to normal in 8. Psychomotor development was normal in 6, mild delay in 3, severe delay in 2. Of the 17 patients with TPM-control IS, 10 were cryptogenic/idiopathic. The age of seizure onset was 5.58 ㊣ 2.09 months. All patients were controlled within a month. At the last follow-up, EEG was normal in 10. Psychomotor development was normal in 8, mild delay in 5, severe delay in 4. Genetic analysis did not show any meaningful results.
Conclusions: The clinical characteristics and disease courses of pyridoxine responsive IS and TPM-control IS were similar, which possibly clued for a same pathogenic mechanism. Pyridoxine should be tried first in all IS patients, even in symptomatic cases. If patients were not responsive to pyridoxine, TPM could be tried.
  [Abstract] [Full Text] [PDF]  
Two novel mutations in the GAN gene causing giant axonal neuropathy
  Monica Irad Normendez-Mart赤nez, Lucero Monterde-Cruz, Roberto Mart赤nez, Magdalena Marquez-Harper, Nayelli Esquitin-Garduno, Margarita Valdes-Flores, Leonora Casas-Avila, Valeria Ponce de Leon-Suarez, Viktor Javier Romero-D赤az, Alberto Hidalgo-Bravo
Background: Giant axonal neuropathy (GAN) is a rare neurodegenerative disease transmitted in an autosomal recessive mode. This disorder presents motor and sensitive symptoms with an onset in early childhood. Progressive neurodegeneration makes the patients wheelchair dependent by the end of the second decade of life. Affected individuals do not survive beyond the third decade of life. Molecular analysis has identifi ed mutations in the gene GAN in patients with this disorder. This gene produces a protein called gigaxonin which is presumably involved in protein degradation via the ubiquitin每proteasome system. However, the underlying molecular mechanism is not clearly understood yet.
Methods: Here we present the first patient from Mexico with clinical data suggesting GAN. Sequencing of the GAN gene was carried out. Changes in the nucleotide sequence were investigated for their possible impact on protein function and structure using the publicly available prediction tools PolyPhen-2 and PANTHER.
Results: The patient is a compound heterozygous carrying two novel mutations in the GAN gene. The sequence analysis revealed two missense mutations in the Kelch repeats domain. In one allele, a C>T transition was found in exon 9 at the nucleotide position 55393 (g.55393C>T). In the other allele, a transversion G>T in exon 11 at the nucleotide position 67471 (g.67471G>T) was observed. Both of the bioinformatic tools predicted that these amino acid substitutions would have a negative impact on gigaxonin's function.
Conclusion: This work provides useful information for health professionals and expands the spectrum of disease-causing mutations in the GAN gene and it is the first documented case in Mexican population.
  [Abstract] [Full Text] [PDF]  
Differential impact of flow and mouth leak on oropharyngeal humidification during high-flow nasal cannula: a neonatal bench study
  Tim Leon Ullrich, Christoph Czernik, Christoph B邦hrer, Gerd Schmalisch, Hendrik Stefan Fischer
Background: Heated humidification is paramount during neonatal high-flow nasal cannula (HFNC) therapy. However, there is little knowledge about the influence of flow rate and mouth leak on oropharyngeal humidification and temperature.
Methods: The effect of the Optiflow HFNC on oropharyngeal gas conditioning was investigated at flow rates of 4, 6 and 8 L min1 with and without mouth leak in a bench model simulating physiological oropharyngeal air conditions during spontaneous breathing. Temperature and absolute humidity (AH) were measured using a digital thermo-hygrosensor.
Results: Without mouth leak, oropharyngeal temperature and AH increased significantly with increasing flow (P < 0.001). Mouth leak did not affect this increase up to 6 L min1, but at 8 L min 1, temperature and AH plateaued, and the effect of mouth leak became statistically significant (P < 0.001).
Conclusions: Mouth leak during HFNC had a negative impact on oropharyngeal gas conditioning when high flows were applied. However, temperature and AH always remained clinically acceptable.
  [Abstract] [Full Text] [PDF]  
Book review:
Book review: healing children〞a surgeon*s stories from the frontiers of pediatric medicine
  Martin R. Eichelberger
  [Abstract] [Full Text] [PDF]  
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