Background：Implementation research refers to systematically integrating evidencebased practice into clinical scenarios to improve the quality and effectiveness of healthcare services and bridge the gap between evidence and clinical practice. However, this type of research has not received much attention.
Objective：To develop implementation strategies of the recommendations for venous access devices (VADs) selection in hospitalized children from Clinical Practice Guideline on Infusion Therapy in Children, to evaluate the impact of evidence implementation on patient outcomes, the evidencebased practice behaviors of healthcare workers, and organization environment changes in the hospital, and to identify conflicts between recommendations and clinical practice in different clinical settings.
Design：Implementation study.
Methods：We developed strategies to promote evidence implementation at Children's Hospital of Fudan University from four perspectives: dissemination, implementation process, integration, and capacity building. These strategies, along with correspongding individualized action plans, were applied in the VAD selection for children's infusion therapy. The implementation process and outcomes were evaluated from four aspects: reach, effectiveness (or efficacy), adoption, and implementation according to the REAIM framework.
Main outcome measures：VAD selection error rate, and compliance of VAD selection among nurses.
Results：The implementation period was from May 30, 2022, to October 30, 2022. We enrolled 2,343 patients in the intervention group and 2,309 patients in the control group. （1）Reach: During the implementation period, 4, 652 pediatric patients met the inclusion criteria. Out of these, 2, 343 patients received the implementation strategy and individualized action plan. (2) Effectiveness: Among the hospitalized children in the 10 wards, there was no statistically significant gender difference between the two groups. However, there were significant differences in patient age, emergency admission status, surgical status, and department. After adjusting for age, emergency admission status, surgical status, and department, compared to the control group, the intervention group had a 25% reduction in VAD selection error rate (OR=0.745, 95%CI: 0.6120.906). There was no statistically significant difference in the incidence of extravasation/infiltration between the control and intervention groups (OR=1.070, 95%CI: 0.8221.393). The nurses' knowledge level in VAD selection was significantly higher in the intervention group (83.9±12.4) compared to that of the control group (56.0±13.1). Compliance rate of five audit indicators was 100% before, during, and after implementation, compliance rate of four indicators significantly improved before, during, and after implementation, compliance rate of seven indicators showed no statistically significant difference before, during, and after implementation. (3) Adoption: During the implementation period, all 10 wards selected by cluster random sampling (100%) fully participated in the strategy implementation and adopted all 17 pieces of evidence (100%). Multiple rounds of course training (4 hours each) and practical training (3 hours each) were conducted to help nurses understand the implementation strategies and action plans, and all 214 nurses (100%) completed the training courses. (4) Implementation: The study developed six implementation strategies, achieving an 83.3% completion rate. The costeffectiveness index of peripheral intravenous catheter (PIVC) infusion materials before and after the intervention was 2.1>0, indicating that the intervention led to cost savings.
Conclusion：The process evaluation of the guideline recommendations indicated a positive result across the four domains of reach, effectiveness (or efficacy), adoption, and implementation based on the REAIM framework. However, a moderate result was indentified in the compliance evaluation of nurses' VAD selection behavior in the effectiveness domain.
Background：Wheezing is a common respiratory symptom in infants and young children. In recent years, the incidence of wheezing has been increasing year by year.
Objective:To investigate the etiology of first-onset wheezing in infants (<3 months old) and the wheezing situation and influencing factors of infant patient within 6 years.
Design:Retrospective cohort study.
Methods:Hospitalized infants with first-time infection-related wheezing (excluding congenital heart disease and developmental anomalies) were followed up via phone six years later. The follow-up information included mother's delivery age, frequency of pregnancy and delivery, delivery method, birth weight and gestational age, family history of asthma, personal allergy history, frequency of wheezing within, age of last wheezing, lung function, and allergen IgE. Cases with first-time only infection-related wheezing were divided into the wheezing group (wheezing episodes ≥3 times) and the control group (wheezing episodes ≤2 times) based on wheezing frequency within 6 consecutive months after discharge. Univariate and multivariate logistic regression analyses were performed.
Main outcome measures:Factors influencing recurrent wheezing six years after initial infection-related wheezing in infants.
Results:Among 229 infants with initial wheezing, 187 cases (81.7%) were due to infection alone, and 42 cases (18.3%) due to infection combined with congenital anomalies, including congenital heart disease (31 cases, 13.5%), congenital laryngomalacia (6 cases, 2.6%), diaphragm elevation, bronchial foreign bodies, lung sequestration, tracheal bronchus, and bronchomalacia (1 case each, 0.4%). Of the 187 only infection-related cases, excluding 16 lost to follow-up, there were 58 cases in the wheezing group and 113 in the control group. Significant differences between the groups were found in factors such as low birth weight, macrosomia, advanced maternal age, family history of asthma, personal allergy history, eczema, elevated peripheral blood eosinophil count, use of IVIG, and combined antibiotic and antiviral therapy. Multivariate logistic analysis showed that eczema (OR=2.19, 95%CI: 1.04-4.62) and allergy history (OR=2.34, 95%CI: 1.09-5.03) doubled the risk of recurrent wheezing six years later. Advanced maternal age (OR=3.06, 95%CI: 1.02-9.21) was a potential risk factor, and family history of asthma (OR=5.07, 95%CI: 1.20-21.45), low birth weight (OR=4.97, 95%CI: 1.62-15.21), macrosomia (OR=9.73, 95%CI: 1.94-48.94), and elevated peripheral blood eosinophil count (OR=3.46, 95%CI: 1.07-11.14) were significant predictors. IVIG use reduced the risk of recurrent wheezing by 57% (OR=0.43, 95%CI: 0.20-0.94).
Conclusion:Eczema and allergy history double the risk of recurrent wheezing six years after initial infection-related wheezing in infants, compared with non-eczema and non-allerty cases. IVIG use can reduce the risk of recurrent wheezing by 57%.
Background：Risdiplam has showed efficacy in Chinsese children with different types of spinal muscular atrophy (SMA) for one-month treatment. However, there is still a lack of real-world data on long-term use of Risdiplam due to the low follow-up visit rates which may caused by the convenience of Risdiplam obtaining and other reasons.
Objective：To observe the efficacy of Risdiplam monotherapy in children with different types of SMA treated for more than 12 months.
Design：Case series report.
Methods：Continuous cases with different types of SMA who were treated with Risdiplam as a monotherapy during the initial and follow-up periods from August 2021 to March 2023 in outpatient or hospital settings were enrolled. The enrolled cases with the age ≥ 16 days when the treatment was initiated were assessed by motor function scales at the beginning of the treatment and during their follow-ups. The oral dose of Risdiplam was calculated based on the patient's age and weight referred to the drug instructions. Patients were followed for at least 6 months and assessed by the qualified doctors with different motor scales. The outcomes of the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND)，the Revised Upper Limb Module Test (RULM)，the Hammersmith Functional Motor Scale Expanded (HFMSE) and the 6-Minute Walk Test (6MWT) were recorded. The adverse events (AEs) and the rate of AEs were reported.
Main outcome measures：Improvement level of motor function score: last follow-up motor function score-baseline motor function score; or motor function score at the last follow-up after switching scales.
Results：In total, 14 SMA pediatric patients were enrolled in this study, including 9 boys (64.3%) and 5 girls. Except for 1 presymptomatic patient, the median age of disease onset of the remaining 13 patients was 9.0 (3.0, 12.0) months; the median age of the 14 patients receiving Risdiplam treatment was 19.5 (6.5, 39.5) months. One patient had one copy number of SMN1 with a point mutation, and the remaining 13 patients occupied 0 copy of SMN1. The nubmer of atients with 1,2,3 and 4 copy numbers of SMN2 was 1,3,9 and 1, respectively. The case number of presymptomatic, type 1, type 2 and type 3 was 1,6,5 and 2, respectively. The interval between the last follow-up and the first drug administration was 20 (11.8, 25.5) months. The improvement in motor function reached clinical significance in 13 SMA patients , and the remained 1 patient also showed improved motor function score scale, but the improvement was not clinically significant. Nine patients had the results of blood routine, liver function and renal function at the baseline and during the follow-ups. The blood routine were normal. Two patients showed abnormal liver function at baseline but with normal results during the follow-ups, and some patients showed abnormal serum creatinine levels, which were caused by the SMA disease itself, and no increase in serum creatinine levels was found during follow-ups. Adverse events that may not be related to the treatment during follow-ups included 11 case of upper respiratory tract infection, 4 case of pneumonia, and 1 case of diarrhea. Except for pneumonia occurred in a child with type 2, the rest of the adverse events occurred in children with type 1. Adverse events that may be related to the treatment included skin color changes in 12 cases (85.7%), rash in 2 cases (14.3%), and constipation in 1 case (7.1%). No serious adverse reactions were found. This article reports one case who maintained normal motor function development after receiving Risdiplam treatment before symptom onset and one case who showed good efficacy of Risdiplam with one copy of SMN2.
Conclusion：Long-term monotherapy of Risdiplam has shown good efficacy in Chinese children with different subtypes of SMA and the most common adverse drug reaction are respiratory tract infections and the change of skin color.
Background：Case reports and case series from abroad have suggested that tocilizumab (TCZ) may be effective in treating refractory myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) that does not respond well to other immunosuppressants, primarily in adults. However, there are no related reports in children in China.
Objective：To analyze the clinical characteristics and of TCZ in two children with MOGAD, and to review the literature on the efficacy and safety of TCZ in treating MOGAD.
Design：Case report and literature review.
Methods：The clinical data of two pediatric patients with MOGAD treated with TCZ were reported, summarizing their clinical characteristics and the efficacy and safety of TCZ. English and Chinese articles published up to November 2023 were searched in PubMed, Embase, Web of Science, Cochrane, Wanfang Data, China National Knowledge Infrastructure (CNKI),and China Science and Technology Journal Database (CQVIP). The search terms include "MOGAD," "myelin oligodendrocyte glycoprotein antibody," "TCZ," "tocilizumab," and "interleukin-6 receptor antagonist".
Main outcome measures：Efficacy and safety of TCZ.
Results：The two pediatric patients with MOGAD had onset at 6 years and 6 months, and 3 years and 7 months, respectively. The duration of illness at the time of TCZ treatment was 9 years and 3 months, and 6 years and 6 months, with 11 and 5 prior acute demyelinating events, respectively. One patient did not experience relapse during 14 months of regular TCZ use, relapsed after stopping, and had one relapse during another 10 months of intermittent use. The other patient had no relapses during 2 years and 4 months of regular TCZ use. Neither of them experienced serious adverse reactions during treatment. A literature review included 9 studies with a total of 27 MOGAD patients (including two reported in this article). Four patients (14.8%) experienced relapse, and the annual relapse rate decreased significantly after treatment in 27 cases. The most common adverse reactions during TCZ treatment were infections and hyperlipidemia. No patients discontinued treatment due to serious adverse reactions. A meta-analysis including 5 studies with 23 patients(including two reported in this article) showed a relapse-free rate of 87% (95%CI: 72%-100%) for TCZ in treating MOGAD.
Conclusion：TCZ is effective and well tolerated in patients with MOGAD who have failed to respond to other traditional immunosuppressant medications. Prospective studies with large sample sizes are needed to further confirm its efficacy.
Background：The clinical phenotypes of Williams syndrome (WS) include special facial features, cardiovascular diseases, connective tissue abnormalities, growth retardation, mental retardation, often accompanied with hearing loss. Previous reports on tympanogram in children with WS are rare and the sample size is small, and none was reported in China.
Objective：To analyze the tympanogram characteristics of children with WS, and to provide clinical evidence for the follow-up of hearing in these children.
Design：Case-control study.
Methods：We included consecutive children followed by two WS follow-up physicians at the Department of Pediatric Health care of the Children's Hospital of Zhejiang University School of Medicine from June 2019 to June 2023 who underwent tympanometric testing and were diagnosed with WS by genetic testing or Lowery score. The control group consisted of healthy children undergoing physical examinations by the same two follow-up physicians at the same department during the same period. Tympanometry was performed using the Titan tympanometry module from Interacoustics in a standard soundproof room with background noise levels <30 dB SPL. The examiner was an audiologist with over 5 years of clinical experience after obtaining an undergraduate degree in audiology. The first tympanogram was analyzed, with type A and type As tympanograms considered negative results, and type B and type C tympanograms considered positive results.
Main outcome measures：Tympanogram characteristics in children with WS.
Results：The WS group included 83 cases (165 ears), with 50 males (60.2%) and 33 females, aged 1.0 to 7.8 years (4.3±1.8 years). The control group included 99 cases (198 ears), with 64 males (64.6%) and 35 females, aged 0.6 to 11.8 years (4.0±2.2 years). The proportion of abnormal ears was higher in the WS group (48/165, 29.1%) than that in the control group (25/198, 12.6%), with a statistically significant difference. The differences in the number of abnormal ears between the WS and control groups were significant in both the -5 years and ≥6 years subgroups. The positive rate of tympanograms was significantly higher in the -5 years (30/84, 35.7%) and ≥6 years (11/32, 34.4%) subgroups compared to the <3 years subgroup (7/49, 14.3%) within the WS group, while there were no significant differences in the positive rate among different age subgroups within the control group. There were no significant differences in the composition ratio of tympanogram types among different age subgroups in the WS group. The control group showed significant differences in the composition ratio of type A and type As tympanograms across age subgroups. The ear canal volume and tympanometric gradient were both significantly greater in the WS group compared to the control group, whereas compliance and peak pressure showed no significant differences. Peak pressure was significantly lower in the -5 years and ≥6 years subgroups compared to the <3 years subgroup within the WS group. In a rescreening of 20 cases (40 ears), 21 ears showed no change in test results, 7 ears changed from positive to negative, and 12 ears changed from negative to positive.
Conclusion：Children with WS have a higher positive rate of tympanograms that may occur repeatedly. The abnormal rate increases with age and negative pressure intensifies with age. The composition ratio of tympanogram is relatively stable among different age groups, which is different from that of control group. Regular long-term tympanogram follow-up is recommended for children with WS.
Background：With advancements in medical care, more children with congenital heart disease (CHD) are surviving into adulthood. The readiness for transition from adolescence to adulthood reflects CHD adolescents' ability to transition and manage their disease. Currently, there is a lack of data on transition readiness among Chinese CHD adolescents.
Objective：To assess the transition readiness of CHD adolescents, understand the current state and transition capabilities of CHD adolescents transitioning to adult care in China, analyze the influencing factors, and provide a basis for developing individualized transition care strategies.
Design：Cross-sectional survey.
Methods：We included CHD adolescents aged 10-18 years and their primary caregivers who were followed up in the Department of Cardiothoracic Surgery at Children's Hospital of Fudan University from January 1, 2018, to August 31, 2023. The transition readiness of CHD adolescents was assessed by collecting data using a researcher-designed general information questionnaire, Self-Management and Transition Readiness Assessment (STARx) questionnaire (both self-report and parent-report versions), the Leuven Knowledge Questionnaire for Congenital Heart Disease (LKQCHD) in Chinese, and the General Self-Efficacy Scale (GSES). Univariate and linear regression analyses were used to identify influencing factors.
Main outcome measures：STARx questionnaire score.
Results：A total of 216 questionnaires were distributed. After excluding 64 invalid questionnaires, 152 questionnaires were included for analysis. The overall scores of the STARx questionnaire for self-report and parent-report were 36.74±7.95 and 36.36±7.70 respectively, with no significant difference (P=0.557). In total, 82.2% (125 cases) of CHD adolescents had low to moderate transition readiness scores (<44), while only 17.8% (27 cases) had high readiness scores (≥44). Besides, 63.2% (96 cases) of primary caregivers preferred follow-up at a children's hospital. Linear regression analysis of factors influencing transition readiness scores indicated that accurate CHD knowledge, age, one-child family, and self-efficacy level were significant factors. Higher levels of readiness were associated with older age, greater CHD knowledge, higher self-efficacy, and being a non-only child.
Conclusion：The transition readiness of CHD adolescents in China is moderate and mainly influenced by their CHD knowledge, age, and self-efficacy. Additionally, caregivers showed a strong preference for continuing care at children's hospitals.
Background：Severe ebstein's anomaly (EA) is challenging to diagnose using prenatal and neonatal echocardiography and generally has a poor prognosis. Although surgical treatments are gradually advancing, the short-term and long-term mortality rates for severe EA cases remain high.
Objective：To explore the specific echocardiographic characteristics of misdiagnosed fetal cases of severe EA and improve the prenatal diagnosis accuracy.
Design：Case series reports.
Methods：Consecutive cases diagnosed with severe EA through fetal or postnatal echocardiography were retrospectively collected from May 2017 to April 2024 in two centers. We retrieved data on the mothers including age, gestational age at prenatal ultrasound, mode of conception, singleton or multiple pregnancies, medication history during pregnancy, and family history and fetuses including heart position, atrial and ventricular proportions, attachment points of the tricuspid valve leaflets, presence of tricuspid valve leaflets, papillary muscles, and chordae tendineae, development of the right ventricular outflow tract, pulmonary artery development, degree of tricuspid regurgitation, direction of ductus arteriosus blood flow, presence of other cardiac anomalies, termination of pregnancy, and surgical treatment.
Main outcome measures：Echocardiographic features.
Results：We enrolled 8 cases diagnosed with severe EA in the antenatal period, 7 with induction of labor, and 1 with delivery. Among the 8 cases, 1 case had ventricular septal defect (VSD) and 1 case had partial atrioventricular septal defect (AVSD). Seven cases had a complete absence and severe underdevelopment of the septal leaflet of the tricuspid valve. Among these, 2 cases also had a complete absence and severe underdevelopment of the posterior leaflet, and one case only had the posterior leaflet completely absent and severely underdeveloped. Specific prenatal echocardiographic features include paradoxical movement of the ventricular septum observed throughout the cardiac cycle; absence of chordae tendineae and papillary muscles on the right ventricular side of the interventricular septum, and a smooth right ventricular surface without soft tissue coverage, termed the "bare sign"; continuity loss of the tricuspid septal leaflet and the coronary sinus wall when the septal leaflet is absent; possible underdeveloped pulmonary artery, but normal one if VSD is present; and to-and-fro flow in the right ventricle without clear tricuspid regurgitation by Color Doppler.
Conclusion：The paradoxical movement of the ventricular septum, the "bare sign" of the right ventricular surface, the tricuspid septum and the coronary sinus wall continuity loss have high specificity in the diagnosis of severe EA. Severe EA requires differential diagnosis from congenitally upguarded tricuspid valve orifice (CUTVO).
Background：There are many factors affecting neonatal hypoglycemia, and severe and persistent hypoglycemia can lead to irreversible neurological damage, posing a great burden to families and society.
Objective：To explore the influencing factors of economic burden during hospitalization for NICU neonates with hypoglycemia.
Design：Cross-sectional study.
Methods：Hypoglycemic neonates admitted to the NICU of Children's Hospital of Zhengzhou University from January 1, 2014 to December 31, 2022 were retrospectively included. The gold standard for neonatal hypoglycemia diagnosis is whole blood glucose <2.2 mmol·L-1 or plasma glucose <2.5 mmol·L-1 , and whole blood glucose <2.6 mmol·L-1 was the cut-off value for clinical management. The classification of neonatal hypoglycemia was based on the Expert Consensus on the Clinical Standardized Management of Neonatal Hypoglycemia (2021). The general condition, perinatal condition, clinical examination index, prognosis and hospitalization expenses of the children were collected. Generalized linear regression was used to investigate the factors affecting medical expenses during hospitalization.
Main outcome measures：The total hospitalization expenses of neonates with hypoglycemia in NICU.
Results：A total of 176 newborns with hypoglycemia were included in this analysis, of which 104 (59.1%) were male and 72 were female. The median age was 4 (2, 9) days. The median total hospitalization cost in RMB was 15,438 (10,670, 23,490) yuan, and the median length of hospital stay was 11.0 (8.0, 16.8) days. Univariate rank-sum test results indicated that symptoms of infection, perinatal brain injury, multiple maternal delivery times, more than four adverse perinatal factors, and improved treatment outcomes all increased the total hospitalization cost, with statistically significant differences. Neonatal blood potassium, C-peptide, abnormal cranial MRI, and hypoglycemic brain injury also increased the total hospitalization cost, with statistically significant differences. Multivariate generalized regression results showed that symptoms of infection, metabolic diseases, multiple maternal delivery times , more than four adverse perinatal factors, and hypoglycemic brain injury were risk factors for the total hospitalization cost.
Conclusion：Newborns with symptoms of infection, metabolic diseases, multiple maternal delivery times, more than four adverse perinatal factors, and hypoglycemic brain injury bear a heavier economic burden during hospitalization.
Background：The clinical manifestations of primary ciliary dyskinesia(PCD) are relatively diverse and often undiagnosed or delayed in diagnosis and treatment.
Objective：To investigate the clinical characteristics and genetic spectrum of primary ciliary dyskinesia in children.
Design：Case series study.
Methods：The medical records system was used to collect clinical information on PCD gene-positive children admitted to Children's Hospital, Zhejiang University School of Medicine between June 1, 2017 and December 31, 2023. This information included gender, age of onset and diagnosis, clinical manifestations, auxiliary examinations, and genetic testing results. A search of Chinese and English databases was conducted to include case series reports of PCD with PCD-related gene positivity in China. The search period spanned from the establishment of the database until December 2023. This study summarises the clinical phenotypes and genotypes of PCD cases in China, as well as their distribution across various regions of the country.
Main outcome measures：Clinical characteristics and genetic spectrum of children in China.
Results：Thirteen children diagnosed with PCD were analysed, comprising of 7 boys (53.8%) and 6 girls. The median age of onset was 9.0 years (ranging from 3 days to 14.3 years), and the median age of diagnosis was 11.3 years (ranging from 24 days to 14.9 years). The study found that the most common clinical manifestations were cough and expectoration in 11 cases (84.6%), sinusitis in 10 cases (76.9%), fever in 7 cases (53.8%), bronchiectasis, visceral transposition, and atelectasis in 6 cases each (46.2%), nasal congestion, purulent nasal discharge, and Kartagener syndrome in 4 cases each (30.8%). Thirteen children were found to have eight gene mutations. Of the 23 double allelic gene mutation sites identified, 4 cases were related to DNAH11 gene mutation (28.6%), 3 cases to DNAH5 gene mutation (21.4%), and 1 case each to CCDC114, DNAH9, DNAAF3, ODAD1, CCNO, and RSPH1 gene mutations. ACMG classified 8 mutations as pathogenic, 7 as possibly pathogenic, and 8 as variants of uncertain significance (VUS). All 8 VUS sites were predicted to be deleterious by protein function software prediction. This analysis includes seventy-two case series reports or case reports including 391 PCD cases and 316 gene-positive cases. A total of 40 PCD-related genes were detected. The top five most frequent gene mutation sites were DNAH5 (21.2%), DNAH11 (17.7%), CCDC40 (7.9%), HYDIN (6.6%), and CCNO (6.0%). The most frequent clinical phenotypes of PCD cases were chronic cough and expectoration (91.3%), chronic sinusitis (87.0%), bronchiectasis (70.6%), and abnormal lung function (64.2%). In Beijing, Shanghai, and Zhejiang province, the main gene variations were DNAH11 and DNAH5. In Chongqing, the main variation was HYDIN (19.1%), while in Guangdong province, it was DNAH1 (22.2%). In Guangxi Zhuang Autonomous Region, the main variations were RSPH4A (13.3%)、HYDIN (10.0%)、DNAH11 (10.0%)、CCDC40 (10.0%), and ZMYND10 (10.0%). In Hunan province, the main variations were DNAH5 (18.2%) and DNAAF4 (13.6%).
Conclusion：In China, the most commonly occurring genes related to PCD are DNAH11 and DNAH5. The main clinical symptoms include respiratory issues, such as persistent coughing, expectoration, and chronic sinusitis.
Background：There is a lack of report in China regarding sinus bradycardia (SB) caused by the use of methylprednisolone pulse therapy for the treatment of pediatric renal and rheumatic disease. There is no consensus on whether to stop pulse therapy after SB occurs.
Objective：To summarize the clinical characteristics of SB during methylprednisolone pulse therapy in children with renal and rheumatic disease.
Design:Case series report.
Methods:Patients who were hospitalized in the Department of Nephrology and Immunology at Children's Hospital of Soochow University from January 1, 2018 to April 1, 2024 and received methylprednisolone pulse therapy were reviewed. During the treatment period, patient with any measurement of heart rate < 60 beats · min-1 and confirmed as SB by electrocardiogram were included in this study. The intercepted information included clinical manifestations, examinations, and prognosis.
Main outcome measures：Characteristics of SB occuring after methylprednisolone pulse therapy.
Results：There were a total of 11 children, including 7 females and 4 males, with an average age of (11.3 ± 2.5) years.There were 3 cases of systemic lupus erythematosus with macrophage activation syndrome (MAS), 2 cases of IgA vasculitis associated nephritis, 2 cases of juvenile idiopathic arthritis with MAS, and 2 case of dermatomyositis with MAS. There was also 1 case of ANCA-associated vasculitis and 1 case of C3 glomerulonephritis. The basal heart rate of the patients was （88±4）beats/min. The average dose of methylprednisolone pulse therapy was （10.7±3.0） mg·kg-1·d-1. The duration of pulse therapy was 3-5（4.3±0.9）d. The time from the start of the first dose of methylprednisolone pulse therapy to the occurrence of SB was 1-3（1.8±0.8）d. The minimum heart rate after pulse therapy was 48-58（53±4） beats/min. The decrease in heart rate was 32.6%-44.6%（40.0%±3.7%）. Blood gas analysis, electrolyte test, cardiac ultrasound, and thyroid function were all normal when SB occurred. No antiarrhythmic treatment was given. The time from the last dose of methylprednisolone pulse therapy to recovery to baseline heart rate was 4-8(6.1±1.1) d. All patients did not experience cardiovascular symptoms such as dizziness, chest tightness, or palpitations during the treatment period. During a follow-up period of (2.4±2.1) years, no cardiovascular abnormalities were found.
Conclusion：The children have no discomfort symptoms when SB occurs after methylprednisolone pulse therapy and therefore the SB is easily overlooked. They generally don't require special treatment and can continue to complete the pulse therapy under close monitoring Their heart rate usually return to normal in a week after the cessation of the pulse therapy.
Background：Children with Munchausen syndrome characterized by factitious fever are often treated in other departments other than psychiatry and psychology. Doctors in these departments do not know enough about Munchausen syndrome. Therefore, it is difficult for children to get correct diagnosis and treatment timely, and the incidence rate may be underestimated.
Objective：To summarize the clinical characteristics of children with Munchausen syndrome manifested as factitious fever , and to improve the understanding.
Design：Case series report.
Methods：Retrospective analysis was performed for consecutive hospitalized cases diagnosed with Munchausen syndrome presenting with factitious fever from January 2022 to January 2024 at nephrology, rheumatology and immunology departments of Children's Hospital of Jiangnan University, Children's Medical Center of Taihe Hospital Affiliated to Hubei Medical University, and the Rheumatology Department of Anhui Children's Hospital. Clinical data were collected from the management information system of each hospital, including gender, age at onset, disease course, medical history, characteristics of the fever, physical examination, and auxiliary examination.
Main outcome measures：Characteristics of the fever.
Results：Ten cases were included in this analysis, all of whom were girls with an onset age of 12 (10-14) years and a disease course of 6.3 (1-18) months. The average number of outpatient visits was 8 (4-12) times, the average number of hospitalizations was 3.5 (2-5) times, and the average number of hospitals visited was 3.5 (3-5). All had a history of repeated glucocorticoid and antibiotic treatments without efficacy. The body temperature of all patients rose to high fever (39.0-40.2°C) within a short period and returned to normal within about 5 minutes. Six cases occasionally experienced dizziness, including two with headaches and one with abdominal pain. There was no shivering or chills before the fever, and the timing was irregular. There was no sweating reaction when the temperature returned to normal. There were no changes in skin temperature, pulse, heart rate, or respiratory rate before and after the fever. Mental state and appetite were normal. Three cases had a slight increase in weight, while the others showed no decrease. No positive signs were found. Auxiliary examinations were all normal. Four cases were from single-parent families, five had long-term parental conflicts, and one was a left-behind child. All were referred to the psychology department for intervention, with a follow-up period of 8 (5-12) months. No similar fever episodes or other symptoms were observed during follow-up.
Conclusion：Munchausen syndrome presenting with factitious fever is more common in female children/adolescents, often seeking treatment at multiple hospitals repeatedly. The body temperature can reach high fever within 3-8 minutes and return to normal in about 5 minutes. There are no typical pathophysiological changes during episodes, and laboratory and auxiliary examination results are normal. Despite a prolonged disease course, there are no changes in disease status.
Background：Gestational diabetes mellitus (GDM) is one of the common metabolic disorders of pregnancy, and the hyperglycemia that occurs in the mother during pregnancy may affect the fetal immune system and lung development, leading to a greater susceptibility to asthma in children. However, in traditional epidemiologic cohort studies, the existing findings may be affected by confounding factors, and there is a need to further explore the causal association between GDM and childhood asthma and develop more effective prevention and management strategies.
Objective：To investigate whether there is a causal association between gestational diabetes mellitus (GDM) and childhood asthma in offspring by using a two-sample Mendelian randomization (TSMR) subgroup, and to provide recommendations for clinical management.
Design：Case-control study.
Methods：Utilizing the most recent and largest sample size genome-wide association study (GWAS) summary data, we selected genetic loci closely related to GDM and childhood asthma, using single nucleotide polymorphisms (SNPs) as instrumental variables, GDM as the exposure factor and childhood asthma as the outcome variable, to analyze the causal relationship between GDM and childhood-onset asthma. A P value (P<5.0×10-7) was set for the screening of instrumental variables, and in order to avoid linkage disequilibrium (LD) bias, the LD of significant SNPs associated with GDM had to satisfy the conditions: r2<0.001 and a genetic distance of 10, 000 kb. SNPs with the F-statistics<10 were excluded. The inverse variance weighted(IVW) method, alongside weighted median and MR-Egger regression methods, were used for TSMR analysis to infer causality. Sensitivity analyses were performed in parallel using MR-Egger regression, Cochran's Q-test, and the "leave-one-out" method. Statistical analyses were performed using R 4.3.1 software package TwoSampleMR with a significance level of α=0.05.
Main outcome measures：Association between GDM and childhood asthma.
Results：In the Finnish GWAS summary data, the GDM dataset included 6,033 cases and 110,330 controls, totaling 16,379,684 SNPs. The asthma dataset included 3,025 cases and 135,449 controls, with a total of 16,379,865 SNPs. According to the screening criteria for research instrumental variables, 10 SNPs were selected as instrumental variables, all with F-statistics>10. IVW results indicated a causal relationship between GDM and increased risk of childhood asthma (OR=1.15, 95%CI: 1.01-1.32, P=0.039). Cochran's Q test showed no heterogeneity among the included SNPs (P> 0.05). MR-Egger regression's intercept was -0.013 (P=0.68), indicating a low likelihood of pleiotropic effects. Sensitivity analysis using the leave-one-out method did not reveal any SNPs with a strong influence on the results, suggesting stability in the causal relationship. Funnel plot analysis demonstrated that the causal effect of GDM on childhood asthma was symmetrically distributed when using individual SNPs as instrumental variables.
Conclusion：There is a positive causal association between GDM and childhood-onset asthma.
