Hospitalization costs of pediatric community-acquired pneumonia in Shanghai / 中华儿科杂志

Objective: To investigate the epidemiology and hospitalization costs of pediatric community-acquired pneumonia (CAP) in Shanghai. Methods: A retrospective case summary was conducted on 63 614 hospitalized children with CAP in 59 public hospitals in Shanghai from January 2018 to December 2020. These children's medical records, including their basic information, diagnosis, procedures, and costs, were extracted. According to the medical institutions they were admitted, the patients were divided into the children's hospital group, the tertiary general hospital group and the secondary hospital group; according to the age, they were divided into <1 year old group, 1-<3 years old group, 3-<6 years old group, 6-<12 years old group and 12-18 years old group; according to the CAP severity, they were divided into severe pneumonia group and non-severe pneumonia group; according to whether an operation was conducted, the patients were divided into the operation group and the non-operation group. The epidemiological characteristics and hospitalization costs were compared among the groups. The χ2 test or Wilcoxon rank sum test was used for the comparisons between two groups as appropriate, and the Kruskal-Wallis H test was conducted for comparisons among multiple groups. Results: A total of 63 614 hospitalized children with CAP were enrolled, including 34 243 males and 29 371 females. Their visiting age was 4 (2, 6) years. The length of stay was 6 (5, 8) days. There were 17 974 cases(28.3%) in the secondary hospital group, 35 331 cases (55.5%) in the tertiary general hospital group and 10 309 cases (16.2%) in the children's hospital group. Compared with the hospitalizations cases in 2018 (27 943), the cases in 2019 (29 009) increased by 3.8% (1 066/27 943), while sharply declined by 76.2% (21 281/27 943) in 2020 (6 662). There were significant differences in the proportion of patients from other provinces and severe pneumonia cases, and the hospitalization costs among the children's hospital, secondary hospital and tertiary general hospital (7 146 cases(69.3%) vs. 2 202 cases (12.3%) vs. 9 598 cases (27.2%), 6 929 cases (67.2%) vs. 2 270 cases (12.6%) vs. 9 397 cases (26.6%), 8 304 (6 261, 11 219) vs. 1 882 (1 304, 2 796) vs. 3 195 (2 364, 4 352) CNY, χ2=10 462.50, 9 702.26, 28 037.23, all P<0.001). The annual total hospitalization costs of pediatric CAP from 2018 to 2020 were 110 million CNY, 130 million CNY and 40 million CNY, respectively. And the cost for each hospitalization increased year by year, which was 2 940 (1 939, 4 438), 3 215 (2 126, 5 011) and 3 673 (2 274, 6 975) CNY, respectively. There were also significant differences in the hospitalization expenses in the different age groups of <1 year old, 1-<3 years old, 3-<6 years old, 6-<12 years old and 12-18 years old (5 941 (2 787, 9 247) vs. 2 793 (1 803, 4 336) vs. 3 013 (2 070, 4 329) vs. 3 473 (2 400, 5 097) vs. 4 290 (2 837, 7 314) CNY, χ2=3 462.39, P<0.001). The hospitalization cost of severe pneumonia was significantly higher than that of non-severe cases (5 076 (3 250, 8 364) vs. 2 685 (1 780, 3 843) CNY, Z=109.77, P<0.001). The cost of patients who received operation was significantly higher than that of whom did not (10 040 (4 583, 14 308) vs. 3 083 (2 025, 4 747) CNY, Z=44.46, P<0.001). Conclusions: The number of children hospitalized with CAP in Shanghai decreased significantly in 2020 was significantly lower than that in 2018 and 2019.The proportion of patients from other provinces and with severe pneumonia are mainly admitted in children's hospitals. Hospitalization costs are higher in children's hospitals, and also for children younger than 1 year old, severe cases and patients undergoing operations.

Efficacy and safety of salmeterol/fluticasone compared with montelukast alone (or add-on therapy to fluticasone) in the treatment of bronchial asthma in children and adolescents: a systematic review and meta-analysis / 中华医学杂志(英文版)

BACKGROUND@#Despite the recommendation of inhaled corticosteroids (ICSs) plus long-acting beta 2-agonist (LABA) and leukotriene receptor antagonist (LTRA) or ICS/LTRA as stepwise approaches in asthmatic children, there is a lack of published systematic review comparing the efficacy and safety of the two therapies in children and adolescents aged 4 to 18 years. This study aimed to compare the safety and efficacy of salmeterol/fluticasone (SFC) vs. montelukast (MON), or combination of montelukast and fluticasone (MFC) in children and adolescents aged 4 to 18 years with bronchial asthma.@*METHODS@#A systematic search was conducted in MEDLINE, EMBASE, the Cochrane Library, China BioMedical Literature Database, Chinese National Knowledge Infrastructure, VIP Database for Chinese Technical Periodical, and Wanfang for randomized controlled trials (RCTs) published from inception to May 24, 2021. Interventions are as follows: SFC vs. MON, or combination of MFC, with no limitation of dosage or duration. Primary and secondary outcome measures were as follows: the primary outcome of interest was the risk of asthma exacerbation. Secondary outcomes included risk of hospitalization, pulmonary function, asthma control level, quality of life, and adverse events (AEs). A random-effects (I2 ≥ 50%) or fixed-effects model (I2 < 50%) was used to calculate pooled effect estimates, comparing the outcomes between the intervention and control groups where feasible.@*RESULTS@#Of the 1006 articles identified, 21 studies met the inclusion criteria with 2643 individuals; two were at low risk of bias. As no primary outcomes were similar after an identical treatment duration in the included studies, meta-analysis could not be performed. However, more studies favored SFC, instead of MON, owing to a lower risk of asthma exacerbation in the SFC group. As for secondary outcome, SFC showed a significant improvement of peak expiratory flow (PEF)%pred after 4 weeks compared with MFC (mean difference [MD]: 5.45; 95% confidence interval [CI]: 1.57-9.34; I2 = 95%; P = 0.006). As for asthma control level, SFC also showed a higher full-controlled level (risk ratio [RR]: 1.51; 95% CI: 1.24-1.85; I2 = 0; P < 0.001) and higher childhood asthma control test score after 4 weeks of treatment (MD: 2.30; 95% CI: 1.39-3.21; I2 = 72%; P < 0.001) compared with MFC.@*CONCLUSIONS@#SFC may be more effective than MFC for the treatment of asthma in children and adolescents, especially in improving asthma control level. However, there is insufficient evidence to make firm conclusive statements on the use of SFC or MON in children and adolescents aged 4 to 18 years with asthma. Further research is needed, particularly a combination of good-quality long-term prospective studies and well-designed RCTs.@*PROSPERO REGISTRATION NUMBER@#CRD42019133156.

Changes of the hemodynamics and extravascular lung water after different-volume fluid resuscitation in a piglet model of endotoxic shock / 中华儿科杂志

<p><b>OBJECTIVE</b>Practice recommendations have evolved, and consensus now exists among leading organizations such as the American College of Critical Care Medicine (ACCM) and Surviving Sepsis Campaign that fluid infusion is best initiated with boluses of 20 ml/kg, commonly requires 40-60 ml/kg but can be as much as 200 ml/kg if the liver is not enlarged and/or rales are not heard. The present study aimed to investigate and compare the changes of the hemodynamics and extravascular lung water after higher volume fluid resuscitation in a piglet model of endotoxic shock.</p><p><b>METHOD</b>Twenty piglets were used for establishing animal models of endotoxic shock by intravenous infusing lipopolysaccharide (LPS). The experimental animals were divided into three groups according to the volume infused during the resuscitation. The three groups received different volume of saline in less than an hour after endotoxic shock. By the PiCCO plus system, we investigated the changes of hemodynamics and extravascular lung water.</p><p><b>RESULT</b>After fluid resuscitation, global end diastolic volume inder, (GEDI) and intrathoracic blood volume index, (ITBI) markedly increased in the group of 80 ml/kg and 120 ml/kg, but there was no change in the group of 40 ml/kg. GEDI: Fifteen min after fluid resuscitation R1 was (261 ± 64) ml/m(2), R2 (457 ± 124) ml/m(2), R3 (413 ± 148) ml/m(2), 4 h R1 (251 ± 68) ml/m(2), R2 (422 ± 70) ml/m(2), R3 (470 ± 160) ml/m(2); ITBI: Fifteen min after fluid resuscitation R1 was (335 ± 69) ml/m(2), R2 (550 ± 179) ml/m(2), R3 (520 ± 183) ml/m(2), 4 h R1 (314 ± 84) ml/m(2), R2 (534 ± 96) ml/m(2), R3 (594 ± 200) ml/m(2) (R1 vs. R2 vs. R3, F = 26.373, P < 0.05; R1 vs. R2, R1 vs. R3, P < 0.05; R2 vs. R3, P > 0.05). CI of all three groups significantly decreased when the models were established. After fluid resuscitation, the base level was maintained in the group of 80 ml/kg and 120 ml/kg, but it was under the basic level in the group of 40 ml/kg.Fifteen min after fluid resuscitation R1 was (4.5 ± 0.7) L/(min·m(2)), R2 (6.4 ± 2.2) L/(min·m(2)), R3 (5.5 ± 0.7) L/(min·m(2)), 4 h R1 (4.1 ± 1.0) L/(min·m(2)), R2 (5.2 ± 0.9) L/(min·m(2)), R3 (5.1 ± 0.8) L/(min·m(2)). There was no significant difference in CI between these two groups (P > 0.05).ELWI of the group of 80 ml/kg and 120 ml/kg were still higher than that of the group of 40 ml/kg, 15 min after fluid resuscitation R1 was (19.2 ± 8.6) ml/kg, R2 (29.2 ± 5.5) ml/kg, R3 (23.4 ± 8.2) ml/kg, 4 h R1 (18.3 ± 6.5) ml/kg, R2 (23.8 ± 2.6) ml/kg, R3 (21.4 ± 3.9) ml/kg, but there was no significant difference in ELWI among the groups (P > 0.05).</p><p><b>CONCLUSION</b>Resuscitation with higher volume of fluid infusion in the early stage of endotoxic shock was more efficient to increase the preload and maintain the cardiac output at the baseline level, and might reduce the need for vasoactive agents. Meanwhile, resuscitation with higher volume of fluid in the early stage of endotoxic shock did not sharply increase the extravascular lung water.</p>

1,25-(OH)2D3 inhibits lipopolysaccharide-induced expression of interleukin-13 and interleukin-17 in cord blood CD4+T cells / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the effect of 1,25-(OH)2D3 on lipopolysaccharide (LPS)-induced expression of interleukin-13 (IL-13) and interleukin-17 (IL-17) in cord blood CD4(+)T cells, providing theoretical basis for clinical reasonable application of vitamin D and prevention of asthma and allergic diseases.</p><p><b>METHODS</b>Mononuclear cells (MNCs) were isolated from umbilical cord blood (50 mL) of 12 normal eutocia term newborns by gravity centrifugation. CD4(+)T cells were isolated using magnetic beads, which was cultured with following three kinds of stimulus for 72 hours: natural state (blank group), LPS (10 μg/mL)stimulation alone and LPS(10 μg/mL)+1,25-(OH)2D3 (10(-8) mmol/L)stimulation. Levels of IL-13 and IL-17 in the culture supernatant and mRNA expressions in cord blood CD4(+)T cells were detected using ELISA and real Time-PCR respectively.</p><p><b>RESULTS</b>Compared with the blank group, levels of IL-13 and IL-17 in the culture supernatant and mRNA expression of IL-13 and IL-17 in the cord blood CD4(+)T cells increased in the LPS stimulation alone group (P<0.01). When co-stimulation of 1,25-(OH)2D3 with LPS, levels of IL-13 and IL-17 in the culture supernatant and mRNA expression of IL-13 and IL-17 in the cord blood CD4(+)T cells decreased compared with LPS-stimulated alone group (P<0.05), but remained higher than the blank group (P<0.01).</p><p><b>CONCLUSIONS</b>LPS can promote expression of IL-13 and IL-17 in cord blood CD4(+)T cells. 1,25-(OH)2D3 inhibits the expression of IL-13 and IL-17, suggesting that vitamin D intake may provide protective effects in the development of atopy-predisposing immune responses in early life.</p>

Effect of 1,25-(OH)2D3 supplementation during gestation and lactation on TGF-β1 and Smad3 expression in lungs of rat offspring with asthma / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the effect of 1,25-(OH)2D3 supplementation during gestation and lactation on TGF-β1 and Smad3 expression in lungs of rat offspring with asthma.</p><p><b>METHODS</b>Thirty-two female Wistar rats were randomly divided into four groups: low-, medium- and high-dose 1,25-(OH)2D3 supplementation and control groups (n=8 each). From the 7th day of gestation, the three 1,25-(OH)2D3 supplementation groups were administered with 2,10 and 20 μg/mL of 1,25-(OH)2D3 respectively every other day until weaning (rat offspring: 21 days old). The control group received normal saline instead. Then, bronchial asthma was induced in rat offspring from the 4 groups. The protein and mRNA expression of TGF-β1 and Smad3 in the lung tissue was measured by immunochemistry and RT-PCR.</p><p><b>RESULTS</b>Eosinophil cell infiltration and airway inflammation decreased in rat offspring from the low- and medium-dose 1,25-(OH)2D3 groups, but increased in rat offspring of the high-dose 1,25-(OH)2D3 group compared with the control group. Immunohistochemistry of lung tissues showed that the expression of TGF-β1 protein and pSmad3 decreased in rat offspring from the low- and medium-dose 1,25-(OH)2D3 groups (P<0.05), but increased significantly in rat offspring from the high-dose 1,25-(OH)2D3 group compared with the control group (P<0.05). PCR showed that the expression of TGF-β1 and Smad3 mRNA in the lung tissue decreased in rat offspring from the low- and medium-dose 1,25-(OH)2D3 groups (P<0.05), but increased significantly in rat offspring from the high-dose 1,25-(OH)2D3 group compared with the control group (P<0.05).</p><p><b>CONCLUSIONS</b>1,25-(OH)2D3 supplementation plays a role in regulating the immune system in asthmatic rats. Its mechanism may be associated with regulation of the expression of TGF-β/Smad signal pathway-related proteins through the vitamin D receptor signal pathway.</p>

Effect of montelukast sodium on TGF-beta(1) of peripheral blood mononuclear cells from children with mild persistent asthma / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the role of transforming growth factor beta(1) (TGF-beta(1)) in the pathogenesis of bronchial asthma in children and assess the effect of montelukast sodium (leukotriene receptor antagonist) on TGF-beta(1) levels.</p><p><b>METHOD</b>A 12 weeks single-blind, placebo-controlled trail was conducted in 60 children with mild persistent asthma [aged 5 - 14 years, mean (7.10 ± 0.27) years]. Patients were randomly assigned to receive 5 mg montelukast sodium or placebo for 12 weeks. And 30 healthy control children [aged 5 - 14 years, mean (7.60 ± 0.25) years] were also recruited in this study from Sep. 2009 to Sep. 2010. Clinical effects and pulmonary function were evaluated before and 12 weeks after treatment. The mRNA expression of TGF-beta(1) in the peripheral blood mononuclear cells was detected by using RT-PCR with beta-actin as internal control. The percentage of the different subpopulations of Foxp(3)(+)CD4(+) T cells was assayed by 4-color flow cytometric analysis system and the levels of TGF-beta(1) in plasma by ELISA.</p><p><b>RESULT</b>(1) The basic characteristics between asthma group and healthy group had no significant difference. (2) Following treatment, there was significant increase in pulmonary function in asthmatic children. The effect in the group of montelukast sodium was superior to that of placebo group (P < 0.05). (3) The serum expression of TGF-beta(1) in asthmatic children was lower than that in control group (q = 20.01, P < 0.01); after 12 weeks of treatment, the mean expression of TGF-beta(1) was (20.03 ± 1.14) ng/L for montelukast sodium group and (12.10 ± 3.91) ng/L for placebo group (P < 0.05). (4) The mRNA expression of TGF-beta(1) in asthma children was lower than that in control group (0.31 ± 0.07 vs 0.61 ± 0.2, q = 8.97, P < 0.05); after 12 weeks of treatment, the mean expression of TGF-beta(1) was (0.46 ± 0.13) for montelukast sodium group and (0.32 ± 0.04) for placebo group (q = 8.25, P < 0.05). (5) It was shown that the total Foxp(3)(+)CD(4)(+) cell percentage was higher in asthmatic children than those of control group (8.30% ± 1.30% vs 6.05% ± 1.80%); the proportion of the three subpopulation was different between groups: CD(45) RA(+)Foxp(3)(lo) was higher in asthmatic group (4.60% ± 1.04% vs 3.27% ± 1.03%) and CD(45) RA(-)Foxp(3)(hi) was lower (0.75% ± 0.13% vs 0.93% ± 0.26%); while CD(45) RA(-)Foxp(3)(lo) had no significant difference among groups (2.40% ± 0.83%, 1.61% ± 1.10%). After 12 weeks of treatment, the percentage of CD(45) RA(-)Foxp(3)(hi) was increased in montelukast sodium group compared with placebo group (1.16% ± 0.24% vs 0.89% ± 0.22%). (6) Spearman correlation analysis revealed that TGF-beta(1) levels had no correlation with the levels of pulmonary function.</p><p><b>CONCLUSION</b>The protein and mRNA expression level of TGF-beta(1) was low in those asthmatic children. Insufficient secretion of TGF-beta(1) and the defective ability of activated regulatory T cells (CD(45) RA(-)Foxp(3)(hi)) in Foxp(3)(+)CD(4)(+) Treg cells might play an important role in pathogenesis of asthma. Up-regulation of the expression of TGF-beta(1) and induction of the expression of CD(45) RA(-)Foxp(3)(hi) in Foxp(3)(+)CD(4)(+)Treg cells by montelukast sodium may be one of the immunomodulatory mechanisms in asthma.</p>

Effect of vitamin D supplementation in early life on the expression of interleukin-10 and intercellular adhesion molecule-1 in rat asthma model / 中华儿科杂志

<p><b>OBJECTIVE</b>To explore the effect and mechanism of vitamin D supplementation in early life on rat asthma model.</p><p><b>METHOD</b>Thirty two sex-mature, female Wistar rats were randomly divided into a control group (n = 8), a low dose group (n = 8), a medium dose group (n = 8) and a high dose group (n = 8). From the seventh day of pregnancy on, the rats in each group were given different doses of vitamin D by intragastric administration, until the offspring rats were 21 days old. The rats in the control group were fed with DMSO-PBS. After the offsprings were weaned, 8 rats were randomly selected from each group. The number of male and female rats was equal. The rats were sensitized to ovalbumin (OVA) and challenged with aerosol OVA to establish the asthma model. The lung tissues were examined for pathologic changes after HE staining. ELISA was used to determine the concentrations of IL-10 in serum and BALF. Immunohistochemical staining methods were used to measure the expression of intercellular adhesion molecule-1 (ICAM-1) in lung tissues.</p><p><b>RESULT</b>(1) Pathologic changes of lung tissues: compared with the control group, light microscope (LM) showed that eosinophil cells infiltration and the airway inflammation decreased in the low dose and medium dose groups, but increased in the high dose group. (2) The concentrations of IL-10 in serum and BALF: In serum, compared with the control group [(18.7 +/- 4.7) pg/ml], the concentrations of IL-10 in the low dose group [(30.2 +/- 2.8) pg/ml, P < 0.05] and the medium dose group [(51.5 +/- 6.6) pg/ml, P < 0.05] were significantly increased. And the IL-10 level of medium dose group was higher than that of the low dose group (P < 0.05). In BALF, compared with the control group [(59.1 +/- 14.4) pg/ml], the concentrations of IL-10 in the medium dose group [(90.0 +/- 14.3) pg/ml, P < 0.05] was significantly increased. There were no significant changes in the low dose group [(58.1 +/- 3.4) pg/ml, P > 0.05], whereas in the high dose group [(45.3 +/- 6.5) pg/ml, P < 0.05] the level significantly decreased. (2) The expression of ICAM-1 in lung tissues: compared with the control group, there were no significant changes in the low dose group (P > 0.05). The expression of ICAM-1 was significantly decreased in the medium dose group (P < 0.05). In the high dose group, the expression of ICAM-1 was significantly increased (P > 0.05).</p><p><b>CONCLUSION</b>Adequate intervention with 1,25(OH)2D3 in the early life could alleviate the inflammation in the lung tissues, reduces eosinophil cell infiltration in rat asthma model. However, overdose might play a detrimental role. Its mechanism may be associated with the effect of 1,25(OH)2D3 on IL-10 secretion and the expression of ICAM-1.</p>

Application of Color Doppler Ultrasonography by Bed Side in the Early Diagnosis of Hypoxic-Ischemic Encephalopathy in Full Term Neonates / 实用儿科临床杂志

Objective To explore the value of color doppler ultrasonography by bed side in the early diagnosis of HIE in full term neonates.Methods The changes of cerebral parenchymal and cerebral arterial blood stream parameter on 35 cases of neonates clinically diagnosed HIE of mild and moderate degree and 40 cases of normal newborns on the 24,48 and 72 hours after birth were observed by color doppler ultrasonography by bed side.Results 1.The cerebral parenchyma was even echo in normal newborns,but it was maldistributed and reinforced in mild asphyxia neonates and it was more serious in moderate degree.The echo of cerebral parenchyma in mild degree was near normal in 48 hours after birth,while the echo of cerebral parenchyma in moderate degree was still maldistributed and reinforced in 48 and 72 hours after birth.2.There was obvious changes in the cerebral arterial blood stream parameter and hemodynamics of the asphyxia newborns compared with normals.The systolic peak velocity(Vs)and end diastolic velocity(Vd)of the cerebral arteries in mild and moderate degree were obviously lower than that of control group in 24,48 hours after birth(Pa0.05).3.Resistance index(RI)of the cerebral arteries in mild and moderate degree were higher than that of control group in 24,48 hours after birth(Pa0.05).Conclusion Color doppler ultrasonography by bed side is a convenient,noninvasive method for diagnosing HIE.