The Efficacy and Safety of Epicutaneous Immunotherapy for Allergic Diseases: A Systematic Review and Meta-Analysis.

OBJECTIVES: To systematically review the effect and safety of epicutaneous immunotherapy (EPIT) for allergic diseases. METHODS: We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, CQ VIP Database, Wanfang Data, and international trial register from their inception to July 29, 2019, without language restrictions, for randomized controlled trials (RCTs) that compared EPIT versus no EPIT for allergen-triggered allergic reactions. We assessed certainty of evidence by the GRADE approach. RESULTS: Ten RCTs with 1,085 participants (aged from 10 months to 65 years) comparing EPIT with placebo for peanut, cow milk, or grass-pollen allergy met the eligibility criteria. A substantial benefit in terms of desensitization in EPIT group was more likely for peanut or cow milk protein allergy (risk ratio [RR] 2.34, 95% CI 1.69-3.23; I2 = 0%; high certainty evidence). EPIT increased local-treatment-related adverse events (L-TRAE; RR 1.56, 95% CI 1.03-2.36; I2 = 82%; moderate certainty evidence). But there were no significantly increased risk of any TRAEs (low certainty evidence) or systemic-TRAEs (S-TRAEs; very low certainty evidence) in EPIT group. The incidence rate of serious AEs, the use of rescue medications, and anaphylactic reactions stratified by organ systems including skin and mucosa, eyes and upper respiratory, lower respiratory, and gastrointestinal system in EPIT group were similar to placebo group. In subgroup analysis, desensitization of EPIT was significantly effective in peanut allergy (RR 2.29, 95% CI 1.64-3.21; I2 = 0%) and children <12 years (RR 2.85, 95% CI 1.92-4.24; I2 = 0%) with high certainty evidence. Only epicutaneous grass-pollen immunotherapy significantly increased the risk of S-TRAE (RR 4.65, 95% CI 1.10-19.64; I2 = 0%). CONCLUSION: The systematic review suggests that EPIT might induce desensitization in peanut allergy and an increased risk of local AEs. These findings should be interpreted with caution owing to the limited study and heterogeneity. More data in the older (children ≥12 years and adults) and other allergic diseases are needed.

[Current status of initial diagnosis of speech sound disorder in a child healthcare clinic].

OBJECTIVE: To investigate the understanding of speech sound disorder (SSD) among child health practitioners. METHODS: The clinical data of 506 children with an initial diagnosis of SSD from January 2017 to May 2019 were retrospectively analyzed. RESULTS: Of the 506 SSD children, 90.5% had a description of developmental behavior in their medical records; 97.6% received a developmental-behavioral evaluation, mostly intellectual and developmental screening tests, which were given to 95.8% (485/506) of the total children. A total of 116 (22.9%) children also had neurodevelopmental disorders, commonly presenting with language disorder, global developmental delay, and intellectual disability; however, 53 (45.7%) of the 116 children had no history records of such abnormal developmental behavior. The incidence of neurodevelopmental disorders was significantly higher in the children with abnormal hearing reported by their families than in the children with normal hearing reported by their families (P<0.001). The children with abnormal response to sound stimulation on physical examination had significantly more frequent neurodevelopmental disorders than those with normal response to sound stimulation (P<0.05). Among the 506 children with SSD, hearing condition was ignored in 33.2% in history records, and in 31.2% on physical examination. Ninety-two children (18.2%) completed the diagnostic hearing test, 12% (11/92) of whom were diagnosed with hearing loss. Of the 11 children with hearing loss, three had passed a hearing screening, three had family-reported normal hearing, and seven had normal response to sound stimulation on physical examination. CONCLUSIONS: SSD is frequently comorbid with neurodevelopmental disorders in children. Children's communication performance is a key to the diagnosis of neurodevelop-mental disorders. It's necessary to the diagnosis of SSD to perform a medical history collection about neuropsychological development and a developmental-behavior evaluation. There is a high proportion of children with SSD receiving the developmental-behavioral evaluation, suggesting that child health practitioners pay close attention to the neuropsychological development of SSD children, but mostly, the evaluation merely involves intellectual developmental screening tests. The detection rate of hearing loss in children with SSD is high. However, child health practitioners underestimate this problem, and have an insufficient understanding of the importance of the diagnostic hearing test. The diagnostic hearing test should be the preferred recommendation for assessing hearing ability rather than past hearing screening results or children's response to sound stimulation in life scenes.

Clinical significance of IgM and C3 deposition in children with primary immunoglobulin A nephropathy.

BACKGROUND: Mesangial IgM and C3 deposition is commonly observed in patients with primary immunoglobulin A nephropathy (IgAN), but its characteristics and prognosis have rarely been reported. The aim of this study was to investigate the relationship between combined mesangial IgM and C3 deposition and disease progression in children with IgAN. METHODS: One hundred sixteen children diagnosed with IgAN between 2016 and 2020 were selected. Renal biopsies were scored by Oxford classification including the presence of mesangial hypercellularity, endocapillary hypercellularity, segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis and crescents. The primary renal outcome was an event of either ≥ 50% reduction of eGFR from the baseline value or the onset of end-stage renal disease within the follow-up period. Cox regression analysis was performed to examine the effect of the combined mesangial IgM and C3 deposition on renal outcomes. RESULTS: Forty-seven (40.52%) patients presented combined mesangial IgM and C3 deposition. Compared with children without combined IgM and C3 deposition, children with combined IgM and C3 deposition presented higher mesangial hypercellularity, endocapillary hypercellularity and cresentic lesions in kidney biopsies, and higher prevalence of renal dysfunction (19.15% versus 2.90%; P = 0.007). Renal outcome was also significantly worse as revealed by Kaplan-Meier curves (P = 0.0034). Multivariable Cox analysis identified tubular atrophy/interstitial fibrosis lesions [hazard ratio (HR) 14.843, 95% CI, 3.497-62.997, P < 0.001] and intensity of IgM deposition (HR 2.838, 95% CI, 1.321-6.094, P = 0.007) as independent risk factors for poor renal function. CONCLUSIONS: Combined mesangial IgM and C3 deposition was associated with unfavorable histopathological features. Mesangial IgM deposition was an independent risk factor for poor renal outcomes in children with primary IgAN.

Efficacy and Safety of Vadadustat for Anemia in Patients With Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

Background: Vadadustat is a novel drug for treating anemia patients with chronic kidney disease (CKD), but its effect and safety remain uncertain. This study aimed to summarize the evidence for vadadustat in the treatment of CKD patients with anemia. Methods: PubMed, Ovid Medline, Embase, Cochrane CENTRAL, Wanfang Data, China National Knowledge Infrastructure and an international trial register were searched from their inception to June 2021 for randomized controlled trials (RCTs) comparing the efficacy and safety of vadadustat to those of placebo or erythropoiesis-stimulating agents (ESAs) in treating anemia in CKD patients. Data were pooled in a meta-analysis, with results expressed as the mean difference for continuous outcomes and relative risk for categorical outcomes with 95% confidence intervals (95% CIs). The certainty of evidence was rated according to Cochrane methods and the GRADE approach. Results: Ten RCTs comparing vadadustat with placebo (4 RCTs) or darbepoetin alfa (6 RCTs) were included (n = 8,438 participants). Compared with placebo, vadadustat increased the hemoglobin (Hb) response rate (risk ratio 5.27; 95% CI: 2.69 to 10.31; p < 0.001; high certainty of evidence) and Hb level from baseline (∆Hb) (mean difference (MD) 1.28; 95% CI: 0.83 to 1.73; p < 0.001; low certainty of evidence). Compared with placebo or darbepoetin alfa, vadadustat decreased hepcidin (MD -36.62; 95% CI: -54.95 to -18.30; p < 0.001) and ferritin (MD -56.24; 95% CI: -77.37 to -35.11; p < 0.001) levels and increased iron-binding capacity (MD 24.38; 95% CI: 13.69 to 35.07; p < 0.001), with a low to moderate certainty of evidence. Moderate to high certainty evidence suggested that compared with placebo or darbepoetin alfa, vadadustat significantly increased the risk of nausea and diarrhea but did not significantly increase the risk of serious adverse events, especially all-cause mortality, cardiac events and nonfatal stroke. Conclusion: Vadadustat may safely improve Hb levels and promote iron utilization in CKD patients with anemia without increasing the incidence of serious adverse events.

High-flow nasal cannula therapy for children with bronchiolitis: a systematic review and meta-analysis.

OBJECTIVES: To review the effects and safety of high-flow nasal cannula (HFNC) for bronchiolitis. METHODS: Six electronic databases including PubMed, EMBASE, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, CQ VIP Database and Wanfang Data were searched from their inception to 1 June 2018. Randomised controlled trials (RCTs) which investigated the effects of HFNC versus other forms of oxygen therapies for bronchiolitis were included. RESULTS: Nine RCTs with 2121 children met the eligibility criteria. There was no significant difference in length of stay in hospital (LOS), length of oxygen supplementation (LOO), transfer to intensive care unit, incidence of intubation, respiratory rate, SpO2 and adverse events in HFNC group compared with standard oxygen therapy (SOT) and nasal continuous positive airway pressure (nCPAP) groups. A significant reduction of the incidence of treatment failure (risk ratio (RR) 0.50, 95% CI 0.40 to 0.62, p<0.01) was observed in HFNC group compared with SOT group, but there was a significant increase of the incidence of treatment failure (RR 1.61, 95% CI 1.06 to 2.42, p0.02) in HFNC group compared with nCPAP group. In subgroup analysis, LOS was significantly decreased in HFNC group compared with SOT group in low-income and middle-income countries. CONCLUSION: The systematic review suggests HFNC is safe as an initial respiratory management, but the evidence is still lacking to show benefits for children with bronchiolitis compared with SOT or nCPAP.