Endoscopic posterior cricoid split and rib grafting (EPCS/RG) for the treatment of posterior laryngeal stenosis has some advantages over traditional open approaches, including improved surgical ...visualization and decreased morbidity. Many pediatric patients who undergo EPCS/RG have indwelling tracheostomy, which may be utilized to help manage the airway perioperatively. The role for de novo tracheostomy placement at the time of EPCS/RG is less clear. We present three cases from a tertiary children's hospital in which EPCS/RG was safely performed without tracheostomy. For patients with posterior laryngeal stenosis but without tracheostomy, EPCS/RG with endotracheal tube stenting might be a safe option. Laryngoscope, 131:E2599–E2602, 2021
Many countries have started to reopen economic activities after the COVID-19 pandemic; however, due to the disease's long incubation period and high infectivity, social distancing remains an ...essential measure despite the start of vaccinations. It is therefore necessary to understand the changes in human mobility from the outbreak's initiation to deceleration to control the disease's transmission and revitalize the economy. This study suggests a methodology for investigating the changes in human mobility and their influencing factors using a case study of Seoul Metropolitan City, Korea. First, the changing patterns of human mobility were investigated based on mobile big data, including the acceleration and deceleration stages. The results showed that it varied by area and travel distance. Second, we clarified the influence of sociodemographic factors such as employee density and land use proportion on the change pattern of human mobility by applying a machine learning method. This finding implies that the effectiveness of policies such as social distancing can vary with sociodemographic factors. For example, areas with more real estate, public administration, and health care employees showed rapid recovery and faced a transmission risk by reopening economic activities. The suggested methodology can help understand human mobility and explore exit strategies.
Abstract
Background
In 2020, the European Medicines Agency approved infliximab subcutaneous (SC) for the treatment of inflammatory bowel disease. This new mode of infliximab administration will ...reduce outpatient visits and costs of intravenous (IV) administration. This article describes a budget impact analysis of introducing infliximab SC to the Big-5 European (E5) market (Germany, France, Italy, Spain and UK) for 5 years, from the healthcare payer’s perspective.
Methods
A prevalence-based budget impact model was developed to examine the financial impact of infliximab SC. “World with” versus “world without” infliximab SC scenarios were compared, including the potential administration costs of IV administration.
Results
Introducing infliximab SC in patients with Crohn’s disease (CD) for 5 years resulted in cost savings of €42.0 million in the UK, €59.4 million in Germany, and €46.4 million in France and Italy, but increased budget expenditure in Spain by €3.8 million. For ulcerative colitis (UC), cost savings of €42.7 million in the UK, €44.9 million in Germany, €44.3 million in France, and €53.0 million in Italy occurred, but with no savings in Spain for 5 years. Cost-savings per patient was calculated by diving the net budget saving by number of treatment eligible patients. Maximum and minimum saving per patient per year ranged between €38.25 and €575.74 in CD, both from Germany, and €105.06 (France) and €647.25 (Germany) in UC.
Conclusion
Healthcare payers in the UK, Germany, France, and Italy, but not in Spain, will make budget savings by using infliximab SC for the treatment of inflammatory bowel disease.
In 1968, OMEP established the
International Journal of Early Childhood
(IJEC)
.
In 50 years of publication, the journal has become an important platform for knowledge-sharing within the early ...childhood education community. Theory, policy, and practice change over time and content of the journal reflects the emergence of various topics. At the same time, the everlasting theme of ‘play’ has remained a common topic. The aim of this article is to examine the thematic trends in published topics, through a systematic analysis of the keywords used in IJEC articles, published from 1969 to 2017, in an analysis of 646 articles. Keyword network analysis can identify the relational structure between keywords, including identification of major research topics, and their relationships through the production of network images. The results showed distinct research trends in early childhood education across different periods. From an historical perspective, the findings demonstrate the changes and continuities in research topics published over time, not only as an academic analysis, but also as representing global directions of research in early childhood research, across countries with very different socio-cultural backgrounds.
There are limited comparative data for infliximab and vedolizumab in inflammatory bowel disease patients.
We conducted a systematic review and meta-analysis to compare the efficacy and safety of ...infliximab and vedolizumab in adult patients with moderate-to-severe Crohn's disease or ulcerative colitis.
We identified six eligible Crohn's disease and seven eligible ulcerative colitis trials that randomised over 1900 participants per disease cohort to infliximab or vedolizumab. In the Crohn's disease and ulcerative colitis cohorts, infliximab yielded better efficacy than vedolizumab for all analysed outcomes (CDAI-70, CDAI-100 responses, and clinical remission for Crohn's disease and clinical response and clinical remission for ulcerative colitis) during the induction phase, with non-overlapping 95% confidence intervals. In the maintenance phase, similar proportions of infliximab- or vedolizumab-treated patients achieved clinical response, clinical remission, or mucosal healing in both Crohn's disease and ulcerative colitis. For the safety outcomes, rates of adverse events, serious adverse events, and discontinuations due to adverse events were similar in infliximab- and vedolizumab-treated patients in both diseases. The infection rate was higher in infliximab for Crohn's disease and higher in vedolizumab when treating patients with ulcerative colitis. There was no difference between the treatments in the proportions of patients who reported serious infections in both indications.
Indirect comparison of infliximab and vedolizumab trials in adult patients with moderate-to severe Crohn's disease or ulcerative colitis demonstrated that infliximab has better efficacy in the induction phase and comparable efficacy during the maintenance phase and overall safety profile compared to vedolizumab.
The α-pyrone antibiotic myxopyronin (Myx) inhibits bacterial RNA polymerase (RNAP). Here, through a combination of genetic, biochemical, and structural approaches, we show that Myx interacts with the ...RNAP “switch region”—the hinge that mediates opening and closing of the RNAP active center cleft—to prevent interaction of RNAP with promoter DNA. We define the contacts between Myx and RNAP and the effects of Myx on RNAP conformation and propose that Myx functions by interfering with opening of the RNAP active-center cleft during transcription initiation. We further show that the structurally related α-pyrone antibiotic corallopyronin (Cor) and the structurally unrelated macrocyclic-lactone antibiotic ripostatin (Rip) function analogously to Myx. The RNAP switch region is distant from targets of previously characterized RNAP inhibitors, and, correspondingly, Myx, Cor, and Rip do not exhibit crossresistance with previously characterized RNAP inhibitors. The RNAP switch region is an attractive target for identification of new broad-spectrum antibacterial therapeutic agents.
This study aims to characterize the association between maternal pregnancy intention and socioemotional developmental outcomes in a Brazilian sample of preschool-aged children.
Data from children ...aged 4 to 5 years and their primary caregivers in Embu das Artes, a Brazilian municipality in the state of São Paulo, were collected in 2016. Maternal pregnancy intention was defined as intended or unintended, which was then further stratified as mistimed or unwanted. Outcomes included socioemotional developmental delay, internalizing and externalizing behaviors, and school readiness. We estimated risk ratios (RRs) for unadjusted and inverse-probability-weighted regression adjustment (IPWRA) analyses using 2-level (intended vs unintended) and 3-level (intended vs mistimed vs unwanted) exposure definitions.
Of 1,034 total mothers, 40.7% reported their pregnancy as intended, 46.0% as mistimed, and 13.4% as unwanted. In both unadjusted and IPWRA analyses comparing intended and unintended pregnancies, all associations failed to reach statistical significance. In the IPWRA analysis using the 3-level exposure definition, unwanted pregnancies were associated with higher risk of socioemotional developmental delay (RR = 1.14; 95% confidence interval CI, 1.01-1.28) and co-occurring internalizing and externalizing behaviors (RR = 1.11, 95% CI, 1.00-1.22), compared with intended pregnancies.
There was higher risk of poor child outcomes among unwanted compared with intended pregnancies, whereas mistimed pregnancies were not associated with poor outcomes. Further research using standardized definitions of pregnancy intention along with targeted interventions that increase access to family planning services and counseling for parents of children born after unintended pregnancies is needed.
In head and neck squamous cell carcinoma (HNSCC), mutations of p53 usually coexist with aberrant activation of NF-kappaB (NF-κB), other transcription factors and microRNAs, which promote tumor ...pathogenesis. However, how these factors and microRNAs interact to globally modulate gene expression and mediate oncogenesis is not fully understood. We devised a novel bioinformatics method to uncover interactive relationships between transcription factors or microRNAs and genes. This approach is based on matrix decomposition modeling under the joint constraints of sparseness and regulator-target connectivity, and able to integrate gene expression profiling and binding data of regulators. We employed this method to infer the gene regulatory networks in HNSCC. We found that the majority of the predicted p53 targets overlapped with those for NF-κB, suggesting that the two transcription factors exert a concerted modulation on regulatory programs in tumor cells. We further investigated the interrelationships of p53 and NF-κB with five additional transcription factors, AP1, CEBPB, EGR1, SP1 and STAT3, and microRNAs mir21 and mir34ac. The resulting gene networks indicate that interactions among NF-κB, p53, and the two miRNAs likely regulate progression of HNSCC. We experimentally validated our findings by determining expression of the predicted NF-κB and p53 target genes by siRNA knock down, and by examining p53 binding activity on promoters of predicted target genes in the tumor cell lines. Our results elucidating the cross-regulations among NF-κB, p53, and microRNAs provide insights into the complex regulatory mechanisms underlying HNSCC, and shows an efficient approach to inferring gene regulatory programs in biological complex systems.
Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has caused over 12 million infections and more than 550 000 deaths.1 Morbidity and mortality appear partly due to ...host inflammatory response.2 Despite rapid, global research, the effect of SARS‐CoV‐2 on the developing fetus remains unclear. Case reports indicate that vertical transmission is uncommon; however, there is evidence that placental and fetal infection can occur.3‐7 Placentas from infected patients show inflammatory, thrombotic, and vascular changes that have been found in other inflammatory conditions.8,9 This suggests that the inflammatory nature of SARS‐CoV‐2 infection during pregnancy could cause adverse obstetric and neonatal events. Exposure to intrauterine inflammation and placental changes could also potentially result in long‐term, multisystemic defects in exposed infants. This review will summarize the known literature on the placenta in SARS‐CoV‐2 infection, evidence of vertical transmission, and possible outcomes of prenatal exposure to the virus.
Accurate and efficient splicing of eukaryotic pre-mRNAs requires recognition by trans-acting factors of a complex array of cis-acting RNA elements. Here, we developed a generalized Bayesian network ...to model the coevolution of splicing cis elements in diverse eukaryotic taxa. Cross-exon but not cross-intron compensatory interactions between the 5' splice site (5'ss) and 3' splice site (3'ss) were observed in human/mouse, indicating that the exon is the primary evolutionary unit in mammals. Studied plants, fungi, and invertebrates exhibited exclusively cross-intron interactions, suggesting that intron definition drives evolution in these organisms. In mammals, 5'ss strength and the strength of several classes of exonic splicing silencers (ESSs) evolved in a correlated way, whereas specific exonic splicing enhancers (ESEs), including motifs associated with hTra2, SRp55, and SRp20, evolved in a compensatory manner relative to the 5'ss and 3'ss. Interactions between specific ESS or ESE motifs were not observed, suggesting that elements bound by different factors are not commonly interchangeable. Thus, the splicing elements defining exons coevolve in a way that preserves overall exon strength, allowing specific elements to substitute for loss or weakening of others.
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