Genome sequencing and analysis of the Tasmanian devil and its transmissible cancer.

The Tasmanian devil (Sarcophilus harrisii), the largest marsupial carnivore, is endangered due to a transmissible facial cancer spread by direct transfer of living cancer cells through biting. Here we describe the sequencing, assembly, and annotation of the Tasmanian devil genome and whole-genome sequences for two geographically distant subclones of the cancer. Genomic analysis suggests that the cancer first arose from a female Tasmanian devil and that the clone has subsequently genetically diverged during its spread across Tasmania. The devil cancer genome contains more than 17,000 somatic base substitution mutations and bears the imprint of a distinct mutational process. Genotyping of somatic mutations in 104 geographically and temporally distributed Tasmanian devil tumors reveals the pattern of evolution and spread of this parasitic clonal lineage, with evidence of a selective sweep in one geographical area and persistence of parallel lineages in other populations.

ArCH: improving the performance of clonal hematopoiesis variant calling and interpretation.

MOTIVATION: The acquisition of somatic mutations in hematopoietic stem and progenitor stem cells with resultant clonal expansion, termed clonal hematopoiesis (CH), is associated with increased risk of hematologic malignancies and other adverse outcomes. CH is generally present at low allelic fractions, but clonal expansion and acquisition of additional mutations leads to hematologic cancers in a small proportion of individuals. With high depth and high sensitivity sequencing, CH can be detected in most adults and its clonal trajectory mapped over time. However, accurate CH variant calling is challenging due to the difficulty in distinguishing low frequency CH mutations from sequencing artifacts. The lack of well-validated bioinformatic pipelines for CH calling may contribute to lack of reproducibility in studies of CH. RESULTS: Here, we developed ArCH, an Artifact filtering Clonal Hematopoiesis variant calling pipeline for detecting single nucleotide variants and short insertions/deletions by combining the output of four variant calling tools and filtering based on variant characteristics and sequencing error rate estimation. ArCH is an end-to-end cloud-based pipeline optimized to accept a variety of inputs with customizable parameters adaptable to multiple sequencing technologies, research questions, and datasets. Using deep targeted sequencing data generated from six acute myeloid leukemia patient tumor: normal dilutions, 31 blood samples with orthogonal validation, and 26 blood samples with technical replicates, we show that ArCH improves the sensitivity and positive predictive value of CH variant detection at low allele frequencies compared to standard application of commonly used variant calling approaches. AVAILABILITY AND IMPLEMENTATION: The code for this workflow is available at: https://github.com/kbolton-lab/ArCH.

Differences in the number of de novo mutations between individuals are due to small family-specific effects and stochasticity.

The number of de novo mutations (DNMs) in the human germline is correlated with parental age at conception, but this explains only part of the observed variation. We investigated whether there is a family-specific contribution to the number of DNMs in offspring. The analysis of DNMs in 111 dizygotic twin pairs did not identify a substantial family-specific contribution. This result was corroborated by comparing DNMs of 1669 siblings to those of age-matched unrelated offspring following correction for parental age. In addition, by modeling DNM data from 1714 multi-offspring families, we estimated that the family-specific contribution explains ∼5.2% of the variation in DNM number. Furthermore, we found no substantial difference between the observed number of DNMs and those predicted by a stochastic Poisson process. We conclude that there is a small family-specific contribution to DNM number and that stochasticity explains a large proportion of variation in DNM counts.

Moving Toward Findable, Accessible, Interoperable, Reusable Practices in Epidemiologic Research.

Data sharing is essential for reproducibility of epidemiologic research, replication of findings, pooled analyses in consortia efforts, and maximizing study value to address multiple research questions. However, barriers related to confidentiality, costs, and incentives often limit the extent and speed of data sharing. Epidemiological practices that follow Findable, Accessible, Interoperable, Reusable (FAIR) principles can address these barriers by making data resources findable with the necessary metadata, accessible to authorized users, and interoperable with other data, to optimize the reuse of resources with appropriate credit to its creators. We provide an overview of these principles and describe approaches for implementation in epidemiology. Increasing degrees of FAIRness can be achieved by moving data and code from on-site locations to remote, accessible ("Cloud") data servers, using machine-readable and nonproprietary files, and developing open-source code. Adoption of these practices will improve daily work and collaborative analyses and facilitate compliance with data sharing policies from funders and scientific journals. Achieving a high degree of FAIRness will require funding, training, organizational support, recognition, and incentives for sharing research resources, both data and code. However, these costs are outweighed by the benefits of making research more reproducible, impactful, and equitable by facilitating the reuse of precious research resources by the scientific community.

PLCOjs, a FAIR GWAS web SDK for the NCI Prostate, Lung, Colorectal and Ovarian Cancer Genetic Atlas project.

MOTIVATION: The Division of Cancer Epidemiology and Genetics (DCEG) and the Division of Cancer Prevention (DCP) at the National Cancer Institute (NCI) have recently generated genome-wide association study (GWAS) data for multiple traits in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Genomic Atlas project. The GWAS included 110 000 participants. The dissemination of the genetic association data through a data portal called GWAS Explorer, in a manner that addresses the modern expectations of FAIR reusability by data scientists and engineers, is the main motivation for the development of the open-source JavaScript software development kit (SDK) reported here. RESULTS: The PLCO GWAS Explorer resource relies on a public stateless HTTP application programming interface (API) deployed as the sole backend service for both the landing page's web application and third-party analytical workflows. The core PLCOjs SDK is mapped to each of the API methods, and also to each of the reference graphic visualizations in the GWAS Explorer. A few additional visualization methods extend it. As is the norm with web SDKs, no download or installation is needed and modularization supports targeted code injection for web applications, reactive notebooks (Observable) and node-based web services. AVAILABILITY AND IMPLEMENTATION: code at https://github.com/episphere/plco; project page at https://episphere.github.io/plco.

Treat and extend regimen for diabetic macular oedema-a systematic review and meta-analysis.

PURPOSE: Various treatment regimens are currently practiced in the treatment of CI-DMO (centre-involving diabetic macular oedema). In recent years, there has been a growing body of evidence supporting a treat and extend (T&E) regimen for DMO which offers the promise of comparable visual and anatomical outcomes while reducing injection burden. This meta-analysis was hence performed to evaluate the aforementioned outcomes in the treatment of DMO. Ten studies met the inclusion criteria. METHODS: A search of PubMed, MEDLINE, Current Contents, and Cochrane Central Register of Controlled Trials (CENTRAL) databases was performed. We employed the terms 'treat AND extend AND (diabetic AND macular AND edema OR oedema)' to ensure a comprehensive search. The search workflow adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. RESULTS: The pooled analysis of the mean number of injections in 1 year for T&E-aflibercept (AFL), T&E-ranibizumab (RBZ) and collectively was 9.1 (95% CI: 7.63-10.63), 10.0 (95% CI: 9.55-10.47) and 9.6 (95% CI: 8.62-10.49), respectively. Improvements in vision at 1 year for T&E-AFL, T&E-RBZ and collectively were 6.26 (95% CI: 3.24-9.29), 7.14 (95% CI: 4.76-9.52) and 7.08 (95% CI: 5.32-8.84) letters, respectively. The improvements in central subfield thickness at 1 year for T&E-AFL, T&E-RBZ and collectively were 131.94 (95% CI: 100.29-163.60), 108.64 (95% CI: 82.82-134.46) and 121.32 (95% CI: 102.89-139.75) microns, respectively. CONCLUSION: The meta-analysis of T&E for DMO did not show a clear advantage in reducing the number of injections compared to landmark clinical trials with pro-re-nata (PRN) treatment regimens in the first year of treatment with limited gains in visual and anatomical outcomes. However, the T&E approach offers the potential for fewer patient visits, thereby reducing treatment burden. Longer term studies on T&E with a standardised protocol would be required to assess the longevity of the vision gain in the first year despite a likely reduced treatment burden compared to the PRN trials.

Magnetic resonance imaging of disorders with white matter changes in children and adolescents: a pictorial essay.

White matter changes are seen in a spectrum of disorders in children and adolescents. Understanding their distribution and appearance helps to reach diagnoses in daily radiologic practice. This pictorial essay will outline the magnetic resonance imaging (MRI) appearances of diseases with white matter changes including demyelinating diseases, dysmyelinating disorders/leukodystrophies, infections, autoimmune diseases, vascular causes, mitochondrial disorders and neurocutaneous syndromes, along with a brief overview of clinical aspects of the diseases such as typical age of presentation, etiology, symptoms and signs and treatment options. This article highlights important features in common white matter diseases in children and adolescents.

Dysfunctional Autophagy, Proteostasis, and Mitochondria as a Prelude to Age-Related Macular Degeneration.

Retinal pigment epithelial (RPE) cell dysfunction is a key driving force of AMD. RPE cells form a metabolic interface between photoreceptors and choriocapillaris, performing essential functions for retinal homeostasis. Through their multiple functions, RPE cells are constantly exposed to oxidative stress, which leads to the accumulation of damaged proteins, lipids, nucleic acids, and cellular organelles, including mitochondria. As miniature chemical engines of the cell, self-replicating mitochondria are heavily implicated in the aging process through a variety of mechanisms. In the eye, mitochondrial dysfunction is strongly associated with several diseases, including age-related macular degeneration (AMD), which is a leading cause of irreversible vision loss in millions of people globally. Aged mitochondria exhibit decreased rates of oxidative phosphorylation, increased reactive oxygen species (ROS) generation, and increased numbers of mitochondrial DNA mutations. Mitochondrial bioenergetics and autophagy decline during aging because of insufficient free radical scavenger systems, the impairment of DNA repair mechanisms, and reductions in mitochondrial turnover. Recent research has uncovered a much more complex role of mitochondrial function and cytosolic protein translation and proteostasis in AMD pathogenesis. The coupling of autophagy and mitochondrial apoptosis modulates the proteostasis and aging processes. This review aims to summarise and provide a perspective on (i) the current evidence of autophagy, proteostasis, and mitochondrial dysfunction in dry AMD; (ii) current in vitro and in vivo disease models relevant to assessing mitochondrial dysfunction in AMD, and their utility in drug screening; and (iii) ongoing clinical trials targeting mitochondrial dysfunction for AMD therapeutics.

Understanding National Nonprofit Data Environments.

We develop the concept of the nonprofit data environment as all data collected and reported in a country resulting from law implemented into practice. We map data environments across 20 countries and propose explanations for differences between the information nongovernmental organizations report (collected) and what is made publicly available (reported). Domestic factors including regime type, civil society autonomy, and regulatory quality increase the amount of information collected and released publicly. Exposure to international political forces, including aid flows and globalization, increases the gap, which runs counter to expectations of greater openness with global engagement. Our findings point to the need for a better understanding of patterns in non-profit organizations (NPOs) data environments; while all governments collect information, countries with similar legal codes have widely varying data environments. This matters for NPOs as their ability to learn and improve depends on access to quality data and coincides with a feared global political backlash.

Navigating communication between conventional medicine and traditional Chinese medicine: a case study of cancer patients in Hong Kong.

BACKGROUND: Traditional Chinese medicine (TCM) is a growing phenomenon worldwide. Despite its historical role in Chinese society, however, few studies have explored the nature of communication among patients with cancer who receive TCM care in addition to conventional medicine. If TCM practitioners acquire adequate knowledge to understand the needs and communication issues for their patients with cancer, particularly those who are simultaneously receiving conventional medicine, this will lead to better quality of care and clinical outcomes, such as high patient satisfaction and treatment compliance. OBJECTIVES: To fill this knowledge gap, this study explored the nature of communication among patients with cancer in Hong Kong who receive TCM treatment in addition to conventional medicine. PARTICIPANTS: We conducted in-depth interviews with 20 patients, 5 oncologists and 5 TCM practitioners to elicit their views on TCM treatments. METHOD: We adopted a qualitative approach using an interpretative phenomenological analysis. RESULTS: Based on the themes that emerged from our interview transcripts, we outlined communication priorities when advising patients with cancer who are receiving both TCM and conventional medical care. We developed a framework to train TCM practitioners to better integrate their patients' conventional medical history when delivering patient care. CONCLUSIONS: Our study findings inform communication priorities when caring for patients who opt for TCM care in addition to conventional treatments. In addition, they provide useful information for developing future clinical research studies to explore integrated approaches between TCM and conventional medicine in treating patients with cancer.

Genomic and molecular characterization of preterm birth.

Preterm birth (PTB) complications are the leading cause of long-term morbidity and mortality in children. By using whole blood samples, we integrated whole-genome sequencing (WGS), RNA sequencing (RNA-seq), and DNA methylation data for 270 PTB and 521 control families. We analyzed this combined dataset to identify genomic variants associated with PTB and secondary analyses to identify variants associated with very early PTB (VEPTB) as well as other subcategories of disease that may contribute to PTB. We identified differentially expressed genes (DEGs) and methylated genomic loci and performed expression and methylation quantitative trait loci analyses to link genomic variants to these expression and methylation changes. We performed enrichment tests to identify overlaps between new and known PTB candidate gene systems. We identified 160 significant genomic variants associated with PTB-related phenotypes. The most significant variants, DEGs, and differentially methylated loci were associated with VEPTB. Integration of all data types identified a set of 72 candidate biomarker genes for VEPTB, encompassing genes and those previously associated with PTB. Notably, PTB-associated genes RAB31 and RBPJ were identified by all three data types (WGS, RNA-seq, and methylation). Pathways associated with VEPTB include EGFR and prolactin signaling pathways, inflammation- and immunity-related pathways, chemokine signaling, IFN-γ signaling, and Notch1 signaling. Progress in identifying molecular components of a complex disease is aided by integrated analyses of multiple molecular data types and clinical data. With these data, and by stratifying PTB by subphenotype, we have identified associations between VEPTB and the underlying biology.

Prioritizing Chinese medicine clinical research questions in cancer palliative care from patient and caregiver perspectives.

BACKGROUND: Chinese medicine (CM) modalities, including acupuncture and Chinese herbal medicine (CHM), are popular palliative interventions among patients with cancer, but further clinical research is required to assess their effectiveness and safety. OBJECTIVE: To prioritize top ten important CM clinical research questions from patients with cancer, cancer survivors and caregivers' perspectives via a face-to-face prioritization workshop in Hong Kong. METHODS: A list of 25 CM clinical research questions for cancer palliative care, which were identified from existing systematic reviews (SRs) and overview of SRs, was presented to 17 participants (patients with cancer [n = 5], cancer survivors [n = 6] and caregivers [n = 6]). The participants were then invited to establish consensus on prioritizing top ten research questions. RESULTS: Among the top ten priorities, five (50%) focused on acupuncture and related therapies, while five (50%) were on CHM. The three most important research priorities were (i) manual acupuncture plus opioids for relieving pain; (ii) CHM for improving quality of life among patients receiving chemotherapy; and (iii) concurrent use of CHM plus loperamide for reducing stomatitis. CONCLUSION: The top ten participant-endorsed CM clinical research priorities for cancer palliative care can guide local researchers on future direction. They can also inform local research funders on patient-centred allocation of limited funding. Under limited research funding, the most important co-prioritized research question from professional and patient perspectives may be addressed first. PATIENT OR PUBLIC CONTRIBUTION: Patients with cancer, cancer survivors and caregivers participated in conduct of the study to prioritize CM clinical research questions.

An Interactive Web-Based Sexual Health Literacy Program for Safe Sex Practice for Female Chinese University Students: Multicenter Randomized Controlled Trial.

BACKGROUND: Sexual health concerns among young adults worldwide help to motivate preventative practices against sexually transmitted infections. To foster better sexual health, sexual health literacy must be enhanced. Little research has been conducted on the impact of gender power dynamics on sexual health, such as sexual coercion, even though the prevalence of sexual coercion remains high in China. OBJECTIVE: This study describes the development and systematic evaluation of a web-based sexual health literacy intervention called "Smart Girlfriend" for female Chinese university students. METHODS: A multicenter randomized controlled trial was conducted with 781 female university students at 5 universities with dormitories in Hong Kong. Inclusion criteria were used to select unmarried, female, Chinese university students who were ≥18 years old and had not received a sexual health intervention in the past 12 months. Participants were randomly assigned to 2 groups: one group received an interactive web-based sexual health literacy intervention and the other group received a single webpage of online information about condom use. The intervention content was based on the Health Belief Model and the Continuum of Conflict and Control theory. The primary outcome was self-reported consistency of condom use with every partner at 3-month and 6-month follow-up assessments, analyzed using zero/one inflated beta (ZOIB) regression. The secondary outcome was an appraisal of the knowledge, attitudes, norms, and self-efficacy of condom use using the 25-item Multidimensional Condom Attitudes Scale (MCAS). The intention to treat was applied in analyses. RESULTS: Of 1503 individuals that were screened, 781 (52%) were randomized into 2 groups. The retention rates at the 3-month and 6-month follow-ups were 92% and 91%, respectively. Most participants were born locally (536/746, 72%), and 18% (134/746) self-reported as a sexual minority. ZOIB results regarding the consistency of condom use were not significant [model 1: odds ratio (OR) 2.25 with a 95% credible interval (CrI) of 0.84-6.36; model 2: OR 8.03 (95% CrI 0.22-330.31); model 3: OR 1.21 (95% CrI 0.78-1.86)]. Consistency in the intervention group was 5% higher (95% CI -1.90 to 11.63) than the control group at the 3-month follow-up, and 1% higher (95% CI -5.81 to 8·02) at the 6-month follow-up. MCAS scores at the 3-month follow-up were significantly higher in the intervention group (mean 122.51, SD 15.97) than the control group (mean 119.86, SD 15.85; P=.02). CONCLUSIONS: An interactive web-based sexual health literacy program did not significantly increase the consistency of condom use compared to a single webpage of condom use information; however, it did temporarily improve knowledge, attitudes, norms, and self-efficacy regarding condom use. Future revisions of this intervention should be personalized and delivered with a proactive approach. TRIAL REGISTRATION: ClinicalTrials.gov NCT03695679; https://clinicaltrials.gov/ct2/show/NCT03695679.

Mother-child histocompatibility and risk of rheumatoid arthritis and systemic lupus erythematosus among mothers.

The study objective was to test the hypothesis that having histocompatible children increases the risk of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), possibly by contributing to the persistence of fetal cells acquired during pregnancy. We conducted a case control study using data from the UC San Francisco Mother Child Immunogenetic Study and studies at the Inova Translational Medicine Institute. We imputed human leukocyte antigen (HLA) alleles and minor histocompatibility antigens (mHags). We created a variable of exposure to histocompatible children. We estimated an average sequence similarity matching (SSM) score for each mother based on discordant mother-child alleles as a measure of histocompatibility. We used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals. A total of 138 RA, 117 SLE, and 913 control mothers were analyzed. Increased risk of RA was associated with having any child compatible at HLA-B (OR 1.9; 1.2-3.1), DPB1 (OR 1.8; 1.2-2.6) or DQB1 (OR 1.8; 1.2-2.7). Compatibility at mHag ZAPHIR was associated with reduced risk of SLE among mothers carrying the HLA-restriction allele B*07:02 (n = 262; OR 0.4; 0.2-0.8). Our findings support the hypothesis that mother-child histocompatibility is associated with risk of RA and SLE.

The ubiquitin ligase XIAP recruits LUBAC for NOD2 signaling in inflammation and innate immunity.

Nucleotide-binding and oligomerization domain (NOD)-like receptors constitute a first line of defense against invading bacteria. X-linked Inhibitor of Apoptosis (XIAP) is implicated in the control of bacterial infections, and mutations in XIAP are causally linked to immunodeficiency in X-linked lymphoproliferative syndrome type-2 (XLP-2). Here, we demonstrate that the RING domain of XIAP is essential for NOD2 signaling and that XIAP contributes to exacerbation of inflammation-induced hepatitis in experimental mice. We find that XIAP ubiquitylates RIPK2 and recruits the linear ubiquitin chain assembly complex (LUBAC) to NOD2. We further show that LUBAC activity is required for efficient NF-κB activation and secretion of proinflammatory cytokines after NOD2 stimulation. Remarkably, XLP-2-derived XIAP variants have impaired ubiquitin ligase activity, fail to ubiquitylate RIPK2, and cannot facilitate NOD2 signaling. We conclude that XIAP and LUBAC constitute essential ubiquitin ligases in NOD2-mediated inflammatory signaling and propose that deregulation of NOD2 signaling contributes to XLP-2 pathogenesis.

Studying the urine microbiome in superficial bladder cancer: samples obtained by midstream voiding versus cystoscopy.

BACKGROUND: Preliminary data suggest that the urinary microbiome may play a role in bladder cancer. Information regarding the most suitable method of collecting urine specimens is needed for the large population studies needed to address this. To compare microbiome metrics resulting from 16S ribosomal RNA gene sequencing between midstream, voided specimens and those obtained at cystoscopy. METHODS: Adults, with a history of superficial urothelial cell carcinoma (non-muscle invasive bladder cancer) being followed with periodic surveillance cystoscopy had a urine sample collected by a mid-stream, voided technique and then from the bladder at cystoscopy. Urine samples underwent 16S ribosomal RNA gene sequencing on the Illumina MiSeq platform. RESULTS: 22 subjects (8 female, 14 male) were included. There was no significant difference in beta diversity (diversity between samples) in all samples between collection methods. However, analysis by sex revealed a difference between voided and cystoscopy samples from the same individual in males (p = 0.006, Adonis test) but not in females (p = 0.317, Adonis test). No differences were seen by collection method in any alpha diversity (diversity within a sample) measurement or differential abundance of taxa. CONCLUSIONS: Beta diversity of the urine microbiome did differ by collection method for males only. This suggests that the urinary microbiomes of the two collection methods are not equivalent to each other, at least in males, which is the sex that bladder cancer occurs most frequently in. Therefore, the same collection method within a given study should be used.

Did the UN convention on the rights of the child reduce child mortality around the world? An interrupted time series analysis.

BACKGROUND: Child mortality has been reduced by more than 50 % over the past 30 years. A range of secular economic and social developments have been considered to explain this phenomenon. In this paper, we examine the association between ratification of the Convention on the Rights of the Child (CRC), which was specifically put in place to ensure the well-being of children, and declines in child mortality. METHODS: Data come from three sources: the United Nations Treaty Series Database, the World Bank World Development Indicators database and, the Polity IV database. Because CRC was widely ratified, leaving few control cases, we used interrupted times series analyses, which uses the trend in the health outcome before policy exposure to mathematically determine what the trend in the health outcome would have been after the policy exposure, if it had continued 'as is' - meaning, if the policy exposure had not occurred. RESULTS: CRC ratification was associated with declining child mortality. CRC ratification was associated with a significant change in shorter-term child mortality trends in all groups except high-income, non-democratic countries and low-imcome democratic countries. CRC ratification was associated with long-term child mortality trends in all groups except middle-income, non-democratic countries. CONCLUSIONS: Child mortality rates would likely have declined even in the absence of CRC ratification, but CRC is associated with a larger decline. Our findings provide a way to assess the effects of widely-held societal norms on health and demonstrate the moderating effects of democracy and income level.

Gut microbial composition difference between pediatric ALL survivors and siblings.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer with high cure rates leading to rising numbers of long-term survivors. Adult survivors of childhood ALL are at increased risk of obesity, cardiovascular disease, and other chronic illnesses. We hypothesize that ALL therapy is associated with long-term gut microbiome alterations that contribute to predisposition to chronic medical conditions. We conducted a pilot study to test whether differences can be detected between stool microbiota of pediatric ALL survivors and their siblings. Stool samples were collected from 38 individuals under age 19 who were at least 1 year after completion of therapy for ALL. Stool samples collected from 16 healthy siblings served as controls. 16S ribosomal RNA gene sequencing was performed on the stool samples. Comparing microbiota of survivors to sibling controls, no statistically significant differences were found in alpha or beta diversity. However, among the top 10 operational taxonomic units (OTUs) from component 1 in sparse partial least squares discriminant analysis (sPLS-DA) with different relative abundance in survivors versus siblings, OTUs mapping to the genus Faecalibacterium were depleted in survivors. Differences in gut microbial composition were found between pediatric survivors of childhood ALL and their siblings. Specifically, the protective Faecalibacterium is depleted in survivors, which is reminiscent of gut microbiota alteration found in adult survivors of childhood ALL and reported in obesity, suggesting that microbiota alterations in pediatric ALL survivors start in childhood and may play a role in predisposition to chronic illness in later years of survivorship.

Safety and Tolerability of Accelerated Infliximab Infusions in Patients With Inflammatory Bowel Disease.

INTRODUCTION: Infliximab for inflammatory bowel disease (IBD) is FDA-approved to be administered 2 h or more. We adopted a new protocol to infuse infliximab over 1 h and in this study, we aimed to determine the safety of a 1-h infusion. METHODS: This retrospective cohort included adult IBD patients who received infliximab between June and December 2017 and compared reaction rates of 1-h maintenance infusions to that of 2-h maintenance infusions. RESULTS: A total of 551 infusions were administered to 179 patients. The infusion groups demonstrated no significant differences in reaction rates. CONCLUSIONS: Infliximab infusion over 1 h is well-tolerated.

Clinical and social factors associated with excess weight in Hispanic and non-Hispanic White children.

BACKGROUND: Hispanic children are disproportionately affected by obesity, with this disparity starting at a young age, and there is a paucity of data comparing factors associated with excess weight in the first year of life in Hispanic vs. non-Hispanic populations. METHODS: Excess weight was defined as weight-for-length ≥95th percentile. The associations of potential risk factors were compared by ethnicity stratification. RESULTS: Of the 1009 children, 302 (30.0%) were Hispanic and 707 (70.0%) were non-Hispanic White. The rate of excess weight was 30.1% and 13.6% among Hispanic and non-Hispanic White children, respectively. Factors associated with excess weight for non-Hispanic White children were higher than recommended weight gain during pregnancy (odds ratio (OR) 1.8 (1.2-3.1)), higher paternal body mass index (BMI) (OR 1.1 (1.02-1.15)), higher birth weight (OR 1.001 (1.001-1.002)), and lower breast milk feedings at 6 months (OR 0.98 (0.96-0.98)). Factors associated with excess weight for Hispanic children were lower maternal education (OR 2.37 (1.1-4.5)) and lower breast milk feedings at 6 months (OR 0.98 (0.96-0.99)). CONCLUSION: There are differential risk factors associated with excess weight at 12 months between Hispanic and non-Hispanic White children. Identification of differential factors in different ethnicities may allow for more targeted anticipatory guidance reduce obesity in at-risk populations.