Showing papers by "Children's Memorial Hospital published in 2016"
TL;DR: The findings suggest that cannabidiol might reduce seizure frequency and might have an adequate safety profile in children and young adults with highly treatment-resistant epilepsy.
Abstract: Summary Background Almost a third of patients with epilepsy have a treatment-resistant form, which is associated with severe morbidity and increased mortality. Cannabis-based treatments for epilepsy have generated much interest, but scientific data are scarce. We aimed to establish whether addition of cannabidiol to existing anti-epileptic regimens would be safe, tolerated, and efficacious in children and young adults with treatment-resistant epilepsy. Methods In this open-label trial, patients (aged 1–30 years) with severe, intractable, childhood-onset, treatment-resistant epilepsy, who were receiving stable doses of antiepileptic drugs before study entry, were enrolled in an expanded-access programme at 11 epilepsy centres across the USA. Patients were given oral cannabidiol at 2–5 mg/kg per day, up-titrated until intolerance or to a maximum dose of 25 mg/kg or 50 mg/kg per day (dependent on study site). The primary objective was to establish the safety and tolerability of cannabidiol and the primary efficacy endpoint was median percentage change in the mean monthly frequency of motor seizures at 12 weeks. The efficacy analysis was by modified intention to treat. Comparisons of the percentage change in frequency of motor seizures were done with a Mann-Whitney U test. Results Between Jan 15, 2014, and Jan 15, 2015, 214 patients were enrolled; 162 (76%) patients who had at least 12 weeks of follow-up after the first dose of cannabidiol were included in the safety and tolerability analysis, and 137 (64%) patients were included in the efficacy analysis. In the safety group, 33 (20%) patients had Dravet syndrome and 31 (19%) patients had Lennox-Gastaut syndrome. The remaining patients had intractable epilepsies of different causes and type. Adverse events were reported in 128 (79%) of the 162 patients within the safety group. Adverse events reported in more than 10% of patients were somnolence (n=41 [25%]), decreased appetite (n=31 [19%]), diarrhoea (n=31 [19%]), fatigue (n=21 [13%]), and convulsion (n=18 [11%]). Five (3%) patients discontinued treatment because of an adverse event. Serious adverse events were reported in 48 (30%) patients, including one death—a sudden unexpected death in epilepsy regarded as unrelated to study drug. 20 (12%) patients had severe adverse events possibly related to cannabidiol use, the most common of which was status epilepticus (n=9 [6%]). The median monthly frequency of motor seizures was 30·0 (IQR 11·0–96·0) at baseline and 15·8 (5·6–57·6) over the 12 week treatment period. The median reduction in monthly motor seizures was 36·5% (IQR 0–64·7). Interpretation Our findings suggest that cannabidiol might reduce seizure frequency and might have an adequate safety profile in children and young adults with highly treatment-resistant epilepsy. Randomised controlled trials are warranted to characterise the safety profile and true efficacy of this compound. Funding GW Pharmaceuticals, Epilepsy Therapy Project of the Epilepsy Foundation, Finding A Cure for Epilepsy and Seizures.
702 citations
TL;DR: The purpose of this manuscript is to briefly review the literature characterizing barriers to healthcare for transgender individuals and to propose research priorities to understand mechanisms of those barriers and interventions to overcome them.
Abstract: Purpose of reviewTransgender persons suffer significant health disparities and may require medical intervention as part of their care. The purpose of this manuscript is to briefly review the literature characterizing barriers to healthcare for transgender individuals and to propose research prioriti
457 citations
Cincinnati Children's Hospital Medical Center1, University of Texas at Austin2, Emory University3, Wayne State University4, University of Toronto5, East Carolina University6, Baylor College of Medicine7, Eastern Virginia Medical School8, Children's National Medical Center9, University of Texas Southwestern Medical Center10, University of Alabama at Birmingham11, Nemours Foundation12, Case Western Reserve University13, Columbia University14, University of Pennsylvania15, Medical University of South Carolina16, State University of New York System17, University of South Carolina18, Harvard University19, University of South Alabama20, University of Miami21, University of Mississippi22, Children's Memorial Hospital23, Duke University24, Georgia Regents University25, University of Southern California26
TL;DR: High-risk children with sickle cell anaemia and abnormal TCD velocities who have received at least 1 year of transfusions, and have no MRA-defined severe vasculopathy, hydroxycarbamide treatment can substitute for chronic transfusions to maintain TCD velocity and help to prevent primary stroke.
363 citations
University of Pennsylvania1, Northwestern University2, Children's Memorial Hospital3, University of Washington4, Seattle Children's5, Johns Hopkins University6, University of Michigan7, University of Texas Health Science Center at Houston8, Boston Children's Hospital9, University of Colorado Denver10, Harvard University11
TL;DR: The results suggest that limiting the number of direct laryngoscopy attempts and quickly transitioning to an indirect technique when direct laryngeal intubation fails would enhance patient safety.
290 citations
Maine Medical Center1, University of Florida2, United States Department of the Army3, University of Utah4, University of California, San Francisco5, University of Western Australia6, Oregon Health & Science University7, Children's Memorial Hospital8, University of Iowa9, Ohio State University10, University of Alabama at Birmingham11, Johns Hopkins University12, University of Washington13, University of New Mexico14, University of Texas Southwestern Medical Center15, University of Pennsylvania16, New York University17
TL;DR: High-dose methotrexate is superior to Capizzi methotreysate for the treatment of high-risk B-acute lymphoblastic leukemia, with no increase in acute toxicity.
Abstract: PurposeSurvival for children and young adults with high-risk B-acute lymphoblastic leukemia has improved significantly, but 20% to 25% of patients are not cured. Children’s Oncology Group study AALL0232 tested two interventions to improve survival.Patients and MethodsBetween January 2004 and January 2011, AALL0232 enrolled 3,154 participants 1 to 30 years old with newly diagnosed high-risk B-acute lymphoblastic leukemia. By using a 2 × 2 factorial design, 2,914 participants were randomly assigned to receive dexamethasone (14 days) versus prednisone (28 days) during induction and high-dose methotrexate versus Capizzi escalating-dose methotrexate plus pegaspargase during interim maintenance 1.ResultsPlanned interim monitoring showed the superiority of the high-dose methotrexate regimens, which exceeded the predefined boundary and led to cessation of enrollment in January 2011. At that time, participants randomly assigned to high-dose methotrexate during interim maintenance 1 versus those randomly assigned t...
262 citations
Harvard University1, University of North Carolina at Chapel Hill2, Memorial Sloan Kettering Cancer Center3, University of Alabama at Birmingham4, University of Southern California5, Stanford University6, University of Pennsylvania7, Duke University8, University of Washington9, Oregon Health & Science University10, Loyola University Chicago11, Children's Memorial Hospital12, University of Manitoba13, University of Minnesota14, University of Texas Health Science Center at Houston15, Rutgers University16, Nationwide Children's Hospital17, Boston University18
TL;DR: Defibrotide was associated with significant improvement in day +100 survival and CR rate and the historical-control methodology offers a novel, meaningful approach for phase 3 evaluation of orphan diseases associated with high mortality.
228 citations
TL;DR: Omalizumab allows subjects with peanut allergy to be rapidly desensitized over as little as 8 weeks of peanut oral immunotherapy, and in the majority of subjects, this desensitization is sustained after omalizuab is discontinued.
Abstract: Background Peanut oral immunotherapy is a promising approach to peanut allergy, but reactions are frequent, and some patients cannot be desensitized. The anti-IgE medication omalizumab (Xolair; Genentech, South San Francisco, Calif) might allow more rapid peanut updosing and decrease reactions. Objective We sought to evaluate whether omalizumab facilitated rapid peanut desensitization in highly allergic patients. Methods Thirty-seven subjects were randomized to omalizumab (n = 29) or placebo (n = 8). After 12 weeks of treatment, subjects underwent a rapid 1-day desensitization of up to 250 mg of peanut protein, followed by weekly increases up to 2000 mg. Omalizumab was then discontinued, and subjects continued on 2000 mg of peanut protein. Subjects underwent an open challenge to 4000 mg of peanut protein 12 weeks after stopping study drug. If tolerated, subjects continued on 4000 mg of peanut protein daily. Results The median peanut dose tolerated on the initial desensitization day was 250 mg for omalizumab-treated subjects versus 22.5 mg for placebo-treated subject. Subsequently, 23 (79%) of 29 subjects randomized to omalizumab tolerated 2000 mg of peanut protein 6 weeks after stopping omalizumab versus 1 (12%) of 8 receiving placebo ( P P = .15), although omalizumab-treated subjects were exposed to much higher peanut doses. Conclusion Omalizumab allows subjects with peanut allergy to be rapidly desensitized over as little as 8 weeks of peanut oral immunotherapy. In the majority of subjects, this desensitization is sustained after omalizumab is discontinued. Additional studies will help clarify which patients would benefit most from this approach.
227 citations
University of California, San Francisco1, Utrecht University2, Leiden University Medical Center3, Children's Memorial Hospital4, Children's Hospital at Westmead5, University of Münster6, Université de Montréal7, Centre Hospitalier Universitaire Sainte-Justine8, Karolinska Institutet9, Boston Children's Hospital10, Great Ormond Street Hospital11, Newcastle University12, University of Minnesota13
TL;DR: The main outcome of interest was event-free survival and improved clinical outcomes are likely to be achieved by targeting the busulfan AUC to 78-101 mg hokinetic model for all indications.
180 citations
Emory University1, University of Wisconsin-Madison2, Pennsylvania State University3, Boston Children's Hospital4, Rush University Medical Center5, Washington University in St. Louis6, University of California, San Francisco7, University of Pittsburgh8, University of Arizona9, Children's Memorial Hospital10, Nemours Foundation11, Case Western Reserve University12, Allegheny General Hospital13, Wake Forest University14, Brigham and Women's Hospital15, University of Illinois at Chicago16, University of Central Florida17, University of New Mexico18, University of California, Los Angeles19, University of Colorado Denver20
TL;DR: In young children with asthma necessitating Step 2 treatment, phenotyping with aeroallergen sensitization and blood eosinophil counts is useful for guiding treatment selection and identifies children with a high exacerbation probability for whom treatment with a daily ICS is beneficial despite possible risks of growth suppression.
Abstract: Background Phenotypic presentations in young children with asthma are varied and might contribute to differential responses to asthma controller medications. Methods The Individualized Therapy for Asthma in Toddlers study was a multicenter, randomized, double-blind, double-dummy clinical trial in children aged 12 to 59 months (n = 300) with asthma necessitating treatment with daily controller (Step 2) therapy. Participants completed a 2- to 8-week run-in period followed by 3 crossover periods with daily inhaled corticosteroids (ICSs), daily leukotriene receptor antagonists, and as-needed ICS treatment coadministered with albuterol. The primary outcome was differential response to asthma medication based on a composite measure of asthma control. The primary analysis involved 2 stages: determination of differential response and assessment of whether 3 prespecified features (aeroallergen sensitization, previous exacerbations, and sex) predicted a differential response. Results Seventy-four percent (170/230) of children with analyzable data had a differential response to the 3 treatment strategies. Within differential responders, the probability of best response was highest for a daily ICS and was predicted by aeroallergen sensitization but not exacerbation history or sex. The probability of best response to daily ICS was further increased in children with both aeroallergen sensitization and blood eosinophil counts of 300/μL or greater. In these children daily ICS use was associated with more asthma control days and fewer exacerbations compared with the other treatments. Conclusions In young children with asthma necessitating Step 2 treatment, phenotyping with aeroallergen sensitization and blood eosinophil counts is useful for guiding treatment selection and identifies children with a high exacerbation probability for whom treatment with a daily ICS is beneficial despite possible risks of growth suppression.
179 citations
University of Toronto1, University Health Network2, McGill University3, Alberta Children's Hospital4, Asan Medical Center5, University of British Columbia6, The Chinese University of Hong Kong7, University of Alberta8, University of Calgary9, Cincinnati Children's Hospital Medical Center10, University of Colorado Denver11, University of Queensland12, Fudan University13, Seoul National University14, Royal Children's Hospital15, Children's Hospital at Westmead16, University of Debrecen17, Semmelweis University18, University of Szeged19, Université de Montréal20, Virginia Commonwealth University21, Children's National Medical Center22, St. Jude Children's Research Hospital23, Taipei Veterans General Hospital24, Kumamoto University25, Hebrew University of Jerusalem26, University of Utah27, Boston Children's Hospital28, McMaster University29, Children's Hospital of Eastern Ontario30, University of Western Ontario31, Dalhousie University32, Mahidol University33, University of Nottingham34, Children's Memorial Hospital35, University of California, San Francisco36, University of Alabama at Birmingham37, University of Würzburg38, University of Hamburg39, University of Bonn40, Children's Hospital Los Angeles41, University of Southern California42
TL;DR: It is discovered that differential methylation of a PDGFRB-associated enhancer confers specific sensitivity of group 2 ATRT cells to dasatinib and nilotinib, and it is suggested that these are promising therapies for this highly lethal ATRT subtype.
175 citations
Columbia University1, Northwestern University2, Nationwide Children's Hospital3, Medical College of Wisconsin4, Boston Children's Hospital5, Lenox Hill Hospital6, Children's Memorial Hospital7, University of California, San Francisco8, Henry Ford Hospital9, Loyola University Medical Center10, Harvard University11, Baylor University12, University of Toronto13, Université de Montréal14, Mayo Clinic15, Cincinnati Children's Hospital Medical Center16
Washington University in St. Louis1, Medical College of Wisconsin2, Children's Hospital of Wisconsin3, Children's National Medical Center4, Children's Memorial Hospital5, Virginia Commonwealth University6, Emory University7, University of North Carolina at Chapel Hill8, Baylor College of Medicine9, University of Miami10, Columbia University Medical Center11, Children's Mercy Hospital12, University of Alabama at Birmingham13, Medical University of South Carolina14, Case Western Reserve University15, University of Michigan16, Boston Children's Hospital17, University of Mississippi Medical Center18, Louisiana State University19, National Institutes of Health20, Children's Hospital Oakland21
TL;DR: Although the 1-year EFS met the prespecified target of ≥75%, this regimen cannot be considered sufficiently safe for widespread adoption without modifications to achieve more effective GVHD prophylaxis.
Johns Hopkins University1, Stanford University2, University of Washington3, University of Maryland, Baltimore4, University of California, San Francisco5, Emory University6, Wake Forest University7, Henry Ford Health System8, University of the West Indies9, Leiden University10, University of Mississippi11, University of Cartagena12, University of North Carolina at Chapel Hill13, Northwestern University14, Children's Memorial Hospital15, Vanderbilt University16, University of Chicago17, Oswaldo Cruz Foundation18, Morehouse School of Medicine19, Brooklyn Hospital Center20, Howard University21, Federal University of Bahia22, Illumina23, Knome24, Icahn School of Medicine at Mount Sinai25, California Institute for Quantitative Biosciences26
TL;DR: Genetic variation from deeply sequenced genomes of 642 individuals from North and South American, Caribbean and West African populations is presented, substantially increasing the lexicon of human genomic variation and suggesting much variation remains to be discovered in African-admixed populations in the Americas.
Abstract: The African Diaspora in the Western Hemisphere represents one of the largest forced migrations in history and had a profound impact on genetic diversity in modern populations. To date, the fine-scale population structure of descendants of the African Diaspora remains largely uncharacterized. Here we present genetic variation from deeply sequenced genomes of 642 individuals from North and South American, Caribbean and West African populations, substantially increasing the lexicon of human genomic variation and suggesting much variation remains to be discovered in African-admixed populations in the Americas. We summarize genetic variation in these populations, quantifying the postcolonial sex-biased European gene flow across multiple regions. Moreover, we refine estimates on the burden of deleterious variants carried across populations and how this varies with African ancestry. Our data are an important resource for empowering disease mapping studies in African-admixed individuals and will facilitate gene discovery for diseases disproportionately affecting individuals of African ancestry.
TL;DR: Methodological challenges, gaps, and opportunities in US transgender health research are described, including standardization of lexicon, agreed upon population definitions, study design, sampling, measurement, outcome ascertainment, and sample size.
Abstract: Purpose of reviewThis article describes methodological challenges, gaps, and opportunities in US transgender health research.Recent findingsLack of large prospective observational studies and intervention trials, limited data on risks and benefits of sex affirmation (e.g., hormones and surgical inte
University of Toronto1, German Cancer Research Center2, Cleveland Clinic3, University of Düsseldorf4, University of Hamburg5, Duke University6, University of British Columbia7, University of Alberta8, University of Pennsylvania9, Erasmus University Rotterdam10, Emory University11, University of Michigan12, University of São Paulo13, Seoul National University14, Mayo Clinic15, University of Lisbon16, Instituto Português de Oncologia Francisco Gentil17, University of Barcelona18, University of Pittsburgh19, Semmelweis University20, McGill University21, Chonnam National University22, The Catholic University of America23, University of Naples Federico II24, University of Debrecen25, University of Washington26, Seattle Children's27, Fred Hutchinson Cancer Research Center28, Washington University in St. Louis29, Vanderbilt University30, Hudson Institute of Medical Research31, Johns Hopkins University32, Sapienza University of Rome33, Children's National Medical Center34, University of California, Los Angeles35, University of Iowa36, University of Zurich37, New York University38, University of Sydney39, University of Navarra40, Ludwig Maximilian University of Munich41, Masaryk University42, University of Calgary43, Saint Louis University44, University of Utah45, University of Southern California46, Stanford University47, University of Cincinnati48, Children's Memorial Hospital49, University of Texas MD Anderson Cancer Center50, Henry Ford Health System51, Memorial Sloan Kettering Cancer Center52, University of California, San Francisco53, University of Wisconsin-Madison54, University of Turin55, University of North Carolina at Chapel Hill56, Heidelberg University57, National Institutes of Health58, University of Texas Health Science Center at Houston59
TL;DR: The most impactful biomarker for posterior fossa ependymoma is molecular subgroup affiliation, independent of other demographic or treatment variables, with the survival rates being particularly poor for subtotally resected EPN_PFA, even with adjuvant radiation therapy.
Abstract: PurposePosterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known.MethodsFour independent nonoverlapping retrospective cohorts of posterior fossa ependymomas (n = 820) were profiled using genome-wide methylation arrays. Risk stratification models were designed based on known clinical and newly described molecular biomarkers identified by multivariable Cox proportional hazards analyses.ResultsMolecular subgroup is a powerful independent predictor of outcome even when accounting for age or treatment regimen. Incompletely resected EPN_PFA ependymomas have a dismal prognosis, with a 5-year progression-free survival ranging from 26.1% to 56.8% across all four cohorts. Although first-line (adjuvant) radiation is clearly beneficial for completely resected EPN_PFA, a substantia...
TL;DR: The recent advances in basic research and clinical progress in these diseases are reviewed, as well as the research needs, and current key questions and controversies are formulated and top priorities to guide future research are identified.
TL;DR: Extensive research is needed to improve understanding of gender dysphoria, and transgender experience, particularly among youth, and recommendations include identification of predictors of persistence ofGender dysphoria from childhood into adolescence and a thorough investigation into the impact of interventions for transgender youth.
Abstract: Purpose of reviewThe review summarizes relevant research focused on prevalence and natural history of gender nonconforming/transgender youth, and outcomes of currently recommended clinical practice guidelines. This review identifies gaps in knowledge, and provides recommendations foci for future res
TL;DR: Blood and marrow transplantation in pediatric CML is currently indicated only for recurrent progressive disease, and the acute and long-term toxicities of this option should be carefully evaluated against the complications associated with lifelong use of TKIs.
TL;DR: A randomized trial of a two-way, personalized daily text messaging intervention to improve adherence to antiretroviral therapy (ART) among poorly adherent HIV-positive adolescents and young adults, ages 16–29, suggests both feasibility and initial efficacy of this approach.
Abstract: HIV-positive adolescents and young adults often experience suboptimal medication adherence, yet few interventions to improve adherence in this group have shown evidence of efficacy. We conducted a randomized trial of a two-way, personalized daily text messaging intervention to improve adherence to antiretroviral therapy (ART) among N = 105 poorly adherent HIV-positive adolescents and young adults, ages 16–29. Adherence to ART was assessed via self-reported visual analogue scale (VAS; 0–100 %) at 3 and 6-months for mean adherence level and proportion ≥90 % adherent. The average effect estimate over the 6-month intervention period was significant for ≥90 % adherence (OR = 2.12, 95 % CI 1.01–4.45, p < .05) and maintained at 12-months (6 months post-intervention). Satisfaction scores for the intervention were very high. These results suggest both feasibility and initial efficacy of this approach. Given study limitations, additional testing of this intervention as part of a larger clinical trial with objective and/or clinical outcome measures of adherence is warranted.
TL;DR: The latest advances in the treatment and prevention of Clostridium difficile infection are summarized, with a focus on limiting further perturbation of the intestinal microbiota and/or restoring the microbiota to its pre-morbid state.
Abstract: This Review summarizes the latest advances in the treatment and prevention of Clostridium difficile infection (CDI), which is now the most common health-care-associated infection in the USA. As traditional, standard CDI antibiotic therapies (metronidazole and vancomycin) are limited by their broad spectrum and further perturbation of the intestinal microbiota, which result in unacceptably high recurrence rates, novel therapeutic strategies for CDI are needed. Emerging CDI therapies are focused on limiting further perturbation of the intestinal microbiota and/or restoring the microbiota to its pre-morbid state, reducing colonization of the intestinal tract by toxigenic strains of C. difficile and bolstering the host immune response against C. difficile toxins. Fidaxomicin is associated with reduced CDI recurrences, and other emerging narrow-spectrum CDI antibiotic therapies might eventually demonstrate a similar benefit. Prevention of intestinal colonization of toxigenic strains of C. difficile can be achieved through restoration of the intestinal microbiota with faecal microbiota transplantation, as well as by colonizing the gut with nontoxigenic C. difficile strains. Finally, emerging immunological therapies, including monoclonal antibodies and vaccines against C. difficile toxins, might protect against CDI and subsequent CDI recurrences. The available clinical data for these emerging therapies, and their relative advantages and disadvantages, are described.
Children's National Medical Center1, University of California, San Francisco2, University of Amsterdam3, National Institutes of Health4, Heidelberg University5, German Cancer Research Center6, University of Toronto7, University of Colorado Denver8, University of Padua9, Harvard University10, University of Texas Southwestern Medical Center11, Children's Memorial Hospital12, Northwestern University13, McGill University14
TL;DR: The conclusions and recommendations of a consensus conference of how best to integrate the growing body of molecular genetic information into tumor classifications and, more importantly, for future treatment of pediatric LGGs are summarized here.
Abstract: For the past decade, it has been recognized that pediatric low-grade gliomas (LGGs) and glial-neuronal tumors carry distinct molecular alterations with resultant aberrant intracellular signaling in the Ras-mitogen-activated protein kinase pathway. The conclusions and recommendations of a consensus conference of how best to integrate the growing body of molecular genetic information into tumor classifications and, more importantly, for future treatment of pediatric LGGs are summarized here. There is uniform agreement that molecular characterization must be incorporated into classification and is increasingly critical for appropriate management. Molecular-targeted therapies should be integrated expeditiously, but also carefully into the management of these tumors and success measured not only by radiographic responses or stability, but also by functional outcomes. These trials need to be carried out with the caveat that the long-term impact of molecularly targeted therapy on the developing nervous system, especially with long duration treatment, is essentially unknown.
TL;DR: PTNFL is defined as a biologically and clinically distinct indolent lymphoma of children and adults characterized by a high prevalence of MAPK pathway mutations and a near absence of mutations in epigenetic modifiers.
Wayne State University1, Children's Memorial Hospital2, Boston University3, Johns Hopkins University School of Medicine4, Cincinnati Children's Hospital Medical Center5, University of Texas Southwestern Medical Center6, Columbia University7, George Washington University8, University of Wisconsin-Madison9, University of Colorado Denver10, National Jewish Health11
TL;DR: Allergy distinguishes asthma phenotypes in urban children and a symptomatic phenotype with little allergy or allergic inflammation was identified among inner-city children receiving guidelines-based management.
Abstract: Background Children with asthma in low-income urban areas have high morbidity. Phenotypic analysis in these children is lacking, but may identify characteristics to inform successful tailored management approaches. Objective We sought to identify distinct asthma phenotypes among inner-city children receiving guidelines-based management. Methods Nine inner-city asthma consortium centers enrolled 717 children aged 6 to 17 years. Data were collected at baseline and prospectively every 2 months for 1 year. Participants' asthma and rhinitis were optimally managed by study physicians on the basis of guidelines. Cluster analysis using 50 baseline and 12 longitudinal variables was performed in 616 participants completing 4 or more follow-up visits. Results Five clusters (designated A through E) were distinguished by indicators of asthma and rhinitis severity, pulmonary physiology, allergy (sensitization and total serum IgE), and allergic inflammation. In comparison to other clusters, cluster A was distinguished by lower allergy/inflammation, minimally symptomatic asthma and rhinitis, and normal pulmonary physiology. Cluster B had highly symptomatic asthma despite high step-level treatment, lower allergy and inflammation, and mildly altered pulmonary physiology. Cluster C had minimally symptomatic asthma and rhinitis, intermediate allergy and inflammation, and mildly impaired pulmonary physiology. Clusters D and E exhibited progressively higher asthma and rhinitis symptoms and allergy/inflammation. Cluster E had the most symptomatic asthma while receiving high step-level treatment and had the highest total serum IgE level (median, 733 kU/L), blood eosinophil count (median, 400 cells/mm 3 ), and allergen sensitizations (15 of 22 tested). Conclusions Allergy distinguishes asthma phenotypes in urban children. Severe asthma often coclusters with highly allergic children. However, a symptomatic phenotype with little allergy or allergic inflammation was identified.
TL;DR: A review of seminal findings pertinent to VM highlights the effects of a novel, small molecular compound, CVM-1118, currently under clinical development to target VM, and illuminates important molecular pathways involved in the suppression of this plastic, aggressive phenotype, using melanoma as a model.
Boston Children's Hospital1, University of Toronto2, Medical College of Wisconsin3, Northwestern University4, Children's Memorial Hospital5, Eduardo Mondlane University6, Harvard University7, University of California, San Francisco8, Brigham and Women's Hospital9, Mongolian National University10, Partners In Health11, Lund University12, King's College London13, University of Colorado Boulder14, Rockefeller Foundation15, University of London16, University of Washington17, University of Connecticut18, University of Utah19, Intermountain Healthcare20, Cornell University21, Vanderbilt University22, University of British Columbia23, World Bank Group24, Duke University25, Massachusetts Eye and Ear Infirmary26
TL;DR: A consensus statement providing practical advice to major actors in global surgery traces a common policy agenda between major actors and provides a roadmap for maximising benefit to surgical patients worldwide.
Abstract: The Millennium Development Goals have ended and the Sustainable Development Goals have begun, marking a shift in the global health landscape. The frame of reference has changed from a focus on 8 development priorities to an expansive set of 17 interrelated goals intended to improve the well-being of all people. In this time of change, several groups, including the Lancet Commission on Global Surgery, have brought a critical problem to the fore: 5 billion people lack access to safe, affordable surgical and anaesthesia care when needed. The magnitude of this problem and the world's new focus on strengthening health systems mandate reimagined roles for and renewed commitments from high income country actors in global surgery. To discuss the way forward, on 6 May 2015, the Commission held its North American launch event in Boston, Massachusetts. Panels of experts outlined the current state of knowledge and agreed on the roles of surgical colleges and academic medical centres; trainees and training programmes; academia; global health funders; the biomedical devices industry, and news media and advocacy organisations in building sustainable, resilient surgical systems. This paper summarises these discussions and serves as a consensus statement providing practical advice to these groups. It traces a common policy agenda between major actors and provides a roadmap for maximising benefit to surgical patients worldwide. To close the access gap by 2030, individuals and organisations must work collectively, interprofessionally and globally. High income country actors must abandon colonial narratives and work alongside low and middle income country partners to build the surgical systems of the future.
TL;DR: There are few pediatric data to indicate the efficacy and safety of pharmacologic or endoscopic therapies as primary prophylaxis or that prevention of a sentinel variceal bleed will ultimately improve survival; therefore, no recommendation for primary proPHylaxis with endoscopicvariceal ligation, sclerotherapy, or nonspecific beta‐blockade in children was proposed.
TL;DR: The findings collectively highlight the importance of age‐matched control data for the characterization of intracranial and cardiac hemodynamics in children and adults over a broad range of ages.
Abstract: Background Cerebral and cardiac blood flow are important to the pathophysiology and development of cerebro‐ and cardiovascular diseases. The purpose of this study was to investigate the age dependence of normal cerebral and cardiac hemodynamics in children and adults over a broad range of ages.
Methods and Results Overall, 52 children (aged 0.6–17.2 years) and 30 adults (aged 19.2–60.7 years) without cerebro‐ and cardiovascular diseases were included in this study. Intracranial 4‐dimensional flow and cardiac 2‐dimensional phase‐contrast magnetic resonance imaging were performed for all participants to measure flow parameters in the major intracranial vessels and aorta. Total cerebral blood flow (TCBF), cardiac and cerebral indexes, brain volume, and global cerebral perfusion (TCBF/brain volume) were evaluated. Flow analysis revealed that TCBF increased significantly from age 7 months to 6 years ( P <0.001) and declined thereafter ( P <0.001). Both cardiac and cerebral indices declined with age ( P <0.001). The ratio of TCBF to ascending aortic flow declined rapidly until age 18 years ( P <0.001) and remained relatively stable thereafter. Age‐related changes of cerebral vascular peak velocities exhibited a trend similar to TCBF. By comparison, aortic peak velocities maintained relatively high levels in children and declined with age in adults ( P <0.001). TCBF significantly correlated with brain volume in adults ( P =0.005) and in 2 pediatric subgroups, aged <7 years ( P <0.001) and 7 to 18 years ( P =0.039).
Conclusions Cerebral and cardiac flow parameters are highly associated with age. The findings collectively highlight the importance of age‐matched control data for the characterization of intracranial and cardiac hemodynamics.
TL;DR: Affirmative care with transgender and gender nonconforming (TGNC) children and adolescents is a new framework under which many mental health clinicians now practice as discussed by the authors, based on a premise that appreciates diverse gender expressions and identities within society, and encourages the highest potential for individuals to follow their own paths to positive emotional well-being.
Abstract: Affirmative care with transgender and gender nonconforming (TGNC) children and adolescents is a new framework under which many mental health clinicians now practice. It rests on a premise that appreciates diverse gender expressions and identities within society, and encourages the highest potential for individuals to follow their own paths to positive emotional well-being. Scientific understanding of the phenomenology of gender development in children and adolescents is scarce, and the gaps in knowledge limit evidence-based practice when working with these youths. Interventions span many domains within the physical and mental health realms, calling for providers to navigate differing interdisciplinary perspectives when optimizing assessment and treatment goals. In addition, interventions differ according to developmental stage, and newer approaches and treatments have become more popular within the last decade. For children, the concept of social gender transition has remained controversial, as relatively historical approaches (discouraging cross-gender behavior) have become outdated and more recent methods (supporting gender transition) have gained backing. Fully reversible pubertal suppression has been introduced for TGNC adolescents as a means of buying time for exploration without the pressures of irreversible pubertal advancement. Given the current deficits in scientific understanding of genderidentity development in youth, the affirmative provider often faces decisions that are challenging, complex, and unclear. This paper describes the theoretical approaches to TGNC youth across development, provides a brief overview of the current research, and offers providers a way to conceptualize and provide care that can be both supportive and scientifically driven when done in a thoughtful, balanced way.
Ohio State University1, University of Iowa2, Northwestern University3, Beth Israel Deaconess Medical Center4, University of Utah5, Boston Children's Hospital6, Nationwide Children's Hospital7, Children's Memorial Hospital8, University of Texas Southwestern Medical Center9, University of Colorado Denver10, Washington University in St. Louis11, Columbia University12, University of California, Davis13, Vanderbilt University14, State University of New York Upstate Medical University15, Children's National Medical Center16, University of California, Los Angeles17, Harvard University18, Nemours Foundation19, The Ohio State University Wexner Medical Center20
TL;DR: This study prospectively assessed putative promising biomarkers for use in assessing infants with spinal muscular atrophy (SMA) and identified several promising targets for further investigation.
Abstract: Objective
This study prospectively assessed putative promising biomarkers for use in assessing infants with spinal muscular atrophy (SMA).
Methods
This prospective, multi-center natural history study targeted the enrollment of SMA infants and healthy control infants less than 6 months of age. Recruitment occurred at 14 centers within the NINDS National Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT) Network. Infant motor function scales and putative electrophysiological, protein and molecular biomarkers were assessed at baseline and subsequent visits.
Results
Enrollment began November, 2012 and ended September, 2014 with 26 SMA infants and 27 healthy infants enrolled. Baseline demographic characteristics of the SMA and control infant cohorts aligned well. Motor function as assessed by the Test for Infant Motor Performance Items (TIMPSI) and the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) revealed significant differences between the SMA and control infants at baseline. Ulnar compound muscle action potential amplitude (CMAP) in SMA infants (1.4 ± 2.2 mV) was significantly reduced compared to controls (5.5 ± 2.0 mV). Electrical impedance myography (EIM) high-frequency reactance slope (Ohms/MHz) was significantly higher in SMA infants than controls SMA infants had lower survival motor neuron (SMN) mRNA levels in blood than controls, and several serum protein analytes were altered between cohorts.
Interpretation
By the time infants were recruited and presented for the baseline visit, SMA infants had reduced motor function compared to controls. Ulnar CMAP, EIM, blood SMN mRNA levels, and serum protein analytes were able to distinguish between cohorts at the enrollment visit.
Boston Children's Hospital1, University of California, San Diego2, Morgan Stanley Children's Hospital3, Johns Hopkins University4, Saint Louis University5, Cincinnati Children's Hospital Medical Center6, Baylor College of Medicine7, Emory University8, Indiana University9, Children's Memorial Hospital10, University of California, San Francisco11, University of Washington12, Washington University in St. Louis13, National Institutes of Health14
TL;DR: It is found that 1 year of CBDR did not reduce overall histologic markers of NAFLD compared with placebo in children, and those taking CBDR had a 4-fold better chance of histologic improvement.