Systematic review of disease-modifying antirheumatic drugs for juvenile idiopathic arthritis

<p>Abstract</p> <p>Background</p> <p>Treatment of juvenile idiopathic arthritis (JIA) with disease-modifying antirheumatic drugs (DMARDs) may improve outcomes compared to conventional therapy (e.g., non-steroidal anti-inflammatory drugs, intra-articular corticosteroids). The purpose of this systematic review was to evaluate the comparative effectiveness and safety of DMARDs versus conventional therapy and versus other DMARDs.</p> <p>Results</p> <p>A systematic evidence review of 156 reports identified in MEDLINE^®, EMBASE^®, and by hand searches. There is some evidence that methotrexate is superior to conventional therapy. Among children who have responded to a biologic DMARD, randomized discontinuation trials suggest that continued treatment decreases the risk of having a flare. However, these studies evaluated DMARDs with different mechanisms of action (abatacept, adalimumab, anakinra, etanercept, intravenous immunoglobulin, tocilizumab) and used varying comparators and follow-up periods. Rates of serious adverse events are similar between DMARDs and placebo in published trials. This review identified 11 incident cases of cancer among several thousand children treated with one or more DMARD.</p> <p>Conclusions</p> <p>Few data are available to evaluate the comparative effectiveness of either specific DMARDs or general classes of DMARDs. However, based on the overall number, quality, and consistency of studies, there is moderate strength of evidence to support that DMARDs improve JIA-associated symptoms. Limited data suggest that short-term risk of cancer is low.</p

International Consensus Recommendations for the Treatment of Pediatric NMDAR Antibody Encephalitis.

OBJECTIVE: To create an international consensus treatment recommendation for pediatric NMDA receptor antibody encephalitis (NMDARE). METHODS: After selection of a panel of 27 experts with representation from all continents, a 2-step Delphi method was adopted to develop consensus on relevant treatment regimens and statements, along with key definitions in pediatric NMDARE (disease severity, failure to improve, and relapse). Finally, an online face-to-face meeting was held to reach consensus (defined as ≥75% agreement). RESULTS: Corticosteroids are recommended in all children with NMDARE (pulsed IV preferred), with additional IV immunoglobulin or plasma exchange in severe patients. Prolonged first-line immunotherapy can be offered for up to 3-12 months (oral corticosteroids or monthly IV corticosteroids/immunoglobulin), dependent on disease severity. Second-line treatments are recommended for cases refractory to first-line therapies (rituximab preferred over cyclophosphamide) and should be considered about 2 weeks after first-line initiation. Further immunotherapies for refractory disease 1-3 months after second-line initiation include another second-line treatment (such as cyclophosphamide) and escalation to tocilizumab. Maintenance immune suppression beyond 6 months (such as rituximab redosing or mycophenolate mofetil) is generally not required, except for patients with a more severe course or prolonged impairments and hospitalization. For patients with relapsing disease, second-line and prolonged maintenance therapy should be considered. The treatment of NMDARE following herpes simplex encephalitis should be similar to idiopathic NMDARE. Broad guidance is provided for the total treatment duration (first line, second line, and maintenance), which is dictated by the severity and clinical course (i.e., median 3, 9 and 18 months in the best, average, and worst responders, respectively). Recommendations on the timing of oncologic searches are provided. CONCLUSION: These international consensus recommendations for the management of pediatric NMDARE aim to standardize the treatment and provide practical guidance for clinicians, rather than absolute rules. A similar recommendation could be applicable to adult patients

Caregiver-reported delay in presentation to pediatric emergency departments for fear of contracting COVID-19: a multi-national cross-sectional study

Objective: To determine if caregivers of children presenting to pediatric emergency departments (EDs) during the COVID-19 pandemic are delaying presenting to care for fear of contracting COVID-19. Methods: This was a pre-planned secondary analysis of a cross-sectional survey study of caregivers accompanying their children aged 0-19 years to 16 pediatric EDs in 5 countries from May to June 2020. An anonymous online survey, completed by caregivers via RedCAP, included caregiver and child demographics, presenting complaints, if they delayed presentation and whether symptoms worsened during this interval, as well as caregiver concern about the child or caregiver having COVID-19 at the time of ED visit. Results: Of 1543 caregivers completing the survey, 287 (18.6%) reported a delay in seeking ED care due to concerns of contracting COVID-19 in the hospital. Of those, 124 (43.2%) stated their child's symptoms worsened during the waiting interval. Caregiver relationship to child [mother] (OR 1.85, 95% CI 1.27-2.76), presence of chronic illness in child (OR 1.78. 95% CI 1.14-2.79), younger age of caregiver (OR 0.965, 95% CI 0.943-0.986), and caregiver concerns about lost work during the pandemic (OR 1.08, 95% CI 1.04-1.12) were independently associated with a COVID-19-related delayed presentation in multivariable regression analysis. Conclusions: Almost one in five caregivers reported delaying ED presentation for their ill or injured child specifically due to fear of contracting COVID-19 while in hospital, with mothers, younger caregivers, caregivers of children with chronic illness, and those concerned about lost work more likely to report delaying ED presentation. Keywords: COVID-19; Caregivers; Children; Emergency department; Presentation dela

Climate Process Team on internal wave–driven ocean mixing

Author Posting. © American Meteorological Society, 2017. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Bulletin of the American Meteorological Society 98 (2017): 2429-2454, doi:10.1175/BAMS-D-16-0030.1.Diapycnal mixing plays a primary role in the thermodynamic balance of the ocean and, consequently, in oceanic heat and carbon uptake and storage. Though observed mixing rates are on average consistent with values required by inverse models, recent attention has focused on the dramatic spatial variability, spanning several orders of magnitude, of mixing rates in both the upper and deep ocean. Away from ocean boundaries, the spatiotemporal patterns of mixing are largely driven by the geography of generation, propagation, and dissipation of internal waves, which supply much of the power for turbulent mixing. Over the last 5 years and under the auspices of U.S. Climate Variability and Predictability Program (CLIVAR), a National Science Foundation (NSF)- and National Oceanic and Atmospheric Administration (NOAA)-supported Climate Process Team has been engaged in developing, implementing, and testing dynamics-based parameterizations for internal wave–driven turbulent mixing in global ocean models. The work has primarily focused on turbulence 1) near sites of internal tide generation, 2) in the upper ocean related to wind-generated near inertial motions, 3) due to internal lee waves generated by low-frequency mesoscale flows over topography, and 4) at ocean margins. Here, we review recent progress, describe the tools developed, and discuss future directions.We are grateful to U.S. CLIVAR for their leadership in instigating and facilitating the Climate Process Team program. We are indebted to NSF and NOAA for sponsoring the CPT series.2018-06-0

Carbohydrate Metabolism Is Essential for the Colonization of Streptococcus thermophilus in the Digestive Tract of Gnotobiotic Rats

Streptococcus thermophilus is the archetype of lactose-adapted bacterium and so far, its sugar metabolism has been mainly investigated in vitro. The objective of this work was to study the impact of lactose and lactose permease on S. thermophilus physiology in the gastrointestinal tract (GIT) of gnotobiotic rats. We used rats mono-associated with LMD-9 strain and receiving 4.5% lactose. This model allowed the analysis of colonization curves of LMD-9, its metabolic profile, its production of lactate and its interaction with the colon epithelium. Lactose induced a rapid and high level of S. thermophilus in the GIT, where its activity led to 49 mM of intra-luminal L-lactate that was related to the induction of mono-carboxylic transporter mRNAs (SLC16A1 and SLC5A8) and p27Kip1 cell cycle arrest protein in epithelial cells. In the presence of a continuous lactose supply, S. thermophilus recruited proteins involved in glycolysis and induced the metabolism of alternative sugars as sucrose, galactose, and glycogen. Moreover, inactivation of the lactose transporter, LacS, delayed S. thermophilus colonization. Our results show i/that lactose constitutes a limiting factor for colonization of S. thermophilus, ii/that activation of enzymes involved in carbohydrate metabolism constitutes the metabolic signature of S. thermophilus in the GIT, iii/that the production of lactate settles the dialogue with colon epithelium. We propose a metabolic model of management of carbohydrate resources by S. thermophilus in the GIT. Our results are in accord with the rationale that nutritional allegation via consumption of yogurt alleviates the symptoms of lactose intolerance

Climate Process Team On Internal Wave-Driven Ocean Mixing

The study summarizes recent advances in our understanding of internal wave–driven turbulent mixing in the ocean interior and introduces new parameterizations for global climate ocean models and their climate impacts

Climate Process Team on Internal-Wave Driven Ocean Mixing

Diapycnal mixing plays a primary role in the thermodynamic balance of the ocean, and consequently, in oceanic heat and carbon uptake and storage. Though observed mixing rates are on average consistent with values required by inverse models, recent attention has focused on the dramatic spatial variability, spanning several orders of magnitude, of mixing rates in both the upper and deep ocean. Climate models have been shown to be very sensitive not only to the overall level but to the detailed distribution of mixing; sub-grid-scale parameterizations based on accurate physical processes will allow model forecasts to evolve with a changing climate. Spatio-temporal patterns of mixing are largely driven by the geography of generation, propagation and destruction of internal waves, which are thought to supply much of the power for turbulent mixing. Over the last five years and under the auspices of US CLIVAR, a NSF and NOAA supported Climate Process Team has been engaged in developing, implementing and testing dynamics-base parameterizations for internal-wave driven turbulent mixing in global ocean models. The work has primarily focused on turbulence 1) near sites of internal tide generation, 2) in the upper ocean related to wind-generated near inertial motions, 3) due to internal lee waves generated by low-frequency mesoscale flows over topography, and 4) at ocean margins. Here we review recent progress, describe the tools developed, and discuss future directions

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic