Summary
Background
The Harmonising Outcome Measures for Eczema (HOME) initiative has defined four core outcome domains for a core outcome set (COS) to be measured in all atopic eczema (AE) trials to ...ensure cross‐trial comparison: clinical signs, symptoms, quality of life and long‐term control.
Objectives
The aim of this paper is to report on the consensus process that was used to select the core instrument to consistently assess symptoms in all future AE trials.
Methods
Following the HOME roadmap, two systematic reviews were performed which identified three instruments that had sufficient evidence of validity, reliability and feasibility to be considered for the final COS.
Results
At the fourth international HOME meeting, there was broad consensus among all stakeholders that the Patient‐Oriented Eczema Measure (POEM) should be used as the core instrument (87·5% agreed, 9·4% unsure, 3·1% disagreed).
Conclusions
All relevant stakeholders are encouraged to use POEM as the chosen instrument to measure the core domain of symptoms in all future AE clinical trials. Other instruments of interest can be used in addition to POEM.
What's already known about this topic?
There is insufficient high‐quality evidence for many of the treatments of atopic eczema (AE), which is partly due to the heterogeneity in outcomes used in clinical trials.
The Harmonising Outcome Measures for Eczema initiative defined ‘symptoms’ as one of the core outcome domains that should be measured in AE clinical trials.
What does this study add?
Consensus was reached on the Patient‐Oriented Eczema Measure (POEM) as the core instrument to measure symptoms.
This statement should promote awareness among all stakeholders.
What are the clinical implications of this work?
Not only itch and sleeplessness are symptoms important for patients with AE.
All relevant stakeholders are encouraged to use POEM as the chosen instrument to measure the core domain of symptoms in all future AE clinical trials.
Respond to this article
Linked Comment: Naldi. Br J Dermatol 2017; 176:852–853
Plain language summary available online
ABSTRACT The Atacama Cosmology Telescope (ACT) makes high angular resolution measurements of anisotropies in the Cosmic Microwave Background (CMB) at millimeter wavelengths. We describe ACTPol, an ...upgraded receiver for ACT, which uses feedhorn-coupled, polarization-sensitive detector arrays, a 3° field of view, 100 mK cryogenics with continuous cooling, and meta material antireflection coatings. ACTPol comprises three arrays with separate cryogenic optics: two arrays at a central frequency of 148 GHz and one array operating simultaneously at both 97 GHz and 148 GHz. The combined instrument sensitivity, angular resolution, and sky coverage are optimized for measuring angular power spectra, clusters via the thermal Sunyaev-Zel'dovich (SZ) and kinetic SZ signals, and CMB lensing due to large-scale structure. The receiver was commissioned with its first 148 GHz array in 2013, observed with both 148 GHz arrays in 2014, and has recently completed its first full season of operations with the full suite of three arrays. This paper provides an overview of the design and initial performance of the receiver and related systems.
Advanced ACTPol is a polarization-sensitive upgrade for the 6 m aperture Atacama Cosmology Telescope, adding new frequencies and increasing sensitivity over the previous ACTPol receiver. In 2016, ...Advanced ACTPol will begin to map approximately half the sky in five frequency bands (28-230 GHz). Its maps of primary and secondary cosmic microwave background anisotropies-imaged in intensity and polarization at few arcminute-scale resolution-will enable precision cosmological constraints and also awide array of cross-correlation science that probes the expansion history of the universe and the growth of structure via gravitational collapse. To accomplish these scientific goals, the AdvancedACTPol receiver will be a significant upgrade to the ACTPol receiver, including four new multichroic arrays of cryogenic, feedhorn-coupled AlMn transition edge sensor polarimeters (fabricated on 150 mm diameter wafers); a system of continuously rotating meta-material silicon half-wave plates; and a new multiplexing readout architecture which uses superconducting quantum interference devices and time division to achieve a 64-row multiplexing factor. Here we present the status and scientific goals of the Advanced ACTPol instrument, emphasizing the design and implementation of the AdvancedACTPol cryogenic detector arrays.
Summary
Background
The Harmonising Outcome Measures for Eczema (HOME) initiative has established a core outcome set of domains for atopic eczema (AE) clinical trials. Previous consensus meetings have ...agreed on preferred instruments for clinician‐reported signs (Eczema Area and Severity Index, EASI) and patient‐reported symptoms (Patient‐Oriented Eczema Measure, POEM). This paper reports consensus decisions from the HOME VII meeting.
Objectives
To complete the core outcome set for AE by agreeing on core outcome instruments for the domains of quality of life (QoL), long‐term control and itch intensity.
Methods
A face‐to‐face consensus meeting was held in Tokyo, Japan (8–10 April 2019) including 75 participants (49 healthcare professionals/methodologists, 14 patients, 12 industry representatives) from 16 countries. Consensus decisions were made by presentations of evidence, followed by whole and small group discussions and anonymous voting using predefined consensus rules.
Results
It was agreed by consensus that QoL should be measured using the Dermatology Life Quality Index (DLQI) for adults, the Children’s Dermatology Life Quality Index (CDLQI) for children and the Infant’s Dermatology Quality of Life Index (IDQoL) for infants. For long‐term control, the Recap of Atopic Eczema (RECAP) instrument or the Atopic Dermatitis Control Test (ADCT) should be used. Consensus was not reached over the frequency of data collection for long‐term control. The peak itch numerical rating scale (NRS)‐11 past 24 h was recommended as an additional instrument for the symptom domain in trials of older children and adults. Agreement was reached that all core outcome instruments should be captured at baseline and at the time of primary outcome assessment as a minimum.
Conclusions
For now, the core outcome set for clinical trials in AE is complete. The specified domains and instruments should be used in all new clinical trials and systematic reviews of eczema treatments.
What is already known about this topic?
Core outcomes sets improve the design and reporting of clinical trials, reduce selective outcome reporting bias and facilitate meta‐analysis of results in systematic reviews.
The HOME core outcome set for eczema recommends the inclusion of four core domains in all atopic eczema trials: clinician‐reported signs, patient‐reported symptoms, health‐related quality of life (HrQoL) and long‐term control.
Clinician‐reported signs should be captured using the Eczema Area and Severity Index (EASI) and patient‐reported symptoms using the Patient‐Oriented Eczema Measure (POEM).
What does this study add?
The HOME core outcome set is now complete and recommended core outcome instruments have been agreed on for all four domains.
Core outcome instruments for HrQoL: Dermatology Life Quality Index (DLQI) for adults, Children’s Dermatology Life Quality Index (CDLQI) for children and Infant’s Dermatology Quality of Life Index (IDQoL) for infants.
Core outcome instruments for long‐term control: either the Recap of Atopic Eczema (RECAP) or the Atopic Dermatitis Control Test (ADCT).
In addition, itch intensity should be measured using the peak NRS‐11 past 24 h for trials including older children and adults.
What are the clinical implications of this work?
If all future trials of eczema treatments include the HOME core outcome instruments, then trial results will be more readily incorporated into meta‐analyses in systematic reviews and clinical care will be informed by the best available evidence.
Linked Comment: D.F. Murrell and C.F. Paul. Br J Dermatol 2021; 185:13–14.
The Tierra Blanca (TB) eruptive suite comprises the last four major eruptions of Ilopango caldera in El Salvador (≤45 ka), including the youngest Tierra Blanca Joven eruption (TBJ; ∼106 km3): the ...most voluminous event during the Holocene in Central America. Despite the protracted and productive history of explosive silicic eruptions at Ilopango caldera, many aspects regarding the longevity and the prevailing physicochemical conditions of the underlying magmatic system remain unknown. Zircon 238U‐230Th geochronology of the TB suite (TBJ, TB2, TB3, and TB4) reveals a continuous and overlapping crystallization history among individual eruptions, suggesting persistent melt presence in thermally and compositionally distinct magma reservoirs over the last ca. 80 kyr. The longevity of zircon is in contrast to previously determined crystallization timescales of <10 kyr for major mineral phases in TBJ. This dichotomy is explained by a process of rhyolitic melt segregation from a crystal‐rich refractory residue that incorporates zircon, whereas a new generation of major mineral phases crystallized shortly before eruption. Ti‐in‐zircon temperatures and amphibole geothermobarometry suggest that rhyolitic melt was extracted from different storage zones of the magma reservoir as indicated by distinct but synchronous thermochemical zircon histories among the TB suite eruptions. Zircon from TBJ and TB2 suggests magma differentiation within deeper and hotter parts of the reservoir, whereas zircon from TB3 and TB4 instead hints at crystallization in comparatively shallower and cooler domains. The assembly of the voluminous TBJ magma reservoir was also likely enhanced by cannibalization of hydrothermally altered components as suggested by low‐δ18O values in zircon (+4.5 ± 0.3‰).
Plain Language Summary
The collapse of a volcano edifice into its shallow magma chamber can produce one of the most dangerous single events in nature, known as a caldera‐forming eruption. The TBJ eruption in El Salvador is of this kind and occurred around 1,500 years ago, having a profound impact on Maya societies. Because of this, it is crucial to understand the inner workings of caldera‐forming eruptions to assess volcanic risks and their mitigation. Beneath Ilopango caldera, the micrometer‐sized radioisotopically datable mineral zircon grew within different storage levels of a silica‐rich magma reservoir suggesting continuous melt presence for up to ca. 80,000 years prior to eruption. The time information given by zircon contrasts with that extracted from other, more abundant minerals from the same rocks (<10,000 years). We explain this time difference between coexisting minerals by the ability of melt to carry along small zircon crystals, whereas coeval, larger, and more abundant minerals are left behind in the partially solidified portion of the magma reservoir. Once the segregated melt coalesced in a shallower and dominantly liquid magma chamber, major minerals resumed crystallization shortly before eruption. In addition, this new magma incorporated parts of older magmatic rocks from preceding volcanic cycles, thus generating even larger magma volumes.
Key Points
U‐Th zircon ages for the last four explosive eruptions of Ilopango caldera reveal a long‐lived magma reservoir (>80 kyr)
Contrasting residence times for major minerals and zircon suggest extraction of zircon along with evolved melt from crystal residue
Melt extraction from vertically extensive, thermally zoned magma reservoir
We present a constraint on the tensor-to-scalar ratio, r, derived from measurements of cosmic microwave background (CMB) polarization B-modes with "delensing," whereby the uncertainty on r ...contributed by the sample variance of the gravitational lensing B-modes is reduced by cross-correlating against a lensing B-mode template. This template is constructed by combining an estimate of the polarized CMB with a tracer of the projected large-scale structure. The large-scale-structure tracer used is a map of the cosmic infrared background derived from Planck satellite data, while the polarized CMB map comes from a combination of South Pole Telescope, bicep/Keck, and Planck data. We expand the bicep/Keck likelihood analysis framework to accept a lensing template and apply it to the bicep/Keck dataset collected through 2014 using the same parametric foreground modeling as in the previous analysis. From simulations, we find that the uncertainty on r is reduced by ∼10%, from σ(r)=0.024 to 0.022, which can be compared with a ∼26% reduction obtained when using a perfect lensing template or if there were zero lensing B-modes. Applying the technique to the real data, the constraint on r is improved from r0.05<0.090 to r0.05<0.082 (95% C.L.). This is the first demonstration of improvement in an r constraint through delensing.
This study evaluates diabetes self-management mobile health applications available from European app stores with respect to quality, concordance with recommended self-management tasks and ...implementation of persuasive system design principles. The European Play Store and Apple App Store were systematically searched and relevant apps were tested. Two raters independently assessed app quality using the Mobile Application Rating Scale and conducted a content analysis of provided persuasive system design principles and self-management tasks. A total of 2,269 mobile health applications were identified and 120 could be included in the evaluation. The overall quality was rated as moderate M = 3.20 (SD = 0.39, min = 2.31, max = 4.62), with shortcomings in the subcategories of engagement (M = 2.80, SD = 0.67) and information quality (M = 2.26, SD = 0.48). Scientific evidence is available for 8% of the apps. The reviewed apps implemented a median of three persuasive system design principles (range 0-15) and targeted a median of 4.5 (range 1-8) self-management tasks, however, with a lack of information about psychosocial coping strategies. Most available diabetes self-management apps lack a scientific evidence base. Persuasive system design features are underrepresented and may form a promising tool to improve app quality. Furthermore, the interaction of physical and behavioral health should be improved in existing diabetes self-management mobile health applications.
Summary
Background
A long‐term prospective observational safety study is essential to characterize fully the safety profile of systemic immunomodulating therapies for patients with atopic eczema. The ...TREatment of ATopic eczema (TREAT) Registry Taskforce offers a large platform to conduct such research using national registries that collect the same data using a predefined core dataset.
Objectives
To present a protocol for a safety study comparing dupilumab with other systemic immunomodulating therapies in children and adults with moderate‐to‐severe atopic eczema, to assess the long‐term safety risk of these therapies in a routine clinical care setting.
Methods
We describe a registry‐embedded international observational prospective cohort study. Adult and paediatric patients who start treatment with dupilumab or another systemic immunomodulating agent for their atopic eczema will be included. The primary end point is the incidence of malignancies (excluding nonmelanoma skin cancer) compared between the treatment groups. Secondary end points include other serious adverse events and adverse events of special interest, such as eye disorders and eosinophilia.
Conclusions
This protocol delineates a safety study for dupilumab in adult and paediatric patients with atopic eczema, using a standardized methodological approach across several national registries. The protocol could also be used for other novel systemic immunomodulating therapies, and could provide licensing and reimbursement authorities, pharmaceutical companies and clinicians with safety evidence from a routine clinical care setting.
What's already known about this topic?
There is a need for long‐term data on the safety of systemic immunomodulating therapies in patients with atopic eczema.
Regulatory bodies, such as the European Medicines Agency, increasingly stipulate the collection of such data as part of the licensing agreement for new treatments, to assess the new agent's long‐term safety profile against established therapies.
Large numbers of patients with a long duration of follow‐up are necessary in order to detect rare events like malignancies.
What does this study add?
The TREAT Registry Taskforce offers a platform to conduct such research with a network of multiple national atopic eczema research registries.
We present a protocol for an investigator‐initiated multicentre safety study comparing dupilumab with other systemic immunomodulating therapies in adults and subsequently adolescents and children with moderate‐to‐severe atopic eczema.
This protocol can be used as a framework for similar studies for other novel systemic immunomodulating therapies across both adult and paediatric populations.
Plain language summary available online
Summary
This report provides a summary of the third meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in San Diego, CA, U.S.A., 6–7 April 2013 (HOME III). The meeting ...addressed the four domains that had previously been agreed should be measured in every eczema clinical trial: clinical signs, patient‐reported symptoms, long‐term control and quality of life. Formal presentations and nominal group techniques were used at this working meeting, attended by 56 voting participants (31 of whom were dermatologists). Significant progress was made on the domain of clinical signs. Without reference to any named scales, it was agreed that the intensity and extent of erythema, excoriation, oedema/papulation and lichenification should be included in the core outcome measure for the scale to have content validity. The group then discussed a systematic review of all scales measuring the clinical signs of eczema and their measurement properties, followed by a consensus vote on which scale to recommend for inclusion in the core outcome set. Research into the remaining three domains was presented, followed by discussions. The symptoms group and quality of life groups need to systematically identify all available tools and rate the quality of the tools. A definition of long‐term control is needed before progress can be made towards recommending a core outcome measure.
What's already known about this topic?
Many different scales have been used to measure eczema, making it difficult to compare trials in meta‐analyses and hampering improvements in clinical practice.
HOME core outcome measures must pass the OMERACT (Outcome Measures in Rheumatology) filter of truth (validity), discrimination (sensitivity to change and responsiveness) and feasibility (ease of use, costs, time to perform and interpret).
It has been previously agreed as part of the consensus process that four domains should be measured by the core outcomes: clinical signs, patient‐reported symptoms, long‐term control and health‐related quality of life.
What does this study add?
Progress was made towards developing a core outcome set for measuring eczema in clinical trials.
The group established the essential items to be included in the outcome measure for the clinical signs of eczema and was able to recommend a scale for the core set.
The remaining three domains of patient‐reported symptoms, long‐term control and health‐related quality of life require further work and meetings to determine the core outcome measures.
PDF
