Matching-Adjusted Indirect Comparison of Crisaborole Ointment 2% vs. Topical Calcineurin Inhibitors in the Treatment of Patients with Mild-to-Moderate Atopic Dermatitis

INTRODUCTION: Crisaborole topical ointment, 2%, is a nonsteroidal, topical anti-inflammatory phosphodiesterase-4 (PDE4) inhibitor that is approved for the treatment of mild-to-moderate atopic dermatitis (AD). The objective of the current analysis was to compare the efficacy of crisaborole 2% relative to pimecrolimus 1%, tacrolimus 0.03% and tacrolimus 0.1% in patients aged ≥ 2 years with mild-to-moderate AD by comparing improvement in Investigator’s Static Global Assessment scores ( (ISGA scores of 0/1 indicating “clear or almost clear”). ISGA was selected as the primary efficacy outcome given the US Food and Drug Administration’s recommendations on the use of ISGA for assessment of global severity in AD and to align with efficacy measurements in the crisaborole registration trials. Safety endpoints could not be analyzed due to differences in outcome definitions across studies. METHODS: Efficacy of crisaborole was evaluated using individual patient data (IPD) from two pivotal phase III randomized controlled trials (RCTs), and efficacy of comparators was evaluated using published RCTs included in a previous network meta-analysis. Vehicle controls were not comparable due to differences in ingredients and population imbalance and, therefore, an unanchored matching-adjusted indirect comparison (MAIC) was used, which reweighted IPD for crisaborole to estimate absolute response in comparator populations. RESULTS: The odds of achieving an improvement in ISGA score was higher with crisaborole 2% versus pimecrolimus 1% (odds ratio [OR] 2.03; 95% confidence interval [CI] 1.45–2.85; effective sample size =  627, reduced from 1021; p value < 0.001) and for crisaborole 2% versus tacrolimus 0.03% (OR 1.50; 95% CI 1.09–2.05; effective sample size = 311, reduced from 1021; p = 0.012). CONCLUSION: The unanchored MAIC suggests that the odds of achieving an improvement in ISGA score is greater with crisaborole 2% than with pimecrolimus 1% or tacrolimus 0.03% in patients aged ≥ 2 years with mild-to-moderate AD. These results are consistent with findings from the previously published network meta-analysis, which used a different methodology for performing indirect treatment comparisons. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13555-021-00646-1

Cost–effectiveness analysis for avelumab first-line maintenance treatment of advanced urothelial carcinoma in Scotland

Aim: The cost–effectiveness of avelumab first-line maintenance treatment for locally advanced or metastatic urothelial carcinoma in Scotland was assessed. Materials &amp; methods: A partitioned survival model was developed comparing avelumab plus best supportive care (BSC) versus BSC alone, incorporating JAVELIN Bladder 100 trial data, costs from national databases and published literature and clinical expert validation of assumptions. Incremental cost–effectiveness ratio (ICER) was estimated using lifetime costs and quality-adjusted life-years (QALY). Results: Avelumab plus BSC had incremental costs of £9446 and a QALY gain of 0.63, leading to a base-case (deterministic) ICER of £15,046 per QALY gained, supported by robust sensitivity analyses. Conclusion: Avelumab first-line maintenance is likely to be a cost-effective treatment for locally advanced or metastatic urothelial carcinoma in Scotland

Neuropathic pain

Neuropathic pain is caused by a lesion or disease of the somatosensory system, including peripheral fibres (Aβ, Aδ and C fibres) and central neurons, and affects 7-10% of the general population. Multiple causes of neuropathic pain have been described and its incidence is likely to increase owing to the ageing global population, increased incidence of diabetes mellitus and improved survival from cancer after chemotherapy. Indeed, imbalances between excitatory and inhibitory somatosensory signalling, alterations in ion channels and variability in the way that pain messages are modulated in the central nervous system all have been implicated in neuropathic pain. The burden of chronic neuropathic pain seems to be related to the complexity of neuropathic symptoms, poor outcomes and difficult treatment decisions. Importantly, quality of life is impaired in patients with neuropathic pain owing to increased drug prescriptions and visits to health care providers, as well as the morbidity from the pain itself and the inciting disease. Despite challenges, progress in the understanding of the pathophysiology of neuropathic pain is spurring the development of new diagnostic procedures and personalized interventions, which emphasize the need for a multidisciplinary approach to the management of neuropathic pain

Equity in Global Health Law - Policy Brief

Equity has been sorely lacking in pandemic preparedness and response, and COVID-19 is but the latest example (O’Cuinn and Switzer, 2019; Rourke, 2019). The response to COVID-19 was characterised by nationalism, inequity in access to diagnostics, vaccines, therapeutics and personal protective equipment (PPE) between the Global North and the Global South, as well as discriminatory, and in some instances racist, border closures chiefly impacting low- and middle-income countries. In response to the widespread inequity witnessed during the COVID-19 pandemic, Member States of the World Health Organisation (WHO) are currently negotiating a new international legal instrument - the Pandemic Treaty - intended to prevent pandemics and mitigate associated inequalities such as vaccine access, and improve compliance with international law during pandemic events. From the initial proposal for the Treaty, through the many rounds of discussions that have occurred to date, it is clear that the new instrument is intended to be grounded in equity, with equity positioned as both an objective and as an operational output (Wenham, Eccleston- Turner & Voss, 2022). However, while equity is recognised as a general principle of international law, it does not have a precise and defined meaning. From the start of negotiations, it was unclear what an instrument ‘grounded’ in equity should look like, what the principle of equity actually means in this context, and how this principle can translate into meaningful obligations within international law more generally, as well as pandemic preparedness and global health governance specifically. In an attempt to answer these questions, we convened - with the assistance of funding from the Scottish Council for Global Affairs and the ESRC IAA Policy Impact Fund - a workshop at King’s College, London at which we gathered together experts on equity from different disciplinary backgrounds in an attempt to understand and conceptualize equity as a legal concept, charting its history, development and application within both domestic and international law. In the following short discussion, we distill some of the lessons at this workshop from both national law as well as other international arenas, before offering suggestions on how this somewhat opaque concept might be effectively operationalised within the Pandemic Treaty. The aim of this discussion is therefore not to engage in a lengthy, academic literature review of the different conceptions of equity found in academic texts - of which there is an abundance of relevant literature - but rather to offer practical insights to the operationalisation of equity to the Pandemic Treaty. What we find is that there is no ‘one’ way to do equity or for an international agreement to be equitable. Our discussions found that equity must be more than an abstract buzzword - simply inserting the word equity into a legal text does not achieve equity. However, international law offers a number of lessons for responding to instances of inequity arising in the absence of a perfect, overarching functional definition of equity

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio

Synthesis and characterisation of the vibrational and electrical properties of antiferromagnetic 6L-Ba2CoTeO6 ceramics

Optimal processing conditions for fabrication of dense single-phase 6L-Ba2CoTeO6 ceramics via the solid-state reaction method were determined. These ceramics possess a room-temperature crystal structure described by the centrosymmetric P[3 with combining macron]m1 space group. Polarized Raman spectroscopy enabled the observation of all the 25 predicted Raman modes and assignment of their symmetries. On cooling, BCTO ceramics exhibit two antiferromagnetic transitions at 3 K and 12.5 K, in broad agreement with a recent single-crystal study [P. Chanlert, N. Kurita, H. Tanaka, D. Goto, A. Matsuo and K. Kindo, Phys. Rev. B: Condens. Matter Mater. Phys., 2016, 93, 094420]. Low temperature Fourier-transform infrared reflectivity analyses suggest the antiferromagnetic phase transitions to be driven by small distortions of the CoO6 octahedra, lowering locally their C3v symmetry. This causes splitting of the associated vibrational modes, but without a long-range structural change. AC impedance spectroscopy revealed BCTO ceramics to be leaky insulators with an activation energy for conduction of ∼0.15−0.25 eV, which suggests electron hopping between mixed oxidation states of Co

The Ariel payload electrical and electronic architecture: a summary of the current design and implementation status

Ariel is the M4 mission of the ESA’s Cosmic Vision Program 2015-2025, whose aim is to characterize by lowresolution transit spectroscopy the atmospheres of over one thousand warm and hot exoplanets orbiting nearby stars. It has been selected by ESA in March 2018 and adopted in November 2020 to be flown, then, in 2029. It is the first survey mission dedicated to measuring the chemical composition and thermal structures of the atmospheres of hundreds of transiting exoplanets, in order to enable planetary science far beyond the boundaries of the Solar System. The Payload (P/L) is based on a cold section (PLM – Payload Module) working at cryogenic temperatures and a warm section, located within the Spacecraft (S/C) Service Vehicle Module (SVM) and hosting five warm units operated at ambient temperature (253-313 K). The P/L and its electrical, electronic and data handling architecture has been designed and optimized to perform transit spectroscopy from space during primary and secondary planetary eclipses in order to achieve a large set of unbiased observations to shed light and fully understand the nature of exoplanets atmospheres, retrieving information about planets interior and determining the key factors affecting the formation and evolution of planetary systems