Crisaborole Ointment, 2%, for Treatment of Patients with Mild-to-Moderate Atopic Dermatitis:Systematic Literature Review and Network Meta-Analysis

The authors would like to replace 2 small sections of the published manuscript that refer to a qualitative review of safety data for included studies (together with an associated safety table), to provide some further clarifications on these safety data and to include some quantitative updates for rates

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

24^{24}Mg(pp, α\alpha)21^{21}Na reaction study for spectroscopy of 21^{21}Na

The $^{24}$Mg($p$, $\alpha$)$^{21}$Na reaction was measured at the Holifield Radioactive Ion Beam Facility at Oak Ridge National Laboratory in order to better constrain spins and parities of energy levels in $^{21}$Na for the astrophysically important $^{17}$F($\alpha, p$)$^{20}$Ne reaction rate calculation. 31 MeV proton beams from the 25-MV tandem accelerator and enriched $^{24}$Mg solid targets were used. Recoiling $^{4}$He particles from the $^{24}$Mg($p$, $\alpha$)$^{21}$Na reaction were detected by a highly segmented silicon detector array which measured the yields of $^{4}$He particles over a range of angles simultaneously. A new level at 6661 $\pm$ 5 keV was observed in the present work. The extracted angular distributions for the first four levels of $^{21}$Na and Distorted Wave Born Approximation (DWBA) calculations were compared to verify and extract angular momentum transfer.Comment: 11 pages, 6 figures, proceedings of the 18th International Conference on Accelerators and Beam Utilization (ICABU2014

Postoperative pain management in children: Guidance from the pain committee of the European Society for Paediatric Anaesthesiology (ESPA Pain Management Ladder Initiative)

The main remit of the European Society for Paediatric Anaesthesiology (ESPA) Pain Committee is to improve the quality of pain management in children. The ESPA Pain Management Ladder is a clinical practice advisory based upon expert consensus to help to ensure a basic standard of perioperative pain management for all children. Further steps are suggested to improve pain management once a basic standard has been achieved. The guidance is grouped by the type of surgical procedure and layered to suggest basic, intermediate, and advanced pain management methods. The committee members are aware that there are marked differences in financial and personal resources in different institutions and countries and also considerable variations in the availability of analgesic drugs across Europe. We recommend that the guidance should be used as a framework to guide best practice

Expertise in research integration and implementation for tackling complex problems: when is it needed, where can it be found and how can it be strengthened?

© 2020, The Author(s). Expertise in research integration and implementation is an essential but often overlooked component of tackling complex societal and environmental problems. We focus on expertise relevant to any complex problem, especially contributory expertise, divided into ‘knowing-that’ and ‘knowing-how.’ We also deal with interactional expertise and the fact that much expertise is tacit. We explore three questions. First, in examining ‘when is expertise in research integration and implementation required?,’ we review tasks essential (a) to developing more comprehensive understandings of complex problems, plus possible ways to address them, and (b) for supporting implementation of those understandings into government policy, community practice, business and social innovation, or other initiatives. Second, in considering ‘where can expertise in research integration and implementation currently be found?,’ we describe three realms: (a) specific approaches, including interdisciplinarity, transdisciplinarity, systems thinking and sustainability science; (b) case-based experience that is independent of these specific approaches; and (c) research examining elements of integration and implementation, specifically considering unknowns and fostering innovation. We highlight examples of expertise in each realm and demonstrate how fragmentation currently precludes clear identification of research integration and implementation expertise. Third, in exploring ‘what is required to strengthen expertise in research integration and implementation?,’ we propose building a knowledge bank. We delve into three key challenges: compiling existing expertise, indexing and organising the expertise to make it widely accessible, and understanding and overcoming the core reasons for the existing fragmentation. A growing knowledge bank of expertise in research integration and implementation on the one hand, and accumulating success in addressing complex societal and environmental problems on the other, will form a virtuous cycle so that each strengthens the other. Building a coalition of researchers and institutions will ensure this expertise and its application are valued and sustained

Smoking Cessation and Cardiovascular Disease Risk Factors: Results from the Third National Health and Nutrition Examination Survey

BACKGROUND: Cigarette smoking is a major risk factor for the development and progression of cardiovascular disease. While smoking is associated with increased levels of inflammatory markers and accelerated atherosclerosis, few studies have examined the impact of smoking cessation on levels of inflammatory markers. The degree and rate at which inflammation subsides after smoking cessation are uncertain. It also remains unclear as to whether traditional risk factors can adequately explain the observed decline in cardiovascular risk following smoking cessation. METHODS AND FINDINGS: Using data from 15,489 individuals who participated in the Third National Health and Nutrition Examination Survey (NHANES III), we analyzed the association between smoking and smoking cessation on levels of inflammatory markers and traditional cardiovascular risk factors. In particular, we examined changes in C-reactive protein, white blood cell count, albumin, and fibrinogen. Inflammatory markers demonstrated a dose-dependent and temporal relationship to smoking and smoking cessation. Both inflammatory and traditional risk factors improved with decreased intensity of smoking. With increased time since smoking cessation, inflammatory markers resolved more slowly than traditional cardiovascular risk factors. CONCLUSION: Inflammatory markers may be more accurate indicators of atherosclerotic disease. Inflammatory markers returned to baseline levels 5 y after smoking cessation, consistent with the time frame associated with cardiovascular risk reduction observed in both the MONICA and Northwick Park Heart studies. Our results suggest that the inflammatory component of cardiovascular disease resulting from smoking is reversible with reduced tobacco exposure and smoking cessation

COVID-19 pandemic in Africa: Is it time for water, sanitation and hygiene to climb up the ladder of global priorities?

The authors would like to thank the authors of the freely-usable images from Unsplash and Pixnio included in the Graphical Abstract: photos by Janice-Haney Carr and Dr. Ray Butler (USCDCP), USCDCP and Crystal Thompsom (USAID) on Pixnio; photos by CDC, UN COVID- 19 response and Raymond Hui on Unsplash.Wewould also like to thank the reviewers for their comments and keen interest in this article.In the current pandemic context, it is necessary to remember the lessons learned from previous outbreaks in Africa, where the incidence of other diseases could rise if most resources are directed to tackle the emergency. Improving the access to water, sanitation and hygiene (WASH) could be a win-win strategy, because the lack of these services not only hampers the implementation of preventive measures against SARS-CoV-2 (e.g. proper handwashing), but it is also connected to high mortality diseases (for example, diarrhoea and lower respiratory infections (LRI)). This study aims to build on the evidence-based link between other LRI andWASH as a proxy for exploring the potential vulnerability of African countries to COVID-19, as well as the role of other socioeconomic variables such as financial sources or demographic factors. The selected methodology combines several machine learning techniques to single out the most representative variables for the analysis, classify the countries according to their capacity to tackle public health emergencies and identify behavioural patterns for each group. Besides, conditional dependences between variables are inferred through a Bayesian network. Results show a strong relationship between low access toWASH services and high LRI mortality rates, and that migrant remittances could significantly improve the access to healthcare and WASH services. However, the role of Official Development Assistance (ODA) in enhancing WASH facilities in the most vulnerable countries cannot be disregarded, but it is unevenly distributed: for each 50–100 US$of ODA per capita, the probability of directing more than 3 US$ toWASH ranges between 48% (Western Africa) and 8% (Central Africa)

Toxin Mediated Diarrhea in the 21st Century: The Pathophysiology of Intestinal Ion Transport in the Course of ETEC, V. cholerae and Rotavirus Infection

An estimated 4 billion episodes of diarrhea occur each year. As a result, 2–3 million children and 0.5–1 million adults succumb to the consequences of this major healthcare concern. The majority of these deaths can be attributed to toxin mediated diarrhea by infectious agents, such as E. coli, V. cholerae or Rotavirus. Our understanding of the pathophysiological processes underlying these infectious diseases has notably improved over the last years. This review will focus on the cellular mechanism of action of the most common enterotoxins and the latest specific therapeutic approaches that have been developed to contain their lethal effects