Summary
Background
Comparative, real‐life and long‐term evidence on the effectiveness and safety of phototherapy and systemic therapy in moderate‐to‐severe atopic eczema (AE) is limited. Such data ...must come from well‐designed prospective patient registries. Standardization of data collection is needed for direct comparisons and data pooling.
Objectives
To reach a consensus on how and when to measure the previously defined domain items of the TREatment of ATopic eczema (TREAT) Registry Taskforce core dataset for research registries for paediatric and adult patients with AE.
Methods
Proposals for the measurement instruments were based on recommendations of the Harmonising Outcome Measures for Eczema (HOME) initiative, the existing AE database of TREATgermany, systematic reviews of the literature and expert opinions. The proposals were discussed at three face‐to‐face consensus meetings, one teleconference and via e‐mail. The frequency of follow‐up visits was determined by an expert survey.
Results
A total of 16 experts from seven countries participated in the ‘how to measure’ consensus process and 12 external experts were consulted. A consensus was reached for all domain items on how they should be measured by assigning measurement instruments. A minimum follow‐up frequency of initially 4 weeks after commencing treatment, then every 3 months while on treatment and every 6 months while off treatment was defined.
Conclusions
This core dataset for national AE research registries will aid in the comparability and pooling of data across centres and country borders, and enables international collaboration to assess the long‐term effectiveness and safety of phototherapy and systemic therapy used in patients with AE.
What's already known about this topic?
Comparable, real‐life and long‐term data on the effectiveness and safety of phototherapy and systemic therapy in patients with atopic eczema (AE) are needed.
There is a high diversity of outcomes and instruments used in AE research, which require harmonization to enhance comparability and allow data pooling.
What does this study add?
Our taskforce has reached international consensus on how and when to measure core domain items for national AE research registries.
This core dataset is now available for use by researchers worldwide and will aid in the collection of unified data.
What are the clinical implications of this work?
The data collected through this core dataset will help to gain better insights into the long‐term effectiveness and safety of phototherapy and systemic therapy in AE and will provide important information for clinical practice.
Standardization of such data collection at the national level will also allow direct data comparisons and pooling across country borders (e.g. in the analysis of treatment‐related adverse events that require large patient numbers).
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Respond to this article
Background
Clinical practice guidelines (CPGs) are essential in delivering optimum healthcare, such as for atopic dermatitis (AD), a highly prevalent skin disease. Although many CPGs are available ...for AD, their quality has not been critically appraised.
Objectives
To identify CPGs on AD worldwide and to assess with validated instruments whether those CPGs are clear, unbiased, trustworthy and evidence based (CUTE).
Methods
We searched MEDLINE, Embase, PubMed, Web of Science, Cochrane Library, Emcare, Epistemonikos, PsycINFO and Academic Search Premier for CPGs on AD published between 1 April 2016 and 1 April 2021. Additionally we hand searched prespecified guideline resources. Screening, data extraction and quality assessment of eligible guidelines were independently carried out by two authors. Instruments used for quality assessment were the AGREE II Reporting Checklist, the US Institute of Medicine (IOM) criteria of trustworthiness and Lenzer’s Red Flags.
Results
Forty CPGs were included, mostly from countries with a high sociodemographic index. The reporting quality varied enormously. Three CPGs scored ‘excellent’ on all AGREE II domains and three scored ‘poor’ on all domains. We found no association between AGREE II scores and a country’s gross domestic product. One CPG fully met all nine IOM criteria and two fully met eight. Three CPGs had no red flags. ‘Applicability’ and ‘rigour of development’ were the lowest scoring AGREE II domains; ‘external review’, ‘updating procedures’ and ‘rating strength of recommendations’ were the IOM criteria least met; and most red flags were for ‘limited or no involvement of methodological expertise’ and ‘no external review’. Management of conflicts of interest (COIs) appeared challenging. When constructs of the instruments overlapped, they showed high concordance, strengthening our conclusions.
Conclusions
Overall, many CPGs are not sufficiently clear, unbiased, trustworthy or evidence based (CUTE) and lack applicability. Therefore improvement is warranted, for which using the AGREE II instrument is recommended. Some improvements can be easily accomplished through robust reporting. Others, such as transparency, applicability, evidence foundation and managing COIs, might require more effort.
What is already known about this topic?
Atopic dermatitis is a skin disease with a high prevalence and high burden of disease.
Clinical practice guidelines are essential for good clinical practice and shared decision making, for both patients and caregivers, in order to reduce disease burden.
Many clinical practice guidelines are available for atopic dermatitis worldwide, but their quality has not yet been critically appraised.
What does this study add?
Forty guidelines <5 years old were identified, mostly from countries with a high sociodemographic index, many of which are not sufficiently clear, unbiased, trustworthy or evidence based (CUTE).
Improvement of guidelines is warranted, for example by using the AGREE II instrument and robust reporting.
Some guideline domains can be improved without much effort, yet improving transparency and applicability and managing conflicts of interest might be more challenging.
Many clinical practice guidelines are available for atopic dermatitis worldwide, but their quality has not been critically appraised as yet. Forty guidelines less than five years old were identified, mostly from countries with a high socio‐demographic index, many of which are not clear, unbiased, trustworthy or evidence based (CUTE) enough; Improvement of guidelines is warranted, e.g. by using the AGREEII instrument and robust reporting
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Anorectal malformations (ARM) are rare congenital malformations, resulting from disturbed hindgut development. A genetic etiology has been suggested, but evidence for the involvement of specific ...genes is scarce. We evaluated the contribution of rare and low-frequency coding variants in ARM etiology, assuming a multifactorial model.
We analyzed 568 Caucasian ARM patients and 1,860 population-based controls using the Illumina HumanExome Beadchip array, which contains >240,000 rare and low-frequency coding variants. GenomeStudio clustering and calling was followed by re-calling of 'no-calls' using zCall for patients and controls simultaneously. Single variant and gene-based analyses were performed to identify statistically significant associations, applying Bonferroni correction. Following an extra quality control step, candidate variants were selected for validation using Sanger sequencing.
When we applied a MAF of ≥1.0%, no variants or genes showed statistically significant associations with ARM. Using a MAF cut-off at 0.4%, 13 variants initially reached statistical significance, but had to be discarded upon further inspection: ten variants represented calling errors of the software, while the minor alleles of the remaining three variants were not confirmed by Sanger sequencing.
Our results show that rare and low-frequency coding variants with large effect sizes, present on the exome chip do not contribute to ARM etiology.
Low prevalence, lack of knowledge about the disease course, and phenotype heterogeneity hamper the development of drugs for rare diseases. Rare disease registries (RDRs) can be helpful by playing a ...role in understanding the course of the disease, and providing information necessary for clinical trial design, if designed and maintained properly. We describe the potential applications of a RDR and what type of information should be incorporated to support the design of clinical trials in the process of drug development, based on a broad inventory of registry experience. We evaluated two existing RDRs in more detail to check the completeness of these RDRs for trial design.
Before and during the application for regulatory approval a RDR can improve the efficiency and quality in clinical trial design by informing the sample size calculation and expected disease course. In exceptional circumstances information from RDRs has been used as historical controls for a one-armed clinical trial, and high quality RDRs may be used for registry-based randomized controlled trials. In the post marketing phase of (conditional) drug approval a disease-specific RDR is likely to provide more relevant information than a product-specific registry.
A RDR can be very helpful to improve the efficiency and quality of clinical trial design in several ways. To enable the applicability and optimal use of a RDR longitudinal data collection is indispensable, and specific data collection, prepared for repeated measurement, is needed. The developed checklist can help to define the appropriate variables to include. Attention should be paid to the inclusion of patient-relevant outcome measures in the RDR from the start. More research and experience is needed on the possibilities and limitations of combining RDR information with clinical trial data to maximize the availability of relevant evidence for regulatory decisions in rare diseases.
IgG4 antibodies are unique to humans. IgG4 is associated with tolerance during immunotherapy in allergy, but also with pathology, as in pemphigus vulgaris and IgG4‐related disease. Its induction is ...largely restricted to nonmicrobial antigens, and requires repeated or prolonged antigenic stimulation, for reasons poorly understood. An important aspect in generating high‐affinity IgG antibodies is chemokine receptor‐mediated migration of B cells into appropriate niches, such as germinal centers. Here, we show that compared to IgG1 B cells, circulating IgG4 B cells express lower levels of CXCR3, CXCR4, CXCR5, CCR6, and CCR7, chemokine receptors involved in GC reactions and generation of long‐lived plasma cells. This phenotype was recapitulated by in vitro priming of naive B cells with an IgG4‐inducing combination of TFH/TH2 cytokines. Consistent with these observations, we found a low abundance of IgG4 B cells in secondary lymphoid tissues in vivo, and the IgG4 antibody response is substantially more short‐lived compared to other IgG subclasses in patient groups undergoing CD20+ B cell depletion therapy with rituximab. These results prompt the hypothesis that factors needed to form IgG4 B cells restrain at the same time the induction of a robust migratory phenotype that could support a long‐lived IgG4 antibody response.
IgG4 B cells express fewer chemokine receptors involved in GC reactions and generation of long‐lived plasma cells. This might restrain induction of a robust migratory phenotype that could support a long‐lived IgG4 antibody response.
The incidence of pancreatic ductal adenocarcinoma (PDAC) is different among males and females. This disparity cannot be fully explained by the difference in terms of exposure to known risk factors; ...therefore, the lower incidence in women could be attributed to sex-specific hormones. A two-phase association study was conducted in 12,387 female subjects (5436 PDAC cases and 6951 controls) to assess the effect on risk of developing PDAC of single nucleotide polymorphisms (SNPs) in 208 genes involved in oestrogen and pregnenolone biosynthesis and oestrogen-mediated signalling. In the discovery phase 14 polymorphisms showed a statistically significant association (P < 0.05). In the replication none of the findings were validated. In addition, a gene-based analysis was performed on the 208 selected genes. Four genes (NR5A2, MED1, NCOA2 and RUNX1) were associated with PDAC risk, but only NR5A2 showed an association (P = 4.08 × 10
) below the Bonferroni-corrected threshold of statistical significance. In conclusion, despite differences in incidence between males and females, our study did not identify an effect of common polymorphisms in the oestrogen and pregnenolone pathways in relation to PDAC susceptibility. However, we validated the previously reported association between NR5A2 gene variants and PDAC risk.
Rosacea: New Concepts in Classification and Treatment van Zuuren, Esther J.; Arents, Bernd W. M.; van der Linden, Mireille M. D. ...
American journal of clinical dermatology,
07/2021, Letnik:
22, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Rosacea is a chronic inflammatory dermatosis mainly affecting the cheeks, nose, chin, and forehead. Rosacea is characterized by recurrent episodes of flushing or transient erythema, persistent ...erythema, phymatous changes, papules, pustules, and telangiectasia. The eyes may also be involved. Due to rosacea affecting the face, it has a profound negative impact on quality of life, self-esteem, and well-being. In addition to general skin care, there are several approved treatment options available for addressing these features, both topical and systemic. For some features, intense pulse light, laser, and surgery are of value. Recent advances in fundamental scientific research have underscored the roles of the innate and adaptive immune systems as well as neurovascular dysregulation underlying the spectrum of clinical features of rosacea. Endogenous and exogenous stimuli may initiate and aggravate several pathways in patients with rosacea. This review covers the new phenotype-based diagnosis and classification system reflecting pathophysiology, and new and emerging treatment options and approaches. We address new topical and systemic formulations, as well as recent evidence on treatment combinations. In addition, ongoing studies investigating novel therapeutic interventions will be summarized.
Abstract
A significant proportion of colorectal cancer (CRC) patients develop peritoneal metastases (PM) in the course of their disease. PMs are associated with a poor quality of life, significant ...morbidity and dismal disease outcome. To improve care for this patient group, a better understanding of the molecular characteristics of CRC-PM is required. Here we present a comprehensive molecular characterization of a cohort of 52 patients. This reveals that CRC-PM represent a distinct CRC molecular subtype, CMS4, but can be further divided in three separate categories, each presenting with unique features. We uncover that the CMS4-associated structural protein Moesin plays a key role in peritoneal dissemination. Finally, we define specific evolutionary features of CRC-PM which indicate that polyclonal metastatic seeding underlies these lesions. Together our results suggest that CRC-PM should be perceived as a distinct disease entity.
The International Initiative on Spatial Lifecourse Epidemiology (ISLE) convened its first International Symposium on Lifecourse Epidemiology and Spatial Science at the Lorentz Center in Leiden, ...Netherlands, 16–20 July 2018. Its aim was to further an emerging transdisciplinary field: Spatial Lifecourse Epidemiology. This field draws from a broad perspective of scientific disciplines including lifecourse epidemiology, environmental epidemiology, community health, spatial science, health geography, biostatistics, spatial statistics, environmental science, climate change, exposure science, health economics, evidence-based public health, and landscape ecology. The participants, spanning 30 institutions in 10 countries, sought to identify the key issues and research priorities in spatial lifecourse epidemiology. The results published here are a synthesis of the top 10 list that emerged out of the discussion by a panel of leading experts, reflecting a set of grand challenges for spatial lifecourse epidemiology in the coming years. https://doi.org/10.1289/EHP4868.
Closed (non-steady state) chamber measurements are often used to determine the gas exchange of N₂O. Many researchers have addressed the underestimation of the emission estimates obtained from closed ...chamber measurements when using linear regression methods. However, the linear regression method is still usually applied to derive the flux. The importance of using non-linear regression methods is demonstrated with data from four fertilizing events each consisting of 1 month of automatic chamber measurements at Cabauw in the Netherlands in the period from July 2005 to July 2006. It is presented that the cumulative emission estimates with the exponential regression method are close to the cumulative emissions estimates with the intercept method. The linear estimates differ by up to 60% of the estimates with the exponential method. The performance of each method is validated using a C₂H₆ tracer and a goodness-of-fit analysis. The goodness-of-fit is much better for the exponential than the linear regression method. The systematic error due to linear regression is of the same order as the estimated uncertainty due to temporal variation. Therefore, closed-chamber data should be tested for non-linearity and an appropriate method should be used to calculate the flux.
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