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Background: Standardized outcome reporting is crucial for trial evidence synthesis and translation of findings into clinical decision‐making. The OMERACT 2.0 Filter and COMET outcome domain taxonomy propose frameworks for consistent reporting of outcomes. There is an absence of a uniform dermatology‐specific reporting strategy that uses precise and consistent outcome definitions. Objectives: Our aim was to map efficacy/effectiveness outcomes assessed in dermatological trials to the OMERACT 2.0 Filter as a starting point for developing an outcome taxonomy in dermatology. Methods: We critically appraised 10 Cochrane Skin Reviews randomly selected from all 69 Cochrane Skin Reviews published until 01/2015 and the 220 trials included covering a broad spectrum of dermatological conditions and interventions. Efficacy/effectiveness outcomes were mapped to core areas and domains according to the OMERACT 2.0 Filter. The extracted trial outcomes were used for critical appraisal of outcome reporting in dermatology trials and for the preliminary development of a dermatology‐specific outcome taxonomy. Results: The allocation of 1086 extracted efficacy/effectiveness outcomes to the OMERACT 2.0 Filter resulted in a hierarchically structured dermatology‐specific outcome classification. In 506 outcomes (47%), the outcome concept to be measured was insufficiently described, hindering meaningful evidence synthesis. Although the core areas assessed in different dermatology trials of the same condition overlap considerably, quantitative evidence synthesis usually failed due to imprecise outcome definitions, non‐comparable outcome measurement instruments, metrics and reporting. Conclusions: We present an efficacy/effectiveness outcome classification as a starting point for a dermatology‐specific taxonomy to provide trialists and reviewers with the opportunity to better synthesize and compare evidence. Linked Commentary: A. Ragamin et al. J Eur Acad Dermatol Venereol 2021; 35: 276‐277. https://doi.org/10.1111/jdv.17103. [ABSTRACT FROM AUTHOR]

Summary: Results of clinical trials are the most important information source for generating external clinical evidence. The use of different outcomes across trials, which investigate similar interventions for similar patient groups, significantly limits the interpretation, comparability and clinical application of trial results. Core outcome sets (COSs) aim to overcome this limitation. A COS is an agreed standardized collection of outcomes that should be measured and reported in all clinical trials for a specific clinical condition. The Core Outcome Set Initiative within the Cochrane Skin Group (CSG‐COUSIN) supports the development of core outcomes in dermatology. In the second CSG‐COUSIN meeting held in 2017, 11 COS development groups working on skin diseases presented their current work. The presentations and discussions identified the following overarching methodological challenges for COS development in dermatology: it is not always easy to define the disease focus of a COS; the optimal method for outcome domain identification and level of detail needed to specify such domains is challenging to many; decision rules within Delphi surveys need to be improved; appropriate ways of patient involvement are not always clear. In addition, there appear to be outcome domains that may be relevant as potential core outcome domains for the majority of skin diseases. The close collaboration between methodologists in the Core Outcome Set Initiative and the international Cochrane Skin Group has major advantages for trialists, systematic reviewers and COS developers. [ABSTRACT FROM AUTHOR]

Summary: 业界需要借助临床试验来查明药物或其他治疗对皮肤病患者是否有效。参与临床试验的患者通常被分成两组。一组接受测试治疗,另一组则接受对照治疗。在进行了一段时间的治疗之后,相关人员就会将两组的治疗效果进行比较。病情改善得越多、副作用越少,治疗的效果就越好。非常重要的一点是,要正确衡量患者对治疗的反应,否则研究结论将毫无用处。以瘙痒症状为例,医生可以直接询问患者,也可以查看抓痕。这两种“结果”会提供不同的信息。同等重要的是,研究人员应在对相似患者组进行临床试验时包含相同的结果。以异位性湿疹为例,如果一位研究人员仅衡量皮肤发红、一位研究人员仅衡量瘙痒,而另一位研究人员仅衡量生活质量,那么就很难比较不同治疗的结果。您可能会想,到如今,全球的研究人员会齐聚一堂来选择在某些皮肤疾病中应衡量哪些结果。但事实是,每个人衡量的结果各不相同,因此几乎不可能将各种研究合并成有意义的成果。如今,一组研究人员、患者和其他专家终于齐聚一堂,讨论如何最好地在皮肤病患者的临床试验中衡量治疗效果(或结果)。在2017年1月于德国举行的一次国际性会议中,与会者在查找最佳证据和询问许多人员之后,就选择“核心”结果的最佳方法达成了一致。但如何使患者充分地参与制定此类决策,以及如何在更大规模的专家中达成一致等一些其他问题则更为棘手。国际Cochrane皮肤小组(CSG)‐COUSIN组致力于坚持完成其工作并期望提出一组对不同的皮肤病患者都能进行衡量的核心结果,如此一来,患者、医生、护士和医疗保健支付方都能更清楚地了解正在进行中的数百种临床试验。 [ABSTRACT FROM AUTHOR]

This article is part of the Dendritic Cell Guidelines article series, which provides a collection of state-of-the-art protocols for the preparation, phenotype analysis by flow cytometry, generation, fluorescence microscopy, and functional characterization of mouse and human DC from lymphoid organs, and various non-lymphoid tissues. Within this chapter, detailed protocols are presented that allow for the generation of single-cell suspensions from mouse lymphohematopoietic tissues including spleen, peripheral lymph nodes, and thymus, with a focus on the subsequent analysis of DC by flow cytometry. However, prepared single-cell suspensions can be subjected to other applications including sorting and cellular enrichment procedures, RNA sequencing, Western blotting, and many more. While all protocols were written by experienced scientists who routinely use them in their work, this article was also peer-reviewed by leading experts and approved by all co-authors, making it an essential resource for basic and clinical DC immunologists., (© 2022 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.)

This article is part of the Dendritic Cell Guidelines article series, which provides a collection of state-of-the-art protocols for the preparation, phenotype analysis by flow cytometry, generation, fluorescence microscopy, and functional characterization of mouse and human dendritic cells (DC) from lymphoid organs and various non-lymphoid tissues. Recent studies have provided evidence for an increasing number of phenotypically distinct conventional DC (cDC) subsets that on one hand exhibit a certain functional plasticity, but on the other hand are characterized by their tissue- and context-dependent functional specialization. Here, we describe a selection of assays for the functional characterization of mouse and human cDC. The first two protocols illustrate analysis of cDC endocytosis and metabolism, followed by guidelines for transcriptomic and proteomic characterization of cDC populations. Then, a larger group of assays describes the characterization of cDC migration in vitro, ex vivo, and in vivo. The final guidelines measure cDC inflammasome and antigen (cross)-presentation activity. While all protocols were written by experienced scientists who routinely use them in their work, this article was also peer-reviewed by leading experts and approved by all co-authors, making it an essential resource for basic and clinical DC immunologists., (© 2022 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.)

This article is part of the Dendritic Cell Guidelines article series, which provides a collection of state-of-the-art protocols for the preparation, phenotype analysis by flow cytometry, generation, fluorescence microscopy and functional characterization of mouse and human dendritic cells (DC) from lymphoid organs and various nonlymphoid tissues. DC are sentinels of the immune system present in almost every mammalian organ. Since they represent a rare cell population, DC need to be extracted from organs with protocols that are specifically developed for each tissue. This article provides detailed protocols for the preparation of single-cell suspensions from various mouse nonlymphoid tissues, including skin, intestine, lung, kidney, mammary glands, oral mucosa and transplantable tumors. Furthermore, our guidelines include comprehensive protocols for multiplex flow cytometry analysis of DC subsets and feature top tricks for their proper discrimination from other myeloid cells. With this collection, we provide guidelines for in-depth analysis of DC subsets that will advance our understanding of their respective roles in healthy and diseased tissues. While all protocols were written by experienced scientists who routinely use them in their work, this article was also peer-reviewed by leading experts and approved by all coauthors, making it an essential resource for basic and clinical DC immunologists., (© 2022 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.)

This study aimed to determine the waiting time from the diagnosis to the first breast cancer treatment at the University Hospital in southern Brazil to verify if the law #12,732/12 is being respected and to identify the impact of this waiting time on breast cancer progression. A retrospective, quantitative, and indirect approach was carried out by reviewing the medical records of 118 patients who underwent oncologic breast surgery at the University Hospital, an exclusive public service, from January 1st 2012 to December 31st 2016. Data analysis revealed that the average waiting time was 104.4 days and the median was 92.5 days. Of the patients who started their treatment by surgery, 85.1% waited for more than 60 days. Meanwhile, 67.6% of the patients who underwent neoadjuvant chemotherapy, started the treatment within 60 days. In addition, the waiting time was not significant for relapse outcomes, metastatic disease, and death due to breast cancer. These results demonstrate the need for proposals that can reduce waiting times to the first treatment, especially if the indication is surgery.

Objective: Investigating retinal thickness may complement existing biological markers for dementia and other neurodegenerative diseases. Although retinal thinning is predictive for cognitive decline, it remains to be investigated if and how this feature aligns with neurodegeneration elsewhere in the brain, specifically in early disease stages., Methods: Using optical coherence tomography and magnetic resonance imaging, we examined retinal thickness as well as hippocampal structure in patients with amnestic mild cognitive impairment and healthy controls., Results: The groups did not differ in hippocampal and retinal thickness measures. However, we detected a correlation of peripapillary retinal nerve fiber layer thickness and hippocampal thickness in healthy people but not in cognitively impaired patients. The ratio of hippocampus to retina thickness was significantly smaller in patients with mild cognitive impairment and correlated positively with cognitive performance., Conclusions: Different temporal trajectories of neurodegeneration may disrupt transregional brain structure associations in patients with amnestic mild cognitive impairment., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Background: Many patients with Parkinson's disease (PD) experience depression., Objective: Evaluate pimavanserin treatment for depression in patients with PD., Methods: Pimavanserin was administered as monotherapy or adjunctive therapy to a selective serotonin reuptake inhibitor or serotonin/noradrenaline reuptake inhibitor in this 8-week, single-arm, open-label phase 2 study (NCT03482882). The primary endpoint was change from baseline to week 8 in Hamilton Depression Scale-17-item version (HAMD-17) score. Safety, including collection of adverse events and the Mini-Mental State Examination (MMSE) and Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III) scores, was assessed in patients who received ≥1 pimavanserin dose., Results: Efficacy was evaluated in 45 patients (21 monotherapy, 24 adjunctive therapy). Mean (SE) baseline HAMD-17 was 19.2 (3.1). Change from baseline to week 8 (least squares [LS] mean [SE]) in the HAMD-17 was -10.8 (0.63) (95% CI, -12.0 to -9.5; p < 0.0001) with significant improvement seen at week 2 (p < 0.0001) and for both monotherapy (week 8, -11.2 [0.99]) and adjunctive therapy (week 8,-10.2 [0.78]). Most patients (60.0%) had ≥50% improvement at week 8, and 44.4% of patients reached remission (HAMD-17 score ≤7). Twenty-one of 47 patients experienced 42 treatment-emergent adverse events; the most common by system organ class were gastrointestinal (n = 7; 14.9%) and psychiatric (n = 7; 14.9%). No negative effects were observed on MMSE or MDS-UPDRS Part III., Conclusion: In this 8-week, single-arm, open-label study, pimavanserin as monotherapy or adjunctive therapy was well tolerated and associated with early and sustained improvement of depressive symptoms in patients with PD.

Objective: To design and evaluate a new vestibular implant and surgical procedure that should reach correct electrode placement in 95% of patients in silico., Design: Computational anatomy driven implant and surgery design study., Setting: Tertiary referral center., Participants: The population comprised 81 patients that had undergone a CT scan of the Mastoid region in the Maastricht University Medical Center. The population was subdivided in a vestibular implant eligible group (28) and a control group (53) without known vestibular loss., Interventions: Canal lengths and relationships between landmarks were calculated for every patient. The relationships in group-anatomy were used to model a fenestration site on all three semicircular canals. Each patient's simulated individual distance from the fenestration site to the ampulla was calculated and compared with the populations average to determine if placement would be successful., Main Outcome Measures: Lengths of the semicircular canals, distances from fenestration site to ampulla (intralabyrinthine electrode length), and rate of successful electrode placement (robustness)., Results: The canal lengths for the lateral, posterior, and superior canal were respectively 12.1 mm ± 1.07, 18.8 mm ± 1.62, and 17.5 mm ± 1.23, the distances from electrode fenestration site to the ampulla were respectively 3.73 mm ± 0.53, 9.02 mm ± 0.90, and 5.31 mm ± 0.73 and electrode insertions were successful for each respective semicircular canal in 92.6%, 66.7%, and 86.4% of insertions in silico. The implant electrode was subsequently revised to include two more electrodes per lead, resulting in a robustness of 100%., Conclusions: The computational anatomy approach can be used to design and test surgical procedures. With small changes in electrode design, the proposed surgical procedure's target robustness was reached.

Evidence-based health care requires that relevant outcomes for patients are included in clinical trials investigating treatment effects, allowing subsequent systematic reviews to summarize all relevant evidence to guide clinical practice. Currently, no gold standard of outcome choice for dermatology trials and reviews exists. We systematically assessed concordance between efficacy outcomes in a random sample of 10 Cochrane Skin systematic reviews and the 220 dermatology trials included. Reviews did not include 742 (68%) of the 1,086 trial outcomes. Of the 60 outcomes the reviews sought, 17 (28%) were not reported in any trial, while 12 were assessed in <50% of trials. For 11 of 23 (48%) primary review outcomes, meta-analysis was impossible, because trial outcomes were absent or unclear. This small overlap of review/trial outcomes could suggest that trials are not measuring the outcomes perceived to be the most important by patients, clinicians, systematic reviewers, and trialists. The lack of standardized outcome measures, poor reporting of outcomes in trials, and low concordance of outcomes between reviews and primary studies could be improved by the development and implementation of Core Outcome Sets. These are an agreed-upon minimum set of key outcomes, for specified conditions, to be reported in all trials., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Interdisciplinary multimodal pain therapy (IMPT) is a biopsychosocial treatment approach for patients with chronic pain that comprises at least psychological and physiotherapeutic interventions. Core outcome sets (COSs) are currently developed in different medical fields to standardize and improve the selection of outcome domains, and measurement instruments in clinical trials, to make trial results meaningful, to pool trial results, and to allow indirect comparison between interventions. The objective of this study was to develop a COS of patient-relevant outcome domains for chronic pain in IMPT clinical trials. An international, multiprofessional panel (patient representatives [n = 5], physicians specialized in pain medicine [n = 5], physiotherapists [n = 5], clinical psychologists [n = 5], and methodological researchers [n = 5]) was recruited for a 3-stage consensus study, which consisted of a mixed-method approach comprising an exploratory systematic review, a preparing online survey to identify important outcome domains, a face-to-face consensus meeting to agree on COS domains, and a second online survey (Delphi) establishing agreement on definitions for the domains included. The panel agreed on the following 8 domains to be included into the COS for IMPT: pain intensity, pain frequency, physical activity, emotional wellbeing, satisfaction with social roles and activities, productivity (paid and unpaid, at home and at work, inclusive presentism and absenteeism), health-related quality of life, and patient's perception of treatment goal achievement. The complexity of chronic pain in a biopsychosocial context is reflected in the current recommendation and includes physical, mental, and social outcomes. In a subsequent step, measurement instruments will be identified via systematic reviews.

Background: Falls are a relevant issue of inpatient treatment. Epidemiological analysis concerning incidence, risk factors for falls and the quality of risk assessments are missing., Methods: In a routine data-based cross-sectional study all patients hospitalized in the University Hospital Dresden, Germany, during 2012 and 2013 were analyzed according to fall incidence and risk factors (items of Dresden fall risk assessment [Dresden-FRA], age, sex, severity of disease, and length of stay. Fall risk and associated risk factors were determined using descriptive methods and logistic regression models. In addition, the quality of the fall risk assessment was evaluated., Results: The risk of falling during the observation period was 1.6 %. Differences exist between the medical disciplines (risk of falling 0.1 % to 9.8 %). The fall rate was 2.9/1,000 days of treatment. Higher age, longer inpatient stay, and a higher level of disease severity were significant predictors of falls. Less serious consequences of falls were more frequently documented (84 %) than consequences of falls requiring treatment (16 %). All nine items of the Dresden-FRA were significant risk factors. The sensitivity and specificity of the Dresden-FRA were 69.9 % and 71.4 %, respectively., Conclusion: Patients at an older age and with more severe disease have a higher risk of falling. The validated assessment of the individual risk of falling is an important tool of medical quality management and risk management. The present study can help to raise awareness about the quality of risk assessments, to further improve fall risk assessment, and to increase patient safety in acute care., (Copyright © 2017. Published by Elsevier GmbH.)

Background: There is a need for accurate and precise food price elasticities (PE, change in consumer demand in response to change in price) to better inform policy on health-related food taxes and subsidies., Methods/design: The Price Experiment and Modelling (Price ExaM) study aims to: I) derive accurate and precise food PE values; II) quantify the impact of price changes on quantity and quality of discrete food group purchases and; III) model the potential health and disease impacts of a range of food taxes and subsidies. To achieve this, we will use a novel method that includes a randomised Virtual Supermarket experiment and econometric methods. Findings will be applied in simulation models to estimate population health impact (quality-adjusted life-years [QALYs]) using a multi-state life-table model. The study will consist of four sequential steps: 1. We generate 5000 price sets with random price variation for all 1412 Virtual Supermarket food and beverage products. Then we add systematic price variation for foods to simulate five taxes and subsidies: a fruit and vegetable subsidy and taxes on sugar, saturated fat, salt, and sugar-sweetened beverages. 2. Using an experimental design, 1000 adult New Zealand shoppers complete five household grocery shops in the Virtual Supermarket where they are randomly assigned to one of the 5000 price sets each time. 3. Output data (i.e., multiple observations of price configurations and purchased amounts) are used as inputs to econometric models (using Bayesian methods) to estimate accurate PE values. 4. A disease simulation model will be run with the new PE values as inputs to estimate QALYs gained and health costs saved for the five policy interventions., Discussion: The Price ExaM study has the potential to enhance public health and economic disciplines by introducing internationally novel scientific methods to estimate accurate and precise food PE values. These values will be used to model the potential health and disease impacts of various food pricing policy options. Findings will inform policy on health-related food taxes and subsidies., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12616000122459 (registered 3 February 2016).

The main phases of arbuscular mycorrhiza (AM) development were analyzed in black medick (Medicago lupulina) with Glomus intraradices. Methods of light and transmission electron microscopy were used to investigate AM. The first mycorrhization was identified on the seventh day after sowing. M. lupulina with AM-fungus Glomus intraradices formed Arum type of AM. Roots of black medick at fruiting stage (on the 88th day) were characterized by the development of forceful mycelium. The thickness of mycelium was comparable with the vascular system of root central cylinder. The development of vesicules into intraradical spores was shown. Micelium, arbuscules, and vesicules developed in close vicinity to the division zone of root tip. This might be evidence of an active symbiotic interaction between partners. All stages of fungal development and breeding, including intraradical spores (in inter-cellular matrix of root cortex), were identified in the roots of black medick, which indicated an active utilization of host plant nutrient substrates by the mycosymbiont. Plant cell cytoplasm extension was identified around young arbuscular branches but not for intracellular hyphae. The presence of active symbiosis was confirmed by increased accumulation of phosphorus in M. lupulina root tissues under conditions of G. intraradices inoculation and low phosphorus level in the soil. Thus, black medick cultivar-population can be characterized as an ecologically obligate mycotrophic plant under conditions of low level of available phosphorus in the soil. Specific features of AM development in intensively mycotrophic black medick, starting from the stage of the first true leaf until host plant fruiting, were evaluated. The obtained plant-microbe system is a perspective model object for further ultracytological and molecular genetic studies of the mechanisms controlling arbuscular mycorrhiza symbiotic efficiency, including selection and investigation of new symbiotic plant mutants.

Although the stigma of obesity in our society is well documented, the measurement of antifat attitudes has been a difficult undertaking. Two studies were conducted to construct and validate the Antifat Attitudes Test (AFAT). In study 1, college students (110 men and 175 women) completed the preliminary 54-item AFAT and specific indices of body image and weight-related concerns. Psychometric and factor analysis revealed a 47-item composite scale and three internally consistent factors that were uncorrelated with social desirability: Social/Character Disparagement, Physical/Romantic Unattractiveness, and Weight Control/Blame. Several body images correlates of antifat prejudice were identified, and men expressed more negative attitudes than women. Study 2 experimentally examined the effects of information about the controllability of weight on the antifat attitudes of 120 participants. Exposure to information on behavioral vs. biogenetic control led to greater blame of persons who are fat for their body size. The implications of the findings and the potential utility of the AFAT are discussed.