Interpreting and Reporting Results Based on Patient-Reported Outcomes

AbstractThis article deals with the incorporation of patient-reported outcomes (PROs) into clinical trials and focuses on issues associated with the interpretation and reporting of PRO data. The primary focus and context of this information relates to the evidentiary support and reporting for a labeling or advertising claim of a PRO benefit for a new or approved pharmaceutical product. This manuscript focuses on issues associated with assessing clinical significance and common pitfalls to avoid in presenting results related to PROs. Specifically, the questions addressed by this manuscript involve: What are the best methods to assess clinical significance for PROs? How should investigators present PRO data most effectively in a Food and Drug Administration (FDA) application? In labeling or in a scientific publication? Guidelinesfor interpreting clinical significance of PROs and for comprehensively reporting on the methods, measures and results of clinical trials that incorporate PROs are important for clinicians, regulatory agencies, and most of all to patients. Clear specifications for considering a finding on a PRO measure, as clinically meaningful, need to be determined by instrument developers and psychometricians; they need to be reported for all clinical trials involving PRO end points. Clinical trial reports need to be comprehensive, clear, and sufficient to enable any reader to understand the methods, PRO measures, statistical analysis, and results

Analysis and Interpretation of Results Based on Patient-Reported Outcomes

AbstractThis article is part of a series of manuscripts dealing with the incorporation of patient-reported outcomes (PROs) into clinical trials. The issues dealt with in this manuscript concern the common pitfalls to avoid in statistical analysis and interpretation of PROs. Specifically, the questions addressed by this manuscript involve the analysis pitfalls with PRO data in clinical trials and how can they be avoided (e.g.,missing data, multiplicity, null results etc.). The manuscript provides key literature for existing resources and proposes new guidelines

Role of goblet cell protein CLCA1 in murine DSS colitis

Background The secreted goblet cell protein CLCA1 (chloride channel regulator, calcium-activated-1) is, in addition to its established role in epithelial chloride conductance regulation, thought to act as a multifunctional signaling protein, including cellular differentiation pathways and induction of mucus production. Specifically, CLCA1 has recently been shown to modulate early immune responses by regulation of cytokines. Here, we analyze the role of CLCA1, which is highly expressed and secreted by colon goblet cells, in the course of murine dextran sodium sulfate-induced colitis. Findings We compared Clca1-deficient and wild type mice under unchallenged and DSS-challenged conditions at various time points, including weight loss, colon weight-length- ratio and histological characterization of inflammation and regeneration. Expression levels of relevant cytokines, trefoil factor 3 and E-cadherin were assessed via quantitative PCR and cytometric bead arrays. Lack of CLCA1 was associated with a more than two-fold increased expression of Cxcl-1- and Il-17-mRNA during DSS colitis. However, no differences were found between Clca1-deficient and wild type mice under unchallenged or DSS-challenged conditions in terms of clinical findings, disease progression, colitis outcome, epithelial defects or regeneration. Conclusions CLCA1 is involved in the modulation of cytokine responses in the colon, albeit differently than what had been observed in the lungs. Obviously, the pathways involved depend on the type of challenge, time point or tissue environment

Setting the Stage for Co-Production

Participatory scenario visioning aims to expose, integrate, and reconcile perspectives and expectations about a sustainable, resilient future from a variety of actors and stakeholders. This chapter considers the settings in which transdisciplinary participatory visioning takes place, highlighting lessons learned from the Urban Resilience to Extremes Sustainability Research Network (UREx SRN). It reflects on the benefits of engaging in the co-production process and the challenges that must be considered amid this process

Interspecies diversity of chloride channel regulators, calcium-activated 3 genes

Members of the chloride channel regulators, calcium-activated (CLCA) family, have been implicated in diverse biomedical conditions, including chronic inflammatory airway diseases such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis, the activation of macrophages, and the growth and metastatic spread of tumor cells. Several observations, however, could not be repeated across species boundaries and increasing evidence suggests that select CLCA genes are particularly prone to dynamic species-specific evolvements. Here, we systematically characterized structural and expressional differences of the CLCA3 gene across mammalian species, revealing a spectrum of gene duplications, e.g., in mice and cows, and of gene silencing via diverse chromosomal modifications in pigs and many primates, including humans. In contrast, expression of a canonical CLCA3 protein from a single functional gene seems to be evolutionarily retained in carnivores, rabbits, guinea pigs, and horses. As an accepted asthma model, we chose the cat to establish the tissue and cellular expression pattern of the CLCA3 protein which was primarily found in mucin-producing cells of the respiratory tract and in stratified epithelia of the esophagus. Our results suggest that, among developmental differences in other CLCA genes, the CLCA3 gene possesses a particularly high dynamic evolutionary diversity with pivotal consequences for humans and other primates that seem to lack a CLCA3 protein. Our data also help to explain previous contradictory results on CLCA3 obtained from different species and warrant caution in extrapolating data from animal models in conditions where CLCA3 may be involved

Sensemaking for Entangled Urban Social, Ecological, and Technological Systems in the Anthropocene

Our urban systems and their underlying sub-systems are designed to deliver only a narrow set of human-centered services, with little or no accounting or understanding of how actions undercut the resilience of social-ecological-technological systems (SETS). Embracing a SETS resilience perspective creates opportunities for novel approaches to adaptation and transformation in complex environments. We: i) frame urban systems through a perspective shift from control to entanglement, ii) position SETS thinking as novel sensemaking to create repertoires of responses commensurate with environmental complexity (i.e., requisite complexity), and iii) describe modes of SETS sensemaking for urban system structures and functions as basic tenets to build requisite complexity. SETS sensemaking is an undertaking to reflexively bring sustained adaptation, anticipatory futures, loose-fit design, and co-governance into organizational decision-making and to help reimagine institutional structures and processes as entangled SETS

A Vision for Resilient Urban Futures

A fundamental systems approach is essential to advancing our understanding of how to address critical challenges caused by the intersection of urbanization and climate change. The social–ecological–technological systems (SETS) conceptual framework brings forward a systems perspective that considers the reality of cities as complex systems and provides a baseline for developing a science of, and practice for, cities. Given the urgency of issues we collectively face to improve livability, justice, sustainability, and resilience in cities, bringing a systems approach to resilience planning and policymaking is critical, as is development of positive visions and scenarios that can provide more realistic and systemic solutions. We provide a vision for more resilient urban futures that learns from coproduced scenario development work in nine US and Latin American cities in the URExSRN. We find that developing an urban systems science that can provide actionable knowledge for decision-making is an emerging, and much needed, transdisciplinary research agenda. It will require true boundary-crossing to bring the knowledge, skills, tools, and ideas together in ways that can help achieve the normative goals and visions we have for our shared urban future

The UREx Guide to Scenarios

This Scenario Planning Guide outlines how the Urban Resilience to Extremes Sustainability Research Network (UREx SRN) supports ongoing efforts in its nine network cities in conducting participatory workshops. The Scenarios Working Group team, together with students, researchers, and collaborators across the network, have synthesized the co-produced visions from Workshop I. City-leads, practitioners, network participants, and participating institutions are encouraged to use the quantitative and qualitative outputs to further develop resilient, equitable, and sustainable transition pathways to help bring about their envisioned futures. The primer begins with a brief description of the UREx SRN, before introducing the innovative framework applied to participatory scenario workshops. This is followed by an outline of the social-ecological-technological systems (SETS) approach that is applied throughout the project. A general explanation of scenarios is given, and a detailed description is provided of why scenario planning is applied, and the types of scenarios produced. The main portion of the primer focuses on the scenario workshops with detailed information provided on pre-workshop events, workshop activities and post-workshop data analysis and product synthesis