Thematic Analysis Nowell, Lorelli S.; Norris, Jill M.; White, Deborah E. ...
International journal of qualitative methods,
12/2017, Letnik:
16, Številka:
1
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As qualitative research becomes increasingly recognized and valued, it is imperative that it is conducted in a rigorous and methodical manner to yield meaningful and useful results. To be accepted as ...trustworthy, qualitative researchers must demonstrate that data analysis has been conducted in a precise, consistent, and exhaustive manner through recording, systematizing, and disclosing the methods of analysis with enough detail to enable the reader to determine whether the process is credible. Although there are numerous examples of how to conduct qualitative research, few sophisticated tools are available to researchers for conducting a rigorous and relevant thematic analysis. The purpose of this article is to guide researchers using thematic analysis as a research method. We offer personal insights and practical examples, while exploring issues of rigor and trustworthiness. The process of conducting a thematic analysis is illustrated through the presentation of an auditable decision trail, guiding interpreting and representing textual data. We detail our step-by-step approach to exploring the effectiveness of strategic clinical networks in Alberta, Canada, in our mixed methods case study. This article contributes a purposeful approach to thematic analysis in order to systematize and increase the traceability and verification of the analysis.
Rheumatoid arthritis (RA) is a prototypical autoimmune arthritis affecting nearly 1% of the world population and is a significant cause of worldwide disability. Though prior studies have demonstrated ...the appearance of RA-related autoantibodies years before the onset of clinical RA, the pattern of immunologic events preceding the development of RA remains unclear. To characterize the evolution of the autoantibody response in the preclinical phase of RA, we used a novel multiplex autoantigen array to evaluate development of the anti-citrullinated protein antibodies (ACPA) and to determine if epitope spread correlates with rise in serum cytokines and imminent onset of clinical RA. To do so, we utilized a cohort of 81 patients with clinical RA for whom stored serum was available from 1-12 years prior to disease onset. We evaluated the accumulation of ACPA subtypes over time and correlated this accumulation with elevations in serum cytokines. We then used logistic regression to identify a profile of biomarkers which predicts the imminent onset of clinical RA (defined as within 2 years of testing). We observed a time-dependent expansion of ACPA specificity with the number of ACPA subtypes. At the earliest timepoints, we found autoantibodies targeting several innate immune ligands including citrullinated histones, fibrinogen, and biglycan, thus providing insights into the earliest autoantigen targets and potential mechanisms underlying the onset and development of autoimmunity in RA. Additionally, expansion of the ACPA response strongly predicted elevations in many inflammatory cytokines including TNF-α, IL-6, IL-12p70, and IFN-γ. Thus, we observe that the preclinical phase of RA is characterized by an accumulation of multiple autoantibody specificities reflecting the process of epitope spread. Epitope expansion is closely correlated with the appearance of preclinical inflammation, and we identify a biomarker profile including autoantibodies and cytokines which predicts the imminent onset of clinical arthritis.
Individuals at high risk of developing seropositive rheumatoid arthritis (RA) can be identified for translational research and disease prevention studies through the presence of highly informative ...and predictive patterns of RA-related autoantibodies, especially anti-citrullinated protein antibodies (ACPAs), in the serum. In serologically positive individuals without arthritis, designated ACPA positive at risk, the presence of mucosal inflammatory processes associated with the presence of local ACPA production has been demonstrated. In other at-risk populations, local RA-related autoantibody production is present even in the absence of serum autoantibodies. Additionally, a proportion of at-risk individuals exhibit local mucosal ACPA production in the lung, as well as radiographic small-airway disease, sputum hypercellularity and increased neutrophil extracellular trap formation. Other mucosal sites in at-risk individuals also exhibit autoantibody production, inflammation and/or evidence of dysbiosis. As the proportion of individuals who exhibit such localized inflammation-associated ACPA production is substantially higher than the likelihood of an individual developing future RA, this finding raises the hypothesis that mucosal ACPAs have biologically relevant protective roles. Identifying the mechanisms that drive both the generation and loss of externally focused mucosal ACPA production and promote systemic autoantibody expression and ultimately arthritis development should provide insights into new therapeutic approaches to prevent RA.
Genetic and environmental risk factors for rheumatoid arthritis Deane, Kevin D.; Demoruelle, M. Kristen; Kelmenson, Lindsay B. ...
Baillière's best practice and research in clinical rheumatology/Baillière's best practice & research. Clinical rheumatology,
February 2017, 2017-02-00, 20170201, Letnik:
31, Številka:
1
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Multiple genetic and environmental factors have been associated with an increased risk for rheumatoid arthritis (RA). Of these, the strongest associations have been seen with female sex, a family ...history of RA, the genetic factor the “shared epitope,” and exposure to tobacco smoke. There is also renewed interest in mucosal inflammation and microbial factors as contributors to the development of RA. However, the identification of a “preclinical” period of RA that can be defined as local or systemic autoimmunity as measured by autoantibodies and other biomarkers prior to the development of clinically apparent synovitis suggests that the risk factors for RA are acting long prior to first clinical evidence of IA. As such, a major challenge to the field will be to investigate the full spectrum of the development of RA, from initiation and propagation of autoimmunity during preclinical RA and transition to clinically apparent synovitis and classifiable RA, to determine which genetic and environmental factors are important at each stage of disease development. Understanding the exact role and timing of action of risk factors for RA is especially important given the advent of prevention trials in RA, and the hope that a full understanding of genetic and environmental factors in RA could lead to effective preventive interventions.
The convergence of advances in medical science, human biology, data science, and technology has enabled the generation of new insights into the phenotype known as "diabetes." Increased knowledge of ...this condition has emerged from populations around the world, illuminating the differences in how diabetes presents, its variable prevalence, and how best practice in treatment varies between populations. In parallel, focus has been placed on the development of tools for the application of precision medicine to numerous conditions. This Consensus Report presents the American Diabetes Association (ADA) Precision Medicine in Diabetes Initiative in partnership with the European Association for the Study of Diabetes (EASD), including its mission, the current state of the field, and prospects for the future. Expert opinions are presented on areas of precision diagnostics and precision therapeutics (including prevention and treatment), and key barriers to and opportunities for implementation of precision diabetes medicine, with better care and outcomes around the globe, are highlighted. Cases where precision diagnosis is already feasible and effective (i.e., monogenic forms of diabetes) are presented, while the major hurdles to the global implementation of precision diagnosis of complex forms of diabetes are discussed. The situation is similar for precision therapeutics, in which the appropriate therapy will often change over time owing to the manner in which diabetes evolves within individual patients. This Consensus Report describes a foundation for precision diabetes medicine, while highlighting what remains to be done to realize its potential. This, combined with a subsequent, detailed evidence-based review (due 2022), will provide a roadmap for precision medicine in diabetes that helps improve the quality of life for all those with diabetes.
We developed a novel approach to minimize batch effects when assigning samples to batches. Our algorithm selects a batch allocation, among all possible ways of assigning samples to batches, that ...minimizes differences in average propensity score between batches. This strategy was compared to randomization and stratified randomization in a case-control study (30 per group) with a covariate (case vs control, represented as β1, set to be null) and two biologically relevant confounding variables (age, represented as β2, and hemoglobin A1c (HbA1c), represented as β3). Gene expression values were obtained from a publicly available dataset of expression data obtained from pancreas islet cells. Batch effects were simulated as twice the median biological variation across the gene expression dataset and were added to the publicly available dataset to simulate a batch effect condition. Bias was calculated as the absolute difference between observed betas under the batch allocation strategies and the true beta (no batch effects). Bias was also evaluated after adjustment for batch effects using ComBat as well as a linear regression model. In order to understand performance of our optimal allocation strategy under the alternative hypothesis, we also evaluated bias at a single gene associated with both age and HbA1c levels in the 'true' dataset (CAPN13 gene).
Pre-batch correction, under the null hypothesis (β1), maximum absolute bias and root mean square (RMS) of maximum absolute bias, were minimized using the optimal allocation strategy. Under the alternative hypothesis (β2 and β3 for the CAPN13 gene), maximum absolute bias and RMS of maximum absolute bias were also consistently lower using the optimal allocation strategy. ComBat and the regression batch adjustment methods performed well as the bias estimates moved towards the true values in all conditions under both the null and alternative hypotheses. Although the differences between methods were less pronounced following batch correction, estimates of bias (average and RMS) were consistently lower using the optimal allocation strategy under both the null and alternative hypotheses.
Our algorithm provides an extremely flexible and effective method for assigning samples to batches by exploiting knowledge of covariates prior to sample allocation.
Recent advances in research into the earliest phases of RA have provided additional insights into the processes leading from the healthy to the diseased state. These insights have opened the way for ...the development of preventive strategies for RA, which represents a significant paradigm shift from treatment to prevention and will have major implications for patients as well as society. It would be a huge step forward if clinical signs and symptoms, disability, impaired quality of life and the need for chronic immunosuppressive treatment could be prevented. RA can be seen as a prototypic autoimmune disease, and discoveries about the preclinical diseased state for RA could potentially facilitate research into prevention of other immune-mediated inflammatory diseases such as type 1 diabetes, SLE and multiple sclerosis. This review focuses on the current knowledge of factors contributing to the development of RA and discusses the opportunities for intervention.
Abstract Autoimmune diseases (AID) are a collection of many complex disorders of unknown etiology resulting in immune responses to self-antigens and are thought to result from interactions between ...genetic and environmental factors. Here we review the epidemiologic evidence for the role of environmental factors in the development of human AID, the conclusions that can be drawn from the existing data, critical knowledge gaps, and research needed to fill these gaps and to resolve uncertainties. We specifically summarize the state of knowledge and our levels of confidence in the role of specific agents in the development of autoimmune diseases, and we define the areas of greatest impact for future investigations. Among our consensus findings we are confident that: 1) crystalline silica exposure can contribute to the development of several AID; 2) solvent exposure can contribute to the development of systemic sclerosis; 3) smoking can contribute to the development of seropositive rheumatoid arthritis; and 4) an inverse association exists between ultraviolet radiation exposure and the risk of development of multiple sclerosis. We suggest that more studies of phenotypes, genotypes, and multiple exposures are needed. Additional knowledge gaps needing investigation include: defining important windows in the timing of exposures and latencies relating to age, developmental state, and hormonal changes; understanding dose–response relationships; and elucidating mechanisms for disease development. Addressing these essential issues will require more resources to support research, particularly of rare AID, but knowledge of the risks conferred by environmental factors in specific genetic contexts could pave the way for prevention of AID in the future.
Recent concerns about suboptimal patient care and a lack of compassion have prompted policymakers to question the preparedness of clinicians for the challenging environment in which they practice. ...Compassionate care is expected by patients and is a professional obligation of clinicians; however, little is known about the state of research on clinical compassion. The purpose of this scoping review was to map the literature on compassion in clinical healthcare.
Searches of eight electronic databases and the grey literature were conducted to identify empirical studies published over the last 25 years. Eligible studies explored perceptions or interventions of compassionate care in clinical populations, healthcare professionals, and healthcare students. Following the title and abstract review, two reviewers independently screened full-texts articles, and extracted study data. A narrative approach to synthesizing and mapping the literature was used.
Of 36,637 records, 648 studies were retrieved and 44 studies were included in the review. Less than one third of studies included patients. Six themes emerged from studies that explored perceptions of compassionate care: nature of compassion, development of compassion, interpersonal factors related to compassion, action and practical compassion, barriers and enablers of compassion, and outcomes of compassion. Intervention studies included two compassionate care trials with patients and eight educational programs that aimed to improve compassionate care in clinicians and students.
This review identifies the limited empirical understanding of compassion in healthcare, highlighting the lack of patient and family voices in compassion research. A deeper understanding of the key behaviors and attitudes that lead to improved patient-reported outcomes through compassionate care is necessary.
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