Summarizing current refractory disease definitions in rheumatoid arthritis and polyarticular juvenile idiopathic arthritis: systematic review

Abstract Objectives To identify how refractory disease (or relevant terminology variations) in RA and polyarticular JIA (polyJIA) is defined and establish the key components of such definitions. Methods Searches were undertaken of English-language articles within six medical databases, including manual searching, from January 1998 to March 2020 (PROSPERO: CRD42019127142). Articles were included if they incorporated a definition of refractory disease, or non-response, in RA/polyJIA, with clear components to the description. Qualitative content analysis was undertaken to describe refractory disease in RA/polyJIA and classify each component within each definition. Results Of 6251 studies screened, 646 met the inclusion criteria; 581 of these applied non-response criteria while 65 provided refractory disease definitions/descriptions. From the non-response studies, 39 different components included various disease activity measures, emphasizing persistent disease activity and symptoms, despite treatment with one or more biologic DMARD (bDMARD). From papers with clear definitions for refractory disease, 41 components were identified and categorized into three key themes: resistance to multiple drugs with different mechanisms of action, typically two or more bDMARDs; persistence of symptoms and disease activity; and other contributing factors. The most common term used was ‘refractory’ (80%), while only 16.9% reported explicitly how their definition was generated (e.g. clinical experience or statistical methods). Conclusion Refractory disease is defined as resistance to multiple drugs with different mechanisms of action by persistence of physical symptoms and high disease activity, including contributing factors. A clear unifying definition needs implementing, as the plethora of different definitions makes study comparisons and appropriate identification of patients difficult.

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P131 Defining refractory disease in RA and polyarticular JIA: a systematic review

Rheumatology ◽

10.1093/rheumatology/keab247.127 ◽

2021 ◽

Vol 60 (Supplement_1) ◽

Author(s):

Hema Chaplin ◽

Lewis Carpenter ◽

Anni Raz ◽

Elena Nikiphorou ◽

Heidi Lempp ◽

...

Keyword(s):

Systematic Review ◽

Disease Activity ◽

Qualitative Content Analysis ◽

Physical Symptoms ◽

Mechanisms Of Action ◽

Refractory Disease ◽

Contributing Factors ◽

Persistent Symptoms ◽

Patient Reported ◽

Multiple Drugs

Abstract Background/Aims A systematic approach to define patients with rheumatoid arthritis (RA) or polyarticular juvenile idiopathic arthritis (PolyJIA) who do not adequately respond to treatment and experience persistent symptoms (refractory disease) is absent. The objective of the systematic review was to identify how refractory disease (or relevant terminology variations) in RA/PolyJIA is defined and establish the key components/constructs of such definitions. Methods Searches were undertaken of English language articles within six medical databases, including manual searching, from January 1998 to March 2020 (PROSPERO: CRD42019127142). Articles were included if they incorporated a definition of refractory disease, or non-response, in RA/PolyJIA, with clear components to the description (e.g. disease activity assessment specified, patient perspective, number of drugs to classify non-response). A narrative synthesis mapping of the definitions was undertaken to describe refractory disease in RA/PolyJIA and classify each component within each definition through a qualitative content analysis. Results Of 6,251 studies screened, 646 studies met the inclusion criteria; 581 reported non-response criteria and 65 reported refractory disease definitions/descriptions. From the non-response studies, 39 different components included various disease activity measures, emphasising persistent disease activity and symptoms, despite treatment with at least one bDMARD. Of the papers with clear definitions for Refractory disease, 41 components were identified and categorised into three key themes: Resistance to multiple drugs/regimes with different mechanisms of action: descriptions of drugs/regimes failed, not tolerated, discontinued/switched, by specifying name, number or class of drugs failed (range 1-8 but typically ≥2 bDMARDs) and duration of treatment, and steroid use/dependency.Persistency of physical symptoms and disease activity: range of various disease activity criteria (including not achieving remission), descriptions of other patient-reported outcomes or symptoms e.g. patient global or pain VAS, presence or absence of inflammation, disease severity including new joint activity, damage or replacements.Other contributing factors: biomechanical or degenerative drivers, adverse event, co-morbidities or extra-articular manifestations, serology (RF Status) or anti-bodies (anti-CCP) and incorrect diagnosis or not relevant treatment. The most common labels were “Refractory” (80%), of which 32.7% used the term “Refractory RA” and 13.5% stating “Refractory to (drug name/class)”. “Difficult-to-treat RA” (23.1%) and “Treatment Resistant RA” (15.4%) were the most popular from remaining terms (20%). Only the minority (16.9%) reported explicitly how their definition was generated e.g. clinical experience or statistical methods. Conclusion Refractory disease can be defined as resistance to multiple drugs/regimes with different mechanisms of action as evidenced by persistency of physical symptoms and high disease activity, including contributing factors. There is a need for a clear unifying definition as the plethora of different definitions makes both study comparisons and appropriate identification of patients difficult. Disclosure H. Chaplin: None. L. Carpenter: None. A. Raz: None. E. Nikiphorou: None. H. Lempp: None. S. Norton: None.

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In my remembered country: what poetry tells us about the changing perceptions of volcanoes between the nineteenth and twenty-first centuries

Geoscience Communication ◽

10.5194/gc-3-73-2020 ◽

2020 ◽

Vol 3 (1) ◽

pp. 73-87

Author(s):

Arianna Soldati ◽

Sam Illingworth

Keyword(s):

English Language ◽

Qualitative Content Analysis ◽

Research Question ◽

Human Perception ◽

Time Frame ◽

Negative Events ◽

Culturally Appropriate ◽

Definition Of ◽

The Relationship ◽

Selection Of

Abstract. In this study we investigate what poetry written about volcanoes from the 1800s to the present day reveals about the relationship between volcanoes and the societies and times represented by poets who wrote about them, including how it evolved over that time frame. In order to address this research question, we conducted a qualitative content analysis of a selection of 34 English-language poems written about human–volcano interactions. Firstly, we identified the overall connotation of each poem. Then, we recognised specific emerging themes and grouped them in categories. Additionally, we performed a quantitative analysis of the frequency with which each category occurs throughout the decades of the dataset. This analysis reveals that a spiritual element is often present in poetry about volcanoes, transcending both the creative and destructive power that they exert. Furthermore, the human–volcano relationship is especially centred around the sense of identity that volcanoes provide to humans, which may follow from both positive and negative events. These results highlight the suitability of poetry as a means to explore the human perception of geologic phenomena. Additionally, our findings may be relevant to the definition of culturally appropriate communication strategies with communities living near active volcanoes.

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In my remembered country: what poetry tells us about the changing perceptions of volcanoes

10.5194/gc-2019-17 ◽

2019 ◽

Author(s):

Arianna Soldati ◽

Sam Illingworth

Keyword(s):

English Language ◽

Qualitative Content Analysis ◽

Research Question ◽

Human Perception ◽

Time Frame ◽

Negative Events ◽

Culturally Appropriate ◽

Definition Of ◽

The Relationship ◽

Selection Of

Abstract. In this study we investigate what poetry written about volcanoes from 1800 to the present day reveals about the relationship between humanity and volcanoes, including how it evolved over that time frame. In order to address this research question, we conducted a qualitative content analysis of a selection of 34 English-language poems written about the human-volcano interactions. Firstly, we identified the overall connotation of each poem. Then, we recognized specific emerging themes and grouped them in categories. Additionally, we performed a quantitative analysis of the frequency with which each category occurs throughout the decades of the dataset. This analysis reveals that a spiritual element is often present in poetry about volcanoes, transcending both the creative and destructive power that they exert. Furthermore, the human-volcano relationship is especially centred around the sense of identity that volcanoes provide to humans, which may follow from both positive and negative events. These results highlight the suitability of poetry as a means to explore the human perception of geologic phenomena. Additionally, our findings may be relevant to the definition of culturally appropriate communication strategies with communities living nearby active volcanoes.

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P132 Redefining refractory disease in RA and adult polyarticular JIA: a Delphi consensus study

Rheumatology ◽

10.1093/rheumatology/keab247.128 ◽

2021 ◽

Vol 60 (Supplement_1) ◽

Author(s):

Hema Chaplin ◽

Ailsa Bosworth ◽

Jessica Meehan ◽

Rona Moss-Morris ◽

Heidi Lempp ◽

...

Keyword(s):

Disease Activity ◽

Inflammatory Arthritis ◽

Healthcare Professionals ◽

Nominal Group ◽

Joint Involvement ◽

Refractory Disease ◽

Juvenile Onset ◽

Persistent Symptoms ◽

Delphi Approach ◽

Definition Of

Abstract Background/Aims Patients who do not achieve sustained low disease activity despite drug treatments are referred to as having refractory disease. However, usage of this term varies and often does not account for any discrepancy between inflammation and persistent symptoms, adult or juvenile onset nor differences between patients’ and healthcare professionals’ perspectives. The study aimed to explore and achieve consensus on a definition of refractory disease across healthcare professionals and patients, through a mixed-methods Delphi approach. Methods Three rounds of voting (one face-to-face nominal group (n = 13), and two online rounds (ns = 40 and 53)) were conducted, in conjunction with the National Rheumatoid Arthritis Society. Participants voted on the inclusion and relevance of statements to generate a broader definition of refractory disease, derived from previous qualitative interviews with multi-disciplinary healthcare professionals and patients (adult and juvenile onset), a systematic review of current definitions and health psychology theory. The process involved voting on: a) name preferences, b) treatment and inflammation statements, c) domains for inclusion regarding symptoms and impact, and d) rating of individual components within each domain, including relevance to: i) Refractory Arthritis and ii) Disease Flare for discriminatory validity. A predetermined cut off was applied to identify which domains needed to be included, until final consensus was reached. Full NHS ethical approval was granted (London-Hampstead-18/LO/1171). Results With minimal attrition (n = 3 in both online rounds), 106 international participants including Patient Representatives, Rheumatologists, Nurses, GPs, Psychologists, Physiotherapists, Researchers, Pharmacist, Podiatrist, Occupational Therapist and a Social Worker participated. Refractory Inflammatory Arthritis was the most popular name, (25% of votes) followed by Persistent Inflammatory Arthritis (19% of votes) hence its application in the presence (Persistent Inflammation) or absence (Persistent Symptoms) of inflammation as part of the definition. Regarding treatment and inflammation, these were voted in the majority to be kept broad rather than specifying rigid cut-offs. From the original 73 components across 10 domains identified to capture symptoms and impact, initial analysis has resulted in six domains reaching consensus for inclusion. These domains cover: 1) Disease Activity, 2) Joint Involvement, 3) Pain, 4) Fatigue, 5) Functioning and Quality of Life, and 6) cs/b/tsDMARD Experiences. Within these, 18 components were identified as related and important e.g. One or two persistently active/affected joints, Reduced mobility, Disease-related Distress, Inability to perform desired activities, Repeated need of short course steroids and Disease Activity not captured by DAS28. These capture the multi-faceted presentation and experience of Refractory Inflammatory Arthritis in these two populations. Conclusion A broader definition for refractory inflammatory arthritis has been generated through a Delphi method to capture the experiences of rheumatologists, patients and multi-disciplinary healthcare professionals. This definition needs further refinement and validation to assess clinical and research utility to identify high risk patients with unmet needs. Disclosure H. Chaplin: None. A. Bosworth: None. J. Meehan: None. R. Moss-Morris: None. H. Lempp: None. S. Norton: None.

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Problems in English Communicating Skills for Learners of English

International Journal of Contemporary Research and Review ◽

10.15520/ijcrr/2018/9/07/548 ◽

2018 ◽

Vol 9 (07) ◽

pp. 20484-20491

Author(s):

Dr. Ishag Adam Hassan Ahmed

Keyword(s):

Reading Comprehension ◽

English Language ◽

Communicative Competence ◽

Daily Practice ◽

Small Component ◽

Curriculum Review ◽

Comprehension Skills ◽

Definition Of ◽

The University ◽

Reading Comprehension Skills

This paper is devoted to presenting the methods in English communicating skills for Learners of English in general and the problems specific to University of Bahri. English language major’s graduates then; it discusses the notion of communicative competence, and defines strategic competence. It also briefly deals with the various definitions of communication strategies and taxonomies of conversation strategies. Also, I give brief definition of the word conversation, that is the act of talking together or exchange ideas, opinions, skills, and information. As accustomed, speaking is natural and automatic but communication is an art which must be learned and practiced. Also the aim of this paper is to present you with suitable suggestions about how you can solve problems while reading English? In order to comply with this objective: we considered two variables. The first one is that within our daily practice at the university we have students with different abilities while reading English. Therefore, we need to help them increase the ability in reading comprehension. However, we don’t have enough teachers and needed resources to supply them with the help they need. The second variable is related to the fact that at University there are different centers where the students’ skills can improve and their reading comprehension skills deficiencies could be overcome by getting help from the teachers. This study is small component of a larger curriculum review exercise. The findings of study in general suggest that both students and English language lecturers were in agreement that Sudanese students had a problem in writing and speaking English and due to that the conversational problems are raised. Finally, the paper concludes by representing the pedagogical implications of conversation strategies.

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L'anglicisme dans la langue française

Digital Press Social Sciences and Humanities ◽

10.29037/digitalpress.43286 ◽

2019 ◽

Vol 3 ◽

pp. 00013

Author(s):

Danny Susanto

Keyword(s):

English Language ◽

Oil Industry ◽

English Word ◽

Public Institutions ◽

Font Size ◽

The World ◽

French Speaking ◽

The Difference ◽

Definition Of ◽

Bibliographic Study

The purpose of this study is to analyze the phenomenon known as “anglicism”: a loan made to the English language by another language. Anglicism arose either from the adoption of an English word as a result of a translation defect despite the existence of an equivalent term in the language of the speaker, or from a wrong translation, as a word-by-word translation. Said phenomenon is very common nowadays and most languages of the world including making use of some linguistic concepts such as anglicism, neologism, syntax, morphology etc, this article addresses various aspects related to Anglicisms in French through a bibliographic study: the definition of Anglicism, the origin of Anglicisms in French and the current situation, the areas most affected by Anglicism, the different categories of Anglicism, the difference between French Anglicism in France and French-speaking Canada, the attitude of French-speaking society towards to the Anglicisms and their efforts to stop this phenomenon. The study shows that the areas affected are, among others, trade, travel, parliamentary and judicial institutions, sports, rail, industrial production and most recently film, industrial production, sport, oil industry, information technology, science and technology. Various initiatives have been implemented either by public institutions or by individuals who share concerns about the increasingly felt threat of the omnipresence of Anglicism in everyday life.

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Is Treat-to-target in Lupus Nephritis Realistic in Clinical Practice?

Current Rheumatology Reviews ◽

10.2174/1573397114666180406100857 ◽

2018 ◽

Vol 15 (1) ◽

pp. 2-6 ◽

Cited By ~ 3

Author(s):

Chi Chiu Mok

Keyword(s):

Lupus Nephritis ◽

Disease Activity ◽

Safety Concern ◽

Real Life ◽

Current Treatment ◽

Treat To Target ◽

Low Disease Activity ◽

Activity State ◽

Definition Of ◽

Comparative Trials

The Treat-to-Target (T2T) principle has been advocated in a number of inflammatory and non-inflammatory medical illnesses. Tight control of disease activity has been shown to improve the outcome of rheumatoid arthritis and psoriatic arthritis as compared to the conventional approach. However, whether T2T can be applied to patients with lupus nephritis is still under emerging discussion. Treatment of lupus nephritis should target at inducing and maintaining remission of the kidney inflammation so as to preserve renal function and improve survival in the longterm. However, there is no universal agreement on the definition of remission or low disease activity state of nephritis, as well as the time points for switching of therapies. Moreover, despite the availability of objective parameters for monitoring such as proteinuria and urinary sediments, differentiation between ongoing activity and damage in some patients with persistent urinary abnormalities remains difficult without a renal biopsy. A large number of serum and urinary biomarkers have been tested in lupus nephritis but none of them have been validated for routine clinical use. In real life practice, therapeutic options for lupus nephritis are limited. As patients with lupus nephritis are more prone to infective complications, tight disease control with aggressive immunosuppressive therapies may have safety concern. Not until the feasibility, efficacy, safety and cost-effectiveness of T2T in lupus nephritis is confirmed by comparative trials, this approach should not be routinely recommended with the current treatment armamentarium and monitoring regimes.

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OP0162 ETANERCEPT RESPONSE CLUSTERS IN JUVENILE IDIOPATHIC ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2505 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 97.1-98

Author(s):

S. Shoop-Worrall ◽

K. Hyrich ◽

L. Wedderburn ◽

W. Thomson ◽

N. Geifman

Keyword(s):

Young People ◽

Disease Activity ◽

Treatment Response ◽

Similar Response ◽

Response Patterns ◽

Active Joint ◽

Research Support ◽

Similar Treatment ◽

Children And Young People ◽

Multiple Drugs

Background:In children and young people (CYP) with JIA, we have previously identified clusters with different patterns of disease impact following methotrexate (MTX) initiation. It is unclear whether clusters of treatment response following etanercept (ETN) therapy exist and whether, in a group of CYP who have responded inadequately to or had adverse events on methotrexate, similar treatment response patterns exist. Novel response patterns would aid stratified treatment approaches through better understanding and potential forecasting of more specific response patterns across multiple domains of disease.Objectives:To identify and characterise trajectories of juvenile arthritis disease activity score (JADAS) components following ETN initiation for JIA.Methods:ETN-naïve CYP with non-systemic JIA were selected if enrolled prior to January 2019 in at least one of four CLUSTER consortium studies: BSPAR-ETN, BCRD, CAPS and CHARMS, at point of starting ETN as their first biological therapy. JADAS components (active joint count, physician’s global assessment (0-10cm), parental global evaluation (0-10cm) and standardised ESR (0-10) were collected at ETN initiation and during the following year.Multivariate group-based trajectory models, that identify clusters of CYP with similar patterns of change over time, were used to explore ETN response clusters across the different JADAS components. Censored-normal (global scores, ESR) and zero-inflated Poisson (active joint count) models were used, adjusting for year of ETN initiation. Optimal models were selected based on a combination of model fit (BIC), parsimony, and clinical plausibility.Results:Of the 1003 CYP included, the majority were female (70%) and of white ethnicity (90%), with rheumatoid factor-negative JIA the most common disease category (39%).The optimal model identified five trajectory clusters of disease activity following initiation of ETN (Figure 1). Clusters following ETN were similar and covered similar proportions of CYP to those previously identified following MTX: Fast (Group 1: 13%) and Slow (Group 2: 10%) response, active joint count improves but either physician (Group 3: 6%) or parent global scores (Group 4: 34%) remain persistently raised and a group with persistent raised scores across all JADAS components (Group 5: 36%). Compared to the persistent disease cluster, those with greater improvement had lower age and higher functional ability at ETN initiation and those with persistent raised parent global scores had lower ESR levels and were less likely to be RF-positive at ETN initiation.Figure 1.Clusters identified following ETN initiation in children and young people recruited to the UK BSPAR-ETN, BCRD, CAPS and CHARMS studies.Conclusion:This study has identified that within CYP initiating ETN, similar response clusters are evident to those previously identified following MTX. This commonality suggests a new framework for understanding treatment response, beyond a simple responder/non-responder analysis at a set point, which applies across multiple drugs despite different mechanisms of action and previous unfavourable treatment outcomes. Understanding both clinical factors associated with, and biological mechanisms underpinning, these clusters would aid stratified medicine in JIA.Acknowledgements:We thank the children, young people and families involved in CLUSTER, as well as clinical staff, administrators and data management teams. Funding for CLUSTER has been provided by generous grants from the MRC, Versus Arthritis, GOSH children’s charity, Olivia’s vision and the NIHR Manchester and GOSH BRC schemes.Disclosure of Interests:Stephanie Shoop-Worrall: None declared, Kimme Hyrich Speakers bureau: Abbvie, Grant/research support from: BMS, UCB, Pfizer, Lucy Wedderburn Speakers bureau: Pfizer, Grant/research support from: Abbvie, Sobi, Wendy Thomson Grant/research support from: Abbvie, Sobi, Nophar Geifman Grant/research support from: Abbvie, Sobi

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“I’ve Heard of It, Yes, but I Can’t Remember What Exactly It Was”—A Qualitative Study on Awareness, Knowledge, and Use of the UV Index

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18041615 ◽

2021 ◽

Vol 18 (4) ◽

pp. 1615

Author(s):

Katharina Diehl ◽

Tatiana Görig ◽

Charlotte Jansen ◽

Maike Carola Hruby ◽

Annette B. Pfahlberg ◽

...

Keyword(s):

Qualitative Study ◽

Qualitative Content Analysis ◽

Sun Protection ◽

Structured Interviews ◽

Protection Factor ◽

Protection Measures ◽

Uv Index ◽

Correct Definition ◽

Definition Of

Pharmacists and pharmaceutical technicians play an important role in counselling customers regarding sunscreen use and sun protection measures. A potentially helpful tool that can be used during counselling is the ultraviolet index (UVI), which informs individuals when and what sun protection measures are needed at a specific place and time. Our aim in this qualitative study was to explore awareness, knowledge, and use of the UVI during counselling in pharmacies. We used semi-structured interviews with pharmacists and pharmaceutical technicians (n = 20) to answer our research questions. Interviews were audiotaped, transcribed verbatim, and analyzed using qualitative content analysis. During the interviews pharmacists and pharmaceutical technicians revealed a lot of uncertainty and lack of knowledge regarding the UVI. Eight professionals were able to give a correct definition of UVI. Amongst others, the UVI was confused with sun protection factor. Overall, the UVI was hardly used during the counselling of customers. The UVI was developed to provide guidance when which type of sun protection is required to avoid detrimental effects of ultraviolet radiation. For effective implementation, both the general population and health professionals (e.g., pharmacists) have to increase their knowledge about the UVI. This would strengthen its use during professional counselling in pharmacies and may help to reduce the incidence of skin cancer over the long term.

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A polymeric approach toward resistance-resistant antimicrobial agent with dual-selective mechanisms of action

Science Advances ◽

10.1126/sciadv.abc9917 ◽

2021 ◽

Vol 7 (5) ◽

pp. eabc9917

Author(s):

Silei Bai ◽

Jianxue Wang ◽

Kailing Yang ◽

Cailing Zhou ◽

Yangfan Xu ◽

...

Keyword(s):

Mammalian Cells ◽

Mechanisms Of Action ◽

Model Systems ◽

General Strategy ◽

Antimicrobial Polymers ◽

Bacterial Dna ◽

Bacterial Membranes ◽

Severe Infections ◽

Multiple Drugs ◽

Resistance Rates

Antibiotic resistance is now a major threat to human health, and one approach to combating this threat is to develop resistance-resistant antibiotics. Synthetic antimicrobial polymers are generally resistance resistant, having good activity with low resistance rates but usually with low therapeutic indices. Here, we report our solution to this problem by introducing dual-selective mechanisms of action to a short amidine-rich polymer, which can simultaneously disrupt bacterial membranes and bind to bacterial DNA. The oligoamidine shows unobservable resistance generation but high therapeutic indices against many bacterial types, such as ESKAPE strains and clinical isolates resistant to multiple drugs, including colistin. The oligomer exhibited excellent effectiveness in various model systems, killing extracellular or intracellular bacteria in the presence of mammalian cells, removing all bacteria from Caenorhabditis elegans, and rescuing mice with severe infections. This “dual mechanisms of action” approach may be a general strategy for future development of antimicrobial polymers.

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