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

Rheumatology ◽  
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.

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

Rheumatology ◽  
2021 ◽  
Author(s):  
Hema Chaplin ◽  
Lewis Carpenter ◽  
Anni Raz ◽  
Elena Nikiphorou ◽  
Heidi Lempp ◽  
...  
Keyword(s):  
Disease Activity ◽  
English Language ◽  
Qualitative Content Analysis ◽  
Physical Symptoms ◽  
Mechanisms Of Action ◽  
Refractory Disease ◽  
Contributing Factors ◽  
Biologic Dmard ◽  
Definition Of ◽  
Multiple Drugs

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.

scholarly journals Placebo response in trials of drug treatments for cancer-related fatigue: a systematic review, meta-analysis and meta-regression

2020 ◽  
Vol 10 (4) ◽  
pp. 385-394 ◽  
Author(s):  
Rocio Roji ◽  
Patrick Stone ◽  
Federico Ricciardi ◽  
Bridget Candy
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Placebo Response ◽  
Risk Of Bias ◽  
Small Samples ◽  
Contributing Factors ◽  
Cancer Related Fatigue ◽  
Study Results ◽  
Meta Regression ◽  
Multiple Drugs

BackgroundCancer-related fatigue (CRF) is one of the most distressing symptoms experienced by patients. There is no gold standard treatment, although multiple drugs have been tested with little evidence of efficacy. Randomised controlled trials (RCTs) of these drugs have commented on the existence or size of the placebo response (PR). The objective of this systematic review was to establish the magnitude of the PR in RCTs of drugs to relieve CRF and to identify contributing factors.MethodRCTs were included in which the objective was to treat CRF. A meta-analysis was conducted using the standardised mean change (SMC) between baseline and final measurement in the placebo group. To explore factors that may be associated with the PR (eg, population or drug), a meta-regression was undertaken. Risk of bias was assessed using the revised Cochrane tool.ResultsFrom 3916 citations, 30 relevant RCTs were identified. All had limitations that increased their risk of bias. The pooled SMC in reduction in fatigue status in placebo groups was −0.23 (95% confidence intervals −0.42 to −0.04). None of the variables analysed in the meta-regression were statistically significant related to PR.ConclusionThere is some evidence, based on trials with small samples, that the PR in trials testing drugs for CRF is non-trivial in size and statistically significant. We recommend that researchers planning drug studies in CRF should consider implementing alternative trial designs to better account for PR and decrease impact on the study results.

Exercise interventions for patients with advanced cancer: A systematic review of recruitment, attrition, and exercise adherence rates

2019 ◽  
Vol 17 (6) ◽  
pp. 686-696
Author(s):  
G. Sheill ◽  
E. Guinan ◽  
L. Brady ◽  
D. Hevey ◽  
J. Hussey
Keyword(s):  
Systematic Review ◽  
Advanced Cancer ◽  
Exercise Adherence ◽  
Physical Symptoms ◽  
Assessment Tools ◽  
Attrition Rate ◽  
Exercise Programs ◽  
Attrition Rates ◽  
Exercise Interventions ◽  
Patient Reported

AbstractPurposePatients with advanced cancer can experience debilitating physical symptoms, making participation in exercise programs difficult. This systematic review investigated the recruitment, adherence, and attrition rates of patients with advanced cancer participating in exercise interventions and examined components of exercise programs that may affect these rates.MethodsRelevant studies were identified in a systematic search of CINAHL, PubMed, PsycINFO, and EMBASE to December 2017. Two quality assessment tools were used, and levels of evidence were assigned according to the Oxford Centre for Evidence-Based Medicine (CEBM) guidelines.ResultsThe search identified 18 studies published between 2004 and 2017. Recruitment, adherence, and attrition rates varied widely among the studies reviewed. The mean recruitment rate was 49% (standard deviation [SD] = 17; range 15–74%). Patient-reported barriers to recruitment included time constraints and difficulties in traveling to exercise centers. Levels of adherence ranged from 44% to 95%; however, the definition of adherence varied substantially among trials. The average attrition rate was 24% (SD = 8; range 10–42%), with progression of disease status reported as the main cause for dropout during exercise interventions.Significance of resultsConcentrated efforts are needed to increase the numbers of patients with advanced disease recruited to exercise programs. Broadening the eligibility criteria for exercise interventions may improve accrual numbers of patients with advanced cancer to exercise trials and ensure patients recruited are representative of clinical practice.

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

Rheumatology ◽  
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.

scholarly journals Disease activity indices in coeliac disease: systematic review and recommendations for clinical trials

Gut ◽  
2016 ◽  
Vol 67 (1) ◽  
pp. 61-69 ◽  
Author(s):  
Pieter Hindryckx ◽  
Barrett G Levesque ◽  
Tom Holvoet ◽  
Serina Durand ◽  
Ceen-Ming Tang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Celiac Disease ◽  
Coeliac Disease ◽  
Disease Activity ◽  
Outcome Measures ◽  
Operating Characteristics ◽  
End Point ◽  
Patient Reported ◽  
Activity Indices

ObjectiveAlthough several pharmacological agents have emerged as potential adjunctive therapies to a gluten-free diet for coeliac disease, there is currently no widely accepted measure of disease activity used in clinical trials. We conducted a systematic review of coeliac disease activity indices to evaluate their operating properties and potential as outcome measures in registration trials.DesignMEDLINE, EMBASE and the Cochrane central library were searched from 1966 to 2015 for eligible studies in adult and/or paediatric patients with coeliac disease that included coeliac disease activity markers in their outcome measures. The operating characteristics of histological indices, patient-reported outcomes (PROs) and endoscopic indices were evaluated for content and construct validity, reliability, responsiveness and feasibility using guidelines proposed by the US Food and Drug Administration (FDA).ResultsOf 19 123 citations, 286 studies were eligible, including 24 randomised-controlled trials. Three of five PROs identified met most key evaluative criteria but only the Celiac Disease Symptom Diary (CDSD) and the Celiac Disease Patient-Reported Outcome (CeD PRO) have been approved by the FDA. All histological and endoscopic scores identified lacked content validity. Quantitative morphometric histological analysis had better reliability and responsiveness compared with qualitative scales. Endoscopic indices were infrequently used, and only one index demonstrated responsiveness to effective therapy.ConclusionsCurrent best evidence suggests that the CDSD and the CeD PRO are appropriate for use in the definition of primary end points in coeliac disease registration trials. Morphometric histology should be included as a key secondary or co-primary end point. Further work is needed to optimise end point configuration to inform efficient drug development.

scholarly journals Systematic review of patient-reported outcome measures (PROMs) for assessing disease activity in rheumatoid arthritis

RMD Open ◽  
2016 ◽  
Vol 2 (2) ◽  
pp. e000202 ◽  
Author(s):  
Jos Hendrikx ◽  
Marieke J de Jonge ◽  
Jaap Fransen ◽  
Wietske Kievit ◽  
Piet LCM van Riel
Keyword(s):  
Rheumatoid Arthritis ◽  
Systematic Review ◽  
Disease Activity ◽  
Outcome Measures ◽  
Patient Reported Outcome Measures ◽  
Patient Reported Outcome ◽  
Patient Reported

scholarly journals Assessment of Somatization and Medically Unexplained Symptoms in Later Life

Assessment ◽  
2017 ◽  
Vol 25 (3) ◽  
pp. 374-393 ◽  
Author(s):  
T. J. W. van Driel ◽  
P. H. Hilderink ◽  
D. J. C. Hanssen ◽  
P. de Boer ◽  
J. G. M. Rosmalen ◽  
...  
Keyword(s):  
Systematic Review ◽  
Older Persons ◽  
Large Scale ◽  
Somatic Symptom ◽  
Medically Unexplained Symptoms ◽  
Physical Symptoms ◽  
Brief Symptom Inventory ◽  
Persistent Symptoms ◽  
Medically Unexplained ◽  
Unexplained Symptoms

The assessment of medically unexplained symptoms and “somatic symptom disorders” in older adults is challenging due to somatic multimorbidity, which threatens the validity of somatization questionnaires. In a systematic review study, the Patient Health Questionnaire–15 (PHQ-15) and the somatization subscale of the Symptom Checklist 90-item version (SCL-90 SOM) are recommended out of 40 questionnaires for usage in large-scale studies. While both scales measure physical symptoms which in younger persons often refer to unexplained symptoms, in older persons, these symptoms may originate from somatic diseases. Using empirical data, we show that PHQ-15 and SCL-90 SOM among older patients correlate with proxies of somatization as with somatic disease burden. Updating the previous systematic review, revealed six additional questionnaires. Cross-validation studies are needed as none of 46 identified scales met the criteria of suitability for an older population. Nonetheless, specific recommendations can be made for studying older persons, namely the SCL-90 SOM and PHQ-15 for population-based studies, the Freiburg Complaint List and somatization subscale of the Brief Symptom Inventory 53-item version for studies in primary care, and finally the Schedule for Evaluating Persistent Symptoms and Somatic Symptom Experiences Questionnaire for monitoring treatment studies.

scholarly journals Patient-Reported Outcome Instruments for Physical Symptoms Among Patients Receiving Maintenance Dialysis: A Systematic Review

2015 ◽  
Vol 66 (6) ◽  
pp. 1033-1046 ◽  
Author(s):  
Jennifer E. Flythe ◽  
Jill D. Powell ◽  
Caroline J. Poulton ◽  
Katherine D. Westreich ◽  
Lara Handler ◽  
...  
Keyword(s):  
Systematic Review ◽  
Physical Symptoms ◽  
Patient Reported Outcome ◽  
Patient Reported ◽  
Maintenance Dialysis

Association of Physical Morbidity and Health-Related Quality of Life in a Representative Sample of Older German People

2018 ◽  
Vol 25 (4) ◽  
pp. 140-151
Author(s):  
Markus A. Wirtz ◽  
Matthias Morfeld ◽  
Elmar Brähler ◽  
Andreas Hinz ◽  
Heide Glaesmer
Keyword(s):  
Quality Of Life ◽  
Representative Sample ◽  
Short Form ◽  
Physical Symptoms ◽  
German Population ◽  
Health Related Quality ◽  
Patient Reported ◽  
Related Quality ◽  
Health Related

Abstract. The association between health-related quality of life (HRQoL; Short-Form Health Survey-12; SF-12) and patient-reported morbidity-related symptoms measured by the Patient Health Questionnaire-15 (PHQ-15) is analyzed in a representative sample of older people in the general German population. Data from 1,659 people aged 60 to 85 years were obtained. Latent class analysis identified six classes of patients, which optimally categorize clusters of physical symptoms the participants reported: musculoskeletal impairments (39.8%), healthy (25.7%), musculoskeletal and respiratory/cardiac impairments (12.8%), musculoskeletal and respiratory impairments, along with bowel and digestion problems (12.9%), general impairments (4.9%), and general impairments with no bowel and digestion problems (4.8%). The participants’ SF-12 Physical Health Scores (η2 = .39) and their Mental Health Scores (η2 = .28) are highly associated with these latent classes. These associations remain virtually identical after controlling for age. The results provide evidence that profiles of patient-reported physical impairments correspond strongly with reduced HRQoL independently from aging processes.

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