Can the General Public Be a Proxy for an "At-Risk" Group in a Patient Preference Study? A Disease Prevention Example in Rheumatoid Arthritis.

BACKGROUND: When selecting samples for patient preference studies, it may be difficult or impractical to recruit participants who are eligible for a particular treatment decision. However, a general public sample may not be an appropriate proxy. OBJECTIVE: This study compares preferences for rheumatoid arthritis (RA) preventive treatments between members of the general public and first-degree relatives (FDRs) of confirmed RA patients to assess whether a sample of the general public can be used as a proxy for FDRs. METHODS: Participants were asked to imagine they were experiencing arthralgia and had screening tests indicating a 60% chance of developing RA within 2 yrs. Using a discrete choice experiment, participants were offered a series of choices between no treatment and 2 unlabeled hypothetical treatments to reduce the risk of RA. To assess data quality, time to complete survey sections and comprehension questions were assessed. A random parameter logit model was used to obtain attribute-level estimates, which were used to calculate relative importance, maximum acceptable risk (MAR), and market shares of hypothetical preventive treatments. RESULTS: The FDR sample (n = 298) spent more time completing the survey and performed better on comprehension questions compared with the general public sample (n = 982). The relative importance ranking was similar between the general public and FDR participant samples; however, other relative preference measures involving weights including MARs and market share differed between groups, with FDRs having numerically higher MARs. CONCLUSION: In the context of RA prevention, the general public (average risk) may be a reasonable proxy for a more at-risk sample (FDRs) for overall relative importance ranking but not weights. The rationale for a proxy sample should be clearly justified. HIGHLIGHTS: Participants from the general public were compared to first-degree relatives on their preferences for rheumatoid arthritis (RA) preventive treatments using a discrete choice experiment.Preferences were similar between groups in terms of the most important and least important attributes of preventive treatments, with effectiveness being the most important attribute. However, relative weights differed.Attention to the survey and predicted market shares of hypothetical RA preventive treatments differed between the general public and first-degree relatives.The general public may be a reasonable proxy for an at-risk group for patient preferences ranks but not weights in the disease prevention context; however, care should be taken in sample selection for patient preference studies when choosing nonpatients.

Exploring preferences of at-risk individuals for preventive treatments for rheumatoid arthritis.

OBJECTIVE: Some immunomodulatory drugs have been shown to delay the onset of, or lower the risk of developing, rheumatoid arthritis (RA), if given to individuals at risk. Several trials are ongoing in this area; however, little evidence is currently available about the views of those at risk of RA regarding preventive treatment. METHOD: Three focus groups and three interviews explored factors that are relevant to first degree relatives (FDRs) of RA patients and members of the general public when considering taking preventive treatment for RA. The semi-structured qualitative interview prompts explored participant responses to hypothetical attributes of preventive RA medicines. Transcripts of focus group/interview proceedings were inductively coded and analysed using a framework approach. RESULTS: Twenty-one individuals (five FDRs, 16 members of the general public) took part in the study. Ten broad themes were identified describing factors that participants felt would influence their decisions about whether to take preventive treatment if they were at increased risk of RA. These related either directly to features of the specific treatment or to other factors, including personal characteristics, attitude towards taking medication, and an individual's actual risk of developing RA. CONCLUSION: This research highlights the importance of non-treatment factors in the decision-making process around preventive treatments, and will inform recruitment to clinical trials as well as information to support shared decision making by those considering preventive treatment. Studies of treatment preferences in individuals with a confirmed high risk of RA would further inform clinical trial design.

[SARS-CoV-2, influenza and norovirus infection : A direct epidemiologic comparison]. / SARS-CoV-2, Influenza und Norovirus : Die Klinikperspektive im Vergleich.

BACKGROUND: Hospitalization rates (HR), emergency care prevalence (ECP) and case fatality proportions (CFP) of hospitalized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients in one municipality have not been studied, including how these differ from other pandemic or seasonal viral diseases, such as influenza A/B or norovirus. These analyses and their comparison with negative-tested hospitalized patients are the purpose of the present study. METHODS: A total of 67,000 cases of hospitalized patients of a tertiary care hospital and data of the regional health institute were analyzed to calculate HR, ECP and CFP of SARS-CoV­2, influenza A/B and norovirus genotype 1/2. RESULTS: In the city and district of Fürth (Germany), 824 persons (0.34%) tested SARS-CoV-2-positive through 7 May 2020, 162 of whom (19.7%) were hospitalized. Furthermore, 48 out of 91 patients died in hospital (CFP 11.0%). During the flu/norovirus season 2019/2020 992 inhabitants were flu-positive and 135 norovirus-positive, of whom 202 (20.3%) and 125 (91.9%), respectively, were hospitalized. The ECPs were 4.1%, 2.0% and 0.6%. The CFPs of the SARS-CoV-2-, influenza- and norovirus-positive hospital cohort were 29.1%, 3.0% and 1.6%, while CFPs of the negative-tested were 5.9%, 4.8% and 6.9% with an in-hospital mortality of 2.1% for 2020. CONCLUSIONS: While HRs of SARS-CoV­2 and influenza were similar, CFPs differ significantly. CFPs of negative-tested patients were comparable between the three infectious diseases.

[Higher prevalence of depressive and anxiety symptoms in early arthritis patients in comparison to the normal population]. / Höhere Prävalenz von depressiven und ängstlichen Symptomen bei Früharthritispatienten im Vergleich zur Normalbevölkerung.

BACKGROUND: Many studies and registry data confirm that depression, often associated with anxiety disorders is very often found in patients with rheumatoid arthritis (RA). To what extent these psychiatric disorders are already relevant at a very early stage of the disease, has currently not been adequately investigated. METHODS: In this study 176 patients with early joint symptoms (<1 year) were surveyed in an early arthritis consultation (EAC). The hospital anxiety and depression scale (HADS) was completed by the patients to examine the prevalence of depressive and anxiety symptoms. The results were compared to normative data of the general German population and between the diagnosis groups. RESULTS: With 47.7% the prevalence of global distress for EA patients was almost twice as high compared to the corresponding group from the general population. This was also confirmed for depressive and anxiety symptoms. The EA patients without confirmed evidence of musculoskeletal inflammatory rheumatic disease (RD) showed nearly the same point prevalence as patients with confirmed RD. In multiple logistic regression the health assessment questionnaire (HAQ) was positively associated with global distress (odds ratio, OR 3.63) while the visual analogue scale (VAS) for global disease activity was positively associated with symptoms of depression (OR 1.03). Female EA patients (OR 5.45) appear to have a higher probability for experiencing corresponding symptoms, whereas patients over 60 years old appear to have less anxiety than younger patients (OR 0.11). CONCLUSION: The high prevalence of symptoms of depression and anxiety in EA patients compared to the general population is a challenge for rheumatologists, orthopedists and general practitioners, particularly with respect to the differentiation of possible psychosomatic components in noninflammatory joint complaints. The results suggest that screening for psychiatric problems in patients with rheumatism should be evaluated as soon as possible as these can have a great impact on the perception of pain and physical functional status from the very beginning.

Safety and efficacy of intravenous cyclophosphamide pulse therapy in therapy refractory Crohn's disease patients.

A major challenge in the management of persistently active Crohn's disease patient's refractory to treatment regimen following the current guidelines is the induction of remission, which is a prerequisite for subsequent maintenance therapy. The aim of this study was to evaluate both the clinical and endoscopic benefit of intravenous cyclophosphamide pulse therapy in patients with active and therapy refractory Crohn's disease. Nine patients with acute moderate to severe Crohn's disease, not responding to conventional as well as biological therapy regimen received 3 - 9 cycles of monthly treatments with intravenous cyclophosphamide (680 - 1000 mg) in an uncontrolled setting and were retrospectively analyzed. Eight of nine patients (88.9%) had a clinical response (measured by a decrease in the Harvey-Bradshaw index, HBI ≥ 3) and two of nine patients (22.2%) achieved clinical remission (HBI ≤ 4) at week 8 after two applications of intravenous cyclophosphamide therapy. These response and remission rates remained unchanged after individual completion of cyclophosphamide therapy. Median HBI decreased from 18 (7 - 25) at the beginning of therapy to 7 (3 - 18) at week 8. 5 of 9 patients (56%) showed endoscopic response (defined by a reduction of ulcers) and one patient (11%) reached endoscopic remission (defined by the absence of ulcers) after the last application of cyclophosphamide. Arthralgia, which was present in 4 of 9 (44%) patients, was unchanged in most patients after cyclophosphamide therapy, although one patient described a marked reduction in joint pain. Cyclophosphamide pulse therapy was well tolerated during the whole treatment course in all subjects. One patient with long-standing Crohn's disease was diagnosed with a high-grade intraepithelial neoplasia in the rectum and underwent surgical intervention, where the diagnosis of an early stage adenocarcinoma was made. We concluded that intravenous cyclophosphamide pulse therapy was well tolerated by most patients and effective for inducing clinical and endoscopic response and remission in patients with therapy refractory Crohn's disease. In patients who are unresponsive to available therapies, including available biological treatment options, cyclophosphamide therefore represents a potential option to induce therapeutic response, which must then be maintained by other treatment modalities.

[Depression and rheumatism: options for measuring depression]. / Depressivität und Rheuma: Möglichkeiten der Depressivitätsmessung.

BACKGROUND: The importance of depressive diseases in the treatment of rheumatism patients cannot be denied. It is well-known from publications in the English speaking literature that the proportion of depressive diseases lies between 10% and 45% in patients with rheumatoid arthritis (RA). However, clearly increased numbers can also be seen in a direct comparison with corresponding prevalence rates in the normal population for other diseases included in the category of rheumatism. OBJECTIVE: This manuscript focusses on the possibilities and challenges in measuring states of depressive mood that might serve as an indicator of depressive diseases in the context of treatment of rheumatism. MATERIAL AND METHODS: A search of the current literature was carried out and the results were evaluated. RESULTS: Starting from appropriate background knowledge, the current state of science is discussed while subsequently taking a closer look at a choice of internationally recognized assessment tools which are feasible for use in rheumatology. Finally, this overview is accompanied by hints for hands-on practice and suggestions on how to respond to conspicuous test results indicative of a depressive mood. DISCUSSION AND CONCLUSION: The potential benefits of appropriate screening with measurement instruments are considered to be high for rheumatism patients. The measurement tools presented must be suitably selected for the individual purpose and for each rheumatology institution. In view of test application consideration must be given not only to the total score but also to the individual responses to test items. In cases of conspicuous test results the further approach must be agreed together with the patient and by choosing adequate treatment options for the situation. In cases of acute suicidal tendencies acceptance, care and support are of key importance, while the precautionary presentation in a specialist clinic must be initiated.

Semiquantitative measurements of capsular contracture with elastography--first results in correlation to Baker Score.

BACKGROUND: To estimate the presence and severity of capsular contracture in patients after breast implants an objective measurement tool is necessary. PATIENTS AND METHODS: Eleven patients (range of age 37 to 53 years) who underwent cosmetic breast augmentation (seven patients with bilateral implants) or breast reconstruction by mammary asymmetry (four patients unilateral) with smooth silicone gel implants were included in this prospective study. In total seventeen implants were examined clinically and with the colour coded Ultrasound Elastography using a multifrequency probe (5-10 MHz Siemens Antares Premium VFX13-5). The grade of capsular contracture was assessed by two examiners with the palpation method and classified according to the Baker score. The Ultrasound Elastography was performed by two radiologists specialized in breast imaging and was correlated with the Baker score, colour coded ultrasound elastography and a high resolution ultrasound B-scan score (0-5). RESULTS: The clinical examination proved following distribution of the Baker degree: 6 breast implants with Baker grade I and Baker grade II, 3 breast implants with Baker grade III and two breast implants with Baker grade IV. There was a high correlation between the Baker score and the objective scoring measured by Ultrasound Elastography (kappa 0.83-0.89). CONCLUSION: The new technology of Ultrasound Elastography represents a useful tool to evaluate the compressibility of the peri-implant capsule, the implant and the surrounding tissue.

[Depression as a systemic feature of rheumatoid arthritis]. / Depression als Systemeffekt bei rheumatoider Arthritis.

The social recognition of depression in general and as a comorbidity in illnesses such as rheumatoid arthritis (RA) has essentially changed in recent years. Previous studies have shown that the occurrence of depression in RA patients is closely related to the individual ways of coping with disease and the corresponding impact of disease on daily life. Patients who are experiencing feelings of helplessness while facing the illness are prone to depressive disorders, especially if effective strategies for managing the impact of disease are lacking. Tools for early recognition of depression include instruments such as patient questionnaires or interview protocols which should be interpreted with caution due to the overlap of symptoms arising from RA and depression. A supplemental cognitive behavioral intervention in addition to medication with antidepressive drugs provides an opportunity to identify the underlying cause of depression and learn about effective coping strategies to at least partially maintain self-control of RA.

[Psoriatric arthritis - a permanent challenge for rheumatologists and patients: part 2: imaging diagnostics, classification and therapy]. / Psoriasisarthritis - eine bleibende Herausforderung für Rheumatologen und Patienten: Teil 2: Bildgebende Diagnostik, Klassifikation, Therapie.

In recent years a considerable number of imaging techniques have been used to demonstrate the onset and progression of arthritis-related changes in psoriatric arthritis (PsA). Moreover the identification of new immunological pathways has resulted in a substantial improvement of available therapies for PsA increasing the chance for the individual to receive effective treatment. Although an all-embracing disease activity score is still lacking, there is a variety of symptom-related tools to adequately reflect the course of disease and to evaluate the corresponding treatment success. This manuscript aims to give an overview of the latest corresponding knowledge with respect to PsA.

[Psoriatic arthritis : a permanent challenge for rheumatologists and patients--Part 1: epidemiology, pathogenesis and clinical course]. / Psoriasisarthritis : Eine bleibende Herausforderung für Rheumatologen und Patienten - Teil 1: Epidemiologie, Pathogenese und Klinik.

Psoriatic arthritis is still one of the big challenges in rheumatology due to the great variety of symptoms. Treatment frequently requires an interdisciplinary collaboration of general practitioners, dermatologists and rheumatologists who are able to recognize the onset of disease early by means of classification criteria and new imaging techniques followed by the implementation of appropriate antirheumatic treatment. During recent years new immunological pathways have been discovered leading to an increasing number of potential therapies, which increases the chance to find effective individualized treatment. However, tracking back the onset of the disease to specific causes is still a challenge which is made even more complex due to the absence of specific serum parameters.

Finalisation and validation of the rheumatoid arthritis impact of disease score, a patient-derived composite measure of impact of rheumatoid arthritis: a EULAR initiative.

OBJECTIVE: A patient-derived composite measure of the impact of rheumatoid arthritis (RA), the rheumatoid arthritis impact of disease (RAID) score, takes into account pain, functional capacity, fatigue, physical and emotional wellbeing, quality of sleep and coping. The objectives were to finalise the RAID and examine its psychometric properties. METHODS: An international multicentre cross-sectional and longitudinal study of consecutive RA patients from 12 European countries was conducted to examine the psychometric properties of the different combinations of instruments that might be included within the RAID combinations scale (numeric rating scales (NRS) or various questionnaires). Construct validity was assessed cross-sectionally by Spearman correlation, reliability by intraclass correlation coefficient (ICC) in 50 stable patients, and sensitivity to change by standardised response means (SRM) in 88 patients whose treatment was intensified. RESULTS: 570 patients (79% women, mean ± SD age 56 ± 13 years, disease duration 12.5 ± 10.3 years, disease activity score (DAS28) 4.1 ± 1.6) participated in the validation study. NRS questions performed as well as longer combinations of questionnaires: the final RAID score is composed of seven NRS questions. The final RAID correlated strongly with patient global (R=0.76) and significantly also with other outcomes (DAS28 R=0.69, short form 36 physical -0.59 and mental -0.55, p<0.0001 for all). Reliability was high (ICC 0.90; 95% CI 0.84 to 0.94) and sensitivity to change was good (SRM 0.98 (0.96 to 1.00) compared with DAS28 SRM 1.06 (1.01 to 1.11)). CONCLUSION: The RAID score is a patient-derived composite score assessing the seven most important domains of impact of RA. This score is now validated; sensitivity to change should be further examined in larger studies.

Measuring joint involvement in polyarticular psoriatic arthritis: an introduction of alternatives.

OBJECTIVE: To compare the reliability of 3 different simplified joint counts with the gold standard 66 swollen/68 tender joint count (JC66/68) for assessing clinical response in patients with polyarticular psoriatic arthritis (PsA). METHODS: The 28-joint count (JC28), in the same way that it is used in rheumatoid arthritis, and 2 measures including distal interphalangeal (DIP) joints (the 32-joint count [JC32], including all finger joints as well as wrists and knees, and 36-joint count [JC36], which additionally included elbows and ankles), were compared with the JC66/68 in 182 patients using data from the Infliximab Multinational Psoriatic Arthritis Controlled Trial 2 trial database. Pearson's correlation coefficients were calculated to compare the swollen and tender JC28, JC32, and JC36 with the corresponding results of the total JC66/68. American College of Rheumatology (ACR) responses based on the individual measures were compared, and their ability in predicting a clinical response of ACR 20% improvement (ACR20) based on the JC66/68 was assessed by calculating the area under the receiver operating characteristic curve via logistic regression and the maximum Youden indices at weeks 14 and 24. RESULTS: All simplified joint counts were highly correlated to the standard JC66/68 both for tenderness and swelling at each individual visit (Pearson's correlation coefficients consistently >0.8, n = 182-200; P < 0.0001). Logistic regression for ACR20 response showed that area under the curve was constantly >0.91, with comparable results for Youden indices of the simplified joint counts. CONCLUSION: All simplified joint counts considered seemed sufficiently sensitive and specific to measure clinical response in trial patients with polyarticular PsA when compared with the JC66/68, no matter whether DIP joints were included (the JC36 and JC32) or excluded (the JC28). Further research will be needed to clarify this issue.

Elaboration of the preliminary Rheumatoid Arthritis Impact of Disease (RAID) score: a EULAR initiative.

BACKGROUND: Current response criteria in rheumatoid arthritis (RA) usually assess only three patient-reported outcomes (PROs): pain, functional disability and patient global assessment. Other important PROs such as fatigue are not included. OBJECTIVE: To elaborate a patient-derived composite response index for use in clinical trials in RA, the RA Impact of Disease (RAID) score. METHODS: Ten patients identified 17 domains or areas of health relevant for inclusion in the score, then 96 patients (10 per country in 10 European countries) ranked these domains in order of decreasing importance. The seven most important domains were selected. Instruments were chosen for each domain after extensive literature research of psychometric properties and expert opinion. The relative weight of each of the domains was obtained from 505 patients who were asked to "distribute 100 points" among the seven domains. The average ranks of importance of these domains were then computed. RESULTS: The RAID score includes seven domains with the following relative weights: pain (21%), functional disability (16%), fatigue (15%), emotional well-being (12%), sleep (12%), coping (12%) and physical well-being (12%). Weights were similar across countries and across patient and disease characteristics. Proposed instruments include the Health Assessment Questionnaire and numerical ratings scales. CONCLUSION: The preliminary RAID score is a patient-derived weighted score to assess the impact of RA. An ongoing study will allow the final choice of questionnaires and assessment of validity. This score can be used in clinical trials as a new composite index that captures information relevant to patients.