[National consensus statement by the Austrian Societies for Rheumatology, Pulmonology, Infectiology, Dermatology and Gastroenterology regarding the management of latent tuberculosis and the associated utilization of biologic and targeted synthetic DMARDS (disease modifying antirheumatic drugs)]. / Consensus Statement der Österreichischen Gesellschaften für Rheumatologie und Rehabilitation, Pneumologie, Infektiologie, Dermatologie und Gastroenterologie zum Umgang mit latenter Tuberkulose bei Therapien mit biologischen oder "targeted synthetic" DMARDs ("disease modifying antirheumatic drugs").

This nationwide Austrian consensus statement summarizes the recommendations on the management of latent tuberculosis by treatment with biologic and targeted synthetic DMARDs. The essential questions with respect to screening and preventive treatment were discussed by experts from the disciplines of rheumatology, pneumology, infectious diseases, dermatology and gastroenterology, based on the available data, and then a joint consensus was formed by agreement. This involved a differentiated discussion on the various forms of treatment, and clear recommendations were formulated.

Torque Teno Virus quantification for monitoring of immunomodulation with biologic compounds in the treatment of rheumatoid arthritis.

OBJECTIVES: RA patients who fail to respond to MTX can receive biologic dMARDs (bDMARDs). The Torque Teno Virus (TTV) is a potential novel candidate for monitoring of immunosuppression. We explore TTV in these patients and its association with clinical response to bDMARDs. METHODS: The BioBio Study is a multicentre randomized open-label trial, including RA patients with insufficient response to MTX. Patients were randomized to either TNFi (infliximab, INF), anti-IL-6 (tocilizumab, TCZ), CTLA4-Ig (abatacept, ABA) or anti-CD20 (rituximab, RTX) in addition to MTX. PCR was used to quantify TTV in the peripheral blood. RESULTS: TTV was measured in 95 patients (INF, n = 23; TCZ, n = 22; ABA, n = 27; RTX; n = 23). TTV increased by a median of 4.5 × 104 copies/ml [c/ml; interquartile range (IQR) 0-7.5 × 105] after 3 months. TTV levels at month 3 were associated with the Simplified Disease Activity Index (SDAI) (P = 0.03) and the Clinical Disease Activity Index (CDAI) response (P = 0.026) at month 6. A TTV cut-off level of 1.2 × 106 c/ml at month 3 had a positive likelihood ratio of 2.7 for prediction of an 85% reduction in SDAI at month 6. CONCLUSION: Our data suggest that TTV levels increase upon TNF, CD20 and costimulation blockade and are associated with the clinical response to bDMARDs in RA patients. TRIAL REGISTRATION: ClinicalTrials.gov; https://clinicaltrials.gov; NCT01638715.

Validity of data collected in BIOREG, the Austrian register for biological treatment in rheumatology: current practice of bDMARD therapy in rheumatoid arthritis in Austria.

BACKGROUND: The purpose of the present study was to check the validity of data collected in BIOREG, the Austrian register for biological treatment in rheumatology, and to elucidate eventual differences with respect to disease activity (DA) in patients with rheumatoid arthritis (RA) on established biological DMARDs (bDMARDs) before inclusion into the register (EST) and beginners at the time point of inclusion (NEW) after 1 year of treatment. METHODS: RA patients with a complete follow-up of 1 year in BIOREG were divided into EST and NEW and compared with respect to DA, remission rates, concomitant synthetic DMARDs (csDMARDs) and glucocorticoid therapy (GC) at baseline and after 1-year follow-up. Safety concerns are listed. Descriptive statistics are applied. RESULTS: For 346 RA patients (284 EST, 62 NEW) out of 970 RA patients included into BIOREG, a full data set for a 1-year follow-up was available. No differences in DA were observed after 1 year as expressed by DAS28 or RADAI-5, and small differences as expressed by remission rates according to DAS28, RADAI-5 or Boolean criteria (namely approximately 1/2, 1/3 to 1/4 and 1/4 to 1/5 of the patients respectively). Sixty-four adverse events (AEs) were noted in 56 (20 %) of EST and 20 in 19 (31 %) of NEW patients. Malignancy occurred in four patients. After 1 year, 48 % of EST patients but only 16 % of NEW patients were on bDMARD monotherapy. CONCLUSION: Regarding DA, the date collected in BIOREG appeared to be valid. After 1 year of bDMARD therapy, all patients, whether EST or NEW, achieved a similar level of DA. AEs occurred more frequently during the early phase of bDMARD treatment. Austrian rheumatologists initiate bDMARD therapy in patients with lower disease levels than in other European countries, leading to high remission rates.

Urinary Albumin Excretion and Vascular Function in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is associated with significant cardiovascular (CV) morbidity and mortality. Increased urinary albumin excretion is a marker of CV risk. There are only few data on urinary albumin excretion in RA patients. Aim of the present study was to investigate urinary albumin excretion in RA patients and analyze, whether there is an association between urinary albumin excretion and vascular function as measured by the augmentation index (AIx). In a total of 341 participants (215 with RA, 126 without RA) urinary albumin-creatinine ratio (ACR) was determined and the AIx was measured. The Kolmogorov-Smirnov-test was used to cluster patient groups whose distributions of ACR can be considered to be equal. A crude analysis showed a median ACR of 6.6 mg/g in the RA group and 5.7 mg/g in patients without RA (P > 0.05). In order to account for diabetes (DM) we formed 4 distinct patient groups. Group 1: RA-/DM- (n = 74); group 2: RA+/DM- (n = 195); group 3: RA-/DM+ (n = 52); group 4: RA+/DM+ (n = 20). Clustering of these groups revealed two distinct patient groups: those without RA and DM, and those with either RA or DM or both. The latter group showed statistically significant higher ACR (median 8.1 mg/g) as the former (median 4.5 mg/g). We found no significant correlation between AIx and ACR. Urinary albumin excretion in patients with RA or DM or both is higher than in subjects without RA and DM. This can be seen as a sign of vascular alteration and increased CV risk in these patients.

Is the state of health of rheumatoid arthritis patients receiving adequate treatment, predictable? - Results of a survey.

BACKGROUND: A survey was conducted to evaluate whether a steady improvement in the quality of life of Rheumatoid Arthritis (RA) patients as frequently reported in clinical studies, does actually occur. The focus of this study laid on the personal perception of RA patients. How do patients who have been treated along accepted guidelines see the state of their health and their joint pain at different points in time? METHODS: RA patients were asked to complete a questionnaire and return it to an opinion research centre. The questionnaire, which was developed by the authors, was divided into the areas: demography, symptom description and medical care, as well as the illness in a personal context. Three telephone interviews followed in monthly intervals when the patients' feelings about their illness, their every-day coping mechanisms and their social lives were rated. Intra-subject correlation and the level of agreement among patients when assessed at three different points within a two month period, was determined. RESULTS: 127 patients replied to the questionnaire. RA exerts a significant impact on a patient's daily life. Average ratings of current state of health and joint pain (answered on a 5-part scale extending from 1 (very good) to 5 (very bad)) range between 2.6 and 2.9 all three times. However, intra-subject correlation between the different assessment times, is in general quite modest. Concerning the question: "How is your join pain today?" only 14 of 127 participants express identical ratings all three times , while in one third of the participants, a difference of two digits on the 5-part scale, at least twice had to be noticed. Intra-class correlation coefficients between answers at different points are often much smaller than 0.5. Results were similar in all subgroups analysed (men vs. women; patients receiving biologics vs. those not receiving biologics; disease duration ≤3 years vs. 4 to 10 years vs. ≥11 years). CONCLUSION: On an individual level personal assessments of health, well-being and joint pain are nevertheless unsteady even within the timeframe of two months. This is why, even now, RA patients still cannot plan their lives as non-affected people can.

Primary malignant tumours of the scapula--a review of 29 cases.

PURPOSE: Primary malignant bone tumours of the scapula are very rare. Apart from limited small series and some case reports, international literature on flat bone sarcoma is exiguous and not much is known about the oncological outcome. METHODS: A retrospective analysis of 29 patients diagnosed with a primary malignant tumour of the scapula was performed. The mean age was 40 years. The average time of follow-up was 60 months. Diagnoses included chondrosarcoma in 11 patients, Ewing's sarcoma/PNET in six, osteosarcoma in three, and others in nine. RESULTS: Five patients (19%) had no surgery. Wide resection was performed in 18 patients (74%) and marginal and intralesional resection in three patients (13%) each. Fifteen patients underwent resection without bony reconstruction, seven patients underwent a Tikhoff-Linberg procedure, and two patients received a custom-made scapula prosthesis. Six patients were diagnosed with metastasis after a mean time of nine months after surgery, while three patients suffered local recurrence at an average of six months after surgery. Disease-specific survival was 70% at one year and 47% at five years. The mean MSTS score was 69% and was highest for patients with scapular prosthesis. CONCLUSION: The overall prognosis of primary malignant bone tumours of the scapula remains to be inferior compared to extremity sarcoma. Endoprosthetic reconstruction, however, shows promising functional results even in cases of total scapulectomy.

Prediction of ineffectiveness of biological drugs using machine learning and explainable AI methods: data from the Austrian Biological Registry BioReg.

OBJECTIVES: Machine learning models can support an individualized approach in the choice of bDMARDs. We developed prediction models for 5 different bDMARDs using machine learning methods based on patient data derived from the Austrian Biologics Registry (BioReg). METHODS: Data from 1397 patients and 19 variables with at least 100 treat-to-target (t2t) courses per drug were derived from the BioReg biologics registry. Different machine learning algorithms were trained to predict the risk of ineffectiveness for each bDMARD within the first 26 weeks. Cross-validation and hyperparameter optimization were applied to generate the best models. Model quality was assessed by area under the receiver operating characteristic (AUROC). Using explainable AI (XAI), risk-reducing and risk-increasing factors were extracted. RESULTS: The best models per drug achieved an AUROC score of the following: abatacept, 0.66 (95% CI, 0.54-0.78); adalimumab, 0.70 (95% CI, 0.68-0.74); certolizumab, 0.84 (95% CI, 0.79-0.89); etanercept, 0.68 (95% CI, 0.55-0.87); tocilizumab, 0.72 (95% CI, 0.69-0.77). The most risk-increasing variables were visual analytic scores (VAS) for abatacept and etanercept and co-therapy with glucocorticoids for adalimumab. Dosage was the most important variable for certolizumab and associated with a lower risk of non-response. Some variables, such as gender and rheumatoid factor (RF), showed opposite impacts depending on the bDMARD. CONCLUSION: Ineffectiveness of biological drugs could be predicted with promising accuracy. Interestingly, individual parameters were found to be associated with drug responses in different directions, indicating highly complex interactions. Machine learning can be of help in the decision-process by disentangling these relations.

Impact of TNF-blocking agents on male sperm characteristics and pregnancy outcomes in fathers exposed to TNF-blocking agents at time of conception.

OBJECTIVES: Published data were analysed to determine if the use of tumour necrosis factor (TNF) blocking agents in male patients during time of conception is associated with an increased risk of fetal abnormalities or complications during pregnancy. Moreover, we were interested in the impact of TNFblocking agents on sperm quality characteristics. METHODS: We performed a systematic literature review (Medline, online archives of Annual European Congress of Rheumatology and the American College of Rheumatology). One-hundred and thirty-nine Articles of potentially relevant reports were identified and screened for retrieval and nine articles were included in the final analysis. RESULTS: Overall, there were sixty cases, where expectant fathers used TNFblocking agents shortly before conception. The outcomes of the pregnancies are documented in twenty-eight events. We did not find any documentation of miscarriages or physical abnormities associated with TNF blocking treatment and paternity; however, we did find documentation evidence that sperm motility and vitality even may improve under TNF-blocking therapy. This improvement may be caused by a decrease in disease activity. CONCLUSIONS: Published data suggest that TNF-blocking therapy in male patients during time of conception does not increase the risk of adverse pregnancy outcome. In addition TNF-blocking therapy does not appear to reduce male fertility.

2022 update of the Austrian Society of Rheumatology and Rehabilitation nutrition and lifestyle recommendations for patients with gout and hyperuricemia.

BACKGROUND: Gout is the most frequent inflammatory joint disease in the western world and has a proven genetic background. Additionally, lifestyle factors like increasing life span and wealth, sufficient to excess nutritional status and a growing prevalence of obesity in the population, as well as e.g. alcohol consumption contribute to the rising incidence of hyperuricemia and gout. Apart from an adequate medication, medical advice on nutrition and lifestyle is an essential part of the management of gout patients, being at high risk of internal comorbidities. OBJECTIVE: In 2015, the ÖGR (Österreichische Gesellschaft für Rheumatologie und Rehabilitation) working group for osteoarthritis and crystal arthropathies already published nutrition and lifestyle recommendations for patients with gout and hyperuricemia. Since then, a multitude of literature has been published addressing this topic, what required an update. METHODS: First, the authors performed a hierarchical literature search to screen the meanwhile published literature. Also considering references of the first publication, the relevant literature was selected, and the 2015 recommendations were either kept as published, reformulated or newly produced. Finally, the evidence level and the level of agreement with each recommendation were added. RESULTS: Following this process, ten recommendations were generated instead of the initial nine. Like in the original publication, a colored icon presentation was provided to complement the written text. CONCLUSION: The Austrian nutrition and lifestyle recommendations for patients with gout and hyperuricemia were updated incorporating the most recent relevant literature, serving as education material for patients and updated information for physicians.

National consensus statement by the Austrian Societies for Rheumatology, Pulmonology, Infectiology, Dermatology and Gastroenterology regarding the management of latent tuberculosis and the associated utilization of biologic and targeted synthetic disease modifying antirheumatic drugs (DMARDs).

This publication provides a thorough analysis of the most relevant topics concerning the management of latent tuberculosis when using biologic and targeted synthetic Disease Modifying Antirheumatic Drugs (DMARDs) by a multidisciplinary, select committee of Austrian physicians. The committee includes members of the Austrian Societies for Rheumatology and Rehabilitation, Pulmonology, Infectiology, Dermatology and Gastroenterology. Consensus was reached on issues regarding screening and treatment of latent tuberculosis and includes separate recommendations for each biologic and targeted synthetic DMARD.

Rheumatological care in rural areas : The Rheuma-Bus project 2018.

OBJECTIVE: To explore the medical care of individuals in rural areas during a public health awareness project on musculoskeletal disorders (MSD). METHODS: A tour bus was adapted to accommodate rheumatological consultations at widely accessible sites in 16 towns, providing individual medical advice with respect to MSD. The participating rheumatologists assessed the nature (e.g. inflammatory/non inflammatory), extent and duration of MSD and, where possible, made a tentative diagnosis and gave further advice on the course of action. In addition, age, sex and pre-existing care were recorded. All individuals were asked to assess their own severity of pain using a numeric ordinal scale from "no" (0) to "extreme" (10). RESULTS: A total of 647 individuals visited the service. Median current pain intensity was 5 (interquartile range [IQR] 3-6), mean 4.9 (standard deviation [SD] 2.3). Osteoarthritis was suspected in 381 clients (59.6%), inflammatory rheumatic disease in 247 (38.7%), and in 104 (16.3%) other diseases. 307 (50%) were treated by a GP, 95 (15.5%) were under orthopaedic care, 204 (33.2%) under rheumatological care and 81 (13.1%) under supervision of other specialists. 104 clients (17%) had never consulted a physician for their MSD symptoms before. 27 (4.2%) of all the clients had a newly detected inflammatory rheumatic disease and 62 (9.6%) patients with suspected inflammatory rheumatic disease were not under previous rheumatological care. CONCLUSION: The findings showed that there is still a lot of negligence in awareness and knowledge of rheumatic diseases, at least in rural areas.

Depression: a common comorbidity in women with rheumatoid arthritis-results from an Austrian cross-sectional study.

OBJECTIVES: Previous research showed that depression is common in rheumatoid arthritis (RA). However, the prevalence very much depends on different assessment tools and sociocultural differences, respectively. The main study aim and research question was to investigate the proportion of depressive symptoms in Austrian female patients with RA. SETTING: A nationwide multicentre study with seven secondary care centres all over Austria (hospital-based rheumatological outpatient clinics and private practices). PARTICIPANTS: 319 patients with RA and 306 healthy controls (HCO), all female Caucasians, were asked to complete a Beck's Depression Inventory-Fast Screen (BDI-FS). Patients and HCO were ≥18 years. Patients had to fulfil the 2010 classification criteria for RA. In addition, disease activity, disability, medication, drinking of alcoholic beverages, smoking and occupational status were evaluated. PRIMARY AND SECONDARY OUTCOME MEASURES: A BDI-FS cut-off value of ≥4, per definition, indicates the presence of a depressive symptomatology. RESULTS: The return rate of questionnaires was high: 235/319 (73.7%) in patients with RA and 180/306 (58.8%), ending up with 392 complete questionnaires from 223 patients with RA (69.9%) and 169 HCO (55.2%). The BDI-FS was significantly higher in patients with RA (median BDI-FS 2 (IQR 0-4) vs median 1 (IQR 0-2) in HCO, p<0.001). BDI-FS scores from ≥4, which by definition indicate depression, were found in 29.6% of patients with RA and 12.4% of HCO (p<0.001). Depressive symptoms were strongly associated with disease activity (Clinical Disease Activity Index, p<0.001) and disability (Health Assessment Questionnaire, p<0.005). No association of depressive symptoms with age, alcohol consumption, smoking, occupational status or use of medication was found. CONCLUSIONS: One-third of female patients with RA showed depressive symptoms. Depression was significantly higher in female patients with RA than in female HCO and was strongly associated with disease activity and disability. It would be of interest to address the same question in male participants.

The Supply of Rheumatology Specialist Care in Real Life. Results of a Nationwide Survey and Analysis of Supply and Needs.

Objectives: To study the balance between the supply and need for rheumatology care in Austria. In addition, to investigate rheumatologists' work-hours, the amount of time rheumatologists dedicate to care for patients with rheumatic and musculoskeletal diseases (RMD), with non-RMD problems, and other professional activities such as research, teaching, and administration. Methods: A questionnaire covering aspects of professional activities was sent to all 215 rheumatologists registered with the Austrian Medical Association. The data collected was set in relation to the need calculated on the basis of recommendations put forward by the German society of rheumatology. Results: 149 of the 215 rheumatologists (69.0%) responded. Median weekly working time was 50 h (IQR 45-60). 47.4% of the working time was spent for care of patients with RMD. The remaining time was dedicated to patients with non-rheumatic diseases (19.6%), research and teaching (8.4%), and administration (24.5%). The number of full-time equivalents (FTE, based on a 40-h work-week) available for rheumatology care, thus, was calculated to be 178.5. Based on disease prevalence/incidence estimates and on the time allocation results of this survey, our study resulted in a need of 4.29 rheumatologists per 100.000 adult inhabitants (301.79 for an adult population of 7.03 × 106). Conclusion: The study demonstrated a substantial mismatch between the available supply and the need for rheumatology care. The results of our study are a conservative estimate, which should be taken into consideration for future healthcare workforce planning. In particular, the rising need for rheumatologists should be met by increasing the numbers of those specialists.

High Burden of Sexual Dysfunction in Female Patients with Rheumatoid Arthritis: Results of a Cross-sectional Study.

OBJECTIVE: To evaluate the effect of rheumatoid arthritis (RA) on impairing women's sexuality regarding motivation, activity, and satisfaction, and to assess the correlation of disease-related physical impairment within sexual functioning. METHODS: An anonymous survey among women with RA and healthy controls (HC) using standardized questionnaires, predominantly the Changes in Sexual Functioning Questionnaire-short form (CSFQ-14). In addition, disease activity, depression, and disability were evaluated. RESULTS: There were 319 questionnaires distributed to patients and 306 to HC. Of these, 235 patient questionnaires (73.7%) and 180 HC questionnaires (58.8%) were returned, of which 203 and 169 were completed, respectively. Of the patients with RA, 47.8% had a total CSFQ-14 score of ≤ 41, indicating female sexual dysfunction (FSD), as compared to 14.2% of HC (p < 0.0001). The median CSFQ-14 score was lower in patients with RA [42 points, interquartile range (IQR) 36-48] than in HC (49 points, IQR 44-54; p < 0.0001), resulting in an OR of 5.53 (95% CI 3.19-9.57; p < 0.0001). After adjustment for confounders, given a higher mean age of patients (55.2 ± 11.3 yrs) than HC (47.4 ± 11.8 yrs; p < 0.0001), the OR for FSD in patients with RA was still 3.04 (95% CI 1.61-5.75; p = 0.001). Neither the Health Assessment Questionnaire-Disability Index nor the Clinical Disease Activity Index was associated with FSD after adjustment. CONCLUSION: FSD apparently is highly prevalent in female patients with RA, affects all subdomains of sexual function, and is most likely underestimated in daily clinical practice. Of note, FSD could not be linked to disability or RA disease activity.

Immunosuppressives and biologics during pregnancy and lactation : A consensus report issued by the Austrian Societies of Gastroenterology and Hepatology and Rheumatology and Rehabilitation.

An increasing and early-onset use of immunosuppressives and biologics has become more frequently seen among patients with inflammatory bowel diseases (IBD) and rheumatic disorders. Many women in their childbearing years currently receive such medications, and some of them in an interdisciplinary setting. Many questions arise in women already pregnant or wishing to conceive with respect to continuing or discontinuing treatment, the risks borne by the newborns and their mothers and long-term safety. Together with the Austrian Society of Rheumatology and Rehabilitation, the IBD working group of the Austrian Society of Gastroenterology and Hepatology has elaborated consensus statements on the use of immunosuppressives and biologics in pregnancy and lactation. This is the first Austrian interdisciplinary consensus on this topic. It is intended to serve as a basis and support for providing advice to our patients and their treating physicians.

[Job satisfaction and prospects of internal medicine specialists in Austria--an analysis of the profession]. / Zufriedenheit und Zukunftsperspektive der Internist/innen in Osterreich--eine Analyse des Berufsbildes.

BACKGROUND: In the second half of the 20th century the medical profession has changed considerably. "The golden age of medicine" seems to be over. This study analyses job satisfaction and prospects of Austrian physicians in the twenty-first century. METHODS: A questionnaire was sent to all 289 internal medicine specialists in Upper Austria (the third largest of the nine Austrian provinces, with more than one million inhabitants). The main topics were: career choice, job satisfaction, and strategies for the future. Also aspects such as group practices, the position of general internal medicine physicians as opposed to those with further specialisation (e.g. cardiologists, nephrologists, etc.) were addressed. RESULTS: Austrian internal medicine specialists are generally content with their job, most of them would study medicine and specialize in internal medicine again. They experience more job satisfaction than their German colleagues. However, Austrian internal medicine specialists suffer from the additional workload caused by administration and bureaucracy. There is a general consensus among most internal medicine physicians that nowadays patients expect them to provide more information. Particularly doctors employed at hospitals experience a more aggressive attitude and an increased readiness to sue in their patients. Although 75% look positively towards the future, two thirds expect a cutback in their economic situation. The majority of Austrian internal medicine specialists consider group practices to be the way of the future. CONCLUSION: The vast majority of Austrian internal medicine specialists are satisfied with their job. Although the majority expects economic cutbacks in the future, most would study medicine and specialize in internal medicine again. Group practices are considered to be the way of the future.