Predictors for severe persisting pain in rheumatoid arthritis are associated with pain origin and appraisal of pain.

OBJECTIVES: To determine the proportion of patients with rheumatoid arthritis (RA) with severe persisting pain and to identify predictive factors despite treatment-controlled disease activity. METHODS: This prospective multicentre study included outpatients with RA scheduled for escalation of anti-inflammatory treatment due to active disease and severe pain (Disease Activity Score 28 (DAS28)>3.2 and Visual Analogue Scale (VAS)>50). At week 24, patients were stratified into reference group (DAS28 improvement>1.2 or DAS28≤3.2 and VAS pain score<50), non-responders (DAS28 improvement≤1.2 and DAS28>3.2, regardless of VAS pain score) and persisting pain group (DAS28 improvement>1.2 or DAS28≤3.2 and VAS pain score≥50). The former two subgroups ended the study at week 24. The latter continued until week 48. Demographic data, DAS28-C reactive protein, VAS for pain, painDETECT Questionnaire (PD-Q) to identify neuropathic pain (NeP) and the Pain Catastrophising Scale were assessed and tested for relation to persisting pain. RESULTS: Of 567 patients, 337 (59.4%) were classified as reference group, 102 (18.0%) as non-responders and 128 (22.6%) as patients with persisting pain. 21 (8.8%) responders, 28 (35.0%) non-responders and 27 (26.5%) persisting pain patients tested positive for NeP at week 24. Pain catastrophising (p=0.002) and number of tender joints (p=0.004) were positively associated with persisting pain at week 24. Baseline PD-Q was not related to subsequent persisting pain. CONCLUSIONS: Persisting and non-nociceptive pain occur frequently in RA. Besides the potential involvement of NeP, pain catastrophising and a higher number of tender joints coincide with persisting pain.

[Number of teeth as indicator for individual risk for delirium]. / Zahnzahl als Indikator für individuelles Delirrisiko.

BACKGROUND: Recent research claims some interdependence between oral health and dementia; however, no empirical data could be found regarding the role of oral hygiene in delirium. This study investigated potential risk indicators related to oral hygiene in relation to development of delirium in the care of older patients. METHODS: A dental examination was performed in 120 patients in the context of a case-control study. The ratio of diseased patients with risk factors to diseased patients without risk factors describes the correlation between risk factors and the risk of disease. A binary logistic regression was performed to determine the correlation of the number of teeth to delirium. RESULTS: Every lost tooth enhances the delirium risk by 4.6%. Edentulous patients had a 2.66-fold higher risk to suffer from delirium. Caries experience and periodontitis has no significant impact on delirium prevalence. DISCUSSION: Both edentulousness and the number of lost teeth could be considered as risk indicators for delirium. Periodontitis or caries experience did not have a direct significant impact. The present study examined the merits of edentulousness and tooth loss as a screening parameter.

Symptoms of older orthopedic and rheumatic patients : A telephone survey about symptoms, symptom communication, treatment and further support after hospital discharge.

BACKGROUND: In older multimorbid orthopedic and rheumatic patients, data on symptoms besides pain or reduced mobility are rarely published. OBJECTIVE: We investigated patients' perspectives on their symptoms after hospital discharge. MATERIAL AND METHODS: Orthopedic and rheumatic patients aged over 70 years were asked via telephone interviews about (i) their symptoms, (ii) communication, (iii) treatment, and (iv) support. RESULTS: (i) The 60 participants (35 women and 25 men) reported a median of 6 (min-max: 1-14) different symptoms, of which 86% (356 of 415) had existed before hospitalization, (ii) patients did not communicate 28% (117) of symptoms to either healthcare professionals, family or friends and (iii) 52 (87%) patients desired improvement. Of the 280 most impairing symptoms, 19% (52) were not treated at all. (iv) Almost all patients (59; 98%) considered it easy to obtain support. CONCLUSION: Remarkably, many symptoms were not communicated or treated despite the patients having been hospitalized.

Two years of pegvaliase in Germany: Experiences and best practice recommendations.

BACKGROUND: In 2019, pegvaliase was approved in Europe for the treatment of phenylketonuria (PKU) in patients aged 16 years and older with blood phenylalanine (Phe) concentrations above 600 µmol/L despite prior management with available treatment options. Since its European approval, German metabolic centres have gained valuable experience, which may be of benefit to other treatment centres managing patients on pegvaliase. METHODS: After a virtual meeting that was attended by nine German physicians, three German dietitians and one American physician, a follow-up discussion was held via an online platform to develop a set of recommendations on the use of pegvaliase in Germany. Eight German physicians contributed to the follow-up discussion and subsequent consensus voting, using a modified Delphi technique. The recommendations were supported by literature and retrospectively collected patient data. RESULTS: Consensus (≥75% agreement) was achieved on 25 recommendations, covering seven topics deemed relevant by the expert panel when considering pegvaliase an option for the treatment of patients with PKU. In addition to the recommendations, a retrospective chart review was conducted in seven of the centres and included 71 patients who initiated treatment with pegvaliase. Twenty-seven patients had been treated for at least 24 months and 23 (85.2%) had achieved blood Phe ≤600 µmol/L with some degree of diet normalisation. Of these patients, 14 had physiological blood Phe on a normalised diet. CONCLUSION: The practical consensus recommendations provide guidance on the different steps along the pegvaliase journey from clinical site requirements to treatment goals and outcomes. The recommendations are intended to support less experienced European metabolic centres with the implementation of pegvaliase, emphasising that a core treatment team consisting of at least a dietitian and metabolic physician is sufficient to initiate pegvaliase and support patients during their treatment journey.

Association between the Ile164 ß2 Adrenergic Receptor Polymorphism and Fatigue in Patients with Rheumatoid Arthritis.

INTRODUCTION: In the present work, the frequency of inherited polymorphisms of the beta 2 adrenergic receptor (ß2AR) gene and their association with fatigue in patients with rheumatoid arthritis (RA) was examined. METHODS: An allele-specific polymerase chain reaction was used to determine the common variants of the ß2AR at position 16, 27, and 164 in 92 German RA outpatients. Health Assessment Questionnaire (HAQ-DI), Beck Depression Inventory (BDI), Perceived Stress Questionnaire (PSQ-30), Multidimensional Fatigue Inventory (MFI-20) were utilized. RESULTS: 34.7% of German RA patients were diagnosed with associated fatigue. Fatigued patients were more likely to carry the Ile allele at position 164 (OR 7.33, 95% CI 1.09-59.8, p = 0.049). Comparing these risk factors' contribution to different fatigue dimensions revealed that Ile164 carriers only had significantly higher MFI-20 mean values for general fatigue (p = 0.014) while the clinical difference among other MFI subscales was the largest for mental fatigue (carrier: 8.23, SD: 4.22, noncarrier: 5.67, SD: 1.56, p = 0.089, Cohen's d = 0.629). Disease activity, perceived stress, and depression were also associated with fatigue with higher mean values for DAS28CRP (p = 0.038), PSQ (p < 0.001), and BDI-II (p < 0.001) in fatigued patients. Physical fatigue was correlated with disease activity (p = 0.009) and depression (p = 0.001) while mental fatigue showed associations with depression (p = 0.001) and perceived stress (p = 0.028). CONCLUSION: The discovery study indicates that the Ile164 polymorphism might in contrast to other ß2AR polymorphisms affect fatigue levels in RA patients. This association was observed especially with mental fatigue. Further replication studies are warranted to determine further role of ß2AR polymorphisms in RA patients.

Management, vaccination status and COVID-19 morbidity of patients with Gaucher disease in Germany during the COVID-19 pandemic.

BACKGROUND: Continuation of standard management of Gaucher disease (GD) has been challenging during the COVID-19 pandemic, resulting in infrequent/missed infusions and follow-up appointments. Little data are available on the consequences of these changes and on the SARS-CoV-2 vaccinations in German GD patients. METHODS: A survey with 22 questions about GD management during the pandemic was sent to 19 German Gaucher centres. It was answered by 11/19 centres caring for 257 GD patients (almost ¾ of the German GD population); 245 patients had type 1 and 12 had type 3 GD; 240 were ≥ 18 years old. RESULTS: Monitoring intervals were prolonged in 8/11 centres from a median of 9 to 12 months. Enzyme replacement therapy (ERT) was changed to home ERT in 4 patients and substituted by oral substrate reduction therapy (SRT) in 6 patients. From March 2020 to October 2021, no serious complications of GD were documented. Only 4 SARS-CoV-2 infections were reported (1.6%). Two infections were asymptomatic and two mild; all occurred in adult type 1, non-splenectomized patients on ERT. Vaccination rate in adult GD was 79.5% (95.3% mRNA vaccines). Serious vaccination complications were not reported. CONCLUSIONS: The COVID-19 pandemic has lowered the threshold for switching from practice- or hospital-based ERT to home therapy or to SRT. No major GD complication was documented during the pandemic. Infection rate with SARS-CoV-2 in GD may rather be lower than expected, and its severity is mild. Vaccination rates are high in GD patients and vaccination was well tolerated.

[Trial of the GeriNOT screening tool : Identification of geriatric risk potentials on admission to hospital care from the age of 70 years]. / Prüfung des Screening-Tools GeriNOT : Identifikation geriatrischer Risikopotenziale bei Aufnahme ab 70-Jähriger in die Krankenhausversorgung.

BACKGROUND: Geriatric-specific characteristics influence patient-relevant outcomes of inpatient hospital care in patients aged 70 years and older: prolonged length of stay, complications, increase in utilization of required services as well as mortality rates. OBJECTIVE: The screening tool GeriNOT, identification of geriatric risk potential with 7 items, of which mobility and cognition are double-weighted, score 9 points, was tested for its predictive content and diagnostic quality. MATERIAL AND METHODS: Diagnostic study from a retrospective, bicentric complete survey in all types of admission from 70 years with 2541 patient cases. Regression analyses in linked samples of the 7 items in GeriNOT and as noncombined end points: prolonged length of stay, complications, increase in need-based service at discharge and death. RESULTS: Mean age ± SD: 77.0 ± 6.4 years. ROC analyses report at a cut-off value calculated using the Youden index of ≥ 4 points in 2541 cases: increase in need-based service at discharge (AUC = 0.693, 95% CI = 0.663-0.723, sensitivity 75.2%, specificity 59.7%), complications (AUC = 0.662, 95% CI = 0.636-0.688, sensitivity 64.2%, specificity 61.6%) and death (AUC = 0.734, 95% CI = 0.682-0.786, sensitivity 76.4%, specificity 57.5%). Possibly suitable for use as screening to identify geriatric risk potentials at a cut-off of ≥ 4 points. DISCUSSION: Provide an initial filter screening with regard to mobility. Such identification could provide the involved persons with the opportunity for an improved treatment outcome by adapting the inpatient process. Prospective validation of GeriNOT needed.

Humoral and cellular response to COVID-19 vaccination in patients with autoimmune inflammatory rheumatic diseases under real-life conditions.

OBJECTIVES: Successful vaccination is key to overcoming the COVID-19 pandemic. Immunosuppressive medication is known to potentially compromise vaccination responses, and expansion of our knowledge on vaccination efficacy in patients with autoimmune inflammatory rheumatic diseases (AIIRD) is therefore of utmost importance. METHODS: We conducted a single-centre observational study and evaluated the efficacy of approved COVID-19 vaccines in 303 adult AIIRD patients. Serum levels of IgG antibodies against the S1 subunit of SARS-CoV-2 spike proteins (anti-S IgG) were measured at least two weeks after vaccination. In a subgroup of patients without humoral response, T-cell responses were determined using an interferon-γ gamma release assay. RESULTS: Overall seropositivity rate was 78.5% and was significantly lower in patients under immunosuppressive therapy (75.7 vs 93.2%, P = 0.009). No difference regarding the vaccination type was observed. Glucocorticoids, mycophenolate-mofetil, TNF inhibitors, tocilizumab, abatacept and rituximab were all associated with non-response after proper vaccination. The risk was highest under RTX therapy (OR 0.004, 95% CI 0.001, 0.023, P < 0.0001). A strong negative correlation was observed between time since vaccination with an mRNA vaccine and anti-S antibody levels (r=-0.6149, P < 0.0001). In patients without humoral response, a T-cell response was found in 50%. CONCLUSIONS: COVID-19 vaccination in patients with AIIRD is effective using any approved vaccine. Humoral response might be impaired depending on the individual immunosuppressive medication. The risk of non-response is highest under rituximab therapy. Anti-S IgG antibody levels wane over time after mRNA vaccination. Importantly, 50% of humoral non-responders showed a T-cellular response, suggesting T-cell-mediated protection to a certain extent.

Impact of pregnancy planning and preconceptual dietary training on metabolic control and offspring's outcome in phenylketonuria.

To prevent maternal phenylketonuria (PKU) syndrome low phenylalanine concentrations (target range, 120-360 µmol/L) during pregnancy are recommended for women with PKU. We evaluated the feasibility and effectiveness of current recommendations and identified factors influencing maternal metabolic control and children's outcome. Retrospective study of first successfully completed pregnancies of 85 women with PKU from 12 German centers using historical data and interviews with the women. Children's outcome was evaluated by standardized IQ tests and parental rating of child behavior. Seventy-four percent (63/85) of women started treatment before conception, 64% (54/85) reached the phenylalanine target range before conception. Pregnancy planning resulted in earlier achievement of the phenylalanine target (18 weeks before conception planned vs. 11 weeks of gestation unplanned, p < 0.001) and lower plasma phenylalanine concentrations during pregnancy, particularly in the first trimester (0-7 weeks of gestation: 247 µmol/L planned vs. 467 µmol/L unplanned, p < 0.0001; 8-12 weeks of gestation: 235 µmol/L planned vs. 414 µmol/L unplanned, p < 0.001). Preconceptual dietary training increased the success rate of achieving the phenylalanine target before conception compared to women without training (19 weeks before conception vs. 9 weeks of gestation, p < 0.001). The majority (93%) of children had normal IQ (mean 103, median age 7.3 years); however, IQ decreased with increasing phenylalanine concentration during pregnancy. Good metabolic control during pregnancy is the prerequisite to prevent maternal PKU syndrome in the offspring. This can be achieved by timely provision of detailed information, preconceptual dietary training, and careful planning of pregnancy.

Sepsis Mortality Is high in Patients With Connective Tissue Diseases Admitted to the Intensive Care Unit (ICU).

OBJECTIVES: Patients with connective tissue diseases (CTD) such as systemic lupus erythematosus (SLE) have an increased risk for infections. This study investigated the outcome and characteristics of CTD patients under intensive care unit (ICU) treatment for sepsis. METHODS: A single-center retrospective analysis was conducted and reviewed all patients with a CTD diagnosis admitted to the ICU of a university hospital for sepsis between 2006 and 2019. Mortality was computed and multivariate logistic regression was used to detect independent risk factors for sepsis mortality. Furthermore, the positive predictive value of ICU scores such as Sequential Organ Failure Assessment (SOFA) score was evaluated. RESULTS: This study included 44 patients with CTD (mean age 59.8 ± 16.1 years, 68.2% females), most of them with a diagnosed SLE (61.4%) followed by systemic sclerosis (15.9%). 56.8% (n = 25) were treated with immunosuppressives and 81.8% (n = 36) received glucocorticoids. Rituximab was used in 3 patients (6.8%). The hospital mortality of septic CTD patients was high with 40.9%. It was highest among systemic sclerosis (SSc) patients (85.7%). SOFA score and diagnosis of SSc were independently associated with mortality in multivariate logistic regression (P = 0.004 and 0.03, respectively). The Simplified Acute Physiology Score II (SAPS II), SOFA and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were good predictors of sepsis mortality in the investigated cohort (SAPS II AUC 0.772, P = 0.002; SOFA AUC 0.756, P = 0.004; APACHE II AUC 0.741, P = 0.007). CONCLUSIONS: In-hospital sepsis mortality is high in CTD patients. SSc diagnoses and SOFA were independently associated with mortality. Additionally, common ICU scores were good predictors for mortality.

Mortality of Sepsis in Patients With Rheumatoid Arthritis: A Single-Center Retrospective Analysis and Comparison With a Control Group.

INTRODUCTION/BACKGROUND: Patients with rheumatoid arthritis (RA) have a high risk of infections that may require intensive care unit (ICU) admission in case of resulting sepsis. Data regarding the mortality of these patients are very limited. This study investigated clinical characteristics and outcomes of patients with RA admitted to the ICU for sepsis and compared the results to a control cohort without RA. METHODS: All patients with RA as well as sex-, age-, and admission year-matched controls admitted to the ICU of a university hospital for sepsis between 2006 and 2019 were retrospectively analyzed. Mortality was calculated for both the groups, and multivariate logistic regression was used to determine independent risk factors for sepsis mortality. The positive predictive value of common ICU scores was also investigated. RESULTS: The study included 49 patients with RA (mean age 67.2 ± 9.0 years, 63.3% females) and 51 matched controls (mean age 67.4 ± 9.5 years, 64.7% females). Among the patients with RA, 42.9% (n = 21) were treated with conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) and 30.6% (n = 15) received glucocorticoids only. Seven (14.3%) patients received biologic (b) DMARDs. The hospital mortality was higher among patients with RA (42.9% vs 15.7%, P = .0016). Rheumatoid arthritis was independently associated with mortality in multivariate logistic regression (P = .001). In patients with RA, renal replacement therapy (P = .024), renal failure (P = .027), and diabetes mellitus (P = .028) were independently associated with mortality. Acute Physiology and Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology Score II (SAPS II), and Sequential Organ Failure Assessment (SOFA) scores were good predictors of sepsis mortality in patients with RA (APACHE II area under the curve [AUC]: 0.78, P = .001; SAPS II AUC: 0.78, P < .001; SOFA AUC 0.78, P < .001), but their predictive power was higher among controls. CONCLUSIONS: Hospital sepsis mortality was higher in patients with RA than in controls. Rheumatoid arthritis itself is independently associated with an increased sepsis mortality. Renal replacement therapy, renal failure, and diabetes were associated with an increased mortality. Common ICU scores were less well predictors of sepsis mortality in patients with RA compared to non-RA controls.

Outcome of Patients With Necrotizing Vasculitis Admitted to the Intensive Care Unit (ICU) for Sepsis: Results of a Single-Centre Retrospective Analysis.

INTRODUCTION/BACKGROUND: Vasculitis patients have a high risk for infections that may require intensive care unit (ICU) treatment in case of resulting sepsis. Since data on sepsis mortality in this patient group is limited, the present study investigated the clinical characteristics and outcomes of vasculitis patients admitted to the ICU for sepsis. METHODS: The medical records of all necrotizing vasculitis patients admitted to the ICU of a tertiary hospital for sepsis in a 13-year period have been reviewed. Mortality was calculated and multivariate logistic regression was used to determine independent risk factors for sepsis mortality. Moreover, the predictive power of common ICU scores was further evaluated. RESULTS: The study included 34 patients with necrotizing vasculitis (mean age 69 ± 9.9 years, 35.3% females). 47.1% (n = 16) were treated with immunosuppressives (mostly cyclophosphamide, n = 35.3%) and 76.5% (n = 26) received glucocorticoids. Rituximab was used in 4 patients (11.8%).The in-hospital mortality of septic vasculitis patients was 41.2%. The Sequential Organ Failure Assessment (SOFA) score (p = 0.003) was independently associated with mortality in multivariate logistic regression. Acute Physiology And Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology Score II (SAPS II) and SOFA scores were good predictors of sepsis mortality in the investigated vasculitis patients (APACHE II AUC 0.73, p = 0.02; SAPS II AUC 0.81, p < 0.01; SOFA AUC 0.898, p < 0.0001). CONCLUSIONS: Sepsis mortality was high in vasculitis patients. SOFA was independently associated with mortality in a logistic regression model. SOFA and other well-established ICU scores were good mortality predictors.

Everyday Life, Dietary Practices, and Health Conditions of Adult PKU Patients: A Multicenter, Cross-Sectional Study.

BACKGROUND: Only few data on dietary management of adult phenylketonuria (PKU) patients are published. OBJECTIVES: This study aimed to assess living situation, dietary practices, and health conditions of early-treated adult PKU patients. METHODS: A total of 183 early-treated PKU patients ≥18 years from 8 German metabolic centers received access to an online survey, containing 91 questions on sociodemographic data, dietary habits, and health conditions. RESULTS: 144/183 patients (66% females) completed the questionnaire. Compared with German population, the proportion of single-person households was higher (22 vs. 47%), the rate of childbirth was lower (1.34 vs. 0.4%), but educational and professional status did not differ. 82% of the patients adhered to a low-protein diet, 45% consumed modified low-protein food almost daily, and 84% took amino acid mixtures regularly. 48% of the patients never interrupted diet, and 14% stopped diet permanently. 69% of the patients reported to feel better with diet, and 91% considered their quality of life at least as good. The prevalence of depressive symptoms was high (29%) and correlated significantly to phenylalanine blood concentrations (p = 0.046). However, depressive symptoms were only mild in the majority of patients. CONCLUSION: This group of early-treated adult German PKU patients is socially well integrated, reveals a surprisingly high adherence to diet and amino acid intake, and considers the restrictions of diet to their daily life as low.

Cost per response for abatacept versus adalimumab in patients with seropositive, erosive early rheumatoid arthritis in the US, Germany, Spain, and Canada.

BACKGROUND: Effective treatment of rheumatoid arthritis (RA) with biologic DMARDs poses a significant economic burden. The AMPLE (Abatacept versus adaliMumab comParison in bioLogic-naïvE RA subjects with background methotrexate) trial was a head-to-head, randomized study comparing abatacept with adalimumab. A post hoc analysis showed improved efficacy for abatacept in patients with versus without seropositive, erosive early RA. OBJECTIVE: The aim of the current study was to evaluate the cost per response (ACR20/50/70/90 and HAQ-DI) and patient in remission (DAS28-CRP, CDAI, and SDAI) for abatacept relative to adalimumab, in patients with seropositive, erosive early RA in the US, Germany, Spain, and Canada. METHODS: A previously published model was used to compare abatacept and adalimumab in a cohort of 1000 patients over 2 years. Clinical inputs were updated based on two subpopulations from the AMPLE trial. Cohort 1 included patients with early RA (disease duration ≤ 6 months), RF and/or ACPA seropositivity, and > 1 radiographic erosion. Cohort 2 included patients with RA in whom at least one of these criteria was absent. RESULTS: For cohort 1, all incremental costs per additional health gain (patient response or patient in remission) favoured abatacept in all countries, except for DAS28-CRP remission in Canada. Cost savings versus adalimumab were greater when more stringent response criteria were applied and also in cohort 1 patient (versus cohort 2 patients). CONCLUSION: The cost per responder and patient in remission favoured abatacept in patients with seropositive, erosive early RA across all the countries. In this patient population, the use of abatacept instead of adalimumab can lead to lower costs in the US, Germany, Spain, and Canada.

[Survey of rheumatologists in Saxony, Saxony-Anhalt and Thuringia regarding the occupational situation and activities in further education: no way out of the undersupply of rheumatological care]. / Befragung von Rheumatologen in Sachsen, Sachsen-Anhalt und Thüringen zu Weiterbildungstätigkeit und beruflicher Situation: Kein Ausweg aus der rheumatologischen Unterversorgung.

INTRODUCTION: Many regions in the middle of Germany have a deficit in specialized rheumatological care. A survey was undertaken to investigate whether the regional capacities for rheumatological advanced training are sufficient to provide an adequate number of rheumatologists in the future. METHODS: All 91 rheumatologists registered in Saxony, Saxony-Anhalt and Thuringia received a questionnaire that was sent back by 66% of the recipients (23 responses from Saxony, 19 from Saxony-Anhalt, 18 from Thuringia). Of the rheumatologists 41 were in private practice, 19 worked in an inpatient department and the mean duration of professional activity was 18 years. RESULTS: Over the last decade the number of patients treated by rheumatologists in private practices increased from 1200 to 1500 per quarter year (p < 0.001), whereas the number of first consultations rose from 100 to 130 per quarter year (p = 0.06). The waiting time for a first consultation rose from 8 to 11 weeks (p = 0.01), 32% of the responders indicated that the conditions for outpatient treatment had either improved or had remained constant during the last 10 years, whereas 60% reported a mild or marked deterioration and 48% stated that the number of rheumatologists had decreased within the same time frame. Only 20% indicated that they had a definite successor in the practice after retirement. All inpatient departments also had an outpatient office. During the last 10 years, the number of consultations per quarter year decreased from 1100 to 700 (not significant), while the waiting time doubled from 6 to 12 weeks (rounded mean). Of the rheumatologists in private practice eight are currently entitled to provide advanced education in rheumatology, with a median training period of 18 months; however, none of the responding physicians had actually brought assistant doctors to the final examination during the last decade and only one prospective rheumatologist was currently completing training in a private practice setting. Only 6 out of 12 inpatient rheumatological facilities are entitled to educate rheumatologists over the whole training period, 5 facilities were not involved in training at all and 7 indicated that they lacked applications for rheumatology training. During the last 10 years, 37 rheumatologists completed the training of which 18 went into private practice, 8 worked as general practitioners and 29 remained in the region of their initial training. CONCLUSION: Given the increase in the number of outpatients served, the volume of training activities in rheumatology is hardly sufficient to improve the deficit of rheumatological care in the middle of Germany.

Cost-effectiveness of early treatment of ACPA-positive rheumatoid arthritis patients with abatacept.

OBJECTIVES: Studies have reported that the presence of elevated anti-citrullinated protein antibodies (ACPA)/RF levels, together with joint erosions, is associated with higher disease burden in terms of disability and mortality in rheumatoid arthritis (RA). Abatacept has been shown to be effective in this patient population with favourable comparative data against adalimumab. However, few studies have investigated the cost-effectiveness of abatacept in this population to similar treatments such as TNFs. The objective of the study was to compare the cost-effectiveness of abatacept to adalimumab as a first bDMARD in ACPA-positive RA patients who failed treatment with methotrexate (MTX) in Germany. METHODS: A decision tree model was used to estimate the cost-effectiveness, from a payer's perspective, of different treatment sequences in RA over a two year time frame. The effectiveness criteria were defined as achieving the treatment target measured by the Disease Activity Score 28 (DAS28(CRP)<2.6; "remission"). A treatment switch to a different biologic as 2nd line and 3rd line bDMARD was allowed - in case of not achieving remission with therapy - every 6 months over a two year time period. Effectiveness data was based on randomised controlled trials (RCT) identified by an updated previous systematic literature search by the Institute for Quality and Efficiency in Health Care (IQWiG). Costs of medication and other direct medical costs were considered. Cost-effectiveness of RA treatment was investigated in ACPA-positive patients and presented as overall costs per day in remission. RESULTS: For ACPA-positive patients, treatment strategies including early treatment with abatacept had lower total costs per clinical outcome compared to later use. Treatment sequences starting with abatacept resulted in lower costs per day in remission (mean 330 €/day, range 328-333 €/day) compared to sequences starting with adalimumab (mean 384 €/day, range 378-390 €/day). Choice of the second or third biologic in the treatment sequences appears to have little impact on the costs per outcome. CONCLUSIONS: The results of this analysis suggest that in ACPA-positive RA patients treatment with abatacept appears to have lower costs per response (remission) compared to treatment with adalimumab as a first bDMARD.

Low vaccination rates among patients with rheumatoid arthritis in a German outpatient clinic.

Patients with rheumatoid arthritis (RA) are at an increased risk of acquiring infections due to two reasons: the disease itself and the immunosuppressive therapy. Vaccinations against preventable diseases are therefore of utmost importance for these group of patients. To estimate vaccination frequencies among patients with rheumatoid arthritis, we studied patients in a survey and calculated vaccination rates based on their vaccination documents. Patients have been recruited from our outpatient clinic during one of their routine visits. For the statistical analysis, they have been divided by age (≥60 vs <60 years) and medication (DMARD, Biologics, TNF inhibitors) for further subgroup analysis. Among the studied patients (n = 331), we found rather low vaccination rates, in particular for the strongly recommended vaccines against Pneumococcus and Influenza (33 and 53%, respectively). Furthermore, protection rates for important basic vaccinations, e.g. against Pertussis, were found to be very low with 12% only. Beside these findings, we saw age-dependent differences for a variety of vaccines: while Pneumococcus and Influenza vaccines were more often given to patients ≥60 years, MMR, Pertussis, Diphtheria and Hepatitis were significantly more often applied to younger patients. Vaccination rates have to be improved among RA patients, in particular for vaccines protecting from respiratory tract infections such as Pneumococcus.

Cost per response for abatacept versus adalimumab in rheumatoid arthritis by ACPA subgroups in Germany, Italy, Spain, US and Canada.

Rheumatoid arthritis (RA) is a chronic inflammatory disorder leading to disability and reduced quality of life. Effective treatment with biologic DMARDs poses a significant economic burden. The Abatacept versus Adalimumab Comparison in Biologic-Naïve RA Subjects with Background Methotrexate (AMPLE) trial was a head-to-head, randomized study comparing abatacept in serum anti-citrullinated protein antibody (ACPA)-positive patients, with increasing efficacy across ACPA quartile levels. The aim of this study was to evaluate the cost per response accrued using abatacept versus adalimumab in ACPA-positive and ACPA-negative patients with RA from the health care perspective in Germany, Italy, Spain, the US and Canada. A cost-consequence analysis (CCA) was designed to compare the monthly costs per responding patient/patient in remission. Efficacy, safety and resource use inputs were based on the AMPLE trial. A one-way deterministic sensitivity analysis (OWSA) was also performed to assess the impact of model inputs on the results for total incremental costs. Cost per response in ACPA-positive patients favoured abatacept compared with adalimumab (ACR20, ACR90 and HAQ-DI). Subgroup analysis favoured abatacept with increasing stringency of response criteria and serum ACPA levels. Cost per remission (DAS28-CRP) favoured abatacept in ACPA-negative patients, while cost per CDAI and SDAI favoured abatacept in ACPA-positive patients. Abatacept was consistently favoured in ACPA-Q4 patients across all outcomes and countries. Cost savings were greater with abatacept when more stringent response criteria were applied and also with increasing ACPA levels, which could lead to a lower overall health care budget impact with abatacept compared with adalimumab.