[Standardized documentation of health-related quality of life in patients with psoriatic arthritis : Validation of the German version of the psoriatic arthritis quality of life (PsAQoL) questionnaire]. / Standardisierte Erfassung der gesundheitsbezogenen Lebensqualität bei Patienten mit Psoriasisarthritis : Validierung der deutschen Version des "Fragebogen zur Lebensqualität von Patienten mit Psoriasisarthritis (PsAQoL)".

BACKGROUND: The standardized assessment of health-related quality of life is becoming increasingly more important. The English questionnaire on psoriatic arthritis quality of life (PsAQoL) is a disease-specific instrument for measuring the quality of life of patients with psoriatic arthritis (PsA). The aim of the present study was to translate the PsAQoL into German and to validate the German version in a cohort of PsA patients recruited from routine care. METHOD: The translation and validation of the PsAQoL questionnaire was carried out in a stepwise procedure involving affected patients with PsA. After translation of the original English questionnaire the German version was evaluated in a field test. The psychometric features of the questionnaire were then examined in a PsA cohort from routine care. In addition to the construct and group validity, the reliability of the questionnaire was tested using test-retest reliability and internal consistency. The physical functioning was measured with the health assessment questionnaire (HAQ) and domains of the quality of life with the Nottingham health profile (NHP). RESULTS: In a field test with 10 patients the German version of the PsAQoL questionnaire proved to be relevant, easily understandable and feasible (processing time 4.7 ± 2.1 min). A total of 126 patients (37.3% male, age 55.6 ± 11.3 years) were included in the validation cohort. The PsAQoL showed moderate correlation with the HAQ (r = 0.65) and moderate to good correlation with the NHP (subdomains r = 0.58-0.75). The internal consistency was high (Cronbach's α 0.92) and reliability in patients with stable disease course was very good (Spearman correlation coefficient 0.94). The PsAQoL can differentiate between different patient groups. CONCLUSION: The German translation of the PsAQoL provides a valid disease-specific instrument for the standardized assessment of health-related quality of life in patients with PsA. The psychometric characteristics of this questionnaire are comparable with the original English version. The German PsAQoL can therefore be recommended for clinical and scientific application.

Warming weather changes the chemical composition of oat hulls.

The current threats of climate change are driving attention away from the petrochemical industry towards more sustainable and bio-based production processes for fuels and speciality chemicals. These processes require suitable low-cost starting material. One potential material assessed here is the oat hull. Its overall chemical composition has so far not been fully characterized. Furthermore, it is not known how it is affected by extreme weather events. Oat hulls (Kerstin and Galant varieties) grown during 'normal' weather years (2016 and 2017) are compared to the harvest of the warmer and drier year (2018). Standard methods for determination of plant chemical composition, with focus on carbohydrate composition, are utilized. Oat hulls grown in 'normal' weather conditions (2017) are rich in lignocellulose (84%), consisting of 35% hemicellulose, 25% lignin and 23% cellulose. Arabinoxylan was found to be the major biopolymer (32%). However, this composition is greatly influenced by weather variations during the oat growth phase. A lignocellulose reduction of 25% was recorded in the warmer and drier 2018 harvest. Additionally, a 6.6-fold increase in starch content, a four-fold increase in protein content and a 60% decrease in phenolic content was noted. Due to its high lignocellulose composition, with an exceptionally large hemicellulose fraction, the chemical composition of oat hulls is unique among agricultural by-products. However, this characteristic is significantly reduced when grown in warmer and drier weather, which could compromise its suitability for use in a successful biorefinery.

A value proposition for trough level-based anti-TNFα drug dosing.

Treatment of inflammatory bowel diseases and rheumatic disorders with anti-tumor necrosis factor alpha (TNFα) drugs is expensive, while a significant proportion of patients does not show adequate clinical response. Therapeutic drug monitoring (TDM) enables patient-specific anti-TNFα therapy. The role of laboratory tests in clinical care has recently been described in a value proposition framework. It describes care processes, stakeholders, costs, risks, benefits and patient outcomes based on the use of a laboratory test in a clinical care pathway. We have applied this concept to the use of TDM for anti-TNFα drugs, describing evidence that supports the intervention and its cost effectiveness, steps that need to be adjusted in the care pathway, possible treatment algorithms and measures to assess adoption of this framework into clinical practice. For effective TDM, an assay for measurement of drug levels together with appropriate target ranges and an anti-drug-antibody assay have to be implemented. Also, instead of only reporting the drug concentration, laboratorians, pharmacists and clinicians should deliver added value by introducing a TDM-based treatment algorithm into clinical practice. Thus, to maximize effectiveness of TDM of anti-TNFα therapy in routine care, adjustment of current care pathways and cooperation of many stakeholders are needed.

Switching from infliximab innovator to biosimilar in patients with inflammatory bowel disease: a 12-month multicentre observational prospective cohort study.

BACKGROUND: Infliximab biosimilars have become available for treatment of inflammatory bowel disease (IBD). However, data showing long-term safety and effectiveness of biosimilars in IBD patients are limited. AIM: To study prospectively the switch from infliximab innovator to biosimilar in an IBD cohort with 12 months follow-up to evaluate safety and effectiveness. METHODS: Adult IBD patients from two hospitals treated with infliximab innovator (Remicade; Janssen Biotech,  Horsham ,  Pennsylvania, USA) were switched to infliximab biosimilar (Inflectra; Hospira, Lake Forest, Illinois, USA) as part of routine care, but in a controlled setting. Blood samples were taken just before the first, second, fourth and seventh infusion of biosimilar. Infliximab trough levels, antibodies-to-infliximab (ATI), CRP and ESR were measured and disease activity scores were calculated. RESULTS: Our cohort consisted of 133 IBD patients (64% CD, 36% UC). Before switching we found widely varying infliximab levels (median 3.5 µg/mL). ATI were detected in eight patients (6%). Most patients were in remission or had mild disease (CD: 82% UC: 90%). After switching to biosimilar, 35 patients (26%) discontinued therapy within 12 months, mostly due to subjective higher disease activity (9%) and adverse events (AE, 9.8%). AE included general malaise/fatigue (n = 7), arthralgia (n = 2), skin problems (n = 2) and infusion reactions (n = 2). No differences in IFX levels, CRP, and disease activity scores were found between the four time points (P ≥ .0917). CONCLUSIONS: We found no differences in drug levels and disease activity between infliximab innovator and biosimilar in our IBD cohort, indicating that biosimilars are safe and effective. The high proportions of discontinuers were mostly due to elective withdrawal or subjective disease worsening.

Therapeutic drug monitoring (TDM) as a tool in the switch from infliximab innovator to biosimilar in rheumatic patients: results of a 12-month observational prospective cohort study.

The objective of this study is to apply therapeutic drug monitoring (TDM) as an objective tool to monitor the switch from infliximab innovator (INX) to infliximab biosimilar (INB) in our diverse rheumatic cohort in daily clinical practice. All rheumatic patients on INX treatment (Remicade®) and ≥18 years were switched to INB (Inflectra®) as part of routine care, but in a controlled setting. Patients were monitored by taking blood samples just before the first infusion of INB (T1), and after the second (T2), fourth (T3), and seventh (T4) infusion of INB. T4 reflects the patients' status after ∼12 months. Infliximab trough levels, antibodies-to-infliximab (ATI), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and validated disease activity scores (if possible) were measured. Our population consisted of 27 patients with seven different rheumatic diseases who had received INX for 143 (58-161) months (median (IQR)). Half of the patients (52%) received concomitant immunosuppressives. We found widely varying infliximab levels, with only 56% within the proposed therapeutic range of 1-5 µg/mL. One patient had very high ATI levels (>880 au/mL), and two had low ATI levels (≤30 au/mL). After switching to INB, seven patients (26%) discontinued the therapy, partially due to subjective reasons. No difference in infliximab levels, CRP levels, and disease activity scores was found between the four time points (p ≥ 0.2460). In conclusion, no pharmacokinetic or clinical differences were found between INX and INB in our diverse rheumatic cohort. TDM is a helpful tool to monitor patients switching from INX to INB.

[Rare presentation of a scleral nevus with progression in size]. / Seltene Präsentation eines skleralen Nävus mit Größenprogredienz.

A 52-year-old male caucasian patient presented with a limbal subconjunctival pigmentation of unknown origin with progressive enlargement over the past years. Differential diagnoses included a malignant melanocytic lesion; therefore, an excisional biopsy was performed. Prior investigations showed no ciliary body or anterior chamber angle involvement. Histological and immunohistochemical analysis revealed the rare diagnosis of a scleral nevus. The clinical, histological and immunohistochemical findings as well as the relevant differential diagnoses are discussed.

Determination of dabigatran and rivaroxaban by ultra-performance liquid chromatography-tandem mass spectrometry and coagulation assays after major orthopaedic surgery.

Major orthopaedic surgery is associated with an increased risk of venous thromboembolism. Direct oral anticoagulants (DOACs) are recommended as thromboprophylactic agents after orthopaedic surgery. Although routine monitoring of DOACs in general is not required, measuring DOAC concentration may be necessary in clinical settings. The effects of DOACs on routine coagulation assays in spiked material are studied extensively, however, few data are available on DOAC concentration in patients after major orthopaedic surgery. We measured trough and peak DOAC concentrations with UPLC-MS/MS and routine coagulation tests in a prospective study including 40 patients receiving thromboprophylactic treatment with dabigatran 220mg od and 40 patients receiving rivaroxaban 10mg od after major orthopaedic surgery. For rivaroxaban, the median trough concentration with UPLC-MS/MS was 17.1ng/mL and median peak concentration was 149ng/mL. The anti-Xa assay displayed a good correlation, but a positive bias in comparison to the reference method. Furthermore, trough levels were mostly below the LOD of the anti-Xa assay. For dabigatran, the median trough concentration with UPLC-MS/MS was 12.1ng/mL, and median peak level was 80.8ng/mL. A positive bias was found when results from coagulation assays were compared to UPLC-MS/MS data. However, the addition of glucuronidated metabolites to dabigatran concentration UPLC-MS/MS data generally resolved most of this bias. Age was found to have a significant influence on dabigatran pharmacokinetics, irrespective of kidney function, whereas no effect of age was found during rivaroxaban treatment. In both treatment groups, female subjects displayed faster pharmacokinetics in comparison to male subjects, although not reaching significance. We conclude that UPLC-MS/MS is the method of choice to measure trough concentrations of DOACs in patients after orthopaedic surgery. Current coagulation assays are not suited for this purpose. We found large heterogeneity in both peak and trough concentrations of DOACs, and showed that pharmacokinetics of novel oral anticoagulants may be influenced by age and gender. Whether patients with high or low trough concentrations are at increased risk for bleeding or thromboembolic events respectively remains to be established.

Determination of dabigatran, rivaroxaban and apixaban by ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) and coagulation assays for therapy monitoring of novel direct oral anticoagulants.

BACKGROUND: Three novel direct oral anticoagulants (DOACs) have recently been registered by the Food and Drug Administration and European Medicines Agency Commission: dabigatran, rivaroxaban, and apixaban. To quantify DOACs in plasma, various dedicated coagulation assays have been developed. OBJECTIVE: To develop and validate a reference ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) method and to evaluate the analytical performance of several coagulation assays for quantification of dabigatran, rivaroxaban, and apixaban. METHODS: The developed UPLC-MS/MS method was validated by determination of precision, accuracy, specificity, matrix effects, lower limits of detection, carry-over, recovery, stability, and robustness. The following coagulation assays were evaluated for accuracy and precision: laboratory-developed (LD) diluted thrombin time (dTT), Hemoclot dTT, Pefakit PiCT, ECA, Liquid anti-Xa, Biophen Heparin (LRT), and Biophen DiXal anti-Xa. Agreement between the various coagulation assays and UPLC-MS/MS was determined with random samples from patients using dabigatran or rivaroxaban. RESULTS: The UPLC-MS/MS method was shown to be accurate, precise, sensitive, stable, and robust. The dabigatran coagulation assay showing the best precision, accuracy and agreement with the UPLC-MS/MS method was the LD dTT test. For rivaroxaban, the anti-factor Xa assays were superior to the PiCT-Xa assay with regard to precision, accuracy, and agreement with the reference method. For apixaban, the Liquid anti-Xa assay was superior to the PiCT-Xa assay. CONCLUSIONS: Statistically significant differences were observed between the various coagulation assays as compared with the UPLC-MS/MS reference method. It is currently unknown whether these differences are clinically relevant. When DOACs are quantified with coagulation assays, comparison with a reference method as part of proficiency testing is therefore pivotal.

[Parameters of quality for aortic valve replacement]. / Qualitätsparameter für den Aortenklappenersatz.

Advantages and disadvantages of mechanical or biological heart valve prostheses in combination with complications during long-term follow-up are responsible for the quality of aortic valve replacement. Anatomical conditions like narrow aortic root, concomitant coronary artery disease or reduced left ventricular function impair the quite good surgical results necessitating surgical intervention or the use of stentless valve implants.