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Objectives Rheumatoid arthritis (RA) patients who fail to respond to methotrexate (MTX) can receive biologic disease-modifying antirheumatic drugs (bDMARDs). The Torque Teno Virus (TTV) is a potential novel candidate for monitoring of immunosuppression. We explore TTV in these patients and 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; inter quartile range [IQR] 0–7.5*105) after 3 months. TTV levels at month 3 were associated with SDAI (p= 0.03) and 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 SDAI85% response at month 6. Conclusion Our data suggest that TTV levels increase upon TNF, CD20 and co-stimulation blockade and associate with clinical response to bDMARDs in RA patients. Trial registration ClinicalTrials.gov; https://clinicaltrials.gov; NCT01638715

Doripenem is a broad-spectrum parenteral carbapenem with enhanced activity against and Current dosing regimens recommend the administration of 0.25 to 0.5 g once daily in patients undergoing intermittent renal replacement therapy. As patients are usually dialyzed thrice weekly, we aimed to investigate a 1-g posthemodialysis regimen, thus reducing treatment costs and enhancing patient compliance. A second objective of this trial was to describe the pharmacokinetics of intradialytic doripenem. Ten oliguric or anuric patients in need of intermittent renal replacement therapy were included in this trial. All patients suffered from a septic episode. The mean hemofilter clearance was 123.46 ± 42.03 ml/min, and the total body clearance between hemodialysis sessions was 16.79 ± 6.02 ml/min. The average prehemodialysis trough concentration was 2.4 ± 1.3 mg/liter, while the EUCAST resistance breakpoint for is set at 2 mg/liter. The interpatient variability was considerably higher than the intrapatient variability. Apart from one patient who suffered an allergic reaction, doripenem was tolerated well by all patients. Our data indicate that posthemodialysis administration of 1 g of doripenem results in sufficient plasma levels in anuric but not oliguric patients during the entire dosing interval. (This trial was registered with EudraCT under registration no. 2009-018010-18 and at ClinicalTrials.gov under registration no. NCT02018939.).

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Musculoskeletal (MSK) diseases affect a substantial proportion of the population. Specialist consultations were offered at the workplace for people with musculoskeletal (MSK)-complaints. We analyzed data on pain and well-being as well as health economic data at baseline. Lasting effects of the consultation were analyzed at a follow-up-interview after 12 months. Baseline data of 344 individuals were available. Occupations were divided into physically highly demanding (HD) or less demanding. Women reported significantly higher pain levels and less QoL than men. Sick leave days were significantly more in HD-workers. Independent of workload, significantly higher percentages of women had cervical- and upper limb-pain than men, with significantly higher pain in upper limbs in HD-workers. 235 participants were available for telephone-follow-up. QoL and MSK-pain improved significantly. Yearly out-of-pocket spendings for treatments significantly increased. NSAID use significantly decreased, whereas use of non-drug musculoskeletal-medical-services was significantly higher after one year. Regarding MSK-symptoms in gainfully employed individuals, the study showed significantly different workload-dependent differences in QoL. Significant effects of a consultation by a MSK-specialist were shown in terms of improved MSK-pain and overall well-being. This workplace-centered consultation had significant effects on beneficial health-behavior such as decreased use of NSAID and increased engagement in gymnastics and physiotherapy.