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IMPORTANCE: Proactive therapeutic drug monitoring (TDM), consisting of individualized treatment based on scheduled assessments of serum drug levels, has been proposed as an alternative to standard therapy to optimize efficacy and safety of infliximab and other biologic drugs. However, it remains unclear whether proactive TDM improves clinical outcomes during maintenance therapy. OBJECTIVE: To assess whether proactive TDM during maintenance therapy with infliximab improves treatment efficacy by preventing disease worsening compared with standard infliximab therapy without TDM. DESIGN, SETTING, AND PARTICIPANTS: Randomized, parallel-group, open-label clinical trial including 458 adults with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, ulcerative colitis, Crohn disease, or psoriasis undergoing maintenance therapy with infliximab in 20 Norwegian hospitals. Patients were recruited from June 7, 2017, to December 12, 2019. Final follow-up took place on December 14, 2020. INTERVENTIONS: Patients were randomized 1:1 to proactive TDM with dose and interval adjustments based on scheduled monitoring of serum drug levels and antidrug antibodies (TDM group; n = 228) or to standard infliximab therapy without drug and antibody level monitoring (standard therapy group; n = 230). MAIN OUTCOME AND MEASURES: The primary outcome was sustained disease control without disease worsening, defined by disease-specific composite scores or consensus about disease worsening between patient and physician leading to a major change in treatment (switching to another biologic drug, adding an immunosuppressive drug including glucocorticoids, or increasing the infliximab dose), during the 52-week study period. RESULTS: Among 458 randomized patients (mean age, 44.8 [SD, 14.3] years; 216 women [49.8%]), 454 received their randomly allocated intervention and were included in the full analysis set. The primary outcome of sustained disease control without disease worsening was observed in 167 patients (73.6%) in the TDM group and 127 patients (55.9%) in the standard therapy group. The estimated adjusted difference was 17.6% (95% CI, 9.0%-26.2%; P

The effect of red wine drinking was tested on fibrinolytic parameters and blood cells in nine healthy students at rest and after acute exercise. The subjects were randomly assigned in a crossover design to one of three treatment regimes: control situation, low-dose wine group, and high-dose wine group. Blood samples were drawn just prior to experimental start, at 2 and 4 hours, and the next morning at 8:00 a.m., at 8:30 a.m. just after exercise, and 2 hours after exercise. The fibrinolytic potential was measured by whole blood clot lysis time (WBCLT), tissue plasminogen activator, and plasminogen activator inhibitor-1 (PAI-1) antigens in plasma. A whole blood system was used to test the reactivity of blood cells by stimulating hirudinized blood with 5 ng/mL lipopolyusaccharide (LPS) for 2 hours at 37 degrees C and measurements of tissue necrosis factor alpha and interleukin-8 (IL-8) in the plasma. Intake of red wine caused impaired fibrinolysis shown by prolonged WBCLT (3.6, 20.7, and 55.7%, respectively, for control, low- and high-dose wine groups) due to increase in PAI-1 antigen (-0.8, 4.8, and 11.0 ng/mL, respectively, in the three groups). There was no effect of the red wine the next morning on the fibrinolytic system. A strong correlation was observed between WBCLT and PAI-1 antigen (p0.0001). Acute exercise caused an immediate rise in both tissue plasminogen activator antigen and PAI-1 antigen levels and WBCLT was significantly shortened. In contrast to that of the wine groups, 2 hours after exercise WBCLT was prolonged in the control group, but not significantly so. Thus the red wine has a negative effect on the fibrinolytic system during rest, but may have a positive effect after strenuous exercise. The red wine had no immediate effect on LPS-induced tissue necrosis factor alpha or IL-8 production, although there was a tendency for higher cytokine production in the control group compared to the wine groups during and just after intake of wine. The next morning after exercise, the LPS-induced IL-8 production increased 137, 89, and 96%, respectively, in control, low-, and high-dose wine groups, probably due to a rise in epinephrine and activation of platelets. Although not significantly so, there was a tendency for red wine intake in the evening to suppress the reactivity of the cells after physical exercise the subsequent morning. It is suggested that the negative effect of red wine ingestion may be due to the toxic effect of ethanol on hepatocytes or adipose tissue and subsequent release of PAI-1, whereas the positive effect may be due to the red wine suppression of platelet activation and release of PAI-1 from activated platelets. It is proposed that at least part of the beneficial effect of red wine ingestion may be associated with the downregulation of cytokine production.