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Background Recurrent or refractory Clostridioides difficile infection (CDI) often affects older and immunocompromised patients, posing clinical and economic challenges. While fidaxomicin has shown lower recurrence rates than vancomycin in the general population, evidence in this population remains limited. Methods This retrospective, multicentre case-control study compared patients aged > 65 years or immunocompromised patients receiving fidaxomicin (case group) with those treated with vancomycin (control group) for recurrent or refractory CDI. A microcosting approach was used to assess direct treatment costs. Results A total of 344 patients were included (172 per group). Compared to the control group, the fidaxomicin group presented a significantly higher rate of symptom reduction on day 10 ( n  = 163, 95% vs. n  = 147, 86%; p  = 0.004) and lower CDI recurrence rates ( n  = 36, 21% vs. n  = 63, 37%; p  = 0.001). While the mean CDI treatment costs per patient were significantly higher in the fidaxomicin group ( p  < 0.001), the hospitalisation and overall treatment costs were comparable (€19,898, 95% CI €16,151-€23,645 vs. €20,469, 95% CI €16,837-€24,101, p  = 0.811; €17,798, 95% CI €14,620-€20,975 vs. €17,300, 95% CI €14,199-€20,400, p  = 0.840). Key cost drivers were hospitalisation, intensive care unit treatment, and severe initial CDI. Conclusions Despite higher drug acquisition costs of fidaxomicin, overall treatment costs were comparable between the two groups with better clinical outcomes in patients treated with fidaxomicin. Clinical trial number Not applicable.

Background: Currently, the duration of tourniquet time in total knee arthroplasty is chosen by the surgeons and varies between 0 and 120 min. Studies evaluating the effect of tourniquet time in this surgery are heterogeneous, and there is limited information on molecular/complement profiling. The purpose of this study was, therefore, to determine whether the duration of tourniquet-induced limb ischemia during total knee arthroplasty influences reperfusion injury, resulting in pain, swelling, and the release of pro-inflammatory markers. Methods: In 40 patients undergoing total knee arthroplasty, a tourniquet was applied for up to 30 min (group A, short tourniquet) or 90–120 min (group B, long tourniquet). Postoperative pain and swelling served as primary outcome parameters. The levels of pro- and anti-inflammatory markers before surgery and 4 h, 24 h, and 48 h after surgery were used as secondary outcome parameters for exploratory testing. Results: There were no differences in numeric rating pain scale (NRS) scores and calf circumference between groups A and B. Patients in group B required patient-controlled intravenous analgesia more frequently than group A patients (47% versus 5%, group B vs. group A, p < 0.0001). In group B, a significantly higher increase in C3a and MIG levels between 4 h and 48 h, and a significantly higher increase for MIG and M-CSF between 24 h and 48 h, were observed. Conclusions: Tourniquet times between 90 and 120 min were not associated with higher pain levels or more swelling, but an increased need for intravenous analgesia and a higher increase in pro-inflammatory markers. This might be a consequence of a more pronounced ischemia/reperfusion injury with tourniquet times longer than 90 min.

Using oral contraceptives has been implicated in the aetiology of stress-related disorders like depression. Here, we followed the hypothesis that oral contraceptives deregulate the HPA-axis by elevating circulating cortisol levels. We report for a sample of 233 pre-menopausal women increased circulating cortisol levels in those using oral contraceptives. For women taking oral contraceptives, we observed alterations in circulating phospholipid levels and elevated triglycerides and found evidence for increased glucocorticoid signalling as the transcript levels of the glucocorticoid-regulated genes DDIT4 and FKBP5 were increased in whole blood. The effects were statistically mediated by cortisol. The associations of oral contraceptives with higher FKBP5 mRNA and altered phospholipid levels were modified by rs1360780, a genetic variance implicated in psychiatric diseases. Accordingly, the methylation pattern of FKBP5 intron 7 was altered in women taking oral contraceptives depending on the rs1360780 genotype. Moreover, oral contraceptives modified the association of circulating cortisol with depressive symptoms, potentially explaining conflicting results in the literature. Finally, women taking oral contraceptives displayed smaller hippocampal volumes than non-using women. In conclusion, the integrative analyses of different types of physiological data provided converging evidence indicating that oral contraceptives may cause effects analogous to chronic psychological stressors regarding the regulation of the HPA axis.