Current Issue : July-September Volume : 2024 Issue Number : 3 Articles : 5 Articles
Immunotherapy has shown clinical benefit in patients with non-small-cell lung cancer (NSCLC). Due to the limited response of monotherapy, combining immune checkpoint inhibitors (ICIs) and chemotherapy is considered a treatment option for advanced NSCLC. However, the mechanism of combined therapy and the potential patient population that could benefit from combined therapy remain undetermined. Here, we developed an NSCLC model based on the published quantitative systems pharmacology (QSP)-immuno-oncology platform by making necessary adjustments. After calibration and validation, the established QSP model could adequately characterise the biological mechanisms of action of the triple combination of atezolizumab, nab-paclitaxel, and carboplatin in patients with NSCLC, and identify predictive biomarkers for precision dosing. The established model could efficiently characterise the objective response rate and duration of response of the IMpower131 trial, reproducing the efficacy of alternative dosing. Furthermore, CD8+ and CD4+ T cell densities in tumours were found to be significantly related to the response status. This significant extension of the QSP model not only broadens its applicability but also more accurately reflects real-world clinical settings. Importantly, it positions the model as a critical foundation for model-informed drug development and the customisation of treatment plans, especially in the context of combining single-agent ICIs with platinum-doublet chemotherapy....
Model-informed precision dosing (MIPD) might be used to optimize antibiotic treatment. Procalcitonin (PCT) is a biomarker for severity of infection and response to antibiotic treatment. The aim of this study was to assess the impact of MIPD on the course of PCT and to investigate the association of PCT with pharmacodynamic target (PDT) aainment in critically ill patients. This is a secondary analysis of the DOLPHIN trial, a multicentre, open-label, randomised controlled trial. Patients with a PCT value available at day 1 (T1), day 3 (T3), or day 5 (T5) after randomisation were included. The primary outcome was the absolute dierence in PCT concentration at T1, T3, and T5 between the MIPD and the standard dosing group. In total, 662 PCT concentrations from 351 critically ill patients were analysed. There was no statistically signicant dierence in PCT concentration between the trial arms at T1, T3, or T5. The median PCT concentration was highest in patients who exceeded 10× PDT at T1 [13.15 ng/mL (IQR 5.43–22.75)]. In 28-day non-survivors and in patients that exceeded PDT at T1, PCT decreased signicantly between T1 and T3, but plateaued between T3 and T5. PCT concentrations were not signicantly dierent between patients receiving antibiotic treatment with or without MIPD guidance. The potential of PCT to guide antibiotic dosing merits further investigation....
In this prospective, observational study (ClinicalTrials.gov Identifier: NCT02661464), longterm safety information was collected from participants previously exposed to the Ebola vaccines Ad26.ZEBOV and/or MVA-BN-Filo while enrolled in phase 1, 2, or 3 clinical studies. The study was conducted at 15 sites in seven countries (Burkina Faso, France, Kenya, Tanzania, Uganda, the United Kingdom, and the United States). Adult participants and offspring from vaccinated female participants who became pregnant (estimated conception ≤28 days after vaccination with MVA-BNFilo or ≤3 months after vaccination with Ad26.ZEBOV) were enrolled. Adults were followed for 60 months after their first vaccination, and children born to female participants were followed for 60 months after birth. In the full analysis set (n = 614 adults; median age [range]: 32.0 [18–65] years), 49 (8.0%) had ≥1 serious adverse event (SAE); the incidence rate of any SAE was 27.4 per 1000 personyears (95% confidence interval: 21.0, 35.2). The unrelated SAEs of malaria were reported in the two infants in the full analysis set, aged 11 and 18 months; both episodes were resolved. No deaths or life-threatening SAEs occurred during the study. Overall, no major safety issues were identified; one related SAE was reported. These findings support the long-term clinical safety of the Ad26.ZEBOV and MVA-BN-Filo vaccines....
No studies are currently evaluating the quality of recovery (QoR) after open radical nephrectomy (ORN) and epidural morphine analgesia. This was a randomized, prospective, and controlled study that explored the QoR on the first postoperative day after ORN. Eighty subjects were randomized into two groups. The first group received general anesthesia combined with epidural anesthesia and postoperative epidural analgesia with morphine and ropivacaine. The second group received general anesthesia and continuous postoperative intravenous analgesia with tramadol. Both groups received multimodal analgesia with metamizole. The primary outcome measure was the total QoR-40 score. The secondary outcome measures were QoR-15, QoR-VAS, and the visual analog scale (VAS) for pain, anxiety, and nausea. The median difference in the QoR-40 score after 24 postoperative hours between the two groups of patients was 10 (95% CI: 15 to 5), p < 0.0001. The median score and IQR of QoR-40 during the first 24 postoperative hours in the epidural group was 180 (9.5), and in the control group, it was 170 (13). The general independence test for secondary outcomes between groups was significant (p < 0.01). QoR-VAS was correlated with QoR-40 (r = 0.63, p ≤ 0.001) and with QoR-15 (r = 0.54, p ≤ 0.001). The total QoR-40 and QoR-15 alpha coefficients with a 95% CI were 0.88 (0.85–0.92) and 0.73 (0.64–0.81), respectively. There was a significant difference in the QoR between the epidural and the control groups after ORN. The QoR-40 and QoR-15 showed good convergent validity and reliability....
Cancer-related fatigue (CRF) is a common distressing complaint of breast cancer (BC) patients treated with chemotherapy. Nutritional quality plays a pivotal role in CRF, while increased interest towards new pharmacological agents has been observed. Melatonin, an endogenous hormone that regulates the human sleep–wake cycle, could alleviate CRF. In the present randomized, placebo-controlled 3-month trial, we investigated the effects of melatonin intake (i.e., 1 mg/day) vs. placebo in BC patients on CRF. In both arms, the Mediterranean diet (MD) was implemented. Medical history, anthropometry and blood withdrawal were performed. CRF was evaluated by the Functional Assessment of Chronic Illness Therapy—Fatigue questionnaire and MD adherence by the MedDietScore. In total, 49 BC women (median age 52 years) were recruited, namely N = 23 in the intervention arm and N = 26 in the placebo arm. At baseline, CRF was positively associated with body mass index (BMI), even when adjusted for age, waist circumference and blood indices related to disease prognosis (beta = −0.882, p = 0.003). At 3 months, both groups showed a BMI decrease (p < 0.05), but only the intervention group improved CRF compared to baseline (p = 0.003). No differences in CRF were observed between the groups. In conclusion, melatonin oral supplementation could ameliorate CRF in BC patients....
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