Purpose: The aim of the study was to evaluate the cost-effectiveness of PEGylated recombinant human granulocyte–stimulating factor (PEG-rhG-CSF) as a means of achieving primary and secondary prophylaxis against chemotherapy-induced neutropenia cancer cases.Methods: Individuals who underwent PEG-rhG-CSF therapeutics were monitored for 12 months, together with thorough examination of individual medical records for extracting medical care costs. Both prophylaxis-based therapeutic options (primary/secondary) were scrutinized for cost-effectiveness, using a decision-making analysis model which derived the perspective of Chinese payers. One-way and probabilistic sensitivity analyses were used to assess the robustness of the model.Results: In summary, 130 clinical cases treated using PEG-rhG-CSF prophylaxis were included in this study: 51 within the primary prophylaxis (PP) group and 79 within the secondary prophylaxis (SP) group. Compared with SP, PP-based PEG-rhG-CSF successfully contributed to a 14.3% reduction in febrile neutropenia. In general, PP was estimated to reduce costs by $4,701.81 in comparison to SP, with a gain of 0.02 quality-adjusted life years (QALYs). Equivalent results were found in differing febrile neutropenia (FN) risk subgroups. Sensitivity analyses found the model outputs to be most affected for the average time of hospitalization and for the cost of FN.Conclusion: From the perspective of Chinese payers, PP with PEG-rhG-CSF should be considered cost-effective compared to SP strategies in patients who received chemotherapy regimens with a middle- to high-risk of FN.
The bladder wall is constantly subjected to intravesical pressure during the filling and voiding cycles. An imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) under elevated intravesical pressure contributes to pathological changes in the bladder. To investigate the changes in human urothelial cells (HUCs) under elevated intravesical pressure, this study analyzed the effect of β‐adrenoceptor signaling on the expression of MMPs and TIMPs in HUCs exposed to pathological hydrostatic pressure (HP) (70 cm H2O) for 6 hours. Quantitative polymerase chain reaction, Western blot analysis, and cell fluorescence staining were used to explore the effect of β‐adrenoceptor signaling on the expression of MMPs and TIMPs in HUCs after agonist and/or antagonist treatment. The expression levels of β2‐ and β3‐adrenoceptor, MMP1, and MMP2 were greatly downregulated, while the expression of TIMP1 was greatly upregulated. Formoterol and BRL 37344, which are agonists of β2‐ and β3‐adrenoceptor, respectively, significantly increased MMP1 and MMP2 expression under 70 cm H2O. As a classic downstream pathway of β2‐ and β3‐adrenoceptor, protein kinase A (PKA) signaling inhibited MMP1 and MMP2 expression by regulating cAMP response element binding protein (CREB) activity. MMP1 and MMP2 expression in HUCs under 70 cm H2O was modified by β2‐ and β3‐adrenoceptor via the PKA/CREB pathway. This outcome suggests that MMPs likely participate in the pathological effects of elevated intravesical pressure. The underlying mechanism of β2‐ and β3‐adrenoceptor in elevated intravesical pressure was also revealed; this mechanism constitutes a new potential therapeutic target for partial bladder outlet obstruction.
Purpose: To determine the effectiveness and safety of superior calyceal access compared with other calyceal access in percutaneous nephrolithotomy (PCNL).Methods: This meta-analysis was carried out according to preferred reporting items for systematic reviews and meta-analysis (PRISMA). We searched Pubmed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI) to identify relevant studies for this meta-analysis. Failed stone clearance event and complication event are two main outcomes, operation time and hospital stay time are two secondary outcomes. Relative data were extracted and assessed by using RevMan 5.3, Stata 15.0 and R 4.0.2.Results: 16 studies (8541 participants) were identified and included in this meta-analysis. Pooled results indicated that superior calyceal access could offer less failed stone clearance than other calyceal access (OR: 0.64, 95%CI: 0.47-0.88, P=0.006). No complication difference was found (OR: 1.10, 95%CI: 0.78-1.56, P=0.57). Superior calyceal access could offer shorter operation time (SMD: -0.57, 95%CI: -0.98, -0.15, P=0.007). No hospital stay difference was found (SMD: 0.07, 95%CI: -0.09, 0.22, P=0.38). Large heterogeneity was detected in stone clearance comparison (I2=71%, P<0.001) and operation time (I2=97%, P<0.001). Significant publication bias was also identified in stone clearance comparison (P=0.026). These defects weaken the credibility of results.Conclusion: Despite the considerable heterogeneity and publication bias, superior calyceal access in PCNL may bring better stone clearance rate, shorter operation time, with no increase in postoperative complication and hospital stay for patients with kidney stones. This finding still needs to be verified by larger randomized controlled trials.
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