Preoperative pelvic floor muscle exercise for continence after radical prostatectomy: a systematic review and meta-analysis.

Objective: We performed a systematic review and meta-analysis to evaluate the effect of preoperative pelvic floor muscle exercise on urinary incontinence after radical prostatectomy. Methods: We searched the literature for randomized controlled trials evaluating the diagnostic analysis of preoperative pelvic floor muscle exercise (PFME) and postprostatectomy incontinence in the MEDLINE, EMBASE, PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO, China Biomedical Literature Database, China Journal Full-text Database, Wanfang Database and Weipu Database. The retrieval time limit is from the establishment of the database to January 2023. We used a risk ratio with accompanying 95% confidence interval (CI) to express estimates. Reviewer Manager (RevMan) 5.1.0 was used to complete all statistical analyses. Results: Twelve studies were included based on the selection criteria. The total number of patients included in the final analysis was 1,365. At 1th month, there was no difference in continence rates between the groups [odds ratio (OR): 0.47; 95% confidence interval (CI), 0.22-1.02, p = 0.06]. At 3th month, there was statistically significant difference in PFME group before operation (OR: 0.61; 95% CI, 0.37-0.98, p = 0.04). At 6th and 12th months, there was no difference between groups (OR: 0.57; 95% CI, 0.28-1.17, p = 0.13), (OR: 0.56; 95% CI, 0.27-1.15, p = 0.12). Conclusion: Preoperative pelvic floor muscle exercise can improve postoperative urinary incontinence at 3rd months after radical prostatectomy, but it cannot improve urinary incontinence at 6th months or longer after surgery, which indicates that preoperative PFME can improve early continence rate, but cannot improve long-term urinary incontinence continence rate.

Ethnicity evaluation of ferric pyrophosphate citrate among Asian and Non-Asian populations: a population pharmacokinetics analysis.

PURPOSE: To evaluate the potential ethnic differences of ferric pyrophosphate citrate (FPC, Triferic) in healthy subjects and patients with hemodialysis-dependent stage 5 chronic kidney disease (CKD-5HD) and identify covariates that may influence pharmacokinetics (PK) of FPC. METHODS: Data were collected from 2 Asian and 4 non-Asian clinical studies involving healthy subjects and CKD-5HD patients. Three population PK models were developed: M1 for intravenous (IV) administration of FPC in healthy subjects; M2 for dialysate administration of FPC in CKD-5HD patients; M3 for pre-dialyzer administration of FPC in CKD-5HD patients. All the models were fitted to concentration versus time data of FPC using the nonlinear mixed effect approach with the NONMEM® program. All statistical analyses were performed using SAS version 9.4. RESULTS: In total, 26 Asians and 65 non-Asians were included in the final model analysis database. Forty healthy subjects were administered FPC via intravenous (IV) route and 51 patients with CKD-5HD via dialysate (N = 50) and pre-dialyzer blood circuit administration (N = 51). The PK parameters of FPC IV were similar. The population PK model showed good parameter precision and reliability as shown by model evaluation, and no relevant influence of ethnicity on PK parameters was observed. In healthy subjects, the maximum observed plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) decreased with increase in lean body mass (LBM) and the average serum total iron at 6 h before the baseline period (Feav), whereas, in both patient populations, Cmax and AUC decreased with increase in LBM and decrease in Febaseline. Other factors such as gender, age, Feav, and ethnicity had no influence on PK exposures in patients. The influence of LBM on PK exposures in patients was smaller than that in healthy subjects (ratio of AUC0-24 for the 5th [68 kg] and 95th [45 kg] patient's LBM was almost 1). The influence of Feav and LBM on PK exposures was < 50%. CONCLUSION: The population pharmacokinetics model successfully described the PK parameters of FPC in healthy subjects and CKD-5HD patients and were comparable between Asian and non-Asian populations.

Pharmacokinetics and Safety of Ferric Pyrophosphate Citrate in Chinese Subjects with and without Hemodialysis-Dependent Stage 5 Chronic Kidney Disease.

BACKGROUND AND OBJECTIVE: Anemia caused by iron depletion is common in patients with hemodialysis-dependent stage 5 chronic kidney disease (CKD-5HD) patients. To maintain the iron levels, external administration of iron is essential. Ferric pyrophosphate citrate (FPC) is a novel, water-soluble complex iron salt. The present study was conducted to evaluate the pharmacokinetic (PK) parameters and safety of FPC in adult healthy Chinese subjects and patients with CKD-5HD. METHODS: Two open-label, single-center studies were conducted in healthy subjects and patients with CKD-5HD. Healthy subjects received a single intravenous dose of 6.5 mg FPC solution, while CKD-5HD patients were randomized to two different sequences of FPC administration at two sequential hemodialysis (HD) treatments (dose 1 and dose 2). Patients received 27.2 mg of FPC at a dialysate concentration of 95 µg/L for 4 h or a single 6.5 mg dose of FPC administered intravenously via the pre-dialyzer blood circuit. The primary objective was to determine the PK parameters of total serum iron (Fetot), while the secondary objective was the safety of the FPC solution. PK parameters were calculated using Phoenix WinNonlin 8.1 and other parameters were analyzed using SAS 9.4 software. Comparison between HD dose 2 and HD dose 1 was performed using the Wilcoxon rank-sum test and analysis of variance (ANOVA). RESULTS: A total of 14 healthy subjects with a mean age of 30.8 ± 5.92 years and 12 HD patients with a mean age of 54.3 ± 16.47 years were included. In healthy subjects, the peak serum concentration was reached at the end of infusion of FPC, with an adjusted mean maximum concentration (Cmax,) of 33.46 ± 4.83 µmol/L at a mean time to reach Cmax (Tmax) of 4.09 ± 0.19 h. In patients with CKD-5HD, the adjusted mean Cmax of HD dose 2 was 25.37 ± 4.30 µmol/L at a Tmax, of 3.09 ± 0.32 h, whereas the Cmax, of HD dose 1 was 24.59 ± 4.77 µmol/L at a Tmax, of 3.96 ± 0.26 h. The Fetot concentration-time curves were observed to be similar for both administration methods (HD doses 1 and 2), while the PK parameters differed significantly for Tmax (p = 0.001; baseline correction) and area under the concentration-time curve from time zero to time t (AUCt) [p = 0.031 for cycle variance; without baseline correction] between HD doses 1 and 2. The geometric mean ratios (HD dose 1/HD dose 2) for Cmax and AUCt were within the 85-125% range (Cmax 96.56%; AUCt 96.07%). A total of three and two incidences of adverse events were reported in healthy subjects and patients with CKD-5HD, respectively. CONCLUSION: FPC showed a good PK and safety profile and hence can be used as maintenance therapy for patients with CKD-5HD by choosing a better method of administration based on clinical feasibility and requirement. CLINICAL TRIAL REGISTRATION: CTR20181113 and CTR20181119.

A Prospective Comparison of Three Strategies for Evaluating Blood Loss in Transurethral Resection of the Prostate.

OBJECTIVE: The aim of the current investigation is to develop a new strategy for evaluating blood loss in the process of transurethral resection of the prostate (TURP). METHODS: 318 patients diagnosed with benign prostatic hyperplasia (BPH) that need TURP were enrolled in this study. Hospitalization information including age, height, weight, surgery time, prostate volume, hemoglobin (Hb) concentration, hematocrit (HCT) percentage, and red blood cell count (RBC) was evaluated for each patient. All statistical analysis drawing were conducted using R software. RESULTS: Three methods were employed for calculating blood loss in TURP. Results from a new method display 0 missing value and got higher confidence (0 of 318, Poisson distribution, P < 0.001) compared with blood loss calculated with hemoglobin concentration (20.44%) and hematocrit percentage (19.18%). Also, the new method demonstrated narrow range (0.03~270.03 ml) and approximate normal distribution compared with blood loss calculated with hemoglobin concentration and hematocrit percentage. More importantly, the new method explained positive correlation with prostate volume (R 2 = 0.138, P < 0.001) and also surgery lasting time (R 2 = 0.193, P < 0.001). CONCLUSION: Methods developed for calculating blood loss in TURP in the current study displayed more accurate and reasonable evaluation of bleeding, which can guide the transfusion blood for patients.

Roles of SP600125 in expression of JNK, RANKL and OPG in cultured dental follicle cells.

OBJECTIVE: To investigate the expression of C-JNK, RANKL and OPG after SP600125 administration in cultured dental follicle cells (DFCs). METHODS: TRAP staining and electron microscope were carried out on day 7 and 9 after coculture of BMMs and DFCs with a ratio of 5:1 in different groups. To determine the effects of SP600125 on the expression of C-JNK, RANKL and OPG mRNA and protein, cultured DFCs were divided into control group, DMSO group and SP600125 groups. Real-time PCR and Western blot analysis were performed to investigate the expression of the mRNA and protein, respectively. RESULTS: TRAP assay indicated that the number of multinucleated osteoclasts in the SP600125 group showed significant decrease compared with that of control (P < 0.05). The expression of JNK protein in the SP600125 groups showed significant decline compared with that of the control group and blank control (P < 0.05). Significant decrease was noticed in the RANKL protein expression with the elevation of SP600125. CONCLUSIONS: SP600125 could inhibit the formation of osteoclast in the coculture system of DFCs and BMMs. After SP600125 treatment, the expression of RANKL and JNK showed a trend of decrease, and the expression of OPG showed gradual increase followed by gradual decrease.