Search

Pramipexole is the first‐line medication recommended by the British National Institute for Health and Care Excellence. Pramipexole is predominantly eliminated by renal excretion. The aim was to develop a physiologically based pharmacokinetic (PBPK) model of pramipexole, providing a basis for its individualized administration. The role of glomerular filtration and organic cation transporter 2 (OCT2) in renal tubular secretion was considered. Plasma concentration‐time profiles of pramipexole were predicted and validated, first in healthy populations and then in PD patients with varied renal function. Finally, the pharmacokinetics of PD patients with different degrees of renal impairment were predicted. The simulated pharmacokinetic parameters, including maximum plasma concentration (Cmax), area under the plasma concentration‐time curve (AUC), time to maximum plasma concentration (tmax), and steady‐state trough plasma concentration values, obtained using the PBPK model were validated using fold error values, which were all smaller than 2. The successfully validated model supported that OCT2‐mediated tubular secretion was affected proportionally to changes in glomerular filtration for various degrees of renal impairment. The predicted AUC0‐inf values were increased 1.16‐, 1.76‐, 3.26‐, and 9.48‐fold in mild, moderate, and severe renal impairment and end‐stage renal disease (ESRD) subjects, resepctively, compared with PD patients with normal renal function. It appears that PD patients with mild renal impairment are unlikely to require dose adjustment (0.125 mg 3 times a day). The pramipexole dose should be reduced to approximately 0.125 mg twice daily, 0.125 mg once daily, and 0.0375 mg once daily in PD patients with moderate renal impairment, severe renal impairment, and ESRD, respectively. [ABSTRACT FROM AUTHOR]

Excessive sulfur and nitrogen deposition is a threat to natural ecosystems. This study investigated the spatio-temporal changes of wet sulfur and nitrogen deposition in Jiuzhaigou to understand the responses of wet deposition chemistry to local and national air pollutant emission changes and to assess relevant ecological risks. The results show that local emission sources (e.g., tourism, post-earthquake reconstruction, and vegetation damages) largely elevated the concentrations of SO 4 2−, NO 3 −, NH 4 +, and Ca2+ at the non-background sites during 2021–2022; However, the gaps of annual sulfur and nitrogen wet deposition fluxes among the background, semi-background, and non-background sites were reduced by annual precipitation. The pH was also higher at the non-background sites due to stronger acid neutralization capacities from crustal dust there, and acid precipitation (pH < 5.6) was not detected at all the sites. During the 2010 to 2022 period, the wet deposition of SO 4 2− and TIN (i.e. total inorganic nitrogen) and the equivalent ratio of SO 4 2−: NO 3 − generally presented a declining trend at the background and semi-background sites, as a result of regional and national emission reductions. The TIN reduction from 2015 to 2016 to 2021–2022 at the background site was more from wet NH 4 + deposition and the site's NO 3 − concentrations and fluxes were relatively stable. Compared to the critical loads (CLs) of sulfur and nitrogen for acidification and eutrophication, the annual wet and wet+dry deposition fluxes of sulfur and nitrogen were lower in almost the entire watershed, except for the CL min of nitrogen for acidification in considerable areas. However, all the wet deposition samples were calcite-unsaturated and had annual TIN concentrations higher than the national environmental standard of total nitrogen for surface water. More field investigations are needed to better assess the ecological risks. [Display omitted] • Acid precipitation (pH < 5.60) was not observed during 2021–2022. • National emission controls decreased acid deposition at the background site. • Local human emissions enhanced acid deposition at the non-background sites. • Alkaline dust well buffered the acidity of precipitation. • CLs were not violated in almost the entire watershed, except for the CL min of nitrogen for acidification. [ABSTRACT FROM AUTHOR]

Background and Study Aim: The commonly used minimally invasive methods for patients with infected pancreatic necrosis (IPN) are initial endoscopic transluminal drainage (ETD) and percutaneous catheter drainage (PCD), which are followed, if necessary, by endoscopic or surgical necrosectomy. This study intends to explore which of the two minimally invasive treatments leads to a better prognosis.Patients and Methods: Patients with IPN and an indication for intervention were prospectively enrolled and underwent either initial ETD or PCD followed, if necessary, by endoscopic or surgical necrosectomy.Results: Initial treatment success occurred in 8 of 11 patients after ETD (72.7%) and in 3 of 13 patients after PCD (30.8%) (risk ratio [RR] with ETD, 2.36; 95% CI 0.97-5.77; P = 0.04). After 1 year of follow-up, 72.7% of patients survived with ETD, and 69.2% survived with PCD (RR 1.05; 95% CI 0.63-1.75; P = 0.85). Intestinal fistula seems to have occurred less in the patients who received initial ETD rather than PCD therapy (9.1 vs. 38.5%; RR 0.24; 95% CI 0.03-1.73; P = 0.098). Fewer patients who underwent an initial ETD were transferred to surgery (9.1 vs. 46.2%; RR 0.20; 95% CI 0.03-1.40; P = 0.047). A higher rate of new-onset diabetes (3 cases) or impaired glucose tolerance (1 case) occurred in initial PCD compared to ETD (40 vs. 0%, P = 0.042).Conclusion: The outcomes of initial endoscopic transluminal drainage are superior to percutaneous drainage for patients with infected pancreatic necrosis (ChiCTR-ONRC-13003653). [ABSTRACT FROM AUTHOR]