Our recent work proposed a pseudo one-compartment model for describing intradialysis and postdialysis rebound kinetics of phosphorus. In this model, phosphorus is removed directly from a central distribution volume with the rate of phosphorus mobilization from a second, very large compartment proportional to the phosphorus mobilization clearance. Here, we evaluated factors of phosphorus mobilization clearance and postdialysis central distribution volume from 774 patients in the HEMO Study. Phosphorus mobilization clearance and postdialysis central distribution volume were 87 (65, 116) ml/min, median (interquartile range), and 9.4 (7.2, 12.0) liter, respectively. The phosphorus mobilization clearance was significantly higher for male patients than for female patients. Both the phosphorus mobilization clearance and the postdialysis central distribution volume were significantly associated with postdialysis body weight but negatively with the predialysis serum phosphorus concentration. The postdialysis central distribution volume was also significantly associated with age. Overall, the postdialysis central distribution volume was 13.6% of the postdialysis body weight. Thus, the phosphorus mobilization clearance during hemodialysis is higher when predialysis serum phosphorus concentration is low and higher in male patients than in female patients. The central distribution volume of phosphorus is a space approximating the extracellular fluid volume.
Bleeding after total knee arthroplasty increases the risk of pain, delayed rehabilitation, blood transfusion, and transfusion-associated complications. The authors compared pre- and postoperative decreases in hemoglobin as a surrogate for blood loss in consecutive patients treated at a single institution by the same surgeon (J.L.C.) using conventional hemostatic methods (electrocautery, suturing, or manual compression) or a gelatin and thrombin-based hemostatic matrix during total knee arthroplasty. Data were collected retrospectively by chart review. The population comprised 165 controls and 184 patients treated with hemostatic matrix. Median age was 66 years (range, 28–89 years); 66% were women. The arithmetic mean±SD for the maximal postoperative decrease in hemoglobin was 3.18±0.94 g/dL for controls and 2.19±0.83 g/dL for the hemostatic matrix group. Least squares means estimates of the group difference (controls–hemostatic matrix) in the maximal decrease in hemoglobin was 0.96 g/dL (95% confidence interval, 0.77–1.14 mg/dL; P <.0001). Statistically significant covariate effects were observed for preoperative hemoglobin level ( P <.0001) and body mass index ( P =.0029). Transfusions were infrequent in both groups. The frequency of acceptable range of motion was high (control, 88%; hemostatic matrix, 84%). In both groups, overall mean tourniquet time was approximately 1 hour, and the most common length of stay was 3 to 5 days. No serious complications related to the hemostatic agent were observed. These data demonstrate that the use of a flowable hemostatic matrix results in less reduction in hemoglobin than the use of conventional hemostatic methods in patient undergoing total knee arthroplasty.
Current therapeutic treatment options for osteoarthritis entail significant safety concerns. A novel ropivacaine crystalline microsuspension for bolus intra-articular (IA) delivery was thus developed and studied in a peptidoglycan polysaccharide (PGPS)-induced ankle swelling rat model. Compared with celecoxib controls, both oral and IA, ropivacaine IA treatment resulted in a significant reduction of pain upon successive PGPS reactivation, as demonstrated in two different pain models, gait analysis and incapacitance testing. The reduction in pain was attended by a significant reduction in histological inflammation, which in turn was accompanied by significant reductions in the cytokines IL-18 and IL-1β. This may have been due to inhibition of substance P, which was also significantly reduced. Pharmacokinetic analysis indicated that the analgesic effects outlasted measurable ropivacaine levels in either blood or tissue. The results are discussed in the context of pharmacologic mechanisms both of local anesthetics as well as inflammatory arthritis.
♦ Background: The use of automated and continuous ambulatory peritoneal dialysis (APD and CAPD) prescriptions (Rxs) to achieve adequate uremic toxin and fluid removal targets is important for attaining optimal patient outcomes. One approach for predicting such Rxs is the use of kinetic modeling. ♦ Methods: Demographic data and peritoneal membrane characteristics derived from a peritoneal equilibration test (PET) were available from 1,005 patients in North American centers who participated in a national adequacy initiative in 1999. Twelve patient subgroups were identified according to peritoneal membrane transport type and tertiles of total body water, assumed equal to urea distribution volume (V urea ). Each patient was then modeled using PD Adequest 2.0 to be treated by 12 CAPD and 34 APD Rxs using both glucose and icodextrin solutions to achieve adequacy targets of weekly urea Kt/V of 1.7 and 1 L of daily ultrafiltration (UF). Residual kidney function (RKF) was assumed to be 0, 2, 4, and 6 mL/min. Feasible peritoneal dialysis (PD) Rxs were identified where: 1) the 95% confidence limit achieved the goal of meeting the targets for urea Kt/V, daily UF, and both in 85%, 75%, and 70% of patients, respectively; 2) average PD solution dextrose concentration was < 2.5%; and 3) the number of daytime exchanges was minimized. ♦ Results: Feasible PD Rxs were similar when RKF was ≥ 2 mL/min, allowing condensed recommendations based on RKF ≥ 2 mL/min or < 2 mL/min. Individuals with lower or slower membrane transport required relatively greater 24-h solution volumes to achieve adequacy targets when RKF fell below 2 mL/min. With increasing V urea , there was disproportionately greater dependence on RKF to achieve targets. While multiple Rxs achieving urea Kt/V and daily UF goals were identified for all membrane transport types, use of icodextrin in the long dwell reduced the need for a midday exchange in APD, glucose exposure, required fill and 24-h dwell volumes, irrespective of RKF and V urea . While these benefits were most notable in high and high-average transporters, similar results were also seen in low and low-average transporters.
PROMAXX technology allowed for safe and efficacious administration of RHIIP to the deep lung with an off-the-shelf DPI. RHIIP showed a fast onset of action and BA/BP comparable to that reported for other inhaled insulin formulations using specifically designed inhalers. Improvements in the insulin delivery technique might allow to optimize drug application in all cases with even higher BA/BP with RHIIP.
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