Reimbursement and economic factors influencing dialysis modality choice around the world

The worldwide incidence of kidney failure is on the rise and treatment is costly; thus, the global burden of illness is growing. Kidney failure patients require either a kidney transplant or dialysis to maintain life. This review focuses on the economics of dialysis. Alternative dialysis modalities are haemodialysis (HD) and peritoneal dialysis (PD). Important economic factors influencing dialysis modality selection include financing, reimbursement and resource availability. In general, where there is little or no facility or physician reimbursement or payment for PD, the share of PD is very low. Regarding resource availability, when centre HD capacity is high, there is an incentive to use that capacity rather than place patients on home dialysis. In certain countries, there is interest in revising the reimbursement structure to favour home-based therapies, including PD and home HD. Modality selection is influenced by employment status, with an association between being employed and PD as the modality choice. Cost drivers differ for PD and HD. PD is driven mainly by variable costs such as solutions and tubing, while HD is driven mainly by fixed costs of facility space and staff. Many cost comparisons of dialysis modalities have been conducted. A key factor to consider in reviewing cost comparisons is the perspective of the analysis because different costs are relevant for different perspectives. In developed countries, HD is generally more expensive than PD to the payer. Additional research is needed in the developing world before conclusive statements may be made regarding the relative costs of HD and PD

Serum Potassium and Mortality Risk in Hemodialysis Patients: A Cohort Study

Rationale & Objective: Both hypo- and hyperkalemia can cause fatal cardiac arrhythmias. Although predialysis serum potassium level is a known modifiable risk factor for death in patients receiving hemodialysis, especially for hypokalemia, this risk may be underestimated. Therefore, we investigated the relationship between predialysis serum potassium level and death in incident hemodialysis patients and whether there is an optimum level. Study Design: Prospective multicenter cohort study. Setting & Participants: 1,117 incident hemodialysis patients (aged >18 years) from the Netherlands Cooperative Study on the Adequacy of Dialysis-2 study were included and followed from their first hemodialysis treatment until death, transplantation, switch to peritoneal dialysis, or a maximum of 10 years. Exposure: Predialysis serum potassium levels were obtained every 6 months and divided into 6 categories: ≤4.0 mmol/L, >4.0 mmol/L to ≤4.5 mmol/L, >4.5 mmol/L to ≤5.0 mmol/L, >5.0 mmol/L to ≤5.5 mmol/L (reference), >5.5 mmol/L to ≤6.0 mmol/L, and >6.0 mmol/L. Outcomes: 6-month all-cause mortality. Analytical Approach: Cox proportional hazards and restricted cubic spline analyses with time-dependent predialysis serum potassium levels were used to calculate the adjusted HRs for death. Results: At baseline, the mean age of the patients was 63 years (standard deviation, 14 years), 58% were men, 26% smoked, 24% had diabetes, 32% had cardiovascular disease, the mean serum potassium level was 5.0 mmol/L (standard deviation, 0.8 mmol/L), 7% had a low subjective global assessment score, and the median residual kidney function was 3.5 mL/min/1.73 m2 (IQR, 1.4-4.8 mL/min/1.73 m2). During the 10-year follow-up, 555 (50%) deaths were observed. Multivariable adjusted HRs for death according to the 6 potassium categories were as follows: 1.42 (95% CI, 1.01-1.99), 1.09 (95% CI, 0.82-1.45), 1.21 (95% CI, 0.94-1.56), 1 (reference), 0.95 (95% CI, 0.71-1.28), and 1.32 (95% CI, 0.97-1.81). Limitations: Shorter intervals between potassium measurements would have allowed for more precise mortality risk estimations. Conclusions: We found a U-shaped relationship between serum potassium level and death in incident hemodialysis patients. A low predialysis serum potassium level was associated with a 1.4-fold stronger risk of death than the optimal level of approximately 5.1 mmol/L. These results may imply the cautious use of potassium-lowering therapy and a potassium-restricted diet in patients receiving hemodialysis

Subjective global assessment of nutritional status is strongly associated with mortality in chronic dialysis patients

Background: The subjective global assessment of nutritional status (SGA) is used to assess the nutritional status of chronic dialysis patients, but longitudinal data in relation to mortality risk are lacking. - \ud \ud Objective: Our objective was to study the long-term and time-dependent associations of the SGA with mortality risk in chronic dialysis patients. - \ud \ud Design: In a prospective, longitudinal, observational, multicenter study of incident dialysis patients, the 7-point SGA [7 = normal nutritional status; 1 = severe protein-energy wasting (PEW)] was assessed 3 and 6 mo after the start of dialysis and subsequently every 6 mo during 7 y of follow-up. With Cox regression analysis, we calculated hazard ratios (HRs) of the baseline and time-dependent SGA measurements, adjusted for age, sex, treatment modality, primary kidney diseases, and comorbidity. - \ud \ud Results: In total, 1601 patients were included [mean (±SD) age: 59 ± 15 y; 61% men; 23% with moderate PEW (SGA4–5), and 5% with severe PEW (SGA1–3)]. There was a dose-dependent trend of the 7-point SGA with mortality. Compared with a normal nutritional status at baseline, SGA4–5 (HR: 1.6; 95% CI: 1.3, 1.9) and SGA1–3 (HR: 2.1; 95% CI: 1.5, 2.8) were associated with an increase in 7-y mortality. Time-dependently, these associations were stronger: SGA4–5 (HR: 2.1; 95% CI: 1.7, 2.5) and SGA1–3 (HR: 5.0; 95% CI: 3.8, 6.5). - \ud \ud Conclusions: In dialysis patients, PEW at baseline assessed with SGA was associated with a 2-fold increased mortality risk in 7 y of follow-up. Time-dependently, this association was even stronger, which indicated that PEW was associated with a remarkably high risk of short-term mortality. These data imply that the 7-point SGA may validly distinguish different degrees of PEW associated with increasing risks of mortality

Is the decline of renal function different before and after the start of dialysis?

The presence of glomerular filtration in dialysis patients is associated with improved survival and quality of life. This study explores the time course of the glomerular filtration rate (GFR) between 1 year before and 1 year after the start of haemodialysis (HD) and peritoneal dialysis (PD). This study included 1861 incident dialysis patients (NECOSAD cohort; 62 male, 60 15 years, 61 HD, GFR 5.2 3.6 mL/min/1.73 m(2)). A decline of the GFR was estimated using linear mixed-effects models adjusted for age, sex, primary kidney disease, cardiovascular disease and diabetes. The rate of decline was allowed to change at a certain point in time. The decline of the GFR attenuated from 0.53 mL/min/1.73 m(2)/month (95 CI: 0.58, 0.48) in the period before the start of dialysis to 0.12 (95 CI: 0.20, 0.04) at 24 months of dialysis in all patients. In HD, decline attenuated from 0.51 (95 CI: 0.57, 0.44) to 0.14 (95 CI: 0.26, 0.02); in PD from 0.55 (95 CI: 0.62, 0.48) to 0.11 (95 CI: 0.23, 0.01). In patients who started dialysis with a GFR equal/above median GFR at dialysis start, the decline attenuated (at 3 months) from 0.70 (95 CI: 0.78; 0.62) to 0.21 (95 CI: 0.36; 0.05). In patients who started dialysis with a GFR below median GFR at dialysis start, the decline attenuated (at 1 month) from 0.73 (95 CI: 0.88; 0.58) to 0.04 (95 CI: 0.27 , 0.19). The apparent decline of the GFR slows down after 24 months of dialysis. This decline was similar in HD and PD patients, although at a different level of GFR. Further studies are needed to examine explanations for this phenomenon

Agreement between different parameters of dialysis dose in achieving treatment targets: results from the NECOSAD study.

BACKGROUND: The recommended parameter of dialysis dose differs between K-DOQI and the European Best Practice Guidelines. It is not well known to what extent an agreement exists between the different parameters, nor if target and delivered dialysis dose are prescribed according to the urea reduction rate (URR), single-pool Kt/V (spKt/V) or equilibrated double-pool Kt/V (eKt/V) and which parameter is most strongly related to mortality. METHODS: In 830 haemodialysis patients from the NECOSAD cohort URR, spKt/V and eKt/V were calculated and compared according to a classification regarding the recommended treatment targets (70%, 1.4 and 1.2, respectively) as well as minimum delivered dialysis dose (65%, 1.2 and 1.05, respectively). Moreover, the relation between treatment dose and survival was assessed using Cox regression analysis. RESULTS: A spKt/V of >/=1.4 and URR >/=70% corresponded with eKt/V >/=1.20 (as reference method) in, respectively, 98.0 and 90.6% of patients. spKt/V of >/=1.2 and URR >/=65% corresponded with eKt/V >/=1.05 in, respectively, 95.5 and 91.2% of patients. Deviations from the reference method were significantly related to differences in urea distribution volume (spKt/V), treatment time (URR) and ultrafiltration volume (URR). The adjusted HR (95% CI) was 0.98 (0.96, 0.99) for URR, 0.51 (0.31, 0.84) for spKt/V and 0.46 (0.30, 0.80) for the eKt/V. CONCLUSION: The use of URR leads to larger disagreement with the reference method (eKt/V) treatment target as compared to spKt/V. Low urea distribution volume, short treatment time and low ultrafiltration volumes are predictive parameters for overestimation of dialysis dose when utilizing the alternative methods spKt/V and URR instead of eKt/V. Delivered eKt/V, spKt/V and URR were all positively related to survival

Patients' representations of their end-stage renal disease: relation with mortality

BACKGROUND: Self-regulation theory explains how patients' illness perceptions influence self-management behaviour (e.g. via adherence to treatment). Following these assumptions, we explored whether illness perceptions of ESRD-patients are related to mortality rates. METHODS: Illness perceptions of 182 patients participating in the NECOSAD-2 study in the period between December 2004 and June 2005 were assessed. Cox proportional hazard models were used to estimate whether subsequent all-cause mortality could be attributed to illness perception dimensions. RESULTS: One-third of the participants had died at the end of the follow-up. Mortality rates were higher among patients who believed that their treatment was less effective in controlling their disease (perceived treatment control; RR = 0.71, P = 0.028). This effect remained stable after adjusting for sociodemographic and clinical variables (RR = 0.65, P = 0.015). CONCLUSIONS: If we consider risk factors for mortality, we tend to rely on clinical parameters rather than on patients' representations of their illness. Nevertheless, results from the current exploration may suggest that addressing patients' personal beliefs regarding the effectiveness of treatment can provide a powerful tool for predicting and perhaps even enhancing surviva

Vergleichende dreidimensionale Vokaltraktbildgebung mittels MRT beim Singen und Sprechen

Hintergrund: Die Magnetresonanztomographie (MRT) ist zur Darstellung des Vokaltraktes beim Singen und Sprechen etabliert, wobei viele Studien auf schnelle zweidimensionale Aufnahmen konzentriert sind. Zusätzlich ist jedoch auch eine dreidimensionale Bildgebung möglich. Durch diese können detailgetreue Modelle geschaffen werden, aus denen ein direkter Rückschluss auf die Vokaltraktresonanzen möglich ist.Material und Methoden: In der vorliegenden Studie wurden Vokaltraktmodelle mittels 3D MRT bei einem professionellen Tenor erstellt. Dafür phonierte der Sänger im MRT die Vokale /a/, /i/ und /u/ in seiner Sprechstimmlage (C3) in Sing- und Sprechstimmfunktion sowie in seiner hohen Singstimmfunktion oberhalb des Passaggios (A4). Aus dem gewonnenen Bildmaterial wurde jeweils der Vokaltrakt segmentiert, ein dreidimensionales Zahnmodell des Probanden anhand von anatomischen Landmarken eingefügt und mittels 3D Drucker ausgedruckt. Die gedruckten Modelle wurden nun durch Einfügen von Breitbandrauschen im Glottisbereich und Ableiten von Transferfunktionen vor der Mundöffnung akustisch analysiert und die Formantfrequenzen bestimmt.Ergebnisse: Vorläufige Ergebnisse zeigen deutliche Vokaltraktmodifikationen zwischen Sing- und Sprechstimme auf gleicher Tonhöhe, sowie für die hohe Singstimme in allen Vokalkonditionen. Insgesamt war der Vokaltrakt in der Singstimmfunktion länger als beim Sprechen und es zeigte sich der supralaryngeale Raum beim Singen vokalunabhängig erweitert. In der akustischen Analyse konnte eine Erhöhung der Formantfrequenzen mit Clusterbildung der Formanten 3-5 in der Singstimmfunktion ermittelt werden.Diskussion: Die Verlängerung des Vokaltraktes und Erweiterung des supralaryngealen Bereichs sind möglicherweise Mechanismen, welche für die Klangformung in der Singstimmfunktion von Bedeutung sind

Correction to: Pharmacokinetics of Fentanyl and Its Derivatives in Children: A Comprehensive Review

Fentanyl and its derivatives sufentanil, alfentanil, and remifentanil are potent opioids. A comprehensive review of the use of fentanyl and its derivatives in the pediatric population was performed using the National Library of Medicine PubMed. Studies were included if they contained original pharmacokinetic parameters or models using established routes of administration in patients younger than 18 years of age. Of 372 retrieved articles, 44 eligible pharmacokinetic studies contained data of 821 patients younger than 18 years of age, including more than 46 preterm infants, 64 full-term neonates, 115 infants/toddlers, 188 children, and 28 adolescents. Underlying diagnoses included congenital heart and pulmonary disease and abdominal disorders. Routes of drug administration were intravenous, epidural, oral-transmucosal, intranasal, and transdermal. Despite extensive use in daily clinical practice, few studies have been performed. Preterm and term infants have lower clearance and protein binding. Pharmacokinetics was not altered by chronic renal or hepatic disease. Analyses of the pooled individual patients’ data revealed that clearance maturation relating to body weight could be best described by the Hill function for sufentanil (R2 = 0.71, Bmax 876 mL/min, K50 16.3 kg) and alfentanil (R2 = 0.70, Bmax (fixed) 420 mL/min, K50 28 kg). The allometric exponent for estimation of clearance of sufentanil was 0.99 and 0.75 for alfentanil clearance. Maturation of remifentanil clearance was described by linear regression to bodyweight (R2 = 0.69). The allometric exponent for estimation of remifentanil clearance was 0.76. For fentanyl, linear regression showed only a weak correlation between clearance and bodyweight in preterm and term neonates (R2 = 0.22) owing to a lack of data in older age groups. A large heterogeneity regarding study design, clinical setting, drug administration, laboratory assays, and pharmacokinetic estimation was observed between studies introducing bias into the analyses performed in this review. A limitation of this review is that pharmacokinetic data, based on different modes of administration, dosing schemes, and parameter estimation methods, were combined