The real-world effectiveness of sucroferric oxyhydroxide in European hemodialysis patients: a 1-year retrospective database analysis.

BACKGROUND: The iron-based phosphate binder (PB), sucroferric oxyhydroxide (SFOH), demonstrated its effectiveness for lowering serum phosphate levels, with low daily pill burden, in clinical trials of dialysis patients with hyperphosphatemia. This retrospective database analysis evaluated the real-world effectiveness of SFOH for controlling serum phosphate in European hemodialysis patients. METHODS: De-identified patient data were extracted from a clinical database (EuCliD®) for adult hemodialysis patients from France, Italy, Portugal, Russia and Spain who were newly prescribed SFOH for up to 1 year as part of routine clinical care. Serum phosphate and pill burden were compared between baseline (3-month period before starting SFOH) and four consecutive quarterly periods of SFOH therapy (Q1-Q4; 12 months) in the overall cohort and three subgroups: PB-naïve patients treated with SFOH monotherapy (mSFOH), and PB-pretreated patients who were either switched to SFOH monotherapy (PB → mSFOH), or received SFOH in addition to another PB (PB + SFOH). RESULTS: 1096 hemodialysis patients (mean age: 60.6 years; 65.8% male) were analyzed, including 796, 188 and 53 patients in, respectively, the PB + SFOH, mSFOH, and PB → mSFOH groups. In the overall cohort, serum phosphate decreased significantly from 1.88 mmol/L at baseline to 1.77-1.69 mmol/L during Q1-Q4, and the proportion of patients achieving serum phosphate ≤1.78 mmol/L increased from 41.3% at baseline to 56.2-62.7% during SFOH treatment. Mean PB pill burden decreased from 6.3 pills/day at baseline to 5.0-5.3 pills/day during Q1-Q4. The subgroup analysis found the proportion of patients achieving serum phosphate ≤1.78 mmol/L increased significantly from baseline during SFOH treatment in the PB + SFOH group (from 38.1% up to 60.9% [Q2]) and the mSFOH group (from 49.5% up to 75.2% [Q2]), but there were no significant changes in the PB → mSFOH group. For the PB + SFOH group, serum phosphate reductions were achieved with a similar number of PB pills prescribed at baseline prior to SFOH treatment (6.5 vs 6.2 pills/day at Q4). SFOH daily pill burden was low across all 3 subgroups (2.1-2.8 pills/day). CONCLUSION: In this real-world study of European hemodialysis patients, prescription of SFOH as monotherapy to PB-naïve patients, or in addition to existing PB therapy, was associated with significant improvements in serum phosphate control and a low daily pill burden.

Serum Uric Acid and Mortality Risk Among Hemodialysis Patients.

INTRODUCTION: Although high serum uric acid (SUA) has been consistently associated with an increased risk of death in the general population and in persons with nondialysis chronic kidney disease (CKD), studies in patients undergoing dialysis are conflicting. It has been postulated that low SUA simply reflects poor nutritional status in dialysis patients. We here characterize the association between SUA and the risk of death in a large dialysis cohort and explore effect modification by underlying nutritional status as reflected by body composition. METHODS: In this retrospective cohort study, we included 16,057 hemodialysis (HD) patients treated during 2007 to 2016 in NephroCare centers as recorded in the European Clinical Database (EuCliD). The association between SUA, all-cause, and cardiovascular (CV)-related mortality was evaluated with competing risk models and characterized with splines. Effect modification was explored by lean tissue index (LTI) and fat tissue index (FTI). RESULTS: During a mean of 1.8 years of follow-up, 2791 patients (17.4%) died. We found a multivariable-adjusted U-shaped pattern between SUA and all-cause mortality. Patients with SUA levels of 6.5 mg/dl (387 µmol/l) were at the lowest risk of death (subdistribution hazard ratio = 0.94 [confidence interval {CI} 0.91; 0.96]). The form of association was not meaningfully affected by underlying LTI and FTI. CONCLUSION: We found a U-shaped pattern between SUA levels and all-cause mortality among HD patients, which was independent of the patients' body composition.

Effects of high-volume online mixed-hemodiafiltration on anemia management in dialysis patients.

BACKGROUND: Anemia is a major comorbidity of patients with end-stage renal disease and poses an enormous economic burden to health-care systems. High dose erythropoiesis-stimulating agents (ESAs) have been associated with unfavorable clinical outcomes. We explored whether mixed-dilution hemodiafiltration (Mixed-HDF), based on its innovative substitution modality, may improve anemia outcomes compared to the traditional post-dilution hemodiafiltration (Post-HDF). METHODS: We included 174 adult prevalent dialysis patients (87 on Mixed-HDF, 87 on Post-HDF) treated in 24 NephroCare dialysis centers between January 2010 and August 2016 into this retrospective cohort study. All patients were dialyzed three times per week and had fistula/graft as vascular access. Patients were matched at baseline and followed over a one-year period. The courses of hemoglobin levels (Hb) and monthly ESA consumption were compared between the two groups with linear mixed models. RESULTS: Mean baseline Hb was 11.9±1.3 and 11.8±1.1g/dl in patients on Mixed- and Post-HDF, respectively. While Hb remained stable in patients on Mixed-HDF, it decreased slightly in patients on Post-HDF (at month 12: 11.8±1.2 vs 11.1±1.2g/dl). This tendency was confirmed by our linear mixed model (p = 0.0514 for treatment x time interaction). Baseline median ESA consumption was 6000 [Q1:0;Q3:16000] IU/4 weeks in both groups. Throughout the observation period ESA doses tended to be lower in the Mixed-HDF group (4000 [Q1:0;Q3:16000] vs 8000 [Q1:0;Q3:20000] IU/4 weeks at month 12; p = 0.0791 for treatment x time interaction). Sensitivity analyses, adjusting for differences not covered by matching at baseline, strengthened our results (Hb: p = 0.0124; ESA: p = 0.0687). CONCLUSIONS: Results of our explorative study suggest that patients on Mixed-HDF may have clinical benefits in terms of anemia management. This may also have a beneficial economic impact. Future studies are needed to confirm our hypothesis-generating results and to provide additional evidence on the potential beneficial effects of Mixed-HDF.

Propofol or benzodiazepines for short- and long-term sedation in intensive care units? An economic evaluation based on meta-analytic results.

PURPOSE: This evaluation compares propofol and benzodiazepine sedation for mechanically ventilated patients in intensive care units (ICUs) in order to identify the potential economic benefits from different payers' perspectives. METHODS: The patient-level simulation model incorporated efficacy estimates from a structured meta-analysis and ICU-related costs from Italy, Germany, France, UK, and the USA. Efficacy outcomes were ICU length of stay (LOS), mechanical ventilation duration, and weaning time. We calculated ICU costs from mechanical ventilation duration and ICU LOS based on national average ICU costs with and without mechanical ventilation. Three scenarios were investigated: 1) long-term sedation >24 hours based on results from randomized controlled trials (RCTs); 2) long-term sedation based on RCT plus non-RCT results; and 3) short-term sedation <24 hours based on RCT results. We tested the model's robustness for input uncertainties by deterministic (DSA) and probabilistic sensitivity analyses (PSA). RESULTS: In the base case, mean savings with propofol versus benzodiazepines in long-term sedation ranged from €406 (95% confidence interval [CI]: 646 to 164) in Italy to 1,632 € (95% CI: 2,362 to 880) in the USA. Inclusion of non-RCT data corroborated these results. Savings in short-term sedation ranged from €148 (95% CI: 291 to 2) in Italy to €502 (95% CI: 936 to 57) in the USA. Parameters related to ICU and mechanical ventilation had a stronger influence in the DSA than drug-related parameters. In PSA, propofol reduced costs and ICU LOS compared to benzodiazepines in 94%-100% of simulations. The largest savings may be possible in the UK and the USA due to higher ICU costs. CONCLUSION: Current ICU sedation guidelines recommend propofol rather than midazolam for mechanically ventilated patients. This evaluation endorses the recommendation as it may lead to better outcomes and savings for health care systems, especially in countries with higher ICU-related costs.

Glutamine dipeptide-supplemented parenteral nutrition improves the clinical outcomes of critically ill patients: A systematic evaluation of randomised controlled trials.

BACKGROUND & AIMS: Early randomised controlled trials (RCTs) testing whether parenteral nutrition regimens that include glutamine dipeptides improves the outcomes of critically ill patients demonstrated convincingly that this regimen associates with reduced mortality, infections, and hospital stays. However, several new RCTs on the same question challenged this. To resolve this controversy, the present meta-analysis was performed. Stringent eligibility criteria were used to select only those RCTs that tested the outcomes of critically ill adult patients without hepatic and/or renal failure who were haemodynamically and metabolically stabilised and who were administered glutamine dipeptide strictly according to current clinical guidelines (via the parenteral route at 0.3-0.5 g/kg/day; max. 30% of the prescribed nitrogen supply) in combination with adequate nutrition. METHODS: The literature research (PubMed, Embase, Cochrane Central Register of Controlled Trials) searched for English and German articles that had been published in peer-review journals (last entry March 31, 2015) and reported the results of RCTs in critically ill adult patients (major surgery, trauma, infection, or organ failure) who received parenteral glutamine dipeptide as part of an isoenergetic and isonitrogenous nutrition therapy. The following data were extracted: infectious complications, lengths of stay (LOS) in the hospital and intensive care unit (ICU), duration of mechanical ventilation, days on inotropic support, and ICU and hospital mortality rates. The selection of and data extraction from studies were performed by two independent reviewers. RESULTS: Fifteen RCTs (16 publications) fulfilled all selection criteria. They involved 842 critically ill patients. None had renal and/or hepatic failure. The average study quality (Jadad score: 3.8 points) was well above the predefined cut-off of 3.0. Common effect estimates indicated that parenteral glutamine dipeptide supplementation significantly reduced infectious complications (relative risk [RR] = 0.70, 95% CI 0.60, 0.83, p < 0.0001), ICU LOS (common mean difference [MD] -1.61 days, 95% CI -3.17, -0.05, p = 0.04), hospital LOS (MD -2.30 days, 95% CI -4.14, -0.45, p = 0.01), and mechanical ventilation duration (MD -1.56 days, 95% CI -2.88, -0.24, p = 0.02). It also lowered the hospital mortality rate by 45% (RR = 0.55, 95% CI 0.32, 0.94, p = 0.03) but had no effect on ICU mortality. Visual inspection of funnel plots did not reveal any potential selective reporting of studies. CONCLUSIONS: This meta-analysis clearly confirms that when critically ill patients are supplemented with parenteral glutamine dipeptide according to clinical guidelines as part of a balanced nutrition regimen, it significantly reduces hospital mortality, infectious complication rates, and hospital LOS. The latter two effects indicate that glutamine dipeptide supplementation also confers economic benefits in this setting. The present analysis indicates the importance of delivering glutamine dipeptides together with adequate parenteral energy and nitrogen so that the administered glutamine serves as precursor in various biosynthetic pathways rather than simply as a fuel.

Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System. Part 8: Nicotine bridging--estimating smoke constituent exposure by their relationships to both nicotine levels in mainstream cigarette smoke and in smokers.

A modeling approach termed 'nicotine bridging' is presented to estimate exposure to mainstream smoke constituents. The method is based on: (1) determination of harmful and potentially harmful constituents (HPHC) and in vitro toxicity parameter-to-nicotine regressions obtained using multiple machine-smoking protocols, (2) nicotine uptake distributions determined from 24-h excretion of nicotine metabolites in a clinical study, and (3) modeled HPHC uptake distributions using steps 1 and 2. An example of 'nicotine bridging' is provided, using a subset of the data reported in Part 2 of this supplement (Zenzen et al., 2012) for two conventional lit-end cigarettes (CC) and the Electrically Heated Cigarette Smoking System (EHCSS) series-K6 cigarette. The bridging method provides justified extrapolations of HPHC exposure distributions that cannot be obtained for smoke constituents due to the lack of specific biomarkers of exposure to cigarette smoke constituents in clinical evaluations. Using this modeling approach, exposure reduction is evident when the HPHC exposure distribution curves between the MRTP and the CC users are substantially separated with little or no overlap between the distribution curves.

Widening of a social gradient in obesity risk? German national health surveys 1990 and 1998.

OBJECTIVE: Whether differences in obesity prevalences across social status levels have widened remains controversial. METHODS: We used German national health surveys (1990-1992 and 1998, n = 7,466 and 5,583, age 25-69 years) to estimate obesity prevalences and its associations with calendar year, age (25-39, 40-60, and 61-69), and educational level (low, middle, and high), as well as an interaction term (year x educational level) in men and women. We used multiple regression models, considering the sample design. RESULTS: Obesity prevalence in 1990 and 1998 was 18.1 (95% CI 16.5-19.7) and 19.9 (18.2-21.6) in men and 20.9 (19.2-22.6) and 21.6 (19.3-23.7) in women, with statistically significantly higher prevalences in higher age and lower education. A statistically significant increase of obesity prevalence was present only in men after adjustment for age and education. The increase seems to be highest in high-educated subjects. However, interaction was not statistically significant, except in middle compared to high-educated men (OR 0.67; 0.47-0.96). CONCLUSIONS: Obesity prevalence increased only moderately in Germany between 1990-1992 and 1998. There was a tendency of reduction of the social gradient in obesity instead of a widening.

Diabetes prevalence and association with social status--widening of a social gradient? German national health surveys 1990-1992 and 1998.

BACKGROUND: Widening of social inequality in health is often discussed. Data regarding trends of the association between diabetes prevalence and social status are lacking. METHODS: Using two German health surveys (age 25-69 years), we estimated diabetes prevalences in 1998 compared to 1990-1992. Interaction of secular time with educational level, adjusted for age and BMI, were estimated in men and women using multiple regression models, considering the sample design. RESULTS: Diabetes prevalences in 1990-1992 and 1998 were 5.1% (95% CI 4.1-6.0) and 4.3% (3.5-5.1) in men, and 4.7% (4.0-5.4) and 3.8% (3.0-4.6) in women. It was significantly higher in older subjects and in obese subjects, and tended to be higher in lower educated subjects. Overall, prevalence tended to be lower in 1998 compared to 1990-1992, however, not statistically significant after adjustment for education and BMI (odds ratio, 95% CI: men 0.73; 0.39-1.37; women 0.41; 0.17-1.03). On a descriptive level, in the lowest education group, the diabetes prevalence was higher in 1998 compared to 1990-1992, whereas, it has decreased in higher educated subjects. However, confidence intervals were large, and we found no statistically significant interaction between calendar year and the educational level. CONCLUSIONS: Diabetes prevalence tended to decrease in Germany during the 1990s. A widening of social disparity in diabetes risk might be present, but a significant increase could not be confirmed.

Impact of age, height, and body mass index on arterial diameters in infants and children: a model for predicting femoral artery diameters prior to cardiovascular procedures.

PURPOSE: To measure common femoral artery (CFA) diameters in infants and children referred for cardiac catheterization and investigate if CFA diameters can be predicted upon the basis of age, body mass index (BMI), and height. METHODS: CFA diameters were measured in 84 infants and children (50 boys; age range 1- 220 months) referred for diagnostic or therapeutic cardiac interventions. Sonographic measurements were made in a supine position utilizing a 7.5-MHz linear transducer; diameters were defined as the intima to intima distance. Age was described in months and height in centimeters. The Spearman correlation coefficient (rho) was used to test the similarity of diameters between sides; the Pearson correlation coefficient (r) was used to analyze the influence of age, height, and BMI on CFA diameter. RESULTS: Diameters of the right and left CFA were similar (rho=0.951). Age and height were highly correlated (rho=0.956), but not BMI and height (rho=0.279). The best model was CFA diameter = -0.838 + 0.031 height + 0.046 BMI. Height was the most relevant determinant for CFA diameter (p<0.0001, 90% CI 0.027 to 0.036; BMI: p=0.093, 90% CI 0.001 to 0.090, and the intercept: p=0.032, 90% CI-1.475 to-0.200). CONCLUSIONS: Common femoral artery diameter can be sufficiently predicted from height and BMI of infants and children prior to femoral catheterization or surgical reconstruction.