Background High interdialytic weight gain (IDWG) is associated with adverse outcomes in hemodialysis (HD) patients. We identified temporal and regional trends in IDWG, predictors of IDWG, and ...associations of IDWG with clinical outcomes. Study Design Analysis 1: sequential cross-sections to identify facility- and patient-level predictors of IDWG and their temporal trends. Analysis 2: prospective cohort study to assess associations between IDWG and mortality and hospitalization risk. Setting & Participants 21,919 participants on HD therapy for 1 year or longer in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 2 to 5 (2002-2014). Predictors Analysis 1: study phase, patient demographics and comorbid conditions, HD facility practices. Analysis 2: relative IDWG, expressed as percentage of post-HD weight (<0%, 0%-0.99%, 1%-2.49%, 2.5%-3.99% reference, 4%-5.69%, and ≥5.7%). Outcomes Analysis 1: relative IDWG as a continuous variable using linear mixed models; analysis 2: mortality; all-cause and cause-specific hospitalization using Cox regression, adjusting for potential confounders. Results From phase 2 to 5, IDWG declined in the United States (−0.29 kg; −0.5% of post-HD weight), Canada (−0.25 kg; −0.8%), and Europe (−0.22 kg; −0.5%), with more modest declines in Japan and Australia/New Zealand. Among modifiable factors associated with IDWG, the most notable was facility mean dialysate sodium concentration: every 1-mEq/L greater dialysate sodium concentration was associated with 0.13 (95% CI, 0.11-0.16) greater relative IDWG. Compared to relative IDWG of 2.5% to 3.99%, there was elevated risk for mortality with relative IDWG ≥ 5.7% (adjusted HR, 1.23; 95% CI, 1.08-1.40) and elevated risk for fluid-overload hospitalization with relative IDWG ≥ 4% (HRs of 1.28 95% CI, 1.09-1.49 and 1.64 95% CI, 1.27-2.13 for relative IDWGs of 4%-5.69% and ≥5.7%, respectively). Limitations Possible residual confounding. No dietary salt intake data. Conclusions Reductions in IDWG during the past decade were partially explained by reductions in dialysate sodium concentration. Focusing quality improvement strategies on reducing occurrences of high IDWG may improve outcomes in HD patients.
Background Patients receiving long-term dialysis have among the highest mortality and hospitalization rates. In the nonrenal literature, functional dependence is recognized as a contributor to ...subsequent disability, recurrent hospitalization, and increased mortality. A higher burden of functional dependence with progressive worsening of kidney function has been observed in several studies, suggesting that functional dependence may contribute to both morbidity and mortality in dialysis patients. Study Design Prospective cohort study. Setting & Participants 7,226 hemodialysis patients from 12 countries in the DOPPS (Dialysis Outcomes and Practice Patterns Study) phase 4 (2009-2011) with self-reported data for functional status. Predictor Patients’ ability to perform 13 basic and instrumental activities of daily living was summarized to create an overall functional status score (range, 1.25 most dependent to 13 functionally independent). Outcome Cox regression was used to estimate the association between functional status and all-cause mortality, adjusting for several demographic and clinical risk factors for mortality. Median follow-up was 17.2 months. Results The proportion of patients who could perform each activity of daily living task without assistance ranged from 97% (eating) to 47% (doing housework). 36% of patients could perform all 13 tasks without assistance (functional status = 13), and 14% of patients had high functional dependence (functional status < 8). Functionally independent patients were younger and had many indicators of better health status, including higher quality of life. Compared with functionally independent patients, the adjusted HR for mortality was 2.37 (95% CI, 1.92-2.94) for patients with functional status < 8. Limitations Possible nonresponse bias and residual confounding. Conclusions We found a high burden of functional dependence across all age groups and across all DOPPS countries. When adjusting for several known mortality risk factors, including age, access type, cachexia, and multimorbidity, functional dependence was a strong consistent predictor of mortality.
Background Sudden death is a leading cause of death in patients on maintenance hemodialysis therapy. During hemodialysis sessions, the gradient between serum and dialysate levels results in rapid ...electrolyte shifts, which may contribute to arrhythmias and sudden death. Controversies exist about the optimal electrolyte concentration in the dialysate; specifically, it is unclear whether patient outcomes differ among those treated with a dialysate potassium concentration of 3 mEq/L compared to 2 mEq/L. Study Design Prospective cohort study. Setting & Participants 55,183 patients from 20 countries in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 1 to 5 (1996-2015). Predictor Dialysate potassium concentration at study entry. Outcomes Cox regression was used to estimate the association between dialysate potassium concentration and both all-cause mortality and an arrhythmia composite outcome (arrhythmia-related hospitalization or sudden death), adjusting for potential confounders. Results During a median follow-up of 16.5 months, 24% of patients died and 7% had an arrhythmia composite outcome. No meaningful difference in clinical outcomes was observed for patients treated with a dialysate potassium concentration of 3 versus 2 mEq/L (adjusted HRs were 0.96 95% CI, 0.91-1.01 for mortality and 0.98 95% CI, 0.88-1.08 for arrhythmia composite). Results were similar across predialysis serum potassium levels. As in prior studies, higher serum potassium level was associated with adverse outcomes. However, dialysate potassium concentration had only minimal impact on serum potassium level measured predialysis (+0.09 95% CI, 0.05-0.14 mEq/L serum potassium per 1 mEq/L greater dialysate potassium concentration). Limitations Data were not available for delivered (vs prescribed) dialysate potassium concentration and postdialysis serum potassium level; possible unmeasured confounding. Conclusions In combination, these results suggest that approaches other than altering dialysate potassium concentration (eg, education on dietary potassium sources and prescription of potassium-binding medications) may merit further attention to reduce risks associated with high serum potassium levels.
Background Since the bundled end-stage renal disease prospective payment system began in 2011 in the United States, some hemodialysis practices have changed substantially, raising the question of ...whether vascular access practice also has changed. We describe monthly US vascular access use from August 2010 to August 2013 with international comparisons, and other aspects of US vascular access practice. Study Design Prospective observational cohort study of vascular access. Setting & Participants Maintenance hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS) Practice Monitor (DPM) in the United States (N = 3,442; US patients) and 19 other nations (N = 8,478). Predictors Country, patient demographics, time period. Outcomes Vascular access use, pre–end-stage renal disease access timing of first nephrologist care and arteriovenous access placement, patient self-reported vascular access preferences (United States only), treatment practices as stated by medical directors. Results In the United States from August 2010 to August 2013, arteriovenous fistula (AVF) use increased from 63% to 68%, while catheter use declined from 19% to 15%. Although AVF use did not differ greatly across age groups, arteriovenous graft use was 2-fold higher among black (26%) versus nonblack US patients (13%) in 2013. Across 20 countries in 2013, AVF use ranged from 49% to 92%, whereas catheter use ranged from 1% to 45%. Patient-reported vascular access preferences differed by sex and race, with 16% to 20% of patients feeling uninformed regarding benefits/risks of different vascular access types. Among new (incident) US hemodialysis patients, AVF use remains low, with ∼70% initiating hemodialysis therapy with a catheter (60% starting with catheter when having ≥4 months of predialysis nephrology care). In the United States, longer typical times to first AVF cannulation were reported. Limitations Noncompletion of surveys may affect the generalizability of findings to the wider hemodialysis population. Conclusions AVF use has increased, with catheter use decreasing among prevalent US hemodialysis patients since the introduction of the prospective payment system. However, AVF use at dialysis therapy initiation remains low, suggesting that reforms affecting predialysis care may be necessary to incentivize improvements in fistula rates at dialysis therapy initiation as achieved for prevalent hemodialysis patients.
•Fruit flavor, but not tobacco flavor, enhances e-liquid consumption and preference.•The nicotine-free flavored e-liquid is not preferred over nicotine alone.•Conditioning rewarding and aversive ...effects are equal between nicotine and e-liquid.
The use of electronic cigarettes has increased over the past decade. To determine how the abuse liability of electronic cigarette liquids (e-liquids) differs from nicotine alone, and to determine the impact of flavor, we compared nicotine-containing fruit- and tobacco-flavored e-liquids, and their nicotine-free versions, to nicotine alone in mouse models of oral consumption, reward and aversion.
Adult male C57BL/6 J mice voluntarily consumed oral nicotine, equivalent nicotine concentrations of fruit- and tobacco-flavored e-liquid, and equivalent dilutions of the nicotine-free versions in 2-bottle choice tests. Conditioned place preference and place aversion were assessed with peripherally administered e-liquids or nicotine. Serum nicotine and cotinine levels were measured after subcutaneous injections of e-liquid or nicotine.
Mice showed higher consumption and preference for the fruit-flavored e-liquid compared with nicotine alone. This increase was not due to the flavor itself as consumption of the nicotine-free fruit-flavored e-liquid was not elevated until the highest concentration tested. The increased consumption and preference were not observed with the tobacco-flavored e-liquid. The conditioned place preference, place aversion and nicotine pharmacokinetics of the fruit-flavored e-liquid were not significantly different from nicotine alone.
Our data suggest that fruit, but not tobacco flavor, increased the oral consumption of e-liquid compared with nicotine alone. Moreover, this enhancement was not due to increased consumption of the flavor itself, altered rewarding or aversive properties after peripheral administration, or altered pharmacokinetics. This flavor-specific enhancement suggests that some flavors may lead to higher nicotine intake and increased use of e-liquids compared with nicotine alone.
There is a growing body of evidence that links nutrition to muscle mass, strength and function in older adults, suggesting that it has an important role to play both in the prevention and management ...of sarcopenia. This review summarises the discussions of a working group ESCEO working group meeting 8th September 2016 that met to review current evidence and to consider its implications for preventive and treatment strategies. The review points to the importance of ‘healthier’ dietary patterns that are adequate in quality in older age, to ensure sufficient intakes of protein, vitamin D, antioxidant nutrients and long-chain polyunsaturated fatty acids. In particular, there is substantial evidence to support the roles of dietary protein and physical activity as key anabolic stimuli for muscle protein synthesis. However, much of the evidence is observational and from high-income countries. Further high-quality trials, particularly from more diverse populations, are needed to enable an understanding of dose and duration effects of individual nutrients on function, to elucidate mechanistic links, and to define optimal profiles and patterns of nutrient intake for older adults.
Background Poor nutritional status and both hyper- and hypophosphatemia are associated with increased mortality in maintenance hemodialysis (HD) patients. We assessed associations of phosphate binder ...prescription with survival and indicators of nutritional status in maintenance HD patients. Study Design Prospective cohort study (DOPPS Dialysis Outcomes and Practice Patterns Study), 1996-2008. Setting & Participants 23,898 maintenance HD patients at 923 facilities in 12 countries. Predictors Patient-level phosphate binder prescription and case-mix–adjusted facility percentage of phosphate binder prescription using an instrumental-variable analysis. Outcome All-cause mortality. Results Overall, 88% of patients were prescribed phosphate binders. Distributions of age, comorbid conditions, and other characteristics showed small differences between facilities with higher and lower percentages of phosphate binder prescription. Patient-level phosphate binder prescription was associated strongly at baseline with indicators of better nutrition, ie, higher values for serum creatinine, albumin, normalized protein catabolic rate, and body mass index and absence of cachectic appearance. Overall, patients prescribed phosphate binders had 25% lower mortality (HR, 0.75; 95% CI, 0.68-0.83) when adjusted for serum phosphorus level and other covariates; further adjustment for nutritional indicators attenuated this association (HR, 0.88; 95% CI, 0.80-0.97). However, this inverse association was observed for only patients with serum phosphorus levels ≥3.5 mg/dL. In the instrumental-variable analysis, case-mix–adjusted facility percentage of phosphate binder prescription (range, 23%-100%) was associated positively with better nutritional status and inversely with mortality (HR for 10% more phosphate binders, 0.93; 95% CI, 0.89-0.96). Further adjustment for nutritional indicators reduced this association to an HR of 0.95 (95% CI, 0.92-0.99). Limitations Results were based on phosphate binder prescription; phosphate binder and nutritional data were cross-sectional; dietary restriction was not assessed; observational design limits causal inference due to possible residual confounding. Conclusions Longer survival and better nutritional status were observed for maintenance HD patients prescribed phosphate binders and in facilities with a greater percentage of phosphate binder prescription. Understanding the mechanisms for explaining this effect and ruling out possible residual confounding require additional research.
The Dzyaloshinskii-Moriya interaction has been shown to stabilise Nèel domain walls in magnetic thin films, allowing high domain wall velocities driven by spin current effects. The interfacial ...Dzyaloshinskii-Moriya interaction (IDMI) occurs at the interface between ferromagnetic and heavy metal layers with strong spin-orbit coupling, but details of the interaction remain to be understood and the role of proximity induced magnetism (PIM) in the heavy metal is unknown. Here IDMI and PIM are reported in Pt determined as a function of Au and Ir spacer layers in Pt/Co/Au,Ir/Pt. Both interactions are found to be sensitive to sub-nanometre changes in the spacer thickness, correlating over sub-monolayer spacer thicknesses, but not for thicker spacers where IDMI continues to change even after PIM is lost.