Association of hematocrit value with cardiovascular morbidity and mortality in incident hemodialysis patients

Association of hematocrit value with cardiovascular morbidity and mortality in incident hemodialysis patients.BackgroundAssociations between hematocrit values and clinical outcome have been studied with conflicting results in cardiac patients, end-stage renal disease (ESRD) patients, and ESRD patients with cardiac disease. We studied dialysis patients to determine the relationship between hematocrit value and cardiac risk under current Dialysis Outcomes Quality Initiative (DOQI) practices.MethodsMedicare data were used to study 50,579 incident hemodialysis patients selected from January 1, 1998, to December 31, 1999, who received hemodialysis for 9 months after the onset of ESRD. Patients were divided into groups on the basis of the hematocrit value: ≤30%, >30% to ≤33%, >33% to ≤36%, >36% to ≤39%, and >39%. For hospitalization, the follow-up extended to 21/2 years; for mortality, 3 years.ResultsCompared to patients with hematocrit values of >33% to ≤36%, patients with values of >36% to ≤39% and those with values of >39% had risk ratios for hospitalization due to cardiac disease of 0.92 (95% CI 0.88 to 0.97) and 0.79 (95% CI 0.72 to 0.87), respectively, and risk ratios for death due to cardiac disease of 0.92 (95% CI 0.87 to 0.98) and 0.83 (95% CI 0.74 to 0.93), respectively, in the follow-up period.ConclusionThe significant associations we report do not establish a causal relationship between higher hematocrit values and lower risks of cardiac morbidity and mortality. A randomized clinical trial in low-risk patients is needed to establish causality

Effect of Inflammation on the Relationship of Pulse Pressure and Mortality in Haemodialysis

The effect of hypertension on mortality in haemodialysis patients is controversial and can be confounded by non-traditional risk factors like systemic inflammation. This study examined the effect of systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) on mortality in haemodialysis patients, separately with and without markers of systemic inflammation

Blood pressure and long-term mortality in United States hemodialysis patients: USRDS Waves 3 and 4 Study11The data reported here were supplied by the United States Renal Data System. Interpretation of these data is the responsibility of the authors, and in no way should be seen as an official policy or interpretation of the U.S. government.

Blood pressure and long-term mortality in United States hemodialysis patients: USRDS Waves 3 and 4 Study.BackgroundThe long-term prognostic associations of pre- and post-dialysis blood pressures, interdialytic weight gain, and antihypertensive use in hemodialysis patients are unclear.MethodsThe United States Renal Data System (USRDS) Dialysis Morbidity and Mortality Waves 3 and 4 Study, a randomly generated sample of 11,142 subjects receiving hemodialysis on December 31, 1993, was examined, with vital status followed until May 2000.ResultsPre- and post-dialysis blood pressure values, interdialytic weight gain and number of antihypertensives averaged 151.8/79.7, 137.0/74, 3.6% and 0.76, respectively. Prognostic discrimination was maximized by considering pre- and post-systolic and diastolic blood pressure values simultaneously, in a pattern suggesting that wide pulse pressures were associated with mortality (P < 0.0001). Comorbidity adjustment markedly affected associations, with low pre-dialysis diastolic (P < 0.05), low post-dialysis dialysis diastolic pressure (P < 0.05), high post-dialysis dialysis systolic pressure (P < 0.05), and high interdialytic weight gains (P = 0.005) associated with mortality. Each class of antihypertensive drug, except angiotensin-converting enzyme (ACE)-inhibitors, was associated with lower mortality in unadjusted models, an effect most pronounced for beta-blockers (hazards ratio 0.72, 95% CI 0.66 to 0.79, P < 0.0001). Comorbidity adjustment eliminated survival associations for each antihypertensive class except beta-blockers.ConclusionsPre- and post-dialysis blood pressure values have independent associations with mortality, in a way that implicates wide pulse pressures. Much of the adverse prognosis of wide pulse pressures probably reflects older age and cardiovascular comorbidity. Large interdialytic weight gains are associated with shorter survival when comorbidity is taken into account. Beta-blocker use shows a robust association with survival, and may be protective

Metrics for linking emissions of gases and aerosols to global precipitation changes

Recent advances in understanding have made it possible to relate global precipitation changes directly to emissions of particular gases and aerosols that influence climate. Using these advances, new indices are developed here called the Global Precipitation-change Potential for pulse (GPP_P) and sustained (GPP_S) emissions, which measure the precipitation change per unit mass of emissions. The GPP can be used as a metric to compare the effects of different emissions. This is akin to the global warming potential (GWP) and the global temperature-change potential (GTP) which are used to place emissions on a common scale. Hence the GPP provides an additional perspective of the relative or absolute effects of emissions. It is however recognised that precipitation changes are predicted to be highly variable in size and sign between different regions and this limits the usefulness of a purely global metric. The GPP_P and GPP_S formulation consists of two terms, one dependent on the surface temperature change and the other dependent on the atmospheric component of the radiative forcing. For some forcing agents, and notably for CO2, these two terms oppose each other – as the forcing and temperature perturbations have different timescales, even the sign of the absolute GPP_P and GPP_S varies with time, and the opposing terms can make values sensitive to uncertainties in input parameters. This makes the choice of CO2 as a reference gas problematic, especially for the GPP_S at time horizons less than about 60 years. In addition, few studies have presented results for the surface/atmosphere partitioning of different forcings, leading to more uncertainty in quantifying the GPP than the GWP or GTP. Values of the GPP_P and GPP_S for five long- and short-lived forcing agents (CO2, CH4, N2O, sulphate and black carbon – BC) are presented, using illustrative values of required parameters. The resulting precipitation changes are given as the change at a specific time horizon (and hence they are end-point metrics) but it is noted that the GPPS can also be interpreted as the time-integrated effect of a pulse emission. Using CO2 as a references gas, the GPP_P and GPP_S for the non-CO2 species are larger than the corresponding GTP values. For BC emissions, the atmospheric forcing is sufficiently strong that the GPP_S is opposite in sign to the GTP_S. The sensitivity of these values to a number of input parameters is explored. The GPP can also be used to evaluate the contribution of different emissions to precipitation change during or after a period of emissions. As an illustration, the precipitation changes resulting from emissions in 2008 (using the GPP_P) and emissions sustained at 2008 levels (using the GPP_S) are presented. These indicate that for periods of 20 years (after the 2008 emissions) and 50 years (for sustained emissions at 2008 levels) methane is the dominant driver of positive precipitation changes due to those emissions. For sustained emissions, the sum of the effect of the five species included here does not become positive until after 50 years, by which time the global surface temperature increase exceeds 1 K

A comparison of transplant outcomes in peritoneal and hemodialysis patients

A comparison of transplant outcomes in peritoneal and hemodialysis patients.BackgroundStudies examining the effect of pre-transplant dialysis modality on graft and patient survival after kidney transplantation have produced conflicting results. Therefore, we studied the effects of pre-transplant dialysis modality on outcomes in a large United States cohort.MethodsWe compared rates of transplantation between peritoneal dialysis and hemodialysis patients from the years 1995 to 1998 in the United States (N = 252,402) and outcomes after transplantation (N = 22,776), using data from the Centers for Medicare and Medicaid Services.ResultsIn a Cox proportional hazards analysis that was adjusted for multiple patient characteristics, kidney transplantation was 1.39 (95% CI = 1.35 to 1.43) times more likely in peritoneal dialysis vs. hemodialysis patients (P < 0.0001). Over the entire follow-up period, the adjusted risk for death-censored graft failure was 1.15 (1.04 to 1.26) times higher in peritoneal dialysis vs. hemodialysis (P < 0.05), but mortality and overall graft failure rates were not different. Pre-transplant dialysis modality did not affect outcomes for patients who survived with a functioning kidney for at least 3 months. However, in adjusted Cox analyses restricted to the first 3 months, peritoneal dialysis was associated with a 1.23 (1.09 to 1.39) times higher risk for early graft failure (P < 0.001) and a 1.33 (1.16 to 1.53) times higher risk for death-censored graft failure (P < 0.001). Peritoneal dialysis patients, however, were seen to have a lower incidence of delayed graft function. In a smaller sample of patients with data on causes of early graft failure, graft thrombosis was more commonly listed as a cause of graft failure among peritoneal dialysis patients, 41% (64/156), compared to hemodialysis patients, 30% (106/349), P < 0.05.ConclusionsKidney transplantation is more frequent in peritoneal dialysis than in hemodialysis patients, and transplantation in peritoneal dialysis patients is more frequently associated with early, but not late, graft failure. Delayed graft function was less common in peritoneal dialysis patients but this potential benefit appears to be offset by other factors which are associated with early graft loss. Additional studies are needed to determine what factors may help understand this early risk of graft failure

Conditional expression in corticothalamic efferents reveals a developmental role for nicotinic acetylcholine receptors in modulation of passive avoidance behavior

Prenatal nicotine exposure has been linked to attention deficit hyperactivity disorder and cognitive impairment, but the sites of action for these effects of nicotine are still under investigation. High-affinity nicotinic acetylcholine receptors (nAChRs) contain the .2 subunit and modulate passive avoidance (PA) learning in mice. Using an inducible, tetracycline-regulated transgenic system, we generated lines of mice with expression of high-affinity nicotinic receptors restored in specific neuronal populations. One line of mice shows functional .2 subunit-containing nAChRs localized exclusively in corticothalamic efferents. Functional, presynaptic nAChRs are present in the thalamus of these mice as detected by nicotine-elicited rubidium efflux assays from synaptosomes. Knock-out mice lacking high-affinity nAChRs show elevated baseline PA learning, whereas normal baseline PA behavior is restored in mice with corticothalamic expression of these nAChRs. In contrast, nicotine can enhance PA learning in adult wild-type animals but not in corticothalamic-expressing transgenic mice. When these transgenic mice are treated with doxycycline in adulthood to switch off nAChR expression, baseline PA is maintained even after transgene expression is abolished. These data suggest that high-affinity nAChRs expressed on corticothalamic neurons during development are critical for baseline PA performance and provide a potential neuroanatomical substrate for changes induced by prenatal nicotine exposure leading to long-term behavioral and cognitive deficits

The differential impact of risk factors on mortality in hemodialysis and peritoneal dialysis

The differential impact of risk factors on mortality in hemodialysis and peritoneal dialysis.BackgroundWhile the survival ramifications of dialysis modality selection are still debated, it seems reasonable to postulate that outcome comparisons are not the same for all patients at all times. Trends in available data indicate the relative risk of death with hemodialysis (HD) compared to peritoneal dialysis (PD) varies by time on dialysis and the presence of various risk factors. This study was undertaken to identify key patient characteristics for which the risk of death differs by dialysis modality.MethodsAnalyses utilized incidence data from 398,940 United States Medicare patients initiating dialysis between 1995 and 2000. Proportional hazards regression identified the presence of diabetes, age, and the presence of comorbidity as factors that significantly interact with treatment modality. Stratifying by these factors, proportional and nonproportional hazards models were used to estimate relative risks of death [RR (HD:PD)].ResultsOf the 398,940 patients studied, 11.6% used PD as initial therapy, 45% had diabetes mellitus (DM), 51% were 65 years or older, and 55% had at least one comorbidity. Among the 178,693 (45%) patients with no baseline comorbidity, adjusted mortality rates in nondiabetic (non-DM) patients were significantly higher on HD than on PD [age 18–44: RR (95% CI) = 1.24 (1.07, 1.44); age 45–64: RR = 1.13 (1.02, 1.25); age 65+: RR = 1.13 (1.05, 1.21)]. Among diabetic (DM) patients with no comorbidity, HD was associated with a higher risk of death among younger patients [age 18–44: RR = 1.22(1.05, 1.42)] and a lower risk of death among older patients [age 45–64: RR = 0.92 (0.85, 1.00); age 65+: RR = 0.86 (0.79, 0.93)]. Within the group of 220,247 (55%) patients with baseline comorbidity, adjusted mortality rates were not different between HD and PD among non-DM patients [age 18–44: RR = 1.19 (0.94, 1.50); age 45–64: RR = 1.01 (0.92, 1.11); age 65+: RR = 0.96 (0.91, 1.01)] and younger DM patients [age 18–44: RR = 1.10 (0.92, 1.32)], but were lower with HD among older DM patients with baseline comorbidity [age 45–64: RR = 0.82 (0.77, 0.87); age 65+: RR = 0.80 (0.76, 0.85)].ConclusionValid mortality comparisons between HD and PD require patient stratification according to major risk factors known to interact with treatment modality. Survival differences between HD and PD are not constant, but vary substantially according to the underlying cause of ESRD, age, and level of baseline comorbidity. These results may help identify technical advances that will improve outcomes of patients on dialysis

Chronic kidney disease: The distribution of health care dollars

Chronic kidney disease: The distribution of health care dollars.BackgroundThe cost of care for end-stage renal disease (ESRD) is known to be high. The factors responsible for higher ESRD cost develop during chronic kidney disease (CKD), where the data on distribution of cost are limited.MethodsThis retrospective cohort study of 1995 through 1998 incident dialysis patients was performed to study the distribution of costs during the 24 months prior to initiation of dialysis. Patient data were obtained from the Centers for Medicare and Medicaid Services (CMS). Patients who were Medicare eligible for at least 2 years prior to initiation of dialysis were included in the study. Financial data were obtained from Medicare Part A and Part B claims and inflationary adjustments were made. The study period was divided into four segments based on overall distribution of cost.ResultsThe mean age was 75 years, 51% were males, 73% were white, and 22% were black. Overall, patient comorbidity increased significantly during the study years. Cost showed a sharp increase in the last 6 months prior to initiation of dialysis. Hospitalization was the major component of cost throughout study period. Patients who initiated hemodialysis incurred a higher cost compared to patients who initiated other modes of kidney replacement therapy. Patients with diabetes or cardiovascular disease incurred higher cost compared to those who had no diabetes or cardiovascular disease, respectively.ConclusionThese data showed that hospitalization was the major component of the sharp increase in cost around the initiation of dialysis. Increased comorbidity was associated with higher cost. A focus on timely management of CKD may prevent future morbidity and costs

Cephalosporin-3’-diazeniumdiolate NO-donor prodrug PYRRO-C3D enhances azithromycin susceptibility of non-typeable Haemophilus influenzae biofilms

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Objectives: PYRRO-C3D is a cephalosporin-3-diazeniumdiolate nitric oxide (NO)-donor prodrug designed to selectively deliver NO to bacterial infection sites. The objective of this study was to assess the activity of PYRRO-C3D against non-typeable Haemophilus influenzae (NTHi) biofilms and examine the role of NO in reducing biofilm-associated antibiotic tolerance. Methods: The activity of PYRRO-C3D on in vitro NTHi biofilms was assessed through CFU enumeration and confocal microscopy. NO release measurements were performed using an ISO-NO probe. NTHi biofilms grown on primary ciliated respiratory epithelia at an air-liquid interface were used to investigate the effects of PYRRO-C3D in the presence of host tissue. Label-free LC/MS proteomic analyses were performed to identify differentially expressed proteins following NO treatment. Results: PYRRO-C3D specifically released NO in the presence of NTHi, while no evidence of spontaneous NO release was observed when the compound was exposed to primary epithelial cells. NTHi lacking β-lactamase activity failed to trigger NO release. Treatment significantly increased the susceptibility of in vitro NTHi biofilms to azithromycin, causing a log-fold reduction in viability (p<0.05) relative to azithromycin alone. The response was more pronounced for biofilms grown on primary respiratory epithelia, where a 2-log reduction was observed (p<0.01). Label-free proteomics showed that NO increased expression of sixteen proteins involved in metabolic and transcriptional/translational functions. Conclusions: NO release from PYRRO-C3D enhances the efficacy of azithromycin against NTHi biofilms, putatively via modulation of NTHi metabolic activity. Adjunctive therapy with NO mediated through PYRRO-C3D represents a promising approach for reducing biofilm associated antibiotic tolerance