Inflammatory markers and risk of cerebrovascular events in patients initiating dialysis.

BACKGROUND AND OBJECTIVES: Stroke remains a leading cause of morbidity and mortality for patients on dialysis; however, its risk factors in this population and measures to prevent it are not well understood. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We investigated whether inflammation was associated with cerebrovascular events in a national US cohort of 1041 incident dialysis patients enrolled from October 1995 to June 1998 and followed until January 31, 2004. Incident cerebrovascular events were defined as nonfatal (hospitalized stroke, carotid endarterectomy) and fatal (stroke death) events after dialysis initiation. With Cox proportional hazards regression analysis accounting for the competing risk of nonstroke death, we assessed the independent event risk associated with baseline levels of multiple inflammatory markers (high-sensitivity C-reactive protein [hsCRP], interleukin-6 (IL-6), matrix metalloproteinase-3 [MMP-3], and P-selectin) and hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin) use, which may have pleiotropic inflammatory effects. RESULTS: 165 patients experienced a cerebrovascular event during 3548 person-years of follow-up; overall incidence rate was 4.9/100 person-years. None of the inflammatory markers were associated with cerebrovascular event risk (adjusted hazard ratios [HRs] per log unit [95% confidence interval]: hsCRP, 0.97 [0.85 to 1.11]; IL-6, 1.04 [0.85 to 1.26]; MMP-3, 1.02 [0.70 to 1.48]; P-selectin, 0.98 [0.57 to 1.68]). Statin use was also not associated with significant risk of events in unadjusted (HR 1.07 [0.69 to 1.68]) or propensity-score adjusted analyses (HR 0.98 [0.61 to 1.56]). CONCLUSIONS: In conclusion, neither inflammatory markers nor statin use was associated with risk of cerebrovascular events. Further studies are needed to understand the pathophysiology and prevention of stroke in patients on dialysis.

Association of residual urine output with mortality, quality of life, and inflammation in incident hemodialysis patients: the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease (CHOICE) Study.

BACKGROUND: Residual kidney function (RKF) is associated with improved survival in peritoneal dialysis patients, but its role in hemodialysis patients is less well known. Urine output may provide an estimate of RKF. The aim of our study is to determine the association of urine output with mortality, quality of life (QOL), and inflammation in incident hemodialysis patients. STUDY DESIGN: Nationally representative prospective cohort study. SETTING & PARTICIPANTS: 734 incident hemodialysis participants treated in 81 clinics; enrollment, 1995-1998; follow-up until December 2004. PREDICTOR: Urine output, defined as producing at least 250 mL (1 cup) of urine daily, ascertained using questionnaires at baseline and year 1. OUTCOMES & MEASUREMENTS: Primary outcomes were all-cause and cardiovascular mortality, analyzed using Cox regression adjusted for demographic, clinical, and treatment characteristics. Secondary outcomes were QOL, inflammation (C-reactive protein and interleukin 6 levels), and erythropoietin (EPO) requirements. RESULTS: 617 of 734 (84%) participants reported urine output at baseline, and 163 of 579 (28%), at year 1. Baseline urine output was not associated with survival. Urine output at year 1, indicating preserved RKF, was independently associated with lower all-cause mortality (HR, 0.70; 95% CI, 0.52-0.93; P = 0.02) and a trend toward lower cardiovascular mortality (HR, 0.69; 95% CI, 0.45-1.05; P = 0.09). Participants with urine output at baseline reported better QOL and had lower C-reactive protein (P = 0.02) and interleukin 6 (P = 0.03) levels. Importantly, EPO dose was 12,000 U/wk lower in those with urine output at year 1 compared with those without (P = 0.001). LIMITATIONS: Urine volume was measured in only a subset of patients (42%), but agreed with self-report (P < 0.001). CONCLUSIONS: RKF in hemodialysis patients is associated with better survival and QOL, lower inflammation, and significantly less EPO use. RKF should be monitored routinely in hemodialysis patients. The development of methods to assess and preserve RKF is important and may improve dialysis care.

Association of social support with outcomes in incident dialysis patients.

BACKGROUND AND OBJECTIVES: The association of social support with outcomes in ESRD, overall and by peritoneal dialysis (PD) versus hemodialysis (HD), remains understudied. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In an incident cohort of 949 dialysis patients from 77 US clinics, we examined functional social support scores (scaled 0 to 100 and categorized by tertile) both overall and in emotional, tangible, affectionate, and social interaction subdomains. Outcomes included 1-year patient satisfaction and quality of life (QOL), dialysis modality switching, and hospitalizations and mortality (through December 2004). Associations were examined using overall and modality-stratified multivariable logistic, Poisson, and Cox proportional hazards models. RESULTS: We found that mean social support scores in this population were higher in PD versus HD patients (overall 80.5 versus 76.1; P < 0.01). After adjustment, highest versus lowest overall support predicted greater 1-year satisfaction and QOL in all patients (odds ratio 2.47 [95% confidence interval (CI) 1.18 to 5.15] and 2.06 [95% CI 1.31 to 3.22] for recommendation of center and higher mental component summary score, respectively). In addition, patients were less likely to be hospitalized (incidence rate ratio 0.86; 95% CI 0.77 to 0.98). Results were similar with subdomain scores. Modality switching and mortality did not differ by social support in these patients, and associations of social support with outcomes did not generally differ by dialysis modality. CONCLUSIONS: Social support is important for both HD and PD patients in terms of greater satisfaction and QOL and fewer hospitalizations. Intervention studies to possibly improve these outcomes are warranted.

Spoken language development in children following cochlear implantation.

CONTEXT: Cochlear implantation is a surgical alternative to traditional amplification (hearing aids) that can facilitate spoken language development in young children with severe to profound sensorineural hearing loss (SNHL). OBJECTIVE: To prospectively assess spoken language acquisition following cochlear implantation in young children. DESIGN, SETTING, AND PARTICIPANTS: Prospective, longitudinal, and multidimensional assessment of spoken language development over a 3-year period in children who underwent cochlear implantation before 5 years of age (n = 188) from 6 US centers and hearing children of similar ages (n = 97) from 2 preschools recruited between November 2002 and December 2004. Follow-up completed between November 2005 and May 2008. MAIN OUTCOME MEASURES: Performance on measures of spoken language comprehension and expression (Reynell Developmental Language Scales). RESULTS: Children undergoing cochlear implantation showed greater improvement in spoken language performance (10.4; 95% confidence interval [CI], 9.6-11.2 points per year in comprehension; 8.4; 95% CI, 7.8-9.0 in expression) than would be predicted by their preimplantation baseline scores (5.4; 95% CI, 4.1-6.7, comprehension; 5.8; 95% CI, 4.6-7.0, expression), although mean scores were not restored to age-appropriate levels after 3 years. Younger age at cochlear implantation was associated with significantly steeper rate increases in comprehension (1.1; 95% CI, 0.5-1.7 points per year younger) and expression (1.0; 95% CI, 0.6-1.5 points per year younger). Similarly, each 1-year shorter history of hearing deficit was associated with steeper rate increases in comprehension (0.8; 95% CI, 0.2-1.2 points per year shorter) and expression (0.6; 95% CI, 0.2-1.0 points per year shorter). In multivariable analyses, greater residual hearing prior to cochlear implantation, higher ratings of parent-child interactions, and higher socioeconomic status were associated with greater rates of improvement in comprehension and expression. CONCLUSION: The use of cochlear implants in young children was associated with better spoken language learning than would be predicted from their preimplantation scores.

Inpatient hemodialysis initiation: reasons, risk factors and outcomes.

BACKGROUND/AIMS: Inpatient initiation of chronic hemodialysis is considered undesirable because of cost and possible harms of hospitalization. We examined the patient characteristics and outcomes associated with inpatient initiation. METHODS: In a prospective cohort study of incident dialysis patients, the independent association of inpatient hemodialysis initiation with patient outcomes was assessed in multivariable analyses with adjustment for patient characteristics and propensity for inpatient initiation. RESULTS: A total of 410 of 652 (63%) hemodialysis patients began as inpatients; uremia and volume overload were the most commonly documented reasons. Compared to outpatients, inpatients were more likely to be unmarried, report less social support, have multiple comorbidities and be referred to a nephrologist 4 months or less prior to initiation. Inpatient initiation was protective for subsequent all-cause hospitalization (incidence rate ratio (IRR) = 0.92, confidence interval (CI) 0.89-0.94); this was most pronounced among those who had the highest propensity for inpatient initiation (IRR = 0.66, CI 0.56-0.78), including those referred late to nephrology. Similar results were found for infectious hospitalization. Mortality [hazard ratio = 1.03, CI 0.82-1.30] and cardiovascular events were not significantly different for inpatients versus outpatients. CONCLUSION: Inpatient hemodialysis initiation has a protective association with hospitalization among those patients referred late to nephrology, with multiple comorbidities and/or little social support.

Correlates and outcomes of fatigue among incident dialysis patients.

BACKGROUND & OBJECTIVES: Fatigue is a debilitating symptom experienced by patients undergoing dialysis, but there is only limited information on its prevalence and its association with patient outcomes. This study examines the correlates of self-reported fatigue at initiation of dialysis and after 1 yr and assesses the extent to which fatigue was associated with health-related quality of life and survival. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A longitudinal cohort of 917 incident hemodialysis and peritoneal dialysis patients who completed the CHOICE Health Experience Questionnaire (CHEQ) participated in the study. Fatigue was assessed using the SF-36 vitality scale. Known predictors of fatigue including sociodemographic and psychosocial factors, dialysis-related factors, biochemical variables including inflammatory markers, comorbidities, and medications were used as covariates. RESULTS: A low vitality score was independently associated with white race, higher Index of Coexistent Disease score, higher body mass index, lack of physical exercise, antidepressant use, and higher C-reactive protein levels (CRP). A lower vitality score was strongly associated with lower SF-36 physical functioning, mental health, bodily pain scores, and decreased sleep quality (all P < 0.001) at baseline. Among surviving participants, higher serum creatinine at baseline was associated with preserved vitality at 1 yr. Patients with the highest baseline vitality scores were associated with longer survival (hazard ratio 0.75; 95% CI 0.58 to 0.96, P = 0.03). CONCLUSIONS: The findings of this study demonstrate that ESRD patients experience profound levels of fatigue and elucidate its correlates. Also, the association of fatigue with survival may have significant implications for this population.

Peripheral vascular disease-related procedures in dialysis patients: predictors and prognosis.

BACKGROUND AND OBJECTIVES: Peripheral vascular disease (PVD) is prevalent among dialysis patients, and many dialysis patients undergo PVD-related procedures. We aimed to examine the risk factors for and prognosis after such procedures in the dialysis setting. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a national prospective cohort study of 1041 incident dialysis patients, we examined the factors that are associated with PVD procedures (lower extremity amputations and bypasses) after the start of dialysis. Adjusted risk for PVD procedures of various factors was estimated using multivariable Cox proportional hazards models. Incidence rates of subsequent cardiovascular events, infectious hospitalizations, PVD- and cardiovascular disease-related mortality, and all-cause mortality were compared for those with and without a PVD procedure. RESULTS: Overall, 217 (21%) patients underwent a PVD procedure after the start of dialysis. For those without diabetes, only PVD history (relative hazard [RH] 2.9; 95% confidence interval [CI] 1.3 to 6.6) and increased fibrinogen (RH 1.2; 95% CI 1.0 to 1.5) predicted PVD procedures. For those with diabetes, increased serum phosphate (RH 1.2; 95% CI 1.1 to 1.4), along with decreased albumin, increased C-reactive protein and fibrinogen, and lower SBP, was associated with risk for PVD procedures. Of those who had a procedure compared with those who did not, 68 versus 30% experienced a subsequent cardiovascular event, 85 versus 66% an infectious hospitalization, 11 versus 2% a PVD-related death, and 81 versus 59% all-cause death (mean follow-up 3.0 yr). CONCLUSIONS: Prognosis after PVD procedures is poor, and providers should be aware that risk factors for PVD procedures may differ by diabetes status.

Association of peritoneal dialysis clinic size with clinical outcomes.

OBJECTIVE: Very few studies have addressed the relationship between number of peritoneal dialysis (PD) patients treated at a clinic (PD clinic size) and clinical outcomes. In a national prospective cohort study of incident PD patients (n = 236, from 26 clinics), we examined whether being treated at a larger PD clinic [>50 PD patients (n = 3 clinics) vs 50 patients was associated with fewer switches to hemodialysis (RH = 0.13, 95% CI 0.06 - 0.31) and fewer cardiovascular events (RH = 0.62, 95% CI 0.06 - 0.98). No associations of PD clinic size with cardiovascular or all-cause mortality were seen. CONCLUSION: PD patients treated at clinics with greater numbers of PD patients may have better outcomes in terms of technique failure and cardiovascular morbidity. PD clinic size may act as a proxy of greater PD experience, more focus on the modality, and better PD practices at the clinic, resulting in better outcomes.

Cerebrovascular disease incidence, characteristics, and outcomes in patients initiating dialysis: the choices for healthy outcomes in caring for ESRD (CHOICE) study.

BACKGROUND: Stroke is the third most common cause of cardiovascular disease death in patients on dialysis therapy; however, characteristics of cerebrovascular disease, including clinical subtypes and subsequent consequences, have not been well described. STUDY DESIGN: Prospective national cohort study, the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease (CHOICE) Study. SETTINGS & PARTICIPANTS: 1,041 incident dialysis patients treated in 81 clinics enrolled from October 1995 to July 1998, followed up until December 31, 2004. PREDICTOR: Time from dialysis therapy initiation. OUTCOMES & MEASUREMENTS: Cerebrovascular disease events were defined as nonfatal (hospitalized stroke and carotid endarterectomy) and fatal (stroke death) events after dialysis therapy initiation. Stroke subtypes were classified by using standardized criteria from the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) system. The incidence of cerebrovascular event subtypes was analyzed by using time-to-event analyses accounting for competing risk of death. Clinical outcomes after stroke were abstracted from medical records. RESULTS: 165 participants experienced a cerebrovascular event with an overall incidence of 4.9 events/100 person-years. Ischemic stroke was the most common (76% of all 200 events), with cardioembolism subtype accounting for 28% of the 95 abstracted ischemic events. Median time from onset of symptoms to first stroke evaluation was 8.5 hours (25th and 75th percentiles, 1 and 42), with only 56% of patients successfully escaping death, nursing home, or skilled nursing facility. LIMITATIONS: Relatively small sample size limits power to determine risk factors. CONCLUSIONS: Cerebrovascular disease is common in dialysis patients, is identified late, and carries a significant risk of morbidity and mortality. Stroke etiologic subtypes on dialysis therapy are multifactorial, suggesting risk factors may change the longer one has end-stage renal disease. Additional studies are needed to address the poor prognosis through prevention, early identification, and treatment.

Predicting behavior problems in deaf and hearing children: the influences of language, attention, and parent-child communication.

The development of language and communication may play an important role in the emergence of behavioral problems in young children, but they are rarely included in predictive models of behavioral development. In this study, cross-sectional relationships between language, attention, and behavior problems were examined using parent report, videotaped observations, and performance measures in a sample of 116 severely and profoundly deaf and 69 normally hearing children ages 1.5 to 5 years. Secondary analyses were performed on data collected as part of the Childhood Development After Cochlear Implantation Study, funded by the National Institutes of Health. Hearing-impaired children showed more language, attention, and behavioral difficulties, and spent less time communicating with their parents than normally hearing children. Structural equation modeling indicated there were significant relationships between language, attention, and child behavior problems. Language was associated with behavior problems both directly and indirectly through effects on attention. Amount of parent-child communication was not related to behavior problems.

Timing, causes, predictors and prognosis of switching from peritoneal dialysis to hemodialysis: a prospective study.

BACKGROUND: The use of peritoneal dialysis (PD) has declined in the United States over the past decade and technique failure is also reportedly higher in PD compared to hemodialysis (HD), but there are little data in the United States addressing the factors and outcomes associated with switching modalities from PD to HD. METHODS: In a prospective cohort study of 262 PD patients enrolled from 28 peritoneal dialysis clinics in 13 U.S. states, we examined potential predictors of switching from PD to HD (including demographics, clinical factors, and laboratory values) and the association of switching with mortality. Cox proportional hazards regression was used to assess relative hazards (RH) of switching and of mortality in PD patients who switched to HD. RESULTS: Among 262 PD patients, 24.8% switched to HD; with more than 70% switching within the first 2 years. Infectious peritonitis was the leading cause of switching. Patients of black race and with higher body mass index were significantly more likely to switch from PD to HD, RH (95% CI) of 5.01 (1.15-21.8) for black versus white and 1.09 (1.03-1.16) per 1 kg/m2 increase in BMI, respectively. There was no difference in survival between switchers and non-switchers, RH (95% CI) of 0.89 (0.41-1.93). CONCLUSION: Switching from PD to HD occurs early and the rate is high, threatening long-term viability of PD programs. Several patient characteristics were associated with the risk of switching. However, there was no survival difference between switchers and non-switchers, reassuring providers and patients that PD technique failure is not necessarily associated with poor prognosis.

The association of sudden cardiac death with inflammation and other traditional risk factors.

Despite the frequency of cardiovascular death in dialysis patients, few studies have prospectively measured sudden cardiac death in these individuals. Here, we sought to determine the frequency of sudden cardiac death and its association with inflammation and other risk factors among the CHOICE (Choices for Healthy Outcomes In Caring for ESRD) cohort of 1,041 incident dialysis patients. Sudden cardiac death was defined as that occurring outside of the hospital with an underlying cardiac cause from death certificate data. Over a median 2.5 years of follow-up, 22% of all mortality in this cohort was due to sudden cardiac death. Using Cox proportional hazards, we found that the highest tertiles of high-sensitivity C-reactive protein and of IL-6 were each associated with twice the risk of sudden cardiac death compared to their lowest tertiles when adjusted for demographics, comorbidities and laboratory factors. A decrement in serum albumin was associated with a 1.35 times increased risk for sudden cardiac death in the highest compared to the lowest tertile. These findings were robust and consistent when accounting for competing risks of death from other causes. Hence, we found that sudden cardiac death is common among patients with end stage renal disease and that inflammation and malnutrition significantly increased its occurrence independent of traditional cardiovascular risk factors.

MYH9 is associated with nondiabetic end-stage renal disease in African Americans.

As end-stage renal disease (ESRD) has a four times higher incidence in African Americans compared to European Americans, we hypothesized that susceptibility alleles for ESRD have a higher frequency in the West African than the European gene pool. We carried out a genome-wide admixture scan in 1,372 ESRD cases and 806 controls and found a highly significant association between excess African ancestry and nondiabetic ESRD (lod score = 5.70) but not diabetic ESRD (lod = 0.47) on chromosome 22q12. Each copy of the European ancestral allele conferred a relative risk of 0.50 (95% CI = 0.39-0.63) compared to African ancestry. Multiple common SNPs (allele frequencies ranging from 0.2 to 0.6) in the gene encoding nonmuscle myosin heavy chain type II isoform A (MYH9) were associated with two to four times greater risk of nondiabetic ESRD and accounted for a large proportion of the excess risk of ESRD observed in African compared to European Americans.

Heparin-induced antibodies and cardiovascular risk in patients on dialysis.

The clinical relevance of heparin-induced antibodies (HIA) in the absence of thrombocytopenia remains to be defined. The aims of this study were (i) to determine the prevalence of HIA in patients treated by dialysis, (ii) to determine the prevalence of thrombocytopenia and heparin-induced thrombocytopenia (HIT), and (iii) to test whether HIA are associated with adverse outcomes. Sera from 740 patients treated by hemodialysis (HD, n=596) and peritoneal dialysis (PD, n=144) were tested for HIA (IgG, IgA or IgM) by masked investigators at approximately six months after enrolment in the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease (CHOICE) study. We assessed, with time-to-event Cox proportional hazards models, whether the presence of HIA predicted any of four clinical outcomes: arterial cardiovascular events, venous thromboembolism, vascular access occlusion and mortality. HIA prevalence was 10.3% overall. HIA positivity did not predict development of thrombocytopenia or any of the four clinical outcomes over a mean follow-up of 3.6 years, with hazard ratios for arterial cardiovascular events of 0.98 (95% confidence interval 0.70-1.37), venous thromboembolism 1.39 (0.17-11.5), vascular access occlusion 0.82 (0.40-1.71), and mortality 1.18 (0.85-1.64). Chronic intermittent heparin exposure was associated with a high seroprevalence of HIA. In dialysis patients these antibodies were not an independent risk factor for cardiovascular events and mortality. Our data do not suggest that dialysis patients should be monitored for HIA antibodies in the absence of thrombocytopenia.

Lipoprotein(a) level as a predictor of cardiovascular disease and small apoliprotein(a) isoforms in dialysis patients: assay-related differences are important.

BACKGROUND: Lipoprotein(a) assays sensitive to apolipoprotein(a) size may underestimate associations of lipoprotein(a) with cardiovascular disease (CVD) and low molecular weight (LMW) apolipoprotein(a) isoforms. This study among 629 dialysis patients compares the value of two lipoprotein(a) assays in predicting CVD events and small isoforms. METHODS: Lipoprotein(a) level was measured by an apolipoprotein(a) size-insensitive ELISA and apolipoprotein(a) size-sensitive immunoturbidometric (IT) assay; and apolipoprotein(a) size by Western blot. Positive/negative predictive values (PPV/NPV) for small isoforms were calculated, and CVD events ascertained prospectively. RESULTS: The ELISA assay predicted CVD more strongly [Relative Hazard, RH=1.8; p=0.045, at the 85th Lipoprotein(a) percentile] than the IT assay (RH=1.3; p=0.37). The PPV for LMW isoforms using the ELISA (Whites, 98%; Blacks, 90%) were much higher than the IT assay (Whites, 75%; Blacks, 68%). Relative to the ELISA assay values, a positive bias in the IT assay values was seen for participants with larger apolipoprotein(a) isoforms, which may explain these findings. CONCLUSIONS: When measured by an apolipoprotein(a) size-insensitive ELISA assay, but not a size-sensitive IT assay, high lipoprotein(a) levels predict both incident CVD and LMW isoforms in dialysis patients. Clinicians ordering lipoprotein(a) levels and research studies of lipoprotein(a) should determine if an apolipoprotein(a)-size related bias is present in the assay they use.

Accuracy of patients' reports of comorbid disease and their association with mortality in ESRD.

BACKGROUND: Patient awareness of chronic diseases is low. Unawareness may represent poor understanding of chronic illness and may be associated with poor outcomes in patients with end-stage renal disease (ESRD). STUDY DESIGN: Concurrent prospective national cohort study. SETTING & PARTICIPANTS: Incident hemodialysis and peritoneal dialysis patients enrolled in the Choices for Healthy Outcomes in Caring for ESRD Study and followed up until 2004. PREDICTOR: Inaccurate patient self-report of 8 comorbid diseases compared with the medical record. OUTCOMES & MEASUREMENTS: All-cause mortality was the primary outcome. Cox proportional hazard models were used to assess the contribution of demographics and clinical measures in the relation of inaccurate self-report to mortality. RESULTS: In 965 patients, the proportion of inaccurate self-reporters ranged from 3% for diabetes mellitus to 35% for congestive heart failure. Generally, inaccurate self-reporters were older and had more chronic diseases. Greater risk of death was found for inaccurate self-reporters of ischemic heart disease (hazard ratio [HR], 1.34; 95% confidence interval, 1.12 to 1.59; P = 0.001), coronary intervention (HR, 1.46; 95% confidence interval, 1.08 to 1.97; P = 0.01), and chronic obstructive pulmonary disease (HR, 1.40; 95% confidence interval, 1.14 to 1.70; P = 0.001). The greater risk of death remained significant for chronic obstructive pulmonary disease (HR, 1.36; 95% confidence interval, 1.11 to 1.66; P = 0.003) after adjustment for age, sex, and race. In patients receiving peritoneal dialysis, greater risk of death (HR, 2.06; 95% confidence interval, 1.34 to 3.15; P = 0.001) was found for inaccurate self-reporters of ischemic heart disease. LIMITATIONS: Includes potential for residual confounding, medical record error, misclassification of patient accuracy of self-report, and low inaccurate self-report of some chronic diseases, reducing the power to measure associations. CONCLUSIONS: Accuracy of self-report depends on the specific comorbid disease. Patients with ESRD, especially those receiving peritoneal dialysis, who inaccurately report heart disease may be less aware of their chronic comorbid disease and may be at greater risk of mortality compared with those who accurately report their comorbid disease.

Phosphate levels and blood pressure in incident hemodialysis patients: a longitudinal study.

An elevated serum phosphate level in hemodialysis patients has been associated with mineral deposition in blood vessels. We studied a possible physiologic consequence of hyperphosphatemia by examining the relation between serum phosphate levels and blood pressure in 707 incident hemodialysis patients from 75 clinics who were enrolled in a prospective cohort study. We conducted cross-sectional and longitudinal multiple linear regression analyses, adjusting for demographics, medical history, and laboratory factors. In cross-sectional analyses at baseline, elevated serum phosphate was associated with higher predialysis systolic blood pressure (SBP) and pulse pressure (PP) at the start of dialysis; each 1 mg/dL higher phosphate level was associated with 1.77 mm Hg higher SBP. In multivariable adjusted longitudinal analyses, for each 1 mg/dL higher serum phosphate at baseline, SBP was higher at 3 months, 1.36 mm Hg (P = .005); 6 months, 1.13 mm Hg (P = .035); 12 months, 1.65 mm Hg (P = .008); 18 months, 1.44 mm Hg (P = .031); and 27 months, 2.54 mm Hg (P = .002). PP was higher at 3 months, 0.80 mm Hg (P = .027); 6 months, 0.91 mm Hg (P = .022); 12 months, 1.45 mm Hg (P < .001); 18 months, 1.06 mm Hg (P = .026); and 27 months, 1.37 mm Hg (P = .020). This study suggests that serum phosphate level is strongly and independently associated with blood pressure in hemodialysis patients. The effect of rigorous control of serum phosphate levels on arterial stiffness and blood pressure should be studied in clinical trials.

Serum phosphate levels and risk of infection in incident dialysis patients.

BACKGROUND AND OBJECTIVES: Hyperphosphatemia is highly prevalent in dialysis patients and may be associated with immune dysfunction. The association of serum phosphate level with infection remains largely unexamined. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In an incident cohort of 1010 dialysis patients enrolled from 1995 to 1998 and treated in 80 US clinics, the association of phosphate level (low <3.5; normal 3.5 to 5.5; high >5.5 mg/dl) at baseline and during follow-up with the risk for incident inpatient and outpatient infection-related events was examined. Infectious events were identified from US Renal Data System data (mean follow-up 3.3 yr). Incidence rate ratios for all infections, sepsis, respiratory tract infections, and osteomyelitis were obtained using multivariable Poisson models, adjusting for potential confounders (age, race, gender, smoking, comorbidity, and laboratory values). RESULTS: Infections of any type (n = 1398) were more frequent among patients with high phosphate levels at baseline, relative to normal; this association was not changed by adjustment for parathyroid hormone level. Similarly, high versus normal baseline phosphate was associated with increased risk for sepsis and osteomyelitis but not respiratory tract infections. Associations with calcium were generally NS, and results with calcium-phosphate product mirrored the phosphate results. CONCLUSIONS: High phosphate levels may be associated with increased risk for infection, contributing further to the rationale for aggressive management of hyperphosphatemia in dialysis patients.

Surgical factors in pediatric cochlear implantation and their early effects on electrode activation and functional outcomes.

OBJECTIVE: To assess the impact of surgical factors on electrode status and early communication outcomes in young children in the first 2 years of cochlear implantation. STUDY DESIGN: Prospective multicenter cohort study. SETTING: Six tertiary referral centers. PATIENTS: Children 5 years or younger before implantation with normal nonverbal intelligence. INTERVENTION: Cochlear implant operations in 209 ears of 188 children. MAIN OUTCOME MEASURES: Percent active channels, auditory behavior as measured by the Infant Toddler Meaningful Auditory Integration Scale/Meaningful Auditory Integration Scale and Reynell receptive language scores. RESULTS: Stable insertion of the full electrode array was accomplished in 96.2% of ears. At least 75% of electrode channels were active in 88% of ears. Electrode deactivation had a significant negative effect on Infant Toddler Meaningful Auditory Integration Scale/Meaningful Auditory Integration Scale scores at 24 months but no effect on receptive language scores. Significantly fewer active electrodes were associated with a history of meningitis. Surgical complications requiring additional hospitalization and/or revision surgery occurred in 6.7% of patients but had no measurable effect on the development of auditory behavior within the first 2 years. Negative, although insignificant, associations were observed between the need for perioperative revision of the device and 1) the percent of active electrodes and 2) the receptive language level at 2-year follow-up. CONCLUSION: Activation of the entire electrode array is associated with better early auditory outcomes. Decrements in the number of active electrodes and lower gains of receptive language after manipulation of the newly implanted device were not statistically significant but may be clinically relevant, underscoring the importance of surgical technique and the effective placement of the electrode array.

Assessing the use of speech and language measures in relation to parental perceptions of development after early cochlear implantation.

OBJECTIVE: Clinicians and investigators use multiple outcome measures after early cochlear implantation (CI) to assess auditory skills, speech, and language effects. Are certain outcome measures better associated with optimal childhood development from the perspective of parents? We studied the association between several commonly used outcome instruments and a measure of parental perceptions of development to gain insight into how our clinical tests reflect parental perceptions of a child's developmental status. STUDY DESIGN: Cross-sectional analysis. SETTING: Six academic centers. PATIENTS: One hundred eighty-eight deaf children (<6 yr) 1 year after CI activation enrolled in the longitudinal Childhood Development after CI study. MAIN OUTCOME MEASURES: Measures of auditory skills, speech, and language. Parental perceptions of development quantified with a visual analogue scale (visual analogue scale-development). METHODS: Nonparametric and parametric regression methods were used to model the relationship between outcome measures and visual analogue scale-development scores. RESULTS: All outcome measures were positively associated with parental perceptions of development, but more robust associations were observed with language measures and a parent-report scale of auditory skills than with a selected measure of closed-set speech. For speech and language data, differences were observed in the trajectories of associations among younger (2-3 yr) versus older (4-5 yr) children. CONCLUSION: Our results demonstrate the importance of measuring multiple outcome measures after early pediatric CI. The degree to which an outcome measure reflects childhood development as perceived by parents may be affected by the child's age. Measures that are based on parental report and broader outcome measures focused on verbal language offer the potential for a fuller understanding of the true effectiveness of early implantation.