Assessing the impact of next-generation rapid diagnostic tests on Plasmodium falciparum malaria elimination strategies.

Mass-screen-and-treat and targeted mass-drug-administration strategies are being considered as a means to interrupt transmission of Plasmodium falciparum malaria. However, the effectiveness of such strategies will depend on the extent to which current and future diagnostics are able to detect those individuals who are infectious to mosquitoes. We estimate the relationship between parasite density and onward infectivity using sensitive quantitative parasite diagnostics and mosquito feeding assays from Burkina Faso. We find that a diagnostic with a lower detection limit of 200 parasites per microlitre would detect 55% of the infectious reservoir (the combined infectivity to mosquitoes of the whole population weighted by how often each individual is bitten) whereas a test with a limit of 20 parasites per microlitre would detect 83% and 2 parasites per microlitre would detect 95% of the infectious reservoir. Using mathematical models, we show that increasing the diagnostic sensitivity from 200 parasites per microlitre (equivalent to microscopy or current rapid diagnostic tests) to 2 parasites per microlitre would increase the number of regions where transmission could be interrupted with a mass-screen-and-treat programme from an entomological inoculation rate below 1 to one of up to 4. The higher sensitivity diagnostic could reduce the number of treatment rounds required to interrupt transmission in areas of lower prevalence. We predict that mass-screen-and-treat with a highly sensitive diagnostic is less effective than mass drug administration owing to the prophylactic protection provided to uninfected individuals by the latter approach. In low-transmission settings such as those in Southeast Asia, we find that a diagnostic tool with a sensitivity of 20 parasites per microlitre may be sufficient for targeted mass drug administration because this diagnostic is predicted to identify a similar village population prevalence compared with that currently detected using polymerase chain reaction if treatment levels are high and screening is conducted during the dry season. Along with other factors, such as coverage, choice of drug, timing of the intervention, importation of infections, and seasonality, the sensitivity of the diagnostic can play a part in increasing the chance of interrupting transmission.

External validation of prediction models for mortality in an incident dialysis population
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AIMS: Different prediction models have been established to estimate mortality in the dialysis population. This study aims to externally validate the different available mortality prediction models in an incident dialysis population. MATERIALS: This was a retrospective cohort study of incident hemodialysis and peritoneal dialysis patients at two academic tertiary care centers. METHODS: Three previously published prediction models were used: the Liu index, the Urea5 score, and a predictive model estimating the survival probability by Hemke et al. [6]. Models were compared using the C-statistic, net reclassification index, and integrated discrimination improvement. Only the subgroup of 193 patients with enough data to be included in all models was used. RESULTS: 377 patients were started on dialysis in both institutions between 2006 and 2011. Median follow-up was 787 days. 104 patients (27.6%) died during follow-up and 181 were admitted to the hospital (48.0%). All three models were predictive of mortality and hospital admissions. The survival probability model by Hemke et al. [6] performed better than the other two models for mortality (C-statistic 0.72). The Liu index had the highest performance for hospital admissions (C-statistic 0.65). Using reclassification statistics (reference = Urea5), the only model to improve discriminatory ability was the Liu index for the outcome of hospital admission. CONCLUSION: The survival probability model by Hemke et al. [6] may be preferred for mortality prediction in incident dialysis patients. The Liu index could be used to predict hospital admissions in the same population. Available models demonstrated only modest performance in predicting either outcome. Therefore, alternative models need to be developed.
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Serial versus single troponin measurements for the prediction of cardiovascular events and mortality in stable chronic haemodialysis patients.

AIM: This study aims to describe the variability of pre-dialysis troponin values in stable haemodialysis patients and compare the performance of single versus fluctuating or persistently elevated troponins in predicting a composite of mortality and cardiac arrest, myocardial infarction or stroke. METHODS: A total of 128 stable ambulatory chronic haemodialysis patients were enrolled. Pre-dialysis troponin I was measured for three consecutive months. The patients were followed for 1 year. A troponin elevation (>0.06 µg/L) was considered high risk, and patients were classified into three risk groups: (i) patients who had normal troponin levels on all three measurements; (ii) patients with at least one elevated and one normal troponin value; and (iii) patients with elevated troponin values on all measurements. RESULTS: A total of 81 patients had all three troponin values in the normal range; 29 had fluctuating values; 18 had all three values elevated. Twenty-seven deaths or composite events were observed: eight in the first risk group, 10 in the second and nine in the third. Persistently elevated and fluctuating troponin values were associated with higher mortality and cardiovascular event rate. Serial troponin measurement had a higher sensitivity for the composite outcome than single troponin measurement when either fluctuating or persistently elevated values were considered to confer high risk. CONCLUSION: Most haemodialysis patients do not have elevated troponin levels at baseline. Troponin levels that remain elevated or fluctuate are associated with worse outcomes. A serial troponin measurement strategy is associated with better sensitivity and higher negative predictive value compared with single troponin measurement.

High Ultrafiltration Rates Increase Troponin Levels in Stable Hemodialysis Patients.

BACKGROUND: An elevated troponin level is commonly found in asymptomatic patients on hemodialysis (HD) and is associated with higher risk of mortality and major adverse cardiovascular events. The underlying mechanism for the association between adverse outcomes and elevated troponin levels has not been elucidated. METHODS: Two hundred thirty-six stable chronic HD patients from 2 tertiary care centers were enrolled in this study. We measured pre-dialysis troponin I levels with routine monthly bloods for 3 consecutive months. Troponin I was considered to be elevated if it exceeded the laboratory reference range of 0.06 µg/l. RESULTS: The study population had a mean age of 67.5, 56% were male, 47% had diabetes and 28% had pre-existing coronary artery disease. Eighty-eight positive troponin values were recorded (13% of the available values) in 52 patients. In a repeated measures linear random effects model (univariate analysis), high ultrafiltration (UF), high inter-dialytic weight gain, and duration of the dialysis session, but not intra-dialytic hypotension, were associated with troponin I elevation. In the multivariate model, only high UF explained troponin I elevation (p = 0.04). The intraclass correlation coefficient was found to be 5.8%, suggesting that observed variability is within and not between subjects, with session-related parameters being more important than inter-individual differences. CONCLUSIONS: A high UF rate during HD is associated with a biochemical evidence of myocardial injury. If confirmed, efforts to avoid rapid UF, protect residual kidney function or minimize weight gain between sessions may impact cardiovascular outcomes in this high-risk population.

Prevention of dialysis catheter malfunction with recombinant tissue plasminogen activator.

BACKGROUND: The effectiveness of various solutions instilled into the central venous catheter lumens after each hemodialysis session (catheter locking solutions) to decrease the risk of catheter malfunction and bacteremia in patients undergoing hemodialysis is unknown. METHODS: We randomly assigned 225 patients undergoing long-term hemodialysis in whom a central venous catheter had been newly inserted to a catheter-locking regimen of heparin (5000 U per milliliter) three times per week or recombinant tissue plasminogen activator (rt-PA) (1 mg in each lumen) substituted for heparin at the midweek session (with heparin used in the other two sessions). The primary outcome was catheter malfunction, and the secondary outcome was catheter-related bacteremia. The treatment period was 6 months; treatment assignments were concealed from the patients, investigators, and trial personnel. RESULTS: A catheter malfunction occurred in 40 of the 115 patients assigned to heparin only (34.8%) and 22 of the 110 patients assigned to rt-PA (20.0%)--an increase in the risk of catheter malfunction by a factor of almost 2 among patients treated with heparin only as compared with those treated with rt-PA once weekly (hazard ratio, 1.91; 95% confidence interval [CI], 1.13 to 3.22; P = 0.02). Catheter-related bacteremia occurred in 15 patients (13.0%) assigned to heparin only, as compared with 5 (4.5%) assigned to rt-PA (corresponding to 1.37 and 0.40 episodes per 1000 patient-days in the heparin and rt-PA groups, respectively; P = 0.02). The risk of bacteremia from any cause was higher in the heparin group than in the rt-PA group by a factor of 3 (hazard ratio, 3.30; 95% CI, 1.18 to 9.22; P = 0.02). The risk of adverse events, including bleeding, was similar in the two groups. CONCLUSIONS: The use of rt-PA instead of heparin once weekly, as compared with the use of heparin three times a week, as a locking solution for central venous catheters significantly reduced the incidence of catheter malfunction and bacteremia. (Current Controlled Trials number, ISRCTN35253449.).

Elevated troponin I levels but not low grade chronic inflammation is associated with cardiac-specific mortality in stable hemodialysis patients.

BACKGROUND: Elevated cardiac troponin I (TnI) levels are associated with all-cause mortality in stable hemodialysis patients. Their relationship to cardiac-specific death has been inconsistent, and the reason for their elevation is not well understood. We hypothesized that elevated TnI levels in chronic stable hemodialysis patients more specifically track with cardiac mortality, and this mechanism is independent of other contributors of cardiac mortality, such as inflammation. METHODS: We conducted a single-centre, cohort study of prevalent hemodialysis patients at a tertiary care hospital. Plasma TnI levels were measured with routine monthly blood tests in clinically stable patients for two consecutive months. Plasma TnI was measured by immunoassay and a value above the laboratory reference range (0.06 µg/L) was considered elevated. The primary outcome of death was adjudicated separately for this study, and classified as cardiac, non-cardiac, or unknown. Cox proportional hazard models were used to examine the association of TnI with the all-cause and cardiac-specific mortality, adjusting for potential confounders, including C-reactive protein (CRP) as a marker of inflammation. RESULTS: Of 133 patients followed for a median of 1.7 years, there were 38 deaths (58% non-cardiac, 39% cardiac, 3% unknown). Elevated TnI was associated with adjusted HR for all-cause mortality of 2.57 (95% CI 1.30-5.09) and an adjusted HR for cardiac death of 3.14 (95% CI 1.07-9.2), after accounting for age, time on dialysis, diabetes status, prior coronary artery disease history, and C-reactive protein. Although CRP was also independently associated with all-cause mortality, it did not add prognostic information to TnI for cardiac-specific death. CONCLUSION: Elevated TnI levels are independently associated with cardiac and all-cause mortality in asymptomatic hemodialysis patients. The mechanism for this risk is likely independent of inflammation, but may reflect chronic subclinical myocardial injury or unmask those with subclinical atherosclerotic heart disease. Whether those with elevated TnI levels may benefit from additional investigations or more aggressive therapies to treat cardiovascular disease remains to be determined.

Vascular access-related bloodstream infections in First Nations, community and teaching Canadian dialysis units, and other centre-level predictors.

BACKGROUND/AIMS: Vascular access-related bloodstream infection (BSI) is frequent among patients undergoing hemodialysis increasing their morbidity and mortality, but its occurrence across various dialysis centre types is not known. The aims of this study were to describe the incidence rates and assess the variability in BSI risk between dialysis centre types and other centre-level variables. METHODS: We conducted a retrospective cohort study of 621 patients initiating hemodialysis in 7 Canadian dialysis centres. Cox regression models, where access type was continuously updated, were used to identify predictors of BSI occurrence. RESULTS: During follow-up of the cohort (median age 68.1 years, 41.7% female, and 76.7% initiating with a central venous catheter, CVC), 73 patients had a BSI (rate: 0.21/1000 person-days). The BSI risk was not different in First Nation units (adjusted relative risk: 0.47, 95% confidence interval: 0.06-3.72) and teaching hospitals (1.33, 0.70-2.54) compared to community hospitals. No other centre-related variables were associated with the risk of BSI. CONCLUSION: We did not find differences in the BSI risk among dialysis unit types, or any other centre-related variables. The rates of BSI in our population were lower than those observed in other settings, but the high proportion of patients using CVCs is concerning.

A prospective evaluation of renal replacement therapy modality eligibility.

BACKGROUND: Patient eligibility for renal replacement therapy (RRT) modalities is frequently debated, but little prospective data are available from large patient cohorts. METHODS: We prospectively evaluated medical and psychosocial eligibility for the three RRT modalities in patients with chronic kidney disease (CKD) stages III-V who were enrolled in an ongoing prospective cohort study conducted at seven North American nephrology practices. RESULTS: Ninety-eight percent of patients were considered medically eligible for haemodialysis (HD), 87% of patients were assessed as medically eligible for peritoneal dialysis (PD) and 54% of patients were judged medically eligible for transplant. Age was the leading cause of non-eligibility for both PD and transplant. Anatomical concerns (adhesions, hernias) were the second most frequent concern for PD eligibility followed by weight. Weight was also a concern for transplant eligibility. The proportion of patients medically eligible for RRT did not vary by CKD stage. There was, however, significant inter-centre variation in the proportion of patients medically eligible for PD and transplant. Ninety-five percent of patients were considered psychosocially eligible for HD, 83% of patients were assessed as psychosocially eligible for PD and 71% of patients were judged psychosocially eligible for transplant. The percentage of patients who were assessed as having neither medical nor psychosocial contraindications for RRT was 95% for HD, 78% for PD and 53% for transplant. CONCLUSIONS: Most CKD patients are considered by their medical care providers to be suitable for PD. Enhanced patient education, promotion of home dialysis for suitable patients and empowerment of patient choice are expected to augment growth of home dialysis modalities.

Perceived knowledge among patients cared for by nephrologists about chronic kidney disease and end-stage renal disease therapies.

The need to educate patients in order to enable them to participate in making appropriate choices for all therapeutic options in end stage renal disease would seem obvious yet there are many barriers to providing such information. We measured 'perceived knowledge' of the therapeutic options for end stage renal disease in a cohort of patients with chronic kidney disease in established treatment programs. A self administered questionnaire was given to 676 patients with stage 3-5 chronic kidney disease as part of the CRIOS study designed to identify trends in practice patterns and outcomes over a 4 year period. The median patient age was 66, about three-fourths were Caucasian and almost half were diabetic. When patients were asked to rate their level of knowledge, about one-third reported limited or no understanding of their chronic kidney disease and no awareness regarding their treatment options. A significant and substantial number of patients indicated they had no familiarity with transplant, hemodialysis, and continuous ambulatory or automated peritoneal dialysis. Perceived knowledge improved with the progression of kidney disease and frequency of nephrology visits; however, only about half of patients with 4 or more nephrology appointments in the prior year reported knowing of hemodialysis, continuous ambulatory peritoneal dialysis or transplant. Age, gender and disease had no impact on levels of patient knowledge, but African-Americans reported having significantly less understanding than Asians or Caucasians. These findings suggest that the lack of perception concerning the treatment options chronic kidney and end stage renal disease reflects, in part, problems with the education of patients by nephrologists and not a lack of referral of these patients to nephrologists for care. The discrepancy of perceived knowledge between African-Americans and other races needs special attention.

Correlation between physical functioning and sleep disturbances in hemodialysis patients.

The study set out to investigate the relationship between physical functioning, inflammatory status, and sleep disturbance in a chronic hemodialysis (HD) population. Forty-six maintenance HD patients from the McGill University Health Centre were enrolled in this study between October 2005 and 2006. The well-validated Human Activity Profile (HAP) questionnaire and the RAND 36-item survey were used to assess physical functioning. Subjects were given the Pittsburgh Sleep Quality Index (PSQI) survey to evaluate the degree of sleep disturbance. Inflammatory status was assessed with the average value of serial C-reactive protein (CRP) levels for each patient, over a period of 12 months before their enrollment in the study. A multivariate logistic regression model was created for these analyses to control for potential confounders, including dialysis adequacy, inflammation, and hemoglobin. Seventy-six percent of the study population had poor sleep as per the Pittsburgh Sleep Quality Index (PSQI score > or = 5). In addition, 65% of subjects had high CRP values (>5 mg/L). On univariate analysis, both a CRP >5 mg/L and a lower adjusted activity score (AAS) on the HAP were significantly associated with poor sleep (PSQI score > or = 5). Multivariate logistic analysis demonstrated that the AAS remained significantly associated with poor sleep, with a 6% decrease in the odds of poor sleep for each score increase in the AAS of the HAP. Poor physical functioning in chronic HD patients, as measured by the HAP, is associated with sleep disturbance, after controlling for inflammation and dialysis adequacy.

The Impact of Intradialytic Pedaling Exercise on Arterial Stiffness: A Pilot Randomized Controlled Trial in a Hemodialysis Population.

OBJECTIVES: Regular exercise is known to reduce arterial stiffness (AS) in hemodialysis patients. However, the impact of a more realistic intradialytic form of exercise, such as pedaling, is unclear. We aimed to examine (i) the effect of intradialytic pedaling exercise on AS over 4 months and (ii) the longer term effect of pedaling on AS 4 months after exercise cessation. METHODS: Patients on stable in-center hemodialysis (3 x/week) were randomly assigned 1:1 to either intradialytic pedaling exercise (EX) or to a control group receiving usual hemodialysis (nonEX) for 4 months. At baseline and 4 months, peripheral and central blood pressure (BP) indices, heart rate (HR), augmentation index HR corrected (AIx75), and carotid-femoral pulse wave velocity (cfPWV) were assessed (applanation tonometry). Measurements were repeated in the EX group 4 months postexercise cessation. RESULTS: As per protocol analysis was completed in 10 EX group participants (58 ± 17 years, body mass index 26 ± 4 kg/m2) and 10 nonEX group participants (53 ± 15 years, body mass index 27 ± 6 kg/m2). Peripheral and central BP was unchanged in both groups. AIx75 was unchanged in the EX group, however, a significant median increase of 3.5% [interquartile range, IQR 1.0, 8.5] was noted in the nonEX group (P = 0.009). We noted a significantly greater absolute decrease in cfPWV in the EX group compared to controls: -1.00 [IQR -1.95, 0.05] vs. 0.20 [IQR -0.10, 0.90] (P = 0.033). Interestingly, the decrease in cfPWV observed in the EX group was partially reversed 4 months after exercise cessation. CONCLUSION: Intradialytic pedaling exercise has a beneficial impact on AS. This relationship warrants further investigation. CLINICAL TRIALS REGISTRATION: Trial Number #NCT03027778 (clinicaltrials.gov).

Predialysis psychoeducational intervention extends survival in CKD: a 20-year follow-up.

BACKGROUND: Predialysis psychoeducational interventions increase patient knowledge about chronic kidney disease (CKD) and its treatment and extend time to dialysis therapy without compromising physical well-being in the short run. The present research examines long-term survival after predialysis psychoeducational intervention. In addition, we examined whether survival differed because of early (ie, > or = 3 months) versus late referral to nephrology. METHODS: We collected follow-up data for patients with CKD who participated in a multicenter randomized controlled trial of predialysis psychoeducational interventions in the mid-1980s. We gathered 20-year survival data from clinical records and databases. RESULTS: Participants included 335 patients with CKD, including 172 patients randomly assigned to receive predialysis psychoeducational interventions (63.0% men; mean age, 50.8 years) and 163 patients assigned to usual care (62.1% men; mean age, 52.7 years). Two hundred forty-six patients (66.8%) died during the course of the study. Mean duration of follow-up was 8.5 +/- 7.23 (SD) years. Analyses were by intention to treat. Adjusting for age, general nonrenal health at inception, and time between identification and predialysis psychoeducational intervention or usual care, Cox proportional hazards multiple regression analyses indicated that median survival was 2.25 years longer after patients with CKD received predialysis psychoeducational interventions compared with usual care (chi-square-change [1] = 3.75; P = 0.053; hazard ratio, 1.32; 95% confidence interval, 1.0 to 1.74). Predialysis psychoeducational intervention recipients survived a median of 8.0 months longer than usual-care patients after the initiation of dialysis therapy (chi-square-change [1] = 4.39; P = 0.036; hazard ratio, 1.35; 95% confidence interval, 1.02 to 1.775). No significant survival advantage was evident for early referral to nephrology or the combination of early referral plus predialysis psychoeducational interventions. CONCLUSION: Predialysis psychoeducational intervention is a safe and useful intervention that contributes valuably to multidisciplinary predialysis care.

Canadian randomized trial of hemoglobin maintenance to prevent or delay left ventricular mass growth in patients with CKD.

BACKGROUND: This randomized clinical trial is designed to assess whether the prevention and/or correction of anemia, by immediate versus delayed treatment with erythropoietin alfa in patients with chronic kidney disease, would delay left ventricular (LV) growth. Study design and sample size calculations were based on previously published Canadian data. METHODS: One hundred seventy-two patients were randomly assigned. The treatment group received therapy with erythropoietin alfa subcutaneously to maintain or achieve hemoglobin (Hgb) level targets of 12.0 to 14.0 g/dL (120 to 140 g/L). The control/delayed treatment group had Hgb levels of 9.0 +/- 0.5 g/dL (90 +/- 5 g/L) before therapy was started: target level was 9.0 to 10.5 g/dL (90 to 105 g/L). Optimal blood pressure and parathyroid hormone, calcium, and phosphate level targets were prescribed; all patients were iron replete. The primary end point is LV growth at 24 months. RESULTS: One hundred fifty-two patients were eligible for the intention-to-treat analysis: mean age was 57 years, 30% were women, 38% had diabetes, and median glomerular filtration rate was 29 mL/min (0.48 mL/s; range, 12 to 55 mL/min [0.20 to 0.92 mL/s]). Blood pressure and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use were similar in the control/delayed treatment and treatment groups at baseline. Erythropoietin therapy was administered to 77 of 78 patients in the treatment group, with a median final dose of 2,000 IU/wk. Sixteen patients in the control/delayed treatment group were administered erythropoietin at a median final dose of 3,000 IU/wk. There was no statistically significant difference between groups for the primary outcome of mean change in LV mass index (LVMI) from baseline to 24 months, which was 5.21 +/- 30.3 g/m2 in the control/delayed treatment group versus 0.37 +/- 25.0 g/m2 in the treatment group. Absolute mean difference between groups was 4.85 g/m2 (95% confidence interval, -4.0 to 13.7; P = 0.28). Mean Hgb level was greater in the treatment group throughout the study and at study end was 12.75 g/dL (127.5 g/L in treatment group versus 11.46 g/dL [114.6 g/L] in control/delayed treatment group; P = 0.0001). LV growth occurred in 20.1% in the treatment group versus 31% in the control/delayed treatment group (P = 0.136). In patients with a stable Hgb level, mean LVMI did not change (-0.25 +/- 26.7 g/m2), but it increased in those with decreasing Hgb levels (19.3 +/- 28.2 g/m2; P = 0.002). CONCLUSION: This trial describes disparity between observational and randomized controlled trial data: observed and randomly assigned Hgb level and LVMI are not linked; thus, there is strong evidence that the association between Hgb level and LVMI likely is not causal. Large randomized controlled trials with unselected patients, using morbidity and mortality as outcomes, are needed.

Cobalamin dose regimen for maximum homocysteine reduction in end-stage renal disease.

Plasma total homocysteine (tHcy) concentrations are markedly increased in end-stage renal disease and only partially corrected by folic acid supplementation. We and others have reported that cobalamin, administered parenterally, reduces plasma tHcy substantially below the lowest concentrations attainable with folic acid. We have now carried out a randomized controlled clinical trial to compare the plasma Hcy-lowering effect of 3 intravenous cyanocobalamin dose regimens in maintenance hemodialysis patients: 1 mg postdialysis every 28, 14, and 7 days in addition to routine oral vitamin B supplementation. All patients in the hemodialysis unit where the study was carried out routinely received 1 mg intravenous cyanocobalamin every month, so participants who were randomized to receive the vitamin every 28 days simply continued with their existing treatment program. Serum cobalamin and plasma tHcy concentrations in the control group did not change over the course of the study. As measured after 8 weeks of therapy, intravenous cyanocobalamin every 14 days increased serum cobalamin approximately 2.5-fold and reduced plasma tHcy by 11.5% ( P = .035) below the concentration previously attained with monthly administration, whereas treatment every 7 days increased serum cobalamin concentrations approximately 5-fold and reduced plasma tHcy by 11.0% ( P = .013). These results show that intravenous cyanocobalamin at 7- or 14-day intervals reduces plasma tHcy concentrations of hemodialysis patients below the levels brought about by prior long-term administration every 4 weeks and confirms that plasma tHcy lowering with parenteral cobalamin is a true pharmacological effect and not merely correction of a latent deficiency state.

Renoprotective effects of continuous positive airway pressure in chronic kidney disease patients with sleep apnea.

PURPOSE: Chronic kidney disease (CKD) is associated with a high incidence of obstructive sleep apnea (OSA). We assessed the effect of continuous positive airway pressure (CPAP) on renal function in patients with CKD and OSA. METHODS: In this retrospective cohort study, 42 patients with Stage 3-5 CKD and OSA were stratified into two groups: patients who use CPAP more (average >4 h/night on >70 % of nights) and patients who use CPAP less (average ≤4 h/night on ≤70 % of nights). Median follow-up time was 2.3 (1.6-2.9) years for greater and 2.0 (0.6-3.5) years for lesser CPAP users. Chart reviews were carried out to record clinical characteristics, proteinuria measurements by urine dipstick, and eGFR values calculated by CKD-EPI equations. Univariate analyses were performed using Wilcoxon rank-sum and Kruskal-Wallis tests. Multivariate logistic regression models were applied to assess eGFR decline after CPAP prescription. RESULTS: Twelve (29 %) of the 42 subjects used CPAP more. Groups were similar with respect to age, body mass index, blood pressure, Charlson Comorbidity Index, and baseline eGFR and proteinuria. The median rate of decline of eGFR was significantly slower at -0.07 mL/min/1.73 m(2)/year (range -30 to 13) in those who used more CPAP compared to those who used it less at -3.15 mL/min/1.73 m(2)/year (range -27 to 7) (p = 0.027).Greater use of CPAP was also associated with a significantly reduced level of proteinuria at 0.15 (range 0.0-3.0) versus 0.70 g/L (range 0.0-3.0) (p = 0.046). Less compliant CPAP users were more likely to have progressive decline of eGFR (decline >3 mL/min/1.73 m(2)/year), with unadjusted OR 5.0 (95 % CI 0.93-26.8) and adjusted OR 8.9 (95 % CI 1.1-72.8), adjusting for CCI and baseline eGFR. CONCLUSIONS: Compliance to CPAP therapy is associated with a slower rate of progression of CKD in patients with CKD and OSA.

Fragmented care and whole-person illness: Decision-making for people with chronic end-stage kidney disease.

PURPOSE: The study reported herein sought to better understand how patients with multi-morbid, chronic illness-who receive care in institutions designed for treatment of acute illness-experience and engage in health-related decisions. METHODS: In an urban Canadian teaching hospital, we studied the interactions of six hemodialysis patients and 11 of the health professionals involved in their care. For 1 year (September 2009 to September 2010), we conducted ethnographic observation and interviews of six cases each comprising one hemodialysis patient and various health professionals including medical specialists, nurses, a social worker, and a dietician. RESULTS: We found that the ubiquity and complexity of health-related decision-making in the lives of these patients suggests the need for a more holistic interpretation of health-related decision-making. DISCUSSION: We propose an interpretation of decision-making as an ongoing process of integrating illness and life; as frequently open-ended, cumulative, and relational; and as fundamentally shaped by the fragmented delivery of care for patients with multiple morbidities. CONCLUSION: Our understanding of decision-making suggests that people living with complex chronic illness need to receive care from institutions that recognize and address their multi-morbidity as a whole illness that is constantly being integrated into the life of a whole person.

Predialysis psychoeducational intervention and coping styles influence time to dialysis in chronic kidney disease.

BACKGROUND: Consensus endorses predialysis intervention before the onset of end-stage renal disease. In a previous study, predialysis psychoeducational intervention (PPI) extended time to dialysis therapy by a median of 6 months. We undertook to replicate and extend this finding by examining hypothesized mechanisms. METHODS: We used an inception-cohort, prospective, randomized, controlled trial with follow-up to evaluate an intervention that included an interactive 1-on-1 slide-supported educational session, a printed summary (booklet), and supportive telephone calls once every 3 weeks. Participants were sampled from 15 Canadian (tertiary care) nephrology units and included 297 patients with progressive chronic kidney disease (CKD) expected to require renal replacement therapy (RRT) within 6 to 18 months. The main outcome was time to dialysis therapy (censored at 18 months if still awaiting RRT). RESULTS: Time to dialysis therapy was significantly longer (median, 17.0 months) for the PPI group than the usual-care control group (median, 14.2 months; Cox's proportional hazards analysis, controlling for general nonrenal health, P < 0.001). Coping by avoidance of threat-related information (called blunting) was associated with shorter times to dialysis therapy (P < 0.032). A group x blunting interaction (P < 0.069) indicated: (1) time to dialysis therapy was shortened in the usual-care group, especially when patients coped by blunting; but (2) time to dialysis therapy was extended with PPI, even among patients who coped by blunting. Knowledge acquisition predicted time to dialysis therapy (r = 0.14; P < 0.013). Time to dialysis therapy was unrelated to depression or social support. CONCLUSION: PPI extends time to dialysis therapy in patients with progressive CKD. The mechanism may involve the acquisition and implementation of illness-related knowledge. Routine follow-up also may be especially important when patients cope by avoiding threat-related information.

Convergence of health ratings across nephrologists, nurses, and patients with end-stage renal disease.

We evaluated a health rating for renal failure patients that was completed by patients, nurses, and nephrologists. The study was a prospective inception-cohort follow-up design. Measurements were taken before initiating dialysis (n=206) or at the initiation of dialysis (n=200) and at 18 (n=225), 30 (n=181), 42 (n=162), 54 (n=137), and 66 (n=112) months after initiating dialysis. Patients, nurses, and nephrologists independently rated patients' health at each measurement occasion. Objective measures of health status, abstracted from the medical record, included emergency and non-emergency admissions, smoking, diabetes mellitus, pulmonary edema, history and number of myocardial infarctions (MI), basal rales, comorbid illnesses, and uremic symptoms. Simultaneous multiple regression analyses examined the correspondence between objective measures of health status and subjective health ratings separately for each rater and measurement occasion. Health ratings were averaged and submitted to the same analyses. Raters showed good agreement (average Pearson r=.43 overall), although agreement was higher between nephrologists and nurses (average r=.64) than between health professional and patients (average r=.34 and .31, respectively). All three ratings and the combined rating corresponded significantly to objective measures of health status. Uremic symptoms, emergency hospital admissions, diabetes mellitus, and recent MI correlated uniquely and most consistently with subjective health ratings. Despite overall convergence, objective measures of health status related to the groups' ratings in a complementary fashion. The health rating is reliable and relates to the current status of the patient. Performance was superior for the combined score that incorporated ratings by patients, nurses, and nephrologists.

Effects of reuse and bleach/formaldehyde reprocessing on polysulfone and polyamide hemodialyzers.

The surface features, morphology, and blood interactions of fibers from pristine, bleach/formaldehyde reprocessed, and reused Fresenius Polysulfone High Flux (Hemoflow F80B) hemodialyzers and Gambro Polyflux 21S Polyamide hemodialyzers have been studied. SEM images of fibers from both hemodialyzer types revealed a dense skin layer on the inner surface and a relatively thick porous layer on the outer surface. The 21S polyamide support layer consisted of interconnected highly porous structures. Environmental scanning electron microscopy and atomic force microscopy images of both membrane types showed alterations in morphology due to reprocessing and reuse; however the changes were more marked for the 21S polyamide dialyzers. Fluorescence microscopy images showed only minimal fluorescence associated with the fibers after patient use and reprocessing, suggesting that blood derived deposits were removed by processing. The protein layers formed on pristine and reused hemodialyzer membranes during clinical use were studied using SDS-PAGE and immunoblotting. Before bleach/formaldehyde treatment, protein layers of considerable amount and complexity were found on the blood side of singly and multiply used dialyzers. Proteins adsorbed on the dialysate side were predominantly in the molecular mass region below 30 kDa. However, some higher molecular mass proteins were detected on the dialysate side of the 21 S polyamide dialyzers. Very little protein was detected on dialyzers that were treated with bleach/formaldehyde after dialysis, regardless of whether they had been used/reprocessed once or 12 times.