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Background End-stage kidney disease (ESKD) continues to fundamentally impact the lives of First Nations (FN) patients. Home peritoneal dialysis (PD) offers patients more mobility and flexibility, but few Manitoba FNs have availed themselves of this option. Objective This paper discusses Manitoba FNs' experience of PD, to highlight enablers and barriers to expanding the use of PD in rural and remote Manitoba communities. Methods We analyzed interviews of individuals living with ESKD (N = 14), family caregivers (N = 14) and healthcare providers and administrators (N = 27). Results Barriers to PD uptake include medical suitability, patients' distrust of home modalities and fear in their ability to manage. Other factors include limited family support and lack of appropriate housing. Conclusions Assisted peritoneal dialysis (APD) is an emerging model where PD supplies are centrally located, and where a cohort of PD patients can provide mutual support with added assistance from an APD worker. This model could mitigate existing treatment barriers.

Strategies to mitigate muscle cramps are a top research priority for patients receiving hemodialysis. As hypomagnesemia is a possible risk factor for cramping, we reviewed the literature to better understand the physiology of cramping as well as the epidemiology of hypomagnesemia and muscle cramps. We also sought to review the evidence from interventional studies on the effect of oral and dialysate magnesium-based therapies on muscle cramps.Peer-reviewed articles.We searched for relevant articles in major bibliographic databases including MEDLINE and EMBASE. The methodological quality of interventional studies was assessed using a modified version of the Downs and Blacks criteria checklist.The etiology of muscle cramps in patients receiving hemodialysis is poorly understood and there are no clear evidence-based prevention or treatment strategies. Several factors may play a role including a low concentration of serum magnesium. The prevalence of hypomagnesemia (concentration of0.7 mmol/L) in patients receiving hemodialysis ranges from 10% to 20%. Causes of hypomagnesemia include a low dietary intake of magnesium, use of medications that inhibit magnesium absorption (eg, proton pump inhibitors), increased magnesium excretion (eg, high-dose loop diuretics), and a low concentration of dialysate magnesium. Dialysate magnesium concentrations of ≤0.5 mmol/L may be associated with a decrease in serum magnesium concentration over time. Preliminary evidence from observational and interventional studies suggests a higher dialysate magnesium concentration will raise serum magnesium concentrations and may reduce the frequency and severity of muscle cramps. However, the quality of evidence supporting this benefit is limited, and larger, multicenter clinical trials are needed to further determine if magnesium-based therapy can reduce muscle cramps in patients receiving hemodialysis. In studies conducted to date, increasing the concentration of dialysate magnesium appears to be well-tolerated and is associated with a low risk of symptomatic hypermagnesemia.Few interventional studies have examined the effect of magnesium-based therapy on muscle cramps in patients receiving hemodialysis and most were nonrandomized, pre-post study designs.Les stratégies visant à atténuer les crampes musculaires sont parmi les principales priorités de recherche des patients hémodialysés. L’hypomagnésémie étant un possible facteur de risque, nous avons procédé à une revue de la littérature afin de mieux en comprendre l’épidémiologie, et d’examiner la physiologie et l’épidémiologie des crampes musculaires. Nous souhaitions également examiner les données probantes issues d’études interventionnelles portant sur l’effet des thérapies à base de dialysat de magnésium et de magnésium oral sur les crampes musculaires.Articles examinés par les pairs.Nous avons cherché les articles pertinents dans les principales bases de données bibliographiques, notamment MEDLINE et EMBASE. La qualité méthodologique a été évaluée à l’aide d’une version modifiée des critères de contrôle de la qualité des études de Downs et Black.L’étiologie des crampes musculaires chez les patients hémodialysés est mal comprise et il n’existe aucune stratégie de prévention ou traitement clairement fondé sur des données probantes. Plusieurs facteurs pourraient jouer un rôle, notamment de faibles concentrations sériques de magnésium. La prévalence de l’hypomagnésémie (concentration inférieure à 0,7 mmol/L) chez les patients hémodialysés variait de 10 à 20 %. Une faible consommation de magnésium dans l’alimentation, la prise de médicaments inhibant l’absorption du magnésium (ex. les inhibiteurs de la pompe à protons), l’excrétion accrue du magnésium (ex. dose élevée de diurétiques de l’anse) et une faible concentration de dialysat de magnésium figuraient parmi les causes d’hypomagnésémie. Un taux de dialysat de magnésium inférieur ou égal à 0,5 mmol/L pourrait être associé à une diminution de la concentration sérique de magnésium au fil du temps. Les résultats préliminaires de certaines études observationnelles et interventionnelles suggèrent qu’une concentration sérique plus élevée de magnésium dans le dialysat augmenterait les concentrations sériques de magnésium et pourrait réduire la fréquence et la sévérité des épisodes de crampes musculaires. La qualité des preuves appuyant ce bienfait est cependant limitée. Des essais multicentriques et à plus vaste échelle sont nécessaires pour juger si un traitement à base de magnésium peut véritablement réduire les crampes musculaires chez les patients hémodialysés. Dans les études menées jusqu’à maintenant, l’augmentation de la concentration de dialysat de magnésium semblait bien tolérée et a été associée à un faible risque d’hypermagnésémie symptomatique.Peu d’études interventionnelles ont examiné l’effet de la prise de magnésium sur les crampes musculaires des patients hémodialysés, et la plupart de celles-ci constituaient des plans pré- ou post-études non randomisées.

Context It has become commonplace to use family caregivers as proxy responders where patients are unable to provide information about their symptoms and concerns to health care providers. Objectives The objective of this study was to determine the degree of concordance between patients' and family members' reports of patient symptoms and concerns at end of life. Methods Sample dyads included a mix of patients residing at home, in a nursing home, in a long-term care facility, or in hospice. Diagnoses included patients with amyotrophic lateral sclerosis (n = 75), chronic obstructive pulmonary disease (n = 52), end-stage renal disease (n = 42), and institutionalized, cognitively intact frail elderly (n = 49). Dyads completed the Patient Dignity Inventory (PDI), the modified Structured Interview Assessment of Symptoms and Concerns in Palliative Care, and Graham and Longman's two-item Quality of Life Scale. Results Concordance was less than 70% for seven of the 25 PDI items, with the lowest concordance (65.1%) for the item “not being able to continue with my usual routines.” For all but one PDI item, discordance was in the direction of family members reporting that the patient was worse off than the patient had indicated. Where discordance was observed on the Structured Interview Assessment of Symptoms and Concerns in Palliative Care and Quality of Life Scales, the trend toward family members overreporting patient distress and poor quality of life continued. Conclusion Understanding discordance between patients and family member reports of symptoms and concerns is a valuable step toward minimizing patient and family burden at end of life.

BACKGROUND AND OBJECTIVES: Early nephrology referral is recommended for people with CKD on the basis of observational studies showing that longer nephrology care before dialysis start (predialysis care) is associated with lower mortality after dialysis start. This association may be observed because predialysis care truly reduces mortality or because healthier people with an uncomplicated course of disease will have both longer predialysis care and lower risk for death. We examined whether the survival benefit of longer predialysis care exists after accounting for the potential confounding effect of disease course that may also be affected by predialysis care. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a retrospective cohort study and used data from 3152 adults with end stage kidney failure starting dialysis between 2004 and 2014 in five Canadian dialysis programs. We obtained duration of predialysis care from the earliest nephrology outpatient visit to dialysis start; markers of disease course, including inpatient or outpatient dialysis start and residual kidney function around dialysis start; and all-cause mortality after dialysis start. RESULTS: The percentages of participants with 0, 1–119, 120–364, and ≥365 days of predialysis care were 23%, 8%, 10%, and 59%, respectively. When we ignored markers of disease course as in previous studies, longer predialysis care was associated with lower mortality (hazard ratio(120–364 versus 0–119 days), 0.60; 95% confidence interval, 0.46 to 0.78]; hazard ratio(≥365 versus 0–119 days), 0.60; 95% confidence interval, 0.51 to 0.71; standard Cox model adjusted for demographics and laboratory and clinical characteristics). When we additionally accounted for markers of disease course using the inverse probability of treatment weighted Cox model, this association was weaker and no longer significant (hazard ratio(120–364 versus 0–119 days), 0.84; 95% confidence interval, 0.60 to 1.18; hazard ratio(≥365 versus 0–119 days), 0.88; 95% confidence interval, 0.69 to 1.13). CONCLUSIONS: The association between longer predialysis care and lower mortality after dialysis start is weaker and imprecise after accounting for patients’ course of disease.

Purpose The objective of this study was to compare the initial safety and efficacy of a novel 30% ethanol/4% sodium citrate catheter-locking solution to heparin in a hemodialysis population. Methods This was a prospective, randomized, pilot study of 40 hemodialysis patients randomized to a 30% ethanol/4% sodium citrate or heparin 1000 units/mL locking solution. The primary outcome was identification of any serious adverse events over the study duration. Secondary outcomes included the rate per 1000 catheter days for catheter-related bloodstream infections (CRBSI), alteplase use, catheter dysfunction, and catheter removal. Results Three serious adverse events were reported as possibly related to the catheter solutions. Only one CRBSI was observed during the study in the heparin arm. The rate of alteplase use was 1.5/1000 catheter days in the heparin arm compared to 2.8/1000 catheter days in the ethanol/citrate arm (rate ratio = 1.85, 90% CI 0.48, 7.07, p value = 0.45), while the rate of catheter dysfunction was 6.8/1000 catheter days in the heparin arm compared to 1.9/1000 catheter days in the ethanol citrate arm (rate ratio = 0.27, 90% CI 0.10, 0.74, p value = 0.04). Catheter survival to first catheter outcome was longer in the ethanol/citrate group compared to heparin and there were no catheter removals due to bacteremia or thrombosis. Conclusions The ethanol/sodium citrate locking solution was safely used in this study. It appears to prevent CRBSI and may improve catheter survival compared to heparin. Trial registration ClinicalTrials.gov Identifier: NCT01394458.

Importance Patients on dialysis are often elderly and frail, with multiple comorbid conditions, and are heavy users of Emergency Department (ED) services. However, objective data on the frequency and pattern of ED utilization by dialysis patients are sparse. Such data could identify periods of highest risk for ED visits and inform health systems interventions to mitigate these risks and improve outcomes Objective To describe the pattern and frequency of presentation to ER by dialysis patients Design Retrospective cohort study using administrative data collected over ten years (2000–2009) in the Province of Manitoba, Canada. Setting Patients presenting to any of 9 ED’s in Winnipeg and Brandon Manitoba. These departments serve >90% of the population of Manitoba, Canada (population 1.2 million). Participants All patients presenting to an ED in any of 9 emergency departments in Manitoba, Canada. Exposure Dialysis status Main outcomes Presentation to the ED Results Over 2.1 million ED visits by more than 1.2 million non-dialysis patients and 17,782 ED visits by 3257 dialysis patients were included. Dialysis patients presented 8.5 times more frequently to the ED than the general population (age and sex adjusted, p

Background: Myocardial injury after noncardiac surgery (MINS) was defined as prognostically relevant myocardial injury due to ischemia that occurs during or within 30 days after noncardiac surgery. The study’s four objectives were to determine the diagnostic criteria, characteristics, predictors, and 30-day outcomes of MINS. Methods: In this international, prospective cohort study of 15,065 patients aged 45 yr or older who underwent in-patient noncardiac surgery, troponin T was measured during the first 3 postoperative days. Patients with a troponin T level of 0.04 ng/ml or greater (elevated “abnormal” laboratory threshold) were assessed for ischemic features (i.e., ischemic symptoms and electrocardiography findings). Patients adjudicated as having a nonischemic troponin elevation (e.g., sepsis) were excluded. To establish diagnostic criteria for MINS, the authors used Cox regression analyses in which the dependent variable was 30-day mortality (260 deaths) and independent variables included preoperative variables, perioperative complications, and potential MINS diagnostic criteria. Results: An elevated troponin after noncardiac surgery, irrespective of the presence of an ischemic feature, independently predicted 30-day mortality. Therefore, the authors’ diagnostic criterion for MINS was a peak troponin T level of 0.03 ng/ml or greater judged due to myocardial ischemia. MINS was an independent predictor of 30-day mortality (adjusted hazard ratio, 3.87; 95% CI, 2.96–5.08) and had the highest population-attributable risk (34.0%, 95% CI, 26.6–41.5) of the perioperative complications. Twelve hundred patients (8.0%) suffered MINS, and 58.2% of these patients would not have fulfilled the universal definition of myocardial infarction. Only 15.8% of patients with MINS experienced an ischemic symptom. Conclusion: Among adults undergoing noncardiac surgery, MINS is common and associated with substantial mortality.

Background Lower extremity complications are a major cause of morbidity and mortality in patients with end-stage renal disease (ESRD) and diabetes mellitus. Patient education programs may decrease the risk of diabetic foot complications. Methods A preventive program was instituted, consisting of regular assessments by a foot care nurse with expertise in foot care and wound management and patient education about foot care practices and footwear selection. Medical records were reviewed and patients were examined. A comparison was made with data about patients from a previous study done from this institution prior to development of the foot care program. Results Diabetic subjects more frequently had weakness of the left tibialis anterior, left tibialis posterior, and left peroneal muscles than non-diabetic subjects. A smaller percentage of diabetic subjects had sensory neuropathy compared with the previous study from 5years earlier, but a greater percentage of diabetic subjects had absent pedal pulses in the current study. The frequency of inadequate or poor quality footwear was less in the current study compared with the previous study. Conclusions The current data suggest that a foot care program consisting of nursing assessments and patient education may be associated with a decrease in frequency of neuropathy and improved footwear adequacy in diabetic patients with ESRD.

Aims Catheter-related thrombosis is a frequent complication of providing hemodialysis via central venous catheters. The primary aim of this study was to compare the efficacy of an alteplase "dwell" protocol over 30 minutes (with an additional 90 minutes where necessary) to a new 30 minute "push" protocol in restoring function to occluded hemodialysis catheters. Methods This was a prospective, randomized, parallel arm, multicenter study. Participants included hemodialysis patients using central venous catheters for vascular access. A new alteplase push protocol was the intervention and was compared to an alteplase dwell protocol. The primary outcome of this study was the proportion of patients with pre-thrombolytic blood flows less than 200 ml/min achieving a post thrombolytic blood flow ≥ 300 ml/ min. Secondary outcomes included recovery of Kt/V and liters processed per hour at the hemodialysis session following the intervention, time from thrombolytic to future catheter interventions, and the presence of serious adverse events. Results 82 patients were included in the intention-to-treat analysis. 65% (28/43) of catheters receiving the dwell protocol achieved blood flow ≥ 300 ml/min compared to 82% (32/39) in the push protocol. The difference was not statistically significant despite a 17% separation in the point estimates, p = 0.84. A non-significant result may have been associated with an inability to enrol the required a priori sample size. Kt/V, liters processed per hour and time to next catheter event were not significantly different. There were no serious adverse events attributed to the study medication. Conclusions The alteplase push protocol was effective and safe for managing dysfunctional hemodialysis catheters and was more practical than a 2 h dwell.

Manitoba has the highest prevalence of ESRD in Canada. Northern Manitoba is a very sparsely settled area with a high proportion of aboriginal ESRD patients. Relocating to urban areas for dialysis is psychosocially and culturally stressful to patients. Delivering dialysis care in a home setting has demonstrated advantages in both clinical, economic, and health related quality of life domains. Establishing home hemodialysis in very remote communities has significant challenges, including poor and inadequate housing, unreliable water supply, limited community medical backup, and poor road access to communities especially for delivery of supplies. These challenges necessitate the development of strong community partnerships, and well documented processes for contingencies. A dedicated interdisciplinary support and training team at the urban hub is essential.

Background. Patients choosing between hemodialysis (HD) and peritoneal dialysis (PD) should be well informed of the risks and benefits of each modality. Invasive access interventions are important outcomes because frequent interventions lower patient’s quality of life and consume limited resources. The objective of this study was to compare the risk of access interventions between the two modalities. Methods. Three hundred and sixty-nine incident chronic dialysis patients were prospectively enrolled at four Canadian centers that were eligible for both modalities, received at least 4 months of pre-dialysis care and started dialysis electively as an outpatient. Two hundred and twenty-four (61%) chose PD and 145 (39%) chose HD. Patients were followed for an average of 1.3 years (range 0.07–3.6 years). Results. In the PD group, there were fewer access interventions (2.5 versus 3.1 interventions per patient, adjusted odds ratio of 0.79 for PD versus HD, P ¼ 0.005) and a lower intervention rate (2.3 versus 1.9 per patient-year, adjusted rate ratio of 0.81 for PD versus HD, P ¼ 0.04). PD catheters were less likely to experience primary failure (4.6 versus 32%, P < 0.0001), showed a trend toward lower intervention rates during use (0.8 versus 1.2 per patientyear, P ¼ 0.06), and had equal patency compared to fistulae (1-year patency of 84 versus 88%, P ¼ 0.48). Patients managed exclusively with HD catheters (28% of the HD group) required 1.7 interventions per patient and an intervention rate of 1.9 per patient-year. Conclusion. Patients who choose PD require fewer access interventions to maintain dialysis access than patients choosing HD.

Introduction Au Canada, on observe des taux d'obésité plus élevés au sein des populations autochtones des Premières nations qu'au sein des autres populations. Nous avons étudié l'obésité et les affections liées à l'obésité dans une communauté des Premières nations du Manitoba. Méthodologie Nous avons mené, en 2003, une étude de dépistage du diabète et des complications du diabète qui nous a permis de sélectionner un échantillon représentatif d'adultes des Premières nations du Manitoba (N = 483). Nous avons évalué les affections chroniques et les facteurs de risque d'affections chroniques. Résultats La prévalence de l'obésité et des affections liées à l'obésité était plus élevée chez les femmes que chez les hommes. À l'aide d'une analyse multivariée, nous avons établi que les facteurs étroitement liés à l'obésité chez les femmes étaient la tension artérielle diastolique, l'insulinorésistance et la situation d'emploi. Chez les hommes, les facteurs relevés étaient l'âge, les taux d'apolipoprotéine A1 et d'apolipoprotéine B et l'insulinorésistance. Soixante-quinze pour cent des participants à l'étude présentaient au moins un des problèmes de santé suivants : obésité, dyslipidémie, hypertension ou diabète. La comorbidité était élevée même dans les groupes d'âge les plus jeunes : 22 % des hommes et 43 % des femmes de 18 à 29 ans présentaient au moins deux affections chroniques. Vingt-deux pour cent des participants étaient atteints d'une hypertension non diagnostiquée. Ces derniers présentaient un nombre sensiblement plus élevé d'affections chroniques et risquaient davantage d'être atteints de microalbuminurie que les sujets sans hypertension. Il n'y avait pas de différence significative quant au nombre d'affections chroniques entre les participants dont le diagnostic d'hypertension venait d'être posé et ceux dont le diagnostic avait déjà été établi. Conclusion La prévalence de l'obésité et d'autres affections chroniques est élevée dans la communauté étudiée, en particulier chez les jeunes. Des interventions communautaires sont actuellement menées dans le but de réduire le taux excessif de problèmes de santé.

Introduction Rates of obesity are higher among Canada's Aboriginal First Nations populations than among non-First Nations populations. We studied obesity and obesity-related illness in a Manitoba First Nation community. Methods We conducted a screening study of diabetes and diabetes complications in 2003, from which we drew a representative sample of Manitoba First Nation adults (N = 483). We assessed chronic disease and chronic disease risk factors. Results Prevalence of obesity and associated comorbidities was higher among women than men. By using multivariate analysis, we found that factors significantly associated with obesity among women were diastolic blood pressure, insulin resistance, and employment status. Among men, factors were age, apolipoprotein A1 level, apolipoprotein B level, and insulin resistance. Seventy-five percent of study participants had at least 1 of the following conditions: obesity, dyslipidemia, hypertension, or diabetes. Comorbidity was high even among the youngest age groups; 22% of men and 43% of women aged 18 to 29 had 2 or more chronic conditions. Twenty-two percent of participants had undiagnosed hypertension. Participants with undiagnosed hypertension had significantly more chronic conditions and were more likely to have microalbuminuria than were those without hypertension. The number of chronic conditions was not significantly different for participants with newly diagnosed hypertension than for those with previously diagnosed hypertension. Conclusion The prevalence of obesity and other chronic conditions in the study community is high, especially considering the number of young people. Community-based interventions are being undertaken to reduce the excessive rate of illness.

Limited data are available about disability associated with upper extremity complications in patients who receive haemodialysis for end-stage renal disease. In this study of 123 patients receiving haemodialysis, the mean Disabilities of the Arm, Shoulder and Hand (DASH) score was 31 ± 22 points, indicating markedly greater disability than in a normal population. Dupuytren's contracture was the most frequent deformity. Brachial, radial and ulnar pulses were present in most upper limbs, but 14 (14%) of 102 patients had poor arterial perfusion pressures. Diabetic patients had residual or complete loss of protective sensation more frequently than nondiabetic patients. Motor testing with the index finger abduction and fifth finger flexion tests showed a significantly greater frequency of weakness in diabetic than nondiabetic patients. In summary, upper extremity disability was noted in haemodialysis patients, including loss of protective sensation and motor strength, both in diabetic and nondiabetic subjects.

Background Targets for peritoneal dialysis (PD) utilization may be difficult to achieve because many older patients have contraindications to PD or barriers to self-care. The objectives of this study were to determine the impact that contraindications and barriers to self-care have on incident PD use, and to determine whether family support increased PD utilization when home care support is available. Methods Consecutive incident dialysis patients were assessed for PD eligibility, offered PD if eligible and followed up for PD use. All patients lived in regions where home care assistance was available. Results The average patient age was 66 years. One hundred and ten (22%) of the 497 patients had absolute medical or social contraindications to PD. Of the remaining 387 patients who were potentially eligible for PD, 245 (63%) had at least one physical or cognitive barrier to self-care PD. Patients with barriers were older, weighed less and were more likely to be female, start dialysis as an inpatient and have a history of vascular disease, cardiac disease and cancer. Family support was associated with an increase in PD eligibility from 63% to 80% (P = 0.003) and PD choice from 40% to 57% (P = 0.03) in patients with barriers to self-care. Family support increased incidence PD utilization from 23% to 39% among patients with barriers to self-care (P = 0.009). When family support was available, 34% received family-assisted PD, 47% received home care-assisted PD, 12% received both family- and home care-assisted PD, and 7% performed only self-care PD. Incident PD use in an incident end-stage renal disease (ESRD) population was 30% (147 of the 497 patients). Conclusions Contraindications, barriers to self-care and the availability of family support are important drivers of PD utilization in the incident ESRD population even when home assistance is available. These factors should be considered when setting targets for PD.

Objective The purpose of this study was to identify four non-cancer populations that might benefit from a palliative approach; and describe and compare the prevalence and patterns of dignity related distress across these diverse clinical populations. Design A prospective, multi-site approach was used. Setting Outpatient clinics, inpatient facilities or personal care homes, located in Winnipeg, Manitoba and Edmonton, Alberta, Canada. Participants Patients with advanced Amyotrophic Lateral Sclerosis (ALS), Chronic Obstructive Pulmonary Disease (COPD), End Stage Renal Disease (ESRD); and the institutionalized alert frail elderly. Main Outcome Measure In addition to standardized measures of physical, psychological and spiritual aspects of patient experience, the Patient Dignity Inventory (PDI). Results Between February 2009 and December 2012, 404 participants were recruited (ALS, 101; COPD, 100; ESRD, 101; and frail elderly, 102). Depending on group designation, 35% to 58% died within one year of taking part in the study. While moderate to severe loss of sense of dignity did not differ significantly across the four study populations (4–11%), the number of PDI items reported as problematic was significantly different i.e. ALS 6.2 (5.2), COPD 5.6 (5.9), frail elderly 3.0 (4.4) and ESRD 2.3 (3.9) [p < .0001]. Each of the study populations also revealed unique and distinct patterns of physical, psychological and existential distress. Conclusion People with ALS, COPD, ESRD and the frail elderly face unique challenges as they move towards the end of life. Knowing the intricacies of distress and how they differ across these groups broadens our understanding of end-of-life experience within non-cancer populations and how best to meet their palliative care needs.

BACKGROUND The use of central venous catheters as a source of vascular access in patients undergoing hemodialysis may be complicated by thrombosis. Frequently, thrombolytics are used in an attempt to reestablish blood flow through partially or completely occluded catheters. OBJECTIVE To compare the efficacy of alteplase (recombinant tissue plasminogen activator) versus urokinase in reestablishing adequate blood flow through partially or completely occluded vascular catheters. METHODS Part 1 of the study prospectively investigated the effect of alteplase in reestablishing adequate blood flow through partially or completely occluded vascular catheters in 30 hemodialysis patients. Part 2 of the trial compared the efficacy of alteplase with that of urokinase in 14 of 30 patients who had also previously received urokinase. A 30-minute push-protocol was used to administer thrombolytics in both parts of the study. The primary endpoint was the proportion of patients with partially or completely occluded catheters achieving post-thrombolytic blood flow of ≥200 mL/min. RESULTS Part 1 showed a large proportion of partially or completely occluded catheters achieving post-alteplase blood flows ≥200 mL/min (70/76, 92.1% vs. 34/40, 85%, respectively). In Part 2 of the study, the proportion of partially occluded catheters achieving post-thrombolytic blood flows ≥200 mL/min was not significantly different between the alteplase and urokinase groups, (36/41, 87.8% vs. 21/28, 75%, respectively; p = 0.205). The proportion of completely occluded catheters achieving post-thrombolytic blood flows ≥200 mL/min was significantly better with alteplase compared with urokinase (15/17, 88.2% vs. 6/14, 42.8%, respectively; p = .018). CONCLUSIONS Alteplase, administered via the 30-minute push-protocol, is an effective thrombolytic for restoring hemodialysis catheter patency. In our study sample, alteplase was generally more effective than urokinase in restoring blood flow through catheters, especially those that were completely occluded.

[This corrects the article DOI: 10.1371/journal.pone.0147607.].

Background: Myocardial injury after noncardiac surgery (MINS) was defined as prognostically relevant myocardial injury due to ischemia that occurs during or within 30 days after noncardiac surgery. The study's four objectives were to determine the diagnostic criteria, characteristics, predictors, and 30-day outcomes of MINS. Methods: In this international, prospective cohort study of 15,065 patients aged 45 yr or older who underwent in-patient noncardiac surgery, troponin T was measured during the first 3 postoperative days. Patients with a troponin T level of 0.04 ng/ml or greater (elevated abnormal laboratory threshold) were assessed for ischemic features (i.e., ischemic symptoms and electrocardiography findings). Patients adjudicated as having a nonischemic troponin elevation (e.g., sepsis) were excluded. To establish diagnostic criteria for MINS, the authors used Cox regression analyses in which the dependent variable was 30-day mortality (260 deaths) and independent variables included preoperative variables, perioperative complications, and potential MINS diagnostic criteria. Results: An elevated troponin after noncardiac surgery, irrespective of the presence of an ischemic feature, independently predicted 30-day mortality. Therefore, the authors' diagnostic criterion for MINS was a peak troponin T level of 0.03 ng/ml or greater judged due to myocardial ischemia. MINS was an independent predictor of 30-day mortality (adjusted hazard ratio, 3.87; 95% CI, 2.96-5.08) and had the highest population-attributable risk (34.0%, 95% CI, 26.6-41.5) of the perioperative complications. Twelve hundred patients (8.0%) suffered MINS, and 58.2% of these patients would not have fulfilled the universal definition of myocardial infarction. Only 15.8% of patients with MINS experienced an ischemic symptom. Conclusion: Among adults undergoing noncardiac surgery, MINS is common and associated with substantial mortality.

Background Hospitalization rates are a relevant consideration when choosing or recommending a dialysis modality. Previous comparisons of peritoneal dialysis (PD) and hemodialysis (HD) have not been restricted to individuals who were eligible for both therapies. Methods We conducted a multicenter prospective cohort study of people 18 years of age and older who were eligible for both PD and HD, and who started outpatient dialysis between 2007 and 2010 in four Canadian dialysis programs. Zero-inflated negative binomial models, adjusted for baseline patient characteristics, were used to examine the association between modality choice and rates of hospitalization. Results The study enrolled 314 patients. A trend in the HD group toward higher rates of hospitalization, observed in the primary analysis, became significant when modality was treated as a time-varying exposure or when the population was restricted to elective outpatient starts in patients with at least 4 months of pre-dialysis care. Cardiovascular disease, infectious complications, and elective surgery were the most common reasons for hospital admission; only 23% of hospital stays were directly related to complications of dialysis or kidney disease. Conclusions Efforts to promote PD utilization are unlikely to result in increased rates of hospitalization, and efforts to reduce hospital admissions should focus on potentially avoidable causes of cardiovascular disease and infectious complications.

Restless legs syndrome (RLS) and periodic limb movements in sleep (PLMS) are disorders that are common and disturbing to uremic patients. The treatment of these is problematic. Eight patients on chronic hemodialysis and continuous peritoneal dialysis completed a double-blind placebo-controlled crossover study using incremental doses of pergolide up to 0.25 mg at bedtime for treatment of RLS and sleep disruption. Five patients (62.5%) noted subjective improvement in restless legs symptoms and sleep quality. Objective results were improved only slightly by treatment. The percentage of the first hour in bed during which leg movements occurred decreased from 20.5 +/- 6.0 to 11.5 +/- 3.3, p < 0.05. However, findings during sleep were less positive. The following measures were not significant between placebo and treatment: leg movements per hour of sleep [53.7 +/- 22.3 vs 35.8 +/- 11.8 (p = 0.2)]; and percentage of sleep time spent with leg movements [5.5% +/- 3.2 vs 4.4% +/- 1.4 (p = 0.37)]. Patients continued to have very disrupted sleep, and we could not document an objective improvement in sleep architecture. Thus, although pergolide at the dose of 0.25 mg at bedtime provided subjective improvement in symptoms of restless legs and quality of sleep, and objectively decreased leg movements during the first hour in bed, objectively sleep continued to be disrupted. In this small patient group, the response to pergolide was not uniform, and further investigation is required to test effectiveness at higher doses.

Background Both diabetic and non-diabetic end stage renal disease (ESRD) are more common among Canadian First Nations people than among the general Canadian population. The purpose of this research was to determine the prevalence of and risk factors for albuminuria in a Canadian First Nation population at high risk for ESRD and dialysis. Methods Data from a community-based screening study of 483 residents of a Plains Ojibway First Nation in Manitoba was used. Participants provided random urine samples. Proteinuria was defined as any dipstick positive for protein (≥1 g/L) or those with ACR in the macroalbuminuric range (≥30 mg/mmol) on at least one sample. Microalbuminuria was defined as ACR ≥2 mg/mmol for males and ≥2.8 mg/mmol for females. Other measures included fasting glucose, haemoglobin A1c, triglycerides, cholesterol, blood pressure, height, weight and waist and hip circumferences. Results Twenty percent of study participants had albuminuria, (5% proteinuria and 15% microalbuminuria). Of participants with diabetes, 42% (56/132) had albuminuria compared to 26% (7/27) among those with impaired fasting glucose and 10% (30/303) among those with normal glucose tolerance. Only 5.3% of those with albuminuria were aware of any degree of renal disease. In a multivariate logistic regression, independent associations with albuminuria were male gender [p = 0.002], increasing fasting glucose [p Conclusions The independent association between BMI and albuminuria has not been previously reported among indigenous populations. There is a high prevalence of albuminuria in this Canadian First Nation population; the high proportion of patients with diabetes and undiagnosed kidney disease demonstrates the need for screening, education and intervention to halt the progression and development of albuminuria and ultimately ESRD and CVD.

Manitoba has the highest prevalence of ESRD in Canada. Northern Manitoba is a very sparsely settled area with a high proportion of aboriginal ESRD patients. Relocating to urban areas for dialysis is psychosocially and culturally stressful to patients. Delivering dialysis care in a home setting has demonstrated advantages in both clinical, economic, and health related quality of life domains. Establishing home hemodialysis in very remote communities has significant challenges, including poor and inadequate housing, unreliable water supply, limited community medical backup, and poor road access to communities especially for delivery of supplies. These challenges necessitate the development of strong community partnerships, and well documented processes for contingencies. A dedicated interdisciplinary support and training team at the urban hub is essential.

Rates of obesity are higher among Canada's Aboriginal First Nations populations than among non-First Nations populations. We studied obesity and obesity-related illness in a Manitoba First Nation community.We conducted a screening study of diabetes and diabetes complications in 2003, from which we drew a representative sample of Manitoba First Nation adults (N = 483). We assessed chronic disease and chronic disease risk factors.Prevalence of obesity and associated comorbidities was higher among women than men. By using multivariate analysis, we found that factors significantly associated with obesity among women were diastolic blood pressure, insulin resistance, and employment status. Among men, factors were age, apolipoprotein A1 level, apolipoprotein B level, and insulin resistance. Seventy-five percent of study participants had at least 1 of the following conditions: obesity, dyslipidemia, hypertension, or diabetes. Comorbidity was high even among the youngest age groups; 22% of men and 43% of women aged 18 to 29 had 2 or more chronic conditions. Twenty-two percent of participants had undiagnosed hypertension. Participants with undiagnosed hypertension had significantly more chronic conditions and were more likely to have microalbuminuria than were those without hypertension. The number of chronic conditions was not significantly different for participants with newly diagnosed hypertension than for those with previously diagnosed hypertension.The prevalence of obesity and other chronic conditions in the study community is high, especially considering the number of young people. Community-based interventions are being undertaken to reduce the excessive rate of illness.

Limited data are available about disability associated with upper extremity complications in patients who receive haemodialysis for end-stage renal disease. In this study of 123 patients receiving haemodialysis, the mean Disabilities of the Arm, Shoulder and Hand (DASH) score was 31 ± 22 points, indicating markedly greater disability than in a normal population. Dupuytren's contracture was the most frequent deformity. Brachial, radial and ulnar pulses were present in most upper limbs, but 14 (14%) of 102 patients had poor arterial perfusion pressures. Diabetic patients had residual or complete loss of protective sensation more frequently than nondiabetic patients. Motor testing with the index finger abduction and fifth finger flexion tests showed a significantly greater frequency of weakness in diabetic than nondiabetic patients. In summary, upper extremity disability was noted in haemodialysis patients, including loss of protective sensation and motor strength, both in diabetic and nondiabetic subjects.

This dissertation argues that black southerners' theology guided their collective action from emancipation to the beginning of the Jim Crow era. Black theology in this time produced both conservative and radical political agendas and set the terms for political debates within African-American communities. This project makes their rich, diverse, and at times confusing religious thought intelligible to the twenty-first-century reader and demonstrates the weight of those theological ideas on the ground in particular places and particular times. The branch of their theology that located them within a divine plan for the race--their eschatology--gave black political leaders more hope and confidence than a mere secular reading of their circumstances could justify. The dissertation focuses on one southern state, North Carolina, to reveal the importance of black theology to local and statewide political issues: emancipation and Reconstruction, migration and black land ownership, temperance and prohibition, and disfranchisement and segregation.

Anti-glomerular basement membrane (anti-GBM) disease is an aggressive form of glomerulonephritis, usually mediated by immunoglobulin G (IgG) autoantibodies to the noncollagenous (NC1) domain of alpha 3(IV) collagen. Less is known about the target antigen(s) in patients with atypical anti-GBM disease involving IgA autoantibodies. We report a new case of IgA anti-GBM disease in a patient with a history of proliferative lupus nephritis who presented with increasing creatinine levels, proteinuria, and hematuria, but no clinical or serological evidence of lupus recurrence. Renal biopsy showed focal and segmental necrotizing glomerulonephritis with strong linear capillary loop IgA staining by means of immunofluorescence. Serological test results were negative for IgG or IgA autoantibodies against the alpha 3NC1 domain. By means of immunoblotting, IgA from patient serum bound to 38- to 48-kd antigens collagenase-solubilized from human GBM, but not to purified NC1 domains of GBM collagen IV. The target of patient's IgA autoantibodies thus was identified as a novel GBM antigen, distinct from the alpha 3NC1 domain or other known targets of anti-GBM IgA autoantibodies. Clinical resolution was attained by means of conventional treatment with steroids and cyclophosphamide. The diversity of antigens recognized by anti-GBM IgA autoantibodies highlights the importance of renal biopsy for the reliable diagnosis of this rare condition because conventional serological immunoassays likely would yield false-negative results.

A retrospective case-control and cohort analysis of hemodialysis patients was done to identify risk factors for spondylodiscitis. These risk factors included bacteremia, receipt of blood products, invasive procedures, and establishment of vascular access. The death rate was greater for case subjects than for control subjects (odds ratio, 2.7).

Background Chronic renal failure patients are at particular risk of hepatitis B virus infection. Early studies have demonstrated that renal failure patients benefit from vaccination; however, not all studies have consistently shown benefit. Objectives To determine the beneficial and harmful effects of hepatitis B vaccine and of a reinforced vaccination series in chronic renal failure patients. Search strategy We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Renal Group Controlled Trials Register, The Cochrane Controlled Trials Register on The Cochrane Library (Issue 1, 2002),PubMed/MEDLINE (1966 to July 2003), EMBASE (1985 to November 2003), Current Clinical Practice Guidelines (Canadian Immunization Guide and Vaccine Preventable Diseases Surveillance Manual), and Science Citation Index as well as journals, published abstracts, and reference lists of articles. Selection criteria Randomised clinical trials comparing plasma vaccine with placebo, recombinant vaccine with placebo, recombinant vaccine with plasma vaccine, and a reinforced vaccination series (ie, more than three inoculations) with three inoculations of vaccine in chronic renal failure patients. Data collection and analysis Primary outcome measures included incidence of patients developing hepatitis B virus antibodies and infections while secondary outcomes included adverse events, liver-related morbidity, and mortality. Random effects models were used and reported relative risks and 95% confidence intervals (RR and 95% CI). Main results We included seven randomised clinical trials. None of them had high quality. Plasma vaccine was significantly more effective than placebo in achieving hepatitis B antibodies (RR 23.0, 95% CI 14.39 to 36.76, 3 trials). We found no statistically significant difference between plasma vaccine or placebo regarding hepatitis B virus infections (RR 0.50, 95% CI 0.20 to 1.24). We found no statistically significant differences between recombinant vaccine and plasma vaccine in achieving hepatitis B antibodies (RR 0.65, 95% CI 0.28 to 1.53, 2 trials). Heterogeneity was significant and appeared to be attributable to the dose of vaccine. Two trials examined a reinforced recombinant vaccine strategy, which was not statistically more effective than three inoculations of recombinant vaccine regarding development of hepatitis B antibodies (RR 1.36, 95% CI 0.85 to 2.16). Reviewers' conclusions Plasma derived vaccines are more effective than placebo in achieving hepatitis B antibodies, while no statistically significant difference was found between recombinant and plasma vaccines. No statistically significant difference of effectiveness was observed between a reinforced vaccination series versus routine vaccinations of three inoculations of recombinant vaccine.

A significant proportion of potential kidney transplant candidates continue to periodically require blood transfusions that carry a risk of allosensitization. Leukocyte reduction (leukoreduction) of blood products has been proved to reduce transfusion-associated allosensitization in patients with hematologic malignancies; however, the effect in potential kidney transplant candidates is unknown. A total of 112 kidney transplant candidates who received red blood cell transfusions while on the transplant waiting list were identified retrospectively. Sixty received a transfusion before leukoreduction (non-LR), and 52 received a transfusion after the local implementation of universal leukoreduction of blood products (LR). There was no difference in transfusion-associated allosensitization rates in patients who received a transfusion during the two eras (non-LR 27% [16 of 60] versus LR 33% [17/52]; NS). Likewise, no difference was observed in subgroups identified as being at high risk of allosensitization (previous pregnancy, transplant, or five or more previous transfusions) or at low risk (no previous allogeneic exposures) (high risk: non-LR 52% versus LR 55%; low risk: non-LR 10% versus LR 8%). Multivariate analysis revealed previous pregnancy to be the only significant risk factor associated with transfusion-associated allosensitization (relative risk, 8.2; 95% confidence interval, 2.4 to 24.0; P = 0.0001). Leukoreduction, in particular, was not associated with any protective effect. In summary, leukoreduction of red blood cell transfusions does not confer any protection against transfusion-associated allosensitization for potential kidney transplant candidates. Physicians who care for patients with ESRD must continue to practice careful transfusion avoidance while alternative strategies to minimize transfusion associated allosensitization are sought.

Background: Aminoglycosides are commonly used in the haemodialysis population. Standard pharmacokinetic approaches require multiple sampling to describe the parameters of drug distribution and elimination in the intra- and interdialytic periods. Objective: To characterise the pharmacokinetics of gentamicin in a haemodialysis population by using Bayesian pharmacokinetic methods and only two plasma concentrations. Design and participants: Prospective case series of 13 adult (aged 36–70 years) haemodialysis patients (Fresenius F80 dialysers were used) receiving gentamicin. Methods: Patients with suspected or confirmed Gram-negative infections were given gentamicin. At 48 hours after receiving the dose (at the next haemodialysis session), patients provided two blood samples, one immediately before the dialysis session and another 1 hour after haemodialysis. Data on dosage, timing and plasma concentrations for all subjects were analysed with PASTRX version 10.6 and Bayesian pharmacokinetic analysis. Volume of distribution (Vd), interdialytic elimination rate constant (kinter), interdialytic elimination half-life (t½β, inter) and interdialytic clearance (CLinter) were determined from a single predialysis plasma concentration. Elimination rate constant (kdinal), elimination half-life (t½β, dial) and clearance (CLdial) during 3.5–4 hours of dialysis were also determined from the pre- and post-plasma concentrations. Results: Pharmacokinetic parameters (mean ± SD) were: Vd 0.288 ± 0.002 L/kg, kinter 0.015 ± 0.004h−1, t½β, inter 48 ± 11h, CLinter 5.9 ± 2.4 mL/min, kdial 0.25 ±0.05 h−1, t½β, dial 3.0 ± 1.0h and CLdial 91 ± 24 mL/min. Conclusion: The rate of elimination of gentamicin was 17-fold greater (95% CI 13.7–20.7) on haemodialysis with a Fresenius F80 than off haemodialysis. All of the pharmacokinetic parameters of interest were determined using Bayesian pharmacokinetic procedures and only two plasma gentamicin concentrations.

Objective To investigate the risk factors for the development of calciphylaxis in renal failure, a poorly understood and often fatal condition characterized by calcium deposition in tissues. Design Retrospective case-control study. Setting University hospital peritoneal dialysis center. Patients Eight continuous ambulatory peritoneal dialysis (CAPD) patients with calciphylaxis were identified in a 3-year period. We matched up to five controls for dialysis modality and length of time on dialysis with each case. Statistics Multivariate conditional logistic regression analysis for matched case-controls. Main Outcome Measures Laboratory data and demographics were collected as well as cumulative calcium and vitamin D ingestion over the year prior to disease onset. Results All the patients were female, versus only 38% (14/37) of controls ( p < 0.0001). While not statistically significant, a majority of the patients were diabetic [62.5% (5/8) vs 32% (12/37)]. Peak and average levels of serum calcium, phosphate, calcium x phosphate product, parathyroid hormone (PTH), albumin, iron, total iron-binding capacity (TIBC), and ferritin were not significantly different in cases compared with controls. The use of calcitriol alone or with calcium carbonate was not found to be a significant risk factor for the development of calciphylaxis. In a multivariate analysis, iron intake seemed to be protective, contrary to previous reports, while the use of calcium carbonate was associated with a strong trend to increased risk of calciphylaxis development (odds ratio = 1.029/g and 1.011/g calcium ingested per month, at 1 and 2 – 3 months prior to calciphylaxis development; p = 0.0556 and 0.0565, respectively). Conclusion These data, although limited by the small numbers of index cases, suggest that calcium ingestion is a risk factor for calciphylaxis. The increased use of calcium salts as a phosphate binder in recent years might explain the apparent increased incidence of calciphylaxis in our and other centers. The preponderance of female diabetics among cases reported elsewhere was confirmed in our study.

Calciphylaxis is usually non-ulcerating: Risk factors, outcome and therapy . Background Calciphylaxis, historically considered rare, seems to be increasing in frequency. In our single center, 36 new cases have accumulated in seven years. The majority of these cases were non-ulcerating, which we believe to be early disease, in contradistinction to the vast majority of published cases that presented with ulcers. Methods Prospective data were collected on all patients with calciphylaxis. As well, a case control study, with two controls per patient, was performed on patients presenting with non-ulcerating plaques. Results The incidence of calciphylaxis in dialysis patients increased with a rate of 4.5/100 patient-years in the past three years. Eighty percent of cases presented with non-ulcerating subcutaneous plaques in the calves, easily confused with cellulitis. In those patients presenting with plaques only, the mortality rate was 33% at six months. Once ulceration develops, the mortality rate increased to above 80%. Bone scan was positive in 97% of patients. Steroid therapy appeared to be beneficial in some patients. Peritoneal dialysis, female sex and diabetes were risk factors. In the case control study of patients presenting with plaques only, serum phosphate (OR 2.6; 95% CI 1.05 to 6.45, P = 0.038) and Ca × P product (OR 1.46; 95% CI 1.02 to 20, P = 0.038) predicted the disease, as did being on calcium salts + vitamin D (OR 4.05; 95% CI 1.14 to 14.5, P = 0.03). Conclusions Calciphylaxis is no longer rare. It is usually nonulcerating and can be diagnosed clinically in all patients. These patients have a high mortality, especially once ulceration occurs. Calcium salts plus vitamin D, as well as serum Ca × P product and high serum P increase the chance of the diseases. Therefore, the disease may be preventable. Steroids may be of benefit to some patients.

To investigate whether the lower the blood pressure (BP) the better the prognosis for the patient with moderate-to-severe hypertension, an assessment was made of 902 patients who received the beta 1-selective beta-blocker atenolol (median dose 100 mg a day), either alone or with other antihypertensive agents, for up to 10 years (mean 6.1). 91 died, 40 from myocardial infarction, 21 from stroke, and 30 from other causes. Initial BP was a poor predictor of mortality from myocardial infarction, whereas treated systolic blood pressure (SBP) was a strong predictor. There was a J-shaped relation, confined to those with evidence of ischaemic heart disease, between frequency of death from myocardial infarction and treated DBP (phase V); the frequency was lowest at treated DBP of 85-90 mm Hg and rose with treated DBP on either side of this range.