Humber River Regional Hospital

BACKGROUND: Treatment of secondary hyperparathyroidism with vitamin D and calcium in patients receiving dialysis is often complicated by hypercalcemia and hyperphosphatemia, which may contribute to cardiovascular disease and adverse clinical outcomes. Calcimimetics target the calcium-sensing receptor and lower parathyroid hormone levels without increasing calcium and phosphorus levels. We report the results of two identical randomized, double-blind, placebo-controlled trials evaluating the safety and effectiveness of the calcimimetic agent cinacalcet hydrochloride. METHODS: Patients who were receiving hemodialysis and who had inadequately controlled secondary hyperparathyroidism despite standard treatment were randomly assigned to receive cinacalcet (371 patients) or placebo (370 patients) for 26 weeks. Once-daily doses were increased from 30 mg to 180 mg to achieve intact parathyroid hormone levels of 250 pg per milliliter or less. The primary end point was the percentage of patients with values in this range during a 14-week efficacy-assessment phase. RESULTS: Forty-three percent of the cinacalcet group reached the primary end point, as compared with 5 percent of the placebo group (P<0.001). Overall, mean parathyroid hormone values decreased 43 percent in those receiving cinacalcet but increased 9 percent in the placebo group (P<0.001). The serum calcium-phosphorus product declined by 15 percent in the cinacalcet group and remained unchanged in the placebo group (P<0.001). Cinacalcet effectively reduced parathyroid hormone levels independently of disease severity or changes in vitamin D sterol dose. CONCLUSIONS: Cinacalcet lowers parathyroid hormone levels and improves calcium-phosphorus homeostasis in patients receiving hemodialysis who have uncontrolled secondary hyperparathyroidism.

BACKGROUND: Pruritus affects many haemodialysis (HD) patients. In this study, pruritus and its relationship to morbidity, mortality, quality of life (QoL), sleep quality and patient laboratory measures were analysed in >300 dialysis units in 12 countries. METHODS: Pruritus data were collected from 18 801 HD patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS) (1996-2004). Analyses were adjusted for age, gender, black race, Kt/V, haemoglobin, serum albumin, albumin-corrected serum calcium, serum phosphorus, 13 comorbidities, depression, years on dialysis, country and facility clustering effects. RESULTS: Moderate to extreme pruritus was experienced by 42% of prevalent HD patients in DOPPS during 2002/2003. Many patient characteristics were significantly associated with pruritus, but this did not explain the large differences in pruritus between countries (ranging from 36% in France to 50% in the UK) and between facilities (5-75%). Pruritus was slightly less common in patients starting HD than in patients on dialysis >3 months. Pruritus in new end-stage renal disease (ESRD) patients likely results from pre-existing conditions and not haemodialysis per se, indicating the need to understand development of pruritus before ESRD. Patients with moderate to extreme pruritus were more likely to feel drained [adjusted odds ratio (AOR) = 2.3-5.2, P < 0.0001] and to have poor sleep quality (AOR = 1.9-4.1, P < or = 0.0002), physician-diagnosed depression (AOR = 1.3-1.7, P < or = 0.004), and QoL mental and physical composite scores 3.1-8.6 points lower (P < 0.0001) than patients with no/mild pruritus. Pruritus in HD patients was associated with a 17% higher mortality risk (P < 0.0001), which was no longer significant after adjusting for sleep quality measures. CONCLUSIONS: The pruritus/mortality relationship may be substantially attributed to poor sleep quality. The many poor outcomes associated with pruritus underscore the need for better therapeutic agents to provide relief for the 40-50% of HD patients affected by pruritus.

BACKGROUND: Sleep apnea is common in patients with chronic renal failure and is not improved by either conventional hemodialysis or peritoneal dialysis. With nocturnal hemodialysis, patients undergo hemodialysis seven nights per week at home while sleeping. We hypothesized that nocturnal hemodialysis would correct sleep apnea in patients with chronic renal failure because of its greater effectiveness. METHODS: Fourteen patients who were undergoing conventional hemodialysis for four hours on each of three days per week underwent overnight polysomnography. The patients were then switched to nocturnal hemodialysis for eight hours during each of six or seven nights a week. They underwent polysomnography again 6 to 15 months later on one night when they were undergoing nocturnal hemodialysis and on another night when they were not. RESULTS: The mean (+/-SD) serum creatinine concentration was significantly lower during the period when the patients were undergoing nocturnal hemodialysis than during the period when they were undergoing conventional hemodialysis (3.9+/-1.1 vs. 12.8+/-3.2 mg per deciliter [342+/-101 vs. 1131+/-287 micromol per liter], P<0.001). The conversion from conventional hemodialysis to nocturnal hemodialysis was associated with a reduction in the frequency of apnea and hypopnea from 25+/-25 to 8+/-8 episodes per hour of sleep (P=0.03). This reduction occurred predominantly in seven patients with sleep apnea, in whom the frequency of episodes fell from 46+/-19 to 9+/-9 per hour (P= 0.006), accompanied by increases in the minimal oxygen saturation (from 89.2+/-1.8 to 94.1+/-1.6 percent, P=0.005), transcutaneous partial pressure of carbon dioxide (from 38.5+/-4.3 to 48.3+/-4.9 mm Hg, P=0.006), and serum bicarbonate concentration (from 23.2+/-1.8 to 27.8+/-0.8 mmol per liter, P<0.001). During the period when these seven patients were undergoing nocturnal hemodialysis, the apnea-hypopnea index measured on nights when they were not undergoing nocturnal hemodialysis was greater than that on nights when they were undergoing nocturnal hemodialysis, but it still remained lower than it had been during the period when they were undergoing conventional hemodialysis (P=0.05). CONCLUSIONS: Nocturnal hemodialysis corrects sleep apnea associated with chronic renal failure.

BACKGROUND: A well-functioning vascular access (VA) is essential to efficient dialysis therapy. Guidelines have been implemented improving care, yet access use varies widely across countries and VA complications remain a problem. This study took advantage of the unique opportunity to utilize data from the Dialysis Outcomes and Practice Patterns Study (DOPPS) to examine international trends in VA use and trends in patient characteristics and practices associated with VA use from 1996 to 2007. DOPPS is a prospective, observational study of haemodialysis (HD) practices and patient outcomes at >300 HD units from 12 countries and has collected data thus far from >35,000 randomly selected patients. METHODS: VA data were collected for each patient at study entry (1996-2007). Practice pattern data from the facility medical director, nurse manager and VA surgeon were also analysed. RESULTS: Since 2005, a native arteriovenous fistula (AVF) was used by 67-91% of prevalent patients in Japan, Italy, Germany, France, Spain, the UK, Australia and New Zealand, and 50-59% in Belgium, Sweden and Canada. From 1996 to 2007, AVF use rose from 24% to 47% in the USA but declined in Italy, Germany and Spain. Moreover, graft use fell by 50% in the USA from 58% use in 1996 to 28% by 2007. Across three phases of data collection, patients consistently were less likely to use an AVF versus other VA types if female, of older age, having greater body mass index, diabetes, peripheral vascular disease or recurrent cellulitis/gangrene. In addition, countries with a greater prevalence of diabetes in HD patients had a significantly lower percentage of patients using an AVF. Despite poorer outcomes for central vein catheters, catheter use rose 1.5- to 3-fold among prevalent patients in many countries from 1996 to 2007, even among non-diabetic patients 18-70 years old. Furthermore, 58-73% of patients new to end-stage renal disease (ESRD) used a catheter for the initiation of HD in five countries despite 60-79% of patients having been seen by a nephrologist >4 months prior to ESRD. Patients were significantly (P < 0.05) less likely to start dialysis with a permanent VA if treated in a faciity that (1) had a longer time from referral to access surgery evaluation or from evaluation to access creation and (2) had longer time from access creation until first AVF cannulation. The median time from referral until access creation varied from 5-6 days in Italy, Japan and Germany to 40-43 days in the UK and Canada. Compared to patients using an AVF, patients with a catheter displayed significantly lower mean Kt/V levels. CONCLUSIONS: Most countries meet the contemporary National Kidney Foundation's Kidney Disease Outcomes Quality Initiative goal for AVF use; however, there is still a wide variation in VA preference. Delays between the creation and cannulation must be improved to enhance the chances of a future permanent VA. Native arteriovenous fistula is the VA of choice ensuring dialysis adequacy and better patient outcomes. Graft is, however, a better alternative than catheter for patients where the creation of an attempted AVF failed or could not be created for different reasons.

PURPOSE: Previous trials have suggested a quality-of-life (QOL) improvement for anemic cancer patients treated with erythropoietin, but few used QOL as the primary outcome. We designed a trial to investigate the effects of epoetin alfa therapy on the QOL of anemic patients with advanced non-small-cell carcinoma of the lung (NSCLC). PATIENTS AND METHODS: A multicenter, randomized, double-blind, placebo-controlled trial was conducted. The proposed sample size was 300 patients. Eligible patients were required to have NSCLC unsuitable for curative therapy and baseline hemoglobin (Hgb) levels less than 121 g/L. Patients were assigned to 12 weekly injections of subcutaneous epoetin alpha or placebo, targeting Hgb levels between 120 and 140 g/L. The primary outcome was the difference in the change in Functional Assessment of Cancer Therapy-Anemia scores between baseline and 12 weeks. RESULTS: Reports of thrombotic events in other epoetin trials prompted an unplanned safety analysis after 70 patients had been randomly assigned (33 to the active arm and 37 to the placebo arm). This revealed a significant difference in the median survival in favor of the patients on the placebo arm of the trial (63 v 129 days; hazard ratio, 1.84; P = .04). The Steering Committee closed the trial. Patient numbers compromised the interpretation of the QOL analysis, but a positive Hgb response was noted with epoetin alfa treatment. CONCLUSION: An unplanned safety analysis suggested decreased overall survival in patients with advanced NSCLC treated with epoetin alfa. Although infrequent, other similar reports highlight the need for ongoing trials evaluating erythropoietin receptor agonists to ensure that overall survival is monitored closely.

About 115 years ago, the first diagnosis of interstitial cystitis (IC) was offered as a reason to explain the pain related to scarring and inflammation in the bladder. Later, Hunner described the pathognomonic ulcer that bears his name, which is only found in about 5% to 10% of patients with IC. Today, IC is considered a controversial diagnosis. There are still a significant number of clinicians that do not believe in the diagnosis. Some people consider it to be only a diagnosis of exclusion -after every other bladder condition has been ruled out. However, population studies have demonstrated that there is a huge number of patients (mainly female) that fulfill the NIH and/or other diagnostic criteria and deserve the treatment for IC. Frequency, urgency and pain (pelvic and/or voiding) with negative urinary cultures should be considered IC and treated as such. Dyspareunia is one of the commonest complaints of the IC sufferer. The physical, sexual and emotional impact of delayed or misdiagnois of this condition can be devastating or even suicide-provoking in some patients. We now have some excellent, effective and safe intravesical and oral therapies that can provide major relief to a significant number of patients.

BACKGROUND AND OBJECTIVES: Very few large-scale studies have investigated the determinants of health-related quality of life (HRQOL) in chronic kidney disease (CKD) patients not on dialysis or the evolution of HRQOL over time. DESIGN AND SETTING: A prospective evaluation was undertaken of HRQOL in a cohort of 1186 CKD patients cared for in nephrology clinics in North America. Baseline and follow-up HRQOL were evaluated using the validated Kidney Disease Quality Of Life instrument. RESULTS: Baseline measures of HRQOL were reduced in CKD patients in proportion to the severity grade of CKD. Physical functioning score declined progressively with more advanced stages of CKD and so did the score for role-physical. Female gender and the presence of diabetes and a history of cardiovascular co-morbidities were also associated with reduced HRQOL (physical composite score: male: 41.0 +/- 10.2; female: 37.7 +/- 10.8; P < 0.0001; diabetic: 37.3 +/- 10.6; nondiabetic: 41.6 +/- 10.2; P < 0.0001; history of congestive heart failure, yes: 35.4 +/- 9.7; no: 40.3 +/- 10.6; P < 0.0001; history of myocardial infarction, yes: 36.1 +/- 10.0; no: 40.2 +/- 10.6; P < 0.0001). Anemia and beta blocker usage were also associated with lower HRQOL scores. HRQOL measures declined over time in this population. The main correlates of change over time were age, albumin level and co-existent co-morbidities. CONCLUSIONS: These observations highlight the profound impact CKD has on HRQOL and suggest potential areas that can be targeted for therapeutic intervention.

Background and objectives Elevated parathyroid hormone levels may be associated with adverse clinical outcomes in patients on dialysis. After the introduction of practice guidelines suggesting higher parathyroid hormone targets than those previously recommended, changes in parathyroid hormone levels and treatment regimens over time have not been well documented. Design, setting, participants, & measurements Using data from the international Dialysis Outcomes and Practice Patterns Study, trends in parathyroid hormone levels and secondary hyperparathyroidism therapies over the past 15 years and the associations between parathyroid hormone and clinical outcomes are reported; 35,655 participants from the Dialysis Outcomes and Practice Patterns Study phases 1–4 (1996–2011) were included. Results Median parathyroid hormone increased from phase 1 to phase 4 in all regions except for Japan, where it remained stable. Prescriptions of intravenous vitamin D analogs and cinacalcet increased and parathyroidectomy rates decreased in all regions over time. Compared with 150–300 pg/ml, in adjusted models, all-cause mortality risk was higher for parathyroid hormone=301–450 (hazard ratio, 1.09; 95% confidence interval, 1.01 to 1.18) and >600 pg/ml (hazard ratio, 1.23; 95% confidence interval, 1.12 to 1.34). Parathyroid hormone >600 pg/ml was also associated with higher risk of cardiovascular mortality as well as all-cause and cardiovascular hospitalizations. In a subgroup analysis of 5387 patients not receiving vitamin D analogs or cinacalcet and with no prior parathyroidectomy, very low parathyroid hormone (<50 pg/ml) was associated with mortality (hazard ratio, 1.25; 95% confidence interval, 1.04 to 1.51). Conclusions In a large international sample of patients on hemodialysis, parathyroid hormone levels increased in most countries, and secondary hyperparathyroidism treatments changed over time. Very low and very high parathyroid hormone levels were associated with adverse outcomes. In the absence of definitive evidence in support of a specific parathyroid hormone target, there is an urgent need for additional research to inform clinical practice.

Pregnancy is rare in women with ESRD and when it occurs, it is often accompanied by significant maternal and fetal morbidity and even mortality. Preliminary data from the Toronto Nocturnal Hemodialysis Program suggested that increased clearance of uremic toxins by intensified hemodialysis improves pregnancy outcomes, but small numbers and the absence of a comparator group limited widespread applicability of these findings. We compared pregnancy outcomes from 22 pregnancies in the Toronto Pregnancy and Kidney Disease Clinic and Registry (2000-2013) with outcomes from 70 pregnancies in the American Registry for Pregnancy in Dialysis Patients (1990-2011). The primary outcome was the live birth rate and secondary outcomes included gestational age and birth weight. The live birth rate in the Canadian cohort (86.4%) was significantly higher than the rate in the American cohort (61.4%; P=0.03). Among patients with established ESRD, the median duration of pregnancy in the more intensively dialyzed Toronto cohort was 36 weeks (interquartile range, 32-37) compared with 27 weeks (interquartile range, 21-35) in the American cohort (P=0.002). Furthermore, a dose response between dialysis intensity and pregnancy outcomes emerged, with live birth rates of 48% in women dialyzed ≤20 hours per week and 85% in women dialyzed >36 hours per week (P=0.02), with a longer gestational age and greater infant birth weight for women dialyzed more intensively. Pregnancy complications were few and manageable. We conclude that pregnancy may be safe and feasible in women with ESRD receiving intensive hemodialysis.

OBJECTIVE: To develop an instrument to evaluate the credibility of anchor based minimal important differences (MIDs) for outcome measures reported by patients, and to assess the reliability of the instrument. DESIGN: Instrument development and reliability study. DATA SOURCES: Initial criteria were developed for evaluating the credibility of anchor based MIDs based on a literature review (Medline, Embase, CINAHL, and PsycInfo databases) and the experience of the authors in the methodology for estimation of MIDs. Iterative discussions by the team and pilot testing with experts and potential users facilitated the development of the final instrument. PARTICIPANTS: With the newly developed instrument, pairs of masters, doctoral, or postdoctoral students with a background in health research methodology independently evaluated the credibility of a sample of MID estimates. MAIN OUTCOME MEASURES: Core credibility criteria applicable to all anchor types, additional criteria for transition rating anchors, and inter-rater reliability coefficients were determined. RESULTS: The credibility instrument has five core criteria: the anchor is rated by the patient; the anchor is interpretable and relevant to the patient; the MID estimate is precise; the correlation between the anchor and the outcome measure reported by the patient is satisfactory; and the authors select a threshold on the anchor that reflects a small but important difference. The additional criteria for transition rating anchors are: the time elapsed between baseline and follow-up measurement for estimation of the MID is optimal; and the correlations of the transition rating with the baseline, follow-up, and change score in the patient reported outcome measures are satisfactory. Inter-rater reliability coefficients (ĸ) for the core criteria and for one item from the additional criteria ranged from 0.70 to 0.94. Reporting issues prevented the evaluation of the reliability of the three other additional criteria for the transition rating anchors. CONCLUSIONS: Researchers, clinicians, and healthcare policy decision makers can consider using this instrument to evaluate the design, conduct, and analysis of studies estimating anchor based minimal important differences.

Background and objectives: Women of childbearing age on conventional hemodialysis (CHD) have decreased fertility when compared with the general population. Even in women who conceived, maternal morbidity and fetal mortality remained elevated. We hypothesized that nocturnal hemodialysis (NHD) (3 to 6 sessions per week, 6 to 8 h per treatment), by augmenting uremic clearance, leads to a more hospitable maternal environment and therefore superior outcomes in fertility and pregnancy compared with CHD. Design, setting, participants, and measurements: This is a descriptive cohort study of all female patients achieving pregnancy and delivering a live infant while on NHD at the University Health Network, St. Michael's Hospital, and Humber River Regional Hospital from 2001 to 2006 in Toronto, Canada. Our primary objective was to describe maternal and fetal outcomes in addition to the changes in biochemical parameters after conception in our cohort. Results: Our cohort included five patients (age range, 31 to 37 yr) who had seven pregnancies while on NHD and delivered six live infants. All had previously been on CHD, but none conceived during that time. In all patients, the amount of hemodialysis was increased (from a weekly mean of 36 ± 10 to 48 ± 5 h; P < 0.01) after pregnancy was diagnosed. Mean predialysis blood urea and mean arterial BP were maintained within normal physiological parameters. The mean gestational age of the cohort was 36.2 ± 3 wk and the mean birth weight was 2417.5 ± 657 g. The maternal and fetal complications observed in the cohort included intrauterine growth restriction or small for gestational age (n = 2), preterm delivery (<32 wk) (n = 1), and shortened cervix threatened labor (n = 1). Anemia was accentuated during pregnancy, and intravenous iron and erythropoietin requirements were increased. To maintain normal physiological indices for plasma phosphate, an augmented dialysate phosphate supplementation regimen was required. Conclusions: NHD may allow for improved fertility. Delivering a live infant at a mature gestational age is feasible for patients on NHD. Our cohort tended to have fewer maternal and fetal complications compared with historical controls. Hemoglobin and phosphate levels must be monitored with treatment adjusted accordingly.

BACKGROUND: Chlorpromazine, formulated in the 1950s, remains a benchmark treatment for people with schizophrenia. OBJECTIVES: To evaluate the effects of chlorpromazine for schizophrenia in comparison with placebo. SEARCH STRATEGY: We updated previous searches of the Cochrane Schizophrenia Group Register (October 1999), Biological Abstracts (1982-1995), the Cochrane Library (1999, Issue 2), EMBASE (1980-1995), MEDLINE (1966-1995), PsycLIT (1974-1995), and the Cochrane Schizophrenia Group Register (June 2002), by searching The Cochrane Schizophrenia Group Trials Register (January 2007). We searched references of all identified studies for further trial citations. We contacted pharmaceutical companies and authors of trials for additional information. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) comparing chlorpromazine with placebo for people with schizophrenia and non-affective serious/chronic mental illness irrespective of mode of diagnosis. Primary outcomes of interest were death, violent behaviours, overall improvement, relapse and satisfaction with care. DATA COLLECTION AND ANALYSIS: We independently inspected citations and abstracts, ordered papers, re-inspected and quality assessed these. BT and JR extracted data. CEA and GA independently checked a 10% sample for reliability. We analysed dichotomous data using fixed effects relative risk (RR) and estimated the 95% confidence interval (CI) around this. Where possible we calculated the number needed to treat (NNT) or number needed to harm (NNH) statistics. We excluded continuous data if more than 50% of participants were lost to follow up; where continuous data were included, we analysed this data using fixed effects weighted mean difference (WMD) with a 95% confidence interval. MAIN RESULTS: We inspected over 1000 electronic records. The review currently includes 302 excluded studies and 50 included studies. We found chlorpromazine reduces relapse over the short (n=74, 2 RCTs, RR 0.29 CI 0.1 to 0.8) and medium term (n=809, 4 RCTs, RR 0.49 CI 0.4 to 0.6) but data are heterogeneous. Longer term homogeneous data also favoured chlorpromazine (n=512, 3 RCTs, RR 0.57 CI 0.5 to 0.7, NNT 4 CI 3 to 5). We found chlorpromazine provided a global improvement in a person's symptoms and functioning (n=1121, 13 RCTs, RR 'no change/not improved' 0.80 CI 0.8 to 0.9, NNT 6 CI 5 to 8). Fewer people allocated to chlorpromazine left trials early (n=1780, 26 RCTs, RR 0.65 CI 0.5 to 0.8, NNT 15 CI 11 to 24) compared with placebo. There are many adverse effects. Chlorpromazine is clearly sedating (n=1404, 19 RCTs, RR 2.63 CI 2.1 to 3.3, NNH 5 CI 4 to 8), it increases a person's chances of experiencing acute movement disorders (n=942, 5 RCTs, RR 3.5 CI 1.5 to 8.0, NNH 32 CI 11 to 154), parkinsonism (n=1265, 12 RCTs, RR 2.01 CI 1.5 to 2.7, NNH 14 CI 9 to 28). Akathisia did not occur more often in the chlorpromazine group than placebo (n=1164, 9 RCTs, RR 0.78 CI 0.5 to 1.1). Chlorpromazine clearly causes a lowering of blood pressure with accompanying dizziness (n=1394, 16 RCTs, RR 2.37 CI 1.7 to 3.2, NNH 11 CI 7 to 21) and considerable weight gain (n=165, 5 RCTs, RR 4.92 CI 2.3 to 10.4, NNH 2 CI 2 to 3). AUTHORS' CONCLUSIONS: The results of this review confirm much that clinicians and recipients of care already know but aim to provide quantification to support clinical impression. Chlorpromazine's global position as a 'benchmark' treatment for psychoses is not threatened by the findings of this review. Chlorpromazine, in common use for half a century, is a well established but imperfect treatment. Judicious use of this best available evidence should lead to improved evidence-based decision making by clinicians, carers and patients.

Patients who have end-stage renal failure and are treated by hemodialysis (HD) face a stressful chronic illness with a demanding treatment regimen that affects quality of life. Quality-of-life domains can be measured by assessment questionnaires that are easy to complete, reliable, valid, and sensitive to change. There is current interest in HD regimens that provide more frequent treatments (e.g., daily) than the conventional thrice weekly. Improvement in quality of life by these regimens has been reported. A published prospective, cohort, controlled study (London Daily/Nocturnal Hemodialysis Study) included the results of a number of quality-of-life indicators that were applied to the study patients. In general, the indicators used were well established and of proven validity. Included was one single question that was added intuitively and had not received previous validation: "How long does it take you to recover from a dialysis session?" The responses to this question allow the validation of this simple question as a tool to be used in HD clinical research. Twenty-three patients who were treated by frequent HD (5 to 7 d or nights) and 22 control subjects who were treated by thrice-weekly dialysis were studied during an 18-mo period. The "time to recovery" question was administered along with a battery of renal disease-specific questionnaires and the Generic Medical Outcomes Survey 36 Item-Short Form (SF-36) plus the global Health Utilities Index. Missing data rates, reliability over time, construct validity, and sensitivity to change were assessed from the "time to recovery" responses by standard methods. The question was administered on a total of 314 occasions and answered successfully on 313. The test-retest correlation over 3-mo intervals was highly significant (r = 0.962, P = 0.000; n = 100). Convergent construct validity was established by significant correlations between time to recovery and fatigue (r = 0.38, P = 0.000; n = 313), dialysis stress (r = 0.348, P = 0.000), disease stress (r = 0.374, P = 0.000), SF-36 subscales especially vitality (r = -0.356 P = 0.000), and the Health Utilities Index (r = -0.232, P = 0.000). These scales captured mainly physical or physiologic domains. Divergent construct validity was established by lack of correlations between "time to recovery" and a number of subscales that captured mainly emotional or psychosocial domains, e.g., SF-36 subscale for "role emotional" (r = -0.102, NS) and dialysis stressors such as access problems (r = -0.015, NS) or equipment malfunction (r = 0.032, NS). Test sensitivity was established when the conventionally dialyzed group showed no significant difference in time to recovery between baseline and other time periods, whereas the daily/nocturnal group had a significant reduction between baseline (while on conventional dialysis) and the result at each other time period (minimum P = 0.05). There also was a significant difference between the control and experimental groups over time (ANOVA P = 0.000). The response to the question, "How long does it take you to recover from a dialysis session?" is interpreted easily, is easy to which to respond, shows stability over time by test-retest, shows both convergent and divergent validity, and is sensitive to change. As such, it should be considered as a standard question in HD-related studies in which a health-related quality-of-life outcome is examined.

In Brief PURPOSE: To enhance the clinician's knowledge about the relationship between increased periwound skin temperature and local wound infection in patients with chronic leg ulcers. TARGET AUDIENCE: This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. OBJECTIVE: After participating in this educational activity, the participant should be better able to: Interpret research findings on chronic wound assessment including skin temperature assessments. Examine the study reported in this article for appropriate use of periwound skin temperature assessment. Analyze this study's findings regarding the relationship between skin temperature and chronic wound infection. OBJECTIVE: Increased local temperature is a classic sign of wound infection, and its quantitative measurement has the potential to assist with assessment and diagnosis of chronic deep wound and surrounding skin infection at the bedside. Evidence supporting such use in chronic wound care is very limited. This clinical pilot study was conducted in an attempt to quantify the relationship between increased periwound skin temperature and wound infection, as well as validate use of a handheld infrared thermometer for the wound care practitioner. DESIGN, SETTING, AND PARTICIPANTS: Using a cross-sectional design, 2 groups of participants were recruited from a chronic wound clinic: without wounds (n = 20) and with chronic leg ulcers (n = 40). Participant and wound characteristics were documented. All skin temperatures were documented using a handheld infrared thermometer under consistent environmental conditions within the clinic. Data analysis was based on the difference (Δ) in skin temperature (in degrees Fahrenheit) between a target or wound site and an equivalent contralateral control site. Wound infection was identified using the combination of a validated assessment tool and clinical judgment. Supplemental semiquantitative bacterial swabs were collected from all wounds. OUTCOME MEASURES: Descriptive statistics were analyzed using the chi-squared calculation. A Pearson r calculation of test-retest skin temperature data collected from nonwounded participants initially determined reliability of the infrared thermometer. Correlation of increased periwound skin temperature to wound infection was determined by calculation of a 1-way analysis of variance. MAIN RESULTS: The infrared thermometer was found to be reliable (r = 0.939, P = .000 at a 95% confidence interval). A statistically significant relationship between increased periwound skin temperature and wound infection was identified (F = 44.238, P = .000 at a 95% confidence interval). Neither patient nor wound characteristics were significantly different between the participants with noninfected or infected wounds. CONCLUSION: The results of this study demonstrate that incorporating quantitative skin temperature measurement into routine wound assessment provides a timely and reliable method for a wound care practitioner to quantify the heat associated with deep and surrounding skin infection and to monitor ongoing wound status. Study limitations may reduce transferability of these findings to wound types other than chronic leg ulcers. Further research is needed to support and strengthen these results. In this continuing education activity, the authors discuss the relationship between increased periwound skin temperature and wound infection, as well as validate use of a handheld infrared thermometer for the wound care practitioner.

PURPOSE: In 1992 we initiated a national randomized prospective trial of 3 months of cyproterone acetate before radical prostatectomy compared to prostatectomy alone. Initial results indicated a 50% decrease in the rate of positive surgical margins. This decrease did not translate into a difference in prostate specific antigen (PSA) progression at 3 years. This report is on the long-term outcome (median followup 6 years) of this cohort. MATERIALS AND METHODS: This prospective, randomized, open label trial compared 100 mg cyproterone acetate 3 times daily for 3 months before surgery to surgery alone. Randomization occurred between January 1993 and April 1994. Patients were stratified according to clinical stage, baseline serum PSA and Gleason sum. A total of 213 patients were accrued. Biochemical progression was defined as 2 consecutive detectable PSAs (greater than 0.2 ng/ml) at least 4 weeks apart, re-treatment or death from prostate cancer. RESULTS: A total of 34 (33.6%) patients undergoing surgery only and 42 (37.5%) patients given neoadjuvant hormone therapy (NHT) had biochemical recurrence during the median followup of 6 years. Despite the significant pathological down staging in this study, there was no significant difference in number of patients with no evidence of biochemical disease (bNED) survival (p = 0.732). A bNED survival benefit favoring NHT was seen in men with a baseline PSA greater than 20 (p = 0.015). CONCLUSIONS: After 6 years of followup there was no overall benefit with 3 months of NHT. Improved bNED survival was seen in the highest risk PSA group (PSA greater than 20). The possibility that high risk patients may benefit from NHT warrants further investigation.

Long-term nocturnal hemodialysis, which uses longer and more frequent sessions than conventional hemodialysis, lowers clinic blood pressure and left ventricular mass. We tested the hypotheses that short-term nocturnal hemodialysis would (1) reduce ambulatory blood pressure; (2) cause peripheral vasodilation; (3) lower plasma norepinephrine concentration; and (4) improve the arterial response to reactive hyperemia (a marker of endothelium-dependent vasodilation). We studied 18 consecutive patients (age, 41+/-2; [mean+/-SEM]) before and 1 and 2 months after conversion from conventional (three 4-hour sessions per week) to nocturnal (six 8-hour sessions per week) hemodialysis. As the dialysis dose per session (Kt/V) increased from 1.24+/-0.06 to 2.04+/-0.08 after 2 months (P=0.02), symptomatic hypotension developed and most antihypertensive medications were withdrawn. Nocturnal hemodialysis nonetheless lowered 24-hour mean arterial pressure (from 102+/-3 to 90+/-2 mm Hg after 2 months; P=0.01), total peripheral resistance (from 1967+/-235 to 1499+/-191 dyne x s x cm(-5); P<0.01) and plasma norepinephrine (from 2.66+/-0.4 to 1.96+/-0.2 nmol; P=0.04). Endothelium-dependent vasodilation could not be elicited during conventional hemodialysis (-2.7+/-1.8%) but was restored (+8.0+/-1.0%; P=0.001) after 2 months of nocturnal hemodialysis. The brachial artery response to nitroglycerin also improved (from 6.9+/-2.8 to 15.7+/-1.6%; P<0.05). Nocturnal hemodialysis had no effect on weight or on stroke volume. Rapid reversal of these markers of adverse cardiovascular events with more intense hemodialysis may translate into improved outcome in this high-risk group of patients.

BACKGROUND: The optimal vascular access for chronic maintenance haemodialysis (HD) is the native arteriovenous fistula (AVF). Vascular access practice patterns are reported for a Canadian cohort of patients from the Dialysis Outcomes and Practice Patterns Study (DOPPS II). METHODS: DOPPS II is a prospective, observational study in 12 countries, including Canada. A representative random sample of 20 Canadian HD facilities and patients within those units were studied during 2002-2004. Canadian results were compared with those found in Europe and the USA. RESULTS: AVF use in Canadian prevalent (53%) and incident (26%) patients was lower than Canadian guidelines recommend (60%), and lower than in Europe [prevalent (74%), incident (50%)]. Despite 85% of Canadian HD patients having seen a nephrologist for > 1 month prior to starting dialysis, central venous catheter use in Canada (33% in prevalent patients, 70% in incident patients) was much higher than in Europe (prevalent 18%, incident 46%) and slightly higher than in the USA (prevalent 25%, incident 66%). This pattern is contrary to the preferences of Canadian medical directors and vascular access surgeons. The typical time from referral until permanent vascular access creation is substantially longer in Canada (61.7 days) than in Europe (29.4 days) or the USA (16 days). This longer delay time and higher catheter use in Canada may be a consequence of the significantly lower number of access surgeons per 100 HD patients in Canada (2.9) compared with the USA (8.1) and Europe (4.6). Furthermore, the median hours per week devoted to vascular access-related surgery per 100 patients is substantially lower in Canada (0.027 h) compared with the USA (0.082 h) and Europe (0.059 h). CONCLUSION: These findings suggest that Canadian chronic HD patients often rely on central venous catheters for vascular access, despite their known association with numerous detrimental outcomes in HD. Nephrologists, vascular access surgeons, interventional radiologists, other physicians and health care funding bodies must be more broadly educated about the priority of AVF creation as the preferred vascular access for chronic HD patients. They must work together to secure both the human and financial resources and other health care system enhancements to increase AVF creation rates in a timely manner.

To achieve sustainable change, quality improvement initiatives must become the new way of working rather than something added on to routine clinical care. However, most organizational change is not maintained. In this next article in this Moving Points in Nephrology feature on quality improvement, we provide health care professionals with strategies to sustain and support quality improvement. Threats to sustainability may be identified both at the beginning of a project and when it is ready for implementation. The National Health Service Sustainability Model is reviewed as one example to help identify issues that affect long-term success of quality improvement projects. Tools to help sustain improvement include process control boards, performance boards, standard work, and improvement huddles. Process control and performance boards are methods to communicate improvement results to staff and leadership. Standard work is a written or visual outline of current best practices for a task and provides a framework to ensure that changes that have improved patient care are consistently and reliably applied to every patient encounter. Improvement huddles are short, regular meetings among staff to anticipate problems, review performance, and support a culture of improvement. Many of these tools rely on principles of visual management, which are systems transparent and simple so that every staff member can rapidly distinguish normal from abnormal working conditions. Even when quality improvement methods are properly applied, the success of a project still depends on contextual factors. Context refers to aspects of the local setting in which the project operates. Context affects resources, leadership support, data infrastructure, team motivation, and team performance. For these reasons, the same project may thrive in a supportive context and fail in a different context. To demonstrate the practical applications of these quality improvement principles, these principles are applied to a hypothetical quality improvement initiative that aims to promote home dialysis (home hemodialysis and peritoneal dialysis).

BACKGROUND: Kidney transplantation is the gold standard renal replacement therapy. Nocturnal haemodialysis (NHD) is an intensive dialysis modality (6-8 h/session, 3-7 sessions/week) associated with a significant improvement of clinical and biochemical parameters compared to conventional dialysis. To date, no studies have compared survival in patients treated with NHD and kidney transplantation. METHODS: Using data from two regional NHD programmes and the USRDS from 1994 to 2006, we performed a matched cohort study comparing survival between NHD and deceased and living donor kidney transplantation (DTX and LTX) by randomly matching NHD patients to transplant recipients in a 1:3:3 ratio. The independent association of treatment modality with survival was determined using Cox multivariate regression. RESULTS: The total study population consisted of 177 NHD patients matched to 1062 DTX and LTX recipients (total 1239 patients) followed for a maximum of 12.4 years. During the follow-up period, the proportion of deaths among NHD, DTX and LTX patients was 14.7%, 14.3% and 8.5%, respectively (P = 0.006). We found no difference in the adjusted survival between NHD and DTX (HR 0.87, 95% CI 0.50-1.51; NHD reference group), while LTX survival was better (HR 0.51, 95% CI 0.28-0.91). CONCLUSIONS: These results indicate that NHD and DTX survival is comparable, and suggest that this intensive dialysis modality may be a bridge to transplantation or even a suitable alternative in the absence of LTX in the current era of growing transplant waiting lists and organ shortage.

New staging systems for CKD account for both reduced eGFR and albuminuria; whether each measure associates with greater risk of hemorrhage is unclear. In this retrospective cohort study (2002-2010), we grouped 516,197 adults ≥40 years old by eGFR (≥90, 60 to <90, 45 to <60, 30 to <45, 15 to <30, or <15 ml/min per 1.73 m(2)) and urine albumin-to-creatinine ratio (ACR; >300, 30-300, or <30 mg/g) to examine incidence of hemorrhage. The 3-year cumulative incidence of hemorrhage increased 20-fold across declining eGFR and increasing urine ACR groupings (highest eGFR/lowest ACR: 0.5%; lowest eGFR/highest ACR: 10.1%). Urine ACR altered the association of eGFR with hemorrhage (P<0.001). In adjusted models using the highest eGFR/lowest ACR grouping as the referent, patients with eGFR=15 to <30 ml/min per 1.73 m(2) had adjusted relative risks of hemorrhage of 1.9 (95% confidence interval [95% CI], 1.5 to 2.4) with the lowest ACR and 3.7 (95% CI, 3.0 to 4.5) with the highest ACR. Patients with the highest eGFR/highest ACR had an adjusted relative risk of hemorrhage of 2.3 (95% CI, 1.8 to 2.9), comparable with the risk for patients with the lowest eGFR/lowest ACR. The associations attenuated but remained significant after adjustment for anticoagulant and antiplatelet use in patients ≥66 years old. The risk of hemorrhage differed by urine ACR in high risk subgroups. Our data show that declining eGFR and increasing albuminuria each independently increase hemorrhage risk. Strategies to reduce hemorrhage events among patients with CKD are warranted.