Randomized Controlled Trials 1: Design.

Today's clinical practice relies on the application of well-designed clinical research, the gold standard test of an intervention being the randomized controlled trial. Principles of the randomized control trial include emphasis on the principal research question, randomization, blinding; definitions of outcome measures, of inclusion and exclusion criteria, and of co-morbid and confounding factors; enrolling an adequate sample size; planning data management and analysis; preventing challenges to trial integrity such as drop-out, drop-in, and bias. The application of pre-trial planning is stressed to ensure the proper application of epidemiological principles resulting in clinical studies that are feasible and generalizable. In addition, funding strategies and trial team composition are discussed.

Acute Exercise Induced Compartment Syndrome in an 22-Year-Old Active-Duty Man and Review of the Literature.

Acute exercise induced compartment syndrome is a rare clinical diagnosis with serious long-term ramifications if not diagnosed in a timely fashion. We present a case of acute exercise induced compartment syndrome of the right lower extremity in a 22-year-old active-duty man that occurred during a physical fitness assessment. He was treated with a two incision four compartment fasciotomy, however required debridement of muscle from the anterior compartment on subsequent washouts of the wound that led to significant foot drop postoperatively. We reviewed the literature for published cases of acute exercise induced compartment syndrome and provide some information from the 47 patients identified in our review. This case highlights a unique pathology for which military providers should have a strong index of suspicion. It additionally stresses the importance of adequate hydration and musculoskeletal conditioning in the setting of military fitness assessments.

NSAID administration post colorectal surgery increases anastomotic leak rate: systematic review/meta-analysis.

BACKGROUND: Current enhanced recovery guidelines suggest that opioid sparing medications should be used for analgesia whenever possible following colorectal surgery. The present study aims to assess whether post-operative NSAID use is associated with an increased anastomotic leak rate after a colonic or rectal anastomosis. METHODS: A systematic review was performed for studies investigating anastomotic leak rate following NSAID use vs control after colonic or rectal anastomosis. Meta-analysis was performed to assess for overall risk of anastomotic leak with NSAID use, as well as sub-group analysis to compare selective vs non-selective NSAIDs and drug-specific NSAID safety profiles. RESULTS: Seven studies were included in the final review. Use of an NSAID post-operatively was associated with an overall increased risk of anastomotic leakage [OR 1.58 (1.23, 2.03), P = 0.0003]. Non-selective NSAIDs were associated with an increased risk [OR 1.79 (1.47, 2.18), P < 0.00001], but selective NSAIDs were not. The non-selective NSAID diclofenac was associated with an increased leak rate [OR 2.79 (1.96, 3.96), P < 0.00001], but ketorolac was not [OR 1.36 (0.89, 2.06), P = 0.16]. CONCLUSIONS: Great caution must be taken when prescribing NSAIDs following colonic or rectal anastomotic creation. The safety profile varies within the NSAID class and further research is needed to clarify which NSAIDs are safe for use and which are not.

Estimates of health utility scores in chronic kidney disease.

INTRODUCTION: Coverage decisions in publicly funded healthcare systems require a formal, systematic and transparent assessment process for policies related to distribution of resources. The process is complex and employs multiple types of information, such as clinical effectiveness, costs and health utility scores which are used to produce quality-adjusted life years. The purpose of this study was to create health utility scores for CKD patients within the Canadian population. METHODS: This is a cross-sectional study of CKD patients. We administered the Short-Form 36 Quality of Life Questions to all participants and employed the Short-Form 6 Dimension index to create health utility scores which were created using a set of parametric preference weights, nonparametric preference weights and ordinal health state valuation techniques obtained from a sample of the general population. RESULTS: Utility values in the dialysis group were lower than in the non-dialysis group. There was a significant relationship between age and health utility scores: As age increases, health utility scores decrease. Diabetes was associated with lower health utility scores in dialysis patients, whereas other covariates did not reach levels of statistical significance in our stepwise regression models. The parametric Bayesian model and standard gamble approach yielded the same results, while the correlation between the nonparametric and parametric methods was above 0.9. CONCLUSION: Health utility scores were low relative to the general population norm in our study cohort. Longitudinal assessment of CKD patients to capture possible fluctuations in health utility scores may add useful information.

Costs Associated With Intravenous Darbepoetin Versus Epoetin Therapy in Hemodialysis Patients: A Randomized Controlled Trial.

BACKGROUND: Anemia of chronic kidney disease is associated with adverse outcomes and a reduced quality of life. Erythropoiesis-stimulating agents (ESAs) have improved anemia management, and 2 agents are available in Canada, epoetin alfa (EPO) and darbepoetin alfa (DA). EPO and DA are considered equally effective in achieving target hemoglobin (Hb), but it is not clear whether there is a cost difference. There have been few head-to-head comparisons; most published studies are observational switch studies. OBJECTIVE: To compare the cost of DA and EPO and to determine the dose conversion ratio over a 12-month period. DESIGN: Randomized controlled trial. SETTING: Canadian outpatient hemodialysis center. PATIENTS: Eligible patients were adult hemodialysis patients requiring ESA therapy. MEASUREMENTS: The primary outcome was ESA cost (Can$) per patient over 12 months. Secondary outcomes included the dose conversion ratio, deviation from target ranges in anemia indices, iron dose and cost, and time and number of dose changes. METHODS: An open-label randomized controlled trial of intravenous (IV) DA versus EPO was conducted in 50 hemodialysis patients. Participants underwent a minimum 6-week run-in phase followed by a 12-month active study phase. ESA and iron were dosed using a study algorithm. RESULTS: The median cost was $4179 (interquartile range [IQR]: $2416-$5955) for EPO and $2303 (IQR: $1178-$4219) for DA with a difference of $1876 (P = .02). The dose conversion ratio was 280:1 (95% confidence interval [CI]: 197-362:1) at the end of the run-in phase, 360:1 (95% CI: 262-457:1) at the 3-month point of the active phase, and 382:1 (95% CI: 235-529:1) at the 6-month point of the active phase. There were no significant differences between the 2 groups in weekly iron dose, Hb, serum ferritin, or transferrin saturation. The number of dose changes and the time to Hb stability were similar. LIMITATIONS: Results may not be generalizable to hemodialysis units without algorithm-based anemia management, with subcutaneous ESA administration, or to the nondialysis chronic kidney disease population. The effective conversion ratio between EPO and DA is known to increase at higher doses; the Hb targets used in the study were slightly higher than those recommended today so it is possible that the doses used were also higher. Because of this, the cost savings estimated for DA could differ somewhat from the savings realizable in current practice. CONCLUSIONS: In this study of hemodialysis patients with comparable anemia management, IV DA cost $1876 less per year per patient than IV EPO. The dose conversion ratio was greater than 350:1 by the 3-month point. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02817555).

CONTEXTE: L'anémie qui résulte de l'insuffisance rénale chronique est associée à des conséquences défavorables sur la santé du patient et par conséquent, à une diminution de sa qualité de vie. Le recours à des agents stimulants l'érythropoïèse (ASE) a permis d'améliorer considérablement le traitement de ce type d'anémie. Deux de ces agents sont disponibles au Canada: l'époétine alfa (EPO) et la darbépoétine alfa (DA). L'efficacité de ces deux molécules à cibler l'hémoglobine (Hb) est considérée comme équivalente, mais la différence de coût de leur utilisation reste à déterminer. Il existe très peu d'études de comparaison directe entre l'EPO et la DA, et la plupart des études publiées consistent en des études observationnelles de transition. OBJECTIFS DE L'ÉTUDE: Comparer les coûts d'utilisation de la DA et de l'EPO et déterminer le ratio de conversion de dose sur une période de 12 mois. TYPE D'ÉTUDE: Il s'agit d'un essai contrôlé randomisé. CADRE DE L'ÉTUDE: Un centre d'hémodialyse ambulatoire canadien. PATIENTS: Les patients admissibles étaient des patients adultes sous hémodialyse et nécessitant un traitement par les ASE. MESURES: Le principal critère évalué était le coût (en dollars canadiens) d'un traitement par les ASE pour chaque patient sur une période de 12 mois. Parmi les résultats secondaires figuraient le ratio de conversion de dose, l'écart de déviation par rapport à la cible pour les indicateurs de l'anémie, la dose de fer et son coût, de même que le temps de stabilisation de la dose et le nombre de changements de dose. MÉTHODOLOGIE: Un essai ouvert, contrôlé et randomisé a été mené auprès de 50 patients en hémodialyse afin de comparer les traitements intraveineux (IV) par la DA et l'EPO. Les participants ont été suivis pour une phase préalable d'une durée minimale de six semaines avant la phase de l'étude active qui s'est étalée sur 12 mois. Les doses de l'ASE et du fer ont été établies à partir d'un algorithme. RÉSULTATS: Le coût médian était de 4 179 $ (Écart interquartile: 2 416 à 5 955 $) pour l'EPO et de 2 303 $ (EI: 1 178 à 4 219 $) pour la DA, soit une différence de 1 876 $ (P = 0,02). Le ratio de conversion de dose était de 280:1 (IC95: 197:1-362:1) à la fin de la phase préalable, de 360:1 (IC à 95%: 262:1-457:1) après trois mois écoulés dans la phase active et de 382:1 (IC95: 235:1-529:1) après 6 mois de phase active. Aucune différence significative n'a été observée entre les deux groupes en ce qui concerne les doses hebdomadaires de fer, les taux d'hémoglobine et de ferritine sérique ou le coefficient de la saturation de la transferrine (TSAT). Enfin, le nombre de modifications de la dose et le temps de stabilisation de l'hémoglobine se sont avérés similaires. LIMITES DE L'ÉTUDE: Il est possible que l'on ne puisse étendre ces résultats aux unités d'hémodialyse où la gestion de l'anémie ne repose pas sur un algorithme. Il est également hasardeux de généraliser ces résultats aux cas où les traitements par un ASE sont administrés par voie sous-cutanée, de même qu'au sein d'une population de patients non-dialysés. Il est connu que le ratio de conversion optimal entre l'EPO et la DA augmente pour les doses élevées. De plus, les cibles d'hémoglobine utilisées dans l'étude étaient légèrement supérieures à celles qui sont recommandées aujourd'hui, il est donc possible que les doses utilisées aient été elles aussi plus élevées. Par conséquent, les économies estimées pour l'administration de DA pourraient différer légèrement des économies réalisables dans la pratique courante. CONCLUSIONS: Cette étude, réalisée auprès de patients hémodialysés dont les traitements de l'anémie par voie intraveineuse étaient comparables, conclut que l'utilisation de la DA permet une économie annuelle de 1 876 $ par rapport à l'utilisation de l'EPO. De plus, le ratio de conversion de dose s'est avéré supérieur à 350:1 après trois mois écoulés dans la phase active de l'étude.

Sleep quality and its correlates in patients with chronic kidney disease: a cross-sectional design.

PURPOSE: Since sympathovagal imbalance influences clinical phenomena, such as hypertension, diabetes mellitus, chronic kidney disease (CKD) and sleeping problems, there should be correlations between these conditions. We hypothesized that sleep quality would be correlated with estimated glomerular filtration rate (eGFR), blood pressure and the presence of diabetes. METHODS: We included 303 CKD patients in this study. We employed the Pittsburgh Sleep Quality Index (PSQI), Beck Depression Inventory (BDI) and Short Form 36 Quality of Life Health Survey Questions (SF-36) to screen sleeping disturbances, depression and quality of life, respectively. A chart review was performed for the patients' demographics, diagnoses and certain laboratory parameters--including blood glucose, hemoglobin, albumin, calcium, phosphate, parathyroid hormone and eGFR. Multivariate logistic regression models were employed to estimate odds ratios with 95% confidence intervals. RESULTS: We included 303 patients in this cross-sectional study. A total of 101 patients were on dialysis. In the univariate models, gender, calcium and mental component summary scores (MCS) reached a significant level of 0.1, and those covariates were included in the multivariate analysis. The reduced models included gender and MCS categories. Female gender increases the risk for poor sleep quality. In our report, evidence suggests MCS domain scores are inversely related to the risk for impaired sleep. CONCLUSION: Our results indicated a high burden of sleep disturbances in kidney patients. In addition, female gender and having low MCS scores may influence sleep quality in kidney patients.

Randomized controlled trials 1: Design.

Today's clinical practice relies on the application of well-designed clinical research, the gold standard test of an intervention being the randomized controlled trial. Principles of the randomized control trial include emphasis on the principal research question, randomization, blinding; definitions of outcome measures, of inclusion and exclusion criteria, and of comorbid and confounding factors; enrolling an adequate sample size; planning data management and analysis; preventing challenges to trial integrity such as drop-out, drop-in, and bias. The application of pretrial planning is stressed to ensure the proper application of epidemiological principles resulting in clinical studies that are feasible and generalizable. In addition, funding strategies and trial team composition are discussed.

Sleep apnea in patients with chronic kidney disease: a single center experience.

PURPOSE: The primary objective of this cross-sectional study was to test factors associated with sleep apnea in patients with chronic kidney disease (CKD). The prevalence of sleep apnea was also assessed. METHODS: We recruited patients with CKD Stage 3-5 who lived in the St. John's area from September 2012 to December 2012. The Berlin Questionnaire and Short Form 36 Quality of Life Health Survey Questions (SF-36) were administered to all participants. RESULTS: We recruited 303 patients (41% female). A total of 157 (51.8%) patients had a high risk for sleep apnea. Higher body mass index and young age were correlated with sleep apnea. Physical component score of SF-36 (PCS) tested as a continuous variable indicated a significant association with the risk for sleep apnea (OR: 0.97, 95% CI: 0.94-0.99, p = 0.03). The association implies 3% change per one point increase in PCS. We categorized mental component score of SF-36 (MCS) into four quartiles, as the linearity assumption was violated. There was a 61% risk increase for poor sleep in those with an MCS score less than the 75th percentile, when compared to those above the 75th percentile (OR: 0.39, 95% CI: 0.21-0.71, p = 0.002). CONCLUSIONS: Sleep apnea is common in kidney patients. People who have low PCS and MCS scores are more prone to sleep apnea or vice versa. Our results also indicate that high BMI and young age are associated with sleep apnea.

Reliability of the interprofessional collaborator assessment rubric (ICAR) in multi source feedback (MSF) with post-graduate medical residents.

BACKGROUND: Increased attention on collaboration and teamwork competency development in medical education has raised the need for valid and reliable approaches to the assessment of collaboration competencies in post-graduate medical education. The purpose of this study was to evaluate the reliability of a modified Interprofessional Collaborator Assessment Rubric (ICAR) in a multi-source feedback (MSF) process for assessing post-graduate medical residents' collaborator competencies. METHODS: Post-graduate medical residents (n = 16) received ICAR assessments from three different rater groups (physicians, nurses and allied health professionals) over a four-week rotation. Internal consistency, inter-rater reliability, inter-group differences and relationship between rater characteristics and ICAR scores were analyzed using Cronbach's alpha, one-way and two-way repeated measures ANOVA, and logistic regression. RESULTS: Missing data decreased from 13.1% using daily assessments to 8.8% utilizing an MSF process, p = .032. High internal consistency measures were demonstrated for overall ICAR scores (α = .981) and individual assessment domains within the ICAR (α = .881 to .963). There were no significant differences between scores of physician, nurse, and allied health raters on collaborator competencies (F2,5 = 1.225, p = .297, η2 = .016). Rater gender was the only significant factor influencing scores with female raters scoring residents significantly lower than male raters (6.12 v. 6.82; F1,5 = 7.184, p = .008, η 2 = .045). CONCLUSION: The study findings suggest that the use of the modified ICAR in a MSF assessment process could be a feasible and reliable assessment approach to providing formative feedback to post-graduate medical residents on collaborator competencies.

Cardiac biomarkers and health-related quality of life in new hemodialysis patients without symptomatic cardiac disease.

BACKGROUND: Health Related Quality of Life (HRQOL) is impaired in hemodialysis patients and cardiac biomarkers are elevated, but their relationship is uncertain. OBJECTIVES: To determine whether the cardiac biomarkers, troponin T and N terminal pro-B type natriuretic peptide (NT-proBNP), predict deterioration in the physical domains of HRQOL. DESIGN: A prospective cohort study of patients in a randomized controlled clinical trial of correction of anemia with erythropoietin. SETTING: Multiple hemodialysis centers located throughout Canada and Europe. PARTICIPANTS: Patients who started maintenance hemodialysis within the previous 3-18 months, with no clinical evidence or prior history of symptomatic cardiac failure or ischemic heart disease, and left ventricular volume < 100 ml/m(2). PREDICTOR: Baseline concentrations of Troponin T and NT-proBNP. OUTCOMES: Physical function and vitality scores using the SF-36 questionnaire and fatigue scores using the FACIT questionnaire at baseline and after 24, 48, and 96 weeks follow-up. METHODS: Univariate analysis of the association between baseline variables and baseline HRQOL scores and change in scores over time was undertaken using linear regression. Multivariate models were created using multiple linear regression, and it was pre-specified that these include the variables which were associated with the outcome at a p < 0.05 in the univariate regression. RESULTS: Baseline median (interquartile range) physical function score was 70 (50-85), vitality 55 (40-75), and fatigue 73 (58-86). The 75th percentile for Troponin T was 0.05 ng/mL and for NT-proBNP 652 ng/mL. High Troponin T levels were significantly associated with deterioration in the 3 physical domains, independent of other risk factors, whereas high NT-proBNP were not associated. In multivariate models baseline Troponin T > 0.05 ng/mL were significantly associated with the change from baseline to 96 weeks follow-up for SF-36 vitality and FACIT-fatigue scores, and approached statistical significance for SF-36 physical function (0.056). LIMITATIONS: Not possible to confirm whether Troponin T associations were independent of subsequent cardiac events. CONCLUSIONS: In hemodialysis patients without prior symptomatic cardiac disease and without a dilated left ventricle at baseline, elevated baseline Troponin T levels, but not NT-pro BNP, were independently associated with deterioration in the physical domains of HRQOL.

CONTEXTE: Chez les patients en hémodialyse, la qualité de vie liée à la santé (QVLS) est diminuée, et les biomarqueurs cardiaques sont élevés, mais la relation entre les deux est incertaine. OBJECTIFS: Déterminer si les biomarquers cardiaques, la troponine T et le N-terminal peptide natriurétique de type B (NT-ProBNP), prédisent la détérioration des domaines physiques de la QVLS. TYPE D'ÉTUDE: Une étude prospective de cohorte sur des patients dans le cadre d'un essai clinique contrôlé randomisé concernant la correction de l'anémie à l'aide de l'érythropoïétine. CONTEXTE: Plusieurs centres d'hémodialyse situés au Canada et en Europe, coordonnés de façon centralisée à partir de St. John's, au Canada, pour les patients canadiens, et de Manchester, en Angleterre, pour les patients européens. PARTICIPANTS: Les patients en hémodialyse chronique de plusieurs centres, qui ont entamé une dialyse au cours des derniers 3 à 18 mois, et qui ne présentent aucune donnée clinique et aucun antécédent d'insuffisance cardiaque symptomatique ou de cardiopathie ischémique, mais un volume ventriculaire gauche < 100 ml/m2. MESURES: Prédicteur: concentration de référence de Troponine T et de NT-proBNP. Résultats: Degré de vitalité et fonction physique à l'aide du questionnaire SF-36 et degré de fatigue à l'aide du questionnaire FACIT, au point de référence, puis après le suivi des 24, 48 et 96 semaines. MÉTHODES: L'analyse unidimensionnelle de l'association entre les variables fondamentales et les scores de référence de la QVLS, et la variation dans les scores a été entreprise au moyen de la régression linéaire. Les modèles multivariables ont été créés en utilisant la régression linéaire multiple, et il a été pré-spécifié que ceux-ci comprenaient les variables associées aux résultats de p < 0,05 dans la régression à une variable. RÉSULTATS: Le score médian de référence (écart interquartile) de la fonction physique était de 70 (50­85), celui de la vitalité de 55 (40­75), et celui de la fatigue 73 (58­86). Le 75e percentile de la troponine T était de 0,05 ng/mL, et pour le NT-proBNP, de 652 ng/mL. Les niveaux élevés de troponine T étaient associés de façon significative à la détérioration des 3 domaines physiques, indépendants des autres facteurs de risque, alors que les niveaux élevés de NT-proBNP ne démontraient aucune association significative. Dans les modèles multivariables, un niveau fondamental de troponine T > 0,05 ng/mL était associé de façon significative à la variation entre le point de référence et le suivi des 96 semaines en ce qui a trait aux scores SF-36 de vitalité et FACIT de fatigue, et avaient une certaine signification statistique à une fonction physique de SF-36 (0,056). LIMITES DE L'ÉTUDE: Impossible de confirmer si les associations avec la troponine T étaient indépendantes d'événements cardiaques subséquents. CONCLUSIONS: Chez les patients en hémodialyse ne présentant pas d'antécédents de maladie cardiaque symptomatique ni une dilatation du ventricule gauche au point de référence, des niveaux élevés de troponine T au point de référence, mais pas de NT-proBNP, ont été indépendamment associés à une détérioration des domaines physiques de QVLS. TRIAL REGISTRATION: Clinical trials.gov # NCT00261521.

Suboptimal initiation of dialysis with and without early referral to a nephrologist.

BACKGROUND: Our objective was to examine patients who initiate renal replacement therapy (RRT) at 10 representative Canadian centers, characterize their initiation as inpatient or outpatient and describe their initial type of dialysis access, duration of pre-dialysis care and clinical status at the time of dialysis initiation. We also examined the impact of an optimal dialysis start (i.e. initiated as an outpatient with an arteriovenous fistula, arteriovenous graft or peritoneal dialysis catheter) on subsequent health outcomes. METHODS: Charts of consecutive incident RRT patients were identified from 1 July to 31 December 2006. Information was collected until 6 months after the initiation or until death, transplant or transfer. RESULTS: Three hundred and thirty-nine incident RRT patients were studied: 39.6% initiated as an inpatient; 54% started hemodialysis (HD) with a central venous catheter; 15.3% had <1 month predialysis care, while 64.6% had >1 year. Optimal starts occurred in 39.5% of patients. For HD patients, optimal starts occurred in 19.8%. Suboptimal starts were noted in patients referred <12 months prior to end-stage renal disease (44%) and in patients referred earlier (56%). The composite end point of death, transfusion or subsequent hospitalization was significantly reduced with an optimal start [hazard ratio 0.47 (95% confidence interval 0.32-0.68), P = 0.0001]. CONCLUSIONS: Suboptimal initiation of dialysis is common in patients referred early or late. The benefits of early referral are lost if dialysis is initiated suboptimally. There is a need to identify factors that lead to suboptimal initiation despite early referral.

Left ventricular hypertrophy in new hemodialysis patients without symptomatic cardiac disease.

BACKGROUND AND OBJECTIVES: Although left ventricular hypertrophy (LVH) is a characteristic finding in hemodialysis (HD) populations, few risk factors for progressive LVH have been identified. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: As part of a multinational, blinded, randomized, controlled trial that demonstrated no effect of hemoglobin targets on LV size, 596 incident HD patients, without symptomatic cardiac disease or cardiac dilation, had baseline echocardiograms within 18 months of starting dialysis and subsequently at 24, 48, and 96 weeks later. A wide array of baseline risk factors were assessed, as were BP and hemoglobin levels during the trial. RESULTS: The median age and duration of dialysis were 51.5 years and 9 months, respectively. LV mass index (LVMI) rose substantially during follow-up (114.2 g/m(2) at baseline, 121 at week 48, 123.4 at week 48, and 128.3 at week 96), as did fractional shortening, whereas LV volume (68.7, 70.1, 68.7, and 68.1 ml/m(2)) and E/A ratio remained unchanged. At baseline, the only multivariate associations of LVMI were gender and N terminal pro-B type natriuretic peptide. Comparing first and last echocardiograms in those without LVH at baseline, independent predictors of increase in LVMI were higher time-integrated systolic BP and cause of ESRD. An unadjusted association between baseline LVMI and subsequent cardiovascular events or death was eliminated by adjusting for age, diabetes, systolic BP, and N terminal pro-B type natriuretic peptide. CONCLUSIONS: Progressive concentric LVH and hyperkinesis occur in HD patients, which is partly explained by hypertension but not by a wide array of potential risk factors, including anemia.

Erythropoietin therapy, hemoglobin targets, and quality of life in healthy hemodialysis patients: a randomized trial.

BACKGROUND AND OBJECTIVES: The effects of different hemoglobin targets when using erythropoiesis-stimulating agents on quality of life are somewhat controversial, and predictors of change in quality of life in endstage renal disease have not been well characterized. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Five hundred ninety-six incident hemodialysis patients without symptomatic cardiac disease were randomly assigned to hemoglobin targets of 9.5 to 11.5 g/dl or 13.5 to 14.5 g/dl for 96 weeks, using epoetin_alfa as primary therapy. Patients and attending physicians were masked to treatment assignment. Quality of life, a secondary outcome, was prospectively recorded using the Kidney Disease Quality of Life (KDQoL) questionnaire at weeks 0, 24, 36, 48, 60, 72, 84, and 96, with prespecified outcomes being fatigue and quality of social interaction. RESULTS: The mean age and prior duration of dialysis therapy of the study population were 50.8 and 0.8 yr. Mortality was low, reflecting the relatively healthy group enrolled. Of 20 domains within the KDQoL only the prespecified domain of fatigue showed significant change over time between the two groups. Improvement in fatigue scores in the high-target group ranged from 3.2 to 7.9 over time (P = 0.007) compared with change in the low-target group. Higher body mass index and lower erythropoietin dose at baseline were independent predictors of improvement in multiple KDQoL domains. CONCLUSIONS: In relatively healthy hemodialysis patients, normal hemoglobin targets may have beneficial effects on fatigue. Improvement in multiple domains of quality of life is associated with higher body mass index and lower erythropoietin requirements.

The design of randomized controlled trials.

Today's clinical practice relies on the application of well-designed clinical research, the gold standard test of an intervention being the randomized controlled trial. Principles of the randomized controlled trial include emphasis on the principal research question, randomization, and blinding; definitions of outcome measures, inclusion and exclusion criteria, and comorbid and confounding factors; enrolling an adequate sample size; planning data management and analysis; preventing challenges to trial integrity, such as dropout, drop-in, and bias. The application of pretrial planning is stressed to ensure the proper application of epidemiological principles, resulting in clinical studies that are feasible and generalizable. In addition, funding strategies and trial team composition are discussed.

Hemoglobin targets and blood transfusions in hemodialysis patients without symptomatic cardiac disease receiving erythropoietin therapy.

BACKGROUND AND OBJECTIVES: Optimal hemoglobin targets for chronic kidney disease patients receiving erythropoiesis-stimulating agents remain controversial. The effects of different hemoglobin targets on blood transfusion requirements have not been well characterized, despite their relevance to clinical decision-making. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Five hundred ninety-six incident hemodialysis patients without symptomatic cardiac disease were randomly assigned to hemoglobin targets of 9.5 to 11.5 g/dl or 13.5 to 14.5 g/dl for 96 wk using epoetin alfa as primary therapy and changes in left ventricular structure as the primary outcome (previously reported). Patients were masked to treatment assignment. Blood transfusion data were prospectively collected at 4-wk intervals. RESULTS: The mean age and prior duration of dialysis therapy of the study population were 50.8 and 0.8 yr, respectively. Previously reported mortality was similar in low and high-target subjects, at 4.7 (95% confidence interval 3.0, 7.3) and 3.1 (1.8, 5.4) per hundred patient years, respectively. Transfusion rates were 0.66 (0.59, 0.74) units of blood per year in low and 0.26 (0.22, 0.32) in high-target subjects (P < 0.0001). Hemoglobin level at transfusion (7.7 [7.5, 7.9]) versus 8.1 [7.6, 8.5] g/dl) were similar with both groups. High hemoglobin target was a significant predictor of time to first transfusion independent of baseline associations (hazard ratio = 0.42; 95% confidence interval = 0.26-0.67). CONCLUSIONS: In hemodialysis patients with comparatively low mortality risks, normal hemoglobin targets may reduce the need for transfusions.

Evaluation and treatment of CKD patients before and at their first nephrologist encounter in Canada.

BACKGROUND: Much of the comorbidity associated with chronic kidney disease (CKD) begins in the early stages. Interventions with proven efficacy exist to decrease progression, morbidity, and mortality. This study examines their use in patients with CKD before and at their first nephrologist encounter in Canada. STUDY DESIGN: Prospective multicenter cohort study. SETTING & PARTICIPANTS: 482 patients at their first nephrologist encounter enrolled from 13 Canadian centers. Inclusion criteria were measured or estimated glomerular filtration rate less than 50 mL/min/1.73 m(2). Exclusion criteria were patients with acute kidney failure or those likely to require dialysis therapy within 3 months of referral. OUTCOMES & MEASUREMENTS: Describe: (1) characteristics of patients at their first nephrology encounter in Canada; (2) the evaluation for cardiac risk factors, cardiac diseases and CKD complications and their management before the encounter; (3) changes in management initiated by nephrologists at the first encounter; and (4) the availability and use of allied health professional services for CKD care. RESULTS: Patients had a mean age of 69.7 years, estimated glomerular filtration rate of 29 mL/min/1.73 m(2) (0.48 mL/s/1.73 m(2), hemoglobin level of 12.1 g/dL (121 g/L), albumin level of 3.6 g/dL (36 g/L), and blood pressure of 147/76 mm Hg. Transmission of results from prior evaluation was variable. At the encounter, nephrologists had available or ordered albumin and calcium/phosphate tests in greater than 70% of patients. Nephrologists did not evaluate parathyroid hormone in 83% of patients, lipids in greater than 50%, iron studies (in those with anemia) in 57%, and urine studies in 30%. Despite a high prevalence of diabetes and coronary artery disease, only 46% were administered medications to interrupt the renin-angiotensin system, 37% were administered acetylsalicylic acid, and 32% were administered lipid medication after the encounter. Availability and use of allied health professional resources varied and was low in an unstructured setting. LIMITATIONS: External validity, referral bias, and inability to make causal inferences. CONCLUSIONS: In Canada, patients with CKD continue to be encountered late by nephrologists (stage IV CKD). Information for prior evaluation is incompletely transmitted. Finally, there appears to be room for improvement in evaluation and treatment at the first nephrologist encounter.

Quality of medical care during and shortly after acute care restructuring in Newfoundland and Labrador.

OBJECTIVES: To critically evaluate the quality of hospital medical care at the beginning, during and shortly after regionalization of health boards in Newfoundland and Labrador, and aggregation of hospitals in the St John's region. METHODS: Retrospective chart audits for the years 1995/96, 1998/99 and 2000/01 (at the beginning, during and after restructuring) focused on outcomes in cardiology, respiratory medicine, neurology, nephrology, psychiatry, surgery and women's health programmes. Where possible, quality of care was judged on measurable outcomes in relation to published statements of likely optimal care. Comparisons were made over time within the St John's region, and separately for hospitals in the rest of the province. RESULTS: There was improvement in the use of thrombolytics and secondary measures post-myocardial infarction in both regions. Mortality and appropriateness of initial antibiotic choice for community-acquired pneumonia remained stable in both regions, with an improvement in admission appropriateness based on the severity in St John's. Aspects of stroke management (referral and time to see allied health professionals, imaging and discharge home) improved in both regions, while mortality remained stable. There was improvement in fistula rate, quality of dialysis and anaemia management in haemodialysis patients, and improvement in the peritoneal dialysis patient peritonitis rate. Readmission rate for schizophrenia remained unchanged. Stable mortality rates were observed for frequently performed surgical procedures. The post-coronary artery bypass grafting (CABG) morbid event rate improved, although access to CABG was not optimal. CONCLUSIONS: Aggregation of acute care hospitals was feasible without attendant deterioration in patient care, and in some areas care improved. However, access to services continued to be a major problem in all regions.