Tracy J. Mayne

Systematic Review and Meta-analysis of Exercise Tolerance and Physical Functioning in Dialysis Patients Treated With Erythropoiesis-Stimulating Agents

BACKGROUND The role of erythropoiesis-stimulating agents (ESAs) in treating the anemia of chronic kidney disease has been reevaluated in view of recent studies suggesting that the use of these agents may be associated with increased morbidity and mortality. This potential increased risk needs to be weighed against the potential benefit of ESAs in improving various aspects of health-related quality of life, in particular, exercise tolerance and physical functioning. STUDY DESIGN A systematic review and meta-analysis of exercise tolerance and physical functioning. SETTING & PARTICIPANTS Adults on maintenance dialysis therapy. SELECTION CRITERIA FOR STUDIES Outcomes measured before and after ESA treatment were required. Studies of physical function were required to include at least 25 participants. INTERVENTION Treatment with any ESA. OUTCOMES Exercise tolerance measured using VO(2peak) (oxygen consumption per minute at the peak workload during the test), duration of exercise, or 6-minute walk distance or physical functioning assessed using > or = 1 patient- or clinician-reported outcome measure that included a physical function domain. RESULTS 28 articles met criteria for inclusion for evaluation of exercise tolerance, and 14 articles, for physical function. Meta-analysis showed a 23.8% increase in VO(2peak) from before to after erythropoietin therapy initiation (15 studies) and a nonsignificant 8.2% increase comparing a higher with a lower hemoglobin target (3 studies). For physical functioning, 4 studies met criteria for inclusion in the meta-analysis: there was a 10.5% increase in Karnofsky score from before to after erythropoietin therapy initiation. LIMITATIONS Many studies of exercise tolerance did not include control groups. A wide variety of instruments was used to assess physical function. CONCLUSIONS Partial correction of anemia through ESA treatment has a consistent and positive impact on VO(2peak). ESA treatment improves patient- and clinician-assessed physical functioning.

Dialysis patients treated with Epoetin alfa show improved anemia symptoms: A new analysis of the Canadian Erythropoietin Study Group trial

The health‐related quality of life (HRQOL) claims in the current Epoetin alfa label are based on the reanalyses of the exercise and physical function data from the Canadian Erythropoietin Study Group trial. The reanalysis was done to comply with the Food and Drug Administrations requirement of using statistical methods that are currently standard in evaluating clinical trial data. Presented here are HRQOL results associated with anemia. The Canadian Erythropoietin Study Group trial was a multicenter, double blind, randomized, placebo‐controlled trial evaluating the effects of Epoetin alfa on HRQOL in anemic hemodialysis patients. A total of 118 patients who were 18–75 years old, on hemodialysis for >3 months, who had a hemoglobin <9.0 g/dL, and did not have coronary artery disease or diabetes mellitus, were randomized to either receive placebo (n=40), or receive intravenous Epoetin alfa to achieve a target hemoglobin of 9.5–11.0 g/dL (n=40) or a target of 11.5–13.0 g/dL (n=38). Patients were followed for 6 months. The two Epoetin alfa‐treatment groups were combined for all analyses performed. This post hoc analysis was conducted using an intent‐to‐treat repeated measures mixed model analysis of variance using Bonferronis multiplicity correction. The Epoetin alfa‐treated group showed a statistically significant improvement in the Kidney Disease Questionnaire symptom of fatigue in comparison with placebo. Additionally, the change in hemoglobin at 2 months was correlated with change in fatigue, energy, shortness of breath, and weakness, but had minimal effect on depression. These analyses confirm previously reported results, which indicate that treating hemodialysis patients with an erythropoiesis‐stimulating agent improves HRQOL.

Secular trends in opioid prescribing in the USA

Opioid abuse and misuse in the USA is a public health crisis. The use of prescription opioid analgesics increased substantially from 2002 through 2010, then plateaued and began to decrease in 2011. This study examined prescriptions of branded and generic immediate- and extended-release opioid analgesics from 1992 to 2016. This was juxtaposed against state and federal policies designed to decrease overutilization and abuse, as well as the launch of new opioid products, including opioids with abuse-deterrent properties (OADPs). The data indicate that these health policies, including the utilization and reimbursement of OADPs, have coincided with decreased opioid utilization. The hypothesis that OADPs will paradoxically increase opioid prescribing is not supported.

A review of the costs and cost effectiveness of interventions in chronic kidney disease: implications for policy.

Given rising healthcare costs and a growing population of patients with chronic kidney disease (CKD), there is an urgent need to identify health interventions that provide good value for money.For this review, the English-language literature was searched for studies of interventions in CKD reporting an original incremental cost-utility (cost per QALY) or cost-effectiveness (cost per life-year) ratio. Published cost studies that did not report cost-effectiveness or cost-utility ratios were also reviewed. League tables were then created for both cost-utility and cost-effectiveness ratios to assess interventions in patients with stage 1–4 CKD, waitlist and transplant patients and those with end-stage renal disease (ESRD). In addition, the percentage of cost-saving or dominant interventions (those that save money and improve health) was compared across these three disease categories.A total of 84 studies were included, contributing 72 cost-utility ratios, 20 cost-effectiveness ratios and 42 other cost measures. Many of the interventions were dominant over the comparator, indicating better health outcomes and lower costs. For the three disease categories, the greatest number of dominant or cost-saving interventions was reported for stage 14 CKD patients, followed by waitlist and transplant recipients and those with ESRD (91%, 87% and 55% of studies reporting a dominant or cost-saving intervention, respectively).There is evidence of opportunities to lower costs in the treatment of patients with CKD, while either improving or maintaining the quality of care. In order to realize these cost savings, efforts will be required to promote and effectively implement changes in treatment practices.

Changes in Hemoglobin Level Distribution in US Dialysis Patients From June 2006 to November 2008

BACKGROUND Erythropoiesis-stimulating agents (ESAs) have had a positive effect on anemia treatment in dialysis patients. However, several events in recent years, including new clinical study results, ESA product label revisions, and coverage and reimbursement policy changes, have had an impact on ESA dosing patterns and consequently on hemoglobin (Hb) distribution characteristics in this patient population. STUDY DESIGN Retrospective observational study using patient-level data from approximately 87% of dialysis centers in the United States. SETTING & PARTICIPANTS Dialysis patients who were receiving outpatient care at dialysis facilities during June 2006-November 2008 were included in this study. PREDICTOR Recent events affecting ESA treatment practice patterns in US dialysis patients. OUTCOMES & MEASUREMENTS Hb level distribution. RESULTS Mean Hb level decreased by 0.37 g/dL during the indicated period. Additionally, standard deviation (SD) of the Hb level distribution decreased by 0.14 g/dL and skewness increased by -0.10. Hb measurements in specific ranges changed as follows: >12 g/dL, decreased by 11.3 percentage points;10-12 g/dL, increased by 9.4 percentage points; and <10 g/dL, increased by 1.9 percentage points. The percentage of patients with Hb level >13 g/dL for > or =3 months decreased by 2.9 percentage points. LIMITATIONS Potential bias in dialysis center selection and lack of information for patient characteristics. CONCLUSIONS Recent events affecting ESA use in dialysis patients have had the desired effect of increasing the proportion of Hb measurements within the US Food and Drug Administration recommended target range of 10-12 g/dL and decreasing the proportion of Hb measurements >12 g/dL. However, the proportion of Hb measurements <10 g/dL also has increased. Benefits of a decrease in Hb measurements in the >12 g/dL range need to be considered, together with risks of having low Hb levels.

Reduced use of erythropoiesis-stimulating agents and intravenous iron with ferric citrate: a managed care cost-offset model

Background Ferric citrate (FC) is a phosphate binder in development for the treatment of hyperphosphatemia in patients with end-stage renal disease (ESRD). In clinical trials, FC improved patient serum phosphorus levels and increased serum ferritin and percent transferrin saturation. Because nephrologists respond to increases in these iron measures by reducing intravenous (IV) iron and erythropoiesis-stimulating agent (ESA) doses, the decreased use of iron and ESA associated with FC may reduce costs. Objectives To develop a cost-offset model from a managed care perspective estimating the cost savings associated with FC use. Methods We created a cost-offset model from the managed care payer perspective that compared the treatment costs of ESRD for patients given FC. The model considered the number of dialysis sessions per month; number of ESRD patients enrolled in the health plan; cost of ESAs, iron, and dialysis sessions; and the proportion of patients on phosphate binder therapy. The model assumed equivalent efficacy and cost neutrality between FC and other phosphate binders. Monte Carlo simulations were conducted by varying model inputs. Results When FC was compared to other phosphate binders, the monthly cost of ESA and IV iron per 500 patients with ESRD (85% treated with phosphate binders) was reduced by 8.15% and 33.2%, respectively. When incorporated into the total cost of dialysis for patients with ESRD (dialysis, ESA, and IV iron), the decrease in the monthly cost of dialysis care was US

The IMPACT (Incident Management of Patients, Actions Centered on Treatment) Program: A Quality Improvement Approach for Caring for Patients Initiating Long-term Hemodialysis

80,214 per 500 ESRD patients. Monte Carlo simulations suggest that a plan serving 500 dialysis patients could save between US

Results of a Pilot Program to Improve Phosphorus Outcomes in Hemodialysis Patients

626,000 and US

Characterizing Hospitalizations of End-Stage Renal Disease Patients on Dialysis and Inpatient Utilization of Erythropoiesis-Stimulating Agent Therapy:

1,106,000 annually with the use of FC. Conclusion The use of FC in ESRD patients with hyperphosphatemia may help reduce treatment costs.

CathAway fistula vascular access program achieves improved outcomes and sets a new standard of treatment for end-stage renal disease.

BACKGROUND Patients beginning dialysis therapy are at risk of death and illness. The IMPACT (Incident Management of Patients, Actions Centered on Treatment) quality improvement program was developed to improve incident hemodialysis patient outcomes through standardized care. STUDY DESIGN Quality improvement report. SETTING & PARTICIPANTS Patients who started hemodialysis therapy between September 2007 and December 2008 at DaVita facilities using the IMPACT program (n = 1,212) constituted the intervention group. Propensity score-matched patients who initiated hemodialysis therapy in the same interval at DaVita facilities not using the IMPACT program (n = 2,424) made up the control group. QUALITY IMPROVEMENT PLAN IMPACT intervention included a structured intake process and monitoring reports; patient enrollment in a 90-day patient education program and 90-day patient management pathway. OUTCOMES Mean dialysis adequacy (Kt/V), hemoglobin and albumin levels, percentage of patients using preferred vascular access (arteriovenous fistula or graft), and mortality at each quarter. RESULTS Compared with the non-IMPACT group, the IMPACT group was associated with a higher proportion of patients dialyzing with a preferred access at 90 days (0.50 [95% CI, 0.47-0.53] vs 0.47 [95% CI, 0.45-0.49]; P = 0.1) and 360 days (0.63 [95% CI, 0.61-0.66] vs 0.48 [95% CI, 0.46-0.50]; P < 0.001) and a lower mortality rate at 90 days (24.8 [95% CI, 19.0-30.7] vs 31.9 [95% CI, 27.1-36.6] deaths/100 patient-years; P = 0.08) and 360 days (17.8 [95% CI, 15.2-20.4] vs 25.1 [95% CI, 20.7-25.2] deaths/100 patient-years; P = 0.01). LIMITATIONS The study does not determine the care processes responsible for the improved outcomes. CONCLUSIONS Intense management of incident dialysis patients with the IMPACT quality improvement program was associated with significantly decreased first-year mortality. Focused attention to the care of incident patients is an important part of a dialysis program.