Implications of a Reduction in the Hemoglobin Target in Erythropoiesis-Stimulating Agent-Treated Hemodialysis Patients

Background: Patients treated with erythropoiesis-stimulating agents (ESAs) to a hemoglobin (Hb) level >12.0 g/dl have increased risk of multiple complications, including death. The optimal Hb target for ESA use has not been established. We hypothesized that reducing the target Hb would prevent levels >12 g/dl and lead to significant cost savings. Methods: Our target Hb range was reduced to 9–11 g/dl from 10–12 g/dl. Thirty-five chronic hemodialysis (HD) patients received erythropoietin (EPO) and intravenous iron from January to December 2009. Data analysis included: Hb level, EPO dose, transferrin saturation and ferritin levels. EPO was administered via subcutaneous injection weekly or twice weekly. Results: The mean monthly Hb level changed from 11.2 to 10.6 g/dl. The percentages of patients with mean Hb >10.0, 12.0 and 13.0 g/dl were 82 ± 6.5, 10 ± 5.6 and 1.8 ± 1.9%, respectively. Weekly EPO dose decreased from 9,500 to 5,600 units, a 40% reduction per dose per patient and costs. The savings exceeded USD 60,000 per year for 35 patients. More than 80% of patients had transferrin saturation >20% and ferritin >200 ng/ml throughout the entire period. Conclusions: Lowering the target Hb range to 9–11 g/dl in HD patients achieved quality anemia management, avoided values >12.0 g/dl and resulted in cost savings. A minimal reduction in quality of life and no change in cardiovascular morbidity or mortality would be expected. The study has important implications in the new American bundled reimbursement model

Access to Care for VA Dialysis Patients During Superstorm Sandy.

Introduction: This study examines the use of dialysis services by end-stage renal disease (ESRD) patients following the Superstorm Sandy-related, months-long closure of the New York campus of the US Department of Veterans Affairs (VA) New York Harbor VA Healthcare System (NYHHS, Manhattan VAMC). Methods: Outpatient visits, dialysis care, emergency department visits, and hospitalizations at VA and non-VA facilities for 47 Manhattan VAMC ESRD patients were examined 12 months pre- and post-Sandy using VA administrative and clinical data. Results: The Brooklyn campus of NYHHS, which is within ten miles of Manhattan VAMC, experienced the largest increase in the number of dialysis encounters after the closure. Dialysis encounters for VA patients also increased at non-VA facilities, rising on average, to 106 per month. For the James J Peters Bronx VAMC, the number of total dialysis encounters for Manhattan VAMC patients fluctuated between 39 and 43 per month, dropping to less than 30 after the Manhattan VAMC dialysis unit reopened. Conclusion: Manhattan VAMC ESRD patients used nearby alternate VA sites and non-VA clinics for their care during the closure of the Manhattan VAMC dialysis unit. The VA electronic health records played an important role in ensuring continuity of care for patients who exclusively used VAMC facilities post-Sandy because patient information was immediately accessible at other VA facilities. The events related to Superstorm Sandy highlight the need for dialysis providers to have a comprehensive disaster plan, including nearby alternate care sites that can increase service capacity when a dialysis facility is closed because of a disaster

Advances in the management of gout: Critical appraisal of febuxostat in the control of hyperuricemia

Gout recently passed rheumatoid arthritis to become the most common inflammatory arthritis in the United States (US). However, epidemiologic studies indicate that the quality of gout management is suboptimal owing to both patient and physician issues. Only three options for urate-lowering therapy are currently available in the US: allopurinol, probenecid, and recently, febuxostat. Probenecid is generally safe except for the occurrence of urolithiasis, but is only effective for the subset of patients with better kidney function. Allopurinol use is limited due to its side effects, potential toxicity of uncertain magnitude in patients with renal disease, and failure to achieve targeted serum urate levels. In part this failure may be due to the necessity for it to be titrated for optimal therapeutic effect. Febuxostat is a new medication that may offer several advantages and can be given as an alternative to allopurinol. We review the basic biology and clinical performance of febuxostat, and consider the potential utility of this agent in comparison to the older, better-established gout therapeutics

Facilitating the transition from physiology to hospital wards through an interdisciplinary case study of septic shock

BACKGROUND: In order to develop clinical reasoning, medical students must be able to integrate knowledge across traditional subject boundaries and multiple disciplines. At least two dimensions of integration have been identified: horizontal integration, bringing together different disciplines in considering a topic; and vertical integration, bridging basic science and clinical practice. Much attention has been focused on curriculum overhauls, but our approach is to facilitate horizontal and vertical integration on a smaller scale through an interdisciplinary case study discussion and then to assess its utility. METHODS: An interdisciplinary case study discussion about a critically ill patient was implemented at the end of an organ system-based, basic sciences module at New York University School of Medicine. Three clinical specialists—a cardiologist, a pulmonologist, and a nephrologist—jointly led a discussion about a complex patient in the intensive care unit with multiple medical problems secondary to septic shock. The discussion emphasized the physiologic underpinnings behind the patient’s presentation and the physiologic considerations across the various systems in determining proper treatment. The discussion also highlighted the interdependence between the cardiovascular, respiratory, and renal systems, which were initially presented in separate units. After the session students were given a brief, anonymous three-question free-response questionnaire in which they were asked to evaluate and freely comment on the exercise. RESULTS: Students not only took away physiological principles but also gained an appreciation for various thematic lessons for bringing basic science to the bedside, especially horizontal and vertical integration. The response of the participants was overwhelmingly positive with many indicating that the exercise integrated the material across organ systems, and strengthened their appreciation of the role of physiology in understanding disease presentations and guiding appropriate therapy. CONCLUSIONS: Horizontal and vertical integration can be presented effectively through a single-session case study, with complex patient cases involving multiple organ systems providing students opportunities to integrate their knowledge across organ systems while emphasizing the importance of physiology in clinical reasoning. Furthermore, having several clinicians from different specialties discuss the case together can reinforce the matter of integration across multiple organ systems and disciplines in students’ minds

Integrated safety studies of the urate reabsorption inhibitor lesinurad in treatment of gout.

ObjectiveLesinurad (LESU) is a selective urate reabsorption inhibitor approved at 200 mg daily for use with a xanthine oxidase inhibitor (XOI) to treat hyperuricaemia in gout patients failing to achieve target serum urate on XOI. The aim of the study was to investigate the long-term safety of LESU + XOI therapy.MethodsSafety data were pooled from three 12-month phase III (core) trials evaluating LESU 200 and 400 mg/day combined with an XOI (LESU200+XOI and LESU400+XOI), and two 12-month extension studies using descriptive statistics. To adjust for treatment duration, treatment-emergent adverse events (TEAEs) were expressed as exposure-adjusted incidence rates (patients with events per 100 person-years).ResultsIn the core studies, exposure-adjusted incidence rates for total and total renal-related TEAEs were comparable for XOI alone and LESU200+XOI but higher with LESU400+XOI. Exposure-adjusted incidence rates for serum creatinine (sCr) elevations ⩾1.5×baseline were 2.9, 7.3 and 18.7, respectively. Resolution (sCr ⩽1.2×baseline) occurred in 75-90% of all events, with 66-75% occurring without any study medication interruption. Major adverse cardiovascular events were 3, 4 and 9 with XOI, LESU200+XOI and LESU400+XOI, respectively. Longer exposure in core+extension studies did not increase rates for any safety signals.ConclusionAt the approved dose of 200 mg once-daily combined with an XOI, LESU did not increase renal, cardiovascular or other adverse events compared with XOI alone, except for sCr elevations. With extended exposure in the core+extension studies, the safety profile was consistent with that observed in the core studies, and no new safety concerns were identified

Empirical Study of Carbon Dioxide Released to the Atmosphere during Commercial Red Grape Fermentation

Carbon dioxide (CO2) is a pollutant (greenhouse gas) that is emitted during winemaking but not currently regulated by the Environmental Protection Agency. While winery CO2 emissions have been modeled, they have never been measured continuously or confirmed during a commercial fermentation. As international interest increases in greenhouse gases, it is important to know the amount of CO2 release and the determining factors; yeast strain, temperature, and dissolved CO2 are potentially important parameters. The study was designed to quantify emissions and test a theoretical model for atmospheric release of CO2 during alcoholic fermentation in a commercial winery. Gas release was channeled through a manifold system with an in-line mass flow meter calibrated for CO2, providing real-time and integrated measurement of atmospheric emission. Intermittent use of a hot-wire anemometer was used as a check on the mass-flow measurements. Initial results indicate that integrated mass of CO2 release is dependent on total Brix decrease and not duration of fermentation, consistent with the Williams and Boulton model. However, the time course of release and the shape of the release curves differed substantially among ferments and were primarily dependent on the length of active fermentation

Economic and health outcomes of capsule endoscopy: Opportunities for improved management of the diagnostic process for obscure gastrointestinal bleeding

The estimated annual incidence of gastrointestinal bleeding in the United States is approximately 100 episodes per 100,000 persons, resulting in 300,000 hospitalizations annually. Diagnostic tools such as radiologic studies and endoscopic examination often fail to identify a source of bleeding, resulting in a cycle of repetitive testing over months or even years. Costs associated with the diagnostic process, and with interim treatment for anemia and other symptoms, can be significant. The diagnostic process also takes a toll on the patient, in terms of worry, pain, and discomfort. Capsule endoscopy, a technology that received FDA clearance in August, 2001, consists of a video capsule that is ingested by the patient, and that transmits images to a wireless data recorder worn on the belt. The recorded stream of approximately 50,000 images can be reviewed on a computer workstation by a physician to identify nature and location of potential sources of bleeding. This paper presents a framework for economic analysis of this new technology. First, we present a review of the literature on the current diagnostic methods. Next, we present a conceptual model for examining contributors to costs in diagnosing obscure intestinal bleeds. We conclude by exploring the potential economic impact of the technology. Analysis of data from the first U.S. clinical trial of capsule endoscopy demonstrates its high diagnostic yield, and patient satisfaction. While further study is required, this analysis indicates that capsule endoscopy may reduce total medical utilization and costs and improve patient quality of life, when used for appropriate indications

Ferric Gluconate Yields Cost-Savings in Hemodialysis Patients with High Ferritin and Low TSAT: Results from the DRIVE Studies

Purpose: One third of hemodialysis patients have high serum ferritin levels and low transferrin saturation (TSAT). The purpose of this analysis was to determine the cost effectiveness of administering 1g of sodium ferric gluconate complex (SFGC: also referred to as ferric gluconate) to patients with serum ferritin \u3e500ng/mL and TSAT ≤25% based on the Dialysis Patients Response to IV Iron with Elevated Ferritin (DRIVE) study and its 6-week observational extension (DRIVE-II). In these studies, IV iron administration resulted in reduced epoetin requirements. Methods: Decision analysis was performed using a time horizon of 12 weeks, consistent with the combined duration of DRIVE and DRIVE II. Treatment effectiveness was based on mean increase in hemoglobin (Hb) for each group (SFGC plus epoetin or epoetin alone) in the intention to treat populations. Costs included drugs (SFGC and epoetin) and hospitalizations due to serious adverse events (SAEs) reported. The primary cost effectiveness measure was cost per g/dL of Hb increase at 12 weeks. Costs were computed from a Medicare perspective using projected 2007 reimbursements. Sensitivity analyses were performed to test the impact of using the safety population, median epoetin and SFGC doses, actual 2005 Medicare reimbursements, median increases in Hb, and SAE rate changes. The model was constructed using TreeAge Pro software. Results: Total cost per patient receiving SFGC plus epoetin was $3675 per g/dL Hb increase, while the total cost per patient receiving epoetin alone was$5065 per g/dL Hb increase. Net savings for SFGC plus epoetin was $1390 per g/dL Hb increase over the 12 week period Sensitivity analyses affirmed the robustness of the model. Conclusion: Administering 1g of SFGC plus epoetin in patients with high ferritin and low TSAT as defined in the DRIVE studies resulted in significant cost-savings compared to epoetin alone

Sex differences in the temperature dependence of kidney stone presentations: a population-based aggregated case-crossover study.

Previous studies assumed a uniform relationship between heat and kidney stone presentations. Determining whether sex and other characteristics modify the temperature dependence of kidney stone presentations has implications for explaining differences in nephrolithiasis prevalence and improving projections of the effect of climate change on nephrolithiasis. We performed an aggregated case-crossover study among 132,597 children and adults who presented with nephrolithiasis to 68 emergency departments throughout South Carolina from 1997 to 2015. We used quasi-Poisson regression with distributed lag non-linear models to estimate sex differences in the cumulative exposure and lagged response between maximum daily wet-bulb temperatures and emergent kidney stone presentations, aggregated at the ZIP-code level. We also explored interactions by age, race, payer, and climate. Compared to 10 °C, daily wet-bulb temperatures at the 99th percentile were associated with a greater increased relative risk (RR) of kidney stone presentations over 10 days for males (RR 1.73; 95% CI 1.56, 1.91) than for females (RR 1.15; 95% CI 1.01, 1.32; interaction P < 0.001). The shape of the lagged response was similar for males and females, with the greatest risk estimated for the 2 days following high temperatures. There were weak differences by age, race, and climatic zone, and no differences by payer status. The estimated risk of presenting emergently with kidney stones within 10 days of high daily wet-bulb temperatures was substantially greater among men than women, and similar between patients with public and private insurance. These findings suggest that the higher risk among males may be due to sexually dimorphic physiologic responses rather than greater exposure to ambient temperatures