Factors Associated With Exacerbation of Heart Failure Include Treatment Adherence and Health Literacy Skills

We determined the factors associated with exacerbation of heart failure, using a cohort (n = 192) nested within a randomized trial at a university-affiliated ambulatory practice. Factors associated with emergency or hospital care included left ventricular ejection fraction, hematocrit and serum sodium levels, refill adherence, and the ability to read a prescription label. Refill adherence of <40% was associated with a threefold higher incidence of hospitalization for heart failure than a refill adherence of ≥80% (P = 0.002). In multivariable analysis, prescription label reading skills were associated with a lower incidence of heart failure–specific emergency care (incidence rate ratio, 0.76; 95% confidence interval (CI), 0.19–0.69), and participants with adequate health literacy had a lower risk of hospitalization for heart failure (incidence rate ratio, 0.34; 95% CI, 0.15–0.76). We conclude that inadequate treatment adherence and health literacy skills are key factors in the exacerbation of heart failure. These findings emphasize the need for careful instruction of patients about their medications

Fuel Cycle Costs for a Plutonium Recycle System

The costs of the chemical and metallurgical steps in the fuel cycle for large desalination reactors are estimated. Both capital and operating costs are presented at varying plant capacities for a Zircaloy-clad fuel element containing depleted uranium and recycled plutonium as the oxides. UO/sup 2/-0.5% PuO/sub 2/. The chemical steps are reported at throughputs of 1, 10, and 30 short tons of uranium per day; and the metallurgical or fabrication step at throughputs of 1, 3, 5, and 10 tons per day, as specified by the Office of Science and Technology. The total estimated cost of all the chemical and metallurgical steps drops from .17 to .68 per kilogram of uranium as the cycle throughput is increased from 1 to 10 tons of uranium per day. All steps decrease in cost as plant capacity is increased, with the most impressive decrease in the irradiated assembly processing step, which decreases from .19 to 10 to 07 per kilogram of uranium as throughput is changed from 1 to 10 to 30 tons of uranium per day. The contained data in conjunction with previous studies of a natural uranium fuel cycle and results of a current reactor optimization study will yield complete fuel cycle costs and plutonium value in recycle. (auth

Application of effect-compartment model to bumetanide-indomethacin interaction in dogs

Analyses of bumetanide's dose-response relationship have been complicated by the hysteresis observed between the drug's urinary excretion rate and its sodium excretion. This apparent time lag reflects the disequilibrium between the urine concentration and effect compartment (biophase) which occurs during the early distribution phase. In the present article, an expanded pharmaco-dynamic model has been introduced in which the hypothetical effect compartment is linked, by a first-order process (K ue ), to the urine compartment. Drug dissipation from the effect compartment occurs by means of the first-order rate constant , K eo . This representation accommodates bumetanide's luminal site of action in the kidney tubule as well as the drug's temporal component. Application of this model to the bumetanide-indomethacin interaction in dogs is examined.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45030/1/10928_2005_Article_BF01058955.pd

Effect of angiotensin II-induced changes in perfusion flow rate on chlorothiazide transport in the isolated perfused rat kidney

Angiotensin II was used as a probe to study the effect of changes in perfusate flow rate on the renal clearance parameters of chlorothiazide in the isolated perfused rat kidney. Perfusion studies were performed in five rats with no angiotensin II present in the perfusate and in five rats with a 1–4 ng/min infusion of angiotensin II into the perfusate. Angiotensin II had a dramatic effect on the renal hemodynamics, resulting in a 43% decrease in perfusate flow, a 16% decrease in glomerular filtration rate (GFR), and a 45% increase in filtration fraction. Values for the fractional excretion of glucose were low and consistent, with or without angiotensin II. Although the unbound fraction (fu) of chlorothiazide was unchanged between treatments, the renal (CL r ) and the secretion clearances were reduced by about 50% in the presence of angiotensin II; the excretion ratio [ER=CL r /(fu·GFR)] was reduced by 38% with angiotensin II present in the perfusate. Analysis of the data was complicated by the presence of a capacity-limited transport for renal tubular secretion. Transport parameters (±SD) were obtained and the corrected intrinsic secretory clearance [(V max /GFR)/K m ] of chlorothiazide was 123 ± 18 without angiotensin II vs. 72.8 ± 30.0 with angiotensin II. These results demonstrate that alterations in organ perfusion can significantly reduce the clearance parameters of chlorothiazide in the rat IPK. These flow-induced changes in intrinsic secretory transport may reflect perturbations other than that of perfusion flow rate alone .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45047/1/10928_2005_Article_BF01071001.pd

A multinational randomized, controlled, clinical trial of etoricoxib in the treatment of rheumatoid arthritis [ISRCTN25142273]

BACKGROUND: Etoricoxib is a highly selective COX-2 inhibitor which was evaluated for the treatment of rheumatoid arthritis (RA). METHODS: Double-blind, randomized, placebo and active comparator-controlled, 12-week study conducted at 67 sites in 28 countries. Eligible patients were chronic NSAID users who demonstrated a clinical worsening of arthritis upon withdrawal of prestudy NSAIDs. Patients received either placebo, etoricoxib 90 mg once daily, or naproxen 500 mg twice daily (2:2:1 allocation ratio). Primary efficacy measures included direct assessment of arthritis by counts of tender and swollen joints, and patient and investigator global assessments of disease activity. Key secondary measures included the Stanford Health Assessment Questionnaire, patient global assessment of pain, and the percentage of patients who achieved ACR20 responder criteria response (a composite of pain, inflammation, function, and global assessments). Tolerability was assessed by adverse events and routine laboratory evaluations. RESULTS: 1171 patients were screened, 891 patients were randomized (N = 357 for placebo, N = 353 for etoricoxib, and N = 181 for naproxen), and 687 completed 12 weeks of treatment (N = 242 for placebo, N = 294 for etoricoxib, and N = 151 for naproxen). Compared with patients receiving placebo, patients receiving etoricoxib and naproxen showed significant improvements in all efficacy endpoints (p<0.05). Treatment responses were similar between the etoricoxib and naproxen groups for all endpoints. The percentage of patients who achieved ACR20 responder criteria response was 41% in the placebo group, 59% in the etoricoxib group, and 58% in the naproxen group. Etoricoxib and naproxen were both generally well tolerated. CONCLUSIONS: In this study, etoricoxib 90 mg once daily was more effective than placebo and similar in efficacy to naproxen 500 mg twice daily for treating patients with RA over 12 weeks. Etoricoxib 90 mg was generally well tolerated in RA patients

Financing U.S. Graduate Medical Education: A Policy Position Paper of the Alliance for Academic Internal Medicine and the American College of Physicians

In this position paper, the Alliance for Academic Internal Medicine and the American College of Physicians examine the state of graduate medical education (GME) financing in the United States and recent proposals to reform GME funding. They make a series of recommendations to reform the current funding system to better align GME with the needs of the nation's health care workforce. These recommendations include using Medicare GME funds to meet policy goals and to ensure an adequate supply of physicians, a proper specialty mix, and appropriate training sites; spreading the costs of financing GME across the health care system; evaluating the true cost of training a resident and establishing a single per-resident amount; increasing transparency and innovation; and ensuring that primary care residents receive training in well-functioning ambulatory settings that are financially supported for their training roles

Tubular transport mechanisms of quinapril and quinaprilat in the isolated perfused rat kidney: Effect of organic anions and cations

The clearance mechanisms of quinapril and quinaprilat were probed using an isolated perfused rat kidney model. Sixty-four experiments were performed with drug in the absence and presence of classic inhibitors of the organic acid (i.e., probenecid and p-aminohippurate) and organic base (i.e., tetraethylammonium and quinine) transport systems of the proximal tubule. Initial perfusate concentrations of quinapril and quinaprilat were approximately 2.36 μM (or 1000 ng/ml), and transport inhibitors were coperfused at 100–10,000 times the drugs' initial μM concentrations. Quinapril and quinaprilat concentrations were determined in perfusate, urine, and perfusate ultrafiltrate using a reversed-phase HPLC procedure with radiochemical detection, coupled to liquid scintillation spectrometry. Perfusate protein binding was determined using an ultrafiltration method at 37°C. Overall, the clearance ratios of quinapril (total renal clearance divided by fu·GFR ) and quinaprilat (urinary clearance divided by fu·GFR ) were significantly reduced, and in a dose-dependent manner, by the coperfusion of organic acids but not organic bases. The data demonstrate that the organic anionic secretory system is the primary mechanism by which quinapril and quinaprilat are transported into and across renal proximal cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45053/1/10928_2006_Article_BF02353517.pd

Determinants of bumetanide response in the dog: Effect of probenecid

The pharmacokinetics and pharmacodynamics of intravenous bumetanide (0.250 mg/kg), alone (treatment I) and after probenecid pretreatment (treatment II), were studied in four mongrel dogs. Lactated Ringer's solution was administered by vein throughout both treatments at a flow rate of 2 ml/min to avoid fluid and electrolyte depletion. Bumetanide and probenecid concentrations were analyzed by HPLC, sodium by flame photometry, and creatinine by colorimetry. Although the probenecid markedly reduced the plasma and renal clearances of bumetanide, as well as the fraction excreted unchanged in the urine, there was no significant difference between treatments I and II in the 4-hr natriuretic and diuretic responses. However, analysis of the dose-response curves between treatments I and II showed that sodium, excretion was better correlated with bumetanide urinary excretion rate than with plasma concentration. The reasons for a poor correlation between treatments during the early time periods are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45029/1/10928_2005_Article_BF01061766.pd

Empirical research on Waldorf education

Waldorf education began in 1919 with the first Waldorf School in Stuttgart and nowadays is widespread in many countries all over the world. Empirical research, however, has been rare until the early nineties and Waldorf education has not been discussed within educational science so far. This has changed during the last decades. This article reviews the results of surveys during the last 20 years and is mainly focused on German Waldorf Schools, because most investigations have been done in this field. Findings are reported with respect to the following central aspects of Waldorf education: the holistic and integrative approach, the self-governance in the organization of the Waldorf schools, the Waldorf curriculum, and the principle of class teachers from 1st to 8th grade. Furthermore, Waldorf education also provides its own unique teacher training. All of these aspects have been explored and evaluated from different points of view and with different methods. The results show strengths as well as weaknesses of Waldorf education in the daily practice in schools, which indicates the kinds of challenges Waldorf education will have to face in the upcoming decades. The authors themselves have contributed in several investigations to the field of Waldorf education

Renal transport kinetics of furosemide in the isolated perfused rat kidney

Direct quantitative data and corresponding theory are provided for the effect of protein binding on the renal transport of furosemide. Drug studies were performed with various combinations of bovine serum albumin and dextran. This resulted in a percent unbound ( fu ) of furosemide ranging from 0.785 to 85.8%. The corrected renal ( CLr/GFR ) and secretion ( CLs/GFR ) clearances of furosemide were observed to increase with percent free, but in a nonproportional manner. Plots of CLr/GFR or CLs/GFR vs. fu appeared to have a prominent y intercept as well as a convex ascending curve. In addition, the excretion ratio [ ER=CLr/ (fu · GFR) ] was reduced from 60.8 to 8.72 as fu increased. Overall, the data were best fitted to a model in which two Michaelis-Menten terms wre used to describe renal tubular transport, and secretion was dependent upon free drug concentrations in the perfusate. The results demonstrate that the renal mechanisms of furosemide excretion are more complex than previously reported and that active secretion may involve two different transport systems over the concentration range studied.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45036/1/10928_2005_Article_BF01065259.pd