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1. The interaction of sex, height, and QRS duration on the effects of cardiac resynchronization therapy on morbidity and mortality: an individual-patient data meta-analysis

Author

Linde, C, Cleland, JGF, Gold, MR, Claude Daubert, J, Tang, ASL, Young, JB, Sherfesee, L, and Abraham, WT

Subjects
Cardiac resynchronization therapy, Cardiovascular System & Hematology, Height, cardiovascular system, Gender, Heart failure, cardiovascular diseases, 1102 Cardiovascular Medicine And Haematology, circulatory and respiratory physiology
Abstract

AIMS: To explore possible associations that may explain the greater benefit from cardiac resynchronization therapy (CRT) reported amongst women. METHODS AND RESULTS: In an individual-patient data meta-analysis of five randomized controlled trials, all-cause mortality and the composite of all-cause mortality or first hospitalization for heart failure (HF) were compared among 794 women and 2702 men assigned to CRT or a control group. Multivariable analyses were performed to assess the impact of sex, QRS duration, HF aetiology, left ventricular end-diastolic diameter (LVEDD), and height on outcome. Women were shorter, had smaller LVEDD, more often left bundle branch block, and less often ischaemic heart disease, but QRS duration was similar between sexes. Women tended to obtain greater benefit from CRT but sex was not an independent predictor of either outcome. For all-cause mortality, QRS duration was the only independent predictor of CRT benefit. For the composite outcome, height and QRS duration, but not sex, were independent predictors of CRT benefit. Further analysis suggested increasing benefit with increasing QRS duration amongst shorter patients, of whom a great proportion were women. CONCLUSIONS: In this individual-patient data meta-analysis, CRT benefit was greater in shorter patients, which may explain reports of enhanced CRT benefit among women. Further analyses are required to determine whether recommendations on the QRS threshold for CRT should be adjusted for height. (ClinicalTrials.gov numbers: NCT00170300, NCT00271154, NCT00251251).

Published
2017

2. Rationale, design, implementation, and baseline characteristics of patients in the dig trial: A large, simple, long-term trial to evaluate the effect of digitalis on mortality in heart failure

Author

Abernathy, GT, Abrams, J, Akhtar, S, Albitar, I, Amidi, M, Anand, IS, Arnold, JMO, Ashton, T, Aubrey, B, Auger, P, Babb, J, Baigrie, R, Baird, MG, Baitz, T, Barber, NC, Barbour, DJ, Barr, DM, Basu, AK, Baughman, KL, Beckham, V, BekheitSaad, S, Berkson, DM, Bertoglio, M, Bessoudo, R, Beaudoin, J, Bhaskar, G, Binder, A, Bloomfield, D, Bodine, K, Boehmer, JP, Borgersen, K, Borts, D, Bouchard, G, Bourassa, MG, Boutros, G, Bozek, B, Brisbin, D, Brophy, J, Brossoit, R, Brown, E, Brown, J, Bruinsma, N, Burton, G, Cameron, A, Campbell, R, Campeau, J, Campos, EE, Cardello, FP, Carter, RP, Chan, YK, Charles, FR, Chaudhry, MA, Chiaramida, A, Chiaramida, S, Chohan, A, Christie, LG, Clemson, BS, Collin, R, Cook, TH, Copen, DL, Cossett, J, Costantino, T, Crawford, MH, Croke, RP, Crowell, R, DAmours, G, Dagenais, GR, Danisa, K, Davidson, S, Davies, ML, Davies, R, Davies, RA, DeLarochelliere, R, DeLeon, AC, Delage, F, Denes, P, Dennish, GW, Denny, DM, DeVilla, MA, DeYoung, JP, Dhurandhar, RW, DibnerDunlap, M, Dodek, A, Doherty, JE, Dominguez, J, Dubbin, J, Dufton, J, Effron, MB, ElSherif, N, Eladasari, B, Fly, D, Ericson, K, Fahrenholtz, D, Fast, A, Fell, DA, Fishman, S, Fitchett, D, Fleg, JL, Flint, E, Folger, JS, Folkins, D, Forker, AD, Fowles, RE, Fraker, TD, Francis, G, Frerking, TR, Friesinger, GC, Fulop, JC, Gagnon, J, Gamble, L, Ganjavi, F, Garrou, BW, Gervais, PB, Gheorghiade, M, Gilbert, L, Gillie, E, Glatter, TR, Godley, ML, Goeres, M, Goldberger, MH, Gollapudi, A, Goode, JE, Goodman, LS, Gordon, R, Gossard, D, Gosselin, G, Goulet, C, Grant, C, Graettinger, WF, Greene, JG, Greenwood, PV, Gregoratos, G, Gregory, JJ, Groden, DL, Grover, J, Gudapati, R, Guess, MA, Gupta, SC, Habib, N, Hack, I, Hamilton, WP, Hankey, TL, Hanna, M, Harper, D, Harris, DE, Hassapoyannes, CA, Hatheway, RJ, Heinsimer, J, Pequignot, MH, Heiselman, DE, Hess, AR, Hickner, J, Hickey, JE, Higgins, T, Higginson, L, Hill, L, Hobbs, RE, Honos, G, Horner, BA, Horwitz, L, Hsieh, A, Hsueh, JT, Hubbard, J, Hughes, DF, Hui, W, Imrie, JR, Jacobs, MH, Jarmukli, N, Johnson, TH, Johnstone, D, Jutila, CK, Kadri, N, Kahl, FR, Kaimal, PK, Karnegis, J, Kay, R, Kelly, KJ, Kenefick, G, Kennelly, BM, Kent, E, Khan, AH, Khanijo, V, Khouri, M, Kinloch, D, Kirlin, PC, Kiwan, GS, Kline, MD, Kohn, RM, Koilpillai, C, Kornder, JM, Kouz, S, Kumar, VA, Kumar, U, Kuntz, A, Kuritzky, RA, Kuruvilla, G, Kwok, KK, Lader, E, Laforest, M, LaForge, D, Lalonde, G, Lalonde, L, Lang, RM, Latour, Y, Lawal, O, LeBlanc, MH, Lee, AB, Lee, RW, Legault, C, Lemay, M, Lenis, JHF, Lepage, S, Letarte, P, Levesque, C, LevinoffRoth, SN, Lewis, BK, Lipshutz, H, Loungani, RR, Lowery, ML, Lubell, DL, Lucariello, R, LugoRodriguez, JE, Lui, C, Lutterodt, AT, Lutz, L, Machel, T, Macina, G, MacLellan, K, Magnan, O, Mansuri, M, Manyari, DE, Mallis, GI, Marr, D, Mast, DJ, Mathew, J, McBarron, FD, McIntyre, KM, McLean, RW, McMahon, DP, Mercier, M, Methe, M, Miller, AB, Minkowitz, J, Milton, JR, Mizgala, HF, Mohanty, PK, Mohiuddin, S, Montero, A, Mookherjee, S, Morris, A, Morris, L, Morrison, J, Moten, M, Nafziger, A, Nair, PH, Nawaz, S, Neiman, JC, Nutting, P, NguyenPho, HT, OBrien, TK, OKelly, RL, OReilly, MV, Okerson, D, Patel, G, Pande, PN, Papa, LA, Patrick, L, Payne, RM, Perry, G, Philbin, EF, Pierpont, G, Pitt, WA, Poirier, C, Pollak, EM, Popio, K, Poulin, JF, Probst, PA, Pruneau, G, Pu, C, Puram, BS, Putatunda, B, Quinn, B, Rabkin, SW, Racine, N, Raco, DL, Radant, L, Radford, MJ, Radwany, S, Rajachar, M, Ramanathan, KB, Rashkow, A, Rausch, DC, Read, L, Reddy, KR, Reid, R, Rich, MW, Ricci, AJ, Richman, HG, Riley, A, Rim, DA, Rinne, C, Roberge, G, Roberts, DK, Robinson, V, Rodeheffer, RT, Rosenstein, R, Roth, DL, Rothbart, R, Rouleau, JL, Ruble, P, Sacco, J, Safford, RE, Salmon, D, Sahay, BM, Sarma, RJ, Sayeed, MAR, Schick, EC, Schroeder, GS, Seifert, M, Senaratne, MPJ, Sestier, F, Shah, A, Shanes, JG, Sheesley, K, Silverman, A, Shiva, T, Shrestha, DD, Silver, MA, Silverberg, L, Simard, L, Singh, BN, Small, RS, Smith, MR, Smith, S, Sochowski, RA, Southern, RF, Sridharan, MR, StHilaire, R, Stein, M, Stewart, JW, Stillabower, ME, Sullivan, BHM, Sturrock, WA, Sussex, BA, Swan, J, Swenson, L, Talbot, P, Talibi, T, Tamilia, M, Tan, A, Tanser, PH, Tarry, L, Teo, KK, Thadani, U, Thagirisa, S, Thompson, B, Thornton, R, Timmis, GC, Tobin, M, Tommaso, C, Toren, M, Tsuyuki, R, Turek, M, Utley, K, Vanderbush, EJ, VanVoorhees, L, Ventura, H, Vertes, G, Vizel, S, Wagner, KR, Wagner, S, Weeks, A, Weingert, ME, Weinstein, C, Weiss, MM, Weiss, R, Wickemeyer, W, Wielgoz, A, Willens, HJ, Williams, WL, Wong, D, Yarows, SA, Yao, L, Shalev, Y, Young, JB, Yousefian, M, Zajac, EJ, Zatuchni, J, Ziperman, DB, Zoble, RG, Zoneraich, S, Gorlin, R, Sleight, P, Cohn, JN, Collins, R, Deykin, D, Hennekens, C, Kjekshus, J, Smith, TW, Tognoni, G, Collins, JF, Williford, WO, Fye, C, Sather, R, Jolly, MK, Held, CP, Verter, J, Yusuf, S, Egan, D, Garg, R, Johnstone, DE, Montague, T, Bristow, D, Engelhardt, HT, Gent, M, Hood, WB, Jones, S, Meier, P, Pitt, B, Waters, D, Baker, A, Barnhill, S, Carew, B, Hagar, S, Liuni, C, Martin, S, Miles, R, Arthur, MM, Feldbush, MW, Highfield, DA, Hobbins, TE, Kurz, R, Leviton, SP, Libonati, JP, Moore, M, Perez, E, Mills, P, Geller, N, Hunsberger, S, Gold, J, Huang, PC, Burns, A, Caleb, H, Cline, DR, Harris, S, Hockenbrock, R, Horney, RA, Jadwin, LM, King, J, Sexton, P, Spence, ME, Chacon, F, Gagne, W, Maple, S, and Martinez, G

Subjects
Heart Failure, Male, Pharmacology, Digoxin, Treatment Outcome, Patient Selection, Digitalis Glycosides, Humans, Multicenter Studies as Topic, Female, Middle Aged, Aged, Randomized Controlled Trials as Topic
Abstract

This article provides a detailed overview of the rationale for key aspects of the protocol of the Digitalis Investigation Group (DIG) trial. It also highlights unusual aspects of the study implementation and the baseline characteristics. The DIG trial is a large, simple, international placebo-controlled trial whose primary objective is to determine the effect of digoxin on all cause mortality in patients with clinical heart failure who are in sinus rhythm and whose ejection fraction isor = 0.45. An ancillary study examines the effect in those with an ejection fraction0.45. Key aspects of the trial include the simplicity of the design, broad eligibility criteria, essential data collection, and inclusion of various types of centers. A total of 302 centers in the United States and Canada enrolled 7788 patients between February 1991 and September 1993. Follow-up continued until December 1995 with the results available in Spring 1996.

Published
1996

5. Liquid Chromatography MALDI MS/MS for Membrane Proteome Analysis

Author

Liang Li, Young Jb, and Wang N

Subjects
chemistry.chemical_compound, Chromatography, Chemistry, Elution, Proteome, medicine, Acid hydrolysis, Membrane proteome, Sodium dodecyl sulfate, Trypsin, Proteomics, Tandem mass spectrometry, medicine.drug
Abstract

Liquid chromatography (LC) can be combined with matrix-assisted laser-desorption ionization (MALDI) mass-spectrometry (MS) by using automated off-line fraction collection of eluates onto a MALDI plate. Commercial tandem MS systems are available for generating product ion spectra of MALDI-produced peptide ions. The MALDI MS/MS spectra can be searched against a proteome database for protein identification. In this chapter, a protocol of sequential solubilization and digestion of membrane proteins involving methanol- and SDS-assisted trypsin digestion and microwave-assisted acid hydrolysis is presented. The process of LC eluate deposition onto a MALDI plate along with practical considerations for achieving optimal performance of eluate deposition is described. Issues related to MALDI MS and MS/MS spectral acquisition are discussed. Database searching and manual inspection of MS/MS spectra of singly charged MALDI-produced peptide ions for positive protein identification are also addressed.

Published
2009

6. Baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF).

Author

McMurray, JJV, Anand, IS, Diaz, R, Maggioni, AP, O'Connor, C, Pfeffer, MA, Solomon, SD, Tendera, M, van Veldhuisen, DJ, Albizem, M, Cheng, S, Scarlata, D, Swedberg, K, Young, JB, RED-HF Committees Investigators, McMurray, JJV, Anand, IS, Diaz, R, Maggioni, AP, O'Connor, C, Pfeffer, MA, Solomon, SD, Tendera, M, van Veldhuisen, DJ, Albizem, M, Cheng, S, Scarlata, D, Swedberg, K, Young, JB, and RED-HF Committees Investigators

Abstract

AIMS: This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes. METHODS AND RESULTS: Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate < 60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106-117) g/L. CONCLUSION: The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.

Published
2013

11. Effects of discontinuation of digoxin versus continuation at low serum digoxin concentrations in chronic heart failure

Author

Ahmed, A, Gambassi, Giovanni, Weaver, Mt, Young, Jb, Wehrmacher, Wh, Rich, Mw, Gambassi, Giovanni (ORCID:0000-0002-7030-9359), Ahmed, A, Gambassi, Giovanni, Weaver, Mt, Young, Jb, Wehrmacher, Wh, Rich, Mw, and Gambassi, Giovanni (ORCID:0000-0002-7030-9359)

Abstract

Discontinuation of digoxin is associated with worsening heart failure (HF) symptoms. However, the long-term effects of discontinuation of digoxin therapy on mortality and morbidity in HF have not been well studied. Of the 7,788 participants in the Digoxin Investigation Group trial, 3,365 received digoxin before randomization. During the trial, digoxin was continued in 1,666 patients and discontinued in 1,699 patients. Using multivariable Cox regression analyses, we first determined the effect of discontinuation of digoxin on mortality and hospitalization during 39.7 months of median follow-up. Of the 1,666 patients continued on digoxin, 457 had low (0.5 to 0.9 ng/ml) and 340 had high (>or=1.0 ng/ml) serum digoxin concentrations (SDC) after 1 month of therapy and of the 1,699 patients whose digoxin was discontinued, 1,674 were alive at 1 month. We examined the effects of continuation of digoxin at low or high SDC. Compared with continuation of long-term digoxin therapy, discontinuation of digoxin was associated with a significant increase in all-cause hospitalization (adjusted hazard ratio [AHR] 1.18, 95% confidence interval [CI] 1.09 to 1.28, p <0.0001) and HF hospitalization (AHR 1.35, 95% CI 1.20 to 1.51, p <0.0001), but had no effect on all-cause mortality (AHR 1.06, 95% CI 0.95 to 1.19, p = 0.272). In contrast, continuation of digoxin at low SDC was associated with a reduction in all-cause mortality (AHR 0.75, 95% CI 0.63 to 0.90, p = 0.002), all-cause hospitalization (AHR 0.80, 95% CI 0.70 to 0.91, p = 0.001), and hospitalization for HF (AHR 0.60, 95% CI 0.50 to 0.73, p <0.0001). In conclusion, continuation of long-term digoxin therapy at low SDC was associated with reduction in mortality and hospitalization in ambulatory patients with chronic HF receiving background therapy with angiotensin-converting enzyme inhibitors and diuretics.

Published
2007

12. An analysis of P times reported in the Reviewed Event Bulletin for Chinese underground explosions

Author

Douglas, A, O'Mongain, A, Porter, D, Young, JB, Douglas, A, O'Mongain, A, Porter, D, and Young, JB

Abstract

Analysis of variance is used to estimate the measurement error and path effects in the P times reported in the Reviewed Event Bulletins (REBs, produced by the provisional International Data Center, Arlington, USA) and in times we have read, for explosions at the Chinese Test Site. Path effects are those differences between traveltimes calculated from tables and the true times that result in epicentre error. The main conclusions of the study are: (1) the estimated variance of the measurement error for P times reported in the REB at large signal-to-noise ratio (SNR) is 0.04 s2, the bulk of the readings being analyst-adjusted automatic-detections, whereas for our times the variance is 0.01 s2 and (2) the standard deviation of the path effects for both sets of observations is about 0.6 s. The study shows that measurement error is about twice (∼0.2 s rather than ∼0.1 s) and path effects about half the values assumed for the REB times. However, uncertainties in the estimated epicentres are poorly described by treating path effects as a random variable with a normal distribution. Only by estimating path effects and using these to correct onset times can reliable estimates of epicentre uncertainty be obtained. There is currently an international programme to do just this. The results imply that with P times from explosions at three or four stations with good SNR (so that the measurement error is around 0.1 s) and well distributed in azimuth, then with correction for path effects the area of the 90 per cent coverage ellipse should be much less than 1000 km2—the area allowed for an on-site inspection under the Comprehensive Test Ban Treaty—and should cover the true epicentre with the given probability.

Published
2005

15. End-systolic volume index at 90 to 180 minutes into reperfusion therapy for acute myocardial infarction is a strong predictor of early and late mortality. The Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO)-I Angiographic Investigators

Author

Migrino, RQ, primary, Young, JB, additional, Ellis, SG, additional, White, HD, additional, Lundergan, CF, additional, Miller, DP, additional, Granger, CB, additional, Ross, AM, additional, Califf, RM, additional, and Topol, EJ, additional

Published
1997
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21. Influence of coronary angiography on the utilization of therapies in patients with acute heart failure syndromes: findings from Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF).

Author

Flaherty JD, Rossi JS, Fonarow GC, Nunez E, Stough WG, Abraham WT, Albert NM, Greenberg BH, O'Connor CM, Yancy CW, Young JB, Davidson CJ, Gheorghiade M, Flaherty, James D, Rossi, Joseph S, Fonarow, Gregg C, Nunez, Eduardo, Stough, Wendy Gattis, Abraham, William T, and Albert, Nancy M

Abstract

Background: Most patients hospitalized for acute heart failure syndromes (AHFS) carry a diagnosis of coronary artery disease (CAD), but coronary angiography is infrequently performed. This purpose of this study was to determine the influence of coronary angiography on use of therapeutics and early postdischarge outcomes in patients with AHFS. Methods: The Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure program enrolled 48,612 patients admitted with AHFS at 259 academic and community hospitals throughout the United States Inhospital treatments and outcomes were tracked in all patients and postdischarge outcomes in a prespecified 10% sample. Outcome data were prospectively collected and analyzed according to whether coronary angiography was performed during the index hospitalization and whether a patient had CAD. Results: Overall, 8.7% of all patients underwent inhospital angiography. Among patients with CAD who underwent angiography, 27.5% underwent inhospital myocardial revascularization. At the time of discharge, patients with CAD who underwent angiography were significantly more likely to be receiving aspirin (68.9% vs 50.3%, P < .0001), statins (56.6% vs 40.6%, P < .0001), beta-blockers (78.6% vs 67.5%, P < .0001), and angiotensin-converting enzyme inhibitors (64.9% vs 51.5%, P < .0001). In patients with AHFS and CAD, the use of inhospital angiography was associated with significantly lower mortality and rehospitalization risk in the first 60 to 90 days post hospital discharge after adjustment for multiple comorbidities and patient factors: mortality (HR 0.31 [95% CI 0.14-0.70], P = .004) and death or rehospitalization (OR 0.65 [95% CI 0.50-0.86], P = .003). There were no significant differences in any of these outcomes in patients with AHFS and a nonischemic etiology based the performance of inhospital angiography. Conclusions: The performance of inhospital angiography on patients with AHFS and CAD is associated with an increased use of aspirin, statins, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors and myocardial revascularization. This corresponded with significantly lower rates of death, rehospitalization, and death or rehospitalization at 60 to 90 days post discharge. [ABSTRACT FROM AUTHOR]

Published
2009
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25. Prevention of heart failure: a scientific statement from the American Heart Association Councils on Epidemiology and Prevention, Clinical Cardiology, Cardiovascular Nursing, and High Blood Pressure Research; Quality of Care and Outcomes Research Interdisciplinary Working Group; and Functional Genomics and Translational Biology Interdisciplinary Working Group.

Author

Schocken DD, Benjamin EJ, Fonarow GC, Krumholz HM, Levy D, Mensah GA, Narula J, Shor ES, Young JB, Hong Y, and American Heart Association. Council on Epidemiology and Prevention

Published
2008

31. Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention.

Author

Maron BJ, Towbin JA, Thiene G, Antzelevitch C, Corrado D, Arnett D, Moss AJ, Seidman CE, Young JB, and American Heart Association

Published
2006

34. Palliation of heart failure.

Author

Davis MP, Albert NM, and Young JB

Abstract

Heart failure is the major cause of morbidity and mortality in the United States. Stage D heart failure has a greater mortality rate than many cancers and has equivalent symptom burden and severity. There has been a paradigm shift in our understanding of the pathophysiology of heart failure. Progressive heart failure is associated with ventricular remodeling and a maladaptive neurohumoral response. Drug classes have evolved that curtail ventricular remodeling, and blunt neurohumoral responses reduce morbidity and mortality. Despite combination drug and device therapies, the management of Stage D heart failure includes palliation. Both cardiology and palliative specialists need to learn from one another in order to palliate these highly symptomatic patients. Such collaboration will enhance care and are the basis for well-conceived research trials. [ABSTRACT FROM AUTHOR]

Published
2005
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36. Mortality and morbidity reduction with candesartan in patients with chronic heart failure and left ventricular systolic dysfunction: results of the CHARM Low-Left Ventricular Ejection Fraction Trials.

Author

Young JB, Dunlap ME, Pfeffer MA, Probstfield JL, Cohen-Solal A, Dietz R, Granger CB, Hradec J, Kuch J, McKelvie RS, McMurray JJV, Michelson EL, Olofsson B, Ostergren J, Held P, Solomon SD, Yusuf S, Swedberg K, and Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity Investigators and Committees

Published
2004

38. Hemodynamic and clinical effects of tezosentan, an intravenous dual endothelin receptor antagonist, in patients hospitalized for acute decompensated heart failure.

Author

Torre-Amione G, Young JB, Colucci WS, Lewis BS, Pratt C, Cotter G, Stangl K, Elkayam U, Teerlink JR, Frey A, Rainisio M, Kobrin I, Torre-Amione, Guillermo, Young, James B, Colucci, Wilson S, Lewis, Basil S, Pratt, Craig, Cotter, Gad, Stangl, Karl, and Elkayam, Uri

Abstract

Objectives: We sought to investigate the efficacy and safety of tezosentan, a dual endothelin receptor antagonist, in patients hospitalized for acute heart failure (HF).Background: Tezosentan has been previously shown to improve hemodynamics in patients with stable chronic HF.Methods: In a double-blind fashion, 292 patients (cardiac index < or =2.5 l/min per m(2) and pulmonary capillary wedge pressure (PCWP) > or =15 mm Hg) who were admitted to the hospital and in need of intravenous treatment for acute HF and central hemodynamic monitoring were randomized to 24-h intravenous treatment with tezosentan (50 or 100 mg/h) or placebo. Central hemodynamic variables, the dyspnea score, and safety variables were measured.Results: After 6 h of treatment, significantly greater increases in the cardiac index and decreases in PCWP were observed with both tezosentan dosages than with placebo (mean treatment effects at 0.38 and 0.37 l/min per m(2) with 50 and 100 mg/h and -3.9 mm Hg for each dose, respectively; p < 0.0001). This effect was maintained during the remaining infusion and for > or =6 h after treatment cessation. A tendency for an improved dyspnea score and a decreased risk of clinical worsening was observed after 24 h of treatment with each tezosentan dose. Adverse events, more frequent with tezosentan than with placebo (headache, asymptomatic hypotension, early worsening of renal function, nausea, vomiting), were dose-related.Conclusions: Intravenous tezosentan rapidly and effectively improved hemodynamics in these patients. The similar beneficial effects of the two dosages and the increased dose-related adverse events with the higher dosage suggest that the optimal dosing regimen is <50 mg/h. [ABSTRACT FROM AUTHOR]

Published
2003
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41. Initial experience with a telemeterized gait analysis system.

Author

Young, JB, Perkins, P., Atkinson, S., and Chamberlain, MA

Abstract

The M I E gait analysis system has been developed to allow a range of objective gait measurements to be readily obtained in a clinical setting. The equipment and its use are described together with a series of repeatability studies. The results suggest that the system is easy to operate and sufficiently reliable for use in clinical departments. [ABSTRACT FROM PUBLISHER]

Published
1989
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42. The contribution of the Stanford Health Assessment Questionnaire in rheumatology clinics.

Author

Young, JB and Chamberlain, MA

Abstract

The contribution of the Stanford Health Assessment Questionnaire (HAQ) to patient management was investigated in patients attending two rheumatology clinics. Additional interventions occurred in 55 (36%) of 147 patients completing the HAQ after the questionnaires had been inspected. It was particularly useful for the review patients compared to the new attenders. The HAQ is a more rational approach to outpatient functional appraisal and improves patient management. [ABSTRACT FROM PUBLISHER]

Published
1987
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