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Biomedical subjects

G Barbash

Publications and source records attributed to G Barbash.

17 recordsLinked to original sources
PubMed2001

Incidence and predictors of bleeding events after fibrinolytic therapy with fibrin-specific agents: a comparison of TNK-tPA and rt-PA.

BACKGROUND: Fibrinolytic therapy increases the risk of bleeding events. TNK-tPA (tenecteplase) is a variant of rt-PA with greater fibrin specificity and reduced plasma clearance that can be given as a single bolus. We compared the incidence and predictors of bleeding events after treatment with TNK-tPA and rt-PA. METHODS AND RESULTS: In the Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT)-2 trial, 16 949 patients with acute myocardial infarction were randomly assigned a single weight-adjusted bolus of TNK-tPA or a 90-min infusion of rt-PA. A total of 4.66% of patients in the TNK-tPA group experienced major non-cerebral bleeding, in comparison with 5.94% in the rt-PA group (P=0.0002). This lower rate was associated with a significant reduction in the need for blood transfusion (4.25% vs 5.49%, P=0.0003) and was consistent across subgroups. Independent risk factors for major bleeding were older age, female gender, lower body weight, enrolment in the U.S.A. and a diastolic blood pressure <70 mmHg. Females at high risk (age >75 years and body weight <67 kg) were less likely to have major bleeding when treated with TNK-tPA even after other risk factors were taken into account. A total of 0.93% of patients in the TNK-tPA and 0.94% of patients in the rt-PA group experienced an intracranial haemorrhage. Female patients >75 years of age who weighed <67 kg tended to have lower rates of intracranial haemorrhage when treated with TNK-tPA (3/264, 1.14% vs 8/265, 3.02%). CONCLUSIONS: The increased fibrin specificity and single bolus administration of TNK-tPA do not increase the risk of intracranial haemorrhage but are associated with less non-cerebral bleeding, especially amongst high-risk patients.

Adult↗
PubMed1999

Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomised trial.

BACKGROUND: Bolus fibrinolytic therapy facilitates early efficient institution of reperfusion therapy. Tenecteplase is a genetically engineered variant of alteplase with slower plasma clearance, better fibrin specificity, and high resistance to plasminogen-activator inhibitor-1. We did a double-blind, randomised, controlled trial to assess the efficacy and safety of tenecteplase compared with alteplase. METHODS: In 1021 hospitals, we randomly assigned 16,949 patients with acute myocardial infarction of less than 6 h duration rapid infusion of alteplase (< or = 100 mg) or single-bolus injection of tenecteplase (30-50 mg according to bodyweight). All patients received aspirin and heparin (target activated partial thromboplastin time 50-75 s). The primary outcome was equivalence in all-cause mortality at 30 days. FINDINGS: Covariate-adjusted 30-day mortality rates were almost identical for the two groups--6.18% for tenecteplase and 6.15% for alteplase. The 95% one-sided upper boundaries of the absolute and relative differences in 30-day mortality were 0.61% and 10.00%, respectively, which met the prespecified criteria of equivalence (1% absolute or 14% relative difference in 30-day mortality, whichever difference proved smaller). Rates of intracranial haemorrhage were similar (0.93% for tenecteplase and 0.94% for alteplase), but fewer non-cerebral bleeding complications (26.43 vs 28.95%, p=0.0003) and less need for blood transfusion (4.25 vs 5.49%, p=0.0002) were seen with tenecteplase. The rate of death or non-fatal stroke at 30 days was 7.11% with tenecteplase and 7.04% with alteplase (relative risk 1.01 [95% CI 0.91-1.13]). INTERPRETATION: Tenecteplase and alteplase were equivalent for 30-day mortality. The ease of administration of tenecteplase may facilitate more rapid treatment in and out of hospital.

Aged↗
PubMed1997

Improved outcome of elderly patients (> or = 75 years of age) with acute myocardial infarction from 1981-1983 to 1992-1994 in Israel. The SPRINT and Thrombolytic Survey Groups. Secondary Prevention Reinfarction Israel Nifedipine Trial.

BACKGROUND: The number of elderly patients experiencing acute myocardial infarction (AMI) is growing rapidly, and their hospital mortality rate remains high, although mortality after AMI declined in the 1990s with the introduction of new therapeutic modalities. METHODS AND RESULTS: We compared the management, in-hospital complications, and 30-day and 1-year mortality rates in two cohorts of elderly (> or = 75 years of age) AMI patients in the coronary care units in Israel before and after the reperfusion era. The first cohort of 789 consecutive patients was from the Secondary Prevention Reinfarction Israel Nifedipine Trial registry in 1981-1983; the second 366 patients came from two prospective nationwide surveys in 1992 and 1994. Reperfusion therapies were not used in 1981-1983 but were used in 1992-1994. The 30-day mortality rate declined from 38% in 1981-1983 to 27% in 1992-1994 (odds ratio, 0.49; 95% confidence interval [CI], 0.34 to 0.71), and the cumulative 1-year mortality rate declined from 52% to 38% (hazard ratio [HR], 0.62; 95% CI, 0.50 to 0.76). In the 1992-1994 cohort, the decline in mortality was most marked in patients reperfused by thrombolysis and/or percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery but was also evident in nonreperfused patients: cumulative 1-year mortality rate was 29% in the former (HR, 0.45; 95% CI, 0.31 to 0.67) and 42% in the latter (HR, 0.60; 95% CI, 0.46 to 0.78). CONCLUSIONS: During the last decade, elderly (> or = 75 years) AMI patients experienced fewer in-hospital complications and lower 30-day and 1-year mortality rates, which declined approximately 30%, most markedly in reperfused patients. The favorable outcome in 1992-1994 was related to changes in patient management. Reperfusion therapy is therefore also advocated in elderly AMI patients, unless specific contraindications are present.

Aged↗
PubMed1996

Prognostic Importance of Previous Myocardial Infarction in Patients Receiving Thrombolytic Therapy for Acute Infarction.

This study evaluated the prognostic significance of reinfarction location by considering the previous site or type of myocardial infarction (MI) among 1601 patients with a history of previous MI who took part in the International (non-Italian) tPA/STK trial and/or the Israeli GUSTO study population. These patients were accordingly divided and hospital mortality was compared by six location groups as follows: acute inferior with previous inferior (8.1% hospital mortality), acute inferior with previous anterior (12.8%), acute anterior with previous inferior (13.3%), acute anterior with previous anterior (11.1%), acute inferior with previous non-Q-wave MI (7.6%), and acute anterior with previous non-Q-wave MI (11.2%) (p = 0.17 for comparison between the six groups). Hospital mortality tended to increase among patients with an anterior reinfarction compared with those with an inferior one (12.1% vs. 9.5%, p = 0.12). Among patients with a reinfarction at a different ECG location from the previous event, mortality tended to be higher compared with patients with two MIs at the same location (13.1% vs. 9.7%, p = 0.07). Recurrent MI following a previous Q-wave MI did not cause a higher mortality compared with a previous non-Q-wave type of MI (11.5% vs. 9.5%, p = 0.24). Among patients sustaining reinfarction, overall mortality did not differ between STK- and tPA-treated patients (11.0% vs. 11.4%, p = NS). In conclusion, the current study identified trends for higher mortality rates in patients with anterior compared with inferior reinfarction, with remote compared with the same ECG location of the two infarctions but not following a previous non-Q-wave compared with Q-wave MI. However, no particular combination of successive MIs location was significantly associated with a higher risk for hospital mortality.

Journal Article↗
PubMed1995

Cost effectiveness of thrombolytic therapy with tissue plasminogen activator as compared with streptokinase for acute myocardial infarction.

BACKGROUND: Patients with acute myocardial infarction who were treated with accelerated tissue plasminogen activator (t-PA) (given over a period of 1 1/2 hours rather than the conventional 3 hours, and with two thirds of the dose given in the first 30 minutes) had a 30-day mortality that was 15 percent lower than that of patients treated with streptokinase in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) study. This was equivalent to an absolute decrease of 1 percent in 30-day mortality. We sought to assess whether the use of t-PA, as compared with streptokinase, is cost effective. METHODS: Our primary, or base-case, analysis of cost effectiveness used data from the GUSTO study and life expectancy projected on the basis of the records of survivors of myocardial infarction in the Duke Cardiovascular Disease Database. In the primary analysis, we assumed that there were no additional treatment costs due to the use of t-PA after the first year and that the comparative survival benefit of t-PA was still evident one year after enrollment. RESULTS: One year after enrollment, patients who received t-PA had both higher costs ($2,845) and a higher survival rate (an increase of 1.1 percent, or 11 per 1000 patients treated) than streptokinase-treated patients. On the basis of the projected life expectancy of each treatment group, the incremental cost-effectiveness ratio--with both future costs and benefits discounted at 5 percent per year--was $32,678 per year of life saved. The use of t-PA was least cost effective in younger patients and most cost effective in older patients. At all ages, the use of t-PA in patients with anterior infarctions yielded more favorable cost-effectiveness values. In our secondary analyses, the cost-effectiveness values were most sensitive to a lowering of the projected long-term survival benefits of t-PA and to moderate or greater increases in the projected medical costs for patients in the t-PA group after the first year. In contrast, our results were not sensitive to even very unfavorable assumptions about the additional costs associated with the higher rate of disabling stroke that was noted in patients treated with t-PA in the GUSTO study. CONCLUSIONS: The cost effectiveness of treatment with accelerated t-PA rather than streptokinase compares favorably with that of other therapies whose added medical benefit for dollars spent is judged by society to be worthwhile.

Adult↗
PubMed1995

Twenty-five-year mortality rate decrease in patients in Israel with a first episode of acute myocardial infarction. Secondary Prevention Reinfarction Israeli Nifedipine Trial Study Group. Israeli Thrombolytic Survey Group.

The aim of our study was to compare the outcome of patients with a first acute myocardial infarction (AMI) among three large cohorts of patients hospitalized between 1966 and 1992 in Israel, in view of changes in treatment facilities and investigation methods. Patients with a first AMI constituted 71% of all myocardial infarctions in 1966, 74% in 1981-1983, and 71% in 1992. The male-female ratio and the distribution of the site of infarction also remained stable from 1966 to 1992. The mean age of patients increased over time. Thrombolytic therapy was not available in 1966 and 1981-1983, whereas 53% of patients were treated with a thrombolytic agent and 22% examined with coronary angiography in 1992. The 21-day mortality rate decreased markedly, from 22% in 1966 to 14% in 1981-1983 and to 8% in 1992. The decrease was similar in both genders and among 10-year age groups. The 1-year postdischarge mortality rate (not evaluated in 1966) decreased from 7% in 1981-1983 to 6% in 1992. We conclude that a significant reduction in mortality rate after a first AMI took place over the 25-year period. Changes in treatment modality and management of the acute phase may explain this decrease in mortality rate over time.

Adult↗
PubMed1992

Confronting the issues of patient safety and investigator conflict of interest in an international clinical trial of myocardial reperfusion. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) Steering Committee.

The Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial is a large scale international trial of new myocardial reperfusion strategies. The primary hypothesis is that early and sustained coronary artery recanalization will be associated with a significant reduction in mortality. The four regimens that are being tested are 1) streptokinase with subcutaneous heparin; 2) streptokinase with intravenous heparin; 3) accelerated recombinant tissue-type plasminogen activator (rt-PA) with intravenous heparin; and 4) combination streptokinase, rt-PA and intravenous heparin. The planned recruitment of 41,600 patients in 1,500 sites from 15 countries is expected to be completed by December 1992 and will enable detection of a 15% reduction or 1% absolute difference in mortality compared with that associated with standard therapy (streptokinase and subcutaneous heparin). In designing the trial, two important issues were directly addressed. First, a strategy was developed to provide assurance of patient safety during large scale investigational use of an aggressive thrombolytic regimen. This includes fascimile transmission of a one-page safety summary form to the Data Coordinating Center within 24 h of death or discharge, acceptance of the concept of "net clinical benefit" and close surveillance of the trial's progress by the independent Data and Safety Monitoring Committee. Second, to avoid potential conflict of interest beyond elimination of any position of financial equity, the Steering Committee unanimously voted to prohibit any honoraria for speaking engagements, payment for consultancy or travel or reimbursement of any kind from any of the five corporate sponsors until 1 year after publication of the results. Incorporation of these approaches may facilitate the design of future large scale randomized trials in cardiovascular medicine.

Biomedical Research↗
PubMed1992

Additional ST segment elevation during the first hour of thrombolytic therapy: an electrocardiographic sign predicting a favorable clinical outcome.

OBJECTIVES: The aim of this study was to investigate the significance of further ST elevation that occurs during the 1st h of thrombolytic therapy before the expected resolution. BACKGROUND: Early resolution of ST segment elevation is commonly accepted as a marker of clinical reperfusion during thrombolytic therapy for acute myocardial infarction. Using frequent electrocardiographic recordings, we observed in some patients further ST elevation that occurred during hour 1 of thrombolysis before the expected resolution. METHODS: To investigate the significance of this pattern, we classified 177 consecutive patients with a first acute myocardial infarction into two groups: Group A, 98 patients with ST elevation > or = 1 mm above the initial ST elevation during the 1st h of thrombolytic therapy, and Group B, 79 patients without this finding. RESULTS: Although the presence or absence of additional ST elevation was not associated with a clinical or prognostic difference in patients with a first inferior or posterior acute myocardial infarction, its presence indicated a more favorable clinical outcome and prognosis in patients with anterior infarction. Among the patients with anterior infarction the 65 patients in Group A had a higher ejection fraction (44 +/- 9% vs. 35 +/- 11%, p < 0.01), less heart failure (15% vs. 35%, p = 0.02) and a lower in-hospital mortality rate (0% vs. 8%, p = 0.04) than did the 37 patients from Group B. CONCLUSIONS: Additional ST elevation early during thrombolytic therapy in patients with anterior infarction suggests a favorable clinical outcome and thus may be indicative of successful reperfusion.

Aged↗
PubMed1991

Incidence of and reasons for excluding patients with acute myocardial infarction from thrombolytic therapy.

The percentage of patients with acute myocardial infarction (AMI) who were eligible for thrombolytic therapy was evaluated prospectively, with analysis of the causes for exclusion, in 857 patients with AMI hospitalized in the Chaim Sheba Medical Center, Tel-Hashomer, in 1988. Thrombolytic therapy was given to 127 patients (14.8%); 99 patients were treated with tissue plasminogen activating factor and 28 patients received streptokinase. Three hundred and sixty patients (42.0%) were rejected because of age (greater than 72 years). Other reasons for exclusion were duration of pain lasting for more than 4 h (28.5%), unknown time of onset of the chest pain (9.7%), absence of ST elevation on admission ECG (8.1%), systemic hypertension (4.4%), and presence of severe congestive heart failure upon admission (10.1%). Restricting thrombolytic therapy only to patients less than 72 years old with chest pain duration of 4 h limits the impact of this treatment on the general welfare of patients with AMI. By raising the age limit and extending the time interval between pain onset and treatment initiation, adding newer indications, and enhancing public awareness for early arrival to hospital, the benefit of thrombolytic therapy may be made available to more patients with AMI.

Adult↗
PubMed1984

Medical air evacuation during the Lebanon War, 1982.

During the Lebanon War, 1982, 85% of the Israel Defence Forces casualties were airlifted from the battle zone by means of the aeromedical evacuation (AME) network of the Air Force. The rescue helicopter was the first point of medical contact for 4.4% of the casualties. A summary is presented of the types of aircraft used in AME and the number of casualties carried in the various flights. A brief description is also given of a new addition to the intensive care capabilities of AME helicopters: the air mobile life support unit used in combat for the first time during this war.

Aircraft↗
PubMed1979

Effect of the MER tubercle bacillus fraction on the responsiveness of mice to T-independent antigens.

The effect of treatment with the methanol extraction residue (MER) mycobacterial fraction on the immunological responsiveness of BALB/c mice to the T-independent antigens pneumococcal polysaccharide type III (SIIII) and trinitrophenyl-lipopolysaccharide conjugate (TNP-LPS) was ascertained. Pretreatment with MER prevented the establishment of immunological paralysis by threshold doses (10 or 15 microgram) of SIII and by a paralyzing dose of 100 microgram TNP-LPS. The induction of immunological paralysis by SIII was unaffected by treatment with the bacterial adjuvant Corynebacterium parvum and with the B cell mitogens PPD, LPS (Escherichia coli lipopolysaccharide), and dextran sulfate.

Animals↗
PubMed1976

An improved quantitative plaque assay for lymphocytes bearing antigen-specific cell receptors.

An improved method for the determination of the number of lymphoid cells bearing antigen-specific receptors is described. The method is based on the use of hapten-coupled bacteriophage (dinitrophenyl-T4) and detection of lytic plaques formed by the action of DNP-T4 on a target E. coli strain. The method is highly specific (up to 90% specific binding) and can be adapted for use with other antigenic determinants chemically attached to an active bacteriophage.

Animals↗
PubMedDate not supplied

Inhibition of specific binding of DNP (dinitrophenyl) determinant to lymphoid-cell receptors by related and unrelated compounds : quantitative studies in vitro.

The effect of related and unrelated compounds on the specific binding of dinitrophenyl-coupled bacteriophage (DNP-T4) to lymphoid cell receptors has been examined and compared with the effect on the neutralization of DNP-T4 by anti-DNP serum. Spleen cells and sera from Balb/c mice immunized with DNP-bovine serum albumin were used. The binding of DNP-T4 to the cells was inhibited by DNP-eAcp, di-DNP-Lys, DNP-Tyr, DNP-p(Ornith) and DNP-BSA (among the DNP-derivatives tested), TNP-BSA, ARS-p(Tyr) and TGA. In addition with the above named DNP and TNP compounds, the DNP-T4neutralization by antiserum was also prevented by DNP-derivatives with either L-cysteic acid, alanine, glutamine or poly-L-glutamic acid, while ARS-p(Tyr) and TGA were not effective. Plain carriers (BSA, HSA, poly-ornithine, polylysine and polyglutaminc acid) and cell-mitogens (ConA, LPS and PPD) had no significant inhibitory effect. The results obtained indicate the occurrence of differences between cell-bound receptors and circulating antibodies in what concerning their specific reaction with the dinitrophenyl determinant.

Animals↗