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Biomedical subjects

B E Lewis

Publications and source records attributed to B E Lewis.

At least 37 records · Page 2Linked to original sources
PubMed1999

Clinical laboratory monitoring of a synthetic antithrombin agent, argatroban, using high performance liquid chromatography and functional methods.

BACKGROUND: Argatroban is a peptidomimetic inhibitor of thrombin which is in clinical trials for thrombotic complications. Clot-based assays measure the cumulative anticoagulant effect of argatroban and its metabolites(s). To monitor the absolute concentrations of argatroban, a specific HPLC method was developed. METHODS: Validation studies included normal volunteers administered with escalating doses of argatroban (ARG 102 Study), patients undergoing coronary interventional procedures (ARG 310), and patients receiving argatroban in conjuction with streptokinase for acute myocardial infarction (ARG 230). Plasma samples were extracted with acetonitrile and reconstituted in a mobile phase. UV detection was made at 333 nm. Calibratrion curves were prepared with known standards of argatroban in normal human plasma. RESULTS: The retention time for argaeroban was 6.0+/-0.5 min and the extraction efficiency was >98% (r2=0.99). In the ARG102 Study, argatroban levels were: 0.84+/-0.23 (day 1), 1.55+/-0.34 (day 2), 2.92+/-0.15 (day 3), and 3.04+/-0.49 (day 4). In the ARG310 trial, the mean argatroban levels were: 0.23+0.09 microg/ml (preinfusion), 5.77+/-0.92 microg/ml (postinfusion/intraprocedure), and 2.23+/-0.29 microg/ml (postprocedure). In the ARG 230 Study, the mean argatroban levels at 2-8 hrs were between 1.5-2.0 microg/ml. Upon completion of the infusion, a time-dependent clearance of argatroban was noted. CONCLUSIONS: Since heparinization, hemodilution and hypofibrinogenemia due to thrombolysis influence the clotting tests, absolute quantitation of argatroban by HPLC in these patients provides a more reliable means of monitoring this anticoagulant and helps in the dosage-optimization of this agent. The current HPLC method is of value in the monitoring of patients who are simultaneously administered with thrombolytic drugs.

Anticoagulants↗
PubMed1999

Laboratory tests for heparin-induced thrombocytopenia: a multicenter study.

A multicenter clinical trial of the thrombin inhibitor argatroban (Novastan; Texas Biotechnology, Houston, TX; Smith-Kline Beecham Pharmaceuticals, Philadelphia, PA) was recently conducted in patients with heparin-induced thrombocytopenia (HIT) and HIT that had progressed to thrombosis (HITTS). In patients defined by the inclusion/exclusion criteria, the utility of three diagnostic HIT assays was investigated: the platelet aggregation assay, the serotonin release assay (SRA), and the enzyme-linked immunosorbent assay (ELISA) for the antibody to the heparin-platelet factor 4 (H-PF4) complex. Confirmation was made in 26%, 55%, and 64% of the patients, respectively (n = 199 patients; 512 to 606 samples; P < .001 platelet aggregation assay v SRA v ELISA). Patients who progressed to HITTS (n = 98) were more often confirmed than were HIT patients without associated thrombosis (n = 101) (P < .05). Confirmation by platelet aggregation assay and SRA results generally was associated with a higher antibody titer. However, a minimum critical titer could not be identified, because all patterns of positive and negative results by the platelet aggregation assay, SRA, and ELISA were observed, and clinically ill patients had a wide range of antibody titers. Over a 30-day period, the percentage of positive responses did not change. Although multiple testing over several days enhanced the chance of confirmation, this difference was not significant. Combined results of the three assays enhanced the positive response to 83% of the total population (P < .005). These data demonstrate that there is no direct correlation between the positive response of these assays, and that clinically positive HIT patients can be missed by all three assays. With these limitations, the combination of platelet aggregation assay, SRA, and ELISA testing with multiple samples offers the best chance of confirming a positive HIT patient. Caution is advised, however, in interpreting all assay results, as no assay is optimal.

Acute Disease↗
PubMed1999

Plasmapheresis in the management of heparin-induced thrombocytopenia.

This study investigated the role of plasmapheresis in the treatment of severe heparin-induced thrombocytopenia (HIT). Patients diagnosed with HIT were divided into three experimental groups. Sixteen patients did not receive plasmapheresis (control). Twenty-one patients received plasmapheresis within 4 days of onset of thrombocytopenia (early group). Seven patients received plasmapheresis 4 days or later after onset (late group). Most patients underwent a second plasmapheresis 24 to 48 hours after the first, when clinically indicated, and platelet aggregation tests became negative in 75% of these patients. Heparin administration was discontinued after 1.4 days in the early group of patients and 4.2 days in the late group, as compared with 2.4 days in the control group. The 30-day mortality rate was 4.8% among patients in the early group and 57% in the late group, as compared with 32% in the control group. Platelet recovery time, incidence of thrombotic events, and length of hospital stay were similar in the early group and controls, but were somewhat higher in the late group. Thus, plasmapheresis within 4 days of the onset of thrombocytopenia reduced mortality in HIT patients, whereas plasmapheresis after 4 days was not beneficial. There were no adverse events related to plasmapheresis. These findings suggest that plasmapheresis may be useful in the treatment of HIT when initiated within 4 days of onset of thrombocytopenia.

Aged↗
PubMed1999

Antithrombin agents as anticoagulants and antithrombotics: implications in drug development.

The development of direct thrombin inhibitors goes back nearly four decades. Organic synthetic benzamidine derivatives were initially developed as direct antithrombin agents. Later, the structural analysis of fibrinogen, leading to the identification of thrombin cleavage sites, resulted in the recognition of specific peptide sequences where thrombin cleaved fibrinogen. These observations led to the development of synthetic peptide derivatives as inhibitors of thrombin. The leech salivary extract contained natural hirudin, the structural elucidation of which led to the development of a recombinant equivalent protein (r-hirudin). Understanding the biochemical actions of thrombin and the structure of various inhibitors prompted the development of hirulogs, a class of hybrid molecules with two sites of action. Currently, several of these thrombin inhibitors are being developed for various indications in both intravenous and subcutaneous protocols. The increased interest in thrombin inhibitors is also prompted by reports of heparin-induced thrombocytopenia (HIT) with heparin and the need to anticoagulate patients with alternate drugs. These agents produce a direct anticoagulant response by targeting thrombin. In addition, the amplification of the coagulation cascade by thrombin activation of factors V and VIII, stabilization of fibrin by activated factor XHI, and platelet activation is also inhibited by these thrombin inhibitors. Some of the synthetic thrombin inhibitors are also capable of inhibiting other enzymes in the coagulation cascade. Thrombin inhibitors therefore exert a complex effect on the coagulation network and should be carefully evaluated in clinical trials. These drugs can be used for prophylactic and therapeutic and surgical indications. However, the different thrombin inhibitors have shown distinct pharmacologic differences. There is now an interest in developing oral antithrombin inhibitors. Such issues as antagonism, laboratory monitoring, drug interactions, and long-term safety remain unresolved. Current research is focused on addressing these issues.

Amino Acid Sequence↗
PubMed1998

Patient noncompliance in the managed care setting. The case of medical therapy for glaucoma.

OBJECTIVES: The authors identify demographic and clinical characteristics associated with noncompliance in patients beginning medical therapy for the treatment of glaucoma in a managed care setting. METHODS: The authors describe a retrospective cohort study in a group-model health maintenance organization in Massachusetts. Patients were members of the health maintenance organization who were newly initiated on topical drug therapy to treat open-angle glaucoma during the period January 1, 1987 through December 31, 1990, who met eligibility requirements, and who had evidence of health services utilization for a 12-month follow-up period. For all study subjects, we determined the number of days without available therapy for glaucoma during the 12-month period. Study subjects who did not fill prescriptions adequate to provide medication to cover at least 80% of days during the study period were considered noncompliant. Logistic regression analysis was used to assess demographic and clinical factors independently associated with noncompliance among patients initiated on medical therapy for the treatment of glaucoma. RESULTS: Of 616 subjects who met inclusion criteria, 152 (24.7%; 95% confidence interval, 21.3%-28.1%) met the study definition for noncompliance. These patients had an average number of days without therapy during the 12-month study period of 103.9 +/- 70.0 days compared with 6.8 +/- 19.5 days for those categorized as compliant. Of a variety of selected demographic and clinical characteristics, having fewer visits with an ophthalmologist during the study period (< 2) was most strongly related to noncompliance (odds ratio 2.99; 95% confidence interval 2.03, 4.40). There were no differences in average intraocular pressure between the compliant and noncompliant groups during the study period. CONCLUSIONS: Noncompliance with prescribed medical therapy for glaucoma was found to be common in a managed care setting characterized by essentially unrestricted access to health care and medications. It remains difficult to identify noncompliant patients based on demographic and clinical characteristics. The use of automated prescription data to identify noncompliant patients is feasible in large managed health care insurance programs where such data are collected routinely for administrative purposes.

Adult↗
PubMed1998

The first report of successful carotid stent implant using argatroban anticoagulation in a patient with heparin-induced thrombocytopenia and thrombosis syndrome: a case report.

We report the first successful carotid stent implant in a patient with heparin-induced thrombocytopenia and thrombosis syndrome who presented with recurrent neurologic deficits secondary to severe carotid stenosis. Argatroban anticoagulation was used for the carotid stent deployment. We also present laboratory data that document effective procedural anticoagulation.

Aged↗
PubMed1997

Anticoagulation with Novastan (argatroban) in patients with heparin-induced thrombocytopenia and heparin-induced thrombocytopenia and thrombosis syndrome.

Heparin-induced thrombocytopenia (HIT) is a syndrome that has been identified with increased frequency. The mortality associated with HIT approaches 35%. Previous strategies for treatment of the associated thrombosis with HIT have frustrated clinicians with poor outcomes. Recent awareness of the complex pathophysiology of HIT combined with the availability of new anticoagulants has led to the development of a rational therapeutic strategy for this group of patients. The foundation of this strategy involves thrombin inhibition and careful patient monitoring. Our preliminary results with the thrombin inhibitor argatroban (Novastan) have been favorable and warrant continued investigation.

Antibodies↗
PubMed1997

Novastan anticoagulation during renal stent implant in a patient with heparin-induced thrombocytopenia.

We describe a case of a 70-year-old male who underwent coronary artery bypass surgery which was complicated by multiple thrombotic events associated with HIT. The thrombotic events were treated with intravenous argatroban (Novastan). During the hospitalization the patient was found to require percutaneous bilateral renal artery revascularization for acute renal failure. The revascularization procedure was successfully accomplished with a high dose argatroban regimen. We present our report of a successful anticoagulation strategy during a peripheral intervention in a patient with HIT and the laboratory data which support this strategy.

Aged↗
PubMed1997

The use of pharmacoeconomic data in managed care: closing the credibility gap.

According to the author, MCOs rarely incorporate the findings of pharmacoeconomic studies in formulary decision making. As a result, managed care plans fail to examine the costs and cost savings of a new drug across the whole health care continuum, but see only how it directly affects their system. Credible pharmacoeconomic data can be valuable to formulary decision makers, offering them a broader perspective. However, what constitutes credible pharmacoeconomic data?

Cost Control↗
PubMed1997

Enhancement of compliance among patients with hypertension.

Studies of patient compliance with medical advice consistently demonstrate a high level of noncompliance. Not following recommendations can have serious negative consequences in the management of disease. This study was an assessment of the effect on compliance of a longitudinal, individualized educational program for patients with hypertension in a managed care setting. A before-and-after self-paired design was used to assess the behavior of 107 patients with hypertension. Trained nurses using an interactive interview format reinforced prescribed treatment and provided appropriate printed material to participants. Brief telephone follow-up interviews at prescribed intervals were used to elicit problems, provide additional education, and reinforce compliance behaviors. Most of the patients who participated showed a statistically significant (P < 0.01) decrease in both systolic and diastolic blood pressure. There was also an effect on various recommended behaviors, including compliance with medication taking, ideal body weight, salt restriction, stress, and exercise. A statistically significant relation existed between improved compliance with individual behavior changes and decreased blood pressure (P < 0.01). Elderly persons were particularly likely to show statistically significant reductions in blood pressure (75.4% versus 50.0%). A chi 2 test indicated that those differences were significant at the 0.01 level. A relatively inexpensive, office-based educational protocol can have a statistically significant effect on treatment compliance among patients with hypertension. The intervention has particular implications for geriatric patients, whose high blood pressure is disproportionately represented.

Adult↗
PubMed1996

Report of successful use of argatroban as an alternative anticoagulant during coronary stent implantation in a patient with heparin-induced thrombocytopenia and thrombosis syndrome.

Heparin-induced thrombocytopenia and thrombosis syndrome (HITTS) is a severe complication of heparin caused by an antibody response to the heparin-platelet factor 4 complex which results in severe thrombosis. Heparin rechallenge in HITTS patients carries a high risk of inducing thrombosis. Antithrombin agents represent treatment alternatives in HITTS patients who require anticoagulation. We report successful coronary stent implantation in a HITTS patient using the antithrombin agent argatroban.

Aged↗
PubMed1996

Research collaboration between an HMO and an academic medical center: lessons learned.

Joint research ventures between health maintenance organizations (HMOs) and academic medical centers (AMCs) can strengthen both organizations from the research and patient care perspectives, by facilitating the exploration of views and cost-effective approaches to diagnoses and treatment. This article describes a research venture between the Fallon Healthcare System, a health maintenance organization (HMO), and the University of Massachusetts Medical Center, an academic medical center (AMC). This research venture, the Worcester Area Trial for Counseling Hyperlipidemia, was a four-year study in which 1,277 participants were recruited from 45 Fallon Clinic physician panels. The study targeted patients with blood cholesterol levels in the upper 25% of the cholesterol distribution. The different priorities and perspectives of the two institutions with regard to health care and research became more apparent as the study progressed. Eventually study personnel needed to re-examine the study objectives and each other's perspectives to accommodate these differences. This learning process showed that research ventures between HMOs and AMCs can prove mutually beneficial. An HMO can gain experience with large government-funded projects. AMCs can study managed care within a controlled setting. However, the differing priorities and perspectives of these institutions' organizational structures require that considerable attention be paid to their representatives' working relationships and perceptions.

Academic Medical Centers↗
PubMed1996

Characterisation of asthma management in the Fallon Community Health Plan from 1988 to 1991.

In order to characterise asthma management in a managed care setting, we identified 10,301 patients who were diagnosed with asthma between 1 January 1988 and 31 December 1991 at a group model health maintenance organisation in central Massachusetts, US. We obtained for these patients automated utilisation files containing data on medications, hospitalisations, emergency room visits, office visits, and estimated costs of these services. The medication dispensed to the greatest proportion of patients was beta 2 agonists either by inhalation (56%) or orally (21%). Theophylline was dispensed to 23% of the patients. Maintenance therapy was inhaled anti-inflammatory medication was uncommon, as inhaled corticosteroids (17%) and sodium cromoglycate (cromolyn sodium) [8%] were dispensed to fewer patients than other asthma medications. Among patients who had been hospitalised in the previous year, 36% were presently receiving inhaled corticosteroids, and among patients who used at least one beta 2 agonist metered-dose inhaler per month, 49% were presently receiving inhaled corticosteroids. Economic analyses showed that only 8% of the patients had either a hospital admission or an emergency room visit, but hospital costs among these patients accounted for 25% of the total costs of asthma care. In addition, the top 10% most expensive patients accounted for 42% of the total cost of asthma care. We conclude that a substantial proportion of patients at increased risk of a severe attack, by virtue of having a recent hospitalisation, do not receive maintenance anti-inflammatory therapy, and that hospitalisations among a relatively small proportion of asthma patients contribute significantly to the cost of asthma care.

Adolescent↗
PubMed1995

Percutaneous balloon pericardiotomy: a double-balloon technique.

We describe a double-balloon technique for performing a percutaneous balloon pericardiotomy. This technique was employed when the large, single dilation balloon customarily used for this procedure failed to fully inflate across the parietal pericardium. Two smaller balloons were advanced through the same skin tract and simultaneously inflated, thus producing an adequate pericardial window. This double-balloon technique allowed for the more secure anchoring of the balloons across the pericardium and for the delivery of greater dilation pressures.

Adenocarcinoma↗
PubMed1995

HMO outcomes research: lessons from the field.

This article examines the field of outcomes research from the perspective of a managed care organization, The Fallon Healthcare System, currently involved in many different types of studies. Outcome studies are characterized by the types of questions they examine. The cost and labor implications for each category are examined. Finally, a partnership among different participants in the outcome research field, including managed care organizations, academic institutions, and pharmaceutical companies, is proposed.

Chronic Disease↗
PubMed1995

Patency of cryopreserved saphenous vein grafts as conduits for coronary artery bypass surgery.

STUDY OBJECTIVE: To determine the angiographic patency of cryopreserved saphenous vein grafts used as conduits during coronary artery bypass surgery and whether this is affected by postoperative immunosuppressive therapy. DESIGN AND SETTING: A retrospective review of medical records and coronary angiograms of patients at a university hospital. PATIENTS: Eleven patients undergoing 12 coronary artery bypass operations during which a total of 26 distal coronary anastomoses were created using cryopreserved vein grafts. MEASUREMENTS: Eight postoperative coronary angiograms were performed in 10 patients surviving longer than 1 week. All angiograms were performed on the basis of symptoms of suspected myocardial ischemia. Angiographic results, postoperative anticoagulation, and therapy with immunosuppressive agents were analyzed. RESULTS: Seventeen cryopreserved vein grafts were studied; one (6%) was patent, 12 (71%) were occluded, and 4 (23%) were stenosed. In patients treated with azathioprine, seven of the eight cryopreserved vein grafts were occluded. In patients not receiving immunosuppression, five were occluded, three were stenosed, and one was patent. All internal mammary grafts were widely patent. CONCLUSION: Cryopreserved vein grafts have a poor angiographic patency which did not appear to be affected by immunosuppressive therapy with azathioprine. The use of this graft should be restricted and alternative arterial conduits utilized.

Aged↗