Search PubMed⌕ Search

Biomedical subjects

Philip M Brown

Publications and source records attributed to Philip M Brown.

8 recordsLinked to original sources
PubMed2005

Alternative parenteral anticoagulation with argatroban, a direct thrombin inhibitor.

Argatroban, a direct thrombin inhibitor, effectively inhibits free and clot-bound thrombin without the need of a cofactor and exerts dose-dependent anticoagulant effects that are rapidly active and rapidly reversible (elimination half-life: 39-51 min). Argatroban provides predictable parenteral anticoagulation and is well tolerated with an acceptably low bleeding risk in a variety of clinical settings, including heparin-induced thrombocytopenia, acute ischemic stroke, percutaneous coronary intervention and hemodialysis. This review will discuss the clinical pharmacology and utility of argatroban; in particular, clinical trial experiences will be discussed in patients with, or at risk of, heparin-induced thrombocytopenia (where heparins must be avoided) including those requiring hemodialysis or percutaneous coronary intervention, and in patients with acute ischemic stroke (where heparins are not generally recommended).

Anticoagulants↗
PubMed2004

Argatroban anticoagulation in patients with acute ischemic stroke (ARGIS-1): a randomized, placebo-controlled safety study.

BACKGROUND AND PURPOSE: Direct thrombin inhibitors, including argatroban, represent an anticoagulant class distinct from heparins. We investigated the safety of 2 levels of argatroban anticoagulation in acute ischemic stroke. METHODS: This multicenter, randomized, double-blinded, placebo-controlled study included 171 patients with acute (< or =12 hours from onset) stroke and National Institutes of Health Stroke Scale (NIHSS) scores of 5 to 22. Patients received continuous intravenous argatroban (100 microg/kg bolus) at 3 microg/kg per minute (n=59) or 1 microg/kg per minute (n=58), respectively, adjusted to target activated partial thromboplastin times (aPTTs) 2.25x and 1.75x baseline or placebo (n=54) for 5 days. The primary outcome was symptomatic intracranial hemorrhage (ICH) at 30 days. RESULTS: Baseline characteristics including neurologic deficits (median NIHSS score 9) were comparable between groups. Argatroban at mean doses of 2.7 and 1.2 microg/kg per minute increased aPTTs significantly (P<0.001), with mean aPTTs at or near target values throughout infusion. Symptomatic ICH was not significantly different between groups (high-dose argatroban, 5.1%; low-dose argatroban, 3.4%; placebo, 0%; P> or =0.18), with 3 events during argatroban infusion and 2 events > or =7 days after stopping infusion. No significant between-group differences occurred in asymptomatic ICH (7 events), major systemic hemorrhage (no event), or 90-day mortality (13.4% overall). CONCLUSIONS: In this first North American randomized, double-blinded, placebo-controlled study of direct thrombin inhibition in acute ischemic stroke, argatroban at each dose evaluated significantly prolonged aPTTs without increasing ICH or major bleeding. These results suggest that argatroban provides safe anticoagulation in acute ischemic stroke, warranting future studies powered to evaluate its efficacy and more precisely estimate event rates.

Aged↗
PubMed2004

Stroke in patients with heparin-induced thrombocytopenia and the effect of argatroban therapy.

OBJECTIVE: To investigate the frequency, mortality rate, and characteristics of stroke in heparin-induced thrombocytopenia and the effect of argatroban therapy in that setting. DESIGN: Retrospective analysis of two prospective studies of argatroban therapy in heparin-induced thrombocytopenia. SETTING: Hospitalized care. PATIENTS: Patients were 960 patients with heparin-induced thrombocytopenia (767 argatroban-treated patients, 193 historical controls). INTERVENTIONS: Argatroban 2 microg x kg x min, adjusted to achieve activated partial thromboplastin times 1.5-3 times baseline MEASUREMENTS AND MAIN RESULTS: Case records were reviewed to identify patients with stroke present at or within 37 days of study entry and to assess 37-day outcomes. Stroke occurred in 30 (3.1%) patients (stroke at entry, n = 9; new stroke during follow-up, n = 24; more than one stroke, n = 4). By logistic regression with treatment, protocol, age, and gender as covariates, females were significantly more likely to suffer stroke (odds ratio, 2.48; 95% confidence interval, 1.11-5.53; p =.026) and stroke-associated mortality (odds ratio, 4.10; 95% CI, 1.12-15.01; p =.033), and argatroban-treated patients had significantly reduced odds, vs. control, of new stroke (odds ratio, 0.31; 95% confidence interval, 0.10-0.96; p =.041) and stroke-associated mortality (odds ratio, 0.18; 95% confidence interval, 0.03-0.92; p =.039). Stroke (odds ratio, 3.66; 95% confidence interval, 1.73-7.73; p <.001) and age (odds ratio per year, 1.017; 95% confidence interval, 1.004-1.029; p =.008) were significant predictors of all-cause death. In the argatroban group, baseline platelet counts were significantly less in patients with, vs. without, stroke (medians, 42 x 10/L vs. 72 x 10/L; p =.006). Of 35 stroke events, 33 (94%) were ischemic and two (6%) were hemorrhagic (one per group, none during argatroban infusion); 30 (86%) were present at or within 13 days of entry. CONCLUSIONS: Stroke, particularly ischemic stroke, is common in heparin-induced thrombocytopenia and significantly increases mortality risk. Stroke in heparin-induced thrombocytopenia occurs most often in females, in patients with more severe thrombocytopenia, and within 2 wks of heparin-induced thrombocytopenia presentation. Argatroban therapy vs. control significantly reduces the likelihood of new stroke and stroke-associated mortality in heparin-induced thrombocytopenia without increasing intracranial hemorrhage.

Aged↗
PubMed2002

Lack of pharmacokinetic interactions between argatroban and warfarin.

The potential for pharmacokinetic interactions between argatroban and warfarin was studied. In a randomized, crossover study, healthy volunteers participated in three treatment periods, each separated by a nine-day washout interval. Drug regimens consisted of a single oral 7.5-mg dose of warfarin, intravenous argatroban infused at a rate of 1.25 micrograms/kg/min for 100 hours, or both. Blood samples were collected at intervals up to 104 hours to determine clearance (CL) and the apparent first-order elimination rate constant (kel) for argatroban and the area under the concentration-versus-time curve (AUC) and maximum concentration (Cmax) for R- and S-warfarin. An interaction was defined as a > 25% difference in the magnitude of the pharmacokinetic values between administration of one drug alone and coadministration with the other agent. Twelve adult subjects were enrolled. The mean CL and lel for argatroban administered alone differed by < 7% from the mean values when the two drugs were coadministered. When warfarin was administered alone, the mean Cmax and AUC of R- and S-warfarin differed from the mean values when the two drugs were coadministered by < 10%. Prothrombin time was prolonged comparably when argatroban was administered alone and with warfarin. No deaths or serious adverse events were reported. No significant pharmacokinetic interactions were detected between i.v. argatroban 1.25 micrograms/kg/min and a single 7.5-mg oral dose of warfarin. Argatroban was well tolerated when administered alone or with warfarin.

Adult↗
PubMed2002

The distribution of carotid endarterectomy procedures among surgeons and hospitals in New York state: is regionalization of specialized vascular care occurring?

INTRODUCTION: In a published analysis of all carotid endarterectomies (CEAs) performed in New York state from 1990 to 1995, perioperative mortality rate was inversely correlated with surgeon and hospital CEA volume, was significantly higher when CEAs were performed by surgeons who performed less than five CEAs annually, and was significantly lower in hospitals where surgeons performed more than 100 CEAs annually. The purpose of this study was to determine whether this information has influenced practice patterns in New York state. METHODS: The database of the Center for Medical Consumers was queried to determine the volume distribution among surgeons and hospitals of all CEAs performed in New York state in 1999 and 2000. RESULTS: During 1999, 695 surgeons in 169 hospitals performed 9458 CEAs (mean, 13.6 per surgeon). Three hundred fifty-three surgeons (51%) performed less than five CEAs, and 180 (26%) performed only one CEA during the year. Only 41 surgeons (6%) performed more than 50 CEAs. Likewise, in only 28 of the hospitals (17%) were more than 100 CEAs performed during 1999, whereas in 73 of the hospitals (43%) 20 or less CEAs were carried out during the year. During 2000, 684 surgeons performed 8196 CEAs in 165 hospitals. Three hundred fifty-three (52%) performed less than five CEAs, and 229 (33%) performed only one CEA during the year. Only 33 surgeons (5%) performed more than 50 CEAs during 2000. In only 26 hospitals (16%) were more than 100 CEAs performed during 2000, whereas in 71 hospitals (43%) 20 or less CEAs were carried out. CONCLUSION: It appears that published compelling evidence that operator and institutional volume influence outcome has not influenced referral patterns or led to a regionalization of CEA care in New York state. Robust educational programs directed to patients and referring physicians appear indicated.

Age Factors↗
PubMed2002

Comparison of acustimulation and ondansetron for the treatment of established postoperative nausea and vomiting.

BACKGROUND: This study was designed to evaluate transcutaneous electrical acupoint stimulation (acustimulation) using the ReliefBand compared with ondansetron for the treatment of established postoperative nausea and vomiting (PONV) after outpatient laparoscopic surgery. METHODS: After the authors obtained institutional review board approval and written informed consent, 268 outpatients were enrolled in this randomized, double-blind, placebo- and sham-controlled study. All patients received antiemetic prophylaxis with metoclopramide, 10 mg intravenously, or droperidol, 0.625 mg intravenously, after induction of anesthesia. A total of 90 patients developed PONV in the recovery units and were randomized to one of three treatment groups: (1) the ondansetron group received 4 mg intravenous ondansetron and a sham ReliefBand; (2) the acustimulation group received 2 ml intravenous saline and a ReliefBand; and (3) the combination group received 4 mg intravenous ondansetron and a ReliefBand. A rescue antiemetic (10 mg intravenous metoclopramide) was administered only if the PONV symptoms persisted for 15 min or longer after initiating the treatment. A blinded observer recorded the recovery times, emetic symptoms, rescue antiemetics, maximum nausea scores, complete response to study treatment, and time to achieve discharge criteria. Postdischarge side effects, as well as patient satisfaction and quality of recovery scores, were assessed at 24 and 72 h after surgery. RESULTS: The combination group had a significantly higher complete response rate than the acustimulation group (73% vs.40%, P <0.01). In addition, fewer patients (8 vs. 18) in the combination (vs. acustimulation) group experienced subsequent emetic events (P < 0.03). However, there were no significant differences between the three groups with respect to patient satisfaction and quality of recovery scores. CONCLUSIONS: Acustimulation with the ReliefBand can be used as an alternative to ondansetron for the treatment of established PONV. However, the use of ondansetron (4 mg intravenously) in combination with the ReliefBand device improved the complete response rate to the acustimulation therapy.

Adult↗