ABSTRACT
Acquired haemophilia A (AHA) is a rare bleeding disorder caused by autoantibodies against human factor VIII (hFVIII). OBI-1 is an investigational, B-domain deleted, recombinant FVIII, porcine sequence, with low cross-reactivity to anti-hFVIII antibodies. Efficacy can be monitored with FVIII activity levels in addition to clinical assessments. This prospective, open label, phase 2/3 study was designed to evaluate the efficacy of OBI-1 treatment for bleeding episodes in subjects with AHA. After an initial dose of 200 U kg(-1) , OBI-1 was titrated to maintain target FVIII activity levels, in correlation with clinical assessments, throughout the treatment phase. All 28 subjects with AHA had a positive response to OBI-1 treatment 24 h after initiation despite inhibition of FVIII activity levels immediately after infusion in 10 subjects with baseline anti-porcine FVIII inhibitors. Control of the qualifying bleed was ultimately achieved in 24 of 28 subjects. No related serious adverse events, thrombotic events, allergic reactions or thrombocytopaenia occurred. The results of this study indicate that OBI-1 is safe and effective in treating bleeding episodes in subjects with AHA. The ability to safely and effectively titrate dosing based on FVIII activity levels in this study demonstrates that OBI-1 fulfils the unmet medical need to monitor the key coagulation parameter in AHA patients.
Subject(s)
Factor VIII/therapeutic use , Hemophilia A/drug therapy , Recombinant Proteins/therapeutic use , Adult , Aged , Aged, 80 and over , Animals , Antibodies, Neutralizing , Autoantibodies/immunology , Cross Reactions/immunology , Factor VIII/administration & dosage , Factor VIII/adverse effects , Factor VIII/immunology , Female , Hemophilia A/immunology , Humans , Male , Middle Aged , Recombinant Proteins/administration & dosage , Recombinant Proteins/adverse effects , Recombinant Proteins/immunology , Swine , Time Factors , Treatment OutcomeABSTRACT
AIM: Considerable evidence shows that cigarette smokers tend to have the dyslipidemic pattern of high plasma triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) concentrations, a highly atherogenic lipoprotein profile also typical of the insulin-resistant state even in the absence of cigarette smoking. However, because cigarette smokers are frequently insulin resistant, it is unclear if this dyslipidaemia is secondary to smoking, per se, or simply to the fact that smokers tend to be insulin resistant. The present study was initiated to determine whether this dyslipidaemia prevalent in cigarette smokers and characteristic of insulin-resistant individuals is a function of cigarette smoking or of insulin resistance. METHODS: As measured using vertical auto profile-II methodology, the lipid and lipoprotein concentrations were compared in 34 cigarette smokers divided into insulin-sensitive and insulin-resistant subgroups. The two groups were similar in age and body mass index, differing only in their insulin-mediated glucose uptake as quantified by the steady-state plasma glucose concentration determined during the insulin suppression test. RESULTS: While levels of TG and very low-density lipoprotein cholesterol (VLDL-C) were significantly elevated in insulin-resistant cigarette smokers, total cholesterol (C), low-density lipoprotein cholesterol (LDL-C), narrow-density (ND) LDL-C, intermediate-density lipoprotein-C (IDL-C), HDL-C and non-HDL-C were not different in the two groups. The insulin-resistant smokers also had a preponderance of small, dense LDL particles, while the reverse was true of the insulin-sensitive cigarette smokers. CONCLUSIONS: These data suggest that the dyslipidaemia previously attributed to smoking occurs primarily in those smokers who are also insulin resistant.
Subject(s)
Dyslipidemias/etiology , Insulin Resistance , Smoking/adverse effects , Adult , Aged , Body Mass Index , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Dyslipidemias/blood , Dyslipidemias/physiopathology , Female , Humans , Lipids/blood , Lipoproteins/blood , Male , Middle Aged , Smoking/blood , Smoking/physiopathology , Triglycerides/bloodSubject(s)
Angina, Unstable/diagnosis , Angina, Unstable/epidemiology , Myocardial Infarction/diagnosis , Myocardial Infarction/epidemiology , Causality , Chest Pain/diagnosis , Chest Pain/epidemiology , Evidence-Based Medicine , Female , Humans , Incidence , Length of Stay/statistics & numerical data , Predictive Value of Tests , Prospective Studies , Risk Assessment , Sensitivity and Specificity , Severity of Illness Index , Survival Rate , United States/epidemiologyABSTRACT
The National Heart Attack Alert Program (NHAAP), which is coordinated by the National Heart, Lung, and Blood Institute (NHLBI), promotes the early detection and optimal treatment of patients with acute myocardial infarction and other acute coronary ischemic syndromes. The NHAAP, having observed the development and growth of chest pain centers in emergency departments with special interest, created a task force to evaluate such centers and make recommendations pertaining to the management of patients with acute cardiac ischemia. This position paper offers recommendations to assist emergency physicians in EDs, including those with chest pain centers, in providing comprehensive care for patients with acute cardiac ischemia.
