Recombinant factor VIIa (rFVIIa) was developed to provide an improved procoagulant component capable of 'by-passing' inhibitor antibodies in the treatment of haemophilic patients. The primary objective of this study was to compare the efficacy of two dosage regimens of rFVIIa (given intravenously at periodic intervals) in the treatment of joint, muscle and mucocutaneous haemorrhages in persons with haemophilia A and B with and without inhibitors. The study was designed as a randomized, double-blind, parallel group, international multicenter trial. Patients were randomly allocated to treatment A: 35 mu kg-1 or B: 70 mu kg-1, in blocks of 2. Within each block, one patient was assigned to the 35 mu kg-1 dosing regimen and the other to 70 mu kg-1 dose. One hundred and fifty subjects from 20 sites were screened for this study and 116 had baseline assessments. Of these, 84 were treated on the protocol and 32 were not treated in the study, in most cases because they did not return to the clinic with an eligible bleeding episode. One hundred and seventy-nine bleeding episodes were treated, of which 145 (81%) were acute haemarthroses. Both treatments were efficacious, with 71% having an excellent (59% and 60%) or effective (12% and 11%) response. Overall, the mean and median number of doses given per episode of joint bleeding were 3.1 and 2, respectively. The mean number of doses was 3.1 for the 70 mu kg-1 group and 2.7 for the 35 mu kg-1 group (P value = 0.142). The study concluded that rFVIIa in a dosage of 35 mu kg-1 or 70 mu kg-1 is both safe and reasonably effective in the treatment of joint or muscle haemorrhages in haemophilic patients with inhibitor antibodies to factor VIII or factor IX. It is concluded that the appropriate dose for the treatment of joint and peripheral muscle bleeding in haemophilic patients with inhibitors is 35-70 mu kg-1 given at 2-3 h intervals until haemostasis is achieved.

Objectives To evaluate the effectiveness of inviting teenagers to general practice consultations to discuss health behaviour concerns and appropriate follow up care. Design Randomised controlled trial, with participants randomised to a consultation (intervention) or usual care (control). Questionnaires completed at baseline, 3 months, and 12 months. Setting Eight general practices in Hertfordshire, England. Participants 1516 teenagers aged 14-15 years. Intervention Consultations with practice nurses to discuss health concerns and develop plans for healthier lifestyles. Main outcome measures Mental and physical health, "stage of change" for health related behaviour, and use of health services. Results At baseline 970 teenagers completed questionnaires; 23% smoked, 35% had been drunk in the previous three months, 64% considered they ate unhealthily, 39% took little exercise, and 36% had possible depression. 41% (304) of teenagers invited attended for a consultation; over one third (112) were offered follow up care. More intervention group teenagers reported positive movement in stage of change for diet and exercise and in at least one of four behaviours (diet, exercise, smoking, drinking alcohol) at 3 months (41% v 31%, P < 0.01), but this did not persist at 12 months. There was marginally more positive change in actual behaviour by intervention teenagers at 3 months (16% v 12%, P=0.06). Recognition of possible depression resulted in improved mental health outcomes at 3 and 12 months. 97% of attenders said they would recommend the intervention to a friend. Conclusions Change in behaviour was slight but encouraging, and the intervention was well received and relatively cheap.

Biochemically atypical strains classified as Vibrio cholerae were characterized by biochemical reactions, serology, antibiotic susceptibility testing, and deoxyribonucleic acid relatedness. Strains with the following atypical reactions were shown to be V. cholerae: mannose negative, mannitol negative, lysine decarboxylase negative, no growth in the presence of 5% NaCI, salicin and cellobiose positive. Sucrose-negative strains were shown to constitute a new species, Vibrio mimicus, whose type strain is 1721-77 (ATCC 33653). In addition to its negative sucrose reaction, V. mimicus was differentiated from V. cholerae by its negative Voges-Proskauer, corn oil, and Jordan tartrate reactions and by its sensitivity to polymyxin. V. mimicus was isolated from shellfish and water, as well as from human diarrheal stools and ear infections. Most strains were typable with antisera against V. cholerae. Strains from three serogroups produced either a heat-labile or a heat-stable enterotoxin.

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This paper summarizes the design and evaluation of an instructional approach aimed at improving the writing skills of a group of undergraduate engineering students. We sought to determine whether student performance in difficult writing skills such as argumentation and synthesis could be improved by integrating a single writing exercise into an upper level engineering course. In designing the exercise, we relied heavily on recommendations for best practices from the learning science community, specifically those codified in the National Academy text How People Learn [1]. We found reliable improvement in student performance in many of the areas targeted, demonstrating that the approach taken was effective. Since we modified the exercise a few times before meeting our objectives for student learning, we could compare the effectiveness of different implementations of our approach. Our success and failures provide guidance for others seeking to improve the competence of engineering undergraduates in writing.

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We report the use of recombinant VIIa (rFVIIa) in the treatment of five ICHs in two factor VIII-deficient patients with inhibitors. In four of five ICHs, rFVIIa was the only factor replacement used at doses of 60-135 micrograms/kg every 2-4 hr for 12-14 days. Hemostasis at the primary site of bleeding was achieved in all cases, and all patients survived with no permanent neurologic deficits. However, the patient who received the highest dose of rFVIIa during the first 4 days of therapy developed clinical symptoms consistent with a cerebral vascular accident of the brainstem characterized by acute onset of truncal ataxia and upward-gaze nystagmus on day 8 of rFVIIa therapy. While receiving rFVIIa therapy for treatment of these five ICHs, four treatment courses were complicated by bleeding at sites other than the primary site, including two episodes of localized oozing at central line insertion sites, two episodes of hemarthrosis, and two episodes of epistaxis. Antifibrinolytic therapy with tranexamic acid was effective in two of these episodes. Laboratory evaluation revealed shortening of the PT, variable shortening without normalization of the APTT, peak factor VII activity levels 7-30-fold higher than normal baseline values, and normal antithrombin III (ATIII) and alpha 2-antiplasmin levels. In four of five ICHs, there was a 20-40% decrease in fibrinogen levels from baseline. The decrease in fibrinogen was accompanied by an increase in fibrin degradation products in 3/5 episodes and a 15-35% decrease in plasminogen activity levels in 2/5 episodes. Tissue factor pathway inhibitor (TFPI) levels remained stable and in the normal range. Although rFVIIa is an effective new therapy for the treatment of ICH in hemophilia patients with inhibitors, its optimal use with respect to safety and efficacy requires further clinical study.