Evaluation of avoralstat, an oral kallikrein inhibitor, in a Phase 3 hereditary angioedema prophylaxis trial: The OPuS-2 study.

BACKGROUND: Effective inhibition of plasma kallikrein may have significant benefits for patients with hereditary angioedema due to deficiency of C1 inhibitor (C1-INH-HAE) by reducing the frequency of angioedema attacks. Avoralstat is a small molecule inhibitor of plasma kallikrein. This study (OPuS-2) evaluated the efficacy and safety of prophylactic avoralstat 300 or 500 mg compared with placebo. METHODS: OPuS-2 was a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Subjects were administered avoralstat 300 mg, avoralstat 500 mg, or placebo orally 3 times per day for 12 weeks. The primary efficacy endpoint was the angioedema attack rate based on adjudicator-confirmed attacks. RESULTS: A total of 110 subjects were randomized and dosed. The least squares (LS) mean attack rates per week were 0.589, 0.675, and 0.593 for subjects receiving avoralstat 500 mg, avoralstat 300 mg, and placebo, respectively. Overall, 1 subject in each of the avoralstat groups and no subjects in the placebo group were attack-free during the 84-day treatment period. The LS mean duration of all confirmed attacks was 25.4, 29.4, and 31.4 hours for the avoralstat 500 mg, avoralstat 300 mg, and placebo groups, respectively. Using the Angioedema Quality of Life Questionnaire (AE-QoL), improved QoL was observed for the avoralstat 500 mg group compared with placebo. Avoralstat was generally safe and well tolerated. CONCLUSIONS: Although this study did not demonstrate efficacy of avoralstat in preventing angioedema attacks in C1-INH-HAE, it provided evidence of shortened angioedema episodes and improved QoL in the avoralstat 500 mg treatment group compared with placebo.

Compartment syndrome in the critically injured following massive resuscitation: case reports.

Compartment syndrome of the extremities is usually associated with locally mediated events such as ischemia or injury. Three cases are presented of patients who did not sustain direct extremity trauma, but who developed compartment syndrome following massive fluid resuscitation. Global ischemia/reperfusion may be responsible for the observed morbidity. Patients undergoing large volume resuscitation should be closely monitored for this entity.

[Bicycle ergometry test and the work incapacity of men 40 to 59]. / Veloérgometricheskaia proba i netrudosposobnost' u muzhchin 40--59 let.

The purpose of the investigation was to study the relationship between indicators of the bicycle ergometry test and temporary disability degree in males aged 40 to 59 residing in the area of 2 district outpatient clinics in Moscow. Disability (temporary, stable) was studied by a method of standard interviewing. The bicycle ergometry test was applied to each patient using a standard scheme. The investigation showed an inverse ration between physical exercise tolerance and disability degree.

[Development of methodical principles and approval of new forms of contact with school children (ages 12-13 years) in carrying out preventive measures (results of a pilot study)]. / Razrabotka metodicheskikh printsipov i aprobatsiia novykh form kontakta so shkol'nikami 12-13 let pri provedenii profilakticheskikh meropriiatii (rezul'taty predvaritel'nogo issledovaniia).

The results of the screening and 1-year follow-up of pupils from two Moscow schools of general education (Moscow secondary schools) are presented. The program on preventive measures was conducted by using the playing forms of contact and influence, at one of the above schools (experimental school). Most of the adolescents of the experimental school (mean 80%) participated in the preventive measures. By the completion of the program the number of the participants increased up to 94%. A reliably significant increase in the education level on the problems about the adverse effects of smoking and beneficial effects of regular nutrition in adolescents of the experimental school was observed. The analysis of the results of the screening and follow-up of schoolchildren aged 12-13 years enables us to conclude that it is necessary to work out new criteria for the assessment of preventive measures among adolescents.

[Bicycle ergometry test results in persons with ischemic heart disease detected in mass screening]. / Rezul'taty veloérgometricheskoi proby u lits s ishemicheskoi bolezn'iu serdtsa, vyiavlennoi pri massovom obsledovanii.

Bicycle ergometry in 40-59 year-old male patients with coronary heart disease, identified during mass prophylactic examination on the basis of epidemiological criteria, has shown that in patients with angina pectoris of effort and no myocardial infarction in history positive exercise tests are observed in 20,8% of cases, while in patients with painless CHD forms positive results are observed in 15.4% of cases. Positive exercise tests are the most often in patients with daily anginal attacks and in those with ST depression and flat negative T waves.