A single blind, placebo-controlled randomized study of the safety, reactogenicity and immunogenicity of the “EpiVacCorona” Vaccine for the prevention of COVID-19, in volunteers aged 18–60 years (phase I–II)

Vaccination of the population is one of the most effective countermeasures in responding to the pandemic caused by novel coronavirus infection. Therefore, scientists all over the world have been working to develop effective and safe vaccines. We have developed a synthetic peptide vaccine, EpiVacCorona, against novel SARS-CoV-2 coronavirus, which is a suspension for intramuscular administration containing a composition of chemically synthesized peptide immunogens of the S protein of SARS-CoV-2 coronavirus conjugated to a carrier protein and adsorbed on aluminum hydroxide. Phase I–II clinical trials of the vaccine have started that consist of two stages: Stage 1 is an open study of the safety, reactogenicity, and immunological activity of the vaccine with the involvement of 14 volunteers aged 18–30 years; Stage 2 is a single blind, comparative, randomized placebo-controlled study with the involvement of 86 volunteers. The study involved volunteers aged 18–60 years; the vaccine was injected intramuscularly twice, spaced 21 days apart between injections. All local reactions in response to vaccine administration were mild, such as a short-term pain at the injection site. There were no signs of development of local or systemic adverse reactions. The two-dose vaccination scheme induced the production of antibodies, specific to the antigens that make up the vaccine, in 100% of the volunteers. Seroconversion with a neutralizing antibody titer ≥ 1:20 was reported in 100% of the volunteers 21 days following the second immunization dose. No seroconversion was reported in the groups of volunteers vaccinated with a placebo. The peptide-based EpiVacCorona Vaccine has low reactogenicity and is a safe, immunogenic product. Clinical Trials Identifier: NCT04527575

Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials

Background Patients with chronic obstructive pulmonary disease (COPD) have few options for treatment. The efficacy and safety of the phosphodiesterase-4 inhibitor roflumilast have been investigated in studies of patients with moderate-to-severe COPD, but not in those concomitantly treated with longacting inhaled bronchodilators. The effect of roflumilast on lung function in patients with COPD that is moderate to severe who are already being treated with salmeterol or tiotropium was investigated. Methods In two double-blind, multicentre studies done in an outpatient setting, after a 4-week run-in, patients older than 40 years with moderate-to-severe COPD were randomly assigned to oral roflumilast 500 mu g or placebo once a day for 24 weeks, in addition to salmeterol (M2-127 study) or tiotropium (M2-128 study). The primary endpoint was change in prebronchodilator forced expiratory volume in 1s (FEV(1)). Analysis was by intention to treat. The studies are registered with ClinicalTrials.gov, number NCT00313209 for M2-127, and NCT00424268 for M2-128. Findings In the salmeterol plus roflumilast trial, 466 patients were assigned to and treated with roflumilast and 467 with placebo; in the tiotropium plus roflumilast trial, 371 patients were assigned to and treated with roflumilast and 372 with placebo. Compared with placebo, roflumilast consistently improved mean prebronchodilator FEV(1) by 49 mL (p<0.0001) in patients treated with salmeterol, and 80 mL (p<0.0001) in those treated with tiotropium. Similar improvement in postbronchodilator FEV(1) was noted in both groups. Furthermore, roflumilast had beneficial effects on other lung function measurements and on selected patient-reported outcomes in both groups. Nausea, diarrhoea, weight loss, and, to a lesser extent, headache were more frequent in patients in the roflumilast groups. These adverse events were associated with increased patient withdrawal. Interpretation Roflumilast improves lung function in patients with COPD treated with salmeterol or tiotropium, and could become an important treatment for these patients

SQ HDM SLIT-tablet (ALK) in treatment of asthma--post hoc results from a randomised trial

In a double-blind, placebo-controlled trial (EudraCT identifier: 2006-001795-20), the standardised quality (SQ) house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet (ALK, Denmark) was investigated

Bond markets and banks in inter-war Japan

The issuance of bonds increased in inter-war Japan, the main investors being banks because the demand for loans declined in this period. Banks that were more tolerant to risk (that is, whose capital ratio was higher) made a larger amount of loans, which were riskier than bonds. While national bonds were traded actively in secondary markets, local bonds, corporate bonds, and bank debentures were not traded actively during this period. After the formation of cartels of banks and securities firms for bond underwriting and trading during the Great Depression, bond trading in secondary markets diminished, except for national bonds.Japanese banks, bond markets, inter-war period, the Great Depression, portfolio management,