Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine (FAKHRAVAC®) in healthy adults aged 18-55 years: Randomized, double-blind, placebo-controlled, phase I clinical trial.

Background: The FAKHRAVAC®, an inactivated SARS-CoV-2 vaccine, was assessed for safety and immunogenicity. Methods and findings: In this double-blind, placebo-controlled, phase I trial, we randomly assigned 135 healthy adults between 18 and 55 to receive vaccine strengths of 5 or 10 µg/dose or placebo (adjuvant only) in 0-14 or 0-21 schedules. This trial was conducted in a single center in a community setting. The safety outcomes in this study were reactogenicity, local and systemic adverse reactions, abnormal laboratory findings, and Medically Attended Adverse Events (MAAE). Immunogenicity outcomes include serum neutralizing antibody activity and specific IgG antibody levels.The most frequent local adverse reaction was tenderness (28.9%), and the most frequent systemic adverse reaction was headache (9.6%). All adverse reactions were mild, occurred at a similar incidence in all six groups, and were resolved within a few days. In the 10-µg/dose vaccine group, the geometric mean ratio for neutralizing antibody titers at two weeks after the second injection compared to the placebo group was 9.03 (95% CI: 3.89-20.95) in the 0-14 schedule and 11.77 (95% CI: 2.77-49.94) in the 0-21 schedule. The corresponding figures for the 5-µg/dose group were 2.74 (1.2-6.28) and 5.2 (1.63-16.55). The highest seroconversion rate (four-fold increase) was related to the 10-µg/dose group (71% and 67% in the 0-14 and 0-21 schedules, respectively). Conclusions: FAKHRAVAC® is safe and induces a strong humoral immune response to the SARS-CoV-2 virus at 10-µg/dose vaccine strength in adults aged 18-55. This vaccine strength was used for further assessment in the phase II trial.Trial registrationThis study is registered with https://www.irct.ir; IRCT20210206050259N1.

Immunogenicity and Safety of a Combined Intramuscular/Intranasal Recombinant Spike Protein COVID-19 Vaccine (RCP) in Healthy Adults Aged 18 to 55 Years Old: A Randomized, Double-Blind, Placebo-Controlled, Phase I Trial.

Objectives: This study aimed to determine the safety and immunogenicity of a combined intramuscular/intranasal recombinant spike protein COVID-19 vaccine (RCP). Methods: We conducted a randomized, double-blind, placebo-controlled, phase I trial. Three vaccine strengths were compared with an adjuvant-only preparation. It included two intramuscular and a third intranasal dose. Eligible participants were followed for adverse reactions. Specific IgG, secretory IgA, neutralizing antibodies, and cell-mediated immunity were assessed. Results: A total of 153 participants were enrolled (13 sentinels, 120 randomized, 20 non-randomized open-labeled for IgA assessment). No related serious adverse event was observed. The geometric mean ratios (GMRs) and 95% CI for serum neutralizing antibodies compared with placebo two weeks after the second injection were 5.82 (1.46-23.13), 11.12 (2.74-45.09), and 20.70 (5.05-84.76) in 5, 10, and 20 µg vaccine groups, respectively. The GMR for anti-RBD IgA in mucosal fluid two weeks after the intranasal dose was 23.27 (21.27-25.45) in the 10 µg vaccine group. The humoral responses were sustained for up to five months. All vaccine strengths indicated a strong T-helper 1 response. Conclusion: RCP is safe and creates strong and durable humoral and cellular immunity and good mucosal immune response in its 10 µg /200 µL vaccine strengths. Trial registration: IRCT20201214049709N1.

Type 2 diabetes remission after Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and one anastomosis gastric bypass (OAGB): results of the longitudinal assessment of bariatric surgery study.

BACKGROUND: Several studies on various bariatric surgeries involving patients with type 2 diabetes mellitus (T2DM) showed an overall rate of remission of hyperglycemia. However, there is little known about predictive factors on remission after different types of surgeries. The aim of this study was to identify the T2DM remission rate and to determine the effects of preoperative factors characteristics of remission of type 2 diabetes in Iran. METHODS: We conducted a retrospective analysis of 1351 patients with T2DM operated by three different types of surgeries (Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and One Anastomosis Gastric Bypass (OAGB)). Diabetes remission was defined according to the American Diabetes Association (ADA) criteria. Binary logistic regression analyses were employed. RESULTS: A total of 1351 patients, 675 patients (50.0%) undergoing OAGB, 475 (35.2%) RYGB, and 201 (14.9%) SG. 80.6%, 84.2% of OAGB, 81.7%, 82.6% of RYGB, and 77.1%, 81.5% of SG participants were in T2DM remission after 1 and 3 years, respectively. 1- and 3-year remission were associated with preoperative age, duration of T2DM, FBS and HbA1c, BMI, insulin therapy, and a family history of obesity (p < 0.05). CONCLUSION: The remission of T2DM after RYGB, SG, and OAGB surgery is dependent on various preoperative factors. Patients with younger age, shorter duration of T2DM, lower preoperative HbA1c and FBS, higher BMI, who were not on insulin therapy, and not having a family history of obesity were the best candidates to achieve a prolonged diabetes remission.

Clinical Trial Data Management Software: A Review of the Technical Features.

BACKGROUND: Data management is an important, complex and multidimensional process in clinical trials. The execution of this process is very difficult and expensive without the use of information technology. A clinical data management system is software that is vastly used for managing the data generated in clinical trials. The objective of this study was to review the technical features of clinical trial data management systems. METHODS: Related articles were identified by searching databases, such as Web of Science, Scopus, Science Direct, ProQuest, Ovid and PubMed. All of the research papers related to clinical data management systems which were published between 2007 and 2017 (n=19) were included in the study. RESULTS: Most of the clinical data management systems were web-based systems developed based on the needs of a specific clinical trial in the shortest possible time. The SQL Server and MySQL databases were used in the development of the systems. These systems did not fully support the process of clinical data management. In addition, most of the systems lacked flexibility and extensibility for system development. CONCLUSION: It seems that most of the systems used in the research centers were weak in terms of supporting the process of data management and managing clinical trial's workflow. Therefore, more attention should be paid to design a more complete, usable, and high quality data management system for clinical trials. More studies are suggested to identify the features of the successful systems used in clinical trials.

A Review of Clinical Data Management Systems Used in Clinical Trials.

BACKGROUND: A clinical data management system is a software supporting the data management process in clinical trials. In this system, the effective support of clinical data management dimensions leads to the increased accuracy of results and prevention of diversion in clinical trials. The aim of this review article was to investigate the dimensions of data management in clinical data management systems. METHODS: This study was conducted in 2017. The used databases included Web of Science, Scopus, Science Direct, ProQuest, Ovid Medline and PubMed. The search was conducted over a period of 10 years from 2007 to 2017. The initial number of studies was 101 reaching 19 in the final stage. The final studies were described and compared in terms of the year, country and dimensions of the clinical data management process in clinical trials. RESULTS: The research findings indicated that none of the systems completely supported the data management dimensions in clinical trials. Although these systems were developed for supporting the clinical data management process, they were similar to electronic data capture systems in many cases. The most significant dimensions of data management in such systems were data collection or entry, report, validation, and security maintenance. CONCLUSION: Seemingly, not sufficient attention has been paid to automate all dimensions of the clinical data management process in clinical trials. However, these systems could take positive steps towards changing the manual processes of clinical data management to electronic processes.

Timing of Anterior Cruciate Ligament Reconstruction and Incidence of Meniscal and Chondral Injury within the Knee.

BACKGROUND: To review a single-surgeon series of 616 athletic patients with anterior cruciate ligament reconstructions in order to evaluate the relationship between the timing of the reconstruction and the incidence of meniscal and chondral injuries. METHODS: SIX GROUP OF PATIENTS WERE CATEGORIZED BASED ON THE TIME INTERVAL FROM THEIR INJURY TO SURGERY IN THE FOLLOWING MANNER: <3 months, 3-6 months, 6-9 months, 9-18 months, 18-36 months, and >36 months. The presence of meniscal tears was documented and chondral pathology was scored based on the Outerbridge classification. RESULTS: Incidence of medial meniscus tear was significantly higher in patients undergoing reconstruction after 3 months from their injury (P = 0.032). The opportunity of patients with chondral pathology was recorded to be significantly higher in the groups operated on after 6 months from their injuries time (P = 0.008). CONCLUSIONS: Considering the effect of time on the rate of having meniscus injury and chondral pathology, reducing the time between the injury and surgery could improve the long-term health outcomes in this population.