Safety and efficacy of RCP recombinant spike protein covid-19 vaccine compared to Sinopharm BBIBP: A phase III, non-inferiority trial.

Background: We conducted a phase III, non-inferiority trial comparing safety and efficacy of RCP recombinant spike protein Covid-19 vaccine to BBIBP (Sinopharm). Methods: Adult Iranian population received RCP or BBIBP in a randomized, double blind and an additional non-randomized open labeled trial arms. Eligible participants signed a written informed consent and received two intramuscular injections three weeks apart. In the randomized arm, an intranasal dose of vaccine or adjuvant-only preparation were given to the RCP and BBIBP recipients at day 51 respectively. Participants were actively followed for up to 4 months for safety and efficacy outcomes. Primary outcome was PCR + symptomatic Covid-19 disease two weeks after the second dose. The non-inferiority margin was 10% of reported BBIBP vaccine efficacy (HR = 1.36). Results: We recruited 23,110 participants (7224 in the randomized and 15,886 in the non-randomized arm). We observed 604 primary outcome events during 4 months of active follow-up including 121 and 133 in the randomized and 157 and 193 cases in the non-randomized arms among recipients of RCP and BBIBP respectively. Adjusted hazard ratios for the primary outcome in those receiving RCP compared with BBIBP interval were 0.91 (0.71-1.16) and 0.62 (0.49-0.77) in the randomized and non-randomized arms respectively. The upper boundary of 99.1% confidence interval of HR = 0.91 (0.67-1.22) remained below the margin of non-inferiority in the randomized arm after observing the early stopping rules using O'Brien Fleming method. Conclusion: Our study showed that the RCP efficacy is non-inferior and its safety profile is comparable to the BBIBP.

Phase II, Safety and Immunogenicity of RAZI Cov Pars (RCP) SARS Cov-2 Vaccine in Adults Aged 18-70 Years; A Randomized, Double-Blind Clinical Trial.

BACKGROUND: This study explores the safety and immunogenicity of the Razi-Cov-Pars (RCP) SARS Cov-2 recombinant spike protein vaccine. METHOD: In a randomized, double-blind, placebo-controlled trial, adults aged 18-70 were randomly allocated to receive selected 10 µg/200 µl vaccine strengths or placebo (adjuvant). It included two intramuscular injections at days 0 and 21, followed by an intranasal dose at day 51. Immediate and delayed solicited local and systemic adverse reactions after each dose up to a week, and specific IgG antibodies against SARS Cov-2 spike antigens two weeks after the 2nd dose were assessed as primary outcomes. Secondary safety outcomes were abnormal laboratory findings and medically attended adverse events (MAAE) over six months follow up. Secondary immunogenicity outcomes were neutralizing antibody activity and cell-mediated immune response. RESULT: Between May 27th and July 15th, 2021, 500 participants were enrolled. Participants' mean (SD) age was 37.8 (9.0), and 67.0 % were male. No immediate adverse reaction was observed following the intervention. All solicited local and systemic adverse events were moderate (Grade I-II). Specific IgG antibody response against S antigen in the vaccine group was 5.28 times (95 %CI: 4.02-6.94) the placebo group with a 75 % seroconversion rate. During six months of follow-up, 8 SAEs were reported, unrelated to the study intervention. The participants sustained their acquired humoral responses at the end of the sixth month. The vaccine predominantly resulted in T-helper 1 cell-mediated immunity, CD8+ cytotoxic T-cell increase, and no increase in inflammatory IL-6 cytokine. CONCLUSION: RCP vaccine is safe and creates strong and durable humoral and cellular immunity. TRIAL REGISTRATION: (IRCT20201214049709N2).

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.

Breast cancer risk factors in Iranian women: a systematic review and meta-analysis of matched case-control studies.

BACKGROUND: Identifying breast cancer risk factors is a critical component of preventative strategies for this disease. This study aims to identify modifiable and non-modifiable risk factors of breast cancer in Iranian women. METHODS: We used international databases (PubMed/Medline, Scopus, Web of Knowledge, and Embase) and national databases (SID, Magiran, and ISC) to retrieve relevant studies until November 13, 2022. The odds ratio (OR) with a 95% confidence interval using the random-effect model was used to estimate the pooled effect. The publication bias was assessed by the Egger and Begg test. A sensitivity analysis was conducted to evaluate the effect of each included study on the final measurement. RESULTS: Of the 30,351 retrieved articles, 24 matched case-control records were included with 12,460 participants (5675 newly diagnosed cases of breast cancer and 6785 control). This meta-analysis showed that of the known modifiable risk factors for breast cancer, obesity (vs normal weight) had the highest risk (OR = 2.17, 95% CI 1.47 to 3.21; I2 = 85.7) followed by age at marriage (25-29 vs < 18 years old) (OR = 2.00, 95% CI 1.53 to 2.61; I2 = 0), second-hand smoking (OR = 1.86, 95% CI 1.58 to 2.19; I2 = 0), smoking (OR = 1.83, 95% CI 1.41 to 2.38; I2 = 18.9), abortion history (OR = 1.44, 95% CI 1.02 to 2.05; I2 = 66.3), oral contraceptive use (OR = 1.35, 95% CI 1.11 to 1.63; I2 = 74.1), age at marriage (18-24 vs < 18 years old) (OR: 1.22, 95% CI 1.02 to 1.47; I2 = 0). Of non-modifiable risk factors, history of radiation exposure (OR = 3.48, 95% CI 2.17 to 5.59; I2 = 0), family history of breast cancer (OR = 2.47, 95% CI 1.83 to 3.33; I2 = 73), and age at menarche (12-13 vs ≥ 14 years old) (OR = 1.67, 95% CI 1.31-2.13; I2 = 25.4) significantly increased the risk of breast cancer. CONCLUSIONS: Since most risk factors related to breast cancer incidence are modifiable, promoting healthy lifestyles can play an influential role in preventing breast cancer. In women with younger menarche age, a family history of breast cancer, or a history of radiation exposure, screening at short intervals is recommended.

The association between current smoking and binge drinking among adults: A systematic review and meta-analysis of cross-sectional studies.

Background: The substantial increasing trend of binge drinking is a global alarm. Our aim was to undertake a systematic review and meta-analysis of cross-sectional studies to explore the association of current smoking with binge drinking among adults. Methods: We systematically searched Web of Knowledge; PubMed; Scopus; Embase and Ovid (MEDLINE, EMBASE, PsycARTICLES, PsycINFO, PsycEXTRA, and PsycTests) (from inception to 27 May 2020) databases to identify cross-sectional studies of the association between current smoking and binge drinking. Study screening, data extraction, and methodological quality assessment were all carried out by two independent authors. Adjusted odds ratio (AOR) was pooled with 95% confidence intervals (CI) using random effects model in the meta-analysis, followed by the investigation of the heterogeneity via Q-test and I 2 statistic. We assessed publication bias using a funnel plot, the Egger's, and Begg's tests. Results: We identified 3,171 studies and included nine cross-sectional studies with 64,516 participants. A significant association was found between current smoking and binge drinking among both genders (AOR = 2.97; 95% CI = 1.98 to 4.45; I 2 = 90.5%). Subgroup analysis showed that this association among women, men, Caucasians, and Asians/Africans were (AOR = 3.68; 95% CI = 1.03 to 13.18; I 2 = 98.9%), (AOR = 2.53; 95% CI = 1.87 to 3.42; I 2 = 73.1%), (AOR = 1.36; 95% CI: 1.01-1.83, I 2 = 47.4%), and (AOR = 3.93; 95% CI: 2.99-5.17, I 2 = 61.3%), respectively. There was no evidence of publication bias. Conclusion: Current smoking is associated with binge drinking and can be used for identifying and screening binge drinkers. Moreover, this association is stronger among men, and Asians/Africans. This meta-analysis estimation was limited to English-language studies, and the full text of about 3.5% of reports for retrieval was not found, then generalization of the results should be done with caution.