Development of a gastric cancer risk calculator for questionnaire-based surveillance of Iranian dyspeptic patients.

BACKGROUND: Gastric cancer (GC) is considered a silent killer, taking more than three quarters of a million lives annually. Therefore, prior to further costly and invasive diagnostic approaches, an initial GC risk screening is desperately in demand. METHODS: In order to develop a simple risk scoring system, the demographic and lifestyle indices from 858 GC and 1132 non-ulcer dyspeptic (NUD) patients were analysed. We applied a multivariate logistic regression approach to identify the association between our target predictors and GC versus NUD. The model performance in classification was assessed by receiver operating characteristic (ROC) analysis. Our questionnaire covering 64 predictors, included known risk factors, such as demographic features, dietary habits, self-reported medical status, narcotics use, and SES indicators. RESULTS: Our model segregated GC from NUD patients with the sensitivity, specificity, and accuracy rates of 85.89, 63.9, and 73.03%, respectively, which was confirmed in the development dataset (AUC equal to 86.37%, P < 0.0001). Predictors which contributed most to our GC risk calculator, based on risk scores (RS) and shared percentages (SP), included: 1) older age group [> 70 (RS:+ 241, SP:7.23), 60-70 (RS:+ 221, SP:6.60), 50-60 (RS:+ 134, SP:4.02), 2) history of gastrointestinal cancers (RS:+ 173, SP:5.19), 3) male gender (RS:+ 119, SP:3.55), 4) non-Fars ethnicity (RS:+ 89, SP:2.66), 5) illiteracy of both parents (RS:+ 78, SP:2.38), 6) rural residence (RS:+ 77, SP:2.3), and modifiable dietary behaviors (RS:+ 32 to + 53, SP:0.96 to 1.58). CONCLUSION: Our developed risk calculator provides a primary screening step, prior to the subsequent costly and invasive measures. Furthermore, public awareness regarding modifiable risk predictors may encourage and promote lifestyle adjustments and healthy behaviours.

The 15-year national trends of urinary cancers incidence among Iranian men and women; 2005-2020.

BACKGROUND: Urinary tract cancers including bladder, kidney, ureter, and pelvis are a common malignancy worldwide with high mortality ratio. Aimed to investigate the prevalence of these cancers, we conducted this study. METHODS: In this study, all the information related to ICD10 codes, gender, age and province of residence of individuals were obtained from the data of Iran's cancer registry by the Ministry of Health, Medicine and Medical Education and demographic evidence for each sub-country from the reports of Statistics Center of Iran (SCI). Also, the data of two Iranian national survey studies CASPIAN-III, IV, and V (information related to the care and prevention of non-communicable diseases (NCD) in childhood and adolescence) and STEPs (including information on NCD in adults over 18 years old) were used. The data was analyzed using Poisson regression with mixed effects to estimate the incidence of cancers. RESULTS: Bladder and kidney neoplasm are the most common cancers of the urinary system in Iran. The prevalence of bladder cancer has increased from 5.82 to 11.50 per 100,000 individuals. The increasing trend is growing faster in men compared with women. The incidence of kidney neoplasm has increased over the years (2.03 in 2005 vs. 7.02 in 2020 per 100,000). Having a higher incidence ratio compared with bladder cancer, kidney cancer is responsible for 35.06% of all urinary cancers in 2020 compared with 23.71% in 2005. Both neoplasms of the ureter and renal pelvis were recorded rarely and with lower incidence in both sexes during this period. CONCLUSION: Considering the increasing trend in the incidence of urinary neoplasms in Iran during these years, the advantage of focusing on the risk of urinary cancers is highlighted. Therefore, investigating the prevalence and incidence of urinary cancers to plan and manage these cancers will result in prevention and reduction of the disease burden on the Iranian society. Future studies in this field can help in the prevention and well-timed diagnosis of these cancers.

The levels and trends of cancer incidence in the elderly population at national and sub-national scales in Iran from 1990 to 2016.

BACKGROUND: Cancer is most commonly associated with aging. It is necessary to gain a better understanding of cancer's trend and distribution among elderlies and provide comprehensive cancer care for this population. AIMS: The aim of the current study was to show the trends in cancer incidence focusing on the population aged 60+ from 1990 to 2016 in Iran. MATERIAL AND RESULTS: We used the dataset of the Iran Cancer Registry to estimate cancer incidences by sex, age, province, and year. In order to account for incomplete data we used a two-stage spatiotemporal model along with random intercept mixed effect models. We calculated annual age-standardized incidence rates (ASIRs) for age groups 60+ and 5-interval age groups. There was an increasing trend of 25.3% to 936.9% (95% uncertainty interval: 769.6-1141.8) in ASIR in the elderly in 2016. ASIR of all cancers were 889.7 (731.3-1083.6) in women and 988.1 (811.1-1205) in men in 2016, per 100 000 respectively, which had an increasing trend comparing 1990. Skin, breast, and stomach cancers in women and prostate, skin, and stomach cancers in men were the most common types in 2016. All the most incident cancer subtypes underwent an increasing trend in both sexes, except for the bladder, esophageal, and skin cancers which almost had a similar level in 1990 and 2016. Most provinces had an increasing trend in ASIR in all cancers combined from 1990 to 2016 except Zanjan with a decreasing trend. CONCLUSION: Regarding the persistent increasing trend of most elderly cancers' incidence, this is crucial for policymakers to establish preventive plans, determine proper resource allocation, and develop specific treatments for elderly cancer patients.

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.

A Bayesian latent class extension of naive Bayesian classifier and its application to the classification of gastric cancer patients.

BACKGROUND: The Naive Bayes (NB) classifier is a powerful supervised algorithm widely used in Machine Learning (ML). However, its effectiveness relies on a strict assumption of conditional independence, which is often violated in real-world scenarios. To address this limitation, various studies have explored extensions of NB that tackle the issue of non-conditional independence in the data. These approaches can be broadly categorized into two main categories: feature selection and structure expansion. In this particular study, we propose a novel approach to enhancing NB by introducing a latent variable as the parent of the attributes. We define this latent variable using a flexible technique called Bayesian Latent Class Analysis (BLCA). As a result, our final model combines the strengths of NB and BLCA, giving rise to what we refer to as NB-BLCA. By incorporating the latent variable, we aim to capture complex dependencies among the attributes and improve the overall performance of the classifier. METHODS: Both Expectation-Maximization (EM) algorithm and the Gibbs sampling approach were offered for parameter learning. A simulation study was conducted to evaluate the classification of the model in comparison with the ordinary NB model. In addition, real-world data related to 976 Gastric Cancer (GC) and 1189 Non-ulcer dyspepsia (NUD) patients was used to show the model's performance in an actual application. The validity of models was evaluated using the 10-fold cross-validation. RESULTS: The presented model was superior to ordinary NB in all the simulation scenarios according to higher classification sensitivity and specificity in test data. The NB-BLCA model using Gibbs sampling accuracy was 87.77 (95% CI: 84.87-90.29). This index was estimated at 77.22 (95% CI: 73.64-80.53) and 74.71 (95% CI: 71.02-78.15) for the NB-BLCA model using the EM algorithm and ordinary NB classifier, respectively. CONCLUSIONS: When considering the modification of the NB classifier, incorporating a latent component into the model offers numerous advantages, particularly within medical and health-related contexts. By doing so, the researchers can bypass the extensive search algorithm and structure learning required in the local learning and structure extension approach. The inclusion of latent class variables allows for the integration of all attributes during model construction. Consequently, the NB-BLCA model serves as a suitable alternative to conventional NB classifiers when the assumption of independence is violated, especially in domains pertaining to health and medicine.

Safety and efficacy of the FAKHRAVAC compared with BBIBP-Corv2 against SARS-CoV-2 in adults: a non-inferiority multi-center trial.

BACKGROUND: We compared Fakhravac and BBIBP-Corv2 vaccines in a phase III trial. METHOD: We conducted a multicenter, parallel-group, active-control, non-inferiority clinical trial with pragmatic considerations assessing the safety and efficacy of Fakhravac and BBIBP-Corv2 vaccines. We started with two randomized double-blind arms and added two non-randomized open-label arms (based on participant preference) because of slow recruitment. The adult population received 0.5 ml (10 µg per dose) intramuscular injections of Fakhravac or BBIBP-Corv-2 vaccines 21 days apart. The primary outcome was the occurrence of PCR-positive symptomatic Covid-19 disease 14 days or more after the second injection. A 10% non-inferiority margin to the reported 72.8% efficacy of BBIBP-Corv2 was assumed. Cox proportional hazard modeling was used to estimate hazard ratios and their 95% confidence intervals. RESULT: We enrolled 24,056 adults in four groups (randomized-Fakhravac: 824, randomized-BBIBP-Corv2: 832; Non-randomized-Fakhravac: 19,429, Non-randomized-BBIBP-Corv2: 2971). All observed local and systemic adverse reactions were generally self-limited and resolved completely. We observed similar Serious Adverse Event (SAE) rates in the BBIBP-Corv2 (2.57, 95% CI 1.33-4.49) and Fakhravac (2.25, 95% CI 1.72-2.89) groups; none of which were related to the vaccines received. We recorded 9815 Medically Attendant Adverse Events (MAAE), 736 of which were categorized as somehow related. The rate of related MAAE in the Fakhravac was similar to the BBIBP-Corv2 groups (0.31 and 0.26 per 1000 person-day) in the randomized and considerably higher (0.24 and 0.07 per 1000 person-day) in the non-randomized arms. We observed 129 (35% of the 365 required by target sample size) events of PCR + symptomatic Covid-19 during four months of active follow-up in the randomized arm, demonstrating that those receiving the Fakhravac vaccine were significantly less likely (HR = 0.69; 95% CI 0.49-0.98) to be diagnosed with PCR + symptomatic Covid-19 compared with those receiving BBIBP-Corv2 vaccine. After adjusting for type I error using the O'Brien Fleming method, the Fakhravac vaccine was non-inferior to the BBIBP-Corv2 (assuming a 10% non-inferiority margin to the reported 72.8% BBIBP-Corv2 vaccine efficacy; HR < 1.35) (One-way test: HR = 0.66; 99.8% CI 0.38-1.15). In the non-randomized arm, the results were inconclusive (HR = 1.23; 95% CI 0.96-1.61). We observed 5 cases of hospitalized Covid-19 in the randomized arm, none of which occurred in the Fakhravac vaccine group. Those receiving the Fakhravac vaccine were four times less likely to go to the hospital because of a Covid-19 diagnosis (HR = 0.24; 95% CI 0.10-0.60). The vaccine efficacy of the Fakhravac vaccine is estimated to be 81.5% (95% CI 81-82.4%). CONCLUSION: Fakhravac inactivated SARS-CoV-2 vaccine has comparable safety and efficacy to the BBIBP-Corv2 vaccine. Trial registration This study was registered with the Iranian Registry of Clinical Trials ( www.irct.ir : IRCT20210206050259N3).

The 15-year national trends of endocrine cancers incidence among Iranian men and women; 2005-2020.

Cancer is one of the important health problems in Iran, which is considered as the third cause of death. Endocrine cancers are rare but mostly curable. Thyroid cancer, the most common endocrine tumors, includes about one percent of malignant cancer. In this study, we examined the 15-year national trend of endocrine cancer incidence in Iranian men and women. The data in each province were evaluated based on age, gender, and cancer type according to International Classification of Disease Codes version 10 (ICD-10) from 2005 to 2020 in Iran. All data were obtained from the reports of the Statistics Center of Iran (SCI), 6 phases of the step-by-step approach to monitoring the risk factors of chronic diseases over 18 years old (STEPs), and 3 periods of the CASPIAN study (survey of non-communicable diseases in childhood and adolescence). Statistical analyzes and graph generation were done using R statistical software. Poisson regression with mixed effects was used for data modeling and incidence rate estimation. The incidence of thyroid gland malignancy is higher in women than in men. On the other hand, the incidence of adrenal gland cancer is slightly higher in men than in women. The same pattern is observed for other endocrine neoplasms and related structures. The incidence rate of these types of cancers has generally increased from 2005 to 2020 in Iran. This increase is more in women than in men. In addition, in the middle of the country, there is a strong region in terms of the occurrence of these types of cancers. The incidence rate in these provinces is relatively higher for both sexes and all studied periods. We conducted a study to observe the changing trends for various types of endocrine cancers over 15 years in men and women. Considering the increasing trend of thyroid cancers in Iran, therefore, creating essential policies for the management of these types of cancers for prevention, rapid diagnosis, and, timely treatment is particularly important.

Clear cell carcinoma of the ovary and venous thromboembolism: a systematic review and meta-analysis.

OBJECTIVES: As the second most common subtype of Epithelial ovarian cancers (EOCs), ovarian clear cell carcinoma (OCCC) is associated with a high rate of cancer-associated thrombosis. Previous studies revealed the wide range prevalence (6-42%) of venous thromboembolism (VTE) among OCCC patients. This study aimed to determine the prevalence of VTE among OCCC patients as well as factors affecting it. METHODS: PubMed, Scopus, Embase, and Cochrane Library databases were searched up to December 12th, 2022. Studies reporting venous thromboembolic events in women with clear cell carcinoma of the ovary were included. Demographic data, clinical, and paraclinical features of the patients were independently extracted by two reviewers. RESULTS: Out of the 2254 records, 43 studies were processed for final review. The qualified studies involved 573 VTE cases among 2965 patients with OCCC. The pooled prevalence of VTE among OCCC patients was 21.32% (95%CI=(17.38-25.87)). Most VTE events were reported in Japanese women (26.15%), followed by Americans (24.41%) and UK (21.57%), and Chinese (13.61%) women. VTE was more common in patients with advanced stages (37.79%) compared to those with early stages of the disease (16.54%). CONCLUSIONS: Ovarian clear cell carcinoma is associated with a high rate of cancer-associated thrombosis. VTE events in OCCC patients were higher in advanced stages and Japanese women.

Chronic Obstructive Pulmonary Disease: Novel Genes Detection with Penalized Logistic Regression.

OBJECTIVE: This study aimed to introduce novel techniques for identifying the genes associated with developing chronic obstructive pulmonary disease (COPD) and to prioritize COPD candidate genes using regression methods. MATERIALS AND METHODS: This is a secondary analysis of the data from an experimental study. We used penalized logistic regressions with three different types of penalties included least absolute shrinkage and selection operator (LASSO), minimax concave penalty (MCP), and smoothly clipped absolute deviation (SCAD). The models were trained using genome-wide expression profiling to define gene networks relevant to the COPD stages. A 10-fold cross-validation scheme was used to evaluate the performance of the methods. In addition, we validate our results by the external validity approach. We reported the sensitivity, specificity, and area under curve (AUC) of the models. RESULTS: There were 21, 22, and 18 significantly associated genes for LASSO, SCAD, and MCP models, respectively. The most statistically conservative method (detecting less significant features) was MCP detected 18 genes that were all detected by the other two approaches. The most appropriate approach was a SCAD penalized logistic regression (AUC= 96.26, sensitivity= 94.2, specificity= 86.96). In this study, we have a common panel of 18 genes in all three models that show a significant positive and negative correlation with COPD, in which RNF130, STX6, PLCB1, CACNA1G, LARP4B, LOC100507634, SLC38A2, and STIM2 showed the odds ratio (OR) more than 1. However, there was a slight difference between penalized methods. CONCLUSION: Regularization solves the serious dimensionality problem in using this kind of regression. More exploration of how these genes affect the outcome and mechanism is possible more quickly in this manner. The regression-based approaches we present could apply to overcoming this issue.

The 15-year national trends of genital cancer incidence among Iranian men and women; 2005-2020.

BACKGROUND: Cancer is a major health problem and cause of mortality worldwide. Despite the prevalence of other cancers in males and females, genital cancers are especially important because of their psychological effects on individuals. Currently, cervical cancer, corpus uteri neoplasm, and ovarian cancer are the most common gynecological cancers in Iran. Prostate cancer has increased in Iranian men in the last decade. Therefore, this study aimed to investigate the 15-year national trend in the incidence of genital cancers in the Iranian population. METHODS: In this study, we used Iranian cancer registration data collected by the Ministry of Health and Medical Education, demographic information from the reports of the Statistics Center of Iran, STEPs (STEPwise approach to non-communicable diseases risk factor surveillance), and Caspian (childhood and adolescence surveillance and prevention of adult non-communicable disease). A list of potential auxiliary variables and secondary variables at all levels of the province-age-sex were evaluated during the years. We used mixed-effects Poisson regression to model the data and calculate the incidence of each cancer. RESULTS: Our results show an enhancement in the outbreak of all types of male cancers, but the most important are prostate (11.46 in 2005 to 25.67 in 2020 per 100,000 males) and testicular cancers (2.39 in 2005 to 5.05 per 100,000 males). As for female cancers, there has been an increase in ovarian and corpus uteri neoplasm incidence with 6.69 and 4.14 incidences per 100,000 females in 2020, making them the most occurring female genital neoplasms. While the occurrence of cervical cancer has decreased over the years (4.65 in 2005 to 3.24 in 2020). In general, the incidence of genital cancers in men and women has amplified in the last 15 years. CONCLUSIONS: Our study examined the trend of change for each malignant genital neoplasm for 15 years in Iranian men and women in each province. Considering the growing trend of the elderly population in Iran, patient awareness and early screening are essential in reducing mortality and costs imposed on patients and the health care system.

Phase II randomized, double blind, placebo controlled, clinical trial of safety and immunogenicity of an inactivated SARS-CoV-2 vaccine FAKHRAVAC in adults aged 18-70 years.

BACKGROUND: The FAKHRAVAC®, an inactivated SARS-CoV-2 vaccine, was assessed for safety and immunogenicity in a phase II trial. METHODS: We did a phase II, single-centered, randomized, double-blind, placebo-controlled clinical trial of the FAKHRAVAC inactivated SARS-CoV-2 vaccine on adults aged 18 to 70. The two parallel groups received two intramuscular injections of either a 10-µg vaccine or a placebo at 2-week intervals. The participants' immunogenicity responses and the occurrence of solicited and unsolicited adverse events were compared over the study period of up to 6 months. Immunogenicity outcomes include serum neutralizing antibody activity and specific IgG antibody levels. RESULTS: Five hundred eligible participants were randomly (1:1) assigned to vaccine or placebo groups. The median age of the participants was 36 years, and 75% were male. The most frequent local adverse reaction was tenderness (21.29% after the first dose and 8.52% after the second dose), and the most frequent systemic adverse reaction was headache (11.24% after the first dose and 8.94% after the second dose). Neutralizing antibody titers two and four weeks after the second injection in the vaccine group showed about 3 and 6 times increase compared to the placebo group (GMR = 2.69, 95% CI 2.32-3.12, N:309) and (GMR = 5.51, 95% CI 3.94-8.35, N:285). A four-fold increase in the neutralizing antibody titer was seen in 69.6% and 73.4% of the participants in the vaccine group two and four weeks after the second dose, respectively. Specific ELIZA antibody response against a combination of S1 and RBD antigens 4 weeks after the second injection increased more than three times in the vaccine compared to the placebo group (GMR = 3.34, 95% CI 2.5-4.47, N:142). CONCLUSIONS: FAKHRAVAC® is safe and induces a significant humoral immune response to the SARS-CoV-2 virus at 10-µg antigen dose in adults aged 18-70. A phase III trial is needed to assess the clinical efficacy. TRIAL REGISTRATION: Trial Registry Number: Ref., IRCT20210206050259N2 ( http://irct.ir ; registered on 08/06/2021).

Comparison of the Safety and Immunogenicity of FAKHRAVAC and BBIBP-CorV Vaccines when Administrated as Booster Dose: A Parallel Two Arms, Randomized, Double Blind Clinical Trial.

Purpose: This study was completed to assess the immunogenicity and safety of the FAKHRAVAC and BBIBP-CorV vaccines as a booster dose in the population with a history of receiving two doses of BBIBP-CorV vaccine. Methods: In this double-blind, parallel clinical trial, we randomly assigned healthy adults with a history of receiving two doses of the BBIBP-CorV vaccine, who then received either the FAKHRAVAC or BBIBP-CorV vaccine as a booster dose. The trial is registered in the Iranian Registry of Clinical Trial document depository (Code: IRCT20210206050259N4). Results: The outcomes that were monitored in this study were serum neutralizing antibody (Nab) activity, immunoglobulin G (IgG) level, local and systemic adverse reactions, serious adverse events, suspected unexpected serious adverse reactions, and medically attended adverse events. After administering vaccines to 435 participants, the most frequent local and systemic adverse reactions were tenderness and nausea in 23.7% and 1.4% of cases, respectively. All adverse events were mild, occurred at a similar incidence in the two groups, and were resolved within a few days. Conclusions: On the 14th day after the booster dose injection, the seroconversion rate (i.e., four-fold increase) of Nabs for seronegative participants were 87% and 84.6% in the FAKHRAVAC® and BBIBP-CorV groups, respectively. This study shows that the FAKHRAVAC® vaccine, as a booster dose, has a similar function to the BBIBP-CorV vaccine in terms of increasing the titer of virus-neutralizing antibodies, the amount of specific antibodies, and safety.

A novel dynamic Bayesian network approach for data mining and survival data analysis.

BACKGROUND: Censorship is the primary challenge in survival modeling, especially in human health studies. The classical methods have been limited by applications like Kaplan-Meier or restricted assumptions like the Cox regression model. On the other hand, Machine learning algorithms commonly rely on the high dimensionality of data and ignore the censorship attribute. In addition, these algorithms are more sophisticated to understand and utilize. We propose a novel approach based on the Bayesian network to address these issues. METHODS: We proposed a two-slice temporal Bayesian network model for the survival data, introducing the survival and censorship status in each observed time as the dynamic states. A score-based algorithm learned the structure of the directed acyclic graph. The likelihood approach conducted parameter learning. We conducted a simulation study to assess the performance of our model in comparison with the Kaplan-Meier and Cox proportional hazard regression. We defined various scenarios according to the sample size, censoring rate, and shapes of survival and censoring distributions across time. Finally, we fit the model on a real-world dataset that includes 760 post gastrectomy surgery due to gastric cancer. The validation of the model was explored using the hold-out technique based on the posterior classification error. Our survival model performance results were compared using the Kaplan-Meier and Cox proportional hazard models. RESULTS: The simulation study shows the superiority of DBN in bias reduction for many scenarios compared with Cox regression and Kaplan-Meier, especially in the late survival times. In the real-world data, the structure of the dynamic Bayesian network model satisfied the finding from Kaplan-Meier and Cox regression classical approaches. The posterior classification error found from the validation technique did not exceed 0.04, representing that our network predicted the state variables with more than 96% accuracy. CONCLUSIONS: Our proposed dynamic Bayesian network model could be used as a data mining technique in the context of survival data analysis. The advantages of this approach are feature selection ability, straightforward interpretation, handling of high-dimensional data, and few assumptions.

Twenty-Six-Year Trend of Mortality Rate Due to Ischemic Heart Diseases (IHDs) in Iran: 1990-2015.

Background: Ischemic Heart Diseases (IHDs) are the main causes of deaths all over the world. Since there is no comprehensive study on IHDs mortality rate in Iran, the present study aimed to estimate age-standardized IHDs mortality rate by sex, age, geography, and time trends at both national and sub-national levels in Iran. Methods: We used the Death Registration System (DRS) data from 1990 to 2015 collected by the Iranian Ministry of Health and Medical Education across the country, Tehran, and Isfahan main cemetery, not included in the DRS. Utilized death distribution methods to overcome the incompleteness of data. Statistical models including Spatio-temporal and Gaussian-Process Regression models were used to extrapolate all-cause and cause-specific mortality rates. Results: Age-standardized IHDs mortality rate in Iran almost doubled from 1990 to 2015. Forty-nine deaths per 100.000 population in 1990, which increased to 91.6 deaths per 100.000 in 2015). Male to female age-standardized mortality rate increased from 1.07 to 1.32 during the studied period. Aging was associated with an increase in age-standardized IHDs mortality rate in both sexes, all provinces, and all of the years. The range of age-standardized IHDs mortality rate for both sexes was from 58 to 136.2 deaths per 100,000 across provinces in 2015. Conclusion: Due to the increase in age-standardized IHDs mortality rate in Iran, it seems necessary to design and implement appropriate public health interventions by health authorities to prevent and control this group of diseases.

Clustering of countries according to the COVID-19 incidence and mortality rates.

BACKGROUND: Two years after the beginning of the COVID-19 pandemic on December 29, 2021, there have been 281,808,270 confirmed cases of COVID-19, including 5,411,759 deaths. This information belongs to almost 216 Countries, areas, or territories facing COVID-19. The disease trend was not homogeneous across these locations, and studying this variation is a crucial source of information for policymakers and researchers. Therefore, we address different patterns in mortality and incidence of COVID-19 across countries using a clustering approach. METHODS: The daily records of new cases and deaths of 216 countries were available on the WHO online COVID-19 dashboard. We used a three-step approach for identifying longitudinal patterns of change in quantitative COVID-19 incidence and mortality rates. At the first, we calculated 27 summary measurements for each trajectory. Then we used factor analysis as a dimension reduction method to capture the correlation between measurements. Finally, we applied a K-means algorithm on the factor scores and clustered the trajectories. RESULTS: We determined three different patterns for the trajectories of COVID-19 incidence and the three different ones for mortality rates. According to incidence rates, among 206 countries the 133 (64.56) countries belong to the second cluster, and 15 (7.28%) and 58 (28.16%) belong to the first and 3rd clusters, respectively. All clusters seem to show an increased rate in the study period, but there are several different patterns. The first one exhibited a mild increasing trend; however, the 3rd and the second clusters followed the severe and moderate increasing trend. According to mortality clusters, the frequency of sets is 37 (18.22%) for the first cluster with moderate increases, 157 (77.34%) for the second one with a mild rise, and 9 (4.34%) for the 3rd one with severe increase. CONCLUSIONS: We determined that besides all variations within the countries, the pattern of a contagious disease follows three different trajectories. This variation looks to be a function of the government's health policies more than geographical distribution. Comparing this trajectory to others declares that death is highly related to the nature of epidemy.

Alcohol consumption and related disorders in Iran: Results from the National Surveillance of Non-Communicable Diseases' Survey (STEPs) 2016.

BACKGROUND: Alcohol consumption is a public health concern which is illegal in Iran. Moreover, due to cultural and religious beliefs, the available population-based research findings on alcohol consumption are inadequate. We aimed to provide an estimate on alcohol consumption using a large-scale population-based survey in Iran. MATERIALS AND METHODS: The National Surveillance of Non-Communicable Risk Factors in Iran was a population-based survey conducted in 2016. The epidemiologic distribution of alcohol consumption and its related disorders were assessed using weighted survey methods and multiple logistic regression models. Age standardized rates were calculated using Iran's national population census in 2016. RESULTS: At the national level, the prevalence rates of lifetime and current alcohol consumption were 8.00% (95% CI: 7.67-8.32) and 4.04% (95% CI: 3.81-4.27), respectively. The highest prevalence was reported among 25 to 34 year-olds. Individuals of higher socioeconomic status consumed significantly greater levels of alcohol. At provincial level, the highest and lowest percentages of the current alcohol drinking rates in Iran's provinces were, 23.92% (95% CI: 17.56-30.28) and 0.4% (95% CI: 0-1.18) in males, 1.58% (95% CI: 0.22-2.94) and 0% in females, respectively. In urban regions, the highest alcohol consumption rate was more than 22 times greater than the lowest alcohol consumption rate. Current alcohol drinkers were 2 times more prone to injury as compared to nondrinkers (ORadj: 2.0, 95%CI: 1.7, 2.3). CONCLUSION: In Iran, the prevalence of alcohol consumption is low, although there is a considerable variation of alcohol consumption at provincial level as well as in different gender groups. Therefore, preventive WHO-recommended measures should be adopted more seriously by vulnerable groups.

Spatio-Temporal Analysis of the Hepatitis B Prevalence in Iranian Blood Donors from 2000 to 2016 at National and Provincial Level.

BACKGROUND: High risk blood transfusions can cause a lot of financial and psychological burden to the community. The prevalence of Hepatitis B is useful for evaluating the blood products' safety and donor selection methods. We aimed to predict the prevalence of hepatitis B in Iranian blood donors from 2000-2016. METHODS: Positive cases of hepatitis B from 2006 to 2014 were collected from Iranian Blood Transfusion Organization. This database was classified according to the age, provinces, and type of donation. Data was not existed in all subnational levels and all years, therefore, for predicting the hepatitis B prevalence, two separate, Spatio-temporal and mixed model (GLMM) were developed. RESULTS: At the national level, the hepatitis B prevalence declined from 0.69 (0.51 to 0.90) in 2000 to 0.27 (0.21 to 0.33) in 2016. In first-time, regular, and repeated donors, this prevalence declined from 2.31 (1.74 to 2.31), 0.26 (0.19 to 0.34), and 0.51 (0.38 to 0.68) in 2000 to 0.87 (0.69 to 1.09), 0.09 (0.07 to 0.12), and 0.19 (0.14 to 0.24) in 2016. At the provincial level, the highest and lowest prevalence in 2016 was observed in North Khorasan and Gilan. With increasing age, the average prevalence of hepatitis B, increased. CONCLUSION: Prevalence of hepatitis B in Iranian blood donors has been reduced significantly over 17 years, but still new cases of hepatitis B are reported. By precise monitoring the donor selection process and implementing more sensitive laboratory screening, we can reduce the risk of new infectious agents.

Diagnostic performance of classification trees and hematological functions in hematologic disorders: an application of multidimensional scaling and cluster analysis.

BACKGROUND: Several hematological indices have been already proposed to discriminate between iron deficiency anemia (IDA) and ß-thalassemia trait (ßTT). This study compared the diagnostic performance of different hematological discrimination indices with decision trees and support vector machines, so as to discriminate IDA from ßTT using multidimensional scaling and cluster analysis. In addition, decision trees were used to determine the diagnostic classification scheme of patients. METHODS: Consisting of 1178 patients with hypochromic microcytic anemia (708 patients with ßTT and 470 patients with IDA), this cross-sectional study compared the diagnostic performance of 43 hematological discrimination indices with classification tree algorithms and support vector machines in order to discriminate IDA from ßTT. Moreover, multidimensional scaling and cluster analysis were used to identify the homogeneous subgroups of discrimination methods with similar performance. RESULTS: All the classification tree algorithms except the LOTUS tree algorithm showed acceptable accuracy measures for discrimination between IDA and ßTT in comparison with other hematological discrimination indices. The results indicated that the CRUISE and C5.0 tree algorithms had better diagnostic performance and efficiency among other discrimination methods. Moreover, the AUC of CRUISE and C5.0 tree algorithms indicated more precise classification with values of 0.940 and 0.999, indicating excellent diagnostic accuracy of such models. Moreover, the CRUISE and C5.0 tree algorithms showed that mean corpuscular volume can be considered as the main variable in discrimination between IDA and ßTT. CONCLUSIONS: CRUISE and C5.0 tree algorithms as powerful methods in data mining techniques can be used to develop accurate differential methods along with other laboratory parameters for the discrimination of IDA and ßTT. In addition, the multidimensional scaling method and cluster analysis can be considered as the most appropriate techniques to determine the discrimination indices with similar performance for future hematological studies.

The level and trend of road traffic injuries attributable mortality rate in Iran, 1990-2015: a story of successful regulations and a roadmap to design future policies.

BACKGROUND: Road-Traffic-Injuries (RTIs) are predicted to rise up to the fifth leading cause of worldwide death by 2030 and Iran has the third highest RTIs mortality among higher-middle income countries. Although the high mortality of RTI in Iran is a warning, it provides the opportunity to indirectly assess the implemented RTI-related regulations' effectiveness via high-resolution relevant statistics and, hence, Iran could serve as a guide for countries with similar context. In order to do so, we utilized this study to report the time and spatial trends of RTIs-related mortality in different age and sex groups and road user classes in Iran. METHODS: Based on the national death-registration-system (DRS), cemeteries data, and the demographic characteristics, and after addressing incompleteness, we estimated mortality rates using spatiotemporal and Gaussian process regression models. We assessed Pearson seatbelt and helmet use and RTIs-attributable Age-Standardized-Morality-Rate (ASMR) associations. We also predicted RTIs-death-numbers, 2012-2020, by fitting a Generalized Additive Model to assess the status of achieving relevant sustainable development goal (SDG), namely reducing the number of RTIs-related deaths by half. RESULTS: Overall RTIs-attributable death and ASMR at the national level increased from 12.64 [95% UI, 9.52-16.86] to 29.1 [22.76-37.14] per 100,000 people in the time period of 1990-2015. The trend consisted of an increasing segment in 1990-2003 followed by a decreasing part till 2015. The highest percentage of death belonged to the three-or-more-wheels motorized vehicles. Pedestrian injuries percentage increased significantly and the highest mortality rate occurred in 85 years and older individuals. Low prevalence of seatbelt and helmet use were observed in provinces with higher than the median ASMR due to the relevant cause of each. RTIs-attributable death number is expected to reduce by 15.99% till 2020 which is lower than the established SDG goal. CONCLUSIONS: Despite the observed substantial moderation in the RTI-ASMR, Iran is till among the leading countries in terms of the highest mortality rates in the world. The enforced regulations including speed limitations (particularly for elder pedestrians) and mandatory use of seatbelt and helmet (for young adult and male drivers) had a considerable effect on ASMR, nevertheless, the RTI burden reduction needs to be sustained and enhanced.

National and Subnational Incidence, Mortality, and Years of Life Lost Due to Breast Cancer in Iran: Trends and Age-Period-Cohort Analysis Since 1990.

Breast cancer is the most common cancer among women, causing considerable burden and mortality. Demographic and lifestyle transitions in low and low-middle income countries have given rise to its increased incidence. The successful management of cancer relies on evidence-based policies taking into account national epidemiologic settings. We aimed to report the national and subnational trends of breast cancer incidence, mortality, years of life lost (YLL) and mortality to incidence ratio (MIR) since 1990. As part of the National and Subnational Burden of Diseases project, we estimated incidence, mortality and YLL of breast cancer by sex, age, province, and year using a two-stage spatio-temporal model, based on the primary dataset of national cancer and death registry. MIR was calculated as a quality of care indicator. Age-period-cohort analysis was used to distinguish the effects of these three collinear factors. A significant threefold increase in age-specific incidence at national and subnational levels along with a twofold extension of provincial disparity was observed. Although mortality has slightly decreased since 2000, a positive mortality annual percent change was detected in patients aged 25-34 years, leading to raised YLLs. A significant declining pattern of MIR and lower provincial MIR disparity was observed. We observed a secular increase of breast cancer incidence. Further evaluation of risk factors and developing national screening policies is recommended. A descending pattern of mortality, YLL and MIR at national and subnational levels reflects improved quality of care, even though mortality among younger age groups should be specifically addressed.